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.
KSCI제16권16호
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Anwar, Sumadi Lukman;Wahyono, Artanto;Aryandono, Teguh;Haryono, Samuel J 6803
Caveolin-1 is a 22-kD trans-membrane protein enriched in particular plasma membrane invaginations known as caveolae. Cav-1 expression is often dysregulated in human breast cancers, being commonly upregulated in cancer cells and downregulated in stromal cells. As an intracellular scaffolding protein, Cav-1, is involved in several vital biological regulations including endocytosis, transcytosis, vesicular transport, and signaling pathways. Several pathways are modulated by Cav-1 including estrogen receptor, EGFR, Her2/neu,$TGF{\beta}$ , and mTOR and represent as major drivers in mammary carcinogenesis. Expression and role of Cav-1 in breast carcinogenesis is highly variable depending on the stage of tumor development as well as context of the cell. However, recent data have shown that downregulation of Cav-1 expression in stromal breast tumors is associated with frequent relapse, resistance to therapy, and poor outcome. Modification of Cav-1 expression for translational cancer therapy is particularly challenging since numerous signaling pathways might be affected. This review focuses on present understanding of Cav-1 in breast carcinogenesis and its potential role as a new biomarker for predicting therapeutic response and prognosis as well as new target for therapeutic manipulation. -
Nana, Andre Wendindonde;Yang, Pei-Ming;Lin, Hung-Yun 6813
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor${\beta}$ ($TGF{\beta}$ ) superfamily is a large group of structurally related proteins including$TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The$TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$ ,${\alpha}5{\beta}1$ ) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the$TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial. -
Kaewpitoon, Natthawut;Kootanavanichpong, Nusorn;Kompor, Ponthip;Chavenkun, Wasugree;Kujapun, Jirawoot;Norkaew, Jun;Ponphimai, Sukanya;Matrakool, Likit;Tongtawee, Taweesak;Panpimanmas, Sukij;Rujirakul, Ratana;Padchasuwan, Natnapa;Pholsripradit, Poowadol;Eksanti, Thawatchai;Phatisena, Tanida;Loyd, Ryan A;Kaewpitoon, Soraya J 6825
Opisthorchis viverrini is remains a public health problem in Thailand, particularly in the northeast and north regions which have the highest incidences of chonalgiocarcinoma (CCA). O. viverrini causes the disease opithorchiasis, and its has been classified as a group 1 biological carcinogen. Humans, dogs, and cats become infected with O. viverrini by ingesting raw or undercooked fish containing infective metacercariae. The first human cases of O. viverrini infection were reported in Thailand 100 years ago, and it's still a problem at the community level. Based on data for the year 2009, more than 6 million people were infected with O. viverrini. Associated medical care and loss of wages in Thailand costs about $120 million annually. This review highlights the current status of O. viverrini infection in communities of Thailand through active surveillance for the five years period from 2010 and 2015. A total of 17 community-based surveys were conducted, most in the northeast region. Some 7 surveys demonstrated a high prevalence over 20%, and the highest was 45.7%. Most commonly infection was found in age group of 35 years and older, males, and agricultural workers. Although, the national prevalence may be decreasing but the results show that the O. viverrini infection is still high in communities of the northeast region. Therefore, the focus in populations living in northeast Thailand should be screening of infection and changing their eating behavior. -
Khan, Muhammad;Maryam, Amara;Mehmood, Tahir;Zhang, Yaofang;Ma, Tonghui 6831
Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs. -
Zhang, Haibin;Zhang, Jing;Wang, Haiyong;Su, Xingyun;Teng, Lisong 6841
Omega-3 polyunsaturated fatty acids (${\omega}$ -3 PUFAs) are essential nutrients for human beings and their potential roles against cancer development and progression have become of wide concern recently. Some studies have suggested that perioperative supplementation with omega-3 fatty acids may have beneficial effects in gastrointestinal cancer patients undergoing surgery, while other researchers reported contrary results. This paper reviews recent research to establish therapeutic effects as well as possible underlying mechanisms of${\omega}$ -3 PUFA actions, and to help explain possible reasons for inconsistent results from different institutions. -
Background: Roles of tobacco and alcohol use in etiology of cancer are well established. Alterationin in P53 have essential roles neoplastic change by preventing genome mutation; the aim of this study was to assess the association between P53 mutation and tobacco and alcohol consumption, as well as to assess the epidemiology of tobacco and alcohol use as risk factors for cancer in the adult population of northern Saudi civilians. Materials and Methods: A cross-sectional survey from October 2014 to January 2015, covering 3,398 adults, was performed. P53 mutation molecular detection was performed for 100 tobacco and alcohol users, usingDNA extracted from buccal cells. Results: Of the 3,398 participants 3,253/3398(95.7%) responded, with a male female ratio of 1.10: 1.00. Out of these, 24.8% had smoked tobacco in their lifetime and 2.7% were consumers of alcoholic beverages. None was identified with any P53 mutation. Conclusions: The prevalence of tobacco smoking among the northern Saudi civilians was relatively high. Females' attitudes in tobacco and alcohol related issues were found to be affected by social stigma. Tobacco and alcohol use has no link to P53 gene mutations.
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Xiang, Hong-Gang;Hao, Jun;Zhang, Wen-Jie;Lu, Wen-Jie;Dong, Ping;Liu, Ying-Bin;Chen, Lei 6851
Background: This study aimed to examine the clinical significance of fatty acid synthase (FASN) expression in gastric cancer (GC), and investigate any prognostic role. Materials and Methods: FASN expression was assessed in gastric cancers by immunohistochemistry using 60 paraffin-embedded tissue specimens, and clinical data were collected by retrospective chart review. Moreover, FASN mRNA expression in 15 fresh resected specimens was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining of PTEN was performed to assess the correlation of PTEN with FASN in gastric cancer. Results: Increased expression of FASN was noted in gastric cancers. The frequency of FASN gene amplification was also significantly higher in gastric cancer than in adjacent normal tissue. FASN expression in human gastric cancer tissues was significantly correlated with patient TNM stage and peritoneal dissemination (p<0.05). Moreover, higher FASN expression significantly correlated with shorter overall survival (p<0.05). Here, upregulation of FASN negatively correlated with PTEN expression in gastric cancer. Conclusions: These findings indicate that FASN expression is upregulated in gastric cancer, and increased FASN may be critical to th peritoneal metastasis and survival. Our results suggest that FASN upregulation and PTEN downregualtion may be involved in peritoneal dissemination for gastric cancer progression. -
Tantitamit, Tanitra;Termrungruanglert, Wichai;Oranratanaphan, Shina;Niruthisard, Somchai;Tanbirojn, Patuou;Havanond, Piyalamporn 6857
Background: To identify the optimal cost effective strategy for the management of women having ASC-US who attended at King Chulalongkorn Memorial Hospital (KMCH). Design: An Economical Analysis based on a retrospective study. Subject: The women who were referred to the gynecological department due to screening result of ASC-US at King Chulalongkorn Memorial Hospital, a general and tertiary referral center in Bangkok Thailand, from Jan 2008 - Dec 2012. Materials and Methods: A decision tree-based was constructed to evaluate the cost effectiveness of three follow up strategies in the management of ASC-US results: repeat cytology, triage with HPV testing and immediate colposcopy. Each ASC-US woman made the decision of each strategy after receiving all details about this algorithm, advantages and disadvantages of each strategy from a doctor. The model compared the incremental costs per case of high-grade cervical intraepithelial neoplasia (CIN2+) detected as measured by incremental cost-effectiveness ratio (ICER). Results: From the provider's perspective, immediate colposcopy is the least costly strategy and also the most effective option among the three follow up strategies. Compared with HPV triage, repeat cytology triage is less costly than HPV triage, whereas the latter provides a more effective option at an incremental cost-effectiveness ratio (ICER) of 56,048 Baht per additional case of CIN 2+ detected. From the patient's perspective, the least costly and least effective is repeat cytology triage. Repeat colposcopy has an incremental cost-effectiveness (ICER) of 2,500 Baht per additional case of CIN2+ detected when compared to colposcopy. From the sensitivity analysis, immediate colposcopy triage is no longer cost effective when the cost exceeds 2,250 Baht or the cost of cytology is less than 50 Baht (1USD = 31.58 THB). Conclusions: In women with ASC-US cytology, colposcopy is more cost-effective than repeat cytology or triage with HPV testing for both provider and patient perspectives. -
Women's Knowledge, Attitudes, and Practices about Breast Cancer in a Rural District of Central IndiaGangane, Nitin;Ng, Nawi;Sebastian, Miguel San 6863
Background: Breast cancer accounted for almost 25% of all cancers in women globally in 2012. Although breast cancer is the most prevalent cancer in India, there is no organised national breast cancer screening programme. Local studies on the burden of breast cancer are essential to develop effective context-specific strategies for an early detection breast cancer programme, considering the cultural and ethnic heterogeneity in India. This study examined the knowledge, attitudes, and practices about breast cancer in rural women in Central India. Materials and Methods: This community-based cross sectional study was conducted in Wardha district, located in Maharashtra state in Central India in 2013. The sample included 1000 women (609 rural, 391 urban) aged 13-50 years, selected as representative from each of the eight development blocks in the district, using stratified cluster sampling. Trained social workers interviewed women and collected demographic and socio-economic data. The instrument also assessed respondents' knowledge about breast cancer and its symptoms, risks, methods of screening, diagnosis and treatment, as well as their attitudes towards breast cancer and selfreported practices of breast cancer screening. Chi-square and t-test were applied to assess differences in the levels of knowledge, attitude, and practice (the outcome variables) between urban and rural respondents. Multivariable linear regression was conducted to analyse the relationship between socio-demographic factors and the outcome variables. Results: While about two-thirds of rural and urban women were aware of breast cancer, less than 7% in rural and urban areas had heard about breast self-examination. Knowledge about breast cancer, its symptoms, risk factors, diagnostic modalities, and treatment was similarly poor in both rural and urban women. Urban women demonstrated more positive attitudes towards breast cancer screening practices than their rural counterparts. Better knowledge of breast cancer symptoms, risk factors, diagnosis, and treatment correlated significantly with older age, higher levels of education, and being office workers or in business. Conclusions: Women in rural Central India have poor knowledge about breast cancer, its symptoms and risk factors. Breast self-examination is hardly practiced, though the willingness to learn is high. Positive attitudes towards screening provide an opportunity to promote breast self-examination. -
Trabelsi, Saoussen;Mama, Nadia;Chourabi, Maroua;Mastouri, Maroua Haddaji;Ladib, Mohamed;Popov, Sergey;Burford, Anna;Mokni, Moncef;Tlili, Kalthoum;Krifa, Hedi;Jones, Chris;Yacoubi, Mohamed Tahar;Saad, Ali;Brahim, Dorra H'mida-Ben 6871
Background: The meningeal hemangiopericytoma (MHPC) is a vascular tumor arising from pericytes. Most intracranial MHPCs resemble meningiomas (MNGs) in their clinical presentation and histological features and may therefore be misdiagnosed, despite important differences in prognosis. Materials and Methods: We report 8 cases of MHPC and 5 cases of MNG collected from 2007 to 2011 from the Neuro-Surgery and Histopathology departments. All 13 samples were re reviewed by two independent pathologists and investigated by immunohistochemistry (IHC) using mesenchymal, epithelial and neuro-glial markers. Additionally, we screened all tumors for a large panel of chromosomal alterations using multiplex ligation probe amplification (MLPA). Presence of the NAB2-STAT6 fusion gene was inferred by immunohistochemical staining for STAT6. Results: Compared with MNG, MHPCs showed strong VIM (100% of cases), CD99 (62%), bcl-2 (87%), and p16 (75%) staining but only focal positivity with EMA (33%) and NSE (37%). The p21 antibody was positive in 62% of MHPC and less than 1% in all MNGs. MLPA data did not distinguish HPC from MNG, with PTEN loss and ERBB2 gain found in both. By contrast, STAT6 nuclear staining was observed in 3 MHPC cases and was absent from MNG. Conclusions: MNG and MHPC comprise a spectrum of tumors that cannot be easily differentiated based on histopathology. The presence of STAT6 nuclear positivity may however be a useful diagnostic marker. -
Aksoy, Asude;Karaoglu, Aziz;Akpolat, Nusret;Naziroglu, Mustafa;Ozturk, Turkan;Karagoz, Zuhal Karaca 6877
Background: Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. We investigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-induced nephrotoxicity in rats. Materials and Methods: In this study, 40 female Wistar rats were randomly divided into five equal groups. The first group, which served as the control, was administered physiological saline (2.5 cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose) plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose of VE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The rats were sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes were measured. Results: The histopathological injury score, plasma levels of MDA, urea, creatinine were found to increase in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased (p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se- VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatinine levels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused by CDDP were also significantly improved after Se-VE treatment (p<0.05). Conclusions: Oxidative stress increases with CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention of CDDP-induced nephrotoxicity in patients. -
Palipudi, Krishna;Mbulo, Lazarous;Kosen, Soewarte;Tjandra, Aditama;Kadarmanto, Kadarmanto;Qureshi, Farukh;Andes, Linda;Sinha, Dhirendra N;Asma, Samira 6883
Background: Tobacco smoking is a major cause of preventable disease and death worldwide. Kreteks are clove-flavored cigarettes made from a combination of tobacco and ground-clove mixed with a sauce, smoked widely in Indonesia. Because health and social consequences of kretek smoking are potentially as great as those of traditional cigarettes, this study examines the prevalence of kretek smoking in Indonesia and associated risk factors. Materials and Methods: The study used nationally representative Indonesia Global Adult Tobacco Survey data. Multiple logistic regression analysis was employed to identify correlates of kretek smoking. Results: One-third of Indonesian adults smoked tobacco of which about 90.0% smoked kreteks. Prevalence of kretek smoking among men (60.9%) was more than 25 times the rate among women (2.3%). Overall, the highest prevalence of kretek use was in the age group 45-54 years (36.5%), followed by 34-44 (35.1%), 25-34 (34.2 %), and 55-64 years (32.8%). By wealth index, prevalence of kreteks smoking among those in the middle index was almost 50% above the rate for the wealthiest group (36.4% vs 24.8% respectively). Logistic regression results showed that being male, being older, having less education, and being less wealthy were significant predictors of kretek smoking, while urban vs rural residence was not. Conclusions: Kretek smoking is common in Indonesia and is entrenched in the sociocultural fabric of the country. However, potential consequences of kretek smoking, particularly as risks for noncommunicable diseases, underscore the importance of a comprehensive approach to tobacco control as outlined in the World Health Organization's MPOWER strategies. -
Amani, F;Ahari, S Sadeghieh;Barzegari, S;Hassanlouei, B;Sadrkabir, M;Farzaneh, Esmaeil 6889
Gastric cancer (GC) is the fifth most common cancer in the world, with a wide variation in incidence rates across different geographical areas. In Iran GC is the most common cancer in males and it is reported to be the third most prevalent after breast and colorectal in females. A geographical information system (GIS) allows investigation of the geographical distribution of diseases. The purpose of the present study was to explore the relationship between gastric cancer and effective climatic factors using GIS. The dispersion distribution and the relationship between environmental factors effective on cancer were measured using Arc GIS. Of all cases, 672 (73.8%) were in males with a sex ratio of 3 to1. The highest incidence by cities was seen in Namin with 137.5 per 100,000. The results of this study showed that the distribution of GC around the Sabalan volcanic mountain was significantly higher than other places in the same province. These results can be considered as a window to future comprehensive research on gastric cancer. -
Chan, Caryn Mei Hsien;Ahmad, Wan Azman Wan;Yusof, Mastura MD;Ho, Gwo Fuang;Krupat, Edward 6895
Background: We aimed to explore whether levels of patient-centredness, job satisfaction and psychological distress varied between oncology nurses and doctors. Materials and Methods: In a cross-sectional study using self-administered questionnaires, a total of 24 nurses and 43 doctors were assessed for patient-centredness, psychological distress, and job satisfaction using the Patient-Practitioner Orientation Scale, Hospital Anxiety and Depression Scale, and Job Satisfaction Scale. Data were analysed using descriptive statistics, independent samples t-test and MANCOVA, with p<0.05 considered significant. Results: Overall response rate was 95.6% (43/45) for physicians and 85.7% (24/28) for nurses. Even after adjusting for known covariates, our principal finding was that doctors reported greater psychological distress compared to nurses (p=0.009). Doctors also reported lower job satisfaction compared to nurses (p = 0.017), despite higher levels of patient-centredness found in nurses (p=0.001). Findings may be explained in part by differences in job characteristics and demands. Conclusions: Mental health is an important concern not just in cancer patients but among healthcare professionals in oncology. -
Wongmas, Piyathida;Jetsrisuparb, Arunee;Komvilaisak, Patcharee;Suwanrungruang, Krittika;Choeyprasert, Worawut;Sriplung, Hutcha;Wiangnon, Surapon 6899
Background: Retinoblastoma (RB) is rare, albeit the most common primary intraocular malignancy among children. To elucidate the true incidence, trend and survival, we studied incidences and trends of retinoblastoma in a large population with long-term follow-up using data from 3 population-based cancer registries. Objective: To describe the incidence, trends and survival of RB between 1990 and 2009 in Khon Kaen, Songkhla and Chiang Mai, Thailand. Materials and Methods: We sourced the data from the cancer registries in Khon Kaen, Songkhla and Chiang Mai on children with retinoblastoma, diagnosed between 1990 and 2009. Retinoblastoma was defined as per the International Classification of Disease for Oncology version 3 using the code 9510/3. Incidence was analyzed using the standard method with the criteria of the International Association of Cancer Registries. The Kaplan-Meier method was applied to calculate cumulative survival. Trends were calculated using the log rank test. Results: We identified 75 cases of children between 0 and 15 years of age diagnosed with RB (Khon Kaen 31, Chiang Mai 20, Songkhla 24). Males and females were equally affected. The most common age group was 0-4 years. The morphological verification of the disease was 90.7%. The respective ASR in Khon Kaen, Chiang Mai and Songkhla was 4.4, 4.0 and 4.6 per million; for which the overall ASR for all 3 areas was 4.3 per million. The respective trend in incidence was 4, 2.8, 5.8 and 5.4 during 1990-4, 1995-9, 2000-4 and 2005-9. Overall, incidence trended gradually upward by 2% annually. The respective survival rate in Khon Kaen, Chiang Mai and Songkhla was 50, 40 and 75% (differences not significantly different at p=0.14) and the overall survival for all centers was 60%. Conclusions: Over the last two decades, the incidence and overall survival of retinoblastoma has increased. The ASRs and survival in Thailand were less than those in resource-rich countries. -
Kristina, Susi Ari;Endarti, Dwi;Prabandari, Yayi Suryo;Ahsan, Abdillah;Thavorncharoensap, Montarat 6903
Background: As smoking is the leading preventable cause of multiple diseases and premature cancer deaths, estimating the burden of cancer attributable to smoking has become the standard in documenting the adverse impact of smoking. In Indonesia, there is a dearth of studies assessing the economic costs of cancers related to smoking. This study aimed to estimate indirect mortality costs of premature cancer deaths and years of potential life lost (YPLL) attributable to smoking among the Indonesian population. Materials and Methods: A prevalence based method was employed. Using national data, we estimated smoking-attributable cancer mortality in 2013. Premature mortality costs and YPLL were estimated by calculating number of cancer deaths, life expectancy, annual income, and workforce participation rate. A human capital approach was used to calculate the present value of lifetime earnings (PVLE). A discount rate of 3% was applied. Results: The study estimated that smoking attributable cancer mortality was 74,440 (30.6% of total cancer deaths), comprised of 95% deaths in men and 5% in women. Cancers attributed to smoking wereresponsible for 1,207,845 YPLL. Cancer mortality costs caused by smoking accounted for USD 1,309 million in 2013. Among all cancers, lung cancer is the leading cause of death and economic burden. Conclusions: Cancers related to smoking pose an enormous economic burden in Indonesia. Therefore, tobacco control efforts need to be prioritized in order to prevent more losses to the nation. The data of this study are important for advocating national tobacco control policy. -
Nayir, Tufan;Okyay, Ramazan Azim;Nazlican, Ersin;Yesilyurt, Hakki;Akbaba, Muhsin;Ilhan, Berrin;Kemik, Aytekin 6909
Cancer is a major public health problem due to the jeavy disease burden, fatality and tendency for increased incidence. Of all cancer types, cervical cancer is reported to be the fourth most common cancer in women, and the seventh overall, with an estimated 528,000 new cases worldwide in 2012. It features a long preclinical phase with slowly progressing precancerous lesions such as CIN 2 and 3 and adenocarcinoma in situ. Therefore, screening programs such as with Pap smear tests may play an important role in cervical cancer prevention. The purpose of this study was to present results of a Pap smear screening survey for cervical cancer targeting women living in an urban area in the province of Mersin, located in the Mediterranean region of Turkey. This community-based descriptive study included women living at Akdeniz county of Mersin province. A total of 1,032 screened women between 30 and 65 ages within the routine screening programme constituted the study population. The mean age of the participants was$43.8{\pm}8.6$ (min. 30, max. 65) years. The percentage of the participants who had previously undergone smears was 40.6%. Epithelial cell changes were found in 26 (2.5%) participants, with ASC-US in 18 (1.7%), ASC-H in 2 (0.2%), LSIL in 5 (0.5%) and HSIL in 1 (0.1%). The most common clinical presentation together with epithelial changes was abnormal vaginal discharge. Taking into account the presence of women who had never undergone Pap test; it should be offered at primary level of health care in the form of a community-based service to achieve reduced morbidity and mortality rates. -
Lee, Hyo Jung;Park, Eun-Cheol;Kim, Seung Ju;Lee, Sang Gyu 6913
Background: Due to the rapid progress of industrialization, the expansion of the nuclear family, and an increase in women's social activities, the burden of care of cancer patients has increased, so that all family members are now involved in care. We compared the health-related quality of life (HRQOL) between members of families of cancer patients (hereafter, cancer families) and members of cancer-free families (non-cancer families). Materials and Methods: The data were from the Community Health Survey (2012). The study population included respondents at least 30 years of age. Data were adjusted for the following covariates: sex, age, education, marital status, household income, economic activity, household type, chronic disease, and perceived health status. Frequency analysis, analyses of variance, and multiple linear regression analysis were performed. Results: Among 163,495 respondents, 3,406 (2.1%) were part of a cancer family and 160,089 (97.9%) were part of a non-cancer family. Cancer families had lower EQ-5D scores than non-cancer families. However, by subgroup, the scores had significant association between cancer and non-cancer families only for females and for those who worked. Conclusions: There was a significant relationship between HRQOL scores and being a family member of a cancer patient. This indicates that the responsibility for care has been extended to the entire family, not only the primary caregiver. -
Rai, Narendra Prakash;Divakar, Darshan Devang;Al Kheraif, Abdulaziz Abdullah;Ramakrishnaiah, Ravikumar;Mustafa, Shabil Mohamed;Durgesh, BH;Basavarajappa, Santhosh;Khan, Aftab Ahmed 6919
Background: The treatment selection for the oral squamous cell carcinoma remains controversial. Radiation therapy or surgical excision of the lesion can be applied as the sole treatment or it can be used in combination with other treatment modalities. Radiotherapy is considered to be the safest of all the treatment modalities and can be used in several situations for oral and oropharyngeal cancers. The aim of this study was to evaluate the survival outcome differences in patients treated with radical and palliative radiotherapy as the primary treatment modality. Materials and Methods: The study included a total of 47 patients with oral cancer reporting to our hospital between years 2009 to 2010. The age group for the selected patients was more than 65 years, treated with radical and palliative radiotherapy with no prior surgical interventions. Patients were evaluated till Dec 2013 for overall survival time. Results: Twenty nine patients were treated with radical radiotherapy as main stay of treatment, out of which 21 died during the follow up time with median survival of$352{\pm}281.7$ days with 8 patients alive. All the 16 patients were dead who received palliative radiotherapy with a median survival time of$112{\pm}144.0$ days. Conclusions: This retrospective study showed improved overall survival time, loco regional control rates and reduced morbidity in patients treated with radical radiotherapy when compared to patients treated with palliative radiotherapy. -
Zekri, Abdel-Rahman N;Bakr, Yasser Mabrouk;Ezzat, Maali Mohamed;Zakaria, Mohamed Serag Eldeen;Elbaz, Tamer Mahmoud 6923
Background: Early detection of various kinds of cancers nowadays is needed including colorectal cancer due to the highly significant effects in improving cancer treatment. The aim of this study was to evaluate the potential value of adiponectin, visfatin and resistin as early biomarkers for colorectal cancer patients. Materials and Methods: Serum levels of adiponectin, visfatin and resistin were measured by a sandwich-enzyme-linked (ELISA) assay technique in 114 serum samples comprising 34 patients with colorectal cancer (CRC), 27 with colonic polyps (CP), 24 with inflammatory bowel disease (IBD) and 29 healthy controls. The diagnostic accuracy of each serum marker was evaluated using receiver-operating characteristic (ROC) curve analysis. Results: The mean concentration of adiponectin was significantly higher in CRC and CP groups than IBD and control groups (P-value <0.05). Also the mean concentration of serum resistin was significantly elevated in the IBD and control groups compared to CRC and CP groups (P-value = 0.014). However, no significant difference was noted in patients of the CRC and CP groups. On the other hand, the mean concentration of visfatin was significantly elevated in CRC and control groups compared to CP and IBD groups (P-value = 0.03). ROC analysis curves for the studied markers revealed that between CRC and IBD groups serum level of adiponectin had a sensitivity of 76.7% and a specificity of 76% at a cut off value of 3940, +LR being 3.2 and -LR 0.31 with AUC 0.852, while serum level of adiponectin between CP and IBD had a sensitivity of 77.8% and a specificity of 75% at a cut off value of 3300, with +LR=3.11 and -LR = 0.3 with AUC 0.852. On the other hand the serum level of visfatin between CRC and CP groups had a sensitivity of 65.5% and a specificity of 66.7 at a cut off value of 2.4, +LR being 1.67 and -LR 0.52 with AUC 0.698. Also the serum level of resistin had a sensitivity of 62.5% and a specificity of 70.3% at a cut off value of 24500, with +LR=2.1 and -LR = 0.53 with AUC 0.685 between control and other groups. On the other hand by comparing control vs CP groups resistin had a sensitivity of 81.8% and a specificity of 70.8% at a cut off value of 17700, with +LR=2.8 and -LR = 0.26 with AUC 0.763 while visfatin had a sensitivity of 68.2% and a specificity of 70.8% at a cut off value of 2.7, with +LR=2.34 and -LR = 0.0.45 with AUC 0.812. Conclusions: These findings support potential roles of adiponectin, visfatin and resistin in early detection of CRC and discrimination of different groups of CRC, CP or IBD patients from normal healthy individuals. -
Alkhatib, Alzhraa;Gomaa, Asmaa;Allam, Naglaa;Rewisha, Eman;Waked, Imam 6929
Background: Real life management of hepatocellular carcinoma occasionally deviates from guidelines for recommended therapy. Aims: To evaluate how frequent this deviation happens in our center and assess its impact on outcome. Materials and Methods: The treatment of 770 patients (87% males, mean age 57.8 years) was analyzed and the effect of deviation on outcome over 36 months was examined. Results: Of Barcelona Clinic liver cancer stages 0 and A patients, 65.8% received resection, ablation, liver transplantation or transarterial chemoembolisation for unresectable tumors more than 5 cm in diameter, and 34.2% received treatment recommended for later stages. Of stage B patients, 62.2% received recommended therapy, 34.3% of patients received supportive therapy or sorafenib and 3.5% received upward treatment stage migration. Among stage C patients, 7.6% received sorafenib, and most (79.2%) were given supportive care. Deviation from recommended therapy occurred in 34.2%, 37.7%, and 92.4% in stages 0-A, B and C. Survival of stage 0-A patients who received downwards treatment stage migration was lower than those who received recommended treatment (p <0.001). Upward treatment stage migration in stages B, C and D did not improve survival compared to those who received recommended treatment. Conclusions: Deviation from recommended therapy had a negative impact on survival in Barcelona Clinic liver cancer stage A patients. -
Maleki, Azam;Ahmadnia, Elahe;Avazeh, Azar;Mazloomzadeh, Saeideh;Molaei, Behnaz;Jalilvand, Ahmad 6935
Background: Currently, a comprehensive program for screening and early detection of cervical cancer does not exist in Iran. This study aimed to determine the prevalence of abnormal Papanicolaou (Pap) smears and some related factors among women living in Zanjan, Iran. Materials and Methods: This cross-sectional study was conducted in 2012 in Zanjan on 4274 married women aged 20-65 years. The study participants were selected through two-stage cluster sampling. After obtaining written consent, demographic and fertility questionnaires were completed. Samples from cervix were obtained through a standard method using the Rover Cervex- Brush. Evaluation and interpretation of the samples were reported using the Bethesda 2001 method. Data were statistically analyzed using chi-square and logistic regression models. Results: Most inflammatory changes in the samples were mild (37.4%). Abnormal atypical changes in the epithelial cells were found in 4.04%. The highest percentage of abnormal changes in the epithelial cells was atypical squamous cells of undetermined significance (ASCUS) (1.9%). Abnormal results of Pap smear was significantly and independently associated with age, papillomavirus infection, and lack of awareness about Pap smear tests. Conclusions: Given the high prevalence of inflammatory and precancerous changes in this study, compared to other studies in Iran and other Muslim countries, and the effect of demographic variables and individual factors on abnormal results, increasing the awareness of women and their families regarding the risk factors for cervical cancer, preventive measures such as screening, and timely treatment seem necessary. -
Aghdam, Alireza Mohajjel;Aghaei, Mir Hossein;Hassankhani, Hadi;Rahmani, Azad 6941
Background: Awareness and attitudes of nurses regarding end of life care are important factors in providing hospice care. In an extensive literature review, we found no related articles investigating Iranian nurses awareness and attitudes about providing such care. Objectives: The aims of this study were to investigate the awareness and attitudes of Iranian nurses in providing hospice care. Materials and Methods: In this descriptive-correlational study, 240 nurses employed in six educational centers were selected by non-randomized stratified sampling. The data collection instruments included an awareness test and attitudes regarding providing end of life care in hospice questionnaire. The data were analyzed using descriptive statistics and independent sample t-tests, one-way ANOVA, and Pearson correlation tests. Results: The nurses' awareness score was 14.3 out of 29 and 55.7% of them stated that they had not received any education in providing end of life care. Also, by obtaining the score of 91.7 out of 120 the attitudes of participants in providing end of life care in hospices were positive. In addition, the highest attitudes score of nurses were in the dimensions of benefits of implementation and health care team. Conclusions: Considering low awareness of nurses about end of life care in hospices, continuing education should be provided for them in this regard. Especially, by considering the positive attitude of nurses, providing such programs could help develop hospice care in Iran. -
Abbasi, Mehran Mesgari;Mehdipour, Masoumeh;Monfaredan, Amir;Jahanban-Esfahlan, Rana 6947
Background: Oral carcinoma (OC) remains one of the most difficult malignancies to cure. Hesa-A is an Iranian herbal-marine compound that has shown promising anti-tumor properties against various human tumors. However, its mechanism of action remains to be addressed. The present study was conducted to evaluate the effect of two doses of Hesa-A on mRNA expression of erb$\backslash$ b2 as a main prognosticator tumor marker for OC in an animal model. Materials and Methods: A total of 60 rats were randomly divided into 5 groups of 12 animals each. Rats in carcinoma groups received 0, 250 and 500mg/kg body weight doses of Hesa-A 3 times a day. The other two groups were considered as treated and untreated control groups. At the end of the experiment, animals were sacrificed and tongue tissues subjected to H and E staining and real time PCR. Results: Our results showed that compared to the control group, erb$\backslash$ b2 was over-expressed ~ 30% in the carcinoma group. After treatment with 250mg/kg and 500mg/kg body weight of Hesa-A, erb$\backslash$ b2 levels dropped by 24.1% and 3.4 % respectively compared to the control carcinoma group (p<0.01, p<0.0001). Moreover, there was a significant relation between erb$\backslash$ b2 mRNA content and observed pathological changes in studied groups (p<0.05). Conclusions: These data provide insight into mechanism(s) by which Hesa-A may improve clinical outcome of oral carcinoma by affecting oncogene erb$\backslash$ b2 expression and suggest Hesa-A as an effective chemotherapeutic agent in treatment of HER+tumors. -
Singh, Seram Anil;Choudhury, Javed Hussain;Kapfo, Wetetsho;Kundu, Sharbadeb;Dhar, Bishal;Laskar, Shaheen;Das, Raima;Kumar, Manish;Ghosh, Sankar Kumar 6953
Background: Tobacco and alcohol contain or may generate carcinogenic compounds related to cancers. CYP1A1 enzymes act upon these carcinogens before elimination from the body. The aim of this study was to investigate whether CYP1A1 T3801C polymorphism modulates the relationship between tobacco and alcohol-associated head and neck cancer (HNC) susceptibility among the northeast Indian population. Materials and Methods: One hundred and seventy histologically confirmed HNC cases and 230 controls were included within the study. The CYP1A1 T3801C polymorphism was determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. Results: The CYP1A1 CC genotype was significantly associated with HNC risk (P=0.045). A significantly increased risk of HNC (OR=6.09; P<0.0001) was observed in individuals with combined habits of smoking, alcohol drinking and tobacco-betel quid chewing. Further, gene-environment interactions revealed enhanced risks of HNC among smokers, alcohol drinkers and tobacco-betel quid chewers carrying CYP1A1 TC or CC genotypes. The highest risk of HNC was observed among smokers (OR=7.55; P=0.009) and chewers (OR=10.8; P<0.0001) carrying the CYP1A1 CC genotype. In MDR analysis, the best model for HNC risk was the three-factor model combination of smoking, tobacco-betel quid chewing and the CYP1A1 variant genotype (CVC=99/100; TBA=0.605; P<0.0001); whereas interaction entropy graphs showed synergistic interaction between tobacco habits and CYP1A1. Conclusions: Our results confirm that the CYP1A1 T3801C polymorphism modifies the risk of HNC and further demonstrated importance of gene-environment interaction. -
Jahanban-Esfahlan, Rana;Abasi, Mozhgan;Sani, Hakimeh Moghaddas;Abbasi, Mehran Mesgari;Akbarzadeh, Abolfazl 6963
Background: During the past few years, Hesa-A, a herbal-marine mixture, has been used to treat cancer as an alternative medicine in Iran. Based on a series of studies, it is speculated that Hesa-A possesses special cytotoxic effects on invasive tumors. To test this hypothesis, we investigated the selective anticancer effects of Hesa-A on several cancer cell lines with different metastatic potential. Materials and Methods: Hesa-A was prepared in normal saline as a stock solution of 10 mg/ml and further diluted to final concentrations of$100{\mu}/ml$ ,$200{\mu}g/ml$ ,$300{\mu}g/ml$ and$400{\mu}g/ml$ . MTT-based cytotoxicity assays were performed with A549 (lung non small cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: All treated cancer cells showed significant (P<0.01) or very significant (P<0.0001) differences in comparison to negative control at almost all of the tested doses ($100-400{\mu}g/ml$ ). At the lower dose ($100{\mu}g/ml$ ), Hesa-A reduced cell viability to 66%, 45.3%, 35.5%, 33.2% in SKOV3, A549, PC-3 and MCF-7 cells, respectively. Moreover, at the highest dose ($400{\mu}g/ml$ ), Hesa-A resulted in 88.5%, 86.6%, 84.9% and 79.3% growth inhibition in A549, MCF-7, PC-3 and SKOV3 cells, respectively. Conclusions: Hesa-A exert potent cytotoxic effects on different human cancer cells, especially those with a high metastatic potential. -
Kumar, Shiv Basant;Chawla, Bhavna;Bisht, Shilpa;Yadav, Raj Kumar;Dada, Rima 6967
Background: Cigarette smoking and tobacco chewing are common modes of consuming tobacco all over the world. Parents need to be aware that germ cell integrity is vital for birth of healthy offspring as biological parenting begins much before birth of a child and even before conception. The present study was conducted to determine the etiology of non-familial sporadic heritable retinoblastoma (NFSHRb), by evaluating oxidative sperm DNA damage in fathers due to use of tobacco (smoking and chewing). Materials and Methods: We recruited 145 fathers of NFSHRb children and 53 fathers of healthy children (controls) in the study. Tobacco history was obtained by personal interview. Seminal reactive oxygen species (ROS) in semen, sperm DNA fragmentation index (DFI) and 8 hydroxy 2' deoxyguanosine (8-OHdG) levels in sperm were evaluated. The RB1 gene was screened in genomic blood DNA of parents of children with NFSHRb and controls. Odds ratios (ORs) derived from conditional logistic regression models. Results: There was significant difference in the levels of ROS (p<0.05), DFI (p<0.05) and 8-OHdG (p<0.05) between tobacco users and non-users. The OR of NFSHRb for smokers was 7.29 (95%CI 2.9-34.5, p<0.01), for tobacco chewers 4.75 (2.07-10.9, p<0.05) and for both 9.11 (3.79-39.2; p<0.01). Conclusions: This study emphasizes the adverse effect of tobacco on the paternal genome and how accumulation of oxidative damage in sperm DNA may contribute to the etiology of NFSHRb. In an ongoing parallel study in our laboratory, 11 of fathers who smoked underwent. Meditation and yoga interventions, showed significant decline in levels of highly mutagenic oxidised DNA adducts after 6 months. Thus our lifestyle and social habits impact sperm DNA integrity and simple interventions like yoga and meditation are therapeutic for oxidative damage to sperm DNA. -
Background: Ovarian cancer is the third most common cause of cancer in Indian women. Despite an initial 70-80% response rate, most patients relapse within 1-2 years and develop chemoresistance. Hence, identification or repositioning of drugs to resensitise ovarian cancer cells to existing chemotherapy is needed. Traditionally immortalized cell lines have been used in research, but these may contain genetic aberrations and chromosomal abnormalities serving as poor indicators of normal cell phenotype and progression of early-stage disease. The use of primary cells, maintained for only short periods of time in vitro, may serve as the best representative for studying in vivo conditions of the tissues from which they are derived. In this study we have attempted to evaluate the effect of metformin (an antidiabetic drug) in primary ovarian cancer cells because of its promising effect in other solid tumours. Materials and Methods: Primary cultures of epithelial ovarian cancer cells established from ascitic fluid of untreated ovarian cancer patients were used. The cells were treated with metformin at doses standardized by MTT assay and its ability to induce apoptosis was studied. The cells were analysed for apoptosis and apoptosis related proteins by flow cytometry and western blotting respectively. Results: Metformin induced apoptosis in ovarian cancer cells, provoking cell cycle arrest in the G0/G1 and S phase. It induced apoptosis in ovarian cancer cells by, down-regulating Bcl-2 and up-regulating Bax expression. Conclusions: Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins. These data are relevant to ongoing translational research efforts exploring the chemotherapeutic potential of metformin.
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Background: Breast cancer is the most common cancer in women. One way to decrease the burden of this cancer is early detection through mammography. This study compared the effectiveness of two different educational methods for teachers' uptake of mammography based on the Health Belief Model. Materials and Methods: The current study was a randomised trial of 120 teachers over 40 years old in two groups receiving multimedia or group education, both based on the Health Belief Model. Participants completed questionnaires before, immediately and three months after educational intervention. Mammography was evaluated before and after educational intervention. Results: The participants in the two groups were demographically similar. Comparison showed no difference noted in the scores of knowledge, perceived barriers, susceptibility, and severity constructs between two groups (p > 0.05). Health motivation and benefit were perceived to be higher in the group education compared to the multimedia group. There was a significant difference in mammography between two groups after the intervention (p= 0.003). Conclusions: Planning and implementation of educational program based on the Health Belief Model can raise knowledge and increase participation in mammography especially with group education.
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Akbari, Narjes;Raeesi, Vajehallah;Khazaei, Tahereh;Ramezanzadeh, Khaironnesa;Ebrahimipour, Sediqe 6987
Background: Oral cancer is one of the most prevalent cancers and one of the top ten causes of death in the whole world. Most oral cancers are diagnosed at late stages. Since dentists play a critical role in early detection of oral cancer, they should be knowledgeable and skillful in oral cancer diagnosis. The aim of this study was to survey dentist knowledge about oral cancer in Southern Khorasan Province. Materials and Methods: This descriptive, cross-sectional study was conducted with dentists who participated in an in-service educational program at the Faculty of Dentistry of Birjand University of Medical Sciences in spring 2014. A questionnaire including demographic information with 11 questions regarding oral cancer was prepared. The participants were required to be complete the questionnaires within a specific time span. The data were analyzed using SPSS 15 software by t-test and one-way ANOVA at 0.05 confidence level. Results: A total of 73 dentists out of 80 answered the questionnaires - 36 (49.3%) were females and 37 (50.7%) were males. Total mean score of knowledge was$7.91{\pm}1$ of 11. Mean scores of knowledge of male and female participants were$7.70{\pm}1.83$ and$8.13{\pm}1.94$ respectively. Mean knowledge score of general dentists was$7.41{\pm}1.79$ and of dental specialists was$9.44{\pm}1.0$ In spite of higher knowledge score of women compared to men and general dentists compared to dental specialists, these differences were not statistically significant (p=0.09). Tukey testing showed a significant difference between groups with 1-4 years of experience (8.74) and over twenty years of experience (6.50) ( p=0.001). Conclusions: Considering the good knowledge level of young dentists and the specialists and the importance of early diagnosis of oral cancer, it seems necessary to pay more attention to academic education for dentistry students, as well as holding retraining courses for experienced dentists, so that their knowledge not be reduced over time. -
Sriraksa, Ruethairat;Limpaiboon, Temduang 6991
In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA. -
Piri, Reza;Ghaffari, Alireza;Gholami, Nasrin;Azami-Aghdash, Saber;PourAli-Akbar, Yasmin;Saleh, Parviz;Naghavi-Behzad, Mohammad 6997
Background: In cervical cancer patients it has been reported that there in a significant Ki-67/MIB-1 expression is correlated with survival in cervical cancer patients. However, the prognostic value is still not well understood. Materials and Methods: In the present meta-analysis the prognostic value of Ki-67/MIB-1 with regard to overall survival (OS) and disease-free survival (DFS) in cervical cancer was investigated. The databases of PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct and Wiley Online Library were used to identify appropriate literature. Results: In order to explore the relationship between Ki-67/MIB-1 and cervical cancer, we have included 13 studies covering 894 patients in the current meta-analysis. The effect of Ki-67/MIB-1 on OS for pooled random effects HR estimate was 1.63 (95%confidence interval (CI) 1.09-2.45; P<0.05). The pooled HR for DFS was 1.26 (95%CI 0.58-2.73; P>0.05) and the subgroup analysis indicated Ki-67/MIB1 was associated with DFS (HR=3.67, 95%CI 2.65-5.09) in Asians. Conclusions: According to this meta-analysis, Ki-67/MIB-1 has prognostic value for OS in patients suffering from cervical cancer. For better evaluation of the prognostic role of Ki-67/MIB-1 on DFS, studies with larger numbers of patients are needed to validate present findings in the future. -
Farooq, Muhammad;Taha, Nael Abu;Butorac, Rachel R;Evans, Daniel A;Elzatahry, Ahmed A;Wadaan, Mohammad AM;Cowley, Alan H 7003
Background: Nanoparticles of gold and silver are offering revolutionary changes in the field of cancer therapy. N-heterocyclic carbene (NHC) metal complexes possess diverse biological activities and are being investigated as potential chemotherapeutic agents. The purpose of this study was to examine the cytotoxicity and possible mechanisms of action of two types of newly synthesized nanofiber composites containing BIAN N-heterocyclic gold carbene complexes in two types of human cancer cells, namely breast cancer (MCF7) and liver cancer (HepG2) cells and also in normal human embryonic kidney cells (HEK 293). Materials and Methods: Cytotoxicity was assessed by MTT cell viability assay and oxidative stress by checking the total glutathione level. Results: Both compounds affected the cell survival of the tested cell lines at very low concentrations (IC50 values in the micro molar range) as compared to a well-known anti-cancer drug, 5 fluorouracil. A 60-80% depletion in total glutathione level was detected in treated cells. Conclusions: Reduction in total glutathione level is one of the biochemical pathways for the induction of oxidative stress which in turn could be a possible mechanism of action by which these compounds induce cytotoxicity in cancer cell lines. The in vitro toxicity towards cancer cells found here means that these molecules could be potential anticancer candidates. -
Background: Tobacco use in various forms, including with Areca nut, causes several potentially malignant disorders. Many lesions may transform into oral squamous cell carcinoma. Although patients may be aware of the hazards of tobacco habits, the lesions by themselves are insidious in nature resulting in failure of patients to present to general dentists/specialists at early stages. Our aim was to study the types of habits prevalent in the region of Rourkela in Orissa and to assess the insidious nature of the lesions associated with these habits. Not many studies have been done from this part of India. Materials and Methods: A camp was conducted for habitual users of tobacco and its products, Areca nut and other mixed habit users. A thorough history was taken of the type, duration and frequency of habits, symptoms of patients along with clinical examination by a single examiner. The data was entered in detail into an excel sheet and analysed. Results: 54.7% had lesions and 60.9 % of them were asymptomatic and rest had mild burning sensation while eating. There was a very low awareness of the presence of lesions among the patients. Conclusions: There is a need to spread the awareness of the ill effects of the tobacco and other associated habits far and wide and more importantly educate the general public on the appearance of associated lesions as these are almost always insidious in nature. The patients can self-examine, detect lesions early when present and approach the dentist at the earliest opportunity.
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Saleh, Ahmad M;Fooladi, Marjaneh M;Petro-Nustas, Wasileh;Dweik, Ghadeer;Abuadas, Mohammad H 7011
Background: Prostate cancer is one of the most common cancers affecting men globally, constituting the sixth leading cause of cancer related death in males, and the eleventh leading cause of death from cancer in all age groups. In Jordan, prostate cancer is the third most common cancer in the male population, accounting for one third (6.2%) of cancer related deaths and in 2010 alone, 218 (9.4%) new cases were identified. Objective: To assess the effectiveness of different health education interventions aimed at enhancing knowledge, beliefs and intention to screen for prostate cancer. Materials and Methods: A literature search from January 2000 to April 2015 was conducted using the key words "prostate disease," "educational program," "knowledge," "prostate cancer," "demographic factors and prostate cancer," "knowledge and prostate cancer," "education for patients with prostate cancer," "factors that affect intention to screen," "knowledge, beliefs, and intention to screen for prostate cancer," "impact of prostate educational program on beliefs," and "impact of educational program on intention to screen." Results: Majority of studies reviewed indicated that men had low levels of knowledge regarding prostate cancer, and mild to moderate beliefs with good intention to screen for prostate cancer. Conclusions: Most studies indicated that men's knowledge levels about prostate cancer were poor and they had mild to moderate beliefs and intentions to screen for prostate cancer. Therefore, development of an assessment strategy based on the Health Belief Model seems essential. An effectively designed and implemented educational program can help identify the needs and priorities of the target population. -
Sahai, Puja;Baghmar, Saphalta;Nath, Devajit;Arora, Saurabh;Bhasker, Suman;Gogia, Ajay;Sikka, Kapil;Kumar, Rakesh;Chander, Subhash 7025
Background: The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. Materials and Methods: Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. Results: The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. Conclusions: The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease. -
Background: Arginine may play important roles in tumor progression by providing ornithine for polyamine biosynthesis, required for cell growth. The aim of this work was to determine the expression of arginine metabolic pathway enzymes in head and neck squamous cell carcinoma (HNSCC) in northeast India. Materials and Methods: The expressions of arginase isoforms (ARG1 and ARG2), ornithine aminotransferase (OAT) and ornithine decarboxylase (ODC) were examined in fifty paired HNSCC and adjacent non-tumor tissues by immunohistochemistry. Immunocytochemistry, semiquantitative reverse transcription sq-PCR and quantitative real-time qPCR were used to assess protein and mRNA expressions in peripheral blood of fifty HNSCC patients and hundred controls. Results: ARG1 and ODC protein and mRNA were strongly expressed in peripheral blood from HNSCC patients. No ARG2 expression was observed. In vivo, expression of ARG1, ARG2 and ODC was significantly higher in tumor than in non-tumor tissues. Most tumors expressed low levels of OAT, with no difference in tissues or blood, compared to controls. The absolute extent of maximal ARG1 upregulation with qPCR showed 6.23 fold increase in HNSCC. Conclusions: These findings strongly suggest that in HNSCCs, the ARG1 pathway is stimulated leading to the formation of polyamines as indicated by higher ODC expression, which promote tumor growth.
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Saito, Keita;Kobayashi, Makoto;Nagashio, Ryo;Ryuge, Shinichiro;Katono, Ken;Nakashima, Hiroyasu;Tsuchiya, Benio;Jiang, Shi-Xu;Saegusa, Makoto;Satoh, Yukitoshi;Masuda, Noriyuki;Sato, Yuichi 7039
Background: Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides. Materials and Methods: To identify proteins controlling function in lung adenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamide in the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with post-translational modifications. To confirm the utility of detected proteins as novel tumor markers for AC, we performed immunohistochemical analysis using 170 formalin-fixed and paraffin-embedded lung AC tissues. Results: Tricine 2-DE revealed that five proteins including S100A16 were overexpressed in lung AC-derived cells compared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinoma-derived cells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissues and a membranous staining status was correlated with the T-factor (P=0.0008), pathological stage (P=0.0015), differentiation extent (P=0.0001), lymphatic invasion (P=0.0007), vascular invasion (P=0.0001), pleural invasion (P=0.0087), and gender (P=0.039), but not with the age or smoking history. More importantly, membranous staining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) or stage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression of S100A16 was an independent adverse prognostic indicator (P=0.0001). Conclusions: The present results suggest that S100A16 protein is a novel prognostic marker for lung AC. -
Eryilmaz, Aylin;Basal, Yesim;Omurlu, Imran Kurt 7045
Background: Mean platelet volume (MPV) is a marker which has been investigated in many cancers but data for head and neck lesions are limited. We aimed to study the MPV levels in head and neck cancers as a diagnostic marker. Materials and Methods: A total of 96 head and neck cancer patients and 31 control patients who did not meet exclusion criteria were enrolled in the study. The cancer locations, the platelet and MPV levels at the first diagnosis time were collected. Results: The head and neck cancer location distribution between these patients was 2 (2.1%) buccal, 9 (9.4%) tongue, 6 (6.3) lip, 1 (1%) gingiva, 1 (1%) hypopharynx, 1 (1%) ear, 58 (60.4%) larynx, 2 (2.1%) maxilla, 2 (2.1%) nasal, 1 (1%) nasopharynx, 2 (2.1%) palatal, 3 (3.1%) primary unknown, 1 (1%) retromolar, 1 (1%) thyroid, 2 (2.1%) tonsil, and 4 (4.2%) salivary gland. MPV levels were significantly different between cancer and control group (p=0.002). The cut-off point for MPV predicting head and neck cancer is >10 fL (sensitivity=55.21, specificity=87.10). Conclusions: MPV level increase, a readily assessable parameter which does not bring extra costs can warn us regarding head and neck cancer risk. -
Tongtawee, Taweesak;Dechsukhum, Chavaboon;Leeanansaksiri, Wilairat;Kaewpitoon, Soraya;Kaewpitoon, Natthawut;Loyd, Ryan A;Matrakool, Likit;Panpimanmas, Sukij 7049
Background: Helicobacter pylori plays an important role in gastric cancer, which has a relatively low inciduence in Thailand. MDM2 is a major negative regulator of p53, the key tumor suppressor involved in tumorigenesis of the majority of human cancers. Whether its expression might explain the relative lack of gastric cancer in Thailand was assessed here. Materials and Methods: This single-center study was conducted in the northeast region of Thailand. Gastric mucosa from 100 patients with Helicobacter pylori associated gastritis was analyzed for MDM2 SNP309 using real-time PCR hybridization (light-cycler) probes. Results: In the total 100 Helicobacter pylori associated gastritis cases the incidence of SNP 309 T/T homozygous was 78 % with SNP309 G/T heterozygous found in 19% and SNP309 G/G homozygous in 3%. The result show SNP 309 T/T and SNP 309 G/T to be rather common in the Thai population. Conclusions: Our study indicates that the MDM2 SNP309 G/G homozygous genotype might be a risk factor for gastric cancer in Thailand and the fact that it is infrequent could explain to some extent the low incidence of gastric cancer in the Thai population. -
Diab, Kawthar AE;Shafik, Reham Ezzat;Yasuda, Shin 7053
In the present work, novel orange peel was extracted with 100%EtOH (ethanol) and fractionated into four fractions namely F1, F2, F3, F4 which were eluted from paper chromatographs using 100%EtOH, 80%EtOH, 50%EtOH and pure water respectively. The crude extract and its four fractions were evaluated for their total polyphenol content (TPC), total flavonoid content (TFC) and radical scavenging activity using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Their cytotoxic activity using WST assay and DNA damage by agarose gel electrophoresis were also evaluated in a human leukemia HL-60 cell line. The findings revealed that F4 had the highest TPC followed by crude extract, F2, F3 and F1. However, the crude extract had the highest TFC followed by F4, F3, F2, and F1. Depending on the values of$EC_{50}$ and trolox equivalent antioxidant capacity, F4 possessed the strongest antioxidant activity while F1 and F2 displayed weak antioxidant activity. Further, incubation HL-60 cells with extract/fractions for 24h caused an inhibition of cell viability in a concentration-dependent manner. F3 and F4 exhibited a high antiproliferative activity with a narrow range of$IC_{50}$ values ($45.9-48.9{\mu}g/ml$ ). Crude extract exhibited the weakest antiproliferative activity with an$IC_{50}$ value of$314.89{\mu}g/ml$ . Analysis of DNA fragmentation displayed DNA degradation in the form of a smear-type pattern upon agarose gel after incubation of HL-60 cells with F3 and F4 for 6 h. Overall, F3 and F4 appear to be good sources of phytochemicals with antioxidant and potential anticancer activities. -
Khaleghian, Malihea;Shakoori, Abbas;Razavi, Amirnader Emami;Azimi, Cyrus 7061
Background: During the past decades, the incidence and mortality rate of stomach cancer has demonstrated a great decrease in the world, but it is still one of the most common and fatal cancers especially among men worldwide, including Iran. The MYC proto-oncogene, which is located at 8q24.1, regulates 15% of genes and is activated in 20% of all human tumors. MYC amplification and overexpression of its protein product has been reported in 15-30% of gastric neoplasias. The aim of this investigation was to find the relative efficacy of CISH (chromogenic in situ hybridization) or IHC (immunohistochemistry) in diagnosis and prognosis of gastric cancer, as well as the relationship of amplification and expression of C-MYC gene with patient survival. Materials and Methods: In this cross-sectional study, 102 samples of gastric cancer were collected from patients who had undergone primary surgical resection at the Cancer Institute Hospital, Tehran University of Medical Sciences, from July 2009 to March 2014. All samples were randomly selected from those who were diagnosed with gastric adenocarcinomas. CISH and IHC methods were performed on all of them. Results: Patients were classified into two groups. The first consisted of stage I and II cases, and the second of stage III and IV. Survival tests for both groups was carried out with referrnce to CISH test reults. Group II (stage III & IV) with CISH+ featured lower survival than those with CISH- (p=0.233), but group I (stage I & II) patients demonstrated no significant variation with CISH+ or CISH- (p=0.630). Kaplan-Meier for both groups was carried out with IHC test findings and showed similar results. This data revealed that both diffuse and intestinal types of gastric cancer occurred significantly more in men than women. Our data also showed that CISH+ patients (43%) were more frequent in comparison with IHC+ patients (14.7%). Conclusions: For planning treatment of gastric cancer patients, by focusing on expanding tumors, which is the greatest concern of the surgeons and patients, CISH is a better and more feasible test than IHC, in regard to sensitivity and specificity. Therefore, CISH can be used as a feasible test for tumor growth and prognosis in stage III and IV lesions. This study also indicated that C-MYC amplification in gastric cancer is correlated with survival in advanced stages. -
Kavitha, Matam;Iravathy, Goud;Adi Maha, Lakshmi M;Ravi, V;Sridhar, K;Vijayanand, Reddy P;Chakravarthy, Srinivas;Prasad, SVSS;Tabassum, Shaik Nazia;Shaik, Noor Ahmad;Syed, Rabbani;Alharbi, Khalid Khalaf;Khan, Imran Ali 7071
Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including lung malignancies. Gefitinib and erlotinib are two available therapeutics that act as specific inhibitors of tyrosine kinase (TK) domains. We performed a case-control study with formalin-fixed paraffin-embedded tissue blocks (FFPE) from tissue biopsies of 167 non-small cell lung carcinoma (NSCLC) patients and 167 healthy controls. The tissue biopsies were studied for mutations in exons 18-21 of the EGFR gene. This study was performed using PCR followed by DNA sequencing. We identified 63 mutations in 33 men and 30 women. Mutations were detected in exon 19 (delE746-A750, delE746-T751, delL747-E749, delL747-P753, delL747-T751) in 32 patients, exon 20 (S786I, T790M) in 16, and exon 21 (L858R) in 15. No mutations were observed in exon 18. The 63 patients with EFGR mutations were considered for upfront therapy with oral tyrosine kinase inhibitor (TKI) drugs and have responded well to therapy over the last 15 months. The control patients had no mutations in any of the exons studied. The advent of EGFR TKI therapy has provided a powerful new treatment modality for patients diagnosed with NSCLC. The study emphasizes the frequency of EGFR mutations in NSCLC patients and its role as an important predictive marker for response to oral TKI in the south Indian population. -
Singh, Vineeta;Husain, Nuzhat;Akhtar, Naseem;Kumar, Vijay;Tewari, Shikha;Mishra, Sridhar;Misra, Sanjeev;Khan, M.Y. 7077
Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy among males in India. While tobacco and alcohol are main aetiological factors, human papilloma virus (HPV) presence has surprisingly increased in head and neck Squamous Cell Carcinoma (HNSCC) in the past two decade but its frequency in OSCCS is still uncertain. We aim to explore the frequency of HPV and its major genotypes in North Indian patients and their association with clinicopathological and histopathological features and p16 expression pattern. Materials and Methods: The study group comprised 250 histologically proven cases of OSCC. HPV was detected by real time PCR in tumor biopsy specimens and confirmed by conventional PCR with PGMY09/PGMY11 primers. Genotyping for high-risk types 16/18 was conducted by type specific PCR. p16 expression was assessed by immunohistochemsitry. Results: HPV presence was confirmed in 23/250 (9.2%) OSCC cases, of which 30.4% had HPV 16 infection, 17.4%were positive for HPV 18 and 26.1% had co-infections. HPV presence was significantly associated with male gender (p=0.02) and habit of pan masala chewing (p=0.01). HPV positive cases also had a history of tobacco consumption in 91.3% cases. p16 over expression was observed in 39.1% of HPV positive cases but this was not significantly different from negative cases (p=0.54). Conclusions: The frequency of HPV in OSCC is low in North-India and majority of cases are associated with a tobacco habit. It appears that tobacco shows a confounding effect in HPV positive cases and use of p16 protein as a reliable marker to assess the potential etiological role of HPV in OSCC in our population is not suggested. -
Bachour, Dala-Maria;Chahin, Emil;Al-Fahoum, Sahar 7085
Background: The high incidence of prostate cancer as the most common malignancy in males in many countries raises the question of developing reliable detection tests. The prostate specific antigen (PSA) test is the most widely used for screening for prostate cancer; however, its low specificity elevates the number of unnecessarily biopsies. Serum human kallikrein-2 (hK2) is considered as a promising marker, and especially its ratio to fPSA, for predicting the presence of malignancy to select the best choice referring to biopsy or surveillance. In this study, we investigated the role of hK2 and its combinations with other markers to discriminate prostate cancer from benign diseases in Syrian patients. Materials and Methods: In this prospective oriented cross-sectional cohort study, serum samples were collected from patients referred to many Hospitals in Damascus, Syria, between May 2011 and March 2012, and diagnosed with biopsy proven benign prostate hyperplasia (BPH) or prostate cancer (PCa). Serum was analyzed for hK2, PSA and fPSA, and the ratios of fPSA/PSA and hK2/fPSA were calculated. Results: We found that mean hK2/fPSA ratios were significantly higher (P=0.01) in prostate cancer patients than in the BPH or control groups. Also the ratio hk2/fPSA gave the largest area under the curve (AUC:0.96) which was significantly larger than for fPSA/PSA (AUC:0.41) indicative of higher specificity. Conclusions: Our results demonstrate that the ratio of hK2/fPSA might be superior to the use of fPSA/PSA alone. The hK2 could be shown to enhance the early detection of prostate cancer; especially the ratio hK2/fPSA improves specificity and hence may reduce the number of negative biopsies. -
Dunna, Nageswara Rao;Kandula, Venkatesh;Girdhar, Amandeep;Pudutha, Amareshwari;Hussain, Tajamul;Bandaru, Srinivas;Nayarisseri, Anuraj 7089
Clinical evidence shows that dual inhibition of kinases as well angiogenesis provides ideal therapeutic option in the treatment of medullary thyroid carcinoma (MTC) than inhibiting either of these with the events separately. Although treatment with dual inhibitors has shown good clinical responses in patients with MTC, it has been associated with serious side effects. Some inhibitors are active agents for both angiogenesis or kinase activity. Owing to narrow therapeutic window of established inhibitors, the present study aims to identify high affinity dual inhibitors targeting RET and VEGFR2 respectively for kinase and angiogenesis activity. Established inhibitors like Vandetanib, Cabozantinib, Motesanib, PP121, RAF265 and Sunitinib served as query parent compounds for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. All the parent inhibitors and respective similar compounds were docked against RET and VEGFR2 in order to retrieve high affinity compounds with these two proteins. AGN-PC-0CUK9P PubCID: 59320403 a compound related to PPI21 showed almost equal affinity for RET and VEGFR2 and unlike other screened compounds with no apparent bias for either of the receptors. Further, AGNPC- 0CUK9P demonstrated appreciable interaction with both RET and VEGFR2 and superior kinase activity in addition to showed optimal ADMET properties and pharmacophore features. From our in silico investigation we suggest AGN-PC-0CUK9P as a superior dual inhibitor targeting RET and VEGFR2 with high efficacy which should be proposed for pharmacodynamic and pharmacokinetic studies for improved treatment of MTC. -
Chong, Vui Heng;Telisinghe, Pemsari Upali;LIM, Edwin;Abdullah, Muhammad Syafiq;Idris, Fidah;Chong, Chee Fui 7097
Background: Nasopharyngeal carcinoma (NPC) is linked to Epstein Barr virus infection and is particularly common in the Far East, particularly among some Chinese groups. Certain ethnicities have been reported to have low incidence of NPC. This study looked at NPC in Brunei Darussalam over a three decade period. Materials and Methods: The cancer registry from 1986 to 2014 maintained by the State Laboratory was retrospectively reviewed. The age standardized rates (ASR) and the age specific incidence rates (ASIR) were calculated. Non NPC tumors were excluded from the study. Results: Altogether, there were a total of 450 NPC cases diagnosed accounting for 4.4% of all total cancer cases over the study period, declining from 10.3% in 1986-1990 to 2.3% in 2011-2014. The most common tumor type was the undifferentiated carcinoma (96.4%). The case characteristics were mean age$50.4{\pm}14.4$ years old, male 69%, and predominately Malays 74.4%, followed by Chinese 16.7%. The mean age of diagnosis increased over the study period from$45.6{\pm}17.1$ years (1986-1989) to$54.1{\pm}12.5$ years (ANOVA, p<0.01 for trend). There were no differences in the mean age of diagnosis between the ethnic groups or genders. The ASR showed a declining trend from 11.1 per 100,000 in 1986-1990 to 5.95 per 100,000 in 2011-2014, similar trends been observedfor both genders. Among the age groups, declining trends were seen in all the other age groups apart from the >70 years group. The overall ASRs for the Malays and Chinese were 7.92/100,000 and 8.83/100,000 respectively, both showing declining trends. Conclusions: The incidence of NPC in Brunei Darussalam is comparable to rates reported from Singapore and Malaysia, but higher than rates reported from the other Southeast Asian nations. Unlike higher rates reported for Chinese compared to the Malays in other countries, the rates between the Malays and Chinese in our study was comparable. Importantly, the ASR is declining overall and for both genders and ethnic groups. -
Abdelrahman, Ibrahim Y;Helwa, Reham;Elkashef, Hausein;Hassan, Nagwa HA 7103
The present study was conducted to investigate the effect of${\gamma}$ -radiation alone or combined with a cytotoxic drug, simvastatin, on viability and cell cycling of a myeloma cell line. P3NS1 myeloma cells were treated with the selected dose of simvastatin ($0.1{\mu}M /l$ ) 24 hours prior to${\gamma}$ -irradiation (0.25, 0.5 and 1Gy). The cell viability, induction of apoptosis, cell death, cell cycling, generation of ROS, and expression of P53, Bax, Bcl2, caspase3, PARP1 and Fas genes were estimated. The results indicated that simvastatin ($0.1{\mu}M/l$ ) treatment for 24 hours prior to${\gamma}$ -irradiation increased cell death to 37.5% as compared to 4.81% by radiation (0.5Gy) alone. It was found that simvastatin treatment before irradiation caused arrest of cells in G0/G1 and G2/M phases as assessed using flow cytometry. Interestingly, simvastatin treatment of P3NS1 cells increased the intracellular ROS production and decreased antioxidant enzyme activity with increased P53, Bax and Caspase3 gene expression while that of Bcl2 was decreased. Consequently, our results indicated that pre-treatment with simvastatin increased radio sensitivity of myeloma tumor cells in addition to apoptotic effects through an intrinsic mitochondrial pathway. -
Wu, Wei;Yang, Sheng-Fu;Liu, Fei-Fei;Zhang, Ji-Hong 7111
Background: The aim of the meta-analysis was to derive a more precise assessment of the association between p16 promoter methylation and thyroid cancer risk. Materials and Methods: The PubMed, Web of Science databases and Chinese CNKI were searched for relevant articles. Ultimately, seventeen case-control studies were included with a total of 804 thyroid cancer cases and 487 controls analysis by R Software (R version 3.1.2) including meta. Crude odds ratios with 95% confidence intervals were calculated using the random-effects model which were used to assess the strength of relationship between p16 methylation and lung carcinogenesis. Funnel plots were carried out to evaluate publication bias. Results: The meta-analysis results showed that the frequency of p16 promoter methylation in cancer tissue/blood was significantly higher than that normal tissue/blood (OR=5.46, 95%CI 3.12-9.55, P<0.0001) by random effects model with small heterogeneity. Conclusions: Thus, p16 promoter methylation may be associated with thyroid cancer risk. -
Shi, Ru-Chun;Meng, Ai-Feng;Zhou, Weng-Lin;Yu, Xiao-Yan;Huang, Xin-En;Ji, Ai-Jun;Chen, Lei 7117
Background: The effects of home nursing intervention on the quality of life in patients with nasopharyngeal carcinoma (NPC) after radiotherapy and chemotherapy are unclear. According to the characteristics of nursing home patients with nasopharyngeal carcinoma, we should continuously improve the nursing plan and improve the quality of life of patients at home. Materials and Methods: We selected 180 patients at home with NPC after radiotherapy and chemotherapy. The patients were randomly divided into experimental and control groups (90 patients each). The experimental group featured intervention with an NPC home nursing plan, while the control group was given routine discharge and outpatient review. Nursing intervention for patients was mainly achieved by regular telephone follow-up and home visits. We use the quality of life scale (QOL-C30), anxiety scale (SAS) and depression scale (SDS) to evaluate these patients before intervention, and during follow-up at 1 month and 3 months after the intervention. Results: Overall health and quality of life were significantly different between the groups (p<0.05), Emotional function score was significantly higher after intervention (p<0.05), as were cognitive function and social function scores after 3 months of intervention (p<0.05). Scores of fatigue, nausea and vomiting, pain, appetite and constipation were also significantly different between the two groups (p<0.05). Rates of anxiety and depression after 3 months of intervention were 11.1%, 22.2% and 34.4%, 53.3%, the differences being significant (p<0.05). Conclusions: NPC home nursing plan could effectively improve overall quality of life, cognitive function, social function (after 3 months) of patients, but improvement regarding body function is not suggested. Fatigue, nausea and vomiting, pain, appetite, constipation were clearly improved. We should further pursue a personalized, comprehensive measurements for nursing interventions and try to improve the quality of life of NPC patients at home. -
Murray, Nigel P;Reyes, Eduardo;Orellana, Nelson;Fuentealba, Cynthia;Jacob, Omar 7123
Purpose: To determine the utility of secondary circulating prostate cells for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomagram. Materials and Methods: A single centre, prospective study of men with prostate cancer treated with radical prostatectomy between 2004 and 2014 was conducted, with registration of clinical-pathological details, total serum PSA pre-surgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Secondary circulating prostate cells were obtained using differential gel centrifugation and assessed using standard immunocytochemistry with anti-PSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values werecalculated using the Walz nomagram and CPC detection. Results: A total of 326 men participated, with a median follow up of 5 years; 64 had biochemical failure within two years. Extracapsular extension, positive surgical margins, pathological stage, Gleason score${\geq}8$ , infiltration of seminal vesicles and lymph nodes were all associated with higher risk of biochemical failure. The discriminative value for the nomogram and circulating prostate cells was high (AUC >0.80), predictive values were higher for circulating prostate cell detection, with a negative predictive value of 99%, sensitivity of 96% and specificity of 75%. Conclusions: The nomagram had good predictive power to identify men with a high risk of biochemical failure within two years. The presence of circulating prostate cells had the same predictive power, with a higher sensitivity and negative predictive value. The presence of secondary circulating prostate cells identifies a group of men with a high risk of early biochemical failure. Those negative for secondary CPCs have a very low risk of early biochemical failure. -
Sekar, Nishu;Nair, Manju;Francis, Glory;Kongath, Parvathy Raj;Babu, Sandhya;Raja, Sudhakaran;Gopalakrishnan, Abilash Valsala 7129
Background: The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility. In this condition there is an imbalance in female sex hormones. All the sequelae symptoms of PCOS gradually lead to cancer in the course of time. It is heterogeneous disorder of unknown etiology so it is essential to find the exact cause. Materials and Methods: In this study both invasive and non-invasive techniques were employed to establish the etiology. Diagnosis was based on Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, PCOM) and multiparameters using buccal samples and dermatoglypic analysis and cytogenetic study for 10 cases and four age and sex matched controls. Results: In clinical analysis we have observed the mean value of total testosterone level was 23.6nmol/L, total hirsutism score was from 12-24, facial acne was found in in 70% patients with 7-12 subcapsular follicular cysts, each measuring 2-8 mm in diameter. In dermatoglypic analysis we observed increases in mean value ($45.9^{\circ}$ ) of ATD angle when compared with control group and also found increased frequency (38%) of Ulnar loops on both fingers (UU), (18%) whorls on the right finger and Ulnar loop on left finger (WU) and (16%) arches on right and left fingers (AA) were observed in PCOS patients when compared with control subjects. Features which could be applied as markers for PCOS patients are the presence of Ulnar loops in middle and little fingers of right and left hand. The buccal micronucleus cytome assay in exfoliated buccal cells, we found decrease in frequency of micronuclei and significant increases in frequency of karyolysed nuclei in polycystic ovarian syndrome patients. Chromosome aberration analysis revealed a significant increase in frequency of chromosome aberrations (CAs) in PCOS patients when compared with controls. Conclusions: From this present work it can be concluded that non-invasive technique like dermatoglypics analysis and buccal micronucleus cytome assays with exfoliated buccal cell can also be effective biomarkers for PCOS, along with increased CAs in lymphocytes as a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer. From this present work it can be concluded to some extent that non-invasive technique like dermatoglypics and buccal cell analysis can also be effective for diagnosis. -
Elsayed, Engy Yousry;Mosalam, Nesreen Ahmed;Mohamed, Noha Refaat 7139
Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer related death overall. The role of insulin resistance in the development of HCC associated with chronic HCV infection has not been established. Resistin is a polypeptide hormone belonging to the adipokine family which could contribute to tumorigenesis and angiogenesis. Our aim was to study serum resistin and insulin resistance as risk factors for HCC in HCV cirrhotic patients. Materials and Methods: This prospective case controlled study included 100 patients with HCV related liver cirrhosis and HCC, 100 patients with HCV related liver cirrhosis without HCC and 50 apparently healthy participants as controls. For all subjects, liver profile, serologic markers for viral hepatitis, lipid profile, alpha-fetoprotein level (AFP), homeostasis model assessment (HOMA) were examined along with resistin. Results: HCC patients had higher mean values of HOMA-IR and resistin than cirrhotic patients and the control subjects (p<0.01). HOMA and resistin were considered independent risk factors in development of HCC, those patients with resistin > 12 ng/ml and HOMA > 4 being 1.6 times more likely to have HCC. Conclusions: HOMA and serum resistin allow for early identification of patients with cirrhosiswho are at substantially increased risk of HCC. Recommendation: HOMA and serum resistin could represent novel markers to identify HCV cirrhotic patients at greater risk of development of HCC. -
Rattanata, Narintorn;Daduang, Sakda;Wongwattanakul, Molin;Leelayuwat, Chanvit;Limpaiboon, Temduang;Lekphrom, Ratsami;Sandee, Alisa;Boonsiri, Patcharee;Chio-Srichan, Sirinart;Daduang, Jureerut 7143
Gold nanoparticles (GNPs) were conjugated with gallic acid (GA) at various concentrations between 30 and$150{\mu}M$ and characterized using transmission electron microscopy (TEM) and UV-Vis spectroscopy (UV-VIS). The anticancer activities of the gallic acid-stabilized gold nanoparticles against well-differentiated (M213) and moderately differentiated (M214) adenocarcinomas were then determined using a neutral red assay. The GA mechanism of action was evaluated using Fourier transform infrared (FTIR) microspectroscopy. Distinctive features of the FTIR spectra between the control and GA-treated cells were confirmed by principal component analysis (PCA). The surface plasmon resonance spectra of the GNPs had a maximum absorption at 520 nm, whereas GNPs-GA shifted the maximum absorption values. In an in vitro study, the complexed GNPs-GA had an increased ability to inhibit the proliferation of cancer cells that was statistically significant (P<0.0001) in both M213 and M214 cells compared to GA alone, indicating that the anticancer activity of GA can be improved by conjugation with GNPs. Moreover, PCA revealed that exposure of the tested cells to GA resulted in significant changes in their cell membrane lipids and fatty acids, which may enhance the efficacy of this anticancer activity regarding apoptosis pathways. -
Malek-Hosseini, Zahra;Taherinejad, Marziye;Malekzadeh, Mahyar;Ghaderi, Abbas;Doroudchi, Mehrnoosh 7149
Background: Inflammation plays a major role in the development and progression of gastric and other gastrointestinal tumors. The IL-17 family of cytokines has been under investigation as targets of immunotherapy. Materials and Methods: We investigated the levels of IL-17A inflammatory cytokine in the sera of 57 patients with gastric cancer (GC) and 90 healthy age/sex matched controls using ELISA methods. Results: In only 5 (8.8%) of the patients' sera was IL-17A detectable. No IL-17A was apparent in the sera of healthy controls. The maximum concentration of IL-17A in patients was 7.004 pg/ml. Vascular and lymphatic invasions were only seen in one of the 5 positive cases. Although all of them were in the age group >60 years, no correlation was seen between age and IL-17A level. These results are somewhat different from our findings for colorectal cancer (CRC) in the same population. Conclusions: It is possible that the inflammopathology of CRC and GC are rather different, at least in Fars, a southern province of Iran. -
Promraksa, Bundit;Daduang, Jureerut;Chaiyarit, Ponlatham;Tavichakorntrakool, Ratree;Khampitak, Tueanjit;Rattanata, Narintorn;Tangrassameeprasert, Roongpet;Boonsiri, Patcharee 7155
Background: Oral cancer is a health problem in Thailand. Cratoxylum formosum subsp. pruniflorum Gogel (Teawdang), normally consumed in northeast Thailand, has proven cytotoxic to cervical cancer cell lines including HeLa, SiHa and C-33A. Recently, Asian oral cancer cell lines, ORL-48 and ORL-136, were established. Therefore, we aimed to study cytotoxicity of Teawdang in these. Total phenolic (TPC) and flavonoid content (TFC), and antioxidant activity of Teawdang were also determined. Materials and Methods: Teawdang was purchased from Khon Kaen market during June-October 2013. Hexane (CHE), ethyl acetate (CEE) and methanol (CME) extracts of its edible part were analyzed for TPC by the folin-ciocalteau method and for TFC by an aluminium colorimetric method. Antioxidant activity and cytotoxicity in normal Vero cells and oral cancer cells were investigated. Cell viability was assessed using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results: CME and CEE had higher TPC and TFC and antioxidant activity than CHE. Both CME and CEE, at$200{\mu}g$ dry wt/mL, were cytotoxic to the studied oral cancer cell lines. However, CME was cytotoxic to Vero cells whereas CEE was not. Compared to Vero cells, CEE significantly inhibited ORL-48 and ORL-136 growth (p=0.03 and p=0.02, respectively). Conclusions: CEE exhibited cytotoxic effects on the studied oral cancer cell lines but not normal Vero cells. The bioactive compounds in CEE should be further purified and elucidated for their mechanisms of action for development as anticancer agents. -
Kumar, Rajeev;Ghosh, Sankar Kumar;Verma, Akalesh Kumar;Talukdar, Anuradha;Deka, Monoj Kumar;Wagh, Mira;Bahar, H.M. Iqbal;Tapkire, Ritesh;Chakraborty, Kali Pankaj;Kannan, R. Ravi 7161
Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer in the north east of India. The present study concerned the prevalence of human papilloma virus (HPV) in the ESCC in north eastern India and its impact on response to chemotherapy. Materials and Methods: p16 expression, a surrogate marker for HPV infection was assessed in 101 pre-treatment biopsies of locally advanced ESCC, reported from a comprehensive cancer centre in north east India, using immunohistochemistry. All patients received neo-adjuvant chemotherapy. Response was assessed clinically and histopathologically with attention to p16 expression. Results: p16 was expressed in 22% of ESCC (22 out of 101) and was more prevalent in patients who were more than 45 years of age (P=0.048). p16 positive tumors appeared more commonly in the upper 2/3 of the thoracic esophagus (18 in 22). Nine of the 22 (41%) p16 positive tumors achieved pathologic complete response following neo-adjuvant chemotherapy (P=0.008). There was a trend towards reduced mortality in this group (P=0.048). Some 9 of the 20 (45%) patients who achieved pathologic complete response were p16 positive. Conclusions: Expression of p16 in ESCC correlates with higher rate of pathologic complete remission in patients undergoing neo adjuvant chemotherapy and could be a predictive marker for response assessment. -
Ghosh, Saptarshi;Rao, Pamidimukkala Bramhananda;Kotne, Sivasankar 7167
Background: Although 3D image based brachytherapy is currently the standard of treatment in cervical cancer, most of the centres in developing countries still practice orthogonal intracavitary brachytherapy due to financial constraints. The quest for optimum dose and fractionation schedule in high dose rate (HDR) intracavitary brachytherapy (ICBT) is still ongoing. While the American Brachytherapy Society recommends four to eight fractions of each less than 7.5 Gy, there are some studies demonstrating similar efficacy and comparable toxicity with higher doses per fraction. Objective: To assess the treatment efficacy and late complications of HDR ICBT with 9 Gy per fraction in two fractions. Materials and Methods: This is a prospective institutional study in Southern India carried on from$1^{st}$ June 2012 to$31^{st}$ July 2014. In this period, 76 patients of cervical cancer satisfying our inclusion criteria were treated with concurrent chemo-radiation following ICBT with 9 Gy per fraction in two fractions, five to seven days apart. Results: The median follow-up period in the study was 24 months (range 10.6 - 31.2 months). The 2 year actuarial local control rate, disease-free survival and overall survival were 88.1%, 84.2% and 81.8% respectively. Although 38.2% patients suffered from late toxicity, only 3 patients had grade III late toxicity. Conclusions: In our experience, HDR brachytherapy with 9 Gy per fraction in two fractions is an effective dose fractionation for the treatment of cervical cancer with acceptable toxicity. -
Background: This descriptive study was performed in order to assess health perspectives of women, who applied to Yildirim Beyazit University Ataturk Education and Research Hospital, Outpatient Clinic of Obstetrics and Gynecology for cervical cancer scans and were in the reproductive years. Factors influencing their perspectives were also assessed. Materials and Methods: In this study, a simple random sampling formula was adopted to calculate the volume (300) of the targeted sample. Results of the research were obtained through individual diagnosis form and cervical cancer and the Pap smear test health belief model scale (HBMS). Results: It was found that 75.0% of the women heard of the Pap smear test before, and 48.7% had undertaken one. Some 51.4% of the women who had Pap smear test expressed that they had the test at irregular periods. Most of the women stated that they heard about the smear test from the health staff (51.7%). Lack of any health complaints (28.3%) and not having adequate information about the test (21.0%) were among the reasons for not undergoing a Pap smear test. It was found that lower dimension average scores of the women obtained from the cervical cancer and Pap smear test HBMS varied from
$7.7{\pm}2.3$ to$33.5{\pm}9.3$ . When the lower dimension average scores of women from the HBMS were examined, the perception of usefulness was high but the susceptibility and health motivations were low. Conclusions: In this study, it was determined that the awareness of women about cervical cancer and the Pap smear test was insufficient, and susceptibility and motivation perception towards having a Pap smear test were low. -
Ahmed, Hanaa H;Abd-Rabou, Ahmed A;Hassan, Amal Z;Kotob, Soheir E 7179
Cancer is a major health obstacle around the world, with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) as major causes of morbidity and mortality. Nowadays, there isgrowing interest in the therapeutic use of natural products for HCC and CRC, owing to the anticancer activity of their bioactive constituents. Boswellia serrata oleo gum resin has long been used in Ayurvedic and traditional Chinese medicine to alleviate a variety of health problems such as inflammatory and arthritic diseases. The current study aimed to identify and explore the in vitro anticancer effect of B. Serrata bioactive constituents on HepG2 and HCT 116 cell lines. Phytochemical analysis of volatile oils of B. Serrata oleo gum resin was carried out using gas chromatography-mass spectrometry (GC/MS). Oleo-gum-resin of B. Serrata was then successively extracted with petroleum ether (extract 1) and methanol (extract 2). Gas-liquid chromatography (GLC) analysis of the lipoidal matter was also performed. In addition, a methanol extract of B. Serrata oleo gum resin was phytochemically studied using column chromatography (CC) and thin layer chromatography (TLC) to obtain four fractions (I, II, III and IV). Sephadex columns were used to isolate${\beta}$ -boswellic acid and identification of the pure compound was done using UV, mass spectra,$^1H$ NMR and$^{13}C$ NMR analysis. Total extracts, fractions and volatile oils of B. Serrata oleo-gum resin were subsequently applied to HCC cells (HepG2 cell line) and CRC cells (HCT 116 cell line) to assess their cytotoxic effects. GLC analysis of the lipoidal matter resulted in identification of tricosane (75.32%) as a major compound with the presence of cholesterol, stigmasterol and${\beta}$ -sitosterol. Twenty two fatty acids were identified of which saturated fatty acids represented 25.6% and unsaturated fatty acids 74.4% of the total saponifiable fraction. GC/MS analysis of three chromatographic fractions (I,II and III) of B. Serrata oleo gum resin revealed the presence of pent-2-ene-1,4-dione, 2-methyl- levulinic acid methyl ester, 3,5- dimethyl- 1-hexane, methyl-1-methylpentadecanoate, 1,1- dimethoxy cyclohexane, 1-methoxy-4-(1-propenyl)benzene and 17a-hydroxy-17a-cyano, preg-4-en-3-one. GC/MS analysis of volatile oils of B. Serrata oleo gum resin revealed the presence of sabinene (19.11%), terpinen-4-ol (14.64%) and terpinyl acetate (13.01%) as major constituents. The anti-cancer effect of two extracts (1 and 2) and four fractions (I, II, III and IV) as well as volatile oils of B. Serrata oleo gum resin on HepG2 and HCT 116 cell lines was investigated using SRB assay. Regarding HepG2 cell line, extracts 1 and 2 elicited the most pronounced cytotoxic activity with$IC_{50}$ values equal 1.58 and$5.82{\mu}g/mL$ at 48 h, respectively which were comparable to doxorubicin with an$IC_{50}$ equal$4.68{\mu}g/mL$ at 48 h. With respect to HCT 116 cells, extracts 1 and 2 exhibited the most obvious cytotoxic effect; with$IC_{50}$ values equal 0.12 and$6.59{\mu}g/mL$ at 48 h, respectively which were comparable to 5-fluorouracil with an$IC_{50}$ equal$3.43{\mu}g/mL$ at 48 h. In conclusion, total extracts, fractions and volatile oils of B. Serrata oleo gum resin proved their usefulness as cytotoxic mediators against HepG2 and HCT 116 cell lines with different potentiality (extracts > fractions > volatile oil). In the two studied cell lines the cytotoxic acivity of each of extract 1 and 2 was comparable to doxorubicin and 5-fluorouracil, respectively. Extensive in vivo research is warranted to explore the precise molecular mechanisms of these bioactive natural products in cytotoxicity against HCC and CRC cells. -
Zahedi, Atefeh;Rafiemanesh, Hosein;Enayatrad, Mostafa;Ghoncheh, Mahshid;Salehiniya, Hamid 7189
Background: Cancer is a leading cause of death throughout the world. Increasing life expectancy and aging population are important factors for increasing cancer incidences in developing countries. National programs are essential for prevention and control of cancer in any society. This study aimed to investigate cancer epidemiology and trends in the province of Hamadan, located in Northwest Iran. Materials and Methods: This analytical study was carried out based on cancer registry data from 2004 to 2009 in the province of Hamadan, analyzed using STATA (version 12) software for descriptive tests and Join point 4.1.1.1 software for analytical tests. Results: There were 7,767 registered cases of cancer during the 6 years studied. Of the total cases registered, 59.1% (4,592 cases) involved men and 40.9% (3,175 cases) occurred in women. Age-standardized incidence rates (ASR) increased from 72.9 to 132.0 in males and 48.2 to 115.0 in females during the 6 years of the study (p<0.001). The most common cancers were skin, stomach, breast, bladder, and leukemia. In women, teh most common were breast, skin, stomach, colorectal, and leukemia, in that order, and in men skin, stomach, bladder, leukemia, and prostate cancers. Conclusions: The cancer incidence is greater in men that women in this region but with increasing trends in both sexes. Planning regarding education in prevention of exposure to risk factors and control strategies is required to decrease the incident cases. Screening programs for common cancers in older age groups might be helpful to reduce the disease impact. -
Background: Since seventeen employees of an offset printing company in Osaka, Japan developed cholangiocarcinoma it has become recognized as an occupational cancer. This study investigated the differences of clinical features between occupational cholangiocarcinoma and sporadic young-onset cholangiocarcinoma. Materials and Methods: Thirty-four young adults (<50 years old) with sporadic cholangiocarcinoma were extracted from the Rosai Hospital Group database (sporadic group) and their clinical features were compared with those of 17 patients with occupational cholangiocarcinoma (occupational group). Results: The 34 patients in the sporadic group were treated for cholangiocarcinoma at 16 different Rosai hospitals. There were significant differences of age (p<0.01), gender (p<0.01), abnormal laboratory tests (p<0.01), and tumor location (p<0.01) between the two groups. The percentage of patients with abnormal laboratory tests was significantly higher in the occupational group than in the sporadic group (p<0.001). Regional dilation of bile ducts, which is a characteristic of occupational cholangiocarcinoma, was not observed in the sporadic group. Conclusions: No cluster of cholangiocarcinoma cases was identified in the Rosai Hospital database. There were differences of clinical features between occupational and sporadic cholangiocarcinoma, which might be helpful for diagnosing occupational cholangiocarcinoma in the future.
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Zhang, Jian-Feng;Liu, Jun-Mao;Zhang, Nin;Du, Chao;Zheng, Qin 7201
Background: This analysis was conducted to evaluate the efficacy and safety of Trans-arterial Chemo-Embolization (TACE) in treating Elderly patients with Hepatocellular Carcinoma (EHPC). Methods: Clinical studies evaluating the efficacy and safety of TACE on response and safety for patients with EHPC were identified by using a predefined search strategy. Pooled response rate of treatment were calculated. Results: In TACE based regimen, clinical studies which including patients with EHPC were considered eligible for the evaluation of response. And, in these TACE based treatments, pooled analysis suggested that, in all 288 patients whose response could be assessed, the pooled reponse rate was 29.5%(85/288) in TACE based treatment. The most commonly encountered TACE-related morbidity was liver function impairment. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred in EHPC patients with TACE based treatments. Conclusion: This evidence based analysis suggests that TACE based treatments are associated with mild response rate and accepted toxicities for treating patients with EHPC. -
Zhang, Qun;Shu, Fu-li;Jiang, Yu-Feng;Huang, Xin-En 7205
Background: In this study, influence caused by expression plasmids of connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) short hairpin RNA (shRNA) on mRNA expression of CTGF,TIMP-1,procol-${\alpha}1$ and PCIII in hepatic tissue with hepatic fibrosis, a precancerous condition, in rats is analyzed. Materials and Methods: To screen and construct shRNA expression plasimid which effectively interferes RNA targets of CTGF and TIMP-1 in rats. 50 cleaning Wistar male rats are allocated randomly at 5 different groups after precancerous fibrosis models and then injection of shRNA expression plasimids. Plasmid psiRNA-GFP-Com (CTGF and TIMP-1 included), psiRNA-GFP-CTGF, psiRNA-GFP-TIMP-1 and psiRNA-DUO-GFPzeo of blank plasmid are injected at group A, B, C and D, respectively, and as model control group that none plasimid is injected at group E. In 2 weeks after last injection, to hepatic tissue at different groups, protein expression of CTGF, TIMP-1, procol-${\alpha}1$ and PC III is tested by immunohistochemical method and,mRNA expression of CTGF,TIMP-1,procol-${\alpha}1$ and PCIII is measured by real-time PCR. One-way ANOVA is used to comparison between-groups. Results: Compared with model group, there is no obvious difference of mRNA expression among CTGF,TIMP-1,procol-${\alpha}1$ , PC III and of protein expression among CTGF, TIMP-1, procol-${\alpha}1$ , PC III in hepatic tissue at group injected with blank plasmid. Expression quantity of mRNA of CTGF, TIMP-1, procol-${\alpha}1$ and PCIII at group A, B and C decreases, protein expression of CTGF, TIMP-1, procol-${\alpha}1$ , PC III in hepatic tissue is lower, where the inhibition of combination RNA interference group (group A) on procol-${\alpha}1$ mRNA transcription and procol-${\alpha}1$ protein expression is superior to that of single interference group (group B and C) (P<0.01 or P<0.05). Conclusions: RNA interference on CTGF and/or TIMP-1 is obviously a inhibiting factor for mRNA and protein expression of CTGF, TIMP-1, procol-${\alpha}1$ and PCIII. Combination RNA interference on genes of CTGF and TIMP-1 is superior to that of single RNA interference, and this could be a contribution for prevention of precancerous condition. -
Chimparlee, Nitinan;Chuaypen, Natthaya;Khlaiphuengsin, Apichaya;Pinjaroen, Nutcha;Payungporn, Sunchai;Poovorawan, Yong;Tangkijvanich, Pisit 7211
Background: The aims of this study were to evaluate the diagnostic and prognostic roles of serum osteopontin (OPN) and single nucleotide polymorphisms (SNPs) in the OPN promoter in patients with hepatitis B-related hepatocellular carcinoma (HCC). Materials and Methods: Four groups were studied, which included 157 patients with HCC, 73 with liver cirrhosis (LC) and 97 with chronic hepatitis (CH), along with 80 healthy subjects. Serum OPN and alpha-fetoprotein (AFP) levels were measured. The SNPs -66 T/G, -156 G/${\Delta}G$ and -433 C/T within the OPN promoter were determined by direct sequencing. Results: Serum OPN levels were significantly higher in patients with HCC than in the other groups. Area under receiver operating characteristics curves in distinguishing HCC from chronic liver disease (CLD; CH and LC) were 0.782 (95% CI; 0.729-0.834) for OPN and 0.888 (95% CI; 0.850-0.927) for AFP. Using the optimal cut-off value (70 ng/mL), OPN had sensitivity and specificity of 72% and 71%, respectively. Serum OPN was superior to AFP in detecting early-stage HCC (68% vs. 46%). A combination of both markers yielded an improved sensitivity for detecting early HCC to 82%. A high OPN level was significantly correlated with advanced BCLC stage and was an independent prognostic factor for HCC. The SNPs -156 and -443 were associated with susceptibility to HCC, but were not related to overall survival. Conclusions: Serum OPN is a useful diagnostic and prognostic marker for HCC. The combined use of serum OPN and AFP improved the diagnosis of early HCC. Genetic variation in the OPN promoter is associated with the risk, but not the prognosis of HCC. -
Bhandari, Prerana;Ahmad, Firoz;Dalvi, Rupa;Koppaka, Neeraja;Kokate, Prajakta;Das, Bibhu Ranjan;Mandava, Swarna 7219
Background: Chromosomal aberrations identified in acute lymphoblastic leukemia (ALL) have an important role in disease diagnosis, prognosis and management. Information on karyotype and associated clinical parameters are essential to physicians for planning cancer control interventions in different geographical regions. Materials and Methods: In this study, we present the overall frequency and distribution patterns of chromosomal aberrations in both children and adult de novo B lineage ALL Indian patients using conventional cytogenetics, interphase FISH and multiplex RT-PCR. Results: Among the 215 subjects, cytogenetic results were achieved in 172 (80%) patients; normal karyotype represented 37.2% and abnormal 62.8% with a distribution as follows: 15.3% hypodiploidy; 10.3% hyperdiploidy; 15.8% t(9;22); 9.8% t(1;19); 3.7% t(12;21); 2.8% t(4;11); 2.8% complex karyotypes. Apart from these, we observed several novel, rare and common chromosomal rearrangements. Also, FISH studies using LSI extra-signal dual-color probes revealed additional structural or numerical changes. Conclusions: These results demonstrate cytogenetic heterogeneity of ALL and confirm that the incidence of chromosomal abnormalities varies considerably. To the best of our knowledge, this is one of the largest reported series of cytogenetic investigations in Indian B-lineage ALL cases. In addition, ongoing cytogenetic studies are warranted in larger groups of B-lineage ALL cases to identify newly acquired chromosomal abnormalities that may contribute to disease diagnosis and management. -
Kingnate, Chalita;Supoken, Amornrat;Kleebkaow, Pilaiwan;Chumworathayi, Bundit;Luanratanakorn, Sanguanchoke;Kietpeerakool, Chumnan 7231
This study was conducted to determine whether advancing age is an independent predictor of increased risk of high-grade pathologies among women referred for colposcopy after abnormal cervical cytology. Medical records were reviewed for women with abnormal cervical cytology who underwent colposcopy at Khon Kaen University Hospital. Logistic regression was used to determine the independent impact of age on the risk of high-grade pathologies. Mean age of the women was 42.8 years. Of 482 women, 97 (20.1%) were postmenopausal, and 92 (19.1%) were nulliparous. The rate of high-grade pathologies included cervical intraepithelial neoplasia 2-3, 99 (20.5%), adenocarcinoma in situ, 4 (0.8%), cervical cancer, 30 (6.2%), and endometrial cancer, 1 (0.2%). The prevalence of significant lesions was 26.9% (95% CI, 23.1%-31.2%). In total, 31 women had cancers (6.4%; 95% CI, 4.4%-9.0%). When controlling for smear types and parity, age was noted to be a significant independent predictor of high-grade histopathology. Women older than 35-40 years were approximately 2 times as likely to have severe histopathology as the younger women. This study illustrates the substantial risk of underlying significant lesions especially invasive cancer in Thai women with abnormal cervical cytology. Age was a significant independent factor predicting the risk of high-grade pathologies. -
Nassar, Hanan Ramadan;Zeeneldin, Ahmed A;Helal, Amany Mohamed;Ismail, Yahia Mahmoud;Elsayed, Abeer Mohamed;Elbassuiony, Mohamed A;Moneer, Manar M 7237
Background: Epithelial ovarian cancer (EOC) is the commonest malignancy involving the ovaries. Maximum surgical cytoreduction (MCR) followed by adjuvant taxane-platinum chemotherapy are the standard of care treatments. Aims: To study treatment outcomes of EOC patients that were maximally cyto-reduced and received adjuvant paclitaxel-carboplatin (PC) chemotherapy. Materials and Methods: This retrospective cohort study included 174 patients with EOC treated at the Egyptian National Cancer Institute between 2006 and 2010. For inclusion, they should have had undergone MCR with no-gross residual followed by adjuvant PC chemotherapy. MCR was total abdominal hysterectomy/bilateral salpingo-oophorectomy [TAH/BSO] or unilateral salpingo-oophorectomy [USO] plus comprehensive staging. Results: The median age was 50 years. Most patients were married (97.1%), had offspring (92.5%), were postmenopausal (53.4%), presented with abdominal/pelvic pain and swelling (93.7%), had tumors involving both ovaries (45.4%) without extra-ovarian extension i.e. stage I (55.2%) of serous histology (79.9%) and grade II (87.4%). TAH/BSO was performed in 97.7% of cases. A total of 1,014 PC chemotherapy cycles were administered and were generally tolerable with 93.7% completing 6 cycles. Alopecia and numbness were the commonest adverse events. The median follow up period was 42 months. The 2-year rates for disease free survival (DFS) and overall survival (OS) were 70.7% and 94.8%, respectively. The respective 5-year rates were 52.6% and 81.3%. Advanced stage and high-grade were significantly associated with poor DFS and OS (p<0.001). Age >65 years was associated with poor OS (p =0.008). Using Cox-regression, stage was independent predictor of poor DFS and OS. Age was an independent predictor of poor OS. -
Sambyal, Vasudha;Guleria, Kamlesh;Kapahi, Ruhi;Manjari, Mridu;Sudan, Meena;Uppal, Manjit Singh;Singh, Neeti Rajan 7243
Background: Monocyte chemoattractant protein-1 (MCP-1) is a major chemokine thought to be responsible for monocyte and T-lymphocyte recruitment in acute inflammatory conditions and recruitment of macrophages in tumors. It is also implicated in cardiovascular disease, rheumatoid arthritis and chronic obstructive pulmonary disease. The aim of the present study was to investigate the correlation between MCP-1 -2518 A/G polymorphism and breast cancer risk in patients from Amritsar city of Punjab state in North-West India. Materials and Methods: We screened DNA samples of 200 sporadic breast cancer patients and 200 age and gender matched unrelated healthy individuals for MCP-1 -2518 A/G polymorphism using the PCR-RFLP method. Results: A significantly increased frequency of the GG genotype was observed in patients as compared to controls. Individuals carrying the MCP1 -2518GG genotype had a two fold risk for breast cancer (OR=2.06, 95%CI, 1.06-3.98; p=0.03). Genetic models analysis revealed a significant association between MCP-1 -2518 A/G polymorphism and cancer risk in homozygous co-dominant (OR=2.06, 95%CI, 1.06-3.98; p=0.03) and recessive (OR=1.97, 95%CI, 1.05-3.70; p=0.03) models. Conclusions: We conclude that the GG genotype of the MCP-1-2518 A/G polymorphism is associated with increased risk to breast cancer in Punjab, North-West India. -
Zeng, Yong;Jiang, Hua-Yong;Wei, Li;Xu, Wei-Dong;Wang, Ya-Jie;Wang, Ya-Di;Liu, Chuan 7249
Background: Previous studies evaluated associations between the CYP1A2 rs762551 polymorphism and bladder cancer risk. However, the results were inconsistent. We therefore performed a meta-analysis of the published case-control studies to assess in detail the association between CYP1A2 rs762551 polymorphism and bladder cancer risk. Materials and Methods: PubMed, Embase and Web of Science were searched to identify relevant studies and the pooled odds ratio (OR) and 95 % confidence interval (95%CI) were calculated. Results: A total of seven articles including 3,013 cases and 2,771 controls were finally included. Overall, a significant association was found between the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for CC vs AA (OR=0.82, 95% CI=0.69~0.99), but no significant associations were found for the other three models (AC vs AA: OR=0.91, 95% CI=0.81~1.02; the dominant model: OR=0.90, 95% CI=0.80~1.00; the recessive model: OR=0.84, 95% CI =0.72~1.00). In the subgroup analysis by ethnicity, we detected significant associations between the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for GA vs GG (OR = 0.78, 95% CI =0.64~0.96) and for the recessive model (OR=0.80, 95% CI=0.66~0.96) in Caucasians, but not for Asians. Conclusions: The results from the meta-analysis suggested that the CYP1A2 rs762551 polymorphism is a protective factor for bladder cancer, especially in Caucasians. -
Background: Recent reports have shown that DLC-1 is widely expressed in normal tissues and is down-regulated in a wide range of human tumors, suggesting it may act as a tumor suppressor gene. We conducted a meta-analysis to determine the correlation between DLC-1 expression and clinicopathological characteristics in cancers. Materials and Methods: A detailed literature search was made for relevant publications from PubMed, EMBASE, Cochrane library databases, Web of Science, CNKI. The methodological quality of the studies was also evaluated. Analyses of pooled data were performed and odds ratios (ORs) were calculated and summarized. Results: Final analysis was performed of 1,815 cancer patients from 19 eligible studies. We observed that DLC- 1 expression was significantly lower in cancers than in normal tissues. DLC-1 expression was not found to be associated with tumor differentiation status. However, DLC-1 expression was obviously lower in advance stage than in early-stage cancers and was more down-regulated in metastatic than non-metastatic cancers. Conclusions: The results of our meta-analysis suggested that DLC-1 expression is significantly lower in cancers than in normal tissues. Aberrant DLC-1 expression may play an important role in cancer genesis and metastasis.
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Shahsavari, Zahra;Karami-Tehrani, Fatemeh;Salami, Siamak 7261
Breast cancer, the most common cancer in the women, is the leading cause of death. Necrotic signaling pathways will enable targeted therapeutic agents to eliminate apoptosis-resistant cancer cells. In the present study, the effect of shikonin on the induction of cell necroptosis or apoptosis was evaluated using the T-47D breast cancer cell line. The cell death modes, caspase-3 and 8 activities and the levels of reactive oxygen species (ROS) were assessed. Cell death mainly occurred through necroptosis. In the presence of Nec-1, caspase-3 mediated apoptosis was apparent in the shikonin treated cells. Shikonin stimulates ROS generation in the mitochondria of T-47D cells, which causes necroptosis or apoptosis. Induction of necroptosis, as a backup-programmed cell death pathway via ROS stimulation, offers a new strategy for the treatment of breast cancer. -
Jalil, Nur Asyilla Che;Zin, Anani Aila Mat;Othman, Nor Hayati 7267
Introduction: Kelantan is one of the states in Malaysia which has a high prevalence of type 2 diabetes (DM2). Other than with endometrial carcinoma, the association of DM2 with particular female cancers is not known. Objective: To determine the proportion of breast, cervical, ovarian and endometrial cancers among females with DM2 diagnosed in Hospital Universiti Sains Malaysia (HUSM) over an 11 year period. Materials and Methods: All histologically confirmed cases of breast, endometrial, cervical and ovarian carcinomas admitted to the Hospital were included in the study. The patient diabetic status was traced from the hospital medical records. Results: There was a total of 860 cases of breast, cervical, ovarian and endometrial carcinomas over this period. Breast carcinoma was the commonest, accounting for 437/860 (50.8%) followed by cervix, 159/860 (18.5%), ovarian, 143/860 (16.6%) and endometrial carcinomas, 121/860 (14.1%). Out of these, 228/860 (26.5%) were confirmed diabetics. Endometrial carcinoma patients showed the highest proportion being diabetics, 42.1% (51/121), followed by ovarian cancer, 25.9% (37/143), breast carcinoma, 23.6% (103/437) and cervical cancer 23.3% (37/159). Conclusions: There is a significant proportion of DM2 among women with these four cancers, endometrial carcinoma being the highest followed by ovarian, breast and cervical carcinoma. The rising trend of these four cancers is in tandem with an increasing trend of DM2 in the community. In populations where diabetes is prevalent, screening for epithelial cancers should be rigourous. Diabetic clinics should include screening for these cancers among their female patients and gynecology clinics should screen the women they treat for their diabetes status. -
Vijakururote, Linlada;Suprasert, Prapaporn;Srisomboon, Jatupol;Siriaunkgul, Sumalee;Settakorn, Jongkolnee;Rewsuwan, Sunida 7271
The objective of this study was to determine the prevalence of significant lesions defined as high grade squamous intraepithelial lesions (HSIL), adenocarcinoma in situ (AIS) and invasive carcinoma in women who had HPV-positive and cytology negative co-testing screening results. This retrospective study was conducted in Chiang Mai University Hospital between May, 2013 and August, 2014. Hybrid capture 2 (HC2) was used for HPV testing and conventional Pap smears for cytologic screening. A repeat liquid-based cytology (LBC) was performed in women with such co-testing results followed by colposcopy. Random biopsy was performed in cases of normal colposcopic findings. Further investigations were carried out according to the biopsy or the repeat LBC results. During the study period, 273 women met the criteria and participated in the study. The mean age of these women was 46.4 years with 30% of them reporting more than one partner. The median interval time to colposcopy was 165 days. About 40% showed an abnormality in the repeat cytology. Significant cervical lesions were found in 20 (7.3%) women, including 2 invasive cancers. Of interest was that only 2 of 20 significant lesions were diagnosed by colposcopic examination while the remainder were initially detected by cervical biopsy and abnormal repeat cytology. In conclusion, the prevalence of significant cervical lesions in HPV positive and cytology negative women in Northern Thailand was 7.3%. Further diagnostic work up with repeat cytology follow by colposcopy is recommended. Random biopsy should be performed even when the colposcopic findings are normal. -
Aristizabal-Pachon, Andres Felipe;Carvalho, Thais Inacio;Carrara, Helio Humberto;Andrade, Jurandyr;Takahashi, Catarina Satie 7277
Background: The Wnt/${\beta}$ -catenin signaling pathway is an important regulator of cellular functions such as proliferation, survival and cell adhesion. Wnt/${\beta}$ -catenin signaling is associated with tumor initiation and progression;${\beta}$ -catenin mutations explain only 30% of aberrant signaling found in breast cancer, indicating that other components and/or regulation of the Wnt/${\beta}$ -catenin pathway may be involved. Objective: We evaluated AXIN2 rs2240308 and rs151279728 polymorphisms, and expression profiles of${\beta}$ -catenin destruction complex genes in breast cancer patients. Materials and Methods: We collected peripheral blood samples from 102 breast cancer and 102 healthy subjects. The identification of the genetic variation was performed using PCR-RFLPs and DNA sequencing. RT-qPCR was used to determine expression profiles. Results: We found significant association of AXIN2 rs151279728 and rs2240308 polymorphisms with breast cancer risk. Significant increase was observed in AXIN2 level expression in breast cancer patients. Further analyses showed APC,${\beta}$ -catenin, CK1${\alpha}$ , GSK3${\beta}$ and PP2A gene expression to be associated to clinic-pathological characteristics. Conclusions: The present study demonstrated, for the first time, that AXIN2 genetic defects and disturbance of${\beta}$ -catenin destruction complex expression may be found in breast cancer patients, providing additional support for roles of Wnt/${\beta}$ -catenin pathway dysfunction in breast cancer tumorigenesis. However, the functional consequences of the genetic alterations remain to be determined. -
Aghamohammadi, Azar;Hosseinimehr, Seyed Jalal;Ghasemi, Arash;Azadbakht, Mohammad;Pourfallah, Tayyeb Allahverdi 7285
Background: Although radiotherapy is one of the most effective strategies in the treatment of cancers, it is associated with short and long term side effects on normal tissues. Zataria multiflora Boiss (Laminacea) (ZM) has several biological properties such as antioxidant and anti-inflammation activities.Here we investigated cell killing effects of a hydroalcoholic Zataria multiflora extract on cell death induced by ionizing radiation in a human glioblastoma cell line (A172) and human non-malignant fibroblasts (HFFF2) in vitro. Materials and Methods: A172 and HFFF2 cells were treated with a hydroalcoholic extract of dried aerial parts of Zataria multiflora at different concentrations (25, 50, 100, 150 and$200{\mu}g/ml$ ) and then exposed to ionizing radiation (IR). Cell proliferation and DNA fragmentation were evaluated. Thymol content in the extract was analyzed and quantified by HPLC methods. Results: A172 cell proliferation was significantly inhibited by ZM. The percentage cell survival was$91.8{\pm}8.57$ for cells treated with$200{\mu}g/ml$ of ZM extract alone while it was$76.0{\pm}4.27$ and$66.2{\pm}8.42$ for cells treated with ZM and exposed to IR at doses of 3Gy and 6Gy, respectively. Radiation-induced apoptosis in A172 cells was significantly increased following treatment with ZM at doses of$200{\mu}g/ml$ . ZM extract did not exhibit any enhanced cell killing effects and apoptosis caused by IR on HFFF2 cells. Conclusions: These data show selective radiosensitization effects of ZM in A172 cells apparently due to increased radiation-induced apoptosis. -
Zhang, Jun-Peng;Liu, Hua-Yan;Ning, Chun-Ping;Chong, Jing;Sun, Yong-Mei 7291
Purpsoe: To investigate the diagnostic value of quantitative analysis of a tissue diffusion and virtual touch tissue imaging quantification (VTIQ) technique with acoustic radiation force impulse (ARFI) elastography for assessing enlarged cervical lymph nodes. Materials and Methods: Fifty-six enlarged cervical lymph nodes confirmed by pathologic diagnoses were covered in the study. According to the results of pathologic diagnosis, patients were classified into benign and malignant groups. All the patients were examined by both conventional ultrasonography and elastography. AREA% and shear wave velocity (SWV) in ROI of different groups were calculated and compared using ROC curves. Cut-off points of AREA% and SWV were determined with receiver operating characteristic curves. Results: Final histopathological results revealed 21 cases of benign and 35 cases of malignant lymph nodes. The mean values of AREA% and SWV in benign and malignant groups were$45.0{\pm}17.9%$ and$2.32{\pm}0.57m/s$ , and$61.3{\pm}21.29%$ and$4.36{\pm}1.25$ )m/s, respectively. For the parameters of elastography, "AREA%" and SWV demonstrated significant differences between groups (p=0.002). AREA% was positively correlated with SWV with a correlation coefficient of 0.809 (P<0.001). Conclusions: Stiffness of different lymph node diseases in patients may differ. Elastography can evaluate changes sensitively and provide valuable information to doctors. The study proved that the VTIQ elastography technique can play an important role in differential diagnosis of lymph nodes. -
Yang, Juan;Zhu, Jian;Zhang, Yong-Hui;Chen, Yong-Sheng;Ding, Lu-Lu;Kensler, Thomas W;Chen, Jian-Guo 7295
Background: Lung cancer has been a major health problem in developed countries for several decades, and has emerged recently as the leading cause of cancer death in many developing countries. The incidence of lung cancer appears to be increasing more rapidly in rural than in urban areas of China. This paper presents the trends of lung cancer incidence and survival derived from a 40-year population-based cancer monitoring program in a rural area, Qidong, China. Materials and Methods: The Qidong cancer registration data of 1972-2011 were used to calculate the crude rate, age-standardized rate by Chinese population (CASR) and by world population (WASR), birth cohort rates, and other descriptive features. Active and passive methods were used to construct the data set, with a deadline of the latest follow-up of April 30, 2012. Results: The total number of lung cancer cases was 15,340, accounting for 16.5% of all sites combined. The crude incidence rate, CASR and WASR of this cancer were 34.1, 15.7 and 25.4 per 100,000, respectively. Males had higher crude rates than females (49.7 vs 19.0). Rapidly increasing trends were found in annual percent change resulting in lung cancer being a number one cancer site after year 2010 in Qidong. Birth cohort analysis showed incidence rates have increased for all age groups over 24 years old. The 5 year observed survival rates were 3.55% in 1973-1977, 3.92 in 1983-1987, 3.69% in 1993-1997, and 6.32% in 2003-2007. Males experienced poorer survival than did females. Conclusions: Lung cancer has become a major cancer-related health problem in this rural area. The rapid increases in incidence likely result from an increased cigarette smoking rate and evolving environmental risk factors. Lung cancer survival, while showing some improvement in prognosis, still remains well below that observed in the developed areas of the world. -
Rezai, Omran;Khodadadi, Ali;Heike, Yuji;Mostafai, Ali;Gerdabi, Nader Dashti;Rashno, Mohammad;Abdoli, Zahra 7303
Background: Leukemia is a common cancer among children and adolescents. Wilms' tumor gene (WT1) is highly expressed in patients with acute leukemia. It is found as a tumor associated antigen (TAA) in various types of hematopoietic malignancies and can be employed as a useful marker for targeted immunotherapy and monitoring of minimal residual disease (MRD). In this regard, WT1 is a transcription factor that promotes gene activation or repression depending on cellular and promoter context. The purpose of this study was assessment of WT1 gene expression in patients with acute leukemia, measurement of IL-12 and C3 levels in serum and evaluation of the relationship between them. Materials and Methods: We evaluated the expression of WT1 mRNA using real-time quantitative RT-PCR and serum levels of IL-12 and C3 using ELISA and nephelometry in peripheral blood of 12 newly diagnosed patients with acute leukemia and 12 controls. Results: The results of our study showed that the average wT1 gene expression in patients was 7.7 times higher than in healthy controls (P <0.05). In addition, IL-12 (P = 0.003) and C3 (P <0.0001) were significantly decreased in the test group compared to controls. Conclusions: WT1 expression levels are significantly higher in patients compared with control subjects whereas serum levels of interleukin-12 and C3 are significantly lower in patients. Wt1 expression levels in patients are inversely related with serum levels of IL-12 and C3. -
Ghosh, Saptarshi;Rao, Pamidimukkala Brahmananda;Kumar, P Ravindra;Manam, Surendra 7309
Background: The organ preservation approach of choice for the treatment of locally advanced head and neck cancers is concurrent chemoradiation with three weekly high doses of cisplatin. Although this is an efficacious treatment policy, it has high acute systemic and mucosal toxicities, which lead to frequent treatment breaks and increased overall treatment time. Hence, the current study was undertaken to evaluate the efficacy of concurrent chemoradiation using 40 mg/m2 weekly cisplatin. Materials and Methods: This is a single institutional retrospective study including the data of 266 locally advanced head and neck cancer patients who were treated with concurrent chemoradiation using 40 mg/m2 weekly cisplatin from January 2012 to January 2014. A p-value of < 0.05 was taken to be significant statistically for all purposes in the study. Results: The mean age of the study patients was 48.8 years. Some 36.1% of the patients had oral cavity primary tumors. The mean overall treatment time was 57.2 days. With a mean follow up of 15.2 months for all study patients and 17.5 months for survivors, 3 year local control, locoregional control and disease free survival were seen in 62.8%, 42.8% and 42.1% of the study patients. Primary tumor site, nodal stage of disease, AJCC stage of the disease and number of cycles of weekly cisplatin demonstrated statistically significant correlations with 3 year local control, locoregional control and disease free survival. Conclusions: Concurrent chemoradiotherapy with moderate dose weekly cisplatin is an efficacious treatment regime for locally advanced head and neck cancers with tolerable toxicity which can be used in developing countries with limited resources. -
Darunikorn, Pichayada;Puataweepong, Putipun;Dhanachai, Mantana;Dangprasert, Somjai;Swangsilpa, Thiti;Sitathanee, Chomporn;Jiarpinitnun, Chuleeporn;Pattaranutaporn, Poompis;Boonyawan, Keeratikan;Chansriwong, Pichai 7315
Objectives: The study analyzed and compared the long term outcome in locally advanced rectal cancer treated with preoperative and postoperative concurrent chemoradiation (CCRT). Materials and Methods: A retrospective review of 105 patients with stage T3-T4 or regional lymph node positive adenocarcinoma of rectum treated with preoperative or postoperative CCRT at Ramathibodi Hospital during 2005 to 2010 was performed. The results of treatment were reported with 5-year overall survival (OS), 5-year locoregional recurrence free survival (LRFS), and toxicity according to preoperative versus postoperative concurrent chemoradiation (CCRT) groups. Results: Among 105 patients, 34 (32%) were treated with preoperative CCRT and 71 (68%) with postoperative CCRT. At the median follow-up time of 50.5 months (range 2-114 months), five-year OS and LRFS of all patients were 87% and 91.6%, respectively. The study found no difference in 5-year OS (81.7% vs 89.2 %) or LRFS (83.4% vs 95.1%) between preoperative versus postoperative CCRT. Seven cases of loco-regional recurrence were diagnosed, 4 (11.8%) after preoperative CCRT and 3 (4.2%) after postoperative CCRT. The recurrent sites were anastomosis in all patients. There was no significant factor associated with outcome after univariate and multivariate testing. Grade 3 or 4 acute and late complications were low in both preoperative and postoperative CCRT groups. Conclusions: Locally advanced rectum cancer patients experience good results with surgery and adjuvant concurrent chemoradiation. -
Mohebbifar, Rafat;Pakpour, Amir H;Nahvijou, Azin;Sadeghi, Atefeh 7321
As the essence of health in humans, spiritual health is a fundamental concept for discussing chronic diseases such as cancer and a major approach for improving quality of life in patients is through creating meaningfulness and purpose. The present descriptive analytical study was conducted to assess the relationship between spiritual health and quality of life in 210 patients with cancer admitted to the Cancer Institute of Iran, selected through convenience sampling in 2014. Data were collected using Spiritual Health Questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ). Patients' performance was assessed through the Karnofsky Performance Status Indicator and their cognitive status through the Mini-Mental State Examination (MMSE). Data were analyzed in SPSS-16 using descriptive statistics and stepwise linear regression. The results obtained reported the mean and standard deviation of the patients' spiritual health scoreas$78.4{\pm}16.1$ and the mean and standard deviation of their quality of life score as$58.1{\pm}18.7$ . The stepwise linear regression analysis confirmed a positive and significant relationship between spiritual health and quality of life in patients with cancer (${\beta}$ =0.688 and r=0.00). The results of the study show that spiritual health should be more emphasized and reinforced as a factor involved in improving quality of life in patients with cancer. Designing care therapies and spiritual interventions is a priority in the treatment of these patients. -
Background: Essential thrombocythemia (ET) is a clonal hemopoietic stem cell myeloproliferative neoplasm characterized by persistent thrombocytosis along with megakaryocytic hyperplasia. In the last decade following the identification of an acquired JAK2 V617F mutation, there has been acceleration in our understanding of this disease. The rational of this study was to determine the mutational profile of JAK2 V617F in Pakistan patients with ET. Materials and Methods: In this retrospective cross sectional study, 21 patients with ET were enrolled from January 2011 to December 2014. Patients were diagnosed based on WHO criteria for essential thrombocythemia. Complete blood count was done on an automated hematology analyzer, while JAK2 V617F expression was evaluated by polymerase chain reaction. Results: The mean age was
$56.7{\pm}19.0$ years (range 18-87) and the male to female ratio was 1:1.1. The frequency of JAK2 V617F positivity in our ET patients was found to be 61.9%. The mean hemoglobin was$11.7{\pm}2.4$ g/dl with a total leukocyte count of$13.3{\pm}8.1{\times}109/l$ and a platelet count of$1188{\pm}522{\times}109/l$ . Positive correlations for JAK2 V617F mutation were established with high TLC count and raised LDH (P<0.05). No correlation of JAK2 V617F could be established with age and gender (P>0.05). Conclusions: JAK2 V617F mutation frequency in our ET patients was similar to those reported previously. Screening for the mutation in all suspected essential thrombocythemia cases could be beneficial in differentiating patients with reactive and clonal thrombocytosis. -
Ghosh, Saptarshi;Rao, Pamidimukkala Brahmananda;Kumar, P Ravindra;Manam, Surendra 7331
Background: Concurrent chemoradiation with three weekly high dose cisplatin is the non-surgical standard of care for the treatment of locally advanced head and neck cancers. Although this treatment regime is efficacious, it has high acute toxicity, which leads not only to increased treatment cost, but also to increased overall treatment time. Hence, the current study was undertaken to evaluate the acute toxicity and tumor response in head and neck cancer patients treated with concurrent chemoradiation using$40mg/m^2$ weekly cisplatin, which has been our institutional practice. Materials and Methods: This single institution retrospective study included data for 287 head and neck cancer patients treated with concurrent chemoradiation from 2012 to 2014. Results: The mean age of the patients was 48.8 years. The most common site of involvement was oral cavity. Most of the study patients presented with advanced stage disease. The mean overall treatment time was 56.9 days. Some 67.2% had overall complete response to treatment as documented till 90 days from the start of treatment. According to the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria, mucositis was seen in 95.1% of the patients. Dermatitis and emesis were observed in 81.9% and 98.6%, respectively. Regarding haematological toxicity, 48.8% and 29.6% suffered from anaemia and leukopenia, respectively, during treatment. Acute kidney injury was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), and was found in 18.8% of the patients. Conclusions: Concurrent chemoradiotherapy with weekly cisplatin is an effective treatment regime for head and neck cancers with reasonable toxicity which can be used in developing countries, where cost of treatment is so important. -
Nugroho, Agung Endro;Akbar, Fiki Fatihah;Wiyani, Anggie;Sudarsono, Sudarsono 7337
The study aimed to investigate the profile of alkaloids in two ethyl acetate soluble fractions, namely fractions A and B from an ethanolic extract of Ficus septica leaves and cytotoxic effect on T47D breast cancer cells. Preparation of both fractions involved maceration of leaves with 70% (v/v) ethanol, filtration with$Al_2O_3$ , precipitation with 0.1 N HCl, Mayer reagent, and 0.1 N NaOH, and also partition with ethyl acetate. Qualitative thin layer chromatography (TLC) was conducted to determine the profile of alkaloids in the two fractions, using alkaloid specific reagents such as Dragendorff, sodium nitrite, and Van Urk-Salkowski. Cytotoxic effects of both fractions on T47D cells were evaluated using MTT assay with a concentration series of 1.56; 3.12; 6.25; 12.5; 25 and$50{\mu}g/mL$ . The TLC test showed that fractions A and B contained alkaloids with Rx values of 0.74 and 0.80 for fraction A and 0.74, 0.84, 0.92 for fraction B with regard to yohimbine using the mobile phase of n-buthanol:glacial acetic acid:distilled water (3:1:1 v/v/v). Moreover, an indole alkaloid was detected with Rx values of 0.80 and 0.84, respectively. Fractions A and B exhibited high cytotoxic effects on T47D cells with IC50 values of 2.57 and$2.73{\mu}g/mL$ , respectively. In conclusion, overall the results of this study showed that fractions of Ficus septica contain alkaloids including indole alkaloid or its derivatives and possess a cytotoxic effect on T47D cells. This research supports the idea that alkaloids in F. septica have anticancer activity. -
Goud, Tadakal Mallana;Al Salmani, Kamla Khalfan;Al Harasi, Salma Mohammed;Al Musalhi, Muhanna;Wasifuddin, Shah Mohammed;Rajab, Anna 7343
Genetic changes associated with acute lymphoblastic leukemia (ALL) provide very important diagnostic and prognostic information with a direct impact on patient management. Detection of chromosome abnormalities by conventional cytogenetics combined with fluorescence in situ hybridization (FISH) play a very significant role in assessing risk stratification. Identification of specific chromosome abnormalities has led to the recognition of genetic subgroups based on reciprocal translocations, deletions and modal number in B or T-cell ALL. In the last twelve years 102 newly diagnosed childhood/adult ALL bone marrow samples were analysed for chromosomal abnormalities with conventional G-banding, and FISH (selected cases) using specific probes in our hospital. G-banded karyotype analysis found clonal numerical and/or structural chromosomal aberrations in 74.2% of cases. Patients with pseudodiploidy represented the most frequent group (38.7%) followed by high hyperdiploidy group (12.9%), low hyperdiploidy group (9.7%), hypodiploidy (<46) group (9.7%) and high hypertriploidy group (3.2%). The highest observed numerical chromosomal alteration was high hyperdiploidy (12.9%) with abnormal karyotypes while abnormal 12p (7.5%) was the highest observed structural abnormality followed by t(12;21)(p13.3;q22) resulting in ETV6/RUNX1 fusion (5.4%) and t(9;22)(q34.1;q11.2) resulting in BCR/ABL1 fusion (4.3%). Interestingly, we identified 16 cases with rare and complex structural aberrations. Application of the FISH technique produced major improvements in the sensitivity and accuracy of cytogenetic analysis with ALL patients. In conclusion it confirmed heterogeneity of ALL by identifying various recurrent chromosomal aberrations along with non-specific rearrangements and their association with specific immunophenotypes. This study pool is representative of paediatric/adult ALL patients in Oman. -
Reza, Malekpour Afshar;Reza, Mollaie Hamid;Mahdiyeh, Lashkarizadeh;Mehdi, Fazlalipour;Hamid, Zeinali Nejad 7351
Breast cancer is the most common cancer among women worldwide. Roles of the Epstein-Barr, Merkel cell polyoma and mouse mammary tumor viruses in breast carcinogenesis are still controversial although any relationship would clearly be important for breast cancer etiology, early detection and prevention. In the present study associations between EBV, MMTV and Merkel cell polyoma virus and breast cancer in 100 Iranian patients were evaluated using paraffin-embedded tissues. EBER RNA and expression of p53 and large T antigen were evaluated by real time PCR and CD34, p63, HER2, PR and ER markers were studied by immunohistochemistry. EBV was detected in 8/100 (8%), MMTV in 12/100 (12%), MPy in 3/100 (3%) and EBER RNA in 18/100 (18%) cases. None of the control samples demonstrated any of the viruses. p53 was suppressed in EBV, MPy and MMTV positive samples. The large T antigen rate was raised in MPy positive samples. Our results showed that EBV, MMTV and the Merkel cell polyoma virus are foundwith some proportion of breast cancers in our patients, suggesting that these viruses might have a significant role in breast cancer in Kerman, southeast of Iran. -
Baghestani, Ahmad Reza;Moghaddam, Sahar Saeedi;Majd, Hamid Alavi;Akbari, Mohammad Esmaeil;Nafissi, Nahid;Gohari, Kimiya 7359
Background: As a result of significant progress made in treatment of many types of cancers during the last few decades, there have been an increased number of patients who do not experience mortality. We refer to these observations as cure or immune and models for survival data which include cure fraction are known as cure rate models or long-term survival models. Materials and Methods: In this study we used the data collected from 438 female patients with breast cancer registered in the Cancer Research Center in Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients had been diagnosed from 1992 to 2012 and were followed up until October 2014. We had to exclude some because of incomplete information. Phone calls were made to confirm whether the patients were still alive or not. Deaths due to breast cancer were regarded as failure. To identify clinical, pathological, and biological characteristics of patients that might have had an effect on survival of the patients we used a non-mixture cure rate model; in addition, a Weibull distribution was proposed for the survival time. Analyses were performed using STATA version 14. The significance level was set at$P{\leq}0.05$ . Results: A total of 75 patients (17.1%) died due to breast cancer during the study, up to the last follow-up. Numbers of metastatic lymph nodes and histologic grade were significant factors. The cure fraction was estimated to be 58%. Conclusions: When a cure fraction is not available, the analysis will be changed to standard approaches of survival analysis; however when the data indicate that the cure fraction is available, we suggest analysis of survival data via cure models. -
Pakzad, Reza;Mohammadian-Hafshejani, Abdollah;Mohammadian, Mahdi;Pakzad, Iraj;Safiri, Saeid;Khazaei, Salman;Salehiniya, Hamid 7365
Background: Over the past decade, bladder cancer was associated with a significant increase. Given the importance of the impact of socioeconomic status on the distribution of cancer incidence and mortality, and the need to information on these parameters for prevention planning, the aim of this study was to evaluate data for bladder cancer and their relationship with human development index (HDI) and its components in Asia in 2012. Materials and Methods: The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). The incidence and mortality rates were drawn for Asian countries. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. Results: A total incidence of 696,231 cases (68.7% in males and 31.3% in females, sex ratio of 2.19:1) and 524,465 deaths (67.0% in men and 32.9% in women, sex ratio was 2.03:1) were recorded in Asian countries in 2012. Correlation between HDI and standardized incidence rate was 0.241 overall (p=0.106), 0.236 in men (p=0.114) and -0.250 in women (p=0.094). Also between HDI and standardized mortality rate 0.025 (p=0.871) in men 0.118 (p=0.903) and in women 0.014 (p=0.927). Conclusions: Bladder cancer incidence is higher in developed countries, but the rate is declining, and in less developed and developing countries it is growing. There was no statistically significant correlation between the standardized incidence rate of bladder cancer and the HDI and its dimensions in Asia, except for the level of education. -
Songserm, Nopparat;Bureelerd, Onanong;Thongprung, Sumaporn;Woradet, Somkiattiyos;Promthet, Supannee 7375
A high prevalence of Opisthorchis viverrini infection is usually found in wetland geographical areas of Thailand where people have traditional behavior of eating uncooked freshwater fish dishes which results in cholangiocarcinoma (CCA) development. There were several approaches for reducing opisthorchiasis-linked CCA, but the prevalence remains high. To develop community participation as a suitable model for CCA prevention is, firstly, to know what factors are related. We therefore aimed to investigate factors associated with the community participation in CCA prevention among rural residents in wetland areas of Ubon Ratchathani, Thailand. This was a cross-sectional analytic study. All participants were 30-69 years of age, and only one member per house was invited to participate. A total of 906 participants were interviewed and asked to complete questionnaires. Independent variables were socio-demographic parameters, knowledge, health belief and behavior to prevent CCA. The dependent variable was community participation for CCA prevention. Descriptive statistics were computed as number, percentage, mean and standard deviation. Associations were assessed using logistic regression analysis with a P-value <0.05 considered statistically significant. Of all the participants, more than 60% had regularly participated in activities to prevent CCA following health officials advice. Age and health behavior to prevent CCA were factors associated with community participation for CCA (p<0.001). Both factors will be taken into consideration for community participation approaches for CCA prevention through participatory action research (PAR) in future studies. -
Tanabodee, Jitraporn;Thepsuwan, Kitisak;Karalak, Anant;Laoaree, Orawan;Krachang, Anong;Manmatt, Kittipong;Anontwatanawong, Nualpan 7381
This study was conducted to 1206 women who had cervical cancer screening at Chonburi Cancer Hospital. The spilt-sample study aimed to compare the efficacy of abnormal cervical cells detection between liquid-based cytology (LBC) and conventional cytology (CC). The collection of cervical cells was performed by broom and directly smeared on a glass slide for CC then the rest of specimen was prepared for LBC. All slides were evaluated and classified by The Bethesda System. The results of the two cytological tests were compared to the gold standard. The LBC smear significantly decreased inflammatory cell and thick smear on slides. These two techniques were not difference in detection rate of abnormal cytology and had high cytological diagnostic agreement of 95.7%. The histologic diagnosis of cervical tissue was used as the gold standard in 103 cases. Sensitivity, specificity, positive predictive value, negative predictive value, false positive, false negative and accuracy of LBC at ASC-US cut off were 81.4, 75.0, 70.0, 84.9, 25.0, 18.6 and 77.7%, respectively. CC had higher false positive and false negative than LBC. LBC had shown higher sensitivity, specificity, PPV, NPV and accuracy than CC but no statistical significance. In conclusion, LBC method can improve specimen quality, more sensitive, specific and accurate at ASC-US cut off and as effective as CC in detecting cervical epithelial cell abnormalities. -
Eftekhar-Javadi, Arezoo;Kumar, Perikala Vijayananda;Mirzaie, Ali Zare;Radfar, Amir;Filip, Irina;Niyazi, Maximilian;Sadeghipour, Alireza 7385
Background: Transthoracic fine needle aspiration (FNA) cytology and core needle biopsy (CNB) are two commonly used approaches for the diagnosis of suspected neoplastic intrathoracic lesions. This study compared the diagnostic accuracy of FNA cytology and concurrent CNB in the evaluation of intrathoracic lesions. Materials and Methods: We studied FNA cytology and concurrent CNB specimens of 127 patients retrospectively, using hematoxylin and eosin (H&E), immunohistochemistry, and, on certain occasions cytochemistry. Information regarding additional tissue tests was derived from the electronic archives of the Department of Pathology and Laboratory Medicine as well as patient records. Diagnostic accuracy was calculated for each test. Results: Of 127 cases, 22 were inconclusive and excluded from the study. The remaining 105 were categorized into 73 (69.5%) malignant lesions and 32 (30.5%) benign lesions. FNA and CNB findings were in complete agreement in 63 cases (60%). The accuracy and confidence intervals (CIs) of FNA and CNB for malignant tumors were 86.3% (CI: 79.3-90.7) and 93.2% (CI: 87.3-96.0) respectively. For epithelial malignant neoplasms, a definitive diagnosis was made in 44.8% of cases by FNA and 80.6% by CNB. The diagnostic accuracy of CNB for nonepithelial malignant neoplasms was 83.3% compared with 50% for FNA. Of the 32 benign cases, we made specific diagnoses in 16 with diagnostic accuracy of 81.3% and 6.3% for CNB and FNA, respectively. Conclusions: Our findings suggest that FNA is comparable to CNB in the diagnosis of malignant epithelial lesions whereas diagnostic accuracy of CNB for nonepithlial malignant neoplasms is superior to that for FNA. Further, for histological typing of tumors and examining tumor origin, immunohistochemical work up plays an important role. -