Asian Pacific Journal of Cancer Prevention
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
- 월간
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
과학기술표준분류
- 보건의료 ＞ 의약품/의약품개발
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
KSCI제13권12호
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Keyvani, Hossein;Fazlalipour, Mehdi;Monavari, Seyed Hamid Reza;Mollaie, Hamid Reza 5917
Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection. -
Abdel-Rahman, Wael M.;Moustafa, Yasser M.;Ahmed, Bassamat O.;Mostafa, Randa M. 5937
The term endocrine disruptors is used to describe a variety of natural and manmade substances that have the capacity to potentially interfere with and modify the normal physiology of endocrine system either by mimicking, blocking or modulating the actions of natural endogenous hormones. The rising incidence of breast cancer over the last 50 years and the documented higher incidence in urban as compared to rural areas suggest a relationship to the introduction and increased use of xenoestrogens in our environment. The literature has developed over the last decades where initial experiments on endocrine disruptors did not support an involvement in breast cancer, and then evidence mounted implicating various environmental factors including hormones, endocrine disrupting chemicals and non-endocrine disrupting environmental carcinogens in the pathogenesis of breast cancer. Available data support the hypothesis that exposure to endocrine disruptors in utero leaves a signature on mammary gland morphogenesis so that the resulting dysgenic gland becomes more predisposed to develop tumors upon exposures to additional insults later on during life. Exceptionally, exposure to phytoestrogens could be beneficial to human health. Most of the available data are from well developed countries while the developing countries are still understudied regarding these issues. Here, we raise a note of caution about potential role of environmental toxins including endocrine disruptors in breast cancer development and call for serious measures to be taken by all involved parties in the developing world. -
Tabarestani, Sanaz;Ghafouri-Fard, Soudeh 5947
The cancer stem cell (CSC) model states that cancers are organized in cellular hierarchies, which explains the functional heterogeneity often seen in tumors. Like normal tissue stem cells, CSCs are capable of self-renewal, either by symmetric or asymmetric cell division, and have the exclusive ability to reproduce malignant tumors indefinitely. Current systemic cancer therapies frequently fail to eliminate advanced tumors, which may be due to their inability to effectively target CSC populations. It has been shown that embryonic pathways such as Wnt, Hedgehog, and Notch control self-renewal and cell fate decisions of stem cells and progenitor cells. These are evolutionary conserved pathways, involved in CSC maintenance. Targeting these pathways may be effective in eradicating CSCs and preventing chemotherapy or radiotherapy resistance. -
Fazeli, Zeinab;Pourhoseingholi, Mohamad Amin;Vahedi, Mohsen;Zali, Mohammad Reza 5955
Hepatocellular carcinoma (HCC), the sixth most prevalent cancer worldwide, continues to have high prevalence in many countries of Asia. The main challenge is the high prevalence of chronic hepatitis and aflatoxin, for example in China. HBV vaccination should be the major preventive tactic in Asian countries. The burden of HCC is low in Iran because most cases are due to HBV and this infection was less common. Although in Iran, a mass vaccination program started in 1993, its impact on decreasing the burden of HCC due to HBV can only be expected in future decades. -
Jena, Pratap Kumar;Bandyopadhyay, Chandan;Mathur, Manu Raj;Das, Sagarika 5959
Background: The term 'hardcore' has been applied to use of smoking tobacco and generally referred to as the inability or unwillingness of regular smokers to quit. The component constructs of hardcore except nicotine dependence are product neutral. With the use of 'time to first chew' as a measure of nicotine dependence, hardcore definition can be extended to characterize smokeless tobacco users. Hardcore users respond less to tobacco cessation interventions, and are prone to tobacco induced diseases including cancer. Thus identifying hardcore users would help in estimate the burden of high risk population for tobacco induced diseases. Smokeless tobacco use is predominant and accounts for more than 50% of oral cancer in India. Hence, hardcore chewing information could be used for planning of tobacco and cancer control interventions. The objective of this study was to assess the prevalence and associated factors of hardcore smokeless tobacco use in India. Materials and Methods: Global Adult Tobacco Survey (GATS)-India 2010 data were analyzed to quantify hardcore smokeless tobacco use in India with following five criteria: (1) current daily smokeless tobacco use; (2) no quit attempt in the past 12 months of survey or last quit attempt of less than 24 hours duration; (3) no intention to quit in next 12 months or not interested in quitting; (4) time to first use of smokeless tobacco product within 30 minutes of waking up; and (5) knowledge of smokeless tobacco hazards. Results: The number of hardcore smokeless tobacco users among adult Indians is estimated to be 5% (39.5 million). This group comprises 23.2% of daily smokeless tobacco users. The population prevalence varied from 1.4-9.1% across different national regions of India. Logistic regression modeling indicated age, education and employment status to be the major predictors of hardcore smokeless tobacco use in India. Conclusions: The presence of a huge number (39.5 million) of hardcore smokeless tobacco users is a challenge to tobacco control and cancer prevention in India. There is an unmet need for a universal tobacco cessation programme and intensification of anti-tobacco education in communities. -
Zand, Ali Mohammad;Imani, Saber;Saadati, Mojtaba;Ziaei, Robabeh;Borna, Hojat;Zaefizadeh, Mohammad;Shazad, Babak 5965
Cancer is now the main cause of increasing mortality throughout the world. Minor alterations in the cell cycle which are inherited and not removed by apoptosis are important rsik factors. Blood cancers are asmong the types which most readily cause death. Here in this study, usual but important factors such as age, gender, Rh and ABO blood typing, weight, and platelet counts are analyzed for impact on blood cancers. Frequencies and distributions, correlations and chi-square test were utilized in order to clarify the perspective of important factors. Our statistical results show males and females to have same risk in blood cancer but A blood type (40%) along with positive Rh (73%) had the highest risk. Low platelet counts are related to more than 80% of cases. Obesity has a statistically ignorable role in blood cancer prevalence. The fact that blood cancer cases increase during the second decade of life (45.7%) which might be because of involvement of maturation processes. -
Panda, Rajmohan;Mathur, Manu Raj;Divya, Persai;Srivastava, Swati;Ramachandra, Srikrishna Sulgodu 5969
Introduction: Andhra Pradesh (AP) is one of the largest tobacco producing states in India. About 29% of adults in AP currently use tobacco in some form. Almost 24% of males and 4% of females are smokers. The prevalence of tobacco use in the state is higher than the national average of 15% for male and 2% for female smokers. However, few attempts have been made to understand the current situation of tobacco control resources, activities and strategies in the context of such a high tobacco prevalence state. The present study aimed to identify the gaps in existing tobacco control program and areas where tobacco control efforts can be integrated. Methods: Data were collected using both quantitative and qualitative methods. Semi-structured interviews were undertaken with a total of 95 key officials of state health departments, program managers, and project directors in six districts to understand ongoing tobacco control efforts. To facilitate the interviews, semi-structured guides were developed. Simple descriptive statistical analysis was conducted on the quantitative data using SPSS version 17. Results: The results of the situational analysis suggest that a sufficient health workforce and infrastructure with the potential to integrate tobacco control activities is available in the surveyed districts. However, lack of integration of the tobacco control program intothe tuberculosis control program and the National Rural Health Mission was observed. Information, education and communication activities were lacking at block level health facilities. Conclusions: Our findings indicate that lack of trained health professionals, paucity of dedicated funds, lack of information, education and communication materials and low priority given to tobacco control activities are some of the factors which impede integration of tobacco control into existing health and developmental programmes in the districts of Andhra Pradesh, India. -
Background: To investigate the influence of telomerase activity, apoptosis, radiosensitivity of cervical cancer after siRNA-mediated knockdown of telomerase RNA and evaluate in vivo growth with gene interference. Methods: We studied siRNA-targeting-telomerase RNA transfection into the Hela cell line. Expression of hTERC mRNA was detected by RT-PCR and telomerase activity was measured by the TRAP assay. Growth inhibition was determined by MTT assay and radiosensitivity of the cervical cancer cells was examined by colony formation assay. In addtion, effects of hTERC inhibition in vivo were studied by injection of siRNA-transfected Hela cells into nude mice. Results: The hTERC siRNA effectively downregulated the expression of hTERC mRNA and also reduced the telomerase activity to 30% of the untreated control vlaue. The viability of hTERC siRNA transfected Hela cells was reduced by 44.7% after transfection. After radiation treatment, the radiosensitivity of Hela cells with hTERC knockdown was increased. In vivo, the tumors developing from the hTERC siRNA-transfected cells were of reduced size, indicating that the hTERT siRNA also depressed the tumorigenic potential of the Hela cells. Conclusions: Our results supported the concept of siRNA-mediated inhibition of telomerase mRNA which could inhibit the expression of hTERC and telomerase activity. Furthermore, radiosensitivity was upregulated after knockdown the hTERC in vivo and in vitro.
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Background: Numerous studies have investigated the association of matrix metalloproteinase 1 (MMP1) rs1799750 single nucleotide polymorphism with lung cancer susceptibility, but the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate any possible association. Methods: We searched publications from MEDLINE, EMBASE and CNKI databases which assessed links between the MMP1 rs1799750 polymorphism and lung cancer risk. We calculated the pooled odds ratio (OR) and its 95% confidence interval (95%CI) using either fixed-effects or random-effects models. Results: The meta-analysis was based on 9 publications encompassing 4,823 cases and 4,298 controls. The overall results suggested there was a significant association between the MMP1 rs1799750 polymorphism and lung cancer risk (1G vs. 2G: OR = 0.83, 95%CI = 0.73-0.94; 1G1G vs. 2G2G: OR = 0.73, 95%CI = 0.59-0.92; 1G1G vs. 1G2G/2G2G: OR = 0.87, 95%CI = 0.79-0.97; 1G1G/1G2G vs. 2G2G: OR = 0.78, 95%CI = 0.64-0.95). In the subgroup analysis by ethnicity, the association was still obvious in Asians (all P values < 0.05), but there was no association in Caucasians (all P values > 0.05). Conclusions: The MMP1 rs1799750 polymorphism is associated with decreased lung cancer risk, and a race-specific effect may exist in this association.
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A cross-sectional study was conducted among nursing staff of a missionary hospital of Delhi in June 2009. All the nurses were invited to participate in the training programme on breast cancer and techniques of breast self examination (BSE). A questionnaire was administered to all 259 participants seeking information on their level of awareness regarding breast cancer and relevant screening guidelines. With the help of 5 training workshops all the nurses were imparted training regarding the most appropriate technique of doing breast self exams. The mean age of the participants was 35.8 years. Out of a total of 259 nursing staff members 77.2% correctly answered all the 10 questions regarding high risk factors for breast cancer and after the training programme this increased to 100% (p<0.05). Only 65.2% of the participants gave correct responses to all the 8 questions regarding correct technique of performing a BSE, which after the training programme increased to 99.3% (p<0.05). At the baseline only 56.8% knew all the three screening methods correctly and after the intervention 98.7% could correctly mark the responses regarding screening (p<0.05). The actual practice of following the screening guidelines amongst the nursing staff was poor. Only 26 (10.03%) had ever done a BSE, none performed it monthly, 58 (22.4%) had ever gone themselves for a CBE and 18 (6. 94%) had ever undergone mammography.
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Cole, Stephen R.;Gregory, Tess;Whibley, Alex;Ward, Paul;Turnbull, Deborah;Wilson, Carlene;Flight, Ingrid;Esterman, Adrian;Young, Graeme P. 5989
Background: There is little information on longitudinal patterns of participation in faecal occult blood test (FOBT) based colorectal cancer (CRC) screening or on demographic or behavioural factors associated with participation in re-screening. The lack of an agreed system for describing participatory behaviour over multiple rounds also hampers our ability to report, understand and make use of observed associations. Our aims were to develop a system for describing patterns of participatory behaviour in FOBT-based CRC screening programs and to identify factors associated with particular behavioural patterns. Methods: A descriptive framework was developed and applied to a data extract of screening invitation outcomes over two rounds of the NBCSP. The proportion of invitees in each behaviour category was determined and associations between behaviour patterns and demographic and program factors were identified using multivariate analyses. Results: We considered Re-Participants, Dropouts, Late Entrants and Never Participants to be the most appropriate labels for the four possible observed participatory categories after two invitation rounds. The screening participation rate of the South Australian cohort of the NBCSP remained stable over two rounds at 51%, with second round Dropouts (10.3%) being balanced by Late Entrants (10.5%). Non-Participants comprised 38.7% of invitees. Relative to Re-Participants, Dropouts were older, more likely to be female, of lower SES, had changed their place of residence between offers had a positive test result in the first round. Late Entrants tended to be in the youngest age band. Conclusions: Specific demographic characteristics are associated with behavioural sub-groups defined by responses to 2 offers of CRC screening. Targeted group-specific strategies could reduce dropout behaviour or encourage those who declined the first invitation to participate in the second round. It will be important to keep first round participants engaged in order to maximise the benefit of a CRC screening program. -
Baghianimoghadam, Mohammad Hosein;Ardakani, Mojtaba Fattahi;Akhoundi, Mohsen;Mortazavizadeh, Mohammad Reza;Fallahzadeh, Mohammad Hosein;Baghianimoghadam, Behnam 5995
Background: Colorectal cancer is one of most common cancers in women and men and one of the major causes of death due to neoplasia. Colonoscopy is considered as the most accurate diagnostic procedure to detect colorectal cancer at the earlier stages. Objectives: The current study aimed to evaluate the effects of an education program using the Theory of Planned Behavior on promoting behavioral intention among first degree relatives of colorectal cancer patients. Materials and Methods: A quasi-experimental study conducted to evaluate the effectiveness of an educational program to promote attitudinal factors associated with early detection of colorectal cancer in 99 first degree relatives of colorectal cancer patients aged more than 20 years in Yazd city, Iran. A researcher made questionnaire forwhich validity and reliability were confirmed by expert point of view and pilot testing was employed for data collection. Questionnaires were filled in before and after educational intervention. The registered data were transferred to SPSS 19 and analyzed by paired T-test, Man-Whitney and Wilcaxon. Results: Mean scores of knowledge, attitude, perceived behavioral control and intention regarding colorectal cancer increased after education significantly (P<0.05). Conclusions: Application of the Theory of Planned Behavior has positive influence on promoting intention behavior. It is therefore recommended to apply educational programs to promote behavioral intention. -
Isa, Mohamad Rodi;Ming, Moy Foong;Razack, Azad Hassan Abdul;Zainuddin, Zulkifli Mohd;Zainal, Nur Zuraida 5999
Measurement of quality of life among prostate cancer patients helps the health care providers to understand the impact of the disease in the patients' own perspective. The main aim of this study is to measure the quality of life among prostate cancer patients at University Malaya Medical Center (UMMC) and Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and to ascertain the association factors for physical coefficient summary (PCS) and mental coefficient summary (MCS). A hospital based, cross sectional study using the Short Form-36 (SF-36) questionnaire was conducted over a period of 6 months. A total of 193 respondents were recruited. Their total quality of life score was$70.1{\pm}14.7$ and the PCS score was lower compared to MCS. The factors associated for PCS were: age, living partner, renal problem, urinary problem of intermittency, dysuria and hematuria. Factors associated for MCS were: age, living partner, renal problem, presenting prostatic specific antigen and urinary problem of intermittency and dysuria. Our prostate cancer patients had moderate quality of life in the physical health components but their mental health was less affected. -
Hashim, Nikman Adli Nor;Ramzi, Nurul Hanis;Velapasamy, Sharmila;Alex, Livy;Chahil, Jagdish Kaur;Lye, Say Hean;Munretnam, Khamsigan;Haron, Mohd Roslan;Ler, Lian Wee 6005
Background: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia. Materials and Methods: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study. Results: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk. Conclusions: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population. -
Dutta, Sudhir K.;Agrawal, Kireet;Girotra, Mohit;Fleisher, A. Steven;Motevalli, Mahnaz;Mah'moud, Mitchell A.;Nair, Padmanabhan P. 6011
Introduction: Epidemiological studies suggest a protective role for${\beta}$ -carotene with several malignancies. Esophageal adenocarcinoma frequently arises from Barrett's esophagus (BE). We postulated that${\beta}$ -carotene therapy maybe protective in BE. Materials and Method: We conducted a prospective study in which 25 mg of${\beta}$ -carotene was administered daily for six-months to six patients. Each patient underwent upper endoscopy before and after therapy and multiple mucosal biopsies were obtained. Additionally, patients completed a gastroesophageal reflux disease (GERD) symptoms questionnaire before and after therapy and severity score was calculated. To study the effect of${\beta}$ -carotene at molecular level, tissue extracts of the esophageal mucosal biopsy were subjected to assessment of heat-shock protein 70 (HSP70). Results: A significant (p<0.05) reduction in mean GERD symptoms severity score from$7.0{\pm}2.4$ to$2.7{\pm}1.7$ following${\beta}$ -carotene therapy was noted. Measurement of Barrett's segment also revealed a significant reduction in mean length after therapy. In fact, two patients had complete disappearance of intestinal metaplasia. Furthermore, marked enhancement of HSP70 expression was demonstrated in biopsy specimens from Barrett's epithelium in four cases that were tested. Conclusions: Long-term${\beta}$ -carotene therapy realizes amelioration of GERD symptoms along with restitution of the histological and molecular changes in esophageal mucosa of patients with BE, associated with concurrent increase in mucosal HSP70 expression. -
Fang, Jie-Yu;Li, Zhi-Hua;Li, Qiang;Huang, Wen-Sheng;Kang, Liang;Wang, Jian-Ping 6017
Background: Resveratrol has been reported to have potential chemopreventive and apoptosis-inducing properties in a variety of tumor cell lines. Objective: In this study, to investigate the effects of resveratrol on protein kinase C (PKC) activity and apoptosis in human colon carcinoma cells, we used HT-29 cells and examined the$PKC{\alpha}$ and ERK1/2 signaling pathways. Methods: To test the effects of resveratrol on the growth of HT-29 cells, the cells were exposed to varying concentrations and assessed with the the MTT cell-viability assay. Fluorescence-activated cell sorter (FACS) analysis was applieded to determine the effects of resveratrol on cell apoptosis. Western blotting was performed to determine the protein levels of$PKC{\alpha}$ and ERK1/2. In inhibition experiments, HT-29 cells were treated with G$\ddot{o}$ 6976 or PD98059 for 30 min, followed by exposure to$200{\mu}M$ resveratrol for 72 h. Results: Resveratrol had a significant inhibitory effect on HT-29 cell growth. FACS revealed that resveratrol induced apoptosis. Western blotting showed that e phosphorylation of$PKC{\alpha}$ and ERK1/2 was significantly increased in response to resveratrol treatment. Pre-treatment with$PKC{\alpha}$ and ERK1/2 inhibitors (G$\ddot{o}$ 6976 and PD98059) promoted apoptosis. Conclusion: Resveratrol has significant anti-proliferative effects on the colon cancer cell line HT-29. The PKC-ERK1/2 signaling pathway can partially mediate resveratrol-induced apoptosis of HT-29 cells. -
The incidence of hepatocellular carcinoma (HCC) in Malaysia for the year 2001 was 2.8 per 100,000 people. The mortality rate is increasing. A retrospective cohort study measuring the survival of HCC patients who received treatment in Selayang Hospital was conducted from 1 January 2003 to 31 December 2006. The main objectives of the study were to measure the survival of the patients and to understand the influencing factors, especially ethnicity. The subjects were newly diagnosed cases of HCC by CT scan and histopathological assessment who underwent futher investigations and treatments in Hospital Selayang (inception cohort). The survival time was measured from the date of diagnosis until the subjects died, or failed to follow-up at the end of the study period (31 December 2007). A total of 299 patients were selected with 95 patients dying, the majority among Chinese (39.1%). Subgroup analysis according to ethnicity proved significantly that Chinese patients who had smaller tumor, less number of nodules, low AFP level, Child Pugh Class A and received surgical treatment had a better median survival rate compared to other ethnic groups. Malay (cHR: 1.3, 95%CI; 0.89-1.85) and Indian (cHR: 1.3, 95%CI; 0.74-2.26) patients had a poor survival compared to Chinese patients, but not in the final model. Therefore ethnicity may play a role in survival of HCC patients, but not as a main hazard prognostic factor.
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Kav, Sultan;Tokdemir, Gamze;Tasdemir, Reyhan;Yalili, Ayse;Dinc, Didem 6027
Purpose: To identify cancer patient and relatives beliefs, information needs, information-seeking behavior and information sources about cancer and treatment. Methods: This research was conducted at two hospitals of a university. Data was collected via questionnaires and the Turkish version of the Miller Behavioral Style Scale (MBSS) to assess information-seeking behavior. The sample included 82 patients and 54 relatives. Results: Patients were receiving treatment mostly for breast, gynecologic, lung cancer and leukemia/ lymphoma. All of them indicated that they want to be informed by a doctor about their diagnosis and treatment first. Other information sources were internet, media and nurses. The majority of the patients and half of their relatives agreed that "cancer is curable and preventable disease". Only 2.5% of patients agreed with the statement "I don't want to get information about disease which disturbs me". According the data obtained from MBSS; the mean patients MBSS score ($6.41{\pm}3.2$ ) was higher than their relatives ($5.46{\pm}3.1$ ). Respondents with higher education and younger age indicated more information-seeking behavior. Conclusions: Patients and their relatives differ in some of their information-seeking behavior. Patients beliefs and their strategies for coping with their illness can constrain their wish for information and their efforts to obtain it. Healthcare professionals need to assess and be sensitive to the information-seeking behavior of cancer patients and their relatives. -
Falzon, Charlene;Chalabaev, Aina;Schuft, Laura;Brizzi, Christophe;Ganga, Marion;d'Arripe-Longueville, Fabienne 6033
This study was designed to identify beliefs about physical activity in cancer patients. Semi- structured interviews were conducted with 20 patients under treatment, who were invited to identify perceived barriers for not adopting a physically active lifestyle and to express their beliefs about physical activity. Content analyses revealed five main categories of beliefs including four types of barriers: (a) barriers related to the side effects of treatment; (b) barriers related to a lack of perceived physical abilities; (c) barriers related to a lack of interest for physical activity; (d) beliefs about the negative effects of physical activity, and (e) beliefs about the positive effects of physical activity. These findings extend the existing literature by indicating how stereotypes may play a role in explaining sedentary lifestyles in cancer patients. -
Singh, Madhulika;Singh, Uma;Mathur, Neeraj;Shukla, Yogeshwer 6039
This study was conducted to assess the predictive value of p-glycoprotein (p-gp) and p53 immunoexpression in human papillomavirus (HPV) infected cases of cervical dysplasia. Expression of both p-gp and p53 proteins was detected in cervical smears from 177 squamous intraepithelial lesions (SIL) cases along with 183 "atypical squamous cells of unknown significance" (ASCUS) and 150 normal cases. HPV 16 and 18 infection was detected by polymerase chain reaction using type-specific primers for HPV sub-types. There were no significant detectable p53 and p-gp expression in the normal cervix smears (p>0.05). In the ASCUS group 10 cases were positive for both p53 and p-gp immunoreactivity. In cervical dysplasia cases, p53 was positive in 86 (48.58%) while p-gp was positive in 93 (52.54%) and the two markers showed a highly significant correlation (r=0.92, p<0.001). Expression of p53 and p-gp was associated with grade of SIL (p<0.001). A positive correlation between the presence of HPV and expression of proteins p53 and p-gp in smears of patients with cervical lesions was also noted (p<0.001). Thus, p53 and p-gp immunostaining in cervical smears may act as an auxiliary biomarker for detection of HPV-associated cervical lesions. Additionally, a significant positive correlation between ascending grades of SIL and labeling indices of markers suggests that p53 and p-gp can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smears. -
Roudsari, Motahhareh Tourchi;Bahrami, Ahmad Reza;Dehghani, Hesam;Iranshahi, Mehrdad;Matin, Maryam Moghadam;Mahmoudi, Mahmud 6047
Bracken fern [Pteridium aquilinem (L.) kuhn (Dennstaedtiaceae)] is one of the most common species on the planet. It has been consumed by humans and animals for centuries. Use by some human groups is because they believe bracken fern is good for health as plant medicine. However, it is also one of the few known plants that can cause tumors in farm animals. Many interested groups have focused their attention on bracken fern because of these interesting features. In order to evaluate the biological effects of exposure to this plant in cellular level, human cancer cell lines were treated with the fern dichloromethane extracts and the genotoxic and cytotoxic effects were studied. Anti-proliferative/cytotoxic effects were evaluated by cell count, MTT assay and flow cytometry methods with three different cancer cell lines, TCC, NTERA2, and MCF-7, and two normal cells, HDF1 and HFF3. Pro-apoptotic effects of the extracts were determined by DAPI staining and comet assay, on TCC cancer cells compared to the normal control cell lines. Cellular morphology was examined by light microscopy. Our present study showed that the extract caused DNA damage and apoptosis at high concentrations ($200{\mu}g/mL$ ) and also it may induce cell cycle arrest (G2/M phase) at mild concentrations (50 and$30{\mu}g/mL$ ) depending on the cell type and tumor origin. These results indicate that bracken fern extract is a potent source of anticancer compounds that could be utilized pharmaceutically. -
Jafary, Fariba;Salehi, Mansoor;Sedghi, Maryam;Nouri, Nayereh;Jafary, Farzaneh;Sadeghi, Farzaneh;Motamedi, Shima;Talebi, Maede 6055
The mismatch repair system (MMR) is a post-replicative DNA repair mechanism whose defects can lead to cancer. The MSH3 protein is an essential component of the system. We postulated that MSH3 gene polymorphisms might therefore be associated with prostate cancer (PC). We studied MSH3 codon 222 and MSH3 codon 1036 polymorphisms in a group of Iranian sporadic PC patients. A total of 60 controls and 18 patients were assessed using the polymerase chain reaction and single strand conformational polymorphism. For comparing the genotype frequencies of patients and controls the chi-square test was applied. The obtained result indicated that there was significantly association between G/A genotype of MSH3 codon 222 and G/G genotype of MSH3 codon 1036 with an increased PC risk (P=0.012 and P=0.02 respectively). Our results demonstrated that MSH3 codon 222 and MSH3 codon 1036 polymorphisms may be risk factors for sporadic prostate cancer in the Iranian population. -
Lasrado, Savita;Prabhu, Prashanth;Kakria, Anjali;Kanchan, Tanuj;Pant, Sadip;Sathian, Brijesh;Gangadharan, P.;Binu, V.S.;Arathisenthil, S.V.;Jeergal, Prabhakar A.;Luis, Neil A.;Menezes, Ritesh G. 6059
Regional cancer epidemiology is an important basis for determining the priorities for cancer control in different countries worldwide. There is no reliable information about the pattern of head and neck cancer in western Nepal and hence an attempt was here made to evaluate the situation based on hospital data, which provide the only source in the western region of Nepal. A clinicopathological analysis of head and neck cancers treated between 2003 and 2006 in Manipal Teaching Hospital affiliated to Manipal College of Medical Sciences, Pokhara, Western Development Region, Nepal was performed. A total of 105 head and neck cancer cases were identified with a male to female ratio of 1.8:1. The median ages of male and female patients were 62 and 64 years, respectively. Ninety-seven (92.4%) of the cancer patients were suffering from carcinoma, three (2.9%) had blastoma, three (2.9%) had sarcoma, and two (1.9%) had lymphoma. The majority (61.9%) of carcinoma cases were squamous cell carcinoma followed by anaplastic carcinoma (7.2%). Of the carcinoma cases, the most common site of primary lesion was larynx (19.6%), followed by the thyroid (14.4%), the tongue and hypopharynx with 10.3% cases each. Comparative analysis among males and females did not reveal any sex difference in type of head and neck cancers. The head and neck cancer pattern revealed by the present study provides valuable leads to cancer epidemiology in western Nepal and useful information for health planning and cancer control, and future research in western Nepal. -
Pirincci, Necip;Gecit, Ilhan;Gunes, Mustafa;Kemik, Ahu Sarbay;Yusel, Mehmet Bilgehan;Kaba, Mehmet;Ceylan, Kadir;Aslan, Mehmet 6063
Although alteration in the haptoglobin phenotype has been reported in patients with bladder cancer, serum haptoglobin levels have not been evaluated. We hypothesized that serum haptoglobin can be used as a biomarker. The aim of this study was to evaluate the expression of haptoglobin in bladder cancer and to determine the relationship with clinicopathological features. A total of 68 serum specimens obtained before surgery were used to investigate haptoglobin expression using the sandwich ELISA technique. Serum haptoglobin levels were higher in the patients with bladder cancer compared to healthy controls (p<0.0001). Additionally, the levels of haptoglobin protein increased with increasing tumor grades (p<0.001) and were significantly higher in patients with metastatic disease and the presence of lymphovascular involvement, lymph node metastases and increasing tumor burden (p<0.0001). This study suggests that elevated haptoglobin levels are associated with a higher stage, grade, and extent of distant metastasis and larger tumor size. Haptoglobin may therefore provide a useful diagnostic and treatment biomarker for patients with bladder cancer. -
Reddy, Neha;Ninan, Tilu;Tabar, Laszlo;Bevers, Therese 6067
Background: Breast cancer in developing countries is on the rise. There are currently no guidelines to screen women at risk in India. Since mammography in the western world is a well-accepted screening tool to prevent late presentation of breast cancer and improve mortality, it is intuitive to adopt mammography as a screening tool of choice. However, it is expensive and fraught with logistical issues in developing countries like India. Materials and Methods: Our breast cancer screening camp was done at a local district hospital in India after approval from the director and administrators. After initial training of local health care workers, a one-day camp was held. Clinical breast examination, mammograms, as well as diagnostic evaluation with ultrasound and fine needle aspiration biopsy were utilized. Results: Out of total 68 women screened only 2 women with previous history of breast cancer were diagnosed with breast cancer recurrence. None of the women in other groups were diagnosed with breast cancer despite suspicious lesions either on clinical exam, mammogram or ultrasound. Most suspicious lesions were fibroadenomas. The average cost of screening women who underwent mammography, ultrasound and fine needle aspiration was $30 dollars, whereas it was $16 in women who had simple clinical breast examination. Conclusions: Local camps act as catalysts for women to seek medical attention or discuss with local health care workers concerns of discovering new lumps or developing breast symptoms. Our camp did diagnose recurrence of breast cancer in two previously treated breast cancer patients, who were promptly referred to a regional cancer hospital. Further studies are needed in countries like India to identify the best screening tool to decrease the presentation of breast cancer in advanced stages and to reduce mortality. -
Mary, J. Stella;Vinotha, P.;Pradeep, Andrew M. 6073
Discovery of anticancer drugs that kill or disable tumor cells in the presence of normal cells without undue toxicity is a potential challenge for therapeutic care. Several papers in the literature have emphasized the potential implications of marine products such as seaweeds which exhibit antitumor activity. Study attempts to screen the antitumor effect of Sargassum sp, against chosen cell lines such as MCF-7 (Breast cancer) and Hep-2 (Liver Cancer). Ethanol extract of Sargassum sp. was concentrated using a Soxhlet apparatus and dissolved in DMSO. In vitro cytotoxic activity of Sargassum sp at various concentrations ($100{\mu}g/ml-300{\mu}g/ml$ ) screened for antitumor effect against the chosen cell lines using MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole). The study documented that the percentage of cell viability has been reduced with increased concentration, as evidenced by cell death. Sargassum sp extract shows potential cytotoxic activity ($P{\leq}0.05$ ) with$IC_{50}$ of$200{\mu}g/ml$ and$250{\mu}g/ml$ against Hep-2 and MCF-7 cell lines respectively. The ethanol fraction of Sargassum sp induced cell shrinkage, cell membrane blebbing and formation of apoptotic bodies with evidence of bioactive components as profound influencing factors for anti-tumor effects. Further research need to be explored for the successful application of Sargassum sp as a potent therapeutic tool against cancer. -
Yu, Min;Liu, Lei;Zhang, Bing-Lan;Chen, Qi;Ma, Xue-Lei;Wu, Yu-Ke;Liang, Chun-Shui;Niu, Zhi-Min;Qin, Xin;Niu, Ting 6077
Background: This study was performed to analyze the prognostic implications of pretreatment or preoperative thrombocytosis in women with gynecologic malignancies. Material and Methods: We surveyed 2 medical databases, PubMed and EMBASE, to identified all relevant studies. A total of 14 (n=3,490) that evaluated the link between thrombocytosis and 5-year survival were included. REVMAN version 5.1 was used for our analysis and publication bias was evaluated using the Begg's funnel plot and tested by STATA 11.0. Risk ratios (RRs) with 95% confidence intervals (CIs) generated by the random effect model were used to assess the strength of any association. Results: 709(20.3%) of the 3,490 patients exhibited thrombocytosis (platelet counts >$400{\times}10^9/L$ ) at primary diagnosis, and their mortality was 1.62-fold higher compared with the others (RR=1.62, 95%CI=[1.28-2.05], p<0.0001). Thrombocytosis failed to have a stronger effect on the survival of advanced patients of stages III to IV in our study (n=478, RR=1.29, 95% CI=[1.13-1.48], p=0.0003), nor in women with cervical cancer in stage IB (n=1371, RR=1.73, 95% CI=[1.71-2.58], p=0.007). In addition, when adjusted for different carcinoma, it was associated with worse prognosis for all except the ones with vulvar cancer (n=201, RR=0.43, 95% CI=[0.14-1.29], p=0.13). Conclusions: This meta-analysis indicated that thrombocytosis might be associated with a worse prognosis for patients with gynecologic malignancies but without specificity or sensitivity for the ones in advanced stage. When adjusted for different gynecologic malignancies, it showed a significant effect on survival of all except vulvar cancers. -
Ahmed, Hussain Gadelkarim;Mustafa, Saadalnour Abusail;Warille, Eyman 6083
Background: The aim of this study was to screen for human papillomavirus (HPV) infections in head and neck squamous cell carcinomas (HNSCCs) using P16 immunostaining. Materials and Methods: A retrospective study was performed on 150 samples from patients diagnosed with HNSCCs. HPV status was determined using$p16^{INK4A}$ . Results: 31 of the 150 (20.7%) HNSCCs were HPV positive. Conclusions: A large proportion of HNSCCs in Sudan are associated with HPV infection. The fact that the prevalence of HPV is high among Sudanese patients with head and neck cancers (HNC) has obvious implications for vaccine therapy. -
Hulikal, Narendra;Ray, Satadru;Thomas, Joseph;Fernandes, Donald J. 6087
Context: Patients diagnosed with a cancer have a life time risk of developing another de novo malignancy depending on various inherited, environmental and iatrogenic risk factors. Of late the detection of new primary has increased mainly due to refinement in both diagnostic and treatment modalities. Cancer victims are surviving longer and thus are more likely to develop a new metachronous malignancy. Aims: To report our observed trend of increase in prevalence of both synchronous and metachronous second malignant neoplasms among cancer victims and to review the relevant literature. Settings and Design: A hospital based retrospective collection of prospective data of patients diagnosed with second denovo malignancy. Materials and Method: The study was conducted over a 5 year period from July 2008 to June 2012. All patients diagnosed with a histologically proven second malignancy as per Warren Gate's criteria were included. Various details regarding sex, age at presentation, synchronous or metachronous, treatment and outcome were recorded. Conclusions: The occurrence of multiple primary malignancies is not rare. Awareness of the possibility alerts the clinician in evaluation of patients with a known malignancy presenting with unusual sites of metastasis. Individualizing the treatment according to the stages of the primaries will result in durable cancer control particularly in synchronous double malignancy. -
Alipour, Sadaf;Afshar, Somayeh;Moini, Ashraf;Dastjerdi, Marzieh Vahid;Saberi, Azin;Bayani, Leila;Eslami, Bita;Hosseini, Ladan 6093
Background: Phytoestrogens may be an alternative therapy in control of menopausal symptoms but their definite effects on breast tissue must be determined. Our study aimed to define the clinical and ultrasonographic changes of the breast after use of soy isoflavones in menopausal women. Materials and Methods: Menopausal women with hot flashes were randomly grouped as cases and controls and cases received soy isoflavones for 12 weeks. Breast examination (BE) and ultrasonography (US) were done at 0, 6 and 12 weeks. Tenderness and nodularity on BE were graded 1-4 by breast surgeons. Results: There were 30 women in the case and 26 in the control group. The mean age was 51.3 years and the mean age of menopause was 49.2 years. There was no change in the BE and US at 6 weeks in controls. In the case group, 10% had grade 1 tenderness and 13.3% grade 2 tenderness and grade 1 nodularity in BE accompanied with diffuse small cysts in US. At 12 weeks, there was no change in BE and US in the 2 groups. Conclusions: There was no statistically significant difference in the BE of the 2 groups at 6 and 12 weeks (p value=0.36 and 0.41 for nodularity and tenderness respectively) and in the US results. Although the literature contains many facts concerning PEs and the breast, further prospective studies are needed to identify structural breast changes produced by PEs in order to identify the appropriate dosage and indications of use. -
Urun, Yuksel;Ozdemir, Nuriye Yildirim;Utkan, Gungor;Akbulut, Hakan;Savas, Berna;Oksuzoglu, Berna;Oztuna, Derya Gokmen;Dogan, Izzet;Yalcin, Bulent;Senler, Filiz Cay;Onur, Handan;Demirkazik, Ahmet;Zengin, Nurullah;Icli, Fikri 6097
Background: Previous studies have observed an association between ABO blood group and risk for certain gastrointestinal malignancies, including pancreatic and gastric cancer. However, it is unclear whether there is such an association with colorectal cancer (CRC). In this study, possible relationships between ABO blood groups and Rh factor and KRAS status in patients with CRC were investigated. Materials and Methods: In 1,620 patients with CRC, blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of the Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with wild type K-ras status was also evaluated. Results: Overall distributions of ABO blood groups as well as Rh factor were comparable between patients (45% A, 7.2% AB, 16.4% B, 31.4% O, and 87.2% Rh+) and controls (42.2% A, 7.6% AB, 16.3% B, 33.9% O, and 87.7% Rh+) (p=0.099). However, there were statistically significant difference between patients and controls with respect to O vs. non O blood group (p=0.033) and marginally significant difference for A vs. non-A blood group (p=0.052). Among patients, the median age was 62 (range 17-97), 58.1% were male. There were no statistically significant differences respect to sex and K-ras status. Conclusion: In present study, the ABO/Rh blood groups were statistically significantly associated with the risk of CRC. There were no relationship between K-ras status and ABO blood group and Rh factor. However further studies with larger numbers of patients are needed to establish the role of blood groups and to define t he mechanisms by which ABO blood type affect CRC. -
Motamedi, Sahar;Majidzadeh, Keivan;Mazaheri, Mahta;Anbiaie, Robab;Mortazavizadeh, Seyed Mohammad Reza;Esmaeili, Rezvan 6101
Background: Breast cancer accounts about one million from total annual ten million new diagnosed cases of neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popular selective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Methods: This case control study was performed on samples taken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactions were conducted for 10 healthy samples using the comparative$C_t$ (Cycles threshold) method, each pair of genes being compared and samples with ratios around 1 were taken as control samples. Proliferation reactions were done by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program and analyzed. Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistant patients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitive patients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients with one and two copies was similar between two groups but patients with three copies were more likely to belong to the drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicating possible protective effects while that for three copies was 1.604. Conclusions: Based on our study there is no significant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer. But more studies considering other influencing factors appear warranted. -
Background: The aim of this study was to examine knowledge about cancer and early diagnosis of cancer among nurses. Materials and Method: This descriptive study was carried out at a University Faculty of Medicine Hospital in Turkey. Study between April and June, 2011, with 325 volunteer nurses. The collection tool consisted of two survey forms. The first was designed for sociodemographic information and the second consisted of 16 questions, prepared in accordance with the literature as open and close-ended, for interviews conducted by researchers. Results: Out of the individuals (n=325), included in the study, 90.8% were female, 63.1% high school-university graduates and 55.1% married, with an average years of service of
$6.34{\pm}5.33$ and an average age of$28.1{\pm}5.10$ . The mean cancer knowledge point was$70.1{\pm}19.5$ . Some 79.1% of nurses had not received cancer related continuing education by specialists. A signified relation was found between the nurse knowledge on cancer and educational level (p<0.05). Conclusions: The nurse, a member of the health staff, is in constant contact with individuals at hospitals, schools, polyclinics, workplaces, and homes. When educating society about cancer, nurses need to have a high level of knowledge regarding early diagnosis and cancer prevention. -
Goot-Heah, Khor;Kwai-Lin, Thong;Froemming, Gabriele Ruth Anisah;Abraham, Mannil Thomas;Rosdy, Nik Mohd Mazuan Nik Mohd;Zain, Rosnah Binti 6109
Background: Oral cancer has become one of the most prevalent cancers worldwide and human Papillomavirus is one of the risk factors for developing oral cancer. For this study HPV18 was chosen as it is one of the high risk HPV types and may lead to carcinogenesis. However, prevalence of HPV18 infection in Oral Squamous Cell Carcinoma in Malaysia remains unclear. Objective: This study aimed to investigate the viral load of HPV18 DNA in OSCC and potentially malignant lesions using saliva samples. Materials and Methods: Genomic DNAs of thirty saliva samples of normal subjects and thirty saliva samples compromised of 16 samples from potentially malignant lesions and 14 of OSCC patients were amplified for HPV18 DNA using a nested polymerase chain reaction analysis. All PCR products were then analyzed using the Bioanalyzer to confirm presence of HPV18 DNA. Result: From thirty patients examined, only one of 30 (3.3%) cases was found to be positive for HPV18 in this study. Conclusion: The finding of this study revealed that there is a low viral detection of HPV18 in Malaysian OSCC by using saliva samples, suggesting that prevalence of HPV18 may not be important in this group of Malaysian OSCC. -
Ghojazadeh, Morteza;Azar, Zahra Fardi;Saleh, Parviz;Naghavi-Behzad, Mohammad;Azar, Nastaran Ghodratnezhad 6115
Introduction: Increasing prevalence of human papilloma virus (HPV) infection and its association with cervical cancer as a leading cause of death make it necessary to evaluate and improve the public knowledge, especially of university students, about this cause of disease. Methods: A cross-sectional study of knowledge and attitude of a total 669 students from Tabriz University of Medical Sciences was therefore performed with a modified validated questionnaire, arranged into 5 parts and containing 55 questions, in July 2011. Questions were directed to study socio-demographic characteristics of the participant, knowledge about HPV disease, transmission route, relationship with cervical cancer, predisposing factors, and participants attitude toward people with HPV infection. Results: All of the participants were Moslem with a mean age$25.6{\pm}5.33$ years of age. All of the participants had heard of HPV, and acquired their knowledge through university courses (90.6%); the majority of them knew that HPV is a sexually transmitted disease and a potential cause for genital warts but general knowledge about details was not high. Mean knowledge score of residents and post graduate midwifery and nursing students was high as compared to other groups (P<0.001). Statements that indicated the presence of fear to communicate with people suffering HPV and people's avoidance to rely on babysitting of these patients were observed. Educational level (${\beta}$ =0.21, P<0.001), age (${\beta}$ =0.18, P=0.002,) and smoking (${\beta}$ =-0.11, P=0.006) were predicted to effect knowledge. Conclusions: Moderate level of knowledge about HPV among medical university students makes it necessary to set effective national public health efforts on HPV education and prevention considering he excess of young population in Iran vulnerable to cervical cancer. -
Xie, Xiao-Xue;Ouyang, Shu-Yu;Jin, He-Kun;Wang, Hui;Zhou, Ju-Mei;Hu, Bing-Qiang 6121
Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repair radiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association between XRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effects in patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine the predictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising 2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity than those with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR, 1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combination with chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele was associated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allele vs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protective against radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs. Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may be independent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selection of genotyping method is an important factor in determining risk factors. No evidence for any predictive value of XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be required to further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patients undergoing whole breast radiotherapy. -
Xie, Cong-Ying;Jin, Xian-Ce;Deng, Xia;Xue, Sheng-Liu;Jing, Zhao;Su, Hua-Fang;Wu, Shi-Xiu 6129
Objectives: To evaluate the feasibility and efficacy of simultaneous accelerated radiation therapy (SMART) and concurrent weekly paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma. Methods: Forty-one patients with pathologically confirmed nasopharyngeal carcinoma were treated by SMART with concurrent weekly paclitaxel. Daily fraction doses of 2.5 Gy and 2.0 Gy were prescribed to the gross tumor volume (GTV) and clinical target volume (CTV) to a total dose of 70 Gy and 56 Gy, respectively. Paclitaxel of$45mg/m^2$ was administered concurrently with radiation therapy every week. Adjuvant chemotherapy was given four weeks after the completion of the radiotherapy (RT) if the tumor demonstrated only a partial response (PR). Results: All patients completed the radiotherapy (RT) course. Adjuvant chemotherapy was administered to 12 patients due to PR. The CR (complete remission) rate was 82.9% three months after RT. Thirty-nine (95.1%) patients completed the concurrent weekly chemotherapy with paclitaxel, and two patients skipped their sixth course. Seven patients had a 15% dosage reduction at the fifth and sixth course due to grade 3 mucositis. The median follow-up was 30 (range, 14-42) months. The three-year overall survival (OS), metastases-free survival (MFS), and local control rates were 77.0%, 64.4%, and 97.6%, respectively. No correlation between survival rate and T or N stage was observed. Grade 3 acute mucositis and xerostomia were present in 17.1% and 7.1%, respectively. Conclusion: SMART with concurrent weekly paclitaxel is a potentially effective and toxicity tolerable approach in the treatment of locally advanced NPC. -
Phua, Chee Ee;Ung, Ngie Min;Tan, Boon Seang;Tan, Ai Lian;Eng, Kae Yann;Ng, Bong Seng 6133
Purpose: To study the effect of bolus versus no bolus in the coverage of the nodal tumour volume with intensity-modulated radiotherapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Methods and Materials: This retrospective study used data from 5 consecutive patients with NPC who were treated with bolus for large neck nodes using IMRT from November 2011-January 2012 in our institute. All these patients were treated radically with IMRT according to our institution's protocol. Re-planning with IMRT without bolus for these patients with exactly the same target volumes were done for comparison. Comparison of the plans was done by comparing the V70 of PTV70-N, V66.5 of PTV70-N, V65.1 of PTV70-N and the surface dose of the PTV70-N. Results: The mean size of the largest diameter of the enlarged lymph nodes for the 5 patients was 3.9 cm. The mean distance of the GTV-N to the skin surface was 0.6 cm. The mean V70 of PTV70-N for the 5 patients showed an absolute advantage of 10.8% (92.4% vs. 81.6%) for the plan with bolus while the V66.5 of PTV70-N had an advantage of 8.1% (97.0% vs. 88.9%). The mean V65.1 also had an advantage of 7.1% (97.6% vs. 90.5%). The mean surface dose for the PTV70-N was also much higher at 61.1 Gy for the plans with bolus compared to only 23.5 Gy for the plans without bolus. Conclusion: Neck node bolus technique should be strongly considered in the treatment of NPC with enlarged lymph nodes treated with IMRT. It yields a superior dosimetry compared t o non-bolus plans with acceptable skin toxicity. -
Liu, Zhe;Wang, Liang;Zhang, Li-Na;Wang, Yue;Yue, Wen-Tao;Li, Qi 6139
Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment. -
Xie, Zi-Jun;Chen, Gang;Zhang, Xu-Chao;Li, Dong-Feng;Huang, Jian;Li, Zi-Jun 6145
Objective: To identify whether saliva supernatant miR-21 can serve as a novel potential biomarker in patients with esophageal cancer (EC). Methods: 32 patients with EC and 16 healthy controls were recruited in this study. Total RNA was extracted from saliva supernatant samples for measurement of miR-21 levels using RT-qPCR and relationships between miR-21 levels and clinical characteristics of EC patients were analyzed. Results: miR-21 was significantly higher in the EC than control groups. The sensitivity and specificity were 84.4% and 62.5% respectively. Supernatant miR-21 levels showed no significant correlation with cancer stage, differentiation and nodal metastasis. Conclusions: Saliva supernatant miR-21 may be a novel biomarker for EC. -
Kos, F. Tugba;Civelek, Burak;Seker, M. Metin;Arik, Zafer;Aksoy, Sercan;Uncu, Dogan;Ozdemir, Nuriye;Zengin, Nurullah 6151
Background: An association between the ABO groups and pancreatic cancer has been shown previously, group A being significantly commoner in affected patients. We conducted the present study to investigate the prognostic effect of ABO blood group on overall survival of pancreas cancer patients. Methods: Patients who were diagnosed between 2005 and 2010 with pancreas cancer at Ankara Numune Education and Research Hospital were analyzed retrospectively. Patient demographics and ABO blood groups were obtained from medical charts. Results: Fifty pancreas cancer patients with known ABO blood group were included, 26 (52%) group A, 12 patients (24%) group 0, 9 (18%) group B, and 3 (6%) group AB. Blood group A pancreas cancer patient median age was 61.5 (39-80) years, with the median age of the other blood groups (B, AB,O) being 55.5 (32-74) years (p=0.14). 18% of patients with blood group A and 11% of the other blood group patients had metastasis (p=0.17) at the time of diagnosis. The median overall survival of blood group A pancreas patients was significantly lower than the other blood group patients, 7.6 (95%CI: 5.0-10.2) months versus 29.0 (95%CI: 0.0-68.8) months (p=0.05). Conclusions: Acccording to previously published cohort studies a relation may exist between ABO blood groups and cancer of pancreas. In this study we observed that pancreas cancer patients with blood group A have significantly worse overall survival than other blood groups. -
Common Docking Domain Mutation E322K of the ERK2 Gene is Infrequent in Oral Squamous Cell CarcinomasValiathan, Gopalakrishnan Mohan;Thenumgal, Siji Jacob;Jayaraman, Bhaskar;Palaniyandi, Arunmozhi;Ramkumar, Hemalatha;Jayakumar, Keerthivasan;Bhaskaran, Sajeev;Ramanathan, Arvind 6155
Background: Mutations in the MAPK (Mitogen Activated Protein Kinase) signaling pathway - EGFR/Ras/RAF/MEK have been associated with the development of several carcinomas. ERK2, a downstream target of the MAPK pathway and a founding member of the MAPK family is activated by cellular signals emanating at the cell membrane. Activated ERK2 translocates into the nucleus to transactivate genes that promote cell proliferation. MKP - a dual specific phosphatase - interacts with activated ERK2 via the common docking (CD) domain of the later to inactivate (dephosphorylate) and effectively terminate further cell proliferation. A constitutively active form of ERK2 carrying a single point mutation - E322K in its CD domain, was earlier reported by our laboratory. In the present study, we investigated the prevalence of this CD domain E322K mutation in 88 well differentiated OSCC tissue samples. Materials and Method: Genomic DNA specimens isolated from 88 oral squamous cell carcinoma tissue samples were amplified with primers flanking the CD domain of the ERK2 gene. Subsequently, PCR amplicons were gel purified and subjected to direct sequencing to screen for mutations. Results: Direct sequencing of eighty eight OSCC samples identified an E322K CD domain mutation in only one (1.1%) OSCC sample. Conclusions: Our result indicates that mutation in the CD domain of ERK2 is rare in OSCC patients, which suggests the role of genetic alterations in other mitogenic genes in the development of carcinoma in the rest of the patients. Nevertheless, the finding is clinically significant, as the relatively rare prevalence of the E322K mutation in OSCC suggests that ERK2, being a common end point signal in the multi-hierarchical mitogen activated signaling pathway may be explored as a viable drug target in the treatment of OSCC. -
Donmez, Yelda Candan;Dolgun, Eda;Yavuz, Meryem 6159
This cross-sectional and descriptive study was aimed to evaluate women breast self-examination (BSE) practice and effects of a planned educational programme for breast cancer and BSE. The samples of the study consisted 266 women. The study data were collected by a questionnaire in six months periods as two times in a month in which the periods were defined and announced to all women. After that all the women were informed about BSE. The statue of performing BSE of women (n=146) was evaluated. They were interviewed on phone after 6 months. The collected data were analyzed by using statistical SPSS program. The average age of women was$35.68{\pm}7.54$ . It is also determined that (61.3%) had no knowledge about BSE, (87.6%) had examined clinical breast examination (CBE) in a year and half of them (50.8%) never practiced BSE, (29.0%) had BSE regularly every month. Concerning the status of BSE practice before the education and after the education significant difference is found statistically (p<0.00). The significance of this study is that it is to give education about breast cancer and BSE for raising awareness among women. -
Seo, Hee Jung;Oh, In-Hwan;Yoon, Seok-Jun 6163
Although much health services research has been conducted using national health insurance claims data in Korea, the validity of this method has not been ascertained. The objective of this study was to validate the use of claims data for health services research by comparing incidence rate of cancers found using insurance claims data against rates of the national cancer registry of Korea. An algorithm to estimate incidence rates using claims data was developed and applied. The claims data from 2005-2008 were acquired and the patients admitted to hospitals due to cancer in 2008 without admission to hospital from 2005-2007 by the same diagnosis code were regarded as incident cases. The acquired results were compared with the values from the National Cancer Registry of Korea. The incidence rate of all cancers found using claims data was 363.1 per 100,000 people, which is very similar to the 361.9 per 100,000 rate of the national cancer registry. Also the age-, gender- and disease-specific rates between the two data sources were similar. Therefore, national health insurance claims data may be a worthwhile resource for health services research if appropriate algorithms are applied, especially considering the cost effectiveness of this method. -
Ghojazadeh, Morteza;Naghavi-Behzad, Mohammad;Azar, Zahra Fardi;Saleh, Parviz;Ghorashi, Sona;Pouri, Ali-Asghar 6169
Infection by human papillomavirus (HPV) is one of common sexually transmitted diseases leading to cervical cancer. Evaluation of parental knowledge and attitudes toward HPV were aims of present study to provide an appropriate method to decrease burden of this infection on society. During this study, 358 parents were assessed for knowledge about HPV and its related disorders. Some 76% of parents had no information about HPV infection and among the informed parents 36% had obtained their information via internet and others from studying medical resources. The average score of mothers information about HPV infection was higher than that of fathers, and also educational level and age had significant impact on knowledge of parents about HPV. Parent knowledge about the hazards of HPV was higher than their knowledge about modes of transmission. Lack of awareness about HPV infection was high in this study, underlining the urgency of education among all adult people in our society. -
Songserm, Nopparat;Promthet, Supannee;Wiangnon, Surapon;Sithithaworn, Paiboon 6175
Intestinal parasitic infections (IPIs) are still important to the health of Thai rural residents. IPIs are the cause of many chronic diseases with, for example, opisthorchiasis resulting in progression to cholangiocarcinoma (CCA). This cross-sectional study in a prospective cohort study aimed to examine the prevalence and co-infection of intestinal parasites among Northeastern Thai rural residents, recruited into the Khon Kaen Cohort Study (KKCS), and who were residing in areas of high-risk for developing CCA. On recruitment, subjects had completed questionnaires and provided fecal samples for IPI testing using the formalin ethyl acetate concentration technique. Data on selected general characteristics and the results of the fecal tests were analysed. IPI test results were available for 18,900 of cohort subjects, and 38.50% were found to be positive for one or more types of intestinal parasite. The prevalence of Opisthorchis viverrini (O. viverrini) infection was the highest (45.7%), followed by intestinal flukes (31.9%), intestinal nematodes (17.7%), intestinal protozoa (3.02%), and intestinal cestodes (1.69%). The pattern of different infections was similar in all age groups. According to a mapping analysis, a higher CCA burden was correlated with a higher prevalence of O. viverrini and intestinal flukes and a greater intensity of O. viverrini. Both prevention and control programs against liver fluke and other intestinal parasites are needed and should be delivered simultaneously. We can anticipate that the design of future control and prevention programmes will accommodate a more community-orientated and participatory approach. -
Derici, Serhan;Sevinc, Ali;Harmancioglu, Omer;Saydam, Serdar;Kocdor, Mehmet;Aksoy, Suleyman;Egeli, Tufan;Canda, Tulay;Ellidokuz, Hulya;Derici, Solen 6181
Background: The aim of the study was to evaluate the available breast nomograms (MSKCC, Stanford, Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine variables for NSLNM in SLN positive breast cancer patients in our population. Materials and Methods: We retrospectively reviewed 170 patients who underwent completion axillary lymph node dissection between Jul 2008 and Aug 2010 in our hospital. We validated three nomograms (MSKCC, Stanford, Tenon). The likelihood of having positive NSLNM based on various factors was evaluated by use of univariate analysis. Stepwise multivariate analysis was applied to estimate a predictive model for NSLNM. Four factors were found to contribute significantly to the logistic regression model, allowing design of a new formula to predict non-sentinel lymph node metastasis. The AUCs of the ROCs were used to describe the performance of the diagnostic value of MSKCC, Stanford, Tenon nomograms and our new nomogram. Results: After stepwise multiple logistic regression analysis, multifocality, proportion of positive SLN to total SLN, LVI, SLN extracapsular extention were found to be statistically significant. AUC results were MSKCC: 0.713/Tenon: 0.671/Stanford: 0.534/DEU: 0.814. Conclusions: The MSKCC nomogram proved to be a good discriminator of NSLN metastasis in SLN positive BC patients for our population. Stanford and Tenon nomograms were not as predictive of NSLN metastasis. Our newly created formula was the best prediction tool for discriminate of NSLN metastasis in SLN positive BC patients for our population. We recommend that nomograms be validated before use in specific populations, and more than one validated nomogram may be used together while consulting patients. -
We aimed to investigate DNA repair gene expression of response to chemotherapy among gastric patients, and roles in the prognosis of gastric cancer. A total of 209 gastric cancer patients were included in this study between January 2007 and December 2008, all treated with chemotherapy. Polymorphisms were detected by real time PCR with TaqMan probes, and genomic DNA was extracted from peripheral blood samples. The overall response rate was 61.2%. The median progression and overall survivals were 8.5 and 18.7 months, respectively. A significant increased treatment response was found among patients with XPG C/T+T/T or XRCC1 399G/A+A/A genotypes, with the OR (95% CI) of 2.14 (1.15-4.01) and 1.75 (1.04-3.35) respectively. We found XPG C/T+T/T and XRCC1 399 G/A+A/A were associated with a longer survival among gastric cancer patients when compared with their wide type genotypes, with HRs and 95% CIs of 0.49 (0.27-0.89) and 0.56 (0.29-0.98) respectively. Selecting specific chemotherapy based on pretreatment genotyping may be an innovative strategy for further studies.
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Liu, Jun;Cai, Shi-Zhong;Zhou, Yue;Zhang, Xian-Ping;Liu, Dian-Feng;Jiang, Rong;Wang, Ya-Ping 6191
Aims and Background: Traditional chemotherapy strategies for human leukemia commonly use drugs based on cytotoxicity to eradicate cancer cells. One predicament is that substantial damage to normal tissues is likely to occur in the course of standard treatments. Obviously, it is urgent to explore therapies that can effectively eliminate malignant cells without affecting normal cells. Our previous studies indicated that ginsenoside$Rg_1$ ($Rg_1$ ), a major active pharmacological ingredient of ginseng, could delay normal hematopoietic stem cell senescence. However, whether$Rg_1$ can induce cancer cell senescence is still unclear. Methods: In the current study, human leukemia K562 cells were subjected to$Rg_1$ exposure. The optimal drug concentration and duration with K562 cells was obtained by MTT colorimetric test. Effects of$Rg_1$ on cell cycle were analyzed using flow cytometry and by SA-${\beta}$ -Gal staining. Colony-forming ability was measured by colony-assay. Telomere lengths were assessed by Southern blotting and expression of senescence-associated proteins P21, P16 and RB by Western blotting. Ultrastructural morphology changes were observed by transmission electron microscopy. Results: K562 cells demonstrated a maximum proliferation inhibition rate with an$Rg_1$ concentration of$20{\mu}\;mol{\cdot}L^{-1}$ for 48h, the cells exhibiting dramatic morphological alterations including an enlarged and flat cellular morphology, larger mitochondria and increased number of lysosomes. Senescence associated-${\beta}$ -galactosidase (SA-${\beta}$ -Gal) activity was increased. K562 cells also had decreased ability for colony formation, and shortened telomere length as well as reduction of proliferating potential and arrestin$G_2$ /M phase after$Rg_1$ interaction. The senescence associated proteins P21, P16 and RB were significantly up-regulated. Conclusion: Ginsenoside$Rg_1$ can induce a state of senescence in human leukemia K562 cells, which is associated with p21-Rb and p16-Rb pathways. -
Yuan, Jun-Bin;Yang, Luo-Yan;Tang, Zheng-Yan;Zu, Xiong-Bing;Qi, Lin 6197
Although enhancer of zeste homolog 2 (EZH2) has been reported as an independent prognostic factor in renal cell carcinoma (RCC), little is known about the exact mechanism of EZH2 in promoting the genesis of RCC. However, several studies have shown that dysregulation of the Wnt/${\beta}$ -catenin signaling pathway plays a crucial role. Therefore, we determined whether EZH2 could affect ACHN human RCC cell proliferation and invasion via the Wnt/${\beta}$ -catenin pathway. In the present study, we investigated the effects of short interfering RNA (siRNA)-mediated EZH2 gene silencing on Wnt/${\beta}$ -catenin signaling in ACHN cells. EZH2-siRNA markedly inhibited the proliferation and invasion capabilities of ACHN, while also reducing the expression of EZH2, Wnt3a and${\beta}$ -catenin. In contrast, cellular expression of GSK-$3{\beta}$ (glycogen synthase kinase-$3{\beta}$ ), an inhibitor of the Wnt/${\beta}$ -catenin pathway, was conspicuously higher after transfection of EZH2 siRNA. These preliminary findings suggest EZH2 may promote proliferation and invasion of ACHN cells via action on the Wnt/${\beta}$ -catenin signaling pathway. -
Ingkapairoj, Navakorn;Luanratanakorn, Sanguanchoke;Chumworathayi, Bandit;Kietpeerakool, Chumnan;Supoken, Amornrat 6203
The aim of this study was to evaluate the outcomes of women with high-grade squamous intraepithelial lesion (HSIL) smears who had undergone the "see and treat" approach compared to those who underwent a conventional approach. The records of women with HSIL smears undergoing colposcopy at Srinagarind Hospital were reviewed. In those undergoing the conventional approach, the final histological diagnosis was made on the most severe histological results obtained after initial colposcopy. In the "see and treat" group, the final histological diagnosis was made on the examination of LEEP specimens obtained after initial colposcopy. Overtreatment in the see and treat group was defined as the LEEP specimens containing cervical intraepithelial neoplasia (CIN) 1 or less. During the study period, 302 women with HSIL underwent colposcopy. Twenty (6.6%) were nulliparous. One hundred and ninety-four (64.2%) underwent conventional management while the remaining 108 (35.8%) received the see and treat management. The prevalence of underlying high-grade lesions in women undergoing the conventional approach was significantly higher than that observed among women undergoing the see and treat approach (89.2% and 47.2%, respectively, P<0.001). The overtreatment rate in the see and treat group was 52.8%. Multivariate analysis revealed that only parity status was a statistically significant factor for predicting the overtreatment after undergoing the see and treat approach. In conclusion, the overtreatment rate among women undergoing see and treat in this study is notably high and therefore this approach should not be routinely practiced. -
Introduction: Although a number of studies were published in the past several years on associations between hsa-mir-27a and cancer risk, the findings remain conflicting rather than conclusive. To derive a more precise effect on the association between SNP hsa-mir-27a rs895819 and breast cancer risk, we conducted a meta-analysis for the first time. Materials and Methods: Through retrieval from PubMed for the period up to August 2012, a total of four studies were identified with 3,287 cases and 4,298 controls for SNP hsa-mir-27a rs895819. We calculated summary odds ratio (ORs) and corresponding 95% confidence intervals (CIs) using a fixed effects model (when the heterogeneity was absent, P>0.10). Otherwise, the random-effects model was used. Results: We found that hsa-mir-27a rs895819 polymorphism also did not reveal any relationship with breast cancer susceptibility (AG versus AA: OR = 0.98; 95%CI, 0.73-1.32; GG versus AA: OR = 0.86; 95% CI, 0.72-1.03; AG/GG versus AA: OR = 0.92; 95% CI, 0.74-1.14), while significantly decreased risk was found among Europeans in AG versus AA and AG/GG versus AA models tested (AG versus AA: OR = 0.83; 95%CI, 0.72-0.97; GG versus AA: OR = 0.86; 95% CI, 0.71-1.05; AG/GG versus AA: OR = 0.84; 95% CI, 0.75-0.94). Conclusion: These findings suggest that hsa-mir-27a rs895819 polymorphism may play an important role in breast cancer development.
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Luo, Guo-Xuan;Cai, Jun;Lin, Jing-Zhi;Luo, Wei-Shi;Luo, Heng-Shan;Jiang, Yu-Yang;Zhang, Yong 6211
Objective: To investigate the effects of gambogic acid (GA) on the growth of human malignant glioma cells. Methods: U251MG and U87MG human glioma cell lines were treated with GA and growth and proliferation were investigated by MTT and colony formation assays. Cell apoptosis was analyzed by annexin V FITC/PI flow cytometry, mitochondrial membrane potential assays and DAPI nuclear staining. Monodansylcadaverine (MDC) staining and GFP-LC3 localisation were used to detect autophagy. Western blotting was used to investigate the molecular changes that occurred in the course of GA treatment. Results: GA treatment significantly suppressed cell proliferation and colony formation, induced apoptosis in U251 and U87MG glioblastoma cells in a time- and dose-dependent manner. GA treatment also lead to the accumulation of monodansylcadaverine (MDC) in autophagic vacuoles, upregulated expressions of Atg5, Beclin 1 and LC3-II, and the increase of punctate fluorescent signals in glioblastoma cells pre-transfected with GFP-tagged LC3 plasmid. After the combination treatment of autophagy inhitors and GA, GA mediated growth inhibition and apoptotic cell death was further potentiated. Conclusion: Our results suggested that autophagic responses play roles as a self-protective mechanism in GA-treated glioblastoma cells, and autophagy inhibition could be a novel adjunctive strategy for enhancing chemotherapeutic effect of GA as an anti-malignant glioma agent. -
Shi, Hai-Zhou;Ren, Peng;Lu, Qing-Jun;Niedrgethmnn, Marco;Wu, Guo-Yang 6217
Introduction: Up to present, EGF$61^*A$ /G, TGF-${\beta}1$ -$509^*T$ /C and TNF-${\alpha}$ -$308^*A$ /G gene polymorphisms have been analysed in other cancer entities than hepatocellular carcinoma (HCC). We here investigated the frequency of these gene polymorphisms among HCC patients. Materials and Methods: A total of 73 HCC patients and 117 cancer-free healthy people were recruited at the Surgical Department of Zhongshan Hospital. Genomic DNA was isolated from peripheral blood and gene polymorphisms were analyzed by PCR-RFLP. Results: The distribution of EGF$61^*G$ /G homozygotes among HCC patients was more frequent than that in the control group (24.7% vs 11.1%, OR=2.618, 95%CI=1.195-5.738). In parallel, the frequency of the "G" allele in the HCC patient group was also higher than that in the control group (45.9% vs 33.3%, OR= 1.696, 95%CI=1.110-2.592). No difference could be found for the TGF-${\beta}1$ -509 and TNF-${\alpha}$ -308 genotypes. Conclusion: EGF$61^*G$ /G genotype and G allele are significantly increased among patients with HCC. TGF-${\beta}1$ -$509^*T$ /C and TNF-${\alpha}$ -$308^*A$ /G gene polymorphisms are not related to this cancer entity. -
Karaca, Halit;Deniz, Kemal;Berk, Veli;Inanc, Mevlude;Ozkan, Metin 6221
Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients, and to explore the relationship between clinicopathological prognostic factors and their effects on survival, based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials and Methods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvant FOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data were analyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and 59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+ was in 13 (16%). FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showed positivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expression and age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, or pTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There was also no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2 expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascular and perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymph node involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a more comprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach. -
Wang, Jia-Yi;Zhou, Yu-Qiao;Li, Xiao-Xu;Jin, Xin;Wang, Li-Li;Lei, Lei;Zhou, Yu;Lu, Jiang;Zeng, Xin;Dan, Hong-Xia;Liao, Ga;Chen, Qian-Ming 6227
Interleukin-4 receptor (IL-4R) gene single nucleotide polymorphisms (SNPs) are implicated in cancer development. However, results from the published reports have remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in IL-4R gene and cancer risk. Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched for case-control studies published up to October 30, 2012 that investigated IL-4R polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of any associations. Three IL-4R polymorphisms (Q576R, rs1801275; I75V, rs1805010; S503P, rs1805015) in 21 case-control studies were analyzed. Our meta-analysis indicated that these three polymorphisms are not associated with cancer risk when all studies were pooled together. In the subgroup analysis by tumor site, the results showed that Q576R G allele carriers were associated with a significantly decreased cervical cancer risk (recessive model: OR = 0.77, 95%CI = 0.60-0.98; homozygote comparison: OR = 0.76, 95%CI = 0.58-0.98). I75V G allele carriers were associated with a decreased risk of renal cancer (dominant model = 0.71, 95%CI = 0.57-0.89, heterozygote comparison: OR = 0.69, 95%CI = 0.55-0.87). When stratified by ethnicity, Q576R G allele carriers were associated with a decreased cancer risk in Caucasians (dominant model: OR = 0.90, 95%CI = 0.83-0.98; heterozygote comparison: OR = 0.89, 95%CI = 0.82-0.98). I75V G allele carriers were associated with a decreased cancer risk in Asians (heterozygote comparison: OR = 0.76, 95%CI = 0.62-0.94). S503P C allele carriers were also associated with a decreased cancer risk in Asians (CC VS TT: OR = 0.29, 95%CI = 0.08-0.99). Our results suggest that Q576R, I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specific ethnic groups. Future case-control studies with large sample size are needed to evaluate these associations in detail. -
Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, both inhibits apoptosis and regulates the cell cycle. It is overexpressed in breast tumor tissues. In this study, we designed two survivin specific DNAzymes (DRz1 and DRz2) targeting survivin mRNA. The results showed that DRz1 could decrease the expression of survivin by nearly 60%. Furthermore, DRz1 significantly inhibited cell proliferation, induced apoptosis and inhibited migration in MCF-7 cells. In addition, down-regulation of survivin expression was associated with increased caspase-3 and -9 activities in MCF-7 cells after 24 h transfection. In our experiments, the efficacy of DRz1 to influence survivin levels and associated effects were better than DRz2. Survivin-DRz1 might have anti-tumorigenic activity and may potentially provide the basis for a novel therapeutic intervention in breast cancer treatment.
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Moad, Ahmed Ismail Hassan;Tan, Mei Lan;Kaur, Gurjeet;Mabruk, Mohamed 6239
Background: The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest.$p15^{INK4b}$ is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of$p15^{INK4b}$ protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of$p15^{INK4b}$ expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that$p15^{INK4b}$ could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate$p15^{INK4b}$ protein expression in BCCs. Materials and Method: Protein expression of$p15^{INK4b}$ in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach. Results: The expression of$p15^{INK4b}$ was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and$p15^{INK4b}$ protein expression. Conclusions: Our finding may indicate that$p15^{INK4b}$ protein expression does not play a role in the genesis of BCC. -
Lalitha, Krishnappa;Suman, Gadicherla;Pruthvish, Sreekantaiah;Mathew, Aleyamma;Murthy, Nandagudi S. 6245
Background: With increase in life expectancy, adoption of newer lifestyles and screening using prostate specific antigen (PSA), the incidence of prostate cancer is on rise. Globally prostate cancer is the second most frequently diagnosed cancer and sixth leading cause of cancer death in men. The present communication makes an attempt to analyze the time trends in incidence for different age groups of the Indian population reported in different Indian registries using relative difference and regression approaches. Materials and Methods: The data published in Cancer Incidence in Five Continents for various Indian registries for different periods and/or publications by the individual registries served as the source materials. Trends were estimated by computing the mean annual percentage change (MAPC) in the incidence rates using the relative difference between two time periods (latest and oldest) and also by estimation of annual percentage change (EAPC) by the Poisson regression model. Results: Age adjusted incidence rates (AAR) of prostate cancer for the period 2005-2008 ranged from 0.8 (Manipur state excluding Imphal west) to 10.9 (Delhi) per$10^5$ person-years. Age specific incidence rates (ASIR) increased in all PBCRs especially after 55 years showing a peak incidence at +65 years clearly indicating that prostate cancer is a cancer of the elderly. MAPC in crude incidence rate(CR) ranged from 0.14 (Ahmedabad) to 8.6 (Chennai). Chennai also recorded the highest MAPC of 5.66 in ASIR in the age group of 65+. Estimated annual percentage change (EAPC) in the AAR ranged from 0.8 to 5.8 among the three registries. Increase in trend was seen in the 55-64 year age group cohort in many registries and in the 35-44 age group in Metropolitan cities such as Delhi and Mumbai. Conclusions: Several Indian registries have revealed an increasing trend in the incidence of prostate cancer and the mean annual percentage change has ranged from 0.14-8.6. -
Radiation proctitis and radiation cystitis are major complications for patients with cervical carcinoma following radiotherapy. In the present study, we aimed to determine the potential risk factors for the development of radiation proctitis and radiation cystitis after irradiation. A total of 1,518 patients with cervical carcinoma received external beam radiotherapy (EBRT) followed by high-dose-rate intracavitary brachytherapy (HDRICB) in our hospital. The incidences of radiation proctitis and radiation cystitis were recorded and associations with different factors (age, time period, tumor stage) were analyzed with
${\chi}^2$ (chi-squared) and Fisher exact tests. We found that 161 and 94 patients with cervical carcinoma were diagnosed with radiation proctitis and radiation cystitis, respectively, following radiotherapy. The prevalence of Grade I-II radiation proctitis or radiation cystitis was significantly lower than that of Grade III (radiation proctitis: 3.82% vs. 6.76%, P < 0.05; radiation cystitis: 2.31% vs. 3.87%, P < 0.05) and was significantly enhanced in patients with late stage (IIIb) tumor progression compared to those in early stage (Ib, IIa) (P < 0.05). Moreover, the incidence of radiation proctitis and cystitis was not correlated with age or, time period following radiation, for each patient (P > 0.05). These observations indicate that a late stage of tumor progression is a potential risk factor for the incidence of radiation proctitis and cystitis in cervical carcinoma patients receiving radiotherapy. -
Cui, Lin;Liu, Xing-Xiang;Jiang, Yong;Wu, Xing-Jun;Liu, Jian-Jun;Zhou, Xiang-Rong;He, Xue-Jun;Huang, Xin-En 6257
Objective: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). Methods: Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. Results: Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). Conclusions: The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases. -
Background: Glutathione-S-transferase (GST) is an important phase II xenobiotic compound metabolizing enzyme family, involved in tolerance to a particular drug or susceptibility to a diseasec. This study focused the GSTM1 and T1 null allele frequency in the Gujarat population with a comparison across other Inter- and Intra-Indian ethnic groups to predict variation in the possible susceptible status. Methods: DNA was isolated by a salting out method and GSTM1 and T1 homozygous null genotypes were detected by multiplex polymerase chain reaction in 504 unrelated individuals. The genotype distribution of null alleles was compared with Indian and non Indian ethnics reported earlier in the literature using Fisher's test. Results: The frequencies of the homozygous null genotypes of GSTM1 and GSTT1 were 20% (95%CI 16.7-23.9) and 35.5% (95%CI 31.4-39.9) respectively. GSTM1 null frequency did not deviate from most other Indian ethnic groups but differed from the majority of those of non Indian ethnicity studied. The frequency of homozygous null type of GSTT1 was significantly higher and deviated from all Indian groups and a few of non Indian ethnicity. Conclusions: Gujarat ethnicity, possibly the most susceptible for GSTT1 dependent drug disposition and diseases regarding effects of pollution. Further, the results have implications for GSTT1 dependent drugs used for treatment, a serious problem which needs to be solved by physicians and clinical researchers.
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Yang, Wan-Guang;Zhang, Shan-Feng;Chen, Ju-Wu;Li, Li;Wang, Wan-Peng;Zhang, Xie-Fu 6269
We conducted a case-control study to determine the association between several potential SNPs of excision repair cross complementing group 5 (XPG) and gastric cancer susceptibility, and roles of XPG polymorphisms in combination with H.pylori infection in determining risk of gastric cancer. In our study, we collected 337 newly diagnosed gastric cancer cases and 347 health controls. Three SNPs of XPG, rs2296147T>C, rs2094258C>T and rs873601G>A, were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detector system. H. pylori infection was diagnosed by ELISA. By multivariate logistic regression analysis, the rs2296147 CC genotype was associated with a decreased risk of gastric cancer (OR=0.52, 95% CI=0.27-0.97), and rs2094258 TT was associated with elevated risk (OR=2.13, 95% CI=1.22-3.35). Positive H.pylori individuals with rs2094258 TT genotypes demonstrated increased risk of gastric cancer (OR=2.13, 95% CI=1.22-3.35), while rs2296147 CC was associated with lower risk among patients with negative H.pylori (OR=0.45, 95%CI=0.22-0.89). Our findings suggested that XPG polymorphisms might contribute to risk of gastric cancer among Chinese populations, but the effect needs to be further validated by larger sample size studies. -
Zhang, Yu-Rong;Xu, Yong;Yang, Kuo;Liu, Ming;Wei, Dong;Zhang, Yao-Guang;Shi, Xiao-Hong;Wang, Jian-Ye;Yang, Fan;Wang, Xin;Liang, Si-Ying;Zhao, Cheng-Xiao;Wang, Fei;Chen, Xin;Sun, Liang;Zhu, Xiao-Quan;Zhu, Ling;Yang, Yi-Ge;Tang, Lei;Jiao, Hai-Yan;Huo, Zheng-Hao;Yang, Ze 6273
Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa. -
Mansour-Ghanaei, Fariborz;Heidarzadeh, Abtin;Naghipour, Mohammad Reza;Joukar, Farahnaz;Valeshabad, Ali Kord;Fallah, Mohammad-Sadegh;Rezvani, Seyed Mahmoud;Sedigh-Rahimabadi, Massih;Rokhshad, Hasan;Dadashi, Arsalan 6277
Background: Northern Iran counts as one of the highest prevalence regions for esophageal cancer (EC) worldwide. This study was designed to assess the epidemiologic aspects of EC in north central and northwest Iran over a 10 year period. Materials and Methods: The Guilan cancer registry study (GCRS) is a population-based cancer registry study featuring retrospective (1996-2003) and prospective (2004-2005) phases. A detailed questionnaire based on WHO standards for cancer registratration was applied to gather the required information. Two trained physicians coded information using ICD-O-3 in close coordination with an expert pathologist. Results: A total of 19,936 cases of malignancy (mean age$55.4{\pm}18.0$ years, range: 1-98 years) were registered, including 1,147 cases (670 males, 447 female; mean age:$64.0{\pm}11.5$ years) of EC. In 1996 the male/female ratio among patients with EC was 1.25 which increased to 1.53 in 2005. The lower third of the esophagus still remained the most common site of tumors. The average age-standardized rate (ASR) was 6.9 and 4.1 per$10^5$ men and women, respectively. In 1996, the ASRs were 7.2 and 5.2 per$10^5$ men and women which decreased to 6.9 and 4.1 per$10^5$ in 2004-2005. Squamous cell carcinoma (SCC) was the most prevalent histological subtype of EC accounting over 80% of cases. Conclusions: However the prevalence of adenocarcinoma (ADC) showed an increase to 18.4%. Guilan province may be considered a relatively low incidence region for EC. -
Background: The aim of this study was to outline the trend in the incidence of colorectal cancer (CRC) in the city of Jeddah, Kingdom of Saudi Arabia (KSA), for comparison with previously published national CRC data. Materials and Methods: A retrospective data analysis was performed on all cases of CRC diagnosed between January 2000 and December 2006 amongst Saudi patients in Jeddah using data retrieved from the Saudi Cancer Registry (SCR). Descriptive analysis was performed and results were compared to national CRC data from the SCR. Results: In Jeddah, 644 cases of CRC were diagnosed during the time period, accounting for 15% of all CRC cases in KSA. Males were more commonly affected than females (58% versus 42%). The male preponderance of CRC was similar to that observed at a national level. In Jeddah, the incidence was higher among those >45 years (77.0%), and the mean age at diagnosis was 57 years. At diagnosis, 10% of patients presented with localized disease; 25% presented with distant metastasis and the remaining patients had various stages of regional extension. Adenocarcinomas accounted for 72% of cases. Statistical analysis did not reveal any clinically significant differences between cases diagnosed in Jeddah and those diagnosed throughout KSA. Conclusions: The increased trend in the incidence of CRC in Jeddah between 2000 and 2006 mirrors the recent trend in KSA. This highlights the magnitude of this healthcare hazard, not only in Jeddah, but also across the country and supports the need for preventive measures and early detection of the disease.
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Ainuddin, Husna A.;Loh, Siew Yim;Low, Wah Yun;Sapihis, Musaropah;Roslani, April Camilla 6289
Background: Research evidence suggests a debilitating impact of the diagnosis of cancer on the quality of life of the afflicted individuals, their spouses and their families. However, relatively few studies have been carried out on the impact on the QOL of adolescents living with parents diagnosed with cancer. This paper presents a sub-analysis on the impact of parental cancer (colorectal, breast and lung) on adolescents. Materials and Methods: This is a cross-sectional study on adolescents aged 13-18 years old. Upon ethical clearance obtained from UMMC Medical Ethics Committee, patients with colorectal, breast or lung cancer and their adolescent children were recruited from the Clinical Oncology Unit of University of Malaya Medical Centre. Respondents who gave consent completed a demographic questionnaire and the Pediatric Quality of Life Inventory, via the post, email, home visit or meetings at the clinics. Results: 95 adolescents from 50 families responded, giving a response rate of 88 percent. The adolescent's mean age was 16 years (ranging between 13-18 years). Adolescents with parental cancer had the lowest mean score in emotional functioning (p<0.05). Male adolescents had significantly higher quality of life overall and in physical functioning compared to female adolescents. Adolescents with a father with cancer had better school functioning compared to adolescents whose mothers had cancer. Families with household income of RM 5000 and above have significantly better quality of life compared to families with lower household income. Conclusions: Adolescent sons and daughters of parents with a cancer diagnosis show lowered QOL, particularly with reference to emotional functioning and school performance. Addressing the needs of this young group has been slow and warrants special attention. Revisiting the risk and resilience factors of adolescents might also inform tailored programs to address the needs of this neglected adolescent population. -
Gupta, Rakesh Kumar;Patel, Amit Kumar;Kumari, Rajni;Chugh, Seema;Shrivastav, Chitrangada;Mehra, Siddharth;Sharma, Ajay Narayan 6295
Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. The objective of this study was to determine changes in the levels of malondialdehyde (MDA), nitric oxide (NO), total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, total antioxidant capacity (TAC), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in serum samples of breast cancer patients (n=30) and healthy subjects (n=100). MDA and NO levels were found to be increased in breast cancer patients compared to the healthy subject group (p<0.05). Total cholesterol and triglycerides were elevated; and HDL-cholesterol level was found to be decreased in the cancer patients as compared to the healthy subjects (p<0.05). Compared to the healthy group, both serum TAC levels (p<0.001) and activity of SOD and GSH-Px (p=0.05) were found to be decreased in the breast cancer patients as compared to the healthy controls. Considering the data presented in this study, we suggest that free radicals induce lipid eroxidation and peroxidation of unsaturated fatty acid with decreased activity of enzymatic antioxidants in breast cancer. -
Mao, Ye-Qing;Xu, Xin;Lin, Yi-Wei;Chen, Hong;Hu, Zheng-Hui;Xu, Xiang-Lai;Zhu, Yi;Wu, Jian;Zheng, Xiang-Yi;Qin, Jie;Xie, Li-Ping 6299
Insulin-like growth factor-binding protein-3 (IGFBP3) has been identified as a putative tumor suppressor with multifunctional roles in the IGF axis. Recently, there have been a growing body of studies investigating the relation between the IGFBP3 A-202C polymorphism, circulating IGFBP3 and prostate cancer risk, but their outcomes varied leading to controversy. Hence, it is necessary to perform a meta-analysis covering all eligible studies to shed a light on the association of IGFBP3 A-202C and cancer risk. Finally, we included a total of 11 relevant articles between 2003 and 2010 covering 14 case-control studies including 9,238 cases and 8,741 controls for our analysis. Our results showed that A-202C was a marginal risk factor of prostate cancer (allele contrast: OR=1.08, 95% CI :1.01-1.16; dominant model: OR=1.11, 95% CI :1.01-1.22; heterozygote codominant model: OR=1.11, 95% CI :1.03-1.18; homozygote contrast: OR=1.19, 95% CI :1.03-1.37). Stratification analysis revealed that sample size and control source were two major heterogeneous meta-factors especially in the recessive model (source: Population-based control group :p=0.30,I2=16.7%, Hospital-based control group: p=0.20, I2=30.3%; sample size: Small: p=0.22,I2= 32.8%, Medium: p=0.09,I2=48%, Large p=0.60,I2=0.0%); However, contrary to previous findings, no significance was found in racial subgroups. No significant publication bias was found in our analysis. Considering the robustness of the results and the discrepancy among some studies, there might be some unsolved confounding factors, and further more critical large studies are needed for confirmation. -
Zheng, Ri-Nan;Li, Shu-Rong;Masahiro, Asaka 6305
Objectives: This study aimed to demonstrate the tyrosine phosphorylation motif (TPM) and 3' region structure of the Helicobacter pylori CagA gene as well as its SHP-2 binding activity in AGS cells and relation to gastric carcinogenesis. Methods: Sixteen clinical isolate H. pylori strains from eight duodenal ulcer and eight gastric adenocarcinoma patients were studied for CagA repeat sequence EPIYA motifs, C-terminal structure, and western blot analysis of CagA protein expression, translocation, and SHP-2 binding in AGS cells. Results: Except for strain 547, all strains from the gastric adenocarcinoma patients were positive for CagA by PCR and had three EPIYA copy motifs. Western blotting showed that all strains were positive for CagA protein expression (100%), CagA protein translocation (100%), and SHP-2 binding (100%). CagA protein expression was significantly higher in the gastric adenocarcinoma patients than in the duodenal ulcer patients (P=0.0023). CagA protein translocation and SHP-2 binding in the gastric adenocarcinoma patients were higher than those in the duodenal ulcer patients, but no significant differences were found between the two groups (P=0.59, P=0.21, respectively). Conclusions: The TPMs and 3' region structures of the H. pylori CagA gene in the duodenal ulcer and gastric adenocarcinoma patients have no significant differences. -
Panagiotou, Ioannis;Georgiannos, Stavros N.;Tsiambas, Evangelos;Karameris, Andreas;Konstantinou, Marios;Lazaris, Andreas C.;Kavantzas, Nikolaos;Vilaras, George;Patsouris, Efstratios 6311
Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC. -
Amid, Azura;Chik, Wan Dalila Wan;Jamal, Parveen;Hashim, Yumi Zuhanis Has-Yun 6319
We previously found cytotoxic effects of tomato leaf extract (TLE) on the MCF-7 breast cancer cell line. The aim of this study was to ascertain the molecular mechanisms associated with the usage of TLE as an anticancer agent by microarray analysis using mRNA from MCF-7 breast cancer cells after treatment with TLE for 1 hr and 48 hrs. Approximately 991 genes out of the 30,000 genes in the human genome were significantly (p<0.05) changed after the treatment. Within this gene set, 88 were significantly changed between the TLE treated cells and the untreated MCF-7 cells (control cells) with a cut-off fold change >2.00. In order to focus on genes that were involved in cancer cell growth, only twenty-nine genes were selected, either down-regulated or up-regulated after treatment with TLE. Microarray assay results were confirmed by analyzing 10 of the most up and down regulated genes related to cancer cells progression using real-time PCR. Treatment with TLE induced significant up-regulation in the expression of the CRYAB, PIM1, BTG1, CYR61, HIF1-${\alpha}$ and CEBP-${\beta}$ genes after 1 hr and 48 hrs, whereas the TXNIP and THBS1 genes were up-regulated after 1 hr of treatment but down-regulated after 48 hrs. In addition both the HMG1L1 and HIST2H3D genes were down-regulated after 1 hr and 48 hrs of treatment. These results demonstrate the potent activity of TLE as an anticancer agent. -
Wang, Shao-Kang;Yang, Lei;Wang, Ting-Ting;Huang, Gui-Ling;Yang, Li-Gang;Sun, Gui-Ju 6327
Esophageal cancer is a common malignant tumor occurring in human esophageal epithelial tissue. The primary purpose of this paper was to define the effects of${\beta}$ -carotene and 1,25-dihydroxyvitamin$D_3$ , alone and in combination, on cell proliferation, cell cycle and apoptosis of human esophageal cancer EC9706 cells. Treatment with different concentrations of${\beta}$ -carotene and/or 1,25-dihydroxyvitamin$D_3$ . MTT assay showed that${\beta}$ -carotene and 1,25-dihydroxyvitamin$D_3$ significantly inhibited proliferation of EC9706 cells in a dose- and time-dependent manner. Further studies also demonstrated that${\beta}$ -carotene alone or 1,25-dihydroxyvitamin$D_3$ alone caused a marked increase on the induction of apoptosis in EC9706 cells. The percentage of G0/G1-phase cells significantly increased on addition of 1,25-dihydroxyvitamin$D_3$ alone, but there were no significant changes with${\beta}$ -carotene alone. These two agents in combination synergistically inhibited cell growth and induced apoptosis. Therefore, our results indicate that${\beta}$ -carotene and 1,25-dihydroxyvitamin$D_3$ in combination may provide a novel strategy for preventing and treating esophageal cancer. -
Hussain, Mohammad Akhtar;Pati, Sanghamitra;Swain, Subhashisa;Prusty, Minakshi;Kadam, Sridhar;Nayak, Sukdev 6333
The burden of cancer is growing globally and is one of the top leading causes of death. Information on cancer patterns are essential for effective planning of cancer control interventions. There is limited published information available on pattern of cancer for the state of Odisha, India. The present study was an attempt to explore the pattern and trend of cancer in Odisha. To fulfill the objectives retrospective data available from 2001-2011 at Acharya Harihar Regional Cancer Center (AHRCC), Cuttack, Odisha, were analyzed. Medical records of cancer patients were reviewed and relevant information on diagnosis, primary site and demographic data were retrieved. Data were entered and analyzed using SPSS 16.0 (SPSS Inc.). A total of 74,861 cancer inpatients were registered at AHRCC for the years 2001-2011. The proportion of females outnumbered males with female:male ratio 1.1:1. The number of female cases increased four folds and that of males three fold over the period studied. Malignancies such as oral cancer (16.93%), acute lymphocytic leukemia/non Hodgkins lymphoma (14.09%) and cancer of gastrointestinal tract (21.07%) are leading cancers among males and carcinomas of breast (28.94%), cervix (23.66%) and ovary (16.11%) were leading among females. Findings from this study indicate an overall increase in cancer reporting which could be regarded as proxy measure for overall cancer situation in Odisha. There is scope and need for integrating other government hospitals, existing private health service providers and research institutions across the state for better planning of cancer control program. -
Loh, Siew Yim;Lee, Shing Yee;Quek, Kia Fatt;Murray, Liam 6337
Background: Clinical trials on cancer subjects have one of the highest dropout rates. Barriers to recruitment range from patient-related, through institutional-related to staff-related factors. This paper highlights the low response rate and the recruitment barriers faced in our Qigong exercises trial. Materials and Method: The Qigong trial is a three-arm trial with a priori power size of 114 patients for 80% power. The University Malaya Medical Centre database showed a total of 1,933 patients from 2006-2010 and 751 patients met our inclusion criteria. These patients were approached via telephone interview. 131 out of 197 patients attended the trial and the final response rate was 48% (n=95/197). Results: Multiple barriers were identified, and were regrouped as patient-related, clinician-related and/or institutional related. A major consistent barrier was logistic difficulty related to transportation and car parking at the Medical Centre. Conclusions: All clinical trials must pay considerable attention to the recruitment process and it should even be piloted to identify potential barriers and facilitators to reduce attrition rate in trials. -
Objective: The NAD(P)H:quinone oxidoreductase 1 (NQO1) rs1800566 polymorphism, leading to proline-toserine amino-acid and enzyme activity changes, has been implicated in bladder cancer risk, but individually published studies showed inconsistent results. We therefore here conducted a meta-analysis to summarize the possible association. Methods: A systematic literature search up to August 27, 2012 was carried out in PubMed, EMBASE and Wanfang databases, and the references of retrieved articles were screened. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed for homozygote contrast (TT vs. CC), additive model (T vs. C), dominant model (TT+CT vs. CC), and recessive model (TT vs. CC+CT) to assess the association using fixed- or random-effect models. Results: We identified 12 case-control studies including 3,041 cases and 3,128 controls for the present meta-analysis. Significant association between NQO1 rs1800566 genetic polymorphism and risk of bladder cancer was observed in the additive model (OR = 1.15, 95% CI = 1.01-1.30, p = 0.030). Moreover, in the subgroup analysis stratified by ethnicity, significant associations were observed in Asians (OR = 1.26, 95% CI = 1.08-1.47, p = 0.003 for T vs. C; OR = 1.68, 95% CI = 1.21-2.32, p = 0.002 for TT vs. CC; OR = 1.50, 95% CI = 1.13-1.98, p = 0.005 for TT vs. CT+CC) but not in Caucasians. Conclusions: The results suggest that NQO1 rs1800566 genetic polymorphism may contribute to bladder cancer development, especially in Asians.
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Zhu, Dai-Hua;Niu, Bai-Lin;Du, Hui-Min;Ren, Ke;Sun, Jian-Ming;Gong, Jian-Ping 6349
Previous studies showed that Math1 homologous to human Hath1 can cause mouse goblet cells to differentiate. In this context it is important that the majority of colon cancers have few goblet cells. In the present study, the potential role of Hath1 in colon carcinogenesis was investigated. Sections of paraffin-embedded tissues were used to investigate the goblet cell population of normal colon mucosa, mucosa adjacent colon cancer and colon cancer samples from 48 patients. Hath1 and Muc2 expression in these samples were tested by immunohistochemistry, quantitative real-time reverse transcription -PCR and Western blotting. After the recombinant plasmid, pcDNA3.1(+)-Hath1 had been transfected into HT29 colon cancer cells, three clones were selected randomly to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time reverse transcription-PCR and Western blotting. Moreover, the proliferative ability of HT29 cells introduced with Hath1 was assessed by means of colony formation assay and xenografting. Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected by Western blotting. No goblet cells were to be found in colon cancer and levels of Hath1 mRNA and Hath1, Muc2 mRNA and Muc2 were significantly down-regulated. Hath1 could decrease cyclin D1, increase p27 and Muc2 in HT29 cells and inhibit their proliferation. Hath1 may be an anti-oncogene in colon carcinogenesis. -
Khemapech, Nipon;Pitchaiprasert, Sunaree;Triratanachat, Surang 6357
Background: To determine the prevalence of mammalian target of rapamycin phosphorylation (p-mTOR) and vascular endothelial growth factor (VEGF) and any correlation with clinical characteristics and prognosis in ovarian clear cell carcinoma patients. Materials and Method: Seventy four paraffin-embedded specimens of such carcinomas frompatients who underwent surgery, received adjuvant chemotherapy and were followed up at King Chulalongkorn Memorial Hospital during January 2002 to December 2008 were stained with rabbit monoclonal IgG p-mTOR and rabbit polyclonal IgG VEGF using immunohistochemical methods. Medical records were reviewed and clinical variables were analysed. Results: The prevalence of positive p-mTOR in ovarian clear cell carcinoma was 87.9% and significantly higher in advance-stage than early-stage patients (100% versus 83.6%, P<0.05). Two-year disease free survival and 2-year overall survival in patients with positive p-mTOR expression were 60% and 69.2% with no differences from patients with negative p-mTOR expression (p>0.05). The prevalence of VEGF expression was 63.5% and significantly higher in chemo-sensitive than chemo-resistant patients (70.7% versus 37.5%, P<0.05). Two-year disease free survival and 2-year overall survival in patients with VEGF expression were 72.3% and 83% respectively which were significantly different from patients with negative VEGF expression (p<0.05). Conclusions: p-mTOR expression in ovarian clear cell carcinoma was significantly correlated with the stage of disease. VEGF expression was significantly correlated with chemosensitivity, and survival. Further studies of related targeted therapy might be promising. -
Objective: The study aim was to prepare poly-DL-lactide-poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase-1 (TIMP-1) in an adenovirus to investigate its inhibition on the proliferation of hepatocellular carcinoma cells HepG2. Methods: Microspheres were prepared by encapsulating the recombinant TIMP-1 adenovirus into biodegradable PELA. The particle size, viral load, encapsulation efficiency and in-vitro release were measured. Microspheres were used to infect HepG2 cells, then infection efficiency was examined under a fluorescent microscope and ultrastructural changes assessed by TEM. Expression of TIMP-1 mRNA in HepG2 cells was examined by semi-quantitative RT-PCR and proliferation by MTT and cell growth curve assays. Results: We successfully prepared microspheres encapsulating recombinant TIMP-1 adenovirus with a diameter of
$1.965{\mu}m$ , an encapsulation efficiency of 60.0%, a viral load of$10.5{\times}10^8/mg$ and approximate 60% of virus release within 120 h, the total releasing time of which was longer than 240 h. The microspheres were confirmed to be non-toxic with blank microspheres. Infected HepG2 cells could stably maintain in-vitro expression of TIMP-1, with significantly effects on biological behaviour Conclusion: PELA microspheres encapsulating a recombinant TIMP-1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for polymer/chemistry-based gene therapy of hepatocellular carcinomas. -
Meng, Fan-Min;Yang, Jing-Bo;Yang, Chun-Hui;Jiang, Yu;Zhou, Yong-Feng;Yu, Bo;Yang, Hong 6369
Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an$IC_{50}{\sim}28.8{\mu}M$ . Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma. -
Zhang, Tie-Feng;Cheng, Ke-Wen;Shi, Wei-Yin;Zhang, Jin-Tao;Liu, Ke-Di;Xu, Shu-Guang;Chen, Ji-Quan 6375
Background: Small-cell lung cancer (also known as SCLC) is an aggressive form and untreated patients generally die within about 3 months. To obtain further insight into mechanism underlying malignancy with this cancer, an miRNA synergistic regulatory network was constructed and analyzed in the present study. Method: A miRNA microarray dataset was downloaded from the NCBI GEO database (GSE27435). A total of 546 miRNAs were identified to be expressed in SCLC cells. Then a miRNA synergistic network was constructed, and the included miRNAs mapped to the network. Topology analysis was also performed to analyze the properties of the synergistic network. Consequently, we could identified constitutive modules. Further, common target genes of each module were identified with CFinder. Finally, enrichment analysis was performed for target genes. Results: In this study, a miRNA synergistic network with 464 miRNAs and 2981 edges was constructed. According to the topology analysis, the topological properties between the networks constructed by LC related miRNAs and LC unrelated miRNAs were significantly different. Moreover, a module cilque0 could be identified in our network using CFinder. The module included three miRNAs (hsa-let-7c, hsa-let-7b and hsa-let-7d). In addition, several genes were found which were predicted to be common targets of cilque0. The enrichment analysis demonstrated that these target genes were enriched in MAPK signaling pathways. Conclusions: Although limitations exist in the current data, the results uncovered here are important for understanding the key roles of miRNAs in SCLC. However, further validation is required since our results were based on microarray data derived from a small sample size. -
Li, Xun;Yang, Shun-E.;Guo, Yun-Quan;Shen, Ming-Xia;Gu, Li;Gulikezi, Gulikezi;Zhao, Bing;Liu, Wei;Tuerxun, Tuerxun;Bai, Jing-Ping 6379
Objective: To investigate the relationship between plasma EBV-DNA concentration and clinicopathologic features of Hodgkin's lymphoma cases. Methods: At first, the positive rate of plasma EBV-DNA was determined with a nested-PCR method using 45 specimens from Uygur HL patients, as well as 110 healthy people sampled as normal controls. Secondly, using fluorescent quantitative nested-PCR, EBV viral load was assessed in the EBV-DNA positive plasma samples. Then, relationships between plasma EBV viral load and clinicopathologic features of HL patients were analyzed. Results: The positive rate of plasma EBV-DNA of HL patients was significantly higher than that of normal controls (53.3% vs 26.4%, P=0.001). There was no significant difference about plasma EBV viral load between EBV-associated HL and EBV-DNA positive normal people (P=0.490). Looking at patients' characteristics, plasma EBV viral load in 10-20 years EBV-associated HL was higher than in EBV cases which were less than 10 years or more than 35 years (P=0.025). Furthermore, in EBV-associated HL, concentration of plasma EBV-DNA was significantly higher in advanced stage disease (stages III-IV; P=0.013), and with B-symptoms (P=0.020). Conclusion: EBV-DNA levels were associated with part of clinicopathologic features of cases. It was of practical use to screen HL. Further etiological studies appear warranted. -
Qian, Ke;Liu, Kui-Jie;Xu, Feng;Chen, Xian-Yu;Chen, Gan-Nong;Yi, Wen-Jun;Zhou, En-Xiang;Tang, Zhong-Hua 6385
A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials. -
Mokhtar, N.M.;Thevarajah, M.;M.A., Noorazmi;M., Isahak 6391
Background: Ovarian cancer is ranked as the fifth most common cause of cancer death in women. In Malaysia, it is the fourth most common cancer in females. CA125 has been the tumor marker of choice in ovarian cancer but its diagnostic specificity in early stages is only 50%. Hence, there is a critical need to identify an alternative tumor marker that is capable of detecting detect ovarian cancer at an early stage. HE4 is a new tumor marker proposed for the early diagnosis of ovarian cancer and disease recurrence. Currently, none of the normal ranges of HE4 quoted in the literature are based on data for a multiethnic Asian population. Therefore, the aim of this study was to determine reference intervals for HE4 in an Asian population presenting in University Malaya Medical Centre, a tertiary reference hospital. Materials and Methods: 300 healthy women were recruited comprising 150 premenopausal and 150 postmenopausal women, aged from 20-76 years. All women were subjected to a pelvic ultrasonograph and were confirmed to be free from ovarian pathology on recruitment. Serum HE4 levels were determined by chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). The reference intervals were determined following CLSI guidelines (C28-A2) using a non-parametric method. Results: The upper limits of the$95^{th}$ percentile reference interval (90%CI) for all the women collectively were 64.6 pmol/L, and 58.4 pmol/L for premenopausal) and 69.0 pmol/L for postmenopausal. The concentration of HE4 was noted to increase with age especially in women who were more than 50 years old. We also noted that our proposed reference limit was lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4 vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group). The study also showed a significant difference in HE4 concentrations between ethnic groups (Malays and Indians). The levels of HE4 in Indians appeared higher than in Malays (p<0.05), while no significant differences were noted between the Malays and Chinese ethnic groups. Conclusions: More data are needed to establish a reference interval that will better represent the multiethnic Malaysian population. Probably a larger sampling size of equal representation of the Malay, Chinese, Indians as well as the other native ethnic communities will give us a greater confidence on whether genetics plays a role in reference interval determination. -
Kara, Oguz;Duman, Berna Bozkurt;Kara, Banu;Erdogan, Seyda;Parsak, Cem Kaan;Sakman, Gurhan 6397
Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma. -
Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protect against xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST) and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate the excretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, has demonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted to investigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line to study the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established the optimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene (
$0-50{\mu}M$ ) on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively. MTT assay of pterostilbene ($0-100{\mu}M$ ) showed no cytotoxicity toward the HT-29 cell line. Treatment increased GST activity in the cell line significantly (p<0.05) at 12.5 and$25.0{\mu}M$ . In addition, treatment at$50{\mu}M$ increased the GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at$12.5{\mu}M$ and$50{\mu}M$ . Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiying enzyme levels in HT-29 cells. -
Wang, Di;Xiao, Pei-Ling;Duan, Hua-Xin;Zhou, Ming;Liu, Jin;Li, Wei;Luo, Ke-Lin;Chen, Jian-Jun;Hu, Jin-Yue 6409
The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-$1{\beta}$ , interleukin-8 and TNF-${\alpha}$ and apoptosis of THP-1 with PGN dose and time dependence. Moreover, in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-${\alpha}$ -dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers. -
Muhammadnejad, Ahad;Keyhani, Elahe;Mortazavi, Pejman;Behjati, Farkhondeh;Haghdoost, Iraj Sohrabi 6415
Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC. Materials and Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically. Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics. Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans. -
Shuai, Han-Lin;Luo, Xin;Yan, Rui-Ling;Li, Jian;Chen, Dan-Liang 6423
Background: Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein 1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; however, most previous case-control studies were small sized and biased. Additionally, recent studies suggested that XRCC1 polymorphisms could be a biomarker of response to platinum-based chemotherapy. Methods: A comprehensive search was conducted to retrieve eligible studies and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure association strength. Results: A total of 13 studies were identified and analyzed. We found that the Arg194Trp polymorphism (Trp vs. Arg, OR=1.342, 95% CI: 1.176) was associated with increased risk of cervical cancer, while no significant association was found with Arg280His (His vs. Arg, OR=1.059, 95% CI: 0.863, 1.299) or Arg399Gln (Gln vs. Arg, OR=1.144, 95% CI: 0.938, 1.394). As for response to platinum-based chemotherapy, the variant XRCC1 399Gln allele (Gln vs. Arg, OR=0.345, 95% CI: 0.163, 0.729) was linked with a poor response; however, the Arg194Trp polymorphism (TrpArg vs. ArgArg, OR=6.421, 95% CI: 1.573, 26.205) predicted a good response. Conclusion: The Arg194Trp polymorphism of XRCC1 increases risk of cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while the Arg194Trp polymorphism indicates a good response. -
To explore a possible new treatment for human ovarian cancer, we studied the effects of sodium valproate on the growth of the HO8910 human cell line. HO8910 cells were cultured in vitro and treated with different concentrations of sodium valproate. Cell proliferation, cell cycling, and apoptosis were measured by flow cytometry, cell morphology under a microscope, and expression levels of WWOX and P27 by Western blotting and RT-PCR. Tumor xenografts were established to determine in vivo effects of sodium valproate. Our results showed that cell proliferation was decreased with increasing concentration of sodium valproate, with features of cytoplasmic retraction and floating cells. Moreover, cell cycle analysis revealed a higher apoptosis rate and
$G_0/G_1$ phase in the sodium valproate experimental group than in the control group. In addition, protein expression levels of WWOX and P27 were elevated. Importantly, sodium valproate decreased in vivo xenograft tumor burden and up-regulated WWOX and P27 expression in nude mice. In conclusion, sodium valproate might play a role in inhibition and control of ovarian cancer cell line HO8910 by inhibiting cell proliferation, interfering with the cell cycle and promoting apoptosis, so that it may be effective in the clinical treatment of ovarian cancer. -
Zhou, Jing;Wei, Yue-Hua;Liao, Mei-Yan;Xiong, Yan;Li, Jie-Lan;Cai, Hong-Bing 6435
Chemoresistance to cancer therapy is a major obstacle to the effective treatment of human cancers with cisplatin (DDP), but the mechanisms of cisplatin-resistance are not clear. In this study, we established a cisplatin-resistant human ovarian cancer cell line (COC1/DDP) and identified differentially expressed proteins related to cisplatin resistance. The proteomic expression profiles in COC1 before and after DDP treatment were examined using 2-dimensional electrophoresis technology. Differentially expressed proteins were identified using matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and high performance liquid chromatography-electrospray tandem MS (NanoUPLC-ESI-MS/MS). 5 protein spots, for cytokeratin 9, keratin 1, deoxyuridine triphosphatase (dUTPase), aarF domain containing kinase 4 (ADCK 4) and cofilin1, were identified to be significantly changed in COC1/DDP compared with its parental cells. The expression of these five proteins was further validated by quantitative PCR and Western blotting, confirming the results of proteomic analysis. Further research on these proteins may help to identify novel resistant biomarkers or reveal the mechanism of cisplatin-resistance in human ovarian cancers. -
Wang, Juan;Xu, Heng-Wei;Li, Bao-Sheng;Zhang, Jian;Cheng, Jian 6441
Background: Radiation therapy plays an important role in lung carcinoma treatment. However, the incidence of symptomatic radiation-induced lung injury is high. This study aimed to evaluate radioprotective effects of flavonoids extracted from Astragalus complanatus and mechanisms of action against radiation damage. Methods: Alteration in antioxidant status and levles of several cytokines were investigated in BABL/C mice treated with 4 mg/kg b.wt. flavonoids after exposure to 10Gy thoracic radiation. Results: Serum levels of SOD in the flavonoids+radiation group were significantly higher compared to the radiation control group, while TGF-${\beta}1$ and IL-6 were lower. Mice in the radiation control group displayed more severe lung damage compared with the flavonoids+radiation group. The expression of TGF-${\beta}1$ and TNF-${\alpha}$ in the radiation control group was markedly increased in alveolar epithelial cells and macrophages of the alveolar septum. Conclusions: From the results of the present study, flavonoids could be excellent candidates as protective agents against radiation-induced lung injury. -
Xiao, Li-Jun;Zhao, Shuang;Zhao, En-Hong;Zheng, Xin;Gou, Wen-Feng;Xing, Ya-Nan;Takano, Yasuo;Zheng, Hua-Chuan 6447
Background: The mucin components of the gastric gel layer function as a protective and lubricating factor against luminal acid and proteolytic enzymes. Alteration of mucin expression in gastric preneoplastic and neoplastic lesions has suggested potential roles in neoplastic processes. This study aimed to assess the clinicopathological and prognostic significance of MUC-2, MUC-4 and MUC-5AC in Japanese gastric cancer. Methods: Expression of MUC-2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas and adjacent non-cancerous mucosa specimens by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients. Results: The three mucins were found to be expressed to a lesser extent in gastric carcinomas in comparison with non-cancerous mucosa (p<0.05). MUC-2 expression was negatively correlated with tumor size, depth of invasion, and TNM staging of gastric cancer (p<0.05), while that of MUC-5AC was negatively associated with the depth of invasion, venous invasion, lymph node metastasis and TNM staging (p<0.05), but positively with MUC-4 and MUC-2 expression (p<0.05). There was higher MUC-2 expression in intestinal- than diffuse-type carcinomas (p<0.05). Kaplan-Meier analysis indicated no relationship between expression of the three mucins and the cumulative survival rate of patients, even stratified according to the depth of invasion (p>0.05). Conclusion: Down-regulated expression of MUC-2, -4 and -5AC may be involved in pathogenesis, invasion, metastasis or differentiation of gastric carcinoma. Their altered expression might therefore be employed as an indicator of pathobiological behavior. -
Jiang, Xue-Mei;Zhang, Ju-Bo;Xiong, Ju;Huang, Xiao-Xi;Ren, Zheng-Gang 6455
Objective: E-cadherin has been identified as a tumor suppressor in many types of carcinoma. However, some studies recently suggested that the role and expression of E-cadherin might be more complex and diverse. In the present study, we evaluated the prognostic value of E-cadherin expression with reference to levels in membranes and cytoplasm, and the membrane/cytoplasm ratio, in hepatocellular carcinomas (HCCs) after curative hepatectomy. Methods: The expression of E-cadherin was assessed by immunohistochemistry in HCC tissue microarrays from 125 patients, and its prognostic values and other clinicopathlogical data were retrospectively analyzed. Patients were followed for a median period of 43.7 months (range 1 to 126 months). Results: Univariate analysis demonstrated that a high membrane/cytoplasm (M/C) ratio of E-cadherin expression was associated with poor overall survival (OS) (P =0.001) and shorter time to recurrence (TTR) (P=0.038), as well as tumor size, intrahepatic metastasis, and TNM stage. In contrast, neither membrane nor cytoplasmic expression of E-cadherin was related with OS and TTR. Furthermore, multivariate analysis confirmed the M/C ratio to be an independent predictor of OS (P=0.031).${\chi}^2$ tests additionally showed that the M/C ratio of E-cadherin expression was related with early stage recurrence (P=0.012), rather than later stage recurrence. Conclusion: The M/C ratio of E-cadherin expression is a strong predictor of postoperative survival and is associated with early stage recurrence in patients with HCC. -
Targeting Renal Cell Carcinoma with Gambogic Acid in Combination with Sunitinib in Vitro and in VivoJiang, Xiao-Liang;Zhang, Yao;Luo, Chun-Li;Wu, Xiao-Hou 6463
Purpose: To evaluated the effect of the gambogic acid (GA), one of the effective components of Garcinia, in combination with a new multi-targeted oral medication, sunitinib (SU) on renal cancer cell proliferation in vitro and on tumor growth in vivo. Methods: After treatment with GA or SU, either alone or in combination, MTT and FACS analysis were used to examine cell viability and cycle distribution of the renal carcinoma cell lines 786-0 and Caki-1. Western blotting was employed to examine the expression of proteins related to the cell cycle and vascular formation. Furthermore, a xenograft model was applied to study the antitumor efficacy of SU or GA alone or in combination, with immunohistochemistry to detect expression of proteins related to xenograft growth and angiogenesis. Western blotting was used to examine NF-${\kappa}B$ signaling pathway elements in xenografts. Results: Treatment of 786-0 and Caki-1 cells with GA or SU resulted in decreased tumor cell proliferation, especially with joint use. Cells accumulated more strongly in the sub-G1 phase after joint treatment with GA and SU than treatment of GA and SU alone. Western blotting arrays showed 1 protein significantly upregulated, 2 proteins downregulated, and 2 proteins unchanged. Moreover, combined use of GA and SU inhibited the growth and angiogenesis of xenografts generated from Caki-1 significantly. Immunohistochemistry arrays showed downregulation of the expression of proteins promoting xenograft growth and angiogenesis, and Western blotting showed inhibition of the NF-${\kappa}B$ signaling pathway after treatment by GA alone and in combination with SU in xenografts. Conclusions: Our results show that the joint use of GA and SU can provide greater antitumor efficacy compared to either drug alone and thus may offer a new treatment strategy for renal cell carcinoma. -
Parine, Narasimha Reddy;Pathan, Akbar Ali Khan;Bobbarala, Varaprasad;Abduljaleel, Zainularifeen;Khan, Wajahatullah;Alanazi, Mohammed 6469
Background: DNA repair is one of the crucial defense mechanism against mutagenic exposure. Inherited SNPs of DNA repair genes may contribute to variation in DNA repair capacity and susceptibility to cancer. Due to the presence of these variants, inter-individual and ethnic differences in DNA repair capacity have been established in various populations. India harbors enormous genetic and cultural diversity. Materials and Methods: In the present study we aimed to determine the genotypes and allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 186 healthy individuals residing in the Hyderabad region of India and to compare them with HapMap and other populations. Results and Conclusions: The genotype and allele frequency distribution at the four DNA repair gene loci among Hyderabad population of India revealed a characteristic pattern. Comparison of these gene polymorphisms with other populations revealed a distinctiveness of Hyderabad population from the Deccan region of India. To the best of our knowledge, this is the first report of such DNA repair gene polymorphisms in the Deccan Indian population. -
Sharma, Manoj;Satyam, Abhigyan;Abhishek, Ashu;Khan, Rehan;Rajappa, Medha;Sharma, Alpana 6475
Background: Recent studies have demonstrated an association between insulin growth factor (IGF) and insulin growth factor binding protein-3 (IGFBP-III) serum levels and increased risk for various cancers. However, little information is available on clinical implications of the IGF system in Indian patients with cervical cancer. This study explored associations by analyzing their expression profiles in cervical cancer cases. Materials and Methods: Totals of 50 patients with advanced cervical cancer and 40 healthy controls were enrolled. Human papillomavirus (HPV) and cervical biopsy sample were obtained from all participating women. Circulatory levels were estimated by ELISA and the tissue expression was assessed using RT-PCR and Western blotting. Results: Levels of IGF-I and II showed significant increase whereas IGFBP-III showed significant decline in all patients as compared to controls. Spearman correlation analysis between IGFs and HPV status showed significant correlations. Conclusions: We demonstrated elevated circulating levels and tissue expression of IGF-I and IGF-II in advancer cancer cervix patients, as compared with controls, with a converse trend being apparent for IGFBP-III. In future, associations of the IGF system and clinical outcome of cervical cancer patients in post treatment samples might point to significance in disease mapping as a prognostic marker after validation with a larger patient series. -
Ortashi, Osman;Shallal, Musa;Osman, Nawal;Raheel, Hina 6481
Background: In 2008, the Health Authority in Abu Dhabi (the capital of the United Arab Emirates) introduced HPV vaccine free of charge for high school girls entering grade 11, becoming the first state in the Middle East to do so. The objectives of this study were to assess the knowledge, attitude and practice of school nurses in the Emirate of Abu Dhabi about HPV infection and the vaccine. Materials and Methods: A quantitative study was designed and conducted from June to August 2012 in Emirate of Abu Dhabi. Data were collected through direct face to face interviews. from one hundred and twenty five nurses. Results: Knowledge of HPV infection and HPV vaccine was almost universal among the school nurses (97%). The majority of the participants (71%) thought that the HPV vaccine was good. Cultural unacceptability (45%) and lack of women's concern about their own health (21%) were rated as the top barriers for the successful introduction of the vaccine in the UAE. More than half of the sampled nurses (58%) have either given this vaccine to school girls or taken it themselves. The majority (95%) did not come across any side effects from the vaccine. The level of qualification and the place of work did not significantly affect the correct knowledge of HPV infection or cervical cancer prevention methods. Conclusions: The knowledge and attitude of the sampled school nurses in Abu Dhabi State about HPV infection and vaccine is very good in both the public and private sectors. However, a knowledge gap in cervical cancer screening methods was identified. -
Cure, Medine Cumhur;Cure, Erkan;Kirbas, Aynur;Yazici, Tarkan;Yuce, Suleyman 6485
Aims: To investigate the incidence of ordering tests for tumor markers which are used in cancer diagnosis, follow-up treatment and detection of recurrence, the rate of elevation in benign diseases and which clinics order them frequently. Materials and Method: Data for the tumor markers carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3) and alpha-fetoprotein (AFP) that were ordered by all the clinics in our Hospital between 2010 and 2011 were screened. When excluding repeated orders the results of 3,416 patients were available. It has been determined that in which benign diseases were the tumor markers frequently ordered and which of these conditions had high levels of them. Results: CA 19-9 was ordered for 1,858 patients 191 (10.3%) were malignant while 1667 (89.7%) were ordered in benign diseases. For CEA the total was 1,710, 226 (13.2%) malignant and 1484 (86.8%) benign, and for CA 125 1267, 111 (8.8%) malignant and 1156 (91.2%) benign. AFP was ordered for 1687 cases, 80 (4.7%) malignant but 1607 (95.3%) benign. CA 15-3 was ordered 1449 times, 174 (12%) for malignant and 1275 (88%) for benign diseases. In all cases, considerable proportions were positive. Conclusions: It was shown that clinicians frequently order tumor markers for benign conditions. The findings of this study has shown that tumor markers are used widely without indications as cancer screening tests. -
Mostert, Saskia;Gunawan, Stefanus;Wolters, Emma;van de Ven, Peter;Sitaresmi, Mei;van Dongen, Josephine;Veerman, Anjo;Mantik, Max;Kaspers, Gertjan 6491
Background: The influence of parental socio-economic status on childhood cancer treatment outcome in low-income countries has not been sufficiently investigated. Our study examined this influence and explored parental experiences during cancer treatment of their children in an Indonesian academic hospital. Materials and Methods: Medical charts of 145 children diagnosed with cancer between 1999 and 2009 were reviewed retrospectively. From October 2011 until January 2012, 40 caretakers were interviewed using semi-structured questionnaires. Results: Of all patients, 48% abandoned treatment, 34% experienced death, 9% had progressive/relapsed disease, and 9% overall event-free survival. Prosperous patients had better treatment outcome than poor patients (P<0.0001). Odds-ratio for treatment abandonment was 3.3 (95%CI: 1.4-8.1, p=0.006) for poor versus prosperous patients. Parents often believed that their child's health was beyond doctor control and determined by luck, fate or God (55%). Causes of cancer were thought to be destiny (35%) or God's punishment (23%). Alternative treatment could (18%) or might (50%) cure cancer. Most parents (95%) would like more information about cancer and treatment. More contact with doctors was desired (98%). Income decreased during treatment (55%). Parents lost employment (48% fathers, 10% mothers), most of whom stated this loss was caused by their child's cancer (84% fathers, 100% mothers). Loss of income led to financial difficulties (63%) and debts (55%). Conclusions: Treatment abandonment was most important reason for treatment failure. Treatment outcome was determined by parental socio-economic status. Childhood cancer survival could improve if financial constraints and provision of information and guidance are better addressed. -
Demirhindi, Hakan;Nazlican, Ersin;Akbaba, Muhsin 6497
Cervical cancer is the second most common cancer in females in the World with around 500,000 new cases occurring annually, but the first in the developing countries with a high mortality if not diagnosed early. Papanicolau (Pap) smear is a cheap, easy-to-apply and widely accepted test which has been long used to detect cervical cancer at very early stages. However, despite being available for nearly 60 years, the test can hardly be considered to have become successfully applied in many communities. We aimed in this study to present the results of a screening survey for cervical cancer which targeted a women population aged between 35 and 40 living in a semi-rural area in the province of Hatay, located in the eastern Mediterranean region of Turkey, with specific aims of increasing early diagnosis, education and raising population awareness about cancers. This community-based descriptive study covered 512 women between 35 and 40 years of age living at Armutlu with a mean age of$37.6{\pm}1.7$ . Gynecologic examinations revealed cervical erosion in 8 (1.6%), vaginitis in 193 (37.7%) and normal findings in 311 (60.7%); pathological evaluation reports of the smears were negative in 290 (56.6%), inflammation in 218 (42.6%) and ASC-US in 4 (0.8%), according to the 2001 Bethesda classification. It can be concluded that Pap smear test - proven to be a very valuable test at the clinical level- should also be widely used at the community level to detect cervical cancer at very early stages to reduce both the mortality and morbidity among healthy people. The need for continuous community-based cervical cancer screening programs is strongly suggested. -
Buchner-Daley, Loretta;Brady-West, Doreen;McGrowder, Donovan 6501
Background: Multiple myeloma is the most common malignant plasma cell dyscrasia and ranks second among primary haematological malignancies. This study describes the epidemiologic, clinical and pathologic profile of monoclonal gammopathies seen in the University Hospital of the West Indies (UHWI), a tertiary care referral centre. Materials and Method: A retrospective analysis of 85 cases diagnosed at UHWI over the 5-year period 2003-2007 was conducted. The cases were identified from the bone marrow records as well as the computerized database of the Medical Records Department. Clinical presentation, family and personal history and demographic data were retrieved. Haematological and biochemical results were also analyzed. Results: There were 85 patients diagnosed with monoclonal gammopathies. The M:F ratio was 1.2:1 and the mean age was$65.7{\pm}1.3$ years. Eighty percent of the patients had skeletal pain and 40% experienced weight loss. Of the patients experiencing bone pain 56.7% had multiple lytic lesions, 26.7% had pathological fractures and 26.7% had compression fractures. Seventy-four patients (87.1%) had a haemoglobin level <12.0 g/dL with 52.9% having values <8.0 g/dL. Renal impairment was evident at diagnosis in 36.5%. Hypercalcemia was seen in 26.5% and hyperuricemia in 45.9%. Of the 79 patients who had serum protein electrophoresis performed, 77.2% had at least one monoclonal band and of these 24.6% had a monoclonal protein also present on urine protein electrophoresis. Conclusions: The demographic profile in this group of patients is largely similar to other studies in predominantly Caucasian populations; however there was a notable increase in prevalence of severe disease at presentation, with the majority of patients presenting at the most advanced stage. It is probable that these differences reflect socioeconomic factors and not merely inherent ethnic variation in disease biology. -
Shahriary, Ghazaleh Mohammadzadeh;Galehdari, Hamid;Jalali, Amir;Zanganeh, Fatemeh;Alavi, Seyed Mohammad Reza;Aghanoori, Mohammad Reza 6505
Background: CYP2E1 encodes an enzyme which is mainly involved in bioactivation of potential carcinogens such as N-nitrosamines. Polymorphisms in the gene have been reported to be associated with cancer. The aim of this study was to evaluate genotype distributions and allele frequencies of five CYP2E1 polymorphisms in Iran Materials and Methods: Two hundred healthy individuals of an Iranian population from the southwest were included in this study. PCR-restriction fragment length polymorphism and Tetra-ARMS PCR methods were applied for CYP2E1 genotyping. Results: The allele frequencies for$^*5B$ ,$^*6$ ,$^*7B$ ,$^*2$ , and$^*3$ were calculated to be 1.5%, 16%, 28.5%, 0%, and 2.75% respectively. Results of this study showed that no significant differences in genotype and allele frequencies of five single nucleotide polymorphisms with respect to the gender and tribes. The chi-square test showed that the genotype frequencies of$CYP2E1^*5B$ were similar to Caucasians, but the distribution of$CYP2E1^*6$ genotypes was similar to Asians. The frequencies of$CYP2E1^*2$ (0%) and$CYP2E1^*3$ (2.75%) alleles were within the range for Caucasians and Orientals. In the case of$CYP2E1^*7B$ , the data werelimited. Accordingly, the results were only compared with Europeans and the comparison showed significant differences. Conclusions: In conclusion, ethnic and geographic differences may explain discrepancies in the prevalence of CYP2E1 polymorphisms. -
Shin, Jae-Sik;Maeng, Hyung-Gun;Hong, Seung-Woo;Moon, Jai-Hee;Kim, Jin-Sun;Suh, Young-Ah;Kim, Eun-Sung;Lee, Young-Min;Kim, Ye-Seul;Choi, Eun-Kyung;Kim, Inki;Lee, Sok-Young;Cho, Dong-Hyung;Hong, Nam-Joo;Kim, Tae-Won;Jin, Dong-Hoon;Lee, Wang Jae 6511
Recently, we reported that an ethanol extract of Iris nertschinskia induces p53-dependent apoptosis in the MCF7 human breast cancer cell line. However, the detailed mechanisms were not fully explored. Here, we demonstrate another aspect of the activity of I. nertschinskia in breast cancer cells. We compared the response to an ethanol extract of I. nertschinskia in two different human breast cancer cell lines, Hs578Tand MDA-MB231, respectively with relatively low and high AKT1/2 activity by trypan blue exclusion assay and FACS analysis. Knockdown of endogenous AKT1 or AKT2 in breast cancer cells by RNA interference determined the sensitivity to I. nertschinskia ethanol extract compared to control cells. The I. nertschinskia ethanol extract induced cell death in a manner that depended on the level of phosphorylated AKT1/2 protein and was associated with a significant increase in the sub-G1 cell population, indicative of apoptosis. Our results indicate that an ethanol extract of I. nertschinskia differentially induces cell death in breast cancer cells depending on their level of phosphorylated AKT1/2. -
Wang, Xin-Jie;Zheng, Yu-Ling;Fan, Qing-Xia;Zhang, Xu-Dong 6517
To analyze the growth, proliferation, apoptosis, invasiveness and chemotherapy sensitivity of EC9706 cells after K-Ras gene silencing, an expression carrier pSilencer-siK-Ras was constructed, and the EC9706 cell line was transfected using a liposome technique. Six groups were established: Control, siRNA NC (transfected with empty vector pSilencer2.1); Ras siRNA (transfected with pSilencer-siK-Ras2); Paclitaxel; Paclitaxel + siRNA NC; and Ras siRNA + Paclitaxel. After the treatment, RT-PCR, Western blotting, MTT assay, flow cytometry and the Transwell technique were used to assess expression of K-Ras mRNA and protein in EC9706 cells, as well as cell growth, proliferation, apoptosis and invasiveness. The effect of Paclitaxel chemotherapy was also tested. pSilencer-siK-Ras2 effectively down-regulated expression of K-Ras mRNA and protein in EC9706 cells, growth being significantly inhibited. Flow cytometry indicated obvious apoptosis of cells in the experimental group, with arrest in the G1 phase; cell migration ability was also reduced. After pSilencer-siK-Ras2 transfection or the addition of Paclitaxel, EC9706 cells were suppressed to different extents; the suppressive effect was strengthened by combined treatment. The results suggested that RNAi-induced K-Ras gene silencing could enhance chemotherapy sensitivity of esophageal cancer. -
Shen, Kang;Huang, Xin-En;Lu, Yan-Yan;Wu, Xue-Yan;Liu, Jin;Xiang, Jin 6523
Objective: This study was designed to investigate treatment efficacy and side effects of concomitant Aisu$^{(R)}$ (docetaxel) with three-dimensional conformal external beam radiotherapy for the treatment of inoperable patients with esophageal cancer. Methods: Inoperable patients were treated with three-dimensional conformal external beam radiotherapy (5/week, 2 GY/day, and total dose 60GY) plus docetaxel ($30-45mg/m^2$ , iv, d1, 8). Results: Twenty eight patients met the study eligibility criteria and the response rate was evaluated according to RICIST guidelines. Among 28 patients, 2 achieved CR, 22 PR, 3 SD and 1 patient was documented PD. Mild gastrointestinal reaction and bone marrow suppression were also documented. All treatment related side effects were tolerable. Conclusion: Three-dimensional conformal external beam radiotherapy combined with docetaxel is an active and safe regimen for inoperable patients with esophageal cancer. -
He, Jian-Rong;Xi, Jing;Ren, Ze-Fang;Qin, Han;Zhang, Ying;Zeng, Yi-Xin;Mo, Hao-Yuan;Jia, Wei-Hua 6527
Purpose: Complement receptor 1 (CR1) is induced by Epstein-Barr virus (EBV) and may be a potential biomarker of nasopharyngeal carcinoma (NPC). We conducted the present study to evaluate the association of CR1 expression with clinicopathological features and prognosis of NPC. Methods: We enrolled 145 NPC patients and 110 controls. Expression levels of CR1 in peripheral blood mononuclear cells (PBMCs) were detected using quantitative real-time PCR and associations with clinicopathological features and prognosis were examined. Results: CR1 levels in the NPC group [3.54 (3.34, 3.79)] were slightly higher than those in the controls [3.33 (3.20, 3.47)] (P<0.001). Increased CR1 expression was associated with histology classification (type III vs. type II, P=0.002), advanced clinical stage (P=0.003), high T stage (P=0.017), and poor overall survival (HR, 4.89; 95% CI, 1.23-19.42; P=0.024). However, there were no statistically significant differences in CR1 expression among N or M stages. Conclusion: These findings indicate that CR1 expression in PBMCs may be a new biomarker for prognosis of NPC and a potential therapeutic target. -
Safdari, Reza;Maserat, Elham;Maserat, Elnaz 6533
Cancers are significant contributors to the mortality and health care expenditures. Cancer can be reduced and monitored by new information technology. Radio frequency identification or RFID is a wireless identification technology. The use of this technology can be employed for identifying and tracking clinical staff, patients, supplies, medications and equipments. RFID can trace and manage chemotherapy drugs. There are different types of RFID. Implantable RFID allowing a chip to be embedded under the skin and that store the cancer patient's identifier. These are concerns about applications of RFID. Privacy, security and legal issues are key problems. This paper describes capabilities, benefits and confidentiality aspects in radio frequency identification systems and solutions for overcoming challenges. -
Taguchi, Satoru;Fujimura, Tetsuya;Kume, Haruki;Homma, Yukio 6539