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.
KSCI제14권6호
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Moore, Malcolm A.;Lim, Min-Kyung;Huang, Xin-En 3377
The APJCP Impact Factor for 2012 is 1.271, returning from 0.659 for 2011 (1.240 for 2010 and 1.108 for 2009). For an Asian Pacific journal publishing over 100 papers a month from countries with very varied resources it is heartening and we thank all those who continued to submit papers and cite references in the APJCP through our difficult period. However, we still have very much room for improvement. As Chief Editors it is our shared responsibility to act for the benefit of the cancer control research community who utilize the journal in our region of over four billion people and provide a prestigious forum for publication of research findings which can be freely shared by all. The motivation for the APOCP/APJCP has never been financial profit but a firm financial base is nevertheless essential. Although we have kind support from the Korean National Cancer Center for our Managing Editor and the website, our ability to maintain our Chinese and Thai offices is totally dependent on the processing charges paid by the authors. In order to expand our staff to cope with increased submissions and provide greater assistance in ensuring comprehensive reference coverage and dissemination of findings published in the APJCP to the worldwide research community, a joint decision has been made to increase formatting charges by 50% from July. We ask for author understanding. In addition, we appeal to scientists to positively consider our requests to make their reference lists as comprehensive as possible, including papers from the APJCP where appropriate. The future of the journal and the APOCP is largely in your own hands. -
The usage and types of chemicals being developed, with diversified new exposure of workers, are of natural concern to occupational disease. In Korea, with industrialization, application of many chemicals has increased. A large proportion of mortality and disease is due to cancer, and the causal hazardous agents include chemical agents, like heavy metals and so on. Due to the long latency period with malignancies and the fact they are usually found after workers' retirement, it is suggested that management policies must be established to prevent occupational cancers occurring among workers in Korea. To give a general description about the efforts to prevent the occupational cancer with exposure to chemicals, articles on the trends of occupational cancers were reviewed and summarized with related research and efforts for prevention in Korea. It is important to improve the understanding of occupational cancer and help to maintain sustainable and appropriate measures to guarantee workers safety and health.
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Fasinu, Pius Sedowhe;Orisakwe, Orish Ebere 3393
The increasing scourge of cancer epidemiology is a global concern. With WHO emphasizing that 40% of all cancer cases are preventable, exposure to known and suspected carcinogens must be discouraged. The battle with communicable diseases and other third world challenges has greatly de-emphasized anti-cancer campaigns in sub-Saharan Africa. The abundant deposit of mineral resources in sub-Saharan Africa has attracted high mining activity with its negative environmental aftermath. Poor regulatory mechanisms have led to environmental contamination by products of mining including heavy metals. In addition to poor urban planning, the springing up of settlements in industrial areas has led to generation and exposure to more hazardous wastes consequent on poor disposal systems. Studies establishing close association between exposure to heavy metals and cancer epidemiology in sub-Saharan Africa are increasing. The current review assesses the level of environmental pollution by heavy metals in sub-Saharan Africa, and brings to the fore available evidence implicating such in the increasing cancer epidemiology in the sub-continent. -
Mahdi, Kooshyar Mohammad;Nassiri, Mohammad Reza;Nasiri, Khadijeh 3403
Breast cancer is the most common cancer among women affecting up to one third of tehm during their lifespans. Increased expression of some genes due to polymorphisms increases the risk of breast cancer incidence. Since mutations that are recognized to increase breast cancer risk within families are quite rare, identification of these SNPs is very important. The most important loci which include mutations are; BRCA1, BRCA2, PTEN, ATM, TP53, CHEK2, PPM1D, CDH1, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, BRIP1, RAD50, RAD51C, STK11 and BARD1. Presence of SNPs in these genes increases the risk of breast cancer and associated diagnostic markers are among the most reliable for assessing prognosis of breast cancer. In this article we reviewed the hereditary genes of breast cancer and SNPs associated with increasing the risk of breast cancer that were recently were reported from candidate gene, meta-analysis and GWAS studies. SNPs of genes associated with breast cancer can be used as a potential tool for improving cancer diagnosis and treatment planning. -
Over the last 10 years, the number of cancer survivors in South Korea has reached nearly one million with a survival rate of 49.4%. However, integrated supportive care for cancer survivors is lagging. One area in which the current cancer control policy needs updating is in the utilization of information and communication technology (ICT). The remarkable progress in the field of ICT over the past 10 years presents exciting new opportunities for health promotion. Recent communication innovations are conducive to the exchange of meta-information, giving rise to a new service area and transforming patients into active medical consumers. Consequently, such innovations encourage active participation in the mutual utilization and sharing of high-quality information. However, these benefits from new ICTs will almost certainly not be equally available to all, leading to so-called communication inequalities where cancer survivors from lower socioeconomic classes will likely have more limited access to the best means of making use of the health information. Therefore, most essentially, emphasis must be placed on helping cancer survivors and their caregivers utilize such advances in ICT to create a more efficient flow of health information, thereby reducing communication inequalities and expanding social support. Once we enhance access to health information and better manage the quality of information, as a matter of fact, we can expect an alleviation of the health inequalities faced by cancer survivors.
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Thanapprapasr, Duangmani;Thanapprapasr, Kamolrat 3419
Of all gynecologic cancers, endometrial cancer is the most common cancer in the US and Europe. In addition, it is presently the second most common gynecologic cancer in the world. As a result of increasing menopausal, obese and tamoxifen use women, the incidence of the cancer seems to be on the increase. Surgery is the major treatment, whereas postoperative radiation therapy in high-intermediate risk patients many prevent locoregional recurrence. Adjuvant chemotherapy can improve progression free survival in advanced or recurrent cancers. Molecular targeted therapies are now a focus of attention including anti-vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) inhibitor and tyrosine kinase inhibitor (TKI). They may provide useful future strategies for control of endometrial malignancies in developing countries and across the world. -
Zarei, Omid;Rezania, Simin;Mousavi, Atefeh 3425
Approximately, 15-20% of all cancers worldwide are caused by infectious agents. Understanding the role of infectious agents on cancer development might be useful for developing new approaches to its prevention. Mycoplasma genitalium is a clinically important sexually transmitted pathogen that has been associated with several human diseases. There have been a few studies suggestive of probable roles of Mycoplasma genitalium in cancer development, including prostate and ovarian cancers and lymphomas, but the role of this microorganism like other Mycoplasma species in neoplasia is still conjectural. Considering the prevalence of Mycoplasma genitalium infections and also the emergence of resistant strains, Mycoplasma genitalium needs more attention in the infectious agent cancer-causing research area. -
Cervical cancer is a major health problem worldwide and is the most frequent cause of cancer in women in India. Early detection and affordable drugs with clinical efficacy have to go hand-in-hand in order to comprehensibly address this serious health challenge. Plant-based drugs with potent anticancer effects should add to the efforts to find a cheap drug with limited clinical side effects. Keeping this very purpose in mind, an attempt has been made in this review to explore the potential of plant extracts or constituents known to exhibit antitumorigenic activity or exert cytotoxic effect in human cervical carcinoma cells. Alkaloids such as those isolated from C. vincetoxicum and T. Tanakae, naucleaorals A and B, isolated from the roots of N. orientalis, (6aR)-normecambroline, isolated from the bark of N. dealbata appear promising in different human cervical carcinoma cells with the
$IC_{50}$ of 4.0-8${\mu}g/mL$ . However, other compounds such as rhinacanthone and neolignans isolated from different plants are not far behind and kill cervical cancer cells at a very low concentrations. Among plant extracts or its constituents that enhance the effect of known anticancer drugs, noni, derived from the plant M. citrifolia perhaps is the best candidate. The cytotoxic potency and apoptotic index of cisplatin was found to significantly enhanced in combination with noni in different human cervical carcinoma cells and it therefore holds significance as promising herbal-based anticancer agent. However, efficacy needs to be further investigated in various cervical cell lines and more importantly, in in vivo cervical cancer models for possible use as an alternative and safe anticancer drug. -
The high incidence of gastric cancer and consequent mortality pose severe threats to human health. Early screening, diagnosis and treatment are the key to improve the prognosis of the patients with gastric cancer. Gastroscopy with biopsy is an efficient method for the diagnosis of early gastric cancer, but the associated discomfort and high cost make it difficult to be a routine method for screening gastric cancer. Serum tumor marker assay is a simple and practical method for detection of gastric cancer, but it is limited by poor sensitivity and specificity. Therefore, people have been looking for novel serum markers of gastric cancer in recent years. Here we review the novel serum tumor markers of gastric cancer and their diagnostic significance, focusing on the discoveries from serum proteomics analyses and epigenetics researches.
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Sun, Jia-Ming;Li, Qiong;Gu, Hai-Yong;Chen, Yi-Jang;Wei, Ji-Shu;Zhu, Quan;Chen, Liang 3443
Aim: Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. The 5 year survival rate for esophageal cancer patients is very poor and accounts for only 12.3%. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. Methods: We conducted a hospital based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): interleukin 9 (IL9) rs31563 C>T, IL9 rs31564 G>T, IL10 rs1800872 T>G, IL12A rs2243115 T>G, IL12B rs3212227 T>G and IL13 rs1800925 C>T on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The IL10 rs1800872 T>G polymorphism was associated with an increased risk of ESCC. However, there were no significant links with the other five SNPs. Stratified analyses indicated no significant risk of ESCC associated with the IL10 rs1800872 T>G polymorphism evident among any subgroups. Conclusion: These findings indicated that functional polymorphism IL10 rs1800872 T>G might contribute to ESCC susceptibility. However, our results were obtained with a limited sample size, so that the power of our analysis was low. Future larger studies with more rigorous study designs of other ethnic populations are required to confirm the current findings. -
Nasiri, Marzieh;Zarghami, Nosratollah;Koshki, Kazem Nejati;Mollazadeh, Mahdieh;Moghaddam, Mohammad Pourhassan;Yamchi, Mohammad Rahmati;Esfahlan, Rana Jahanban;Barkhordari, Amin;Alibakhshi, Abbas 3449
Background: Telomerase has been considered as an attractive molecular target for breast cancer therapy. The main objective of this work is to assess the inhibitory effects of silibinin and curcumin, two herbal substances, on telomerase gene expression in breast cancer cells. Materials and Methods: For determination of cell viability tetrazolium-based assays were conducted after 24, 48, and 72 h exposure times and expression of human telomerase reverse transcriptase gene was measured with real-time PCR. Results: Each compound exerted cytotoxic effects on T47D cells and inhibited telomerase gene expression, both in a time-and dose-dependent manner. The mixture of curcumin and silibinin showed relatively more inhibitory effect on growth of T47D cells and hTERT gene expression as compared with either agent alone. Conclusions: These findings suggest that cell viability along with hTERT gene expression in breast cancer cells could be reduced by curcumin and silibinin. -
Philip, Phinse Mappalakayil;Parambil, Neetu Ambali;Bhaskarapillai, Binukumar;Balasubramanian, Satheesan 3455
Background: Smoking and smokeless tobacco use are almost always initiated and established during adolescence. More than 80% of adult smokers begin smoking before 18 years of age. The main objective of the present study is to assess the feasibility of preventing adolescent tobacco use with the help of a specially designed tobacco control program. Materials and Methods: A cross sectional survey on tobacco use and related health effects was conducted using a structured questionnaire in 13 randomly selected schools in Kannur district of Kerala. These students were followed for a period of one academic year with multiple spaced interventions such as anti-tobacco awareness classes, formation of anti-tobacco task forces, inter-school competitions, supplying IEC (information, education and communication) materials and providing a handbook on tobacco control for school personnel. Final evaluation was at the end of one year. Results: There were 4,144 school children who participated in the first phase of the study. The prevalence of tobacco smoking and chewing habits were 9.85% and 2.24% respectively. Ninety-one percent had parental advice against tobacco use and only 3.79% expressed desire for future tobacco use. The final evaluation witnessed a sharp decline in the current tobacco use as 4.68%. We observed a statistically significant difference towards the future use of tobacco (p<0.001) and awareness about the ill effects of passive smoking (p<0.001) among boys and girls. Further a significantly increased knowledge was observed among boys compared to girls about tobacco and oral cancer (p=0.046). Conclusions: The comprehensive school based tobacco control project significantly reduced the tobacco use pattern in the target population. School tobacco projects incorporating frequent follow ups and multiple interventions appear more effective than projects with single intervention. -
Yildirim, Mustafa;Karakilinc, Hulya;Yildiz, Mustafa;Kurtoglu, Erdal;Dilli, Utku Donem;Goktas, Sevil;Demirpence, Ozlem;Kaya, Vildan 3461
Background: Non-Hodgkin lymphoma (NHL) is a solid tumour of lymphocytes, important elements in the immune system. According to 2006 data, in Turkey the incidence was 6.5 per 100,000 in males, and 4.4 in females. The relationship between the use of pesticides and development of NHL has been extensively investigated in many studies, and it has been demonstrated that the risk of NHL is increased by exposure to such compounds. Antalya is a region of intensive agricultural activity. In this study, the relationship between the incidence of lymphoma in Antalya and the amount of pesticides employed was investigated. Materials and Methods: The study used data from 1995 to 2010 on the patients from the databank of TR Ministry of Health, Antalya Provincial Health Directorate, Cancer Registration Center and the patients who were histopathologically diagnosed with NHL during these years. Results: The relationship between the amount of pesticide used and the incidence was studied with the Spearman correlation analysis and the p value was found as 0.05. The correlation coefficient was 0.497. An increase in the NHL incidence over the years was identified, with a 2.42-fold increment found from 1995 to 2005 and a 2.77 fold elevation from 1995 to 2010. The use of pesticides increased 1.89 fold over the same period. Conclusions: Our study investigated the relationship of the pesticides used with NHL patients diagnosed during the same year. Since the time elapsing after exposure to pesticides until the development of cancer is not clear, no comparison can be made at present. We believe that the increase in use of pesticides since 1995 may be associated with the increase in the incidence of NHLand therefore that further studies on the issue including measurements of serum pesticide levels, are required. -
Khurshid, Amna;Faridi, Naveen;Arif, Afreen M.;Naqvi, Hanna;Tahir, Muhammad 3465
Background: Breast cancer is the most frequent malignant disease amongst young women. If we review local data in Pakistan then breast cancer represents approximately a third of all cancers in females. The age standardized incidence rate (ASR) world per 100,000 is 53.8 and crude incidence rate is 30.9. We have observed during our surgical pathology practice and it is also reported by other Asian studies that breast carcinoma is amongst the leading malignancies in the region and the patients are at least a decade younger than counterparts in developed nations. Age is an important issue in effective screening, diagnosis and management of breast cancer, especially in this geographical region where late presentation and poor prognosis are a hallmark of the disease. Objective: The aim of this study is to determine the frequency of malignant breast lesions in symptomatic young females presenting with breast lumps. Materials and Methods: This is a retrospective study conducted at the Pathology Department, Liaquat National Hospital and Medical College, Karachi. Descriptive and pathology data of malignant breast tumors 1st January 2004 to 31st December 2009 were reviewed, using the departmental archived data. It included both male and female patients up to the age of 25 years. Results: A total of 714 surgical specimens from/of symptomatic breast lesions were received at the pathology department of Liaquat National Medical, in the five years study period, in young females. There were 575 (80%) benign, 119 (16%) inflammatory and 20 (2.8%) malignant lumps. Conclusions: The obtained data for females only up to 25 years of age suggest a massive burden which requires urgent attention. Early assessment of lesions is essential in order to avoid mortality from malignancies. -
Suzuki, Nobutaka;Takimoto, Yuko;Suzuki, Riho;Arai, Takanari;Uebaba, Kazuo;Nakai, Masuo;Strong, Jeffry Michael;Tokuda, Harukuni 3469
Extract of Lentinula edodes mycelia (LEM) is currently utilized as an oral biological response modifier (BRM) medicine for cancer patients. However, its effectiveness for breast cancer patients with postoperative adjuvant hormone therapy has not yet been scientifically verified. In this study, we investigated the influence of LEM on the quality of life (QOL) and immune response in breast cancer patients undergoing postoperative adjuvant hormone therapy. Twenty patients were studied in total. They received only hormone therapy in the first 4 weeks followed by hormone therapy and LEM during the next 8 weeks. Laboratory tests, QOL score and peripheral blood cytokine production levels were evaluated during the study period. No changes in QOL or cytokines were noted after the first 4 weeks. In contrast, during the following combined therapy period, improvements were noted in QOL and cytokine levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant use of LEM with postoperative adjuvant hormone therapy improves the QOL and immune function of patients. -
Chong, Raymond Jih Yeong;Abdullah, Mohd Syafiq;Hossain, Mohammad Moshaddeque;Telisinghe, Pemasari Upali;Chong, Vui Heng 3473
Background: Primary liver cancer (PLC) is the fifth most common malignancy worldwide and is still associated with high mortality. Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the two most common PLCs, and their incidence varies across regions. Currently there are no published data available on the incidence of PLC in Brunei Darussalam. Materials and Methods: All proven PLCs between 2000 and 2009 were identified from the National Cancer Registry and reviewed. Metastatic diseases were excluded. A total of 123 cases (male 65.8%, female 34.2%) were identified and their data collected for calculation of the age standardised rate (ASR). Results: The most common type of PLC was HCC (87.8%) followed by cholangiocarcinoma (10.6%). There were two cases of hepatoblastoma. The mean age at diagnosis was 63.2 years. The overall ASR of PLC was 8.2/100,000, increasing from 4.5/100,000 population in 2000 to 11.4/100,000 population in 2009. The rates were higher among males (12.0/100,000) than females (4.7/100,000). Among the ethnic groups, Chinese had the highest rates (overall 13.1/100,000 with none recorded in 2000 to 30.3/100,000 in 2009) compared to the Malays (overall 8.5/100,000 increasing from 4.5/100,000 in 2000 to 12.3/100,000 in 2009) and the indigenous groups. The incidence increased after the age of 50 and was highest among the 75-79 age groups. Increase was seen for HCC but not for cholangiocarcinoma. Conclusions: The most common type of PLC is HCC and the annual incidence of PLC is increasing in Brunei Darussalam,rates being higher in males and Chinese. -
Ashkavandi, Zohreh Jaafari;Najvani, Ali Dehghani;Tadbir, Azadeh Andishe;Pardis, Soheil;Ranjbar, Mohammad Ali;Ashraf, Mohammad Javad 3479
Background: Proliferation markers widely have been used to diagnose and determine the behaviour and prognosis of benign and malignant tumours. Minichromosome maintenance 3 (MCM3) is a novel proliferation marker. The aim of this study was to evaluate and compare MCM3 with Ki-67 in diagnosis of salivary gland tumours. Materials and Methods: In this retrospective study, immunohistochemical expression of MCM3 and Ki-67 was evaluated in 15 pleomorphic adenomas (PA), 17 mucoepidermoid carcinomas (MEC) and 18 adenoid cystic carcinomas (ADCC). Labeling indices (LIs) for the two markers were calculated and compared. Results: MCM3 and Ki-67 LIs were significantly higher in MEC and ADCC compared to PA. The LI of MCM3 was significantly higher than that of Ki-67 in MEC and PA. There was no significant difference between the two markers in ADCC. A cut-off point of 8% with 74.3% sensitivity and 93.3% specificity for MCM3 was obtained to discern between benign and malignant tumors. Conclusions: These results suggest that MCM3 might be a useful proliferation marker for differential diagnosis and recognition of clinical behavior of salivary gland tumors. -
Jeganathan, Premila Devi;Hairi, Noran N.;Al Sadat, Nabilla;Chinna, Karuthan 3483
Background: To identify the prevalence of different stages of smoking and differences in associated risk factors. Materials and Methods: Thos longitudinal study started in February 2011 and the subjects were 2552 form one students aged between twelve to thirteen years of from 15 government secondary schools of Kinta, Perak. Data on demographic, parental, school and peer factors were collected using a self-administered questionnaire. We examined the effects of peer, school and parental factors on the five stages of smoking; never smokers, susceptible never smokers, experimenters, current smokers and ex-smokers, at baseline. Results: In the sample, 19.3% were susceptible never smokers, 5.5% were current smokers 6% were experimenters and 3.1% were ex-smokers. Gender, ethnicity, best friends' smoking status, high peer pressure, higher number of relatives who smoked and parental monitoring were found to be associated with smoking stages. Presence of parent-teen conflict was only associated with susceptible never smokers and experimenters whereas absence of home discussion on smoking hazards was associated with susceptible never smokers and current smokers. Conclusions: We identified variations in the factors associated with the different stages of smoking. Our results highlight that anti-smoking strategies should be tailored according to the different smoking stages. -
Hajmanoochehri, Fatemeh;Mohammadi, Navid;Nasirian, Neda;Hosseinkhani, Mohsen 3491
Background: Gastric and esophageal cancers are among the most lethal human malignancies worldwide. Of all malignancies estimated in Iran (47,100), gastric and esophageal cancers were responsible for 7,800 and 3,500 deaths in 2008 respectively. The present study aimed to provide an image of patho-epidemiological characteristics with their trends during two past decades with emphasis on topographic, morphologic, and some demographic features. Materials and Methods: In a hospital-based retrospective study in 2009, all pathological reports from esophageal endoscopies and gastric biopsies through a 20 years period (1989-2008) were collected and analyzed in four interval periods(five years each). Also, all eligible samples in hospital archives were enrolled for further testing. Besides, demography, topography and morphology of all samples were determined and analyzed by statistical software. Results: No significant statistical difference was seen in frequency of espohageal and gastric tumors throughout the study. Esophageal cancer cases were older than gastric. Sex ratio was 2.33/1 and men had a higher rate of both esophageal and gastric tumors. Stomach cancer included 64.3% of all cases. Inferior third and end of esophagus were common locations for esophageal tumors whereas proximal stomach was common for gastric tumors. Squamous cell carcinoma and adenocarcinoma were common morphological types of tumors in esophagus and stomach respectively. Conclusions: Morphological trends showed an increase of esophageal adenocarcinoma and diffuse/intestinal ratio in stomach cancers. Trends in incidence from gastric cancer decreased based on topographic studies but we could not find a topographical trend toward cadia. -
MicroRNAs (miRNAs) are a class of endogenously expressed small, non-coding, single-stranded RNAs that negatively regulate gene expression, mainly by binding to 3'- untranslated regions (3'UTR) of their target messenger RNAs (mRNAs), which cause blocks of translation and/or mRNA cleavage. Recently, miRNAprofiling studies demonstrated the microRNA-497 (miR-497) level to be down-regulated in all prostate carcinomas compared with BPH samples. The purpose of this study was to investigate the potential role of miR-497 in human prostate cancer. Proliferation, cell cycle and apoptosis assays were conducted to explore the potential function of miR-497 in human prostate cancer cells. Results showed that miR-497 suppressed cellular growth and initiated G0/G1 phase arrest of LNCaP and PC-3 cells. We also observed that miR-497 increased the percentage of apoptotic cells by increasing caspase-3/7 activity. Taken together, our results demonstrated that miR-497 can inhibit growth and induce apoptosis by caspase-3 activation in prostate cancer cells, which suggest its use as a potential therapeutic target in the future.
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Pouladi, Nasser;Kouhsari, Shideh Montasser;Feizi, Mohammadali Hosseinpour;Gavgani, Reyhaneh Ravanbakhsh;Azarfam, Parvin 3503
Background: Although the majority of investigations concerned with TP53 and its protein have focused on coding regions, recently a set of studies highlighted significant roles of regulatory elements located in p53 mRNA, especially 5'UTR. The wrap53${\alpha}$ transcript is one of those that acts as a natural antisense agent, forming RNA-RNA hybrids with p53 mRNA and protecting it from degradation. Materials and Methods: In this study, we focused on the mutation status of exon$1{\alpha}$ of the WRAP53 gene (according to exon 1 of p53) in 160 breast tumor tissue samples and conducted a bioinformatics search for probable miRNA binding site in the p53/wrap53 overlapping region. Mutations were detected, using single stranded conformation polymorphism (SSCP) and sequencing. We applied the miRBase database for prediction of miRNAs which target overlapping region of p53/wrap53 transcripts. Results: Our results showed all samples to have wild type alleles in exon 1 of TP53 gene. We could detect a novel and unreported intronic mutation (IVS1+56, G>C) outside overlapping regions of p53/wrap53 genes in breast cancer tissues and also predict the presence of a binding site for miR-4732-5p in the 5'UTR of Wrap53 mRNA. Conclusions: From our findings we propose designing further studies focused on overexpression of miRNA-4732-5p and introducing different mutations in the overlapping region of wrap53 and p53 genes in order to study their effects on p53 and its${\Delta}N$ isoform (${\Delta}$ 40p53) expression. The results may provide new pieces in the p53 targeting puzzle for cancer therapy. -
Li, Nan;Hu, Wen-Jun;Shi, Jie;Xue, Jie;Guo, Wei-Xing;Zhang, Yang;Guan, Dong-Xian;Liu, Shu-Peng;Cheng, Yu-Qiang;Wu, Meng-Chao;Xie, Dong;Liu, Shan-Rong;Cheng, Shu-Qun 3509
The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson${\chi}^2$ test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy. -
Aysan, Erhan;Bayrak, Omer Faruk;Aydemir, Esra;Telci, Dilek;Sahin, Fikrettin;Yardimci, Cem;Muslumanoglu, Mahmut 3515
Background: Effects of whole cell type immunization on mice Ehrlich tumours were evaluated. Materials and Methods: After preliminary study, mice were divided two major groups;$1{\times}1000$ and$100{\times}1000$ live Ehrlich cell transferred major groups, each divided into four subgroups (n: 10). Study groups were immunized with Ehrlich cell lysates in 0, 3, 7,$14^{th}$ days and after 30 days of last immunization, live Ehrlich cells were transferred. Mice were observed for six months and evaluated for total and cancer free days. Results: Out of$100{\times}1000$ cell transferred solid type study group, all study group mean and tumour free periods were statistically longer than control groups. All$1{\times}1000$ Ehrlich cell transferred study groups survived significantly longer than$100{\times}1000$ Ehrlich cell transferred groups. Conclusions: Ehrlich mice tumours were prevented and survival prolonged with whole cell type immunization. Effects are related to the number of transferred tumor cells. -
Zhang, Bing-Hui;Liu, Wei;Li, Liang;Lu, Jian-Guang;Sun, Ya-Nan;Jin, De-Jun;Xu, Xiu-Yu 3521
Objective: The current study explored the expression of KAI1/CD82 and MRP1/CD9 and its significance in laryngeal squamous cell carcinoma (LSCC). Methods: The expression levels of KAI1/CD82 and MRP1/CD9 in 100 LSCC tissue specimens, as well as in 30 para-LSCC non-carcinomatous tissue specimens randomly taken from the patients, were assessed using the quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry and correlations with pathological parameters of LSCC and their influence on survival function were analyzed. Results: KAI1/CD82 and MRP1/CD9 showed basically consistent changes in both mRNA and protein expression. Their expression in the 30 LSCC specimens was significantly lower compared with that in the corresponding non-carcinous tissues (P < 0.01 or 0.05), notably correlating with TNM stage, differentiation degree, clinical stage, and lymphatic metastasis (P < 0.01 or 0.05), but not gender, age, and LSCC growth sites (P > 0.05). The median survival of patients with positive KAI1/CD82 and MRP1/CD9 protein expression was longer than that of patients with negative protein expression (P < 0.01 or 0.05). KAI1/CD82 protein expression negatively correlated with MRP1/CD9 protein expression in LSCC (${\chi}^2$ = 31.25, P < 0.01). Conclusion: KAI1/CD82 and MRP1/CD9 may jointly participate in the development of LSCC. They may serve as the markers for judging the infiltration, metastasis, and prognosis of LSCC. -
Ismail, Said Ibrahim;Soubani, Majd;Nimri, Jena Monther;Al-Zeer, Ali Hazem 3527
Background: Cancer is a major health problem facing the entire world, and Jordan is no exception. However, patterns of cancer incidence and cancer burden in Jordan have never been explored thoroughly, and the aim of this study was to close this knowldege gap. Materials and Methods: The study was based on data obtained from the Jordan cancer registry from 1996 to 2009. All cancer cases that were diagnosed during the study period were registered and included in this study. Results: A total of 51,626 cases were registered in Jordan during the 14- year period. The incidence rate showed no significant increase in males (percent change PC 6.8%), while in females a marked increase was observed (PC 14.8%). The major cancer sites for males were bronchus and lung, colorectal, bladder, leukemia and prostate. In females, the leading cancer sites were breast, colorectal, leukemia, thyroid and NHL. Conclusions: Compared to other countries in the region, Jordan has comparable rates. On the other hand the rates of cancer are markedly lower in Jordan compared to more industrialized countries such as the US and Europe. There was an overall increase in the incidence of cancer in Jordan, especially among females, which stresses the need for programs to raise awareness on the importance of early diagnosis and preventive life style measures. -
Masood, Nosheen;Yasmin, Azra;Kayani, Mahmood A. 3535
Head and neck cancer is one of the leading causes of deaths worldwide. Two genes GSTM1 and GSTT1 involved in phase II of carcinogen detoxification have been frequently studied in the literature. Their null genotypes are thought to be associated with increased head and neck cancer risk. However, the published reviews are not up to date and many important papers have been skipped. The current literature review was restricted to the null genotypes of the GSTM1 and GSTT1 genes with special emphasis on the genotypic status. We found that the size of study sample varied greatly and the oral cavity cancer was more influenced by GSTM1 and GSTT1 gene deletions. With respect to ethnicity Asians are more prone to head and neck cancers with these null genotypes as compared to Europeans and Americans. The current review showed significant associations (OR=9.0, 95%CI; 1.4-9.5; OR=3.7, 95%CI; 1.4-9.5) of GSTM1 and GSTT1 null genotypes with head and neck cancers. Review confirms the data of previous reviews that GSTM1 and GSTT1 gene polymorphisms may be risk factors for cancer initiation. -
Sarkar, Madhutandra;Konar, Hiralal;Raut, Deepak 3541
Background: This cross-sectional observational study was undertaken to establish clinico-pathological characteristics of patients with gynecological malignancies, focusing mainly on symptoms, histological type and stage of the disease at presentation, in a tertiary care setting in Eastern India. Materials and Methods: In the gynecology out-patient clinic of a tertiary care hospital in Kolkata, India, the patients with suggestive symptoms of gynecological malignancies were screened. Their diagnoses were confirmed by histopathology. One hundred thirteen patients with histopathologically confirmed gynecological malignancies were interviewed. Results: The most frequently reported symptoms by the patients with histopathologically confirmed gynecological malignancies were excessive, offensive with or without blood stained vaginal discharge (69.0%), irregular, heavy or prolonged vaginal bleeding (36.3%) and postmenopausal bleeding (31.9%). The majority of the patients (61.0%) had squamous cell carcinoma on histopathological examination, followed by adenocarcinoma (30.1%). Nearly half of the patients (48.7%) were suffering from the Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage III, followed by stage II (40.7%) malignancy. Conclusions: This study highlights that most of the patients with gynecological malignancies present late at an appropriate health care facility. Ovarian cancer may often have non-specific or misleading symptomatic presentation, whereas cervical cancer often presents with some specific symptoms. These observations point to the need for increasing awareness about gynecological malignancies in the community and providing easily accessible adequate facilities for early detection and treatment of the disease by optimal use of available resources, i.e. strengthening the primary health care system. -
Mansour-Ghanaei, Fariborz;Joukar, Farahnaz;Soati, Fatemeh;Mansour-Ghanaei, Alireza;Atrkar-Roushan, Zahra 3549
Background: It is generally accepted that gastric carcinomas are preceded by a sequential multistage process that includes chronic gastritis, gastric atrophy, usually with intestinal metaplasia (IM), and dysplasia. This series of changes in gastric carcinogenesis is often initiated by Helicobacter pylori (H pylori) infection. The aim of the present study was determination of gastric histopathologic changes in IM patients after at least one year in Guilan province, Iran. Materials and Methods: This case-series study was conducted in Guilan Gastrointestinal and Liver Disease Research Center (GLDRC) during 2010 to 2011. Gastric biopsy was performed for all 71 known cases of IM and precanceric lesions including gastric atrophy, IM, dysplasia and H pylori infection were determined after at least one year. Results: Of the total of 71 patients with established IM who were enrolled, 50 had complete-type IM and 21 had incomplete-type IM. Fifty two people had H pylori infection. H pylori eradication was achieved in 39 patients (75%). Secondary pathology findings of patients with IM were complete metaplasia (39.4%), incomplete metaplasia (32.4%), dysplasia (23.9%) and other precanceric lesions (4.2%). Dysplasia (20%vs 33%) occurred in patients who had complete and incomplete IM at baseline respectively (p>0.05). Age, gender, family history of gastric cancer(GC); smoking habits and NSAIDs use were not associated with gastric premalignant lesions in initial and secondary pathologies (p>0.05). The difference became statistically significant between H pylori infection in patients with more than 3 years diagnostic intervals (p<0.05). Statistical difference between eradicators and non-eradicators was not significant. Conclusions: We found that incomplete IM increased the risk of subsequent dysplasia in this study. -
Thongbai, Chureeporn;Sa-nguanmoo, Pattaratida;Kranokpiruk, Pavanrat;Poovorawan, Kittiyod;Poovorawan, Yong;Tangkijvanich, Pisit 3555
Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factors for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variation and the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infected with HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249S mutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP) in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basal core promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group. R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was not significantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations was independently associated with the risk of HCC in Thai patients. -
Background: The negative effects of gynecologic cancer on women's health is multidimensional. Sexual problems arising after chemotherapy are decreased interest and vaginal lubrication, lack of orgasm and dyspareunia and sense of reduction in sexual attractiveness in general. The purpose of this study was to evaluate changes that patients who receive chemotherapy for a gynecologic oncology disorder experience in their sexual functions. Materials and Methods: A descriptive/cross-sectional and qualitative study was performed. The Female Sexual Function Index (FSFI) was used in order to collect data on sexual capacity. The quantitative data obtained were evaluated with frequency and percentage calculations while content analysis was performed for the qualitative data. Results: All of the information related to sexuality was provided by the physician. Chemotherapy treatment affected sexuality negatively in 55.9%. Since receiving the diagnosis, 52.9% of women had experienced no sexual intercourse at all. Those who had an FSFI score of 30 and below made up 75% of the women. After the content analysis of data obtained during in in-depth interviewing, we focused on three main themes: desire for sexual intercourse, problems experienced during sexual intercourse, and coping with problems. Conclusions: An integrated system where sexual problems can be handled professionally should be present during gynecological cancer treatment.
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Butthongkomvong, Kritiya;Sirachainan, Ekaphop;Jhankumpha, Supattra;Kumdang, Surang;Sukhontharot, On-Usa 3565
Background: Cholangiocarcinoma is the most common cancer in males in Thailand. The outcome is poor although systemic chemotherapy has been used in attempts to improve disease control, quality of life and prolong survival in patient with unresectable and advanced disease. Materials and Methods: In this retrospective study the medical records of all patients diagnosed as having unresectable and metastatic cholangiocarcinoma and receiving systemic chemotherapy at Udonthani Cancer Hospital during January 2007 to December 2010 were reviewed. Results: Among the total of 105 patients, 21 received gemcitabine-based chemotherapy and 84 5FU-based chemotherapy. Most received platinum doublet regimens. 5FU-based regimens yielded an overall response rate (tumor control) of 23.8% and a median survival of 7.2 months while gemcitabine-based regimens yielded an overall response rate (tumor control) 19.1% and a median survival of 10.0 months. Conclusions: Tumor control and survival of patient with advanced cholangiocarcinoma treated with gemcitabine-based and 5FU-based chemotherapy do not markedly differ. -
Huang, Xian-Ju;Ren, Wei;Li, Jun;Chen, Lv-Yi;Mei, Zhi-Nan 3569
Aim: Pendulous monkshood root is traditionally used for the treatment of several inflammatory pathologies such as rheumatisms, wounds, pain and tumors in China. In this study, the anti-inflammatory and anticancer activities and the mechanism of crude ethanol extract of pendulous monkshood root (EPMR) were evaluated and investigated in vitro. Materials and Methods: The cytotoxic effects of EPMR on different tumor cell lines were determined by the MTT method. Cell apoptosis and cell nucleus morphology were assessed by Hoechst 33258 staining. Moreover, nitric oxide (NO) levels and intracellular oxidative stress in peritoneal macrophages were determined to further elucidate mechanisms of action. Results: The data showed that EPMR could produce significant dose-dependent toxicity on three kinds of tumor cells. Furthermore, EPMR displayed obvious anti-inflammatory effects on LPS-induced mouse peritoneal macrophages at the dosage of 4 - 200${\mu}g/mL$ . The results demonstrated the therapeutic potential of Pendulous Monkshood Root on cancer and inflammatory diseases. Conclusion: Our results indicate that EPMR has anti-inflammatory and anticancer properties, suggesting that pendulous monkshood root may be a useful anti-tumor and anti-inflammatory reagent in the clinic. -
Jia, Liu-Qun;Shen, Yong-Chun;Guo, Shu-Jin;Hu, Qian-Jing;Pang, Cai-Shuang;Wang, Tao;Chen, Lei;Wen, Fu-Qiang 3575
Background: The 2518 A/G polymorphism in the MCP-1 gene has been extensively studied for association swith cancer; however, results from replication studies have been inconsistent. The aim of this investigation was to determine links with risk of cancer by meta-analysis. Methods: We searched Pubmed, Embase, CNKI, Weipu and Wanfang databases, covering all case-control studies until March, 2013. Statistical analyses were performed using the Revman 5.0 software. Results: A total of 11 case-control studies met our inclusion criteria, including 1,422 cases and 2,237 controls. The results indicated that the MCP-1 2518 gene polymorphism had no association with cancer risk overall (GG vs.GA+ AA: OR = 0.89, 95%CI = 0.61-1.28, P = 0.52). However, in the subgroup analysis by ethnicity, a decrease of cancer risk was found in Asian populations (GG vs.GA+ AA: OR = 0.79, 95%CI = 0.63-0.99, P = 0.04). Conclusion: This meta-analysis suggested that the 2518A/G polymorphism of MCP-1 gene is associated with risk of cancer among Asian, but not in Caucasian populations. -
Background: Accurate statistics on the cancer burden are essential, both for purposes of research and for setting priorities in healthcare management. So that in vast countries with partial registration coverage, such as Iran, local data are more useful. We here estimated the incidence, prevalence and mortality time trend of four major cancer site, lung, stomach, breast and prostate, over the period 2001-2010 and provided short-range projections to 2015 in Isfahan. Materials and Methods: Estimates were derived by applying the mortality-incidence analysis method, a back-calculation approach to estimate and project incidence, prevalence and mortality of chronic degenerative disease, starting from knowledge of mortality and relative survival information. Results: Age adjusted incidence, mortality and prevalence rates in Isfahan exhibited a clear upward trend for all four sites during the period 2001-2015, with marked increasees in prostate and breast predicted for the future. Difference in incidence trends between males and females might be attributable to the difference in risk factors specific to certain cancer sites, with smoking being the main risk factor. Conclusions: In this study, males and females displayed an increasing pattern for incidence and mortality rate over the entire study period until 2015. This information can be used as basis for planning healthcare management and allocating recourses in public health.
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Jin, Cong-Guo;Chen, Xiao-Qun;Li, Jia;Wu, Zhi-Pin;Liu, Xin;Wang, Xi-Cai 3587
Aims: To study the CIK cell treatment effects on regulation of cellular immune function disorders in patients with lung cancer, and to analyze the time characteristics. Methods: Cellular immune function was assessed by FCM, and patients with functional disorders were randomly divided into two groups, one given CIK cell therapy within 18 months (5 courses) and the other the controls, which were followed up for 1 year with cellular immune functions tested once a month. Results: There were 5 types of cellular immunity, 4 of which are disorders; after CIK treatment, the improvement rate of the 4 groups were 79.1%, 70.8%, 76.0% and 70.0%, intergroup differences not being statistically significant (P=0.675), all significantly higher than in the control group (P=0.000). The median maintenance times for the 4 groups were 10.4 months (9.76-11.04), 8.4 months (7.86-8.94), 9.8 months (9.20-10.4) and 7.9 months (6.25-9.55), respectively. Conclusions: CIK cells were able to improve the immune functions of patients with lung cancer, the rate of improvement and maintenance time being related to the immune function before the treatment and CIK-cell-therapy courses. -
Background: For a number of reasons from cultural compatibility, to accessibility, to cost, traditional healers are a major source of health care in developing countries. In Malaysia, it's been estimated that upwards of 80% of the population consult traditional healers even if simultaneously seeking treatment from the Western medical system. Partially as a result of the widespread practice of visiting traditional healers, cancer diagnosis and treatment in Malaysia is often delayed or interrupted resulting in late presentation, advanced stage diagnosis, and a higher mortality rate than in Western countries. However, there is very little research on the role of traditional healers in cancer treatment in Malaysia. Materials and Methods: This qualitative study was designed to identify the roles traditional healers play in cancer diagnosis and treatment, with an eye to alleviating the cancer burden through educational responses with four publics in mind-policy makers, Western medical personnel, traditional healers, and the general public. In-depth interviews were conducted with 14 Malay traditional healers, 13 cancer survivors who had seen both traditional healers and Western doctors, and 12 cancer medical specialists. Results: Analysis of the data from these 39 participants revealed four roles traditional healers play in cancer treatment-medicinal healer, emotional comforter, spiritual guide, and palliative caregiver. Conclusions: Three roles (emotional, spiritual, palliative) can be seen as complementary to the allopathic system. Emotional and spiritual roles may augment the effectiveness of biomedical treatment. Cancer awareness and education programs need to position traditional healers as complementary, rather than an alternative to Western medical treatment; Validating the roles Traditional Healers can play in cancer treatment in MY through health promotion and education will contribute to alleviating the nation's cancer burden.
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Background: To investigate the infection status and predominant genotype distribution of human papillomavirus (HPV) infection among Chinese patients with mucopurulent cervicitis (MPC) or cervical cancer (CC) in Hangzhou. Methods: Initially, 217 cases of healthy cervix controls (n=50), acute MPC (n=89), and CC (n=78) were included; samples were collected between January 1, 2010, and January 30, 2013. Cervical specimens were screened for HPV using a nested polymerase chain reaction assay and DNA sequencing. Results: Overall prevalence of HPV infection was 16.7% in the control group, 51.9% in the MPC group, and 84.4% in the CC group. The predominant genotype detected in all 3 groups was the oncogenic variant HPV 16 (55.8%, 17.3%, and 6.3% in the CC, MPC and control specimens, respectively), HPV58 was the second most predominant HPV type in CC (9.1%), MPC (8.6%), and control group (4.2%). Most or all of the genotypes were oncogenic in the three groups. Conclusions: Infection with HPV was found to be prevalent among Chinese women with MPC or CC and oncogenic variants were in the majority. Therefore, peoples who suffered MPC with HPV DNA positive should be regularly followed-up, for prevention and early treatment of cervical cancer.
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Li, Cong;Lu, Hua-Jun;Na, Fei-Fei;Deng, Lei;Xue, Jian-Xin;Wang, Jing-Wen;Wang, Yu-Qing;Li, Qiao-Ling;Lu, You 3607
Introduction: Reported prognostic roles of hypoxic inducible factor (HIF) expression in non-small cell lung cancer (NSCLC) have varied. This meta-analysis aimed to examine the relationship between HIF expression and clinical outcome in NSCLC patients. Methods: PubMed were used to identify relevant literature with the last report up to December$20^{th}$ , 2012. After careful review, survival data were collected from eligible studies. We completed the meta-analysis using Stata statistical software (Version 11) and combined hazard ratio (HR) for overall survival (OS). Subgroup specificity, heterogeneity and publication bias were also assessed. All of the results were verified by two persons to ensure accuracy. Results: Eight studies were finally stepped into this meta-analysis in which seven had available data for HIF-$1{\alpha}$ and three for HIF-$2{\alpha}$ . Combined HRs suggested that higher expression of$HIF1{\alpha}$ had a negative impact on NSCLC patient survival (HR=1.50; 95%CI=1.07-2.10; p=0.019). The expression of HIF-$2{\alpha}$ was also relative to a poorer survival (HR=2.02; 95%CI=1.47-2.77; p=0.000). No bias existed in either of the two groups. Conclusion: This study suggests that elevations of HIF-$1{\alpha}$ and HIF-$2{\alpha}$ expression are both associated with poor outcome for patients with NSCLC. The data support further and high quality investigation of HIF expression for predicting poor outcome in patients with NSCLC. -
Ping, Wei;Jiang, Wen-Yang;Chen, Wen-Shu;Sun, Wei;Fu, Xiang-Ning 3613
Object: To detect expression of hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$ ) and lysyl oxidase (LOX) in non-small cell lung cancer (NSCLC) and explore their roles in prognosis. Methods: The mRNA levels of HIF-$1{\alpha}$ and LOX were investigated by real-time reverse-transcriptase polymerase chain reaction in 40 cases of tumour and paired normal tissues. In addition, protein expression of HIF-$1{\alpha}$ and LOX was examined by immunohistochemistry in 82 cases of tumour and 45 paired normal tissues. The relationship between HIF-$1{\alpha}$ or LOX and clinicopathologic characteristics, as well as the correlation between HIF-$1{\alpha}$ and LOX, were also examined. Kaplan-Meier survival curves and the log-rank test were used to analyze progression-free survival. Results: HIF-$1{\alpha}$ or LOX mRNA levels in tumor tissues was significantly higher than those in paired normal tissues (p<0.01). Positive HIF-$1{\alpha}$ or LOX protein expression in tumor tissues was noted in 46/82 (56.1%) and 49/82 (59.8%) of the cases, respectively, being significantly higher than those in paired normal tissues (p<0.05). There was significant correlation between the expression of HIF-$1{\alpha}$ or LOX and tumor size, lymph node metastasis and pathological stage (p<0.05). The expression of HIF-$1{\alpha}$ and LOX had a significant inverse impact on survival of patients with NSCLC. Conclusion: HIF-$1{\alpha}$ and LOX may play a pivotal role in the development of NSCLC, and may act in synergy to promote the progression of NSCLC. -
Halawany, Hassan Suliman;Jacob, Vimal;Abraham, Nimmi Biju;Al-Maflehi, Nassr 3619
Background: The scientific evidence relating to the burden of oral diseases attributable to tobacco use has been reviewed and the need for a well-structured dental teaching program concentrating on oral cancer education and tobacco cessation interventions has been emphasized. The aim of our study was to evaluate the awareness of oral cancer and perception of tobacco use cessation counseling among dental students at all study levels in India, Saudi Arabia, the United Arab Emirates, and Yemen. Materials and Methods: A structured, pre-tested, self-administered 15-item questionnaire was used to conduct a cross-sectional survey. Data analyses including percentages, frequency distributions and tests of chi-square were generated. Results: A total of 621 (97.6%) Indian, 493 (96.5%) Saudi, 194 (96.5%) Yemeni and 187 (98.4%) United Arab Emirates respondents recognized the association between oral cancer and cigarette smoking. Although more than 96% of the students surveyed recognized the association between oral cancer and cigarette smoking and about 55% reported cigarette smoking as one of the etiological factors of oral cancer, more than 66% of students who reported cigarette smoking as an etiological factor of oral cancer disagreed/strongly disagreed with all the statements concerning tobacco use cessation. Conclusions: A higher level of oral cancer awareness did not have a positive impact on the perception of tobacco use cessation counseling among the sample surveyed. -
Kim, Myung-Chul;Cui, Feng-Ji;Kim, Yongbaek 3625
Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by$H_2O_2$ in human malignant mesothelioma (HMM) cells. Cultured HMM cells were treated with$H_2O_2$ , followed by measuring expression levels of EMT-related genes and proteins. Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not in epithelioid cells. Treatment of HMM cells with$H_2O_2$ promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with$H_2O_2$ . Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-$1{\alpha}$ ) and transforming growth factor beta 1 (TGF-${\beta}1$ ). Considering that treatment with$H_2O_2$ results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes. -
Li, Hong-Yan;Zhang, Yan;Cai, Jian-Hui;Bian, Hong-Lei 3631
MicroRNAs (MiRNAs) play important roles in coordinating a variety of cellular processes and abnormal expression has been linked to the occurrence of several cancers. The miRNA miR-451 is downregulated in colorectal carcinoma (CRC) cells, suggested by several research groups including our own. In this study, synthetic miR-451 mimics were transfected into the SW620 human CRC cell line using Lipofectamine 2000 and expression of miR-451 was analyzed by real time PCR, while expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2 was analyzed by Western blot, and cell growth was detected by MTT assay. In comparison to the controls, a significant increase in the expression of miR-451 was associated with significantly decreased expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2. The capacity of cell proliferation was significantly decreased by miR-451 expression, which also inhibited cell growth. Our study confirmed that miR-451 has a repressive role in CRC cells by inhibiting cell growth through down-regulating the P13K/AKT pathway. -
Keshavarz, Hooman;Jafari, Ahmad;Khami, Mohammad Reza;Virtanen, Jorma Ilmari 3635
Background: Conclusive evidence exists about associations between several life-threatening diseases and passive smoking. The objective of our study was to investigate the prevalence of passive smoking among Iranian dental students, to assess their attitudes towards tobacco control programs, and to explore the association between these two and tobacco use. Methods: In eight randomly selected dental schools, all fourth-year students were surveyed by means of a self-administered anonymous questionnaire in December 2010. The Global Health Professions Student Survey (GHPSS) questionnaire served as the data collection instrument. Exposure to environmental tobacco smoke (ETS) was assessed during the previous week. Chi-square test, logistic regression, and linear regression served for statistical analyses. Results: The response rate was 84% (325 students, 66% female). Exposure to ETS was reported by 74% of the participants. Men were significantly more exposed to ETS at home, and in other places than were women. Most of the students agreed on queried tobacco control policies. The lowest agreement (72%) was for banning smoking in coffee shops and teahouses. A logistic regression model showed that adjusted for gender, passive smoking at home is significantly associated with current tobacco use. A linear regression model suggested that the total score of attitudes is significantly associated with passive smoking at home, passive smoking in other places, tobacco use experience, and current tobacco use. Conclusions: The study reports high exposure to ETS among dental students, and its association with current tobacco use and attitudes towards tobacco control. -
Shekhar, Shashank;Sharma, Chanderdeep;Thakur, Sita;Raina, Nidhi 3641
Background: Assessment of the nursing staff knowledge, attitude and practices about cervical cancer screening in a tertiary care teaching institute of rural India. Materials and Methods: A cross sectional, descriptive, interview-based survey was conducted with a pretested questionnaire among 262 staff nurses of a tertiary care teaching and research institute. Results: In this study 77% respondents knew that Pap smear is used for detection of cervical cancer, but less than half knew that Pap smear can detect even precancerous lesions of cervix. Only 23.4% knew human papilloma virus infection as a risk factor. Only 26.7% of the respondents were judged as having adequate knowledge based on scores allotted for questions evaluating knowledge about cervical cancer and screening. Only 17 (7%) of the staff nurses had themselves been screened by Pap smear, while 85% had never taken a Pap smear of a patient. Adequate knowledge of cervical cancer and screening, higher parity and age >30 years were significantly associated with self screening for cervical cancer. Most nurese held a view that Pap test is a doctor procedure, and nearly 90% of nurses had never referred a patient for Pap testing. Conclusions: The majority of nursing staff in rural India may have inadequate knowledge about cervical cancer screening, and their attitude and practices towards cervical cancer screening could not be termed positive. -
Liu, Ning-Bo;Zhu, Lei;Li, Ming-Huan;Sun, Xiao-Rong;Hu, Man;Huo, Zong-Wei;Xu, Wen-Gui;Yu, Jin-Ming 3647
Purpose: To evaluate the diagnostic value of$^{18}F$ -FDG PET/CT for detection of bone metastasis in comparison with the efficacies of$^{18}F$ -FDG PET/CT, CT,$^{18}F$ -FDG PET and conventional planar bone scintigraphy in a series of cancer patients. Methods: Five hundred and thirty patients who underwent both$^{18}F$ -FDG PET/CT and bone scintigraphy within 1 month were retrospectively analyzed. The skeletal system was classified into 10 anatomic segments and interpreted blindly and separately. For each modality, the sensitivity, specificity, accuracy, PPV and NPV were calculated and the results were statistically analyzed. Results: Bone metastases were confirmed in 117 patients with 459 positive segments. On patient-based analysis, the sensitivity, specificity, accuracy, PPV and NPV of$^{18}F$ -FDG PET/CT were significantly higher than bone scintigraphy, CT and$^{18}F$ -FDG PET (P<0.05). On segment-based analysis, the sensitivity of CT, bone scintigraphy,$^{18}F$ -FDG PET and$^{18}F$ -FDG PET/CT were 70.4%, 89.5%, 89.1% and 97.8%, respectively (P<0.05, compared with$^{18}F$ -FDG PET/CT). The overall specificity and accuracy of the four modalities were 89.1%, 91.8%, 90.3%, 98.2% and 90.3%, 90.9%, 89.8%, 98.0%, respectively (P<0.05, compared with$^{18}F$ -FDG PET/CT). The PPV and NPV were 89.8%, 87.6%, 85.6%, 97.2% and 85.6%, 93.2%, 92.8%, 98.6%, respectively. Three hundred and twelve lesions or segments were presented as lytic or sclerotic changes on CT images at the corresponding sites of increased$^{18}F$ -FDG uptake. In lytic or mixed lesions, the sensitivity of$^{18}F$ -FDG PET/CT and$^{18}F$ -FDG PET were better than bone scintigraphy, while in osteoblastic lesions bone scintigraphy had a similar performance with$^{18}F$ -FDG PET/CT but better than$^{18}F$ -FDG PET alone. Conclusion: Our data allow the conclusion that$^{18}F$ -FDG PET/CT is superior to planar bone scintigraphy, CT or$^{18}F$ -FDG PET in detecting bone metastasis.$^{18}F$ -FDG PET/CT may enhance our diagnosis of tumor bone metastasis and provide more information for cancer treatment. -
Pongpiachan, Siwatt;Choochuay, Chomsri;Chonchalar, Jittiphan;Kanchai, Panatda;Phonpiboon, Tidarat;Wongsuesat, Sornsawan;Chomkhae, Kanokwan;Kittikoon, Itthipon;Hiranyatrakul, Phoosak;Cao, Junji;Thamrongthanyawong, Sombat 3653
Along with rapid economic growth and enhanced agricultural productivity, particulate matter emissions in the northern cities of Thailand have been increasing for the past two decades. This trend is expected to continue in the coming decade. Emissions of particulate matter have brought about a series of public health concerns, particularly chronic respiratory diseases. It is well known that lung cancer incidence among northern Thai women is one of the highest in Asia (an annual age-adjusted incidence rate of 37.4 per 100,000). This fact has aroused serious concern among the public and the government and has drawn much attention and interest from the scientific community. To investigate the potential causes of this relatively high lung cancer incidence, this study employed Fourier transform infrared spectroscopy (FTIR) transmission spectroscopy to identify the chemical composition of the$PM_{2.5}$ collected using Quartz Fibre Filters (QFFs) coupled with MiniVol$^{TM}$ portable air samplers (Airmetrics).$PM_{2.5}$ samples collected in nine administrative provinces in northern Thailand before and after the "Haze Episode" in 2013 were categorised based on three-dimensional plots of a principal component analysis (PCA) with Varimax rotation. In addition, the incremental lifetime exposure to$PM_{2.5}$ of both genders was calculated, and the first derivative of the FTIR spectrum of individual samples is here discussed. -
Mehdi, Wesen A.;Zainulabdeen, Jwan A.;Mehde, Atheer A. 3663
Background: Multiple myeloma is a malignant silent incurable plasma cell disorder. The present study aimed to assessed the activation of the oxidative stress pathway in afected patients Materials and Methods: Advanced oxidation protein products (AOPPs), malondialdehyde (MDA), adenosine deaminase (ADA), total antioxidant capacity (TAC) levels, glutathione, ascorbic acid (vitamin C),${\alpha}$ -tocopherol (vitamin E) in addition to related enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R) and superoxide dismutase (SOD) were analyzed in sixty patients with multiple myeloma before and after one month treatment with induction therapy. Results: The results of the study showed a significant elevation in AOPPs, MDA, ADA levels in patients with multiple myeloma before and after treatment in comparison to healthy control samples In contrast TAC glutathione, vitamin C and E, and the antioxidant enzymes levels were decreased significantly. On comparing samples of MM patients after treatment, there was significant increase of TAC glutathione, vitamin C and E, and the antioxidant enzymes in parallel with decreasing AOPPs, MDA and ADA levels in comparison with samples of patients before treatment. Conclusions: The results indicate oxidative stress and DNA damage activity increase in MM and are alleviated in response to therapy. -
Zineldeen, Doaa H.;Wagih, Ayman A.;Nakanishi, Makoto 3669
Faithful transmission of genetic information depends on accurate chromosome segregation as cells exit from mitosis, and errors in chromosomal segregation are catastrophic and may lead to aneuploidy which is the hallmark of cancer. In eukaryotes, an elaborate molecular control system ensures proper orchestration of events at mitotic exit. Phosphorylation of specific tyrosyl residues is a major control mechanism for cellular proliferation and the activities of protein tyrosine kinases and phosphatases must be integrated. Although mitotic kinases are well characterized, phosphatases involved in mitosis remain largely elusive. Here we identify a novel variant of mouse protein tyrosine phosphatase containing domain 1 (Ptpcd1), that we named Ptpcd2. Ptpcd1 is a Cdc14 related centrosomal phosphatase. Our newly identified Ptpcd2 shared a significant homology to yeast Cdc14p (34.1%) and other Cdc14 family of phosphatases. By subcellular fractionation Ptpcd2 was found to be enriched in the cytoplasm and nuclear pellets with catalytic phosphatase activity. By means of immunofluorescence, Ptpcd2 was spatiotemporally regulated in a cell cycle dependent manner with cytoplasmic abundance during mitosis, followed by nuclear localization during interphase. Overexpression of Ptpcd2 induced mitotic exit with decreased levels of some mitotic markers. Moreover, Ptpcd2 failed to colocalize with the centrosomal marker${\gamma}$ -tubulin, suggesting it as a non-centrosomal protein. Taken together, Ptpcd2 phosphatase appears a non-centrosomal variant of Ptpcd1 with probable mitotic functions. The identification of this new phosphatase suggests the existence of an interacting phosphatase network that controls mammalian mitosis and provides new drug targets for anticancer modalities. -
Bai, Sheng-Bin;Chen, Hong-Xiang;Bao, Yong-Xing;Luo, Xue-Gang;Zhong, Jin-Jie 3677
We aimed to assess the role of XPG, XPC and MMS19L polymorphisms on response to chemotherapy in osteosarcomas, and the clinical outcomes. One hundred and eighty five osteosarcoma patients who were histologically confirmed were enrolled in our study between January 2007 and December 2009. Genotyping of XPG, XPC and MMS19L was performed in a 384-well plate format on the MassARRAY$^{(R)}$ platform. Individuals with XPG TT genotype and T allele were more likely to be better response to chemotherapy than CC genotype, with the OR (95% CI) of 4.17 (1.64-11.54) and 2.66 (1.39-5.11), respectively. Those carrying MMS19L TT genotype and T allele showed better response to chemotherapy, with ORs (95% CI) of 4.8 (1.56-17.7) and 2.3 (1.22-4.36), respectively. Patients carrying TT genotype of XPG and MMS19L showed a significantly longer overall survival than CC genotype, with a 0.47 and 0.30-fold risk of death when compared with the wild-type of the gene. XPG and MMS19L are correlated with response to chemotherapy and prognosis of osteosarcoma, so that they could be used as predictive markers for prognosis. -
Jin, Jie;Cai, Lin;Liu, Zhi-Ming;Zhou, Xue-Song 3681
Deregulated miRNAs participate in osteosarcoma genesis. In this study, the expression of miRNA-218 in human osteosarcomas, adjacent normal tissues and Saos-2 human osteosarcoma cells was first assessed. Then the precise role of miRNA-218 in osteosarcoma cells was investigated. Upon transfection with a miR-218 expression vector, the proliferation of Saos-2 human osteosarcoma cells determined using the ATPlite assay was significantly suppressed, whilw migration of Saos-2 cells detected by wound healing and invasion determined using transwells were dramatically inhibited. Potential target genes of miR-218 were predicted and T-cell lymphoma invasion and metastasis 1 (TIAM1) and matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were identified. This was confirmed by western blotting, which showed that miR-218 expression inhibited TIAM1, MMP2 and MMP9 protein expression. Collectively, these data suggest that miR-218 acts as a tumor suppressor in osteosarcomas by down-regulating TIAM1, MMP2 and MMP9 expression. -
Alipour, Sadaf;Bayani, Leila;Saberi, Azin;Alikhassi, Afsaneh;Hosseini, Ladan;Eslami, Bita 3685
Background: Clinicians determine degree of mammographic density based on tissue firmness on breast examination. The study aimed to compare breast density in mammography and clinical breast examination. Materials and Methods: Six-hundred sixty three women 40 years of age or older were studied. The breast exam density was graded from 1 to 4 by two expert surgeons and the mammographic parenchymal density by two expert radiologists. Then for practical reasons, grades 1 and 2 were considered as low-density and grades 3 and 4 as high-density. Results: High and low densities were detected in 84.5% and 15.5% of clinical breast examinations and 59.7% and 40.3% of mammographies, respectively. The statistical analysis showed a significant difference between the breast tissue densities in breast examination with those in mammography. Conclusions: A clinically dense breast does not necessarily imply a dense mammographic picture. -
Yusuf, Azlina;Ab Hadi, Imi Sairi;Mahamood, Zainal;Ahmad, Zulkifli;Keng, Soon Lean 3689
Breast cancer is the most common and leading cause of cancer mortality among Malaysian women. Despite good survival rates, the diagnosis of cancer still invokes the feeling of stress, fear and uncertainty. Because very little is known about the experiences of Malaysian women with breast cancer, a qualitative study using semi-structured interviews to explore the lived experience of newly diagnosed breast cancer. Using a purposive sampling method, 20 Malaysian women newly diagnosed with breast cancer, including Malays (n=10) and Chinese (n=10) were recruited in two main public hospitals in Kelantan. Similarities and divergence in women's experience were identified through thematic analysis of interview transcripts. Three themes emerged from the data: uncertainty experience of the illness, transition process and fatalistic view of breast cancer. In many ways, these findings were parallel with previous studies, suggesting that the experience of breast cancer is to a certain extent similar among women newly diagnosed with breast cancer. This study adds to the sparse literature concerning the experience of illness following breast cancer diagnosis among the Malays and Chinese. More importantly, this study addressed areas that were previously lacking, specifically in depth information on breast cancer experience from a developing country with a multi-ethnic population. The results of this investigation provide preliminary information to healthcare professionals on the impact of illness and cultural influence on survivorship to plan for appropriate education and supportive programme in order to meet the needs of breast cancer women more effectively. -
Panahi, Marzieh;Saki, Najmaldin;Ashourzadeh, Sara;Rahim, Fakher 3699
Background: This study aimed to show the localization of estrogen / progesterone receptors, human epidermal growth factor receptor 2 (Her-2) and protein 53 (p53) by immunohistochemistry in a series of consecutive breast cancer patients. Materials and Methods: The study covered invasive breast cancers from 299 patients presenting at the Oncogenetic Clinic and Pathology Centers of Ahwaz Jondishapour University of Medical Sciences Hospital in Iran during the time period from 2009 to 2011. The Scarff-Bloom Richardson scoring method was used. Results: Of the 299, 27% (80/299) were <40, 33% (100/299) were 41-50, and the remaining 40% (119/299) were>50 years old. The highest incidence of breast cancer in this study population was in the group of more than 50 year age, and the most common histological type of breast cancer was the invasive ductal carcinoma, which accounted for 68% (203/299) of the cases. Out of possible total of 207, 6% (13/207), 41% (85/207), and 53% (109/207) were scored as grade I, II, III, respectively. Conclusion: Our findings demonstrated a lack of association between labeling for the markers studied and tumor size and age of the patients. We confirmed an association between ER labeling and nuclear grade of breast cancer. The conflicting results obtained compared with the literature be because of differences in the immunohistochemical techniques applied in the various studies and to the scoring systems used. -
Unal, Olcun Umit;Oztop, Ilhan;Calibasi, Gizem;Baskin, Yasemin;Koca, Dogan;Demir, Necla;Akman, Tulay;Ellidokuz, Hulya;Yilmaz, Ahmet Ugur 3705
Background: To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non-small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. Materials and Methods: EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. Results: EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild-type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. Conclusions: EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis. -
Erten, Cigdem;Demir, Lutfiye;Somali, Isil;Alacacioglu, Ahmet;Kucukzeybek, Yuksel;Akyol, Murat;Can, Alper;Dirican, Ahmet;Bayoglu, Vedat;Tarhan, Mustafa Oktay 3711
Background: To assess the efficacy and tolerability of Cisplatin plus Gemcitabine combination in patients with brain metastases (BM) from breast cancer (BC). Materials and Methods: Eighteen BC patients with BM who were treated with Cisplatin plus Gemcitabine regimen between 2003-2011 were evaluated. Results: A median of 6 cycles of this regimen were received, in fifteen patients (83.3%) as first-line chemotherapy, in 2 as second-line and in 1 as third-line after diagnosis of BM. Dose reduction was performed in 11 (61.1%) patients; major reasons were neutropenia and leukopenia. Grade III neutropenia and Grade II trombocytopenia rates were 33.3% and 16.7% respectively. Overall response rate (ORR; complete+partial response rate) was 33.4% (n=6) for the entire study population; triple negative patients achieved an 66.6% ORR while hormone receptor (HR) positive patients had 25% and HER2 positive patients 12.5%. Median progression-free survival was 5.6 months (2.4-8.8 months, 95%CI) and longer in patients with triple negative breast cancer (TNBC) (median 7.4 months, 95%CI, 2.4-12.3 months) than the patients with other subtypes (median 5 months for HER2 positive and 3.6 months for HR positive patients). Median PFS of the patients with TNBC who received this regimen as first-line was 9.2 months (5.2-13.2 months, 95%CI). Conclusions: Cisplatin plus Gemcitabine may be a treatment option for patients with BM from breast cancer. Longer PFS and higher response rates are results that support the usage of this regimen especially for the triple negative subtype. However, further prospective and randomized trials are clearly required to provide more exact information. -
Liu, Wen-Jian;Tan, Xiao-Hong;Guo, Bao-Ping;Ke, Qing;Sun, Jie;Cen, Hong 3719
Background: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features. Methods: Eligible studies were identified through searching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Results: Nineteen studies involving 2,063 cases of NSCLC and 1,184 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and NSCLC in the complete data set (OR = 19.42, 95% CI: 14.04-26.85, P < 0.001). Pooling the control tissue subgroups (heterogeneous/autologous) gave pooled ORs of 32.4 (95% CI, 12.4-84.5) and 17.7 (95% CI, 12.5-25.0) respectively. Racial subgroup (Caucasian/Asian) analysis gave pooled ORs of 26.6 (95% CI, 10.9-64.9) and 20.9 (95% CI, 14.4-30.4) respectively. The OR for RASSF1A methylation in poorly-differentiated vs. moderately/well-differentiated NSCLC tissues was 1.88 (95% CI, 1.32-2.68, P<0.001), whereas there were no significant differences in RASSF1A methylation in relation to gender, pathology, TNM stage and smoking behavior among NSCLC cases. Conclusion: This meta-analysis suggests a significant association between RASSF1A methylation and NSCLC, confirming the role of RASSF1A as a tumor suppressor gene. Large-scale and well-designed case-control studies are needed to validate the associations identified in the present meta-analysis. -
Background: The mammalian target of rapamycin (mTOR) /RPS6KB1 activation has recently been implicated in tumour development, but its role in lung cancer remains unclear. The aim of this study was to explore the role of mTOR/RPS6KB1 signaling pathway in non-small-cell lung cancer (NSCLC). Methods: Immunohistochemistry was performed to assess the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and its downstream ribosomal phosphorylated RPS6KB1 (p-RPS6KB1) in NSCLC patients. We also analyzed p-mTOR/p-RPS6KB1 protein expression in 45 fresh NSCLC tissues using Western blotting. Results: The expression level of p-mTOR and p-RPS6KB1 was significantly higher in NSCLC tumor specimens than that in adjacent noncancerous normal lung tissues (P<0.01). p-mTOR expression correlated with p-RPS6KB1. Furthermore, high expression level of p-mTOR or p-RPS6KB1 in NSCLC was associated with a shorter overall survival (both P<0.01). Multivariate analysis indicated high level of p-mTOR expression was an independent prognostic factor (HR=2.642, 95%CI 1.157-4.904, p=0.002). Conclusions: p-mTOR and p-RPS6KB1 could be useful prognostic markers for NSCLC.
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Yu, Zu-Hu;Zhang, Qiang;Wang, Ya-Dong;Chen, Jing;Jiang, Zhi-Mao;Shi, Min;Guo, Xin;Qin, Jie;Cui, Guang-Hui;Cai, Zhi-Ming;Gui, Yao-Ting;Lai, Yong-Qing 3729
The aim of this study was to evaluate expression of COX-1 in renal cell carcinoma (RCC) and its prognostic value. mRNA of COX-1 was detected in 42 paired RCC and adjacent normal tissues with quantitative realtime polymerase chain reaction (qRT-PCR). Expression of COX-1 was also evaluated in 196 RCC sections and 91 adjacent normal tissues with immunohistochemistry. Statistical analysis was performed to assess COX-1 expression in RCC and its prognostic significance. The results of qRT-PCR showed mRNA levels of COX-1 in RCC tissues to be significantly higher than that in adjacent normal tissues (p < 0.001). Immunohistochemical assays also revealed COX-1 to be overexpressed in RCC tissues (p < 0.001). Statistical analysis demonstrated high expression of COX-1 was correlated with tumour size (p = 0.002), pathological stage (p = 0.003), TNM stage (p = 0.003, 0.007, 0.027, respectively), and tumour recurrence (p < 0.001). Survival analysis indicated patients with high expression of COX-1 had shorter survival time (p < 0.001), and COX-1 was an independent predictor. This is the first study to reveal overexpression of COX-1 in RRC and point to use as a prognostic marker in affected patients. -
Background: Cardamom (Elettaria cardamom), also known as "Queen of Spices", has been traditionally used as a culinary ingredient due to its pleasant aroma and taste. In addition to this role, studies on cardamom have demonstrated cancer chemopreventive potential in in vitro and in vivo systems. Nevertheless, the precise poly-pharmacological nature of naturally occurring chemo-preventive compounds in cardamom has still not been fully demystified. Methods:In this study, an effort has been made to identify the proapoptopic, anti-inflammatory, anti-proliferative, anti-invasive and anti-angiogenic targets of Cardamom's bioactive principles (eucalyptol, alpha-pinene, beta-pinene, d-limonene and geraniol) by employing a dual reverse virtual screening protocol. Experimentally proven target information of the bioactive principles was annotated from bioassay databases and compared with the virtually screened set of targets to evaluate the reliability of the computational identification. To study the molecular interaction pattern of the anti-tumor action, molecular docking simulation was performed with Auto Dock Pyrx. Interaction studies of binding pose of eucalyptol with Caspase 3 were conducted to obtain an insight into the interacting amino acids and their inter-molecular bondings. Results:A prioritized list of target proteins associated with multiple forms of cancer and ranked by their Fit Score (Pharm Mapper) and descending 3D score (Reverse Screen 3D) were obtained from the two independent inverse screening platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that H- bonds and electrostatic interactions forms the chief contributing factor in inter-molecular interactions associated with anti-tumor activity. Eucalyptol binds to the Caspase 3 with a specific framework that is well-suited for nucleophilic attacks by polar residues inside the Caspase 3 catalytic site. Conclusion:This study revealed vital information about the poly-pharmacological anti-tumor mode-of-action of essential oils in cardamom. In addition, a probabilistic set of anti-tumor targets for cardamom was generated, which can be further confirmed by in vivo and in vitro experiments.
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Mutlu, Hasan;Buyukcelik, Abdullah;Erden, Abdulsamet;Aslan, Tuncay;Akca, Zeki;Kaya, Eser;Kibar, Mustafa;Seyrek, Ertugrul;Yavuz, Sinan;Calikusu, Zuleyha 3743
Background: Of patients with non small cell lung cancer (NSCLC), around one third are locally advanced at the time of diagnosis. Because only a proprotion of stage III patients can be cured by surgery, in order to improve the outcomes, sequential or concurrent chemoradiation, or concurrent chemoradiation with induction or consolidation is offered to the patients with locally advanced NSCLC. Today, PET combined with computerized tomography (PET-CT) is accepted as the most sensitive technique for detecting mediastinal lymph node and extracranial metastases from NSCLC. We aimed to compare PET-CT and conventional staging procedures for decisions regarding curative treatment of locally advanced NSCLC. Materials and Methods: A total of 168 consecutive patients were included from Acibadem Kayseri Hospital, Acibadem Adana Hospital and Kayseri Research and Training Hospital in this study. Results: While the median PFS was$13.0{\pm}1.9$ months in the PET-CT group, it was only$6.0{\pm}0.9$ in the others (p<0.001). The median OS values were$20.5{\pm}15.6$ and$11.5{\pm}1.5$ months, respectively (p<0.001). Discussion: As a result, we found that staging with PET CT has better results in terms of survival staging. This superiority leads to survival advantage in patients with locally advanced NSCLC. -
Liu, Yang-Chen;Zhou, Shao-Bing;Gao, Fei;Yin, Xiao-Xiang;Zhao, Ying;Huang, Xin-En 3747
Purpose: To evaluate the efficacy of conservative surgery plus chemo-, radio-therapy in treating patients with early stage breast cancer. Patients and Methods: Eligible patients were treated by postoperative chemotherapy as well as whole-breast irradiation with tumor bed boost. Postoperative radiotherapy consisted of 6 MV whole breast linear accelerator irradiation with two tangential half fields to a total dose of 45~50 Gy, followed by$10{\sim}15MeV{\beta}$ boost irradiation to tumor bed for 10~20Gy, total dose 56~66Gy. Results: Fifty-two patients were enrolled. Overall 1-, 2- and 3 year survival rates were 98.1%, 92.3%, and 90.4%, respectively, with a local recurrence rate of 5.77%. Cosmetic results were evaluated as good by doctors in 90.4% of patients. Conclusions: Breast conservative surgery combined with chemo- radio-therapy could be a treatment option for Chinese patients with early stage breast cancer. -
Bao, Yun-Ping;Yi, Yang;Peng, Li-Lin;Fang, Jing;Liu, Ke-Bin;Li, Wu-Zhou;Luo, Hua-Song 3751
Backgroud and Aims: MicroRNA-206 has proven to be down-regulated in many human malignancies in correlation with tumour progression. Our study aimed to characterize miR-206 contributions to initiation and malignant progression of human osteosarcoma. Methods: MiR-206 expression was detected in human osteosarcoma cell 1ine MG63, human normal osteoblastic cell line hFOB 1.19, and paired osteosarcoma and normal adjacent tissues from 65 patients using quantitative RT-PCR. Relationships of miR-206 levels to clinicopathological characteristics were also investigated. Moreover, miR-206 mimics and negative control siRNA were transfected into MG63 cells to observe effects on cell viability, apoptosis, invasion and migration. Results: We found that miR-206 was down-regulated in the osteosarcoma cell line MG63 and primary tumor samples, and decreased miR-206 expression was significantly associated with advanced clinical stage, T classification, metastasis and poor histological differentiation. Additionally, transfection of miR-206 mimics could reduce MG-63 cell viability, promote cell apoptosis, and inhibit cell invasion and migration. Conclusions: These findings indicate that miR-206 may have a key role in osteosarcoma pathogenesis and development. It could serve as a useful biomarker for prediction of osteosarcoma progression, and provide a potential target for gene therapy. -
Anaya-Ruiz, Maricruz;Bandala, Cindy;Perez-Santos, Jose Luis Martin 3757
MicroRNAs (miRNAs) are small, non-coding RNAs (18-25 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In this context, the present study aimed to evaluate the in vitro effects of miR-485 mimics in breast carcinoma T47D cells. Forty-eight hours after T47D cells were transfected with miR-485 mimics, an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects on cell viability. Colony formation and cell migration assays were adopted to determine whether miR-485 affects the proliferation rates and cell migration of breast carcinoma T47D cells. Our results showed that ectopic expression of miR-485 resulted in a significant decrease in cell growth, cell colony formation, and cell migration. These findings suggest that miR-485 might play an important role in breast cancer by suppressing cell proliferation and migration. -
Saeed, Hesham Mahmoud;Alanazi, Mohammad Saud;Nounou, Howaida Attia;Shalaby, Manal Ali;Semlali, Abdelhabib;Azzam, Nahla;Aljebreen, Abdeulrahan;Alharby, Othman;Parine, Narasimha Reddy;Shaik, Jilani;Maha, Maha 3761
Background: The Saudi population has experienced a sharp increase in colorectal and gastric cancer incidences within the last few years. The relationship between gene polymorphisms of xenobiotic metabolizing enzymes and colorectal cancer (CRC) incidence has not previously investigated among the Saudi population. The aim of the present study was to investigate contributions of CYP1A1, CYP2E1, and GSTM1 gene polymorphisms. Materials and Methods: Blood samples were collected from CRC patients and healthy controls and genotypes were determined by polymerase chain reaction restriction fragment length polymorphism and sequencing. Results and Conclusions:$CYP2E1^*6$ was not significantly associated with CRC development (odd ratio=1.29; confidence interval 0.68-2.45). A remarkable and statistically significant association was observed among patients with$CYP1Awt/^*2A$ (odd ratio=3.65; 95% confidence interval 1.39-9.57). The$GSTM1^*0/^*0$ genotype was found in 2% of CRC patients under investigation. The levels of CYP1A1, CYP2E1 and GSTM1 mRNA gene expression were found to be 4, 4.2 and 4.8 fold, respectively, by quantitative real time PCR. The results of the present case-control study show that the studied Saudi population resembles Caucasians with respect to the considered polymorphisms. Investigation of genetic risk factors and susceptibility gene polymorphisms in our Saudi population should be helpful for better understanding of CRC etiology. -
Nadoshan, Jamal Jafari;Omranipour, Ramesh;Beiki, Omid;Zendedel, Kazem;Alibakhshi, Abbas;Mahmoodzadeh, Habibollah 3769
Background: To investigate the impact of the lymph node ratio (LNR) on the prognosis of patients with locally advanced rectal cancer undergoing pre-operative chemoradiation. Methods: Clinicopathologic and follow up data of 128 patients with stage III rectal cancer who underwent curative resection from 1996 to 2007 were reviewed. The patients were divided into two groups according to the lymph node ratio: LNR${\leq}$ 0.2 (n=28), and >0.2 (n=100). Kaplan-Meier and the Cox proportional hazard regression models were used to evaluate the prognostic effects according to LNR. Results: Median numbers of lymph nodes examined and lymph nodes involved by tumour were 10.3 (range 2-28) and 5.8 (range 1-25), respectively, and the median LNR was 0.5 (range, 0-1.6). The 5-year survival rate significantly differed by LNR (${\leq}$ 0.2, 69%; >0.2, 19%; Log-rank p value < 0.001). LNR was also a significant prognostic factor of survival adjusted for age, sex, post-operative chemotherapy, total number of examined lymph nodes, metastasis and local recurrence (${\leq}$ 0.2, HR=1; >0.2, HR=4.8, 95%CI=2.1-11.1) and a significant predictor of local recurrence and distant metastasis during follow-up independently of total number of examined lymph node. Conclusions: Total number of examined lymph nodes and LNR were significant prognostic factors for survival in patients with stage III rectal cancer undergoing pre-operative chemoradiotherapy. -
Wongpaiboonwattana, Wikrom;Tosukhowong, Piyaratana;Dissayabutra, Thasinas;Mutirangura, Apiwat;Boonla, Chanchai 3773
Increased oxidative stress and changes in DNA methylation are frequently detected in bladder cancer patients. We previously demonstrated a relationship between increased oxidative stress and hypomethylation of the transposable long-interspersed nuclear element-1 (LINE-1). Promoter hypermethylation of a tumor suppressor gene, runt-related transcription factor 3 (RUNX3), may also be associated with bladder cancer genesis. In this study, we investigated changes of DNA methylation in LINE-1 and RUNX3 promoter in a bladder cancer cell (UM-UC-3) under oxidative stress conditions, stimulated by challenge with$H_2O_2$ for 72 h. Cells were pretreated with an antioxidant, tocopheryl acetate for 1 h to attenuate oxidative stress. Methylation levels of LINE-1 and RUNX3 promoter were measured by combined bisulfite restriction analysis PCR and methylation-specific PCR, respectively. Levels of LINE-1 methylation were significantly decreased in$H_2O_2$ -treated cells, and reestablished after pretreated with tocopheryl acetate. Methylation of RUNX3 promoter was significantly increased in cells exposed to$H_2O_2$ . In tocopheryl acetate pretreated cells, it was markedly decreased. In conclusion, hypomethylation of LINE-1 and hypermethylation of RUNX3 promoter in bladder cancer cell line was experimentally induced by reactive oxygen species (ROS). The present findings support the hypothesis that oxidative stress promotes urothelial cell carcinogenesis through modulation of DNA methylation. Our data also imply that mechanistic pathways of ROS-induced alteration of DNA methylation in a repetitive DNA element and a gene promoter might differ. -
Li, Chun-Yan;Zhang, Sheng;Zhang, Xiao-Bei;Wang, Pei;Hou, Guo-Fang;Zhang, Jin 3779
Aims: To determine the clinical, pathological and prognostic features associated with triple-negative breast cancer (TNBC). Methods: Clinical and histologic data of 21,749 breast cancer patients who were treated at Tianjin Medical University Cancer Institute and Hospital between July 2002 and December 2011 were collected. Patients were divided into two groups: those with TNBC and those with other types of breast cancer. Patients and tumor characteristics were compared between the two groups using the Chi-square test. The prognostic results of 9,823 patients in the study population were also analyzed to determine long-term survival rates in the two groups of breast cancer patients. Results: Among the breast cancer patients treated in our hospital between 2003 and 2011, 10.4%-13.5% of them had triple-negative breast cancers. Data analyses revealed significant differences in disease onset age, family history of breast cancer, tumor size, tumor histologic grade, lymph note positivity and metastatic status between TNBC and non-TNBC patients. There were also significant differences in 5-year, 7-year and 9-year disease-free and 7-year and 9-year overall survival probability between the groups. Conclusions:TNBC are associated with younger disease onset age, larger tumor size, higher rate of axillary lymph node positivity, and higher tumor histologic grade. TNBC is also related to family history of breast cancer, increased metastatic risk and poor prognosis. -
Cho, Eun;Park, Eun-Cheol;Kang, Myoung Sheen 3785
This study aimed to discover to what extent ethical issues are considered in the reimbursement decision process based on health technology assessment (HTA) in Korea, especially for oncology medications. Public summary documents (PSDs) published by the Health Insurance Review and Assessment Service (HIRA) were analyzed for empirical and normative factors. For external comparison, PSDs presented by corresponding institutions of Australia and the United Kingdom were employed. Furthermore, the opinions of eight expert oncologists were obtained regarding the accountability of the evidence in PSDs. Among 7 oncology drugs, there were differences in the final decisions and empirical factors considered, such as selected comparators and interpretation of evidence between the PSDs from the three institutions. From an ethical viewpoint, the following matters were deficient in the HTA decision-making process for oncology drugs: clear and reasonable standards; identifying and evaluating ethical values; and public accountability for reasonableness about decisions and due process. -
Jiang, Ping;Yu, Guo-Yu;Zhang, Yong;Xiang, Yang;Hua, Hai-Rong;Bian, Li;Wang, Chun-Yan;Lee, Wen-Hui;Zhang, Yun 3793
The role of protease-activated receptors (PARs) in lung tumors is controversial. Although PAR4 is preferentially expressed in human lung tissues, its possible significance in lung cancer has not been defined. The studies reported herein used a combination of clinical observations and molecular methods. Surgically resected lung adenocarcinomas and associated adjacent normal lung tissues were collected and BEAS-2B and NCI-H157 cell lines were grown in tissue culture. PAR4 expression was evaluated by RT-PCR, RT-qPCR, Western blotting and immunohistochemistry analysis. The results showed that PAR4 mRNA expression was generally decreased in lung adenocarcinoma tissues as compared with matched noncancerous tissues (67.7%) and was associated with poor differentiation (p=0.017) and metastasis (p=0.04). Western blotting and immunohistochemical analysis also showed that PAR4 protein levels were mostly decreased in lung adenocarcinoma tissues (61.3%), and were also associated with poor differentiation (p=0.035) and clinical stage (p=0.027). Moreover, PAR4 expression was decreased in NCI-H157 cells as compared with BEAS-2B cells. In conclusion, PAR4 expression is significantly decreased in lung adenocarcinoma, and down-regulation of PAR4 is associated with a more clinically aggressive phenotype. PAR4 may acts as a tumor suppressor in lung adenocarcinoma. -
Loh, Kwong Weng;Majid, Hazreen Abdul;Dahlui, Maznah;Roslani, April Camilla;Su, Tin Tin 3799
Background: Colorectal cancer is the second most common cancer in Malaysia. The prognosis of the disease is excellent if detected at an early stage, but the majority of Malaysian patients present at late stages. We aimed to assess the awareness of cancer warning signs and anticipated delay in help-seeking as possible contributors to this phenomenon. Materials and Methods: A population-based cross-sectional survey using the Colorectal Cancer Awareness Measure was initiated in Perak, Malaysia. A total of 2,379 respondents aged 18 years and above were recruited using a multi-stage sampling in five locations. Analysis of covariance was used to examine independent sociodemographic predictors of scores for symptom awareness. Results: Younger age, being female, a higher education, and higher income were significantly associated with better scores for both recall and recognition of warning symptoms. Among the ethnic groups, Malays had better recognition of symptoms whereas Chinese recalled the most symptoms. Passing bloody stool was associated with the least anticipated delay and unexplained anal pain had the highest anticipated delay. Conclusions: The level of awareness across all ethnicities in Malaysia is generally low, especially among minorities. Targeted public education, which is culturally and linguistically appropriate, should be developed to encourage early help-seeking and improve clinical outcomes. -
Jia, Jie;Tian, Qing;Liu, Yong;Shao, Zeng-Wu;Yang, Shu-Hua 3805
Background: Osteosarcomas have many established risk factors, both genetic and environmental, but by themselves these explain only part of the total cancer incidence. Bisphenol A (BPA) is an environmental estrogen associated with risk of several kinds of tumour. The lysyl oxidase gene (LOX) may also contribute to risk of tumours including osteosarcomas. Here, we investigated possible interactions of BPA and a LOX polymorphism on the risk of osteosarcoma. Method: The present hospital-based case-control study included 106 cancer patients and 112 controls from a Chinese population. Internal burden of BPA exposure was assessed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) method. Genotypes were determined using PCR-RFLP methods. Results: Compared with those in low BPA exposure group, subjects with BPA more than or equal to median value had significant increased risk of osteosarcoma among subjects who carried GC or CC genotypes. A significant interaction with BPA level and the -22G/C polymorphism was observed for osteosarcoma overall, osteosarcoma affecting knee and osteosarcoma affecting hip, as$P_{forinteraction}$ = 0.036 for osteosarcoma overall;$P_{forinteraction}$ = 0.024 for osteosarcoma affecting knee; and$P_{forinteraction}$ = 0.017 for osteosarcoma affecting hip. Conclusions: The results suggest that BPA exposure interacts with the -22G/C polymorphism of the LOX gene to increase the risk of osteosarcoma. -
Al Mutairi, Fatima Masoud;Alanazi, Mohammed;Shalaby, Manal;Alabdulkarim, Huda A.;Pathan, Akbar Ali Khan;Parine, Narasimha Reddy 3809
Background: X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. XRCC1 is reported to be a candidate influence on cancer risk. The aim of our present study was to assess the association of rs1799782 (Arg194Trp) and rs25487 (Arg399Gln) XRCC1 gene polymorphisms with breast cancer in the Saudi population. Materials and Methods: The two SNP's were analyzed in breast cancer patients and healthy control subjects. Genotypes were determined by TaqMan SNP genotype analysis technique and data were analyzed using Chi-square or t test and logistic regression analysis by SPSS16.0 software. Results and Conclusions: Results showed that rs1799782 significantly increased susceptibility to breast cancer with Arg/Trp, Arg/Trp+Trp/Trp genotypes and at Trp allele overall study. It also increased risk of breast cancer in older age patients (above 48) and with the ER positive category. XRCC1rs25487 (Arg399Gln) did not showed any significant association. In conclusion the XRCC1rs1799782 polymorphism may be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of different ethnicities is warranted. -
Background: Breast cancer is a common cancer worldwide. With the establishment of Thailand's population-based cancer registry and availability of complete data from 2002-2011, it is of interest to investigate the epidemiologic and clinic-pathological profiles of breast cancer based on the population-based registry data. Methods: The data of all breast cancer patients in the registry for the period of 2002-2011 were included. All medical records of the patients diagnosed from documents of National Cancer Registry of Thailand were retrieved and the following information abstracted: age, clinical characteristics, and histological variables. Thailand census data for the period of 2002-2011 were used to provide the general population's statistics on age, gender, and other related demographic factors. Results: Over the 10 year-period, 7,711 breast cancer cases were included. The disease incidence under age 40 years was relatively low (4.13/
$10^5$ ) while the incidence in the age groups 40 and older was very high (39.2/$10^5$ ). The vast majority of breast cancer cases (88.8%) were diagnosed by histology as primary lesions in the breast. The most common of patients with breast cancer (36.4%) had regional lymph node involvement and the most common of histopathology diagnosed in patients (84.2%) was an infiltrating duct carcinoma. Conclusions: This study showed a high incidence of breast cancer in older subjects, and high rate of breast cancer in Thailand. Future studies should explore clinical and molecular disease patterns. -
Youns, Mahmoud M.;Abdel Wahab, Abdel Hady A.;Hassan, Zeinab A.;Attia, Mohamed S. 3819
Background: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. The outcome of HCC depends mainly on its early diagnosis. To date, the performance of traditional biomarkers is unsatisfactory. Talins were firstly identified as cytoplasmic protein partners of integrins but Talin-1 appears to play a crucial role in cancer formation and progression. Our study was conducted to assess the diagnostic value of serum Talin-1 (TLN1) compared to the most feasible traditional biomarker alpha-fetoprotein (AFP) for the diagnosis of HCC. Methods: TLN1 was detected using enzyme linked immunosorbent assay (ELISA) in serum samples from 120 Egyptian subjects including 40 with HCC, 40 with liver cirrhosis (LC) and 40 healthy controls (HC). Results: ROC curve analysis was used to create a predictive model for TLN1 relative to AFP in HCC diagnosis. Serum levels of TLN1 in hepatocellular carcinoma patients were significantly higher compared to the other groups (p<0.0001). The diagnostic accuracy of TLN1 was higher than that of AFP regarding sensitivity, specificity, positive predictive value and negative predictive value in diagnosis of HCC. Conclusions: The present study showed for the first time that Talin-1 (TLN1) is a potential diagnostic marker for HCC, with a higher sensitivity and specificity compared to the traditional biomarker AFP. -
Chen, Shao-Bin;Weng, Hong-Rui;Wang, Geng;Yang, Jie-Sheng;Yang, Wei-Ping;Liu, Di-Tian;Chen, Yu-Ping;Zhang, Hao 3825
More studies are needed to clarify treatments and prognosis of early esophageal squamous cell carcinoma (ESCC). This retrospective study was designed to review the outcome of surgical treatment for early ESCC, evaluate the results of a left thoracotomy for selected patients with early ESCC, and identify factors affecting lymph node metastases and survival. The clinicopathological data of 228 patients with early ESCC who underwent transthoracic esophagectomy with lymphadenectomy without preoperative adjuvant treatment were reviewed. The${\chi}^2$ test or Fisher's exact test were used to detect factors related to lymph node metastasis. Univariate and multivariate analyses were performed to identify prognostic factors. There were 152 males and 76 females with a median age of 55 years. Two hundred and eight patients underwent a left thoracotomy, and the remaining 20 patients with lymph nodes in the upper mediastinum more than 5 mm in short-axis diameter by computed tomography scan underwent a right thoracotomy. No lymph node metastasis was found in the 18 patients with carcinoma in situ, while lymph node metastases were detected in 1.6% (1/62) of patients with mucosal tumours and 18.2% (27/148) of patients with submucosal tumours. Only 7 patients showed upper mediastinal lymph node metastases in the follow-up. The 5- and 10-year overall survival rates were 81.4% and 70.1%, respectively. Only histologic grade (P<0.001) and pT category (P=0.001) significantly correlated with the presence of lymph node metastases. In multivariate analysis, only histologic grade (P=0.026) and pT category (P=0.008) were independent prognostic factors. A left thoracotomy is acceptable for selected patients with early ESCC. Histologic grade and pT category affected the presence of lymph node metastases and were independent prognostic factors for early ESCC. -
Zhao, Fu-Tao;Jia, Zhan-Sheng;Yang, Qun;Song, Le;Jiang, Xiao-Jing 3831
Background: S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigated using MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model. Results: S100A14 was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner grade and vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant and independent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidence interval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro and in vivo. Conclusion: These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC. -
Wang, Li;Dai, Shu-Zhen;Chu, Hui-Jun;Cui, Hong-Fei;Xu, Xiao-Yan 3837
Objectives: To analyse HPV integration prevalence and genotype distributions in cervical intraepithelial neoplasia (CIN) in east part of China, furthermore to assess preferential sites for common HPV integrations and provide baseline information for cervical abnormality screening and prevention. Methods: Integration of HPV in 113 paraffin-embedded cervical intraepithelial neoplasia samples was assessed using Gencap technology in Key Laboratory of Biotechnologies in BGI-Shenzhen. Results: 64 samples were HPV-integrated and as the cervical lesions increased, the integration rate became higher significantly (P=0.002). Fifteen different HPV genotypes were detected, 14 high-risk (16, 18, 31, 33, 51, 52, 56, 58, 66, 68) and 1 low-risk (11). The most common genotypes were HPV-16, 58, 33, 52, 66, and 56. Thirteen patients had co-integration involving mainly HPV-16 and 58. The frequency of HPV gene disruption was higher in L1 and E1 genes than in other regions of the viral genomes. Conclusion: Some 56.6% of CIN lesions in Qingdao had HPV integrations, and 67.2% of HPV-integrated patients were HPV-16 and 58, more prone to be integrated in younger patients below 45 years old. There exist preferential sites for HPV-16 and HPV-58 integration, and they are more likely to be disrupted in the L1 and E1 loci. -
Kang, Nai-Min;Xiao, Ning;Sun, Xiao-Jun;Han, Yi;Luo, Bao-Jian;Liu, Zhi-Dong 3843
Objective: The purpose of this study was to assess prognosis after resection of giant tumors (including lobectomy or pneumonectomy) in the mediastinum. Materials and Methods: Patients with resection of a giant tumor in the mediastinum of the thoracic cavity received ICU treatment including dynamic monitoring of vital signs, arterial blood pressure and CVP detection, determination of hemorrhage, pulmonary function and blood gas assay, treatment of relevant complications, examination and treatment with fiber optic bronchoscopy, transfusion and hemostasis as well as postoperative removal of ventilators by invasive and non-invasive sequential mechanical ventilation technologies. Results: Six patients were rehabilitated successfully after ICU treatment with controlled postoperative errhysis and pulmonary infection by examination and treatment with fiber optic bronchoscopy without second application of ventilators and tubes after sequential mechanical ventilation technology. One patient died from multiple organ failure under ICU treatment due to postoperative active hemorrhage after second operative hemostasis. Conclusions: During peri-operative period of resection of giant tumor (including lobectomy or pneumonectomy) in mediastinum ofthe thoracic cavity, the ICU plays an important role in dynamic monitoring of vital signs, treatment of postoperative stress state, postoperative hemostasis and successful removal of ventilators after sequential mechanical ventilation. -
Zhang, Yu;Wang, Ji-Hong;Liu, Bin;Qu, Ping-Bao 3847
The three homologous members of the p160 SRC family (SRC-1, SRC-2 and SRC-3) mediate the transcriptional functions of nuclear receptors and other transcription factors, and are the most studied of all the transcriptional co-activators. Recent work has indicated that the SRC-3 gene is subject to amplification and overexpression in various human cancers. Some of the molecular mechanisms responsible for SRC overexpression, along with the mechanisms by which SRC-3 promotes breast and prostate cancer cell proliferation and survival, have been identified. However, the function of SRC-3 in bladder cancer remains poorly understood. In the present study, our results indicate that overexpression of SRC-3 promotes bladder cancer cell proliferation whereas knockdown of SRC-3 results in inhibition. At the molecular level, we further established that CXCR4 is a transcriptional target of SRC-3. Therefore, our study first identified that SRC-3 plays a critical role in the bladder cancer, which may be a target beneficial for its prevention and treatment. -
Liang, Jun;Qian, Ying;Xu, Dan;Yin, Qun;Pan, Hui-Juan 3851
Objective: To explore changes in the serum tumor makers, hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$ ) and vascular endothelial growth factor (VEGF) level and their relations in patients with non-small cell lung cancer (NSCLC) before and after intervention. Materials and Methods: Forty patients with NSCLC and 40 healthy individuals undergoing physical examination in our hospital provided the observation and control groups. HIF-$1{\alpha}$ and VEGF levels in serum were detected by enzyme-linked immuno-sorbent assay (ELISA) in the observation group before and after intervention and in control group on the day of physical examination, along with serum carcino-embryonic antigen (CEA), neuron-speci ic enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group with a fully automatic biochemical analyzer. Clinical effects and improvement of life quality in the observation group were also evaluated. Results: The total effective rate and improvement of life quality after treatment in observation group were 30.0% and 32.5%, respectively. Serum HIF-$1{\alpha}$ and VEGF levels in the control group were lower than that in observation group (p<0.01), but remarkably elevatedafter intervention (p<0.01). In addition, serum CEA, NSE and SCC levels were apparently lowered by treatment (p<0.01). Serum HIF-$1{\alpha}$ demonstrated a positive relation with VEGF level (p<0.01) and was inversely related with CEA, NSE and SCC levels (p<0.01). Conclusions: Significant correlations exist between marked increase of serum HIF-$1{\alpha}$ and VEGF levels and decrease of indexes related to hematological tumor markers in NSCLC patients after intervention. -
Dai, Xin-Zheng;Yin, Hai-Tao;Sun, Ling-Fei;Hu, Xiang;Zhou, Chong;Zhou, Yun;Zhang, Wei;Huang, Xin-En;Li, Xiang-Cheng 3855
Purpose: Liver cancer, one of the most common cancers in China, is reported to feature relatively high morbidity and mortality. Curcumin (Cum) is considered as a drug possessing anti-angiogenic, anti-inflammation and anti-oxidation effect. Previous research has demonstrated antitumor effects in a series of cancers. Materials and Methods: In this study the in vitro cytotoxicity of Cum was measured by MTT assay and pro-apoptotic effects were assessed by DAPI staining and measurement of caspase-3 activity. In vivo anti-hepatoma efficacy of Cum was assessed with HepG2 xenografts. Results: It is found that Cum dose-dependently inhibited cell growth in HepG2 cells with activation of apoptosis. Moreover, Cum delayed the growth of liver cancer in a dose-dependent manner in nude mice. Conclusions: Cum might be a promising phytomedicine in cancer therapy and further efforts are needed to explore this therapeutic strategy. -
Zhou, Lei;Zhu, Yan-Yun;Zhang, Xiao-Dong;Li, Yang;Liu, Zhuo-Gang 3861
Glutathione S-transferase (GST) enzyme levels are associated with risk of many cancers, including hematologic tumours. We here aimed to investigate the relationships between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of AML. Genotyping of GSTs was based upon duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method in 163 cases and 204 controls. Individuals carrying null GSTT1 genotype had a 1.64 fold risk of acute leukemia relative to a non-null genotype (P<0.05). A heavy risk was observed in those carrying combination of null genotypes of GSTM1 and GSTT1 and GSTP1 Val allele genotypes when compared with those carrying wild genotypes, with an OR (95% CI) of 3.39 (1.26-9.26) (P<0.05). These findings indicate that genetic variants of GST and especially the GSTT1 gene have a critical function in the development of AML. Our study offers important insights into the molecular etiology of AML. -
Jena, Pratap Kumar;Kishore, Jugal;Jahnavi, G. 3865
Background: Cigarette per day (CPD) use is a key smoking behaviour indicator. It reflects smoking intensity which is directly proportional to the occurrence of tobacco induced cancers. Self reported CPD assessment in surveys may suffer from digit bias and under reporting. Estimates from such surveys could influence the policy decision for tobacco control efforts. In this context, this study aimed at identifying underlying factors of digit bias and its implications for Global Adult Tobacco Surveillance. Materials or Methods: Daily manufactured cigarette users CPD frequencies from Global Adult Tobacco Survey (GATS) - India data were analyzed. Adapted Whipple Index was estimated to assess digit bias and data quality of reported CPD frequency. Digit bias was quantified by considering reporting of '0' or '5' as the terminal digits in the CPD frequency. The factors influencing it were identified by bivariate and logistic regression analysis. Results: The mean and mode of CPD frequency was 6.7 and 10 respectively. Around 14.5%, 15.1% and 15.2% of daily smokers had reported their CPD frequency as 2, 5 and 10 respectively. Modified Whipple index was estimated to be 226.3 indicating poor data quality. Digit bias was observed in 38% of the daily smokers. Heavy smoking, urban residence, North, South, North- East region of India, less than primary, secondary or higher educated and fourth asset index quintile group were significantly associated with digit bias. Discussion: The present study highlighted poor quality of CPD frequency data in the GATS-India survey and need for its improvement. Modeling of digit preference and smoothing of the CPD frequency data is required to improve quality of data. Marketing of 10 cigarette sticks per pack may influence CPD frequency reporting, but this needs further examination. Exploring alternative methods to reduce digit bias in cross sectional surveys should be given priority. -
Chen, Gang;Shen, Zhi-Li;Wang, Ling;Lv, Chun-Ye;Huang, Xin-En;Zhou, Rong-Ping 3871
Purpose: MicroRNAs (miRNAs) are small endogenous, non-coding, single-stranded RNAs (approximately 22 nt). Accumulating evidence has shown that aberrant miRNA expression is pronounced and correlated with gastric cancer genesis and progression. Materials and Methods: Expression levels of miR-181a-5p in GC tissues and cell lines were assessed by qRT-PCR and tested for correlation with clinical features. In addition, effects of miR-181a-5p on GC cell growth were investigated. Results: Our findings indicate that miR-181a-5p is upregulated in GC, in correlation with lymph node invasion, nerve invasion and vascular invasion (P<0.05). Enforced expression of miR-181a -5p promoted cell proliferation ability. Conclusions: This study suggested that increased miR-181a-5p is related to GC progression. MiR-181a-5p may represent a potential therapeutic target for GC. -
Hu, Yi;Wang, Jing-Liang;Tao, Hai-Tao;Wu, Bai-Shou;Sun, Jin;Cheng, Yao;Dong, Wei-Wei;Li, Rui-Xin 3877
Objective: To explore the expression and significance of tumor specific growth factor (TSGF), carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) in cancer tissue and serum of patients with colon cancer. Materials and Methods: Radical surgery for colon cancer was performed on 43 patients with laparoscopu under conditions of general anesthesia. The Elisa method was used to detect the levels of serum TSGF, CEA and AFP before and after radical operation, and cancer tissue underwent TSGF, CEA and AFP immunohistochemistry staining after laparoscopic surgery. The decreased conditions of serum TSGF, CEA and AFP in patients with colon cancer at different levels of differentiation and clinical stagings were analyzed, and the relationships of expression rates between histological types, colon cancer morphology, lymph node metastasis and TSGF, CEA as well as AFP in cancer tissue were assessed. Results: Compared with before radical surgery, the levels of serum TSGF, CEA and AFP decreased notably in patients after operations (p<0.01). The decreased degree of TSGF and CEA was the largest in patients with poorly differentiated cancer tissue (p<0.01), while that of AFP was noted in patients with moderately differentiated cancer tissue (p<0.01). The decreased degree of TSGF and AFP was the largest in patients at phase Dukes A (p<0.01), while that of CEA in patients at phase Dukes C (p<0.01). There were no significant differences among the positive expression rates of TSGF, CEA and AFP with different histological types and colon cancer morphologies (p>0.05). The positive expression rates of TSGF and CEA in patients with lymph node metastasis were significantly higher than those without lymph node metastasis (p<0.01). Conclusions: TSGF, CEA and AFP can be used to evaluate the effect of radical operation for colon cancer, and the changed levels of different markers are associated with tumor differentiation, clinical stating and presence or absence of lymph node metastasis. -
Dou, Xue;Wang, Ren-Ben;Yan, Hong-Jiang;Jiang, Shu-Mei;Meng, Xiang-Jiao;Zhu, Kun-Li;Xu, Xiao-Qing;Mu, Dian-Bin 3881
Objective: The objective of this study was to identify clinical predictive factors for tumor response after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Methods: All factors were evaluated in 88 patients with LARC treated with nCRT. After a long period of 4-8 weeks of chemoradiotherapy, 3 patients achieved clinical complete response (cCR) and thus aggressive surgery was avoided, and the remaining 85 patients underwent a curative-intent operation. The response to nCRT was evaluated by tumor regression grade (TRG) system. Results: There were 32 patients (36.4%) with good tumor regression (TRG 3-4) and 56 (63.6%) with poor tumor regression (TRG 0-2). Lymphocyte counts and ratios were higher in good response cases (P=0.01, 0.03, respectively) while neutrophil ratios and N/L ratios were higher in poor response cases (P=0.04, 0.02, respectively). High lymphocyte ratios before nCRT and good tumor regression (TRG3-4) were significantly associated with improved 5-year disease-free survival (P<0.05). Pretreatment nodal status was also significantly associated with 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment lymphocyte ratio and lymph nodal status were independent prognostic factors. Conclusion: Our study suggested that LARC patients with high lymphocyte ratios before nCRT would have good tumor response and high 5-year DFS and OS. -
Mutlu, Hasan;Buyukcelik, Abdullah;Karaca, Halit;Aksahin, Arzu;Berk, Veli;Aslan, Tuncay;Erden, Abdulsamet;Akca, Zeki;Ozkan, Metin 3887
Introduction: Mesothelioma is a rare neoplasm arising from mesothelial surfaces with the malignant pleural mesothelioma (MPM) as the most common form. Secondline chemotherapy in MPM is still controversial and in this study we evaluated whether it is superior to best supportive care. Materials and Methods: A total of 51 patients with MPM from Acibadem Kayseri Hospital, Kayseri Training and Research Hospital and Erciyes University were analyzed retrospectively. The patients treated with secondline chemotherapies (SLCT) were compared with those treated with best supportive care (BSC) for overall survival. Results: The median overall survival (OS) for firstline chemotherapy${\rightarrow}$ SLCT and firstline chemotherapy${\rightarrow}$ BSC groups were 20.3 and 14.7 months respectively (p=0.079). After firstline chemotherapy the median OS for SLCT and BSC were 5.9 and 4.7 months (p=0.355). Discussion: Although there was a trend for improvement in overall survival in patients treated with secondline chemotherapy, the difference was not statistically significant. Our results do not support the proposal that secondline chemotherapy could be effective in patients with MPM. -
Wang, Hua-Yi;Chen, Zhe;Wang, Zhu-Hui;Wang, Hong;Huang, Li-Ming 3891
The purpose of this study was to evaluate the association of expression of${\alpha}5{\beta}1$ -integrin with clinicopathologic features and prognosis in cervical cancer. Levels of${\alpha}5{\beta}1$ -integrin in normal cervical mucosa and cervical cancer tissue were detected with immunohistochemistry. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance.${\alpha}5{\beta} 1$ -integrin expression was detected in 84.6% (143/169) cervical cancer samples, significantly different from that in normal cervical mucosa (P < 0.05). Positive expression rates of${\alpha}5{\beta}1$ -integrin in patients with poor histologic differentiation, lymph node metastasis, and recurrence were elevated. Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expression of${\alpha}5{\beta}1$ -integrin revealed a highly significant difference in human cervical cancer cases (P < 0.05), suggesting that overexpression of${\alpha}5{\beta}1$ -integrin is associated with a worse prognosis.The${\alpha}5{\beta}1$ -integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of cervical cancer. The current study indicated that${\alpha}5{\beta}1$ -integrin may be an independent prognostic factor for cervical cancer patients. -
Piao, Yong-Rui;Piao, Long-Zhen;Zhu, Lian-Hua;Jin, Zhe-Hu;Dong, Xiu-Zhe 3897
Background: Optimal treatment for prostate cancer remains a challenge worldwide. Recently, T cell immunoglobulin mucin-3 (TIM-3) has been implicated in tumor biology but its contribution prostate cancer remains unclear. The aim of this study was to investigate the role of TIM-3 as a prognostic marker in patients with prostate cancer. Methods: TIM-3 protein expression was determined by immunohistochemistry and Western blotting in 137 prostate cancer tumor samples and paired adjacent benign tissue. We also performed cell proliferation assays using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl- 2H tetrazolium bromide (MTT) and cell invasion assays. The effects of small interfering RNA (siRNA)-mediated knockdown of TIM-3 (TIM-3 siRNA) in two human prostate cancer cell lines were also evaluated. Results: TIM-3 expression was higher in prostate cancer tissue than in the adjacent benign tissue (P<0.001). High TIM-3 expression was an independent predictor of both recurrence-free survival and progression-free survival. TIM-3 protein was expressed in both prostate cancer cell lines and knockdown suppressed their proliferation and invasion capacity. Conclusions: TIM-3 expression is associated with a poor prognosis in prostate cancer. Taken together, our resutlts indicate that TIM-3 is a potential prognostic marker in prostate cancer. -
Khiewkhern, Santisith;Promthet, Supannee;Sukprasert, Aemkhea;Eunhpinitpong, Wichai;Bradshaw, Peter 3903
Background: Patients with colorectal cancer are usually treated with chemotherapy, which reduces the number of blood cells, especially white blood cells, and consequently increases the risk of infections. Some research studies have reported that aromatherapy massage affects the immune system and improves immune function by, for example, increasing the numbers of natural killer cells and peripheral blood lymphocytes. However, there has been no report of any study which provided good evidence as to whether aromatherapy with Thai massage could improve the immune system in patients with colorectal cancer. The objectives of this study were to determine whether the use of aromatherapy with light Thai massage in patients with colorectal cancer, who have received chemotherapy, can result in improvement of the cellular immunity and reduce the severity of the common symptoms of side effects. Materials and Methods: Sixty-six patients with colorectal cancer in Phichit Hospital, Thailand, were enrolled in a single-blind, randomised-controlled trial. The intervention consisted of three massage sessions with ginger and coconut oil over a 1-week period. The control group received standard supportive care only. Assessments were conducted at pre-assessment and at the end of one week of massage or standard care. Changes from pre-assessment to the end of treatment were measured in terms of white blood cells, neutrophils, lymphocytes, CD4 and CD8 cells and the CD4/CD8 ratio and also the severity of self-rated symptom scores. Results: The main finding was that after adjusting for pre-assessment values the mean lymphocyte count at the post-assessment was significantly higher (P=0.04) in the treatment group than in the controls. The size of this difference suggested that aromatherapy with Thai massage could boost lymphocyte numbers by 11%. The secondary outcomes were that at the post assessment the symptom severity scores for fatigue, presenting symptom, pain and stress were significantly lower in the massage group than in the standard care controls. Conclusions: Aromatherapy with light Thai massage can be beneficial for the immune systems of cancer patients who are undergoing chemotherapy by increasing the number of lymphocytes and can help to reduce the severity of common symptoms. -
Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekaran 3909
The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (${\gamma}$ -GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$ ), interleukin-1 beta (IL-$1{\beta}$ ), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-${\gamma}$ ) in animals with DLA induced solid tumours. Increase in$CD4^+$ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent. -
Mirinezhad, Seyed Kazem;Somi, Mohammad Hossein;Shirmohamadi, Masoud;Seyednejad, Farshad;Jangjoo, Amir Ghasemi;Ghojazadeh, Morteza;Mohammadzadeh, Mohammad;Naseri, Ali Reza;Nasiri, Behnam 3921
Background: To investigate the role of surgical treatment for locally advanced esophageal cancer, we compared the outcomes of chemoradiotheroy alone (CRT) to postoperative chemoradiotherapy (S/CRT), using, Regional Radiotherapy Center, database. Materials and Methods: This retrospective study was conducted in North-West of Iran, included of 255 consecutive patients with esophageal cancer. Eligible operable and non-operable, were treated with S/CRT and CRT respectively. Radiotherapy (RT) was delivered at 1.8-2 Gy/day for five consecutive days in a given week. Chemotherapy (CT) consisted of cisplatin and 5-fluorouracil. Results: From March 2006 to March 2011 255 patients: male/female 129/96, median age 68 (35-90), squamous/adeno 213/12, received CRT/S+CRT 166/59, median radiation dose$45{\pm}13.6Gy$ , Median survival 13.5 (11-15), overall survival (OS) One/Two/Three 57/21/16%, Died/alive 158/97, Univariate analysis prognostic factors: age/stag/differentiation/dose of RT/fraction/treatment, Multivariate analysis predictor factor: dose of RT/fraction. Conclusions: Although this treatment offers some possibility for improvement of patients with esophageal cancer, there remains a significant need for development of new drug and new therapeutic approaches that can substantially impact survival. -
Berber, Ufuk;Yilmaz, Ismail;Yilmaz, Omer;Haholu, Aptullah;Kucukodaci, Zafer;Ates, Ferhat;Demirel, Dilaver 3925
We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk. -
Serum Gastrin and the Pepsinogen I/II Ratio as Markers for Diagnosis of Premalignant Gastric LesionsShafaghi, Afshin;Mansour-Ghanaei, Fariborz;Joukar, Farahnaz;Sharafkhah, Maryam;Mesbah, Alireza;Askari, Kurosh;Geranmayeh, Siamak;Mehrvarz, Alireza;Souti, Fatemeh;Sokhanvar, Homayoon;Fakhrieh, Saba;Aminian, Keyvan;Yousefi-Mashhour, Mahmud;Khosh-Sorur, Mahmud;Rasoulian, Javid 3931
Background: Iran is a country with very high incidences of stomach cancer, especially in Northern parts. Here we assessed prognostic value of serum screening biomarkers among people >50 years old for early detection of precancerous lesions in a hot spot for gastric carcinoma in Guilan Province, North Iran. Methods: A cross-sectional population-based survey was conducted on 1,390 residents of Lashtenasha city with the mean age (SD) of 61.8 (9.02) years old (50.8% females) to assess the association of gastrin and the pepsinogen (PG) I/II ratio with premalignant gastric lesions. Blood samples were taken for CBC, blood group, and serologic exams (PGI, PGII, and gastrin 17) from each subject. Expert gastroenterologists performed upper GI endoscopy and ROC curves were generated to determine appropriate cutoff points. Results: Mean values of PGI, PGII, PGI/PGII and gastrin were significantly different between patients with and without atrophy or metaplasia (P<0.05). To diagnose atrophy and intestinal metaplasia, a significantly higher AUC was observed for the PGI/PGII ratio (70 and 72%, respectively) compared to the PGI (56, 55%), PGII (63, 64%) and gastrin (59, 61%) (all p<0.001). Conclusions: Biomarker tests such as the PGI/II ratio can be used in the screening and diagnosis of subjects at high gastric cancer risk in our region. -
Zhang, Su-Jie;Hu, Yi;Qian, Hai-Li;Jiao, Shun-Chang;Liu, Zhe-Feng;Tao, Hai-Tao;Han, Lu 3937
Objective: To explore the expression and significance of estrogen receptor (ER), progestrone receptor (PR), vascular endothelial growth factor (VEGF), CA15-3, CA125 and carcinoma embryonic antigen (CEA) expression in judging the prognosis of breast cancer. Materials and Methods: Sixty-five patients with breast cancer undergoing operations in the general surgery department were considered as the observation group, and 50 healthy outpatients of our hospital as the control group. Cubital venous blood was drawn in the morning from fasting patients in the two groups and chemiluminescence immunoassays were used to detect the levels of CA15-3, CA125 and CEA in serum. The follow-up duration was from 4 months to 2 years, and change in levels of the indicators was detected by dynamically drawing blood. After surgery, cancer tissue samples of patients in observation group remained on file (the non-recurrent patients were biopsied). Immunohistochemistry was applied to determine the expression of ER, PR and VEGF in tissue. Results: The effective rate of 12 patients with negative ER and PR expression was 33.3% in the observation group, being associated with prognosis to varying extents. Serum CA15-3, CA125 and CEA in the observation group were all significantly higher than in control group (p<0.01). With increase in pathological staging, levels of serum CA15-3, CA125 and CEA gradually increased (p<0.01). Levels in patients with lymph node metastasis were markedly higher than in those without (p<0.01). In addition, values with distal lymph node metastasis were notably higher than with adjacent lymph node metastasis (p<0.01). The postoperative follow-up results revealed that positive VEGF and levels of serum VEGF, CA15-3, CA125 and CEA in recurrence group were obviously higher than in non-recurrence group (p<0.01). Conclusions: Joint detection of ER and PR expression as well as levels of serum VEGF, CA15-3, CA125 and CEA is meaningful and can guide the diagnosis and treatment for breast cancer. -
Lee, Wei Ching;Yusof, Mastura Md.;Lau, Fen Nee;Ee Phua, Vincent Chee 3941
Background: The use of preoperative chemoirradiation is the commonest treatment strategy employed in Malaysia for locally advanced rectal cancer. We need to determine the local control and survival rates for comparison with established rates in the literature. Materials and Methods: This retrospective study analyzed all newly diagnosed patients with rectal adenocarcinoma who underwent long course preoperative radiotherapy (RT) at the Department of Radiotherapy and Oncology, Kuala Lumpur Hospital (HKL) between$1^{st}$ January 2004 and$31^{st}$ December 2010. The aim of the study was to determine the radiological response post radiotherapy, pathological response including circumferential resection margin (CRM) status, 3 years local control, 3 years overall survival (OS) and 3 years disease free survival (DFS). Statistical analysis was performed using the SPSS software. Kaplan-Meier and log rank analysis were used to determine survival outcomes. Results: A total of 507 patients with rectal cancer underwent RT at HKL. Sixty seven who underwent long course preoperative RT were eligible for this study. The median age at diagnosis was 60 years old with a range of 26-78 years. The median tumour location was 6 cm from the anal verge. Most patients had suspicion of mesorectum involvement (95.5%) while 28.4% of patients had enlarged pelvic nodes on staging CT scan. All patients underwent preoperative chemo-irradiation except for five who had preoperative RT alone. Only 38 patients underwent definitive surgery (56.7%). Five patients were deemed to be inoperable radiologically and 3 patients were found to have unresectable disease intraoperatively. The remaining 21 patients defaulted surgery (31.3%). The median time from completion of RT to surgery was 8 weeks (range 5.6 to 29.4 weeks). Fifteen patients (39.5%) had surgery more than 8 weeks after completion of RT. Complete pathological response was noted in 4 patients (10.5%). The pathological CRM positive rate after RT was 18.4%. With a median follow-up of 38.8 months, the 3 year local control rate was 67%. The 3 years rate for CRM positive (<2 mm), CRM clear (>2 mm) and pCR groups were 0%, 88.1% and 100% respectively (p-value of 0.007). The 3 year OS and DFS were 57.3% and 44.8% respectively. Conclusions: In conclusion, the approach of long course preoperative chemoirradiation for rectal cancer needs to be re-examined in our local setting. The high rate of local recurrence is worrying and is mainly due to patient defaulting post-preoperative chemoirradiation or delayed definitive surgery. -
Unal, Dilek;Eroglu, Celalettin;Kurtul, Neslihan;Oguz, Arzu;Tasdemir, Arzu;Kaplan, Bunyamin 3945
Background: Lung cancer is the leading cause of cancer death, late diagnosis being the main obstacle to improving the outcomes with stage at diagnosis as an important prognostic factor. Relationships between ABO blood groups and risk of benign or malignant diseases have been observed and in this study, we aimed to investigate whether they might affect prognosis and response to chemoradiotherapy in patients with local advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eighty-one patients with non-metastatic local advanced NSCLC were included in the study. ABO blood groups were A in 45 (55.6%), B in 7 (8.6%), AB in 8 (9.9%), and O in 21 (25.9%) patients. The patients were also divided two groups according to blood group A (45 patients) and non-A (B, AB and O; 36 patients). Response to chemoradiotherapy was complete remission in 10 (12.3%), disease regression in 42 (51.9%), stable disease in 12 (14.8%), and disease progression in 17 (21.0%) patients. Results: There was no significant difference among ABO blood group categories or between patients with A blood group and those with non-A blood group in terms of responses to chemoradiotherapy (p>0.05). There were also no significant differences regarding overall and disease-free survival rates. Conclusion: The ABO blood group system has no significant effect on prognosis and response to chemoradiotherapy in patients with non-metastatic NSCLC. -
Yuan, Shao-Fei;Zhang, Lian-Ping;Zhu, Lin-Jia;Chen, Wen-Jun;Zheng, Wei-E;Xiong, Jian-Ping 3949
Aim: To investigate the effectiveness and adverse effects of gemcitabine by fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as second-line therapy for advanced ovarian cancer. Methods: 64 patients with advanced ovarian cancer were divided into an experimental group (44 cases) and a control group (20 cases). The experimental group was treated with continuous intravenous infusion of gemcitabine at 1000$mg/m^2$ with a fixed-dose rate of 10$mg/m^2/min$ , on days 1 and 8 and oxaliplatin at 100$mg/m^2$ on day 1, IVGTT, repeated every 3 weeks. The control group was treated with intravenous infusion of gemcitabine at 1000$mg/m^2$ within 30 min on days 1 and and oxaliplatin at 100$mg/m^2$ on day 1, IVGTT, again repeated every 3 weeks. CT scans or MRI were used for review every 1-2 cycles. Results: The effective rate in the experimental group was significantly high than control group (43.2% vs 35.0%; P < 0.05), with no obvious difference of hematologic or non-hematologic toxicity between the two groups (P > 0.05). Conclusion: GEMOX regimen is very effective to treat advanced ovarian cancer, with low toxicity, good tolerance and improved life quality in patients. -
Attatippaholkun, Watcharee;Wikainapakul, Kornwipa 3955
Background: Defects of manganese superoxide dismutase (MnSOD) have long been implicated in generation of oxidative stress and risk susceptibility to various cancers. Two functional polymorphisms within the MnSOD gene, including the Val-9Ala of the mitochondrial targeting sequence (MTS) and the Ile58Thr of the exon-3, have been proposed to reduce its enzyme activity and antioxidant potential. Materials and Methods: A high-throughput multiplex SNaPshot$^{(R)}$ system was developed herein for simultaneous analyses of Val-9Ala and Ile58Thr in a single reaction. Genomic DNA extracted from each whole blood sample of 248 patients including 107 with cervical cancer and 141 with breast cancer and from 136 healthy women as controls was analyzed by the multiplex SNaPshot$^{(R)}$ system. Results: The Val/Val, Val/Ala genotypes and the Val allele of the MTS were predominant in patients with cervical or breast cancer as well as healthy women in Thailand. The Ile/Ile genotype and the Ile allele of the exon-3 were found in all of them whereas none of the Ile/Thr, the Thr/Thr genotypes and the Thr allele was detected. Genotypic association of both Val-9Ala and Ile58Thr polymorphisms with cervical cancer and breast cancer of these patients comparing to healthy women was not statistically significant (p<0.05). Conclusions: The Val/Val, Val/Ala genotypes and the Val allele of the MTS were found predominantly but the Ile/Ile genotype and the Ile allele of the exon-3 were detected in patients with cervical cancer, breast cancer and healthy women in Thailand. These two functional polymorphisms (Val-9Ala and Ile58Thr) in MnSOD gene did not associate with susceptibility risk of these cancer patients in Thailand. -
Ishtiaq, Sheeba;Hassan, Usman;Mushtaq, Sajid;Akhtar, Noreen 3963
Background: The presence of Epstein-Barr virus (EBV) in Non-Hodgkin's lymphoma can be identified by immunohistochemistry for detection of EBV latent membrane protein (LMP). The role of EBV as an etiologic agent in the development of non-Hodgkin lymphoma has been supported by detection of high levels of latent membrane protein 1 (LMP-1) expression in tumors. However, no study has been conducted in a Pakistani population up till now to determine the frequency of Epstein-Barr virus positivity. The objective of our study was to determine a value for non-Hodgkin lymphoma patients using EBV LMP-1 immunostaining in our institution. Materials and Methods: This study was carried out at the Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Pakistan from December 2011 to December 2012. It was a cross sectional study. A total of 71 patients who were diagnosed with various subtypes of NHL after histological and EBV LMP-1 immunohistochemical evaluation were studied. Sampling technique was non-probability purposive. Statistical analysis was achieved using SPSS version 17.0. Mean and SD were calculated for quantitative variables like patient age. Frequencies and percentages were calculated for qualitative variables like subgroup of NHL, results outcome of IHC for EBV and gender distribution. Results: Mean age of the patients was$53.6{\pm}16$ years (Mean${\pm}$ SD). A total of 50 (70.4%) were male and 21 (29.6%) were female. Some 9 (12.7%) out of 71 cases were positive for EBV-LMP-1 immunostaining, 2 (22.2%) follicular lymphoma cases, 1 (11.1%) case of T-cell lymphoblastic lymphoma, 4 (44.4%) cases of diffuse large B cell lymphomas, 1 (11.1%) mantle cell lymphoma and 1 (11.1%) angioimmunoblastic T cell lymphoma case. Conclusion: In our study, frequency of EBV in NHL is 12.7% and is mostly seen in diffuse large B cell lymphoma. This requires further evaluation to find out whether this positivity is due to co-infection or has a role in pathogenesis. -
Igissinov, Nurbek;Zatoskikh, Vera;Moore, Malcolm Anthony;Igissinov, Saginbek;Toulebaeyev, Rais;Mustafina, Meruert;Valieva, Saule;Aldiyarova, Gulmira;Bukeyeva, Zhanar;Venglovskiy, Anatoly 3969
The purpose was to provide a descriptive epidemiological assessment of the incidence of cancer of the larynx in Kazakhstan and spatial evaluation with gender characteristics. Thgis retrospective study covered all new cases of laryngeal cancer in 11 years (1999-2009). The total number was 4,967 cases, 4,535 (91.3%) in males and 432 (8.7%) in women, with a ratio of 10.5:1. The higher incidence in men compared to women was evident in all age groups, the differences being statistically significant (p<0.05). At the same time revealed a unimodal growth with age, peaking at 70 years and older both sexes. In the dynamics, incidence rates of laryngeal cancer demonstrated a tendency to decrease, in women (T=-6.7%) this being more pronounced than in men (T=-3.3%). Levels were determined to produce cartograms of cancer of the larynx for male and female populations, clear geographical variation being evidenced. The data are discussed with reference to possible risk factors. -
Rakashanda, Syed;Qazi, Asif Khurshid;Majeed, Rabiya;Rafiq, Shaista;Dar, Ishaq Mohammad;Masood, Akbar;Hamid, Abid;Amin, Shajrul 3975
Background: Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies to combat these pathologies seems to be the use of protease inhibitors. LC-pi I, II, III and IV (Lavatera cashmerian-protease inhibitors) have been found in vitro to strongly inhibit trypsin, chymotrypsin and elastase, proteases contributing to tumour invasion and metastasis, indicated possible anticancer effects. The purpose of this study was to check in vitro anticancer activity of these four inhibitors on human lung cancer cell lines. Material and Methods: In order to assess whether these inhibitors induced in vitro cytoxicity, SRB assay was conducted with THP-1 (leukemia), NCIH322 (lung) and Colo205, HCT-116 (colon) lines. Results: LC-pi I significantly inhibited the cell proliferation of all cells tested and also LC-pi II was active in all except HCT-116. Inhibition of cell growth by LC-pi III and IV was negligible.$IC_{50}$ values of LC-pi I and II for NCIH322, were less compared to other cell lines suggesting that lung cancer cells are more inhibited. Conclusion: These investigations might point to future preventive as well as curative solutions using plant protease inhibitors for various cancers, especially in the lung, hence warranting their further investigation. -
Jazayeri, Seyed Behzad;Rahimi-Movaghar, Vafa;Shokraneh, Farhad;Saadat, Soheil;Ramezani, Rashid 3979
Background: Although primary malignant CNS tumors are registered in the national cancer registry (NCR) of Iran, there are no available data on the incidence of the primary malignant or benign CNS tumors and their common histopathologies in the country. This study analyzed the 10-year data of the Iranian NCR from March 21, 2000 to March 20, 2010, including a systematic review. Materials and Methods: The international and national scientific databases were searched using the search keywords CNS, tumor, malignancy, brain, spine, neoplasm and Iran. Results: Of the 1,086 primary results, 9 papers were selected and reviewed, along with analysis of 10-year NCR data. The results showed that primary malignant brain tumors have an overall incidence of 2.74 per 100,000 person-years. The analysis of the papers revealed a benign to malignant ratio of 1.07. The most common histopathologies are meningioma, astrocytoma, glioblastoma and ependymoma. These tumors are more common in men (M/F=1.48). Primary malignant spinal cord tumors constitute 7.1% of the primary malignant CNS tumors with incidence of 0.21/100,000. Conclusions: This study shows that CNS tumors in Iran are in compliance with the pattern of CNS tumors in developing countries. The NCR must include benign lesions to understand the definitive epidemiology of primary CNS tumors in Iran. -
Hegde, Mahabaleshwar Vishnu;Mali, Aniket Vijay;Chandorkar, Shubha Sandeep 3987
This is a commentary on what a cancer cell is and why cancer cells metastasize. Normal cell get transformed to a cancer cell, with excessive production of free radicals that mutate the DNA of a normal cell. The immortality and malignant stage of transformed cell is maintained by higher GSH levels. With the faster rate of proliferation, when the cancer cell finds the place of origin is not conducive to its further growth, cancer cell chooses to take the metastatic course. We argue that if we can stop the exit of cancer cell from place of origin, cancer spread can be stopped or even cured. -
Gaunkar, Ridhima Birmani;Arora, Varun;Loomba, Kapil;Dixit, Seema;Dixit, Ashutosh;Gaur, Amit 3991