Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
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.
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Yeganeh, Marjan Zarif;Sheikholeslami, Sara;Hedayati, Mehdi 2107
Thyroid cancer is the most common endocrine neoplasia. The medullary thyroid carcinoma (MTC) is one of the most aggressive forms of thyroid malignancy,accounting for up to 10% of all types of this disease. The mode of inheritance of MTC is autosomal dominantly and gain of function mutations in the RET proto-oncogene are well known to contribute to its development. MTC occurs as hereditary (25%) and sporadic (75%) forms. Hereditary MTC has syndromic (multiple endocrine neoplasia type 2A, B; MEN2A, MEN2B) and non-syndromic (Familial MTC, FMTC) types. Over the last two decades, elucidation of the genetic basis of tumorigenesis has provided useful screening tools for affected families. Advances in genetic screening of the RET have enabled early detection of hereditary MTCs and prophylactic thyroidectomy for relatives who may not show any symptom sof the disease. In this review we emphasize the main RET mutations in syndromic and non syndromic forms of MTC, and focus on the importance of RET genetic screening for early diagnosis and management of MTC patients, based on American Thyroid Association guidelines and genotype-phenotype correlation. -
Zeng, Ya-Wen;Du, Juan;Pu, Xiao-Ying;Yang, Jia-Zhen;Yang, Tao;Yang, Shu-Ming;Yang, Xiao-Meng 2119
Cancer is the leading cause of death around the world. Anticancer activities from many functional food sources have been reported in years, but correlation between cancer prevalence and types of food with anticancer activities from crop origin center in the world as well as food source with human migration are unclear. Hunger from food shortage is the cause of early human evolution from Africa to Asia and later into Eurasia. The richest functional foods are found in crop origin centers, housing about 70% in the world populations. Crop origin centers have lower cancer incidence and mortality in the world, especially Central Asia, Middle East, Southwest China, India and Ethiopia. Asia and Africa with the richest anticancer crops is not only the most important evolution base of humans and origin center of anticancer functional crop, but also is the lowest mortality and incidence of cancers in the world. Cancer prevention of early human migrations was associated with functional foods from crop origin centers, especially Asia with four centers and one subcenter of crop origin, accounting for 58% of the world population. These results reveal that coevolution between human's anticancer activities associated with functional foods for crop origin centers, especially in Asia and Africa. -
Goldar, Samira;Khaniani, Mahmoud Shekari;Derakhshan, Sima Mansoori;Baradaran, Behzad 2129
Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis. -
Multifaceted Usage of HPV Related Tests and Products in the Management of Cervical Cancer - a ReviewNalliah, Sivalingam;Karikalan, Barani;Kademane, Kumaraswamy 2145
HPV viruses are integral to the development of cervical cancer. The pathogenesis has been extensively studied. To date, numerous HPV tests and products have been developed and successfully utilized in diagnosis, treatment and prevention of cervical cancer. The HPV DNA test, when combined with other routine cervical cancer screening and diagnostic tests namely exfoliative cytology, visual inspection with acetic acid (VIA) and colposcopy has increased the detection rate of cervical cancer. HPV DNA products could also be measured in other body fluids like urine, lymph node tissue, and serum. HPV association could also be quantified by measuring other parameters like HPV mRNA, viral load, viral integration and methylation status. Vaccination against HPV has been found to decrease the incidence of cervical cancer. Further, therapeutic vaccines for cervical cancer against HPV continue to evolve. All these findings pertaining to HPV could possibly decrease the incidence of cervical cancer in the near future. This review aims to give an overview of the HPV tests and products in use and those under trial currently. -
Pancreatic neuroendocrine tumors (pNETs) are rare and heterogenous tumors and surgery to remove the primary tumor is the mainstay of treatment for resectable disease. However, curative surgery is often not feasible, because half of patients with pNET have metastases at the time of diagnosis. Palliative dubulking surgery and liver-directed therapies are appropriate options for these patients. Streptozocin-based regimens are standard, although temozolamide-based treatments are rapidly gaining wide clinical application. Somatostatin analogs are mainly indicated in hormonally active tumors to ameliorate symptoms. In addition, anti-tumoral activity has been proven in well-differentiated NETs. Recently, there has been tremendous progress in the molecular biology of pNETs; thereby, the efficacy of sunitinib and everolimus in the treatment of patients with metastatic pNETs has been proven by large placebo-controlled phase III trials. Currently, there are no definitively proven predictive biomarkers to evaluate response to medical therapies in patients with pNET. Therefore, further studies are needed to individualize and optimize their management. This article reviews systemic chemotherapy, targeted therapies, and anti-secretory treatments for the management of patients with unresectable or metastatic pNETs, summarized in the light of recent advances.
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Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human
$ER{\alpha}$ , mouse$ER{\alpha}$ , rat$ER{\alpha}$ , dog$ER{\alpha}$ , and cat$ER{\alpha}$ are above 90%, but structures of$ER{ \alpha}$ may different among species. Estrogen can be agonist and antagonist depending on its target organs. This hormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to$17{\beta}-estradiol$ (E2), which is a natural ligand of both$ER{\alpha}$ and$ER{\beta}$ . The RBA of the estrogen species are as following: diethyl stilbestrol (DES) > hexestrol > dienestrol >$17{\beta}-estradiol$ (E2) > 17- estradiol > moxestrol > estriol (E3) >4-OH estradiol > estrone-3-sulfate. Estrogen mimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ER positive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have become effective tools for modern drug discovery. These provide three dimensional structures of many transmembrane receptors and enzymes, which are important targets of de novo drug development. The estimated inhibition constants (Ki) from computational model have been used as a screening procedure before in vitro and in vivo studies. -
Xu, Dong-Wei;Zhang, Guan-Qing;Wang, Zong-Wei;Xu, Xiao-Yin;Liu, Tong-Xiang 2167
Autophagy is a self-digestion process, wrapping cytoplasmic proteins or organelles to form vesicles for degradation in lysosomes. The process plays an important role in the maintenance of intracellular homostasis. Here we overview articles on autophagy and cancer/tumors in Pubmed and found 327 articles. Autophagy exists in many tumors and is involved in cell malignant transformation and tumor cell growth. In early phases of tumorigenesis, autophagy clears the abnormally folded proteins and dysfunctional organelles such as mitochondria. Autophagy can also inhibit cell stress responses and prevent genetic damage. When a tumor develops, autophagy helps tumor cells survive nutritional deficiencies and hypoxic conditions. Studies of autophagy in the occurrence and progression of tumors should provide new therapeutic strategies for tumors. -
Sheikh, Asfandyar;Hussain, Syed Ather;Ghori, Quratulain;Naeem, Nida;Fazil, Abul;Giri, Smith;Sathian, Brijesh;Mainali, Prajeena;Al Tamimi, Dalal M 2177
Breast cancer is the most common malignancy in women around the world. About one in 12 women in the West develop breast cancer at some point in life. It is estimated that 5%-10% of all breast cancer cases in women are linked to hereditary susceptibility due to mutations in autosomal dominant genes. The two key players associated with high breast cancer risk are mutations in BRCA 1 and BRCA 2. Another highly important mutation can occur in TP53 resulting in a triple negative breast cancer. However, the great majority of breast cancer cases are not related to a mutated gene of high penetrance, but to genes of low penetrance such as CHEK2, CDH1, NBS1, RAD50, BRIP1 and PALB2, which are frequently mutated in the general population. In this review, we discuss the entire spectrum of mutations which are associated with breast cancer. -
Alblazi, Kamila Mohamed Om;Siar, Chong Huat 2187
Background: Protrusive structures formed by migrating and invading cells are termed lamellipodia, filopodia, invadopodia and podosomes. Lamellipodia and filopodia appear on the leading edges of migrating cells and function to command the direction of the migrating cells. Invadopodia and podosomes are special F-actin-rich matrix-degrading structures that arise on the ventral surface of the cell membrane. Invadopodia are found in a variety of carcinomatous cells including squamous cell carcinoma of head and neck region whereas podosomes are found in normal highly motile cells of mesenchymal and myelomonocytic lineage. Invadopodia-associated protein markers consisted of 129 proteins belonging to different functional classes including WASP, NWASP, cortactin, Src kinase, Arp 2/3 complex, MT1-MMP and F-actin. To date, our current understanding on the role(s) of these regulators of actin dynamics in tumors of the orofacial region indicates that upregulation of these proteins promotes invasion and metastasis in oral squamous cell carcinoma, is associated with poor/worst prognostic outcome in laryngeal cancers, contributes to the persistent growth and metastasis characteristics of salivary gland adenoid cystic carcinoma, is a significant predictor of increased cancer risk in oral mucosal premalignant lesions and enhances local invasiveness in jawbone ameloblastomas. -
Cervical cancer, mostly progressing from cervical intraepithelial neoplasia, is a major cause of morbidity and mortality in Chinese women. This is largely due to high prevalence of high-risk human papillomaviruses (hr-HPVs) in the population. The prevalence of hr-HPV DNA in women and in cervical lesions women ranged from 9.9% to 17.% and from 50.5% to 70.9% in different regions of China, respectively. The most common genotypes somewhat differ between regions throughout the country and from those in many other countries. This may be a challenge to cervical cancer screening and prevention in China. Combined detection of particular HPV genotypes should be recommended in all geographical regions in China and greater attention must be paid to specific hr-HPV types during cervical cancer screening and follow-up of cervical lesions. Besides, vaccination for prevention of cervical cancer by particular HPV genotypes, has not been introduced to China so far. Updated knowledge on prevalent HPV genotypes should be provided to public health organizations to help with the development of more effective HPV vaccines, which can protect Chinese women against HPV types prevalent in local China and thus have a substantial impact on the cervical cancer burden.
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Polat, Fikriye;Diler, Songul Budak;Azazi, Irfan;Oden, Artun 2199
The aim of the present study was to determine whether endothelial nitric oxide synthase (eNOS) gene polymorphisms play a role in development of bladder cancer in the Turkish population. The study was performed on 75 patients (64 men, 11 women) with bladder cancer and 143 healthy individuals (107 men, 36 women) with any kind of cancer history. Three eNOS gene polymorphisms (T-786C promoter region, G894T and intron 4 VNTR 4a/b) were determined with polymerase chain reaction and restriction fragment lenght polymorphism methods. In our study, GT and TT genotypes for eNOS G894T polymorphism were found to significantly vary among patients with bladder cancer and control group (OR: 0.185, CI: 0.078-0.439, p=0.0001 and OR: 0.324, CI: 0.106-0.990, p=0.026). Also, the frequency of the 894T allele was significantly higher in patients with bladder cancer (51%). No association was identified for eNOS T-786C and intron 4 VNTR 4a/b polymorphisms between patients with bladder cancer and control groups in our Turkish population. -
Olfatbakhsh, Asiie;Mehrdad, Neda;Ebrahimi, Mandana;Alavi, Nasrin;Hashemi, Esmat;Kaviani, Ahmad;Najafi, Masoume;Haghighat, Shahpar;Arefanian, Saeed 2203
Background: Breast conservative surgery (BCS) followed by radiotherapy is the standard approach in management of stage I-II breast cancer. Several factors can affect cosmetic outcomes. The aim of this study was to evaluate the cosmetic results of BCS and influencing factors in the Iranian Breast Cancer Research Center. Materials and Methods: Patients who had undergone BCS were included. Photographs were taken of both breasts of the patients in three aspects and were evaluated by three specialists. The cosmetic scores were calculated based on a standard questionnaire. The data were analyzed using univariate and multivariate regression for relationships between cosmetic scores and clinical data. Results: A total number of 103 patients were included in the study. Mean age and BMI of the patients were$46.8{\pm}8.9$ and$28.1{\pm}3.9$ , respectively. Breast cup sizes C and D accounted for 74.7% of the study group. The mean cosmetic score obtained from three referees was 5.72+2.06, consisting of 35.9% excellent-good, 35% moderate, and 29.1% unsatisfactory results. Patient BMI, volume of the resected tissue and breast cup size (D) showed significant correlation with the cosmetic score. On multivariate regression analysis, cosmetic score and BMI (p=0.022,) as well as breast cup size (p=0.040), remained significant. Conclusions: Immediate or delayed symmetrization of the breasts is suggested during breast conservative surgery, meanwhile performing oncoplastic techniques to improve the results significantly. Also it is suggested to discuss anticipation of less satisfactory results with patients having higher BMI and large breast cup size. -
Truong, Phuong Kim;Lao, Thuan Duc;Doan, Thao Phuong Thi;Huyen Le, Thuy Ai 2209
DNA methylation of tumor suppressor gene promoters is the most frequent phenomenon leading to inactivation of function, consequently driving malignant cell transformation. Cyclin D2 is implicated in tumor suppression. In our study, we carried out the MSP assay to evaluation the methylation status at CpG islands in the cyclin D2 promoter in breast cancer cases from the Vietnamese population. The results showed that the frequency of methylation reached 62.1% (59 of 95 breast cancer tumors), but was low in non-cancer specimens at 10% (2 of 20 non-cancer specimens). Additionally, with an RR (relative risk) and OR (odd ratios) of 6.21 and 14.8, DNA hypermethylation of cyclin D2 increased the possibility of malignant transformation. Our results confirmed the cyclin D2 hypermethylation could be used as the potential biomarker which could be applied in prognosis and early diagnosis of Vietnamese breast cancer patients. -
Wang, Huo-Qiang;Zhao, Long;Zhao, Juan;Wang, Qiang 2215
Background: This systemic analysis was conducted to to evaluate the application value of positron emission tomography/computed tomography (PET/CT) in early diagnosis of lung cancer. Methods: Clinical studies evaluating the application value of PET/CT for patients underwent PET/CT imaging. The histological diagnosis served as the standard of truth. Results: Four clinical studies which including 1330 patients with pulmonary spaceoccupying lesions were considered eligible for inclusion. Systemic analysis suggested that, in all 1330 patients, pooled sensitivity was 98.7% (1313.2/1330) and specificity was 58.2%(276.85/476). Conclusion: This systemic analysis suggests that integrated PET/CT imaging provides high sensitivity, and reasonably high specificity, and could be applied for early diagnosis of lung cancer. -
Yang, Jun-Jun;Chen, Hui;Zheng, Xiao-Qun;Li, Hai-Ying;Wu, Jian-Bo;Tang, Li-Yuan;Gao, Shen-Meng 2219
SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients. -
Atoum, Manar Fayiz;AlKateeb, Dena;Mahmoud, Sameer Ahmed AlHaj 2227
Background: Prostate cancer (PCa) is one of the most commonly diagnosed neoplasms and the second leading cause of cancer death in men in the Western world. Vitamin D (1,25dihydroxy vitamin D) is linked to many biological processes that influence oncogenesis but data on relations between its genetic variants and cancer risk have been inconsistent. The aim of this study was to determine associations between a vitamin D genetic polymorphism and 25-hydroxyvitamin D [25(OH)D] levels and prostate cancer. Materials and Methods: Genomic DNA was extracted from 124 Jordanian prostate cancer patients and 100 healthy volunteers. Ethical approval was granted from the ethical committee at Hashemite University and written consent was given by all patients. PCR was used to amplify the vitamin D receptor Fok1 polymorphism fragment. 25(OH)D serum levels were measured by competitive immunoassay. Results: All genotypes were in Hardy-Weinberg equilibrium. Genotype frequency for Fok1 genotypes FF, Ff and ff was 30.7%, 61.3% and 8.06%, for prostate cancer patients, while frequencies for the control group was 28.0%, 66.0% and 6.0%, respectively, with no significant differences. Vitamin D serum level was significantly lower in prostate cancer patients (mean 7.7 ng/ml) compared to the control group (21.8 ng/ml). No significant association was noted between 25(OH)D and VDR Fok1 gene polymorphism among Jordanians overall, but significant associations were evident among prostate cancer patients (FF, Ff and ff : 25(OH)D levels of 6.2, 8.2 and 9.9) and controls (19.0, 22.5 and 26.3, respectively). An inverse association was noted between 25(OH)D serum level less than 10ng/ml and prostate cancer risk (OR 35.5 and 95% CI 14.3- 88.0). Conclusions: There is strong inverse association between 25(OH)D serum level less than 10ng/ml level and prostate cancer risk. -
Haryono, Samuel J;Datasena, I Gusti Bagus;Santosa, Wahyu Budi;Mulyarahardja, Raymond;Sari, Kartika 2231
Genome-wide association studies (GWASs) of the entire genome provide a systematic approach for revealing novel genetic susceptibility loci for breast cancer. However, genetic association studies have hitherto been primarily conducted in women of European ancestry. Therefofre we here performed a pilot GWAS with a single nucleotide polymorphism (SNP) array 5.0 platform from$Affymetrix^{(R)}$ that contains 443,813 SNPs to search for new genetic risk factors in 89 breast cancer cases and 46 healthy women of Indonesian ancestry. The case-control association of the GWAS finding set was evaluated using PLINK. The strengths of allelic and genotypic associations were assessed using logistic regression analysis and reported as odds ratios (ORs) and P values; P values less than$1.00{\times}10^{-8}$ and$5.00{\times}10^{-5}$ were required for significant association and suggestive association, respectively. After analyzing 292,887 SNPs, we recognized 11 chromosome loci that possessed suggestive associations with breast cancer risk. Of these, however, there were only four chromosome loci with identified genes: chromosome 2p.12 with the CTNNA2 gene [Odds ratio (OR)=1.20, 95% confidence interval (CI)=1.13-1.33,$P=1.08{\times}10^{-7}$ ]; chromosome 18p11.2 with the SOGA2 gene (OR=1.32, 95%CI=1.17-1.44,$P=6.88{\times}10^{-6}$ ); chromosome 5q14.1 with the SSBP2 gene (OR=1.22, 95%CI=1.11-1.34,$P=4.00{\times}10^{-5}$ ); and chromosome 9q31.1 with the TEX10 gene (OR=1.24, 95%CI=1.12-1.35,$P=4.68{\times}10^{-5}$ ). This study identified 11 chromosome loci which exhibited suggestive associations with the risk of breast cancer among Indonesian women. -
Hassan, Astrid Sinarti;Naicker, Manimalar;Yusof, Khairul Hazdi;Ishak, Wan Zamaniah Wan 2237
Background: Adjuvant chemotherapy improves survival in Dukes C colon cancers post-curative resection. However, the evidence for a role with Dukes B lesions remains unproven despite frequent use for disease characterized by poor prognostic features. In view of limited Asia-specific data, this study aimed to determine survival outcomes and identify prognostic factors in a tertiary teaching hospital in Malaysia. Materials and Methods: A total of 116 subjects who underwent curative surgery with and without adjuvant chemotherapy for Duke B and C primary colon adenocarcinomas diagnosed from 2004-2009 were recruited and data were collected retrospectively. Five-year overall survival (OS) and disease free survival (DFS) were analysed using Kaplan-Meier survival analysis and log-rank (Mantel-Cox) test. Prognostic factors were determined using Cox proportional hazards regression with both univariate and multivariate analyses. Results: The survival analysis demonstrated a 5-year OS of 74.0% for all patients, with 74.9% for Dukes C subjects receiving chemotherapy compared to 28.6% in those not receiving chemotherapy (p=0.001). For Dukes B disease, the 5-year survival rate was 82.6% compared to 75.0% for subjects receiving and not receiving chemotherapy, respectively (p=0.17). Independent prognostic factors identified included a CEA level more than 3.5 ng/ml (hazard ratio (HR)=4.78; p=0.008), serosal involvement (HR=3.75; p=0.028) and completion of chemotherapy (HR= 0.20; p=0.007). Conclusions: In a regional context, this study supports current evidence from the West that adjuvant chemotherapy improves survival in Dukes C colon cancers post curative surgery. However, although a clear benefit has yet to be proven for Dukes B disease, our results suggest survival improvement in selected cases. -
Han, Li-Hui;Jia, Yi-Bin;Song, Qing-Xu;Wang, Jian-Bo;Wang, Na-Na;Cheng, Yu-Feng 2245
Background: The interaction between tumor cells and inflammatory cells has not been systematically investigated in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to evaluate whether preoperative the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (NLR), and the platelet-lymphocyte ratio (PLR) could predict the prognosis of ESCC patients undergoing esophagectomy. Materials and Methods: Records from 218 patients with histologically diagnosed ESCC who underwent attempted curative surgery from January 2007 to December 2008 were retrospectively reviewed. Besides clinicopathological prognostic factors, we evaluated the prognostic value of the LMR, the NLR, and the PLR using Kaplan-Meier curves and Cox regression models. Results: The median follow-up was 38.6 months (range 3-71 months). The cut-off values of 2.57 for the LMR, 2.60 for the NLR and 244 for the PLR were chosen as optimal to discriminate between survival and death by applying receiver operating curve (ROC) analysis. Kaplan-Meier survival analysis of patients with low preoperative LMR demonstrated a significant worse prognosis for DFS (p=0.004) and OS (p=0.002) than those with high preoperative LMR. The high NLR cohort had lower DFS (p=0.004) and OS (p=0.011). Marginally reduced DFS (p=0.068) and lower OS (p=0.039) were found in the high PLR cohort. On multivariate analysis, only preoperative LMR was an independent prognostic factor for both DFS (p=0.009, HR=1.639, 95% CI 1.129-2.381) and OS (p=0.004, HR=1.759, 95% CI 1.201-2.576) in ESCC patients. Conclusions: Preoperative LMR better predicts cancer survival compared with the cellular components of systemic inflammation in patients with ESCC undergoing esophagectomy. -
Zhang, Ya-Ping;Kong, Qing-Hong;Huang, Ying;Wang, Guan-Lin;Chang, Kwen-Jen 2251
To study effects of cellular FLICE (FADD-like IL-$1{\beta}$ -converting enzyme)-inhibitory protein (c-FLIP) inhibition by RNA interference (RNAi) on sensitivity of U2OS cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, plasmid pSUPER-c-FLIP-siRNA was constructed and then transfected into U2OS cells. A stable transfection cell clone U2OS/pSUPER-c-FLIP-siRNA was screened from the c-FLIP-siRNA transfected cells. RT-PCR and Western blotting were applied to measure the expression of c-FLIP at the levels of mRNA and protein. The results indicated that the expression of c-FLIP was significantly suppressed by the c-FLIP-siRNA in the cloned U2OS/pSUPER-c-FLIP-siRNA as compared with the control cells of U2OS/pSUPER. The cloned cell line of U2OS/pSUPER-c-FLIP-siRNA was further examined for TRAILinduced cell death and apoptosis in the presence of a pan-antagonist of inhibitor of apoptosis proteins (IAPs) AT406, with or without 4 hrs pretreatment with rocaglamide, an inhibitor of c-FLIP biosynthesis, for 24 hrs. Cell death effects and apoptosis were measured by the methods of MTT assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry, respectively. The results indicated that TRAIL-induced cell death in U2OS/pSUPER-c-FLIP-siRNA was increased compared with control cells U2OS/pSUPER in the presence or absence of AT406. Flow cytometry indicated that TRAIL-induced cell death effects proceeded through cell apoptosis pathway. However, in the presence of rocaglamide, cell death or apoptotic effects of TRAIL were similar and profound in both cell lines, suggesting that the mechanism of action for both c-FLIP-siRNA and rocaglamide was identical. We conclude that the inhibition of c-FLIP by either c-FLIP-siRNA or rocaglamide can enhance the sensitivity of U2OS to TRAIL-induced apopotosis, suggesting that inhibition of c-FLIP is a good target for anti-cancer therapy. -
Ghasempour, Mostafa;Rahmani, Azad;Davoodi, Arefeh;Sheikhalipour, Zahra;Ziaeei, Jamal Evazie;Abri, Fariba 2257
Background: Return to work after treatment completion is important for both cancer survivors and society. Financial distress is one of the factors that may influence the return to work in cancer survivors. However, this relationship has not been well investigated. This study aimed to determine the rate of return to work and its relation to financial distress among Iranian cancer survivors. Materials and Methods: This descriptive-correlational study was undertaken among 165 cancer survivors who completed their initial treatments and had no signs of active cancer. The Return to Work questionnaire and Financial Distress/Financial Well-Being Scale were used for data collection. Data were analyzed using SPSS statistical software. Results: After initial treatments, 120 cancer survivors (72%) had returned to work, of which 50 patients (42%) had returned to full-time work and 70 (58%) reduced their work hours and returned to part-time work. Cancer survivors also reported high levels of financial distress. In addition, the financial distress was lower among patients who had returned completely to work, in comparison to patients who had quit working for cancer-related reasons (p= 0.001) or returned to work as part-time workers (p=0.001). Conclusions: The findings showed that a high percent of Iranian cancer survivors had not returned to their jobs or considerably reduced working hours after treatment completion. Accordingly, due to high levels of financial distress experienced by participants and its relation to return to work, designing rehabilitation programs to facilitate cancer survivor return to work should be considered. -
Namazi, Abolfazl;Abedinzadeh, Maryam;Nourbaksh, Parisa;Neamatzadeh, Hossein 2263
Background: Many studies have reported associations of the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism with colorectal cancer (CRC) risk, but the results remained controversial. Hence, we performed the present meta-analysis with different inheritance models. Materials and Methods: We searched the PubMed and Google scholar databases for studies relating to associations between XRCC3 Thr241Met polymorphism and risk of CRC. 16 studies with 5,193 cases and 6,645 controls were finally included into the meta-analysis. Results: We found that the XRCC3 Thr241Met polymorphism was associated with increased CRC risk only under a dominant genetic model (CC+CT vs. TT: OR 0.575, 95%CI 0.498-1.665, p<0.001,$P_{heterogeneity}=0.00$ ,$I^2=83%$ ). There was a significant association between XRCC3 Thr241Met polymorphism and CRC risk in Caucasian in the overall 8 studies under only in the heterozygote genetic model (CT vs. TT: OR=0.929, 95%CI =0.806-1.070, P=0.308,$P_{heterogeneity}=0.002$ ,$I^2=57%$ ). Four studies evaluated the XRCC3 Thr241Met polymorphism and CRC risk in Asians. Two genetic models of the XRCC3 polymorphism were significantly correlated with increasing risk in Asians (dominant model: CC+CT vs. TT: OR= 0.609, 95%CI=411-0.902, P=0.013,$P_{heterogeneity}=0.54$ ,$I^2=0.00%$ ; Allele model: C vs. T: OR=0.708, 95 %=CI 0.605-0.829, p=0.000,$P_{heterogeneity}=0.000$ ,$I^2=92%$ ). The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. Conclusions: In conclusion, this meta-analysis indicates that XRCC3 Thr241Met shows an increased CRC risk, particularly in Asians rather than Caucasians. -
Saengow, Udomsak;Chongsuwiwatvong, Virasakdi;Geater, Alan;Birch, Stephen 2269
Colorectal cancer (CRC) is now common in Thailand with an increase in incidence over time. Health authorities are planning to implement a nationwide CRC screening program using fecal immunochemical test (FIT) as a primary screening tool. This study aimed to estimate preferences and acceptance of FIT and colonoscopy, explore factors influencing the acceptance, and investigate reasons behind choosing and rejecting to screen before the program was implemented. Patients aged 50-69, visiting the primary care unit during the study period, were invited to join this study. Patients with a history of cancer or past CRC screening were excluded. Face-to-face interviews were conducted. Subjects were informed about CRC and the screening tests: FIT and colonoscopy. Then, they were asked for their opinions regarding the screening. The total number of subjects was 437 (86.7% response rate). Fifty-eight percent were females. The median age was 58 years. FIT was accepted by 74.1% of subjects compared to 55.6% for colonoscopy. The acceptance of colonoscopy was associated with perceived susceptibility to CRC and family history of cancer. No symptoms, unwilling to screen, healthy, too busy and anxious about diagnosis were reasons for refusing to screen. FIT was preferred for its simplicity and non-invasiveness compared with colonoscopy. Those rejecting FIT expressed a strong preference for colonoscopy. Subjects chose colonoscopy because of its accuracy; it was refused for the process and complications. If the screening program is implemented for the entire target population in Thailand, we estimate that 106,546 will have a positive FIT, between 8,618 and 12,749 identified with advanced adenoma and between 2,645 and 3,912 identified with CRC in the first round of the program. -
Yu, Jian-Qin;Zhou, Qing;Zhu, Hua;Zheng, Fei-Yun;Chen, Zhi-Wen 2277
Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were$0.186{\pm}0.043$ in cervical cancer and$0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression. -
Wu, Kun;Xu, Xiao-Ning;Chen, Yu;Pu, Xiao-Lin;Wang, Bo-Yuan;Tang, Xiao-Dan 2283
In order to explore the association between RASSF1A methylation and nasopharyngeal carcinoma (NPC) risk of Chinese, we carried out a meta-analysis with searches of PubMed, Web of Science, ProQest and Medline databases. Ultimately, 14 articles were identified and analysised using R Software (R version 3.1.2) including meta packages. Overall, we found a significant relationship between RASSF1A methylation and NPC risk (OR 30.7; 95 % CI, 16.71~56.23; z=11.0591; p<0.0001) in a fixed effects model and (OR 32.1; 95% CI, 14.27~72.01; z=8.3984; p<0.0001) in a random effects model pooled. In tissue and NP brushings groups, similar results were found. Hence, our study identified a strong association between RASSF1A methylation and NPC and highlighted a promising potential for RASSF1A methylation in NPC risk prediction of Chinese. -
Igissinov, Nurbek;Akshulakov, Serik;Kerimbayev, Talgat;Adilbekov, Yerzhan;Aldiyarova, Nurgul;Rakhimbekov, Alexandr;Akpolatova, Gulnur;Tarzhanova, Dinar 2289
The paper presents the incidence rates of malignant tumors of the central nervous system assessed by the component analysis. The data on primary registered cases of malignant tumors of the central nervous system in the country were used as the material of the study for the period from 2004 to 2011. A general trend of increase in the number of patients with malignant tumors of the central nervous system in Kazakhstan was determined and the potential of their increase was evaluated, which can be due to changes in the morbidity risk and age specifics, as well as the increase in population. -
Takai, Tomoaki;Inamoto, Teruo;Komura, Kazumasa;Yoshikawa, Yuki;Uchimoto, Taizo;Saito, Kenkichi;Tanda, Naoki;Kouno, Junko;Minami, Koichiro;Uehara, Hirofumi;Takahara, Kiyoshi;Hirano, Hajime;Nomi, Hayahito;Kiyama, Satoshi;Azuma, Haruhito 2297
Background: Despite widely adopted standard methods for follow-up including cystoscopy plus cytology, recurrence rates of non muscle-invasive bladder cancer (NMIBC) have not improved over the past decades, still ranging from 60% through 70%. Hence, widely acceptable surveillance strategies with excellent sensitivity are needed. Early recurrence has led to the development of a novel cystoscopy technique utilizing photodynamic diagnosis (PDD). Although, no studies have evaluated the efficacy of PDD for patients of MIBC, BCG failure or 2nd-transurethelial resection (TUR). Materials and Methods: The present study was performed from October 2012 through May 2013. IRB approved 25 patients initially underwent a cystoscopy examination of white light and blue light followed by the resection of tumors identified. Resections were performed from bladder mucosa areas considered suspicious at PDD, along with PDD negative normal bladder mucosa area resected by random biopsy. Specimens were divided into two groups, PDD positive and negative. Primary endpoints were sensitivity and specificity. Results: A total of 147 specimens extracted from 25 patients were included in the analysis. Some 45 out of 92 PDD-positive specimens were confirmed to have bladder cancer, and 51 out of PDD-negative 55 specimens were confirmed to be cancer negative. The sensitivity of PDD was 91.8% (45/49) and specificity was 52.0% (51/98). The sensitivity:specificity was 89.5% (17/19) : 47.6% (30/63) in 12 2nd-TUR patients, 90.5% (19/21) : 61.1% (11/18) in seven MIBC patients, and 95.0% (19/20) : 48.5% (16/33) in eight failed BCG cases. Conclusions: PDD-TURBT has high sensitivity to diagnose BC even for 2nd-TUR, MIBC or BCG failure cases. -
Baykan, Halit;Cihan, Yasemin Benderli;Ozyurt, Kemal 2303
Objective: Skin tumors are the most commonly seen cancer type worldwide. Regarding pathogenesis, it is thought that disruption of kinetics through T lymphocyte-mediated development of chronic inflammation may be involved. The present study was intended to identify role of inflammatory cells such as neutrophils, monocytes and lymphocytes in the determination of risk for skin cancer. Materials and Methods: We retrospectively reviewed charts of 569 cases diagnosed as having primary skin tumors. Data regarding age, gender and histopathological subtype were recorded. Blood parameters studied on the day before surgery including WBCs, neutrophils, and lymphocyte counts, neutrophil:lymphocyte and neutrophil:monocyte ratios were also recorded. Two-hundred and two healthy individuals presented for check-up in an outpatient clinic were selected as the control group. Parameters studied in cases with skin cancer were compared to those healthy individuals. Findings: Of the cases with skin cancer, 401 were basal cell carcinoma (BCC) while 144 were squamous cell carcinoma (SCC) and 13 were malignant melanoma (MM). WBC, neutrophil and monocyte counts and the neutrophil:lymphocyte ratio were found to be lower in the patient group than in the healthy control group (p<0.001) while no significant difference was found in other parameters reviewed (p>0.05). No significant difference was found in WBC, neutrophil, neutrophil: monocyte ratio according to gender (p>0.05). Monocyte count was found to be$0.68{\pm}0.61$ in men and$0.55{\pm}0.25$ in women, indicating strong statistical significance (p<0.001). WBC, neutrophil and monocyte values were highest in control group while lowest in BCC. When BCC and SCC groups were compared to controls, significant differences found (p<0.001). There were no significant differences in lymphocyte counts among groups (p=0.976). Neutrophil:lymphocyte ratios were 3.24 in BCC, 3.59 in SCC, 3.44 in MM and 5.06 in control group (p<0.001). Conclusions: In our study, it was found that there were significant differences in complete blood count, neutrophil, monocyte and neutrophil:lymphocyte levels among groups. Neutrophil: lymphocyte ratio was found to be lowest in BCC among skin cancers. -
Tang, Qi-Ling;Guo, Ji-Quan;Wang, Qi-You;Lin, Hai-Shu;Yang, Zhou-Ping;Peng, Tong;Pan, Xue-Diao;Liu, Bing;Wang, Su-Jun;Zang, Lin-Quan 2307
Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/ kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development. -
Meng, Xin-Yu;Liu, Juan;Lv, Feng;Liu, Ming-Qiu;Wan, Jing-Ming 2313
Objective: To investigate the correlation between extracellular matrix protein-1 (ECM1) and the growth, metastasis and angiogenesis of laryngeal carcinoma. Materials and Methods: Forty-five samples with laryngeal benign and malignant tumors confirmed by pathology in Laiwu City People's Hospital from March 2006 to March 2011 were collected, in which there were 29 cases with laryngeal carcinoma and 16 with benign tumors. The expression of ECM1 and factor VIII-related antigens in patients with laryngeal carcinoma and those with benign tumors was respectively detected using immunohistochemical method, and the correlation between ECM1 staining grade and microvessel density (MVD) was analyzed. Results: In laryngeal carcinoma tissue, ECM1 was mainly expressed in cytoplasm, less in cytomembrane or intercellular substance. With abundant expression in the tissue of laryngeal benign tumors (benign mesenchymoma and hemangioma), ECM1 was primarily expressed in the connective tissue, which was different from the expression in laryngeal carcinoma tissue. The proportion of positive ECM1 staining (++) in patients with laryngeal carcinoma was dramatically higher than those with benign tumors (p<0.05), and that of strongly-positive ECM1 staining (+++) slightly higher. The results of Spearman nonparametric correlation analysis revealed that ECM1 staining grade in laryngeal carcinoma tissue had a significantly-positive correlation with MVD (r=0.866, p=0.000). Conclusions: ECM1 expression in laryngeal carcinoma is closely associated with tumor cell growth, metastasis and angiogenesis, which can be considered as an effective predictor in the occurrence and postoperative recurrence of laryngeal carcinoma. -
Ko, Min Jung;Kim, Jimin;Kim, Younhee;Lee, Yoon Jae;Hong, Sung Ran;Lee, Jae Kwan 2317
Background: Despite the increasing number of screening examinations performed for cervical cancer utilizing the Papanicolaou smear test (Pap test), few studies have examined whether this strategy is cost-effective in Korea. Objective: This study was conducted to evaluate the cost-effectiveness of cervical cancer screening strategies incorporating the Pap test based on age at the start and end of screening as well as screening interval. Materials and Methods: We designed four alternative screening strategies based on patient age when screening was started (20 or 30 years) and discontinued (lifetime, 79 years). Each strategy was assessed at screening intervals of 1, 2, 3, or 5 years. A Markov model was developed to determine the cost-effectiveness of the 16 possible cervical cancer screening strategies, and this was evaluated from a societal perspective. The main outcome measures were average lifetime cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Results: Compared with various strategies comprising younger starting age, discontinuation age, and longer screening intervals, strategies employing annual screening for cervical cancer starting at a target age of 30 years and above were the most cost-effective, with an ICER of 21,012.98 dollars per QALY gained (with a Korean threshold of 30,000,000 KRW or US$27,272). Conclusions: We found that annual screening for cervical cancer beginning at a target age of 30 years and above is most cost-effective screening strategy. Considering the potential economic advantages, more intense screening policies for cervical cancer might be favorable among countries with high rates of cervical cancer and relatively low screening costs. -
Rujirakul, Ratana;Ueng-arporn, Naporn;Kaewpitoon, Soraya;Loyd, Ryan J;Kaewthani, Sarochinee;Kaewpitoon, Natthawut 2323
It is urgently necessary to be aware of the distribution and risk areas of liver fluke, Opisthorchis viverrini, for proper allocation of prevention and control measures. This study aimed to investigate the human behavior, and environmental factors influencing the distribution in Surin Province of Thailand, and to build a model using stepwise multiple regression analysis with a geographic information system (GIS) on environment and climate data. The relationship between the human behavior, attitudes (<50%;$X_{111}$ ), environmental factors like population density ($148-169pop/km^2$ ;$X_{73}$ ), and land use as wetland ($X_{64}$ ), were correlated with the liver fluke disease distribution at 0.000, 0.034, and 0.006 levels, respectively. Multiple regression analysis, by equations OV= -0.599 + 0.005(population density ($148-169pop/km^2$ );$X_{73}$ ) + 0.040 (human attitude (<50%);$X_{111}$ ) +0.022 (land used (wetland; X64), was used to predict the distribution of liver fluke. OV is the patients of liver fluke infection, R Square= 0.878, and, Adjust R Square= 0.849. By GIS analysis, we found Si Narong, Sangkha, Phanom Dong Rak, Mueang Surin, Non Narai, Samrong Thap, Chumphon Buri, and Rattanaburi to have the highest distributions in Surin province. In conclusion, the combination of GIS and statistical analysis can help simulate the spatial distribution and risk areas of liver fluke, and thus may be an important tool for future planning of prevention and control measures. -
Purpose: To determine the accuracy of visual inspection with acetic acid (VIA) in detecting high-grade cervical intraepithelial neoplasia (CIN) in pre- and post-menopausal women with atypical squamous cells of undetermined significance (ASC-US) and low grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) smears. Materials and Methods: Two hundred women (150 pre-menopausal and 50 post-menopausal) with ASC-US and LSIL cytology who attended the colposcopy clinic, Thammasat University Hospital, between March 2013 and August 2014 were included. All women underwent VIA testing and colposcopy by gynecologic oncologists. Diagnostic values of VIA testing including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting high-grade CIN were determined using the histopathology obtained from colposcopic-directed biopsy as a gold standard. Results: VIA testing was positive in 54/150 (36%) pre-menopausal women and 5/50 (10%) post-menopausal women. Out of 54 pre-menopausal women with positive VIA testing, 15 (27.8%) had high-grade CIN and 39 (72.2%) had either CIN 1 or insignificant pathology. Ten (10.4%), 43 (44.8%) and 43 (44.8%) out of the remaining 96 pre-menopausal women with negative VIA testing had high-grade CIN, CIN 1 and insignificant pathology, respectively. Out of 5 post-menopausal women with positive VIA testing, there were 4 (80%) women with high-grade CIN, and 1 (20%) women with insignificant pathology. Out of 45 VIA-negative post-menopausal women, 42 (93.3%) women had CIN 1 and insignificant pathology, and 3 (6.7%) had high-grade CIN. Sensitivity, specificity, PPV and NPV of the VIA testing were 59.4%, 76.2%, 32.2% and 90.8%, respectively (60%, 68.8%, 27.8% and 89.6% in pre-menopausal women and 57.1%, 97.7%, 80% and 93.3% in post-menopausal women). Conclusions: VIA testing may be used as a screening tool for detecting high-grade CIN in women with minor cervical cytological abnormalities in a low-resource setting in order to lower the rate of colposcopy referral.
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Zhao, Jing;Zhi, Zheng;Song, Guangyao;Wang, Juan;Wang, Chao;Ma, Huijuan;Yu, Xian;Sui, Aixia;Zhang, Hongtao 2333
Background: Due to the strong inhibitory effects of$PPAR{\gamma}$ gene on the growth of cancer cells, the role of Pro12Ala polymorphism in$PPAR{\gamma}$ gene has been extensively investigated in cancer recently. However, the results were inconsistent according to cancer type. The aim of this study was to comprehensively evaluate the$PPAR{\gamma}$ Pro12Ala polymorphism and gastric cancer susceptibility. Materials and Methods: Search strategies were conducted in Pubmed, Medline (Ovid), Chinese biomedical database (CBM), China national knowledge infrastructure (CNKI), VIP, and Wanfang database, covering all publications, with the last search up to November 01, 2014. The strength of association between$PPAR{\gamma}$ Pro12Ala polymorphism and gastric cancer risk was assessed by OR with 95%CI. Results: A total of 546 cases and 827 controls in 5 case-control studies were included in this meta-analysis. The results indicated that the variant G allele carriers (CG+GG) had a 2.31 times higher risk for gastric cancer when compared with the homozygote CC (odds ratio (OR)=2.31, 95% confidence interval (CI)=1.67-3.21 for CG+GG vs. CC). In the subgroup analysis by ethnicity, significantly elevated risks were both found in Asians (OR=2.56, 95% CI=1.42-4.64) and Caucasians (OR=2.20, 95% CI=1.48-3.25). Similarly, in the subgroup analysis by H. pylori status, a significantly increased risk was identified in H. pylori (+) populations (OR=3.68, 95%CI=2.07-6.52), but not in H. pylori(-) populations (OR=1.17, 95%CI=0.58-2.39). Conclusions: This pooled analysis suggested that the$PPAR{\gamma}$ Pro12Ala polymorphism could be an independent predictive risk factor for gastric cancer especially in H. pylori infected populations in Asians and Caucasians. Nevertheless, prospectively designed cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirm the combined effects of$PPAR{\gamma}$ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk. -
Cai, Jun-Hong;Fu, Sheng-Miao;Tu, Zhi-Hua;Deng, Li-Qun;Liang, Zhu;Chen, Xin-Ping;Gong, Xuan-Ju;Wan, Li-Hua 2341
This study aimed to investigate the relationship between prognosis and protein and mRNA expression of an apoptotic inhibitor gene, survivin, in patients with nasopharyngeal carcinoma. Furthermore, functions of the survivin gene in the CNE2 nasopharyngeal carcinoma cell line were assessed. Immunohistochemistry and in situ hybridization were used in detecting the survivin protein and mRNA in 44 nasopharyngeal carcinoma specimens, and 30 chronic nasopharyngitis samples as controls. Survivin gene expression in CNE2 cell line was suppressed with an shRNA (short hairpin RNA). The positive ratios of expression for survivin protein and mRNA in nasopharyngeal carcinoma were 79.5% and 75.0% respectively, obviously higher than in the control group (p<0.01), and there is very good consistency between the two methods. The mean survival time of patients with higher survivin protein or mRNA expression was shorter than in patients with lower levelsv(p<0.01). Proliferation of the CNE2 cell line was distinctly inhibited by the shRNA. The results indicate that overexpression of the survivin gene plays an important role in onset and development of nasopharyngeal carcinoma, and it may be helpful for prognostic appraisal. -
Tabrizi, Maral Mazloomi;Bidgoli, Sepideh Arbabi 2347
Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies, accounting for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring.This study aimed to evaluted the role of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL.This cross-sectional case control study was carried out on 22 cases and 100 controls who were born and lived in low socioeconomic families in Isfahan and hospitalized for therapeutic purposes in different hospitals from 2013-2014.With regard to the underlying risk factors, familial history and parental factors were noted but in this age, socioeonomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factors of ALL (p=0.006, OR=3.651, CI 95%, 1.692-7.878). As the population was of low socioeconomic background, use of mobiles, computers and microwave was negligible. Moreover prenatal and postnatal exposure to indoor electrically charged objects was not determined to be a significant environmental factor. Thus, pre and post natal exposure to high voltage power lines and living in pollutant regions as well as familial influence could be described as risk factors of ALL for the first time in a low socioeconomic status Iranian population. -
In this study, the antiproliferative effects of the metformin was evaluated on MCF-7 Cells (human breast adenocarcinoma cell line). For this purpose cell kinetic parameters including cell proliferation assay, mitotic index and labelling index analysis were used.
$30{\mu}M$ ,$65{\mu}M$ and$130{\mu}M$ Metformin doses were applied to cells for 24, 48 and 72 hours. The results showed that there was a significant decrease in cell proliferation, mitotic index and labelling index for all experimental groups (p<0.05) for all applications. -
Hacibekiroglu, Ilhan;Kodaz, Hilmi;Erdogan, Bulent;Turkmen, Esma;Esenkaya, Asim;Uzunoglu, Sernaz;Cicin, Irfan 2355
Background: Combination chemotherapy of 5 fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin, mainly FOLFOX regimens, has shown considerable antitumor activity and a tolerable toxicity profile in gastric cancer. The goal of this study was to retrospectively compare the efficacy and toxicity of modified FOLFOX-6 (mFOLFOX6) regimen in advanced gastric cancer (AGC) patients with good and poor performance status (PS). Materials and Methods: AGC patients receiving the mFOLFOX6 regimen including oxaliplatin$85mg/m^2$ , bolus of 5-FU$400mg/m^2$ and LV$400mg/m^2$ on the first day, followed by$2400mg/m^2$ of 5- FU as a continious infusion over 46 hour for first-line treatment were eligible for the study. Results: A total 58 patients with a median age of 59.5 (32-81) were included. The median follow up of the study was 9.2 months. Thirty patients (51.7%) with an ECOG PS 0-1 were assigned to the good PS arm, while 28 patients (48.3%) with ECOG PS 2 were in the poor PS arm. Overall response rates were 36.6 and 28.8%, respectively (p=0.91). Median PFS was 6.7 and 6.3 months in good PS and poor PS arms (p=0.50) and median OS was 9.6 and 10.4 months (p=0.55). As compared with good PS arm, poor PS arm was associated with more grade 3-4 neutropenia and anemia. Dose reduction and dose delays were also significantly higher. Conclusions: In this study, mFOLFOX6 was similarly effective in both arms. Although hematologic toxicity was significantly higher in patients with poor PS, it remained manageable. Our results suggest that this regimen may be an effective treatment option for AGC patients with poor PS. -
Jin, Ya;He, Yu-Shuang;Zhang, Ming-Ming;Parajuly, Shyam Sundar;Chen, Shuang;Zhao, Hai-Na;Peng, Yu-Lan 2361
Objective: To evaluate the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) in differentiating between benign and malignant enlarged lymph nodes using meta-analysis. Materials and Methods: Pubmed, Embase, SCI and Cochrane databases were searched for studies (up to September 1, 2014) reporting the diagnostic performance of CEUS in discriminating between benign and malignant lymph nodes. Inclusion criteria were: prospective study; histopathology as the reference standard; and sufficient data to construct$2{\times}2$ contingency tables. Methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Patient clinical characteristics, sensitivity and specificity were extracted. The summary receiver operating characteristic curve was used to examine the accuracy of CEUS. A meta-analysis was performed to evaluate the clinical utility in identification of benign and malignant lymph nodes. Sensitivity analysis was performed after omitting outliers identified in a bivariate boxplot and publication bias was assessed with Egger testing. Results: The pooled sensitivity, specificity and AUROC were 0.92 (95%CI, 0.85-0.96), 0.91 (95%CI, 0.82-0.95) and 0.97 (95%CI, 0.95-0.98), respectively. After omitting 3 outlier studies, heterogeneity decreased. Sensitivity analysis demonstrated no disproportionate influences of individual studies. Publication bias was not significant. Conclusions: CEUS is a promising diagnostic modality in differentiating between benign and malignant lymph nodes and can potentially reduce unnecessary fine-needle aspiration biopsies of benign nodes. -
Zhao, Dan;Wu, Ling-Ying;Wang, Xiao-Bing;Li, Xiao-Guang 2369
Objective: To analyze efficacy of neoadjuvant chemotherapy for advanced ovarian cancer. Materials and Methods: A total of 107 patients with advanced ovarian cancer undergoing cytoreductive surgery were divided into a neoadjuvant chemotherapy group (n=61) and a primary debulking group (n=46) and retrospectively analyzed. Platinum-based adjuvant chemotherapy was applied to both groups after cytoreductive surgery ande overall and progression-free survival times were calculated. Results: No significant difference was observed in duration of hospitalization ($20.8{\pm}6.1$ vs.$20.2{\pm}5.4$ days, p>0.05). The operation time of neoadjuvant chemotherapy group was shorter than the initial surgery group ($3.1{\pm}0.7$ vs.$3.4{\pm}0.8$ h, p<0.05). There were no significant differences in median overall survival time between neoadjuvant chemotherapy group and surgery group (42 vs. 55 months, p>0.05). Similarly, there was no difference in median progression-free survival between neoadjuvant chemotherapy group and surgery group (16 vs. 17 months, p>0.05). The surgical residual tumor size demonstrated no significant difference between initial surgery and neoadjuvant chemotherapy groups (p>0.05). Multivariate analysis showed that more than 3 cycles of regimen with neoadjuvant chemotherapy was associated with more resistance to chemotherapy compared with patients without receiving neoadjuvant chemotherapy (OR: 5.962, 95%CI: 1.184-30.030, p<0.05). Conclusions:Neoadjuvant chemotherapy can shorten the operation time. However, it does not improve survival rates of advanced ovarian cancer patients. -
Bashir, Muhammad Naeem;Malik, Muhammad Akram 2375
Background: The effects of diet on epidemiology of prostate cancer are inconclusive. Therefore a hospitalbased, case-control study was conducted in a rural population of Faisalabad, Pakistan, to examine the impact of dietary factors on risk of cancer development. Materials and Methods: This study was based on 102 confirmed cases of prostate cancer and 204 normal controls. Logistic regression was used to estimate odds ratios and 95% confidence intervals for odds ratios to evaluate the relationship between prostate cancer and diet. Results: Consumption of red meat and fat items significantly increased the prostate cancer risk having odds ratios and 95% confidence intervals of 3.41; 1.46-7.96 and 2.45; 1.17-5.15, respectively. On the other hand, more consumption of vegetables, fluid intake and fruit significantly decreased the prostate cancer risk (odd ratios and corresponding 95% confidence intervals of 0.21; 0.10-0.44, 0.10; 0.05- 0.19 and 0.09; 0.03- 0.23, respectively. Conclusions: The present study supports the hypothesis that frequent consumption of red meat and fat items may increase prostate cancer risk while more intake of fruit, vegetables and fluid intake may protect against prostate cancer in the relatively low risk group in rural Pakistan. -
Bekmukhambetov, Yerbol;Imangazina, Zina;Jarkenov, Timur;Mamyrbayev, Arstan 2379
The article provides an assessment of the dynamics of cancer incidence and mortality in the territory of Aktobe city for the period 2000-2010. The most common cancers were found in the lungs, stomach, esophagus and breast throughout the period, with slight increase in colon cancer and decrease in esophageal cancer being apparent. In an attempt to cast light on effects of environmental pollution, the authors also compared data on total emissions of chemicals into the air. While preliminary, the findings provide a basic picture of cancer burden in this industrialised city in Kazakhstan which should be followed up by more comprehensive monitoring. -
Ameli, Fereshteh;Rose, Isa Mohd;Masir, Noraidah 2385
Background: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC. Objectives: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC. Materials and Methods: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records. Results: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC. Conclusions: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours. -
Huang, Yu-Jing;He, Ai-Na;Sun, Yuan-Jue;Shen, Zan;Min, Da-Liu;Yao, Yang 2391
Objective: The aim of this retrospective study was to evaluate the feasibility and efficacy of response to continuous-infusion ifosfamide and doxorubicin combination as second-line chemotherapy for patients with recurrent or refractory osteosarcoma. Materials and Methods: Eighteen recurrent or refractory osteosarcoma patients who were treated with continuous-infusion ifosfamide and doxorubicin combination between May 1999 and April 2011 were included in the analysis. Ifosfamide at$12g/m^2$ was administered by intravenous continuous infusion over 3 days, and doxorubicin$60mg/m^2$ was administered as an intravenous bolus injection on day 1. The combination therapy was repeated every 3 weeks. Treatment was continued until evidence of disease progression or unacceptable toxicity. Results: The patients (ages 7-53 years) received a total of 42 cycles of chemotherapy (median: 2 courses; range: 2-5 courses). The overall response rate was 0% and the disease control rate was 22.3%, with four patients having stable disease. The median time to progression and overall survival time were 2 months (range: 2-5 months) and 9 months (range: 3-29 months), respectively. Major severe toxicities were leucopenia 7 (38.9%), nausea and vomiting 3 (16.7%) and alopecia 9 (50%). There were no treatment-related deaths. Conclusions: In our experience, continuous-infusion ifosfamide and doxorubicin combination therapy at this dosage and schedule was found to be well tolerated and moderate effective, which could be considered as salvage therapy for patients with recurrent or refractory osteosarcoma. Further assessment is necessary to confirm the safety and efficacy of this treatment. -
Liang, Hong-Liang;Hu, Ai-Ping;Li, Sen-Lin;Xie, Jia-Ping;Ma, Qing-Zhu;Liu, Ji-Yong 2397
Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression. -
Background: Very few analytical studies are available on any association between stressful life events (SLE) and colorectal cancer (CRC), at least in Iran. The aim of this case control study was to determine the association between stressful life events (SLE) and colorectal cancer. Materials and Methods: This study was conducted in four hospital colonoscopy units in Tabriz city of Iran including 414 participants aged 40-75 years: 207 cases with CRC confirmed by pathology and colonoscopy findings and 207 controls free of neoplastic conditions were selected (from the same hospitals at the same period for the cases and after matching for age and sex). Stressful life events were assessed using a 43-item Holmes and Rahe Life Events Questionnaire. Multivariate logistic regression was used to estimate adjusted odds ratios for SLE and risk of CRC. Results: The stressful life event mean score in the case group was 141.3, in contrast to 63.8 in the control group (p<0.011). After adjusting for confounders, death of dear ones increased the risk of CRC (OR: 2.49; 95%CI: 1.41-5.13). Other types of stressful life events (family and husband disputes, serious occupational problems, unemployment of > 6 months, and Serious financial problems) were also associated with CRC, but without statistical significance. Conclusions: According to our findings, it seems that SLE may increase the risk of CRC.
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Okuturlar, Yildiz;Gunaldi, Meral;Tiken, Elif Eda;Oztosun, Bugra;Inan, Yesim Ozdem;Ercan, Tarik;Tuna, Savas;Kaya, Ali Osman;Harmankaya, Ozlem;Kumbasar, Abdulbaki 2409
Purpose: We aimed to study the inflammatory parameters of complete blood count in breast cancer cases. Materials and Methods: This retrospective study covered 178 breast cancer patients and 107 age and body mass index matched healthy women. Complete blood count parameters, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and MPV/platelet were analyzed. Results: The leukocyte, neutrophil and neutrophil/lymphocyte ratio were higher in the patient group (p values 0.001, 0.0001 and 0.0001, respectively) while haemoglobin and hematocrit were higher in the control group (p=0.0001 for both). Logistic regression analysis showed that elevated neutrophils and platelet distribution width (PDW) (OR: 0.627, 95%CI: 0.508-0.774, p=0.001 and OR: 1.191 95%CI: 1.057-1.342 p=0.003) were independent variables for predicting breast cancer. The cut-off value for the neutrophil/lymphocyte ratio was 2.56. Conclusions: According to our study results, neutrophil levels as part of complete blood count may be used as an independent predictor of breast cancer risk. -
Kucukzeybek, Yuksel;Dirican, Ahmet;Demir, Lutfiye;Yildirim, Serkan;Akyol, Murat;Yildiz, Yasar;Bayoglu, Ibrahim Vedat;Alacacioglu, Ahmet;Varol, Umut;Salman, Tarik;Yildiz, Ibrahim;Can, Huseyin;Tarhan, Mustafa Oktay 2413
Background: Although adjuvant chemotherapy is a standard treatment in stage III colon cancer, its benefit is not as clear for stage II patients. In this retrospective analysis, we aimed to evaluate the survival of patients with low-risk stage II colon cancer, the efficacy of adjuvant chemotherapy in high-risk stage II colon cancer patients, and prognostic factors in stage II disease. Materials and Methods: One hundred and seventeen patients who were diagnosed with stage II colon cancer between January 2006 and December 2011 were included in the study. Patients were stratified into two groups as being low-risk and high-risk according to risk factors for stage II disease. Adjuvant 5-fluorouracil-based chemotherapy were administered to the patients with risk factors. Results: Ninety-four patients were treated with adjuvant chemotherapy due to high risk factors and 23 were monitored without treatment. Median follow-up time was 43 months. In terms of disease free survival and overall survival, adjuvant chemotherapy did not provide a statistically significant difference. Univariate analysis demonstrated that bowel obstruction was the major risk factor for shortened disease-free survival, while bowel perforation and perineural invasion were both negative prognostic factors for overall survival. Conclusions: The recommendation of adjuvant chemotherapy for stage II colon cancer is not clear. In our study, it was found that adjuvant chemotherapy did not contribute to survival in high-risk stage II patients. Due to the fact that prognosis of stage II patients is good, many more patients will be needed for statistically significant differences in survival. Adjuvant chemotherapy containing 5 fluorouracil is being used to high-risk stage II patients although it is not a standard treatment approach. -
Zhao, Yan-Jie;Jiang, Ni;Song, Qing-Kun;Wu, Jiang-Ping;Song, Yu-Guang;Zhang, Hong-Mei;Chen, Feng;Zhou, Lei;Wang, Xiao-Li;Zhou, Xin-Na;Yang, Hua-Bing;Ren, Jun;Lyerly, Herbert Kim 2419
Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of$5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic$CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive$CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of$CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment. -
Zhou, Wen;Wang, Jian;Man, Wang-Ying;Zhang, Qing-Wei;Xu, Wen-Gui 2425
Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2. -
Roder, David;Karapetis, Christos S;Wattchow, David;Moore, James;Singhal, Nimit;Joshi, Rohit;Keefe, Dorothy;Fusco, Kellie;Powell, Kate;Eckert, Marion;Price, Timothy J 2431
Background: Registry data from four major public hospitals indicate trends in clinical care and survival from colorectal cancer over three decades, from 1980 to 2010. Materials and Methods: Kaplan-Meier productlimit estimates and Cox proportional hazards models were used to investigate disease-specific survival and multiple logistic regression analyses to explore first-round treatment trends. Results: Five-year survivals increased from 48% for 1980-1986 to 63% for 2005-2010 diagnoses. Survival increases applied to each ACPS stage (Australian Clinico-Pathological Stage), and particularly stage C (an increase from 38% to 68%). Risk of death from colorectal cancer halved (hazards ratio: 0.50 (0.45, 0.56)) over the study period after adjusting for age, sex, stage, differentiation, primary sub-site, health administrative region, and measures of socioeconomic status and geographic remoteness. Decreases in stage were not observed. Survivals did not vary by sex or place of residence, suggesting reasonable equity in service access and outcomes. Of staged cases, 91% were treated surgically with lower surgical rates for older ages and more advanced stage. Proportions of surgical cases having adjuvant therapy during primary courses of treatment increased for all stages and were highest for stage C (an increase from 5% in 1980-1986 to 63% for 2005-2010). Radiotherapy was more common for rectal than colonic cases. Proportions of rectal cases receiving radiotherapy increased, particularly for stage C where the increase was from 8% in 1980-1986 to 60% in 2005-2010. The percentage of stage C colorectal cases less than 70 years of age having systemic therapy as part of their first treatment round increased from 3% in 1980-1986 to 81% by 1995-2010. Based on survey data on uptake of adjuvant therapy among those offered this care, it is likely that all these younger patients were offered systemic treatment. Conclusions: We conclude that pronounced increases in survivals from colorectal cancer have occurred at major public hospitals in South Australia due to increases in stage-specific survivals. Use of adjuvant therapies has increased and the patterns of change accord with clinical guideline recommendations. Reasons for sub-optimal use of radiotherapy for rectal cases warrant further investigation, including the potential for limited rural access to impede uptake of treatments at metropolitan-based radiotherapy centres. -
Pradjatmo, Heru;Dasuki, Djaswadi;Dwianingsih, Ery Kus;Triningsih, Ediati 2441
Background: Several risk factors leading to malignant transformation of hydatidiform moles have been described previously. Many studies showed that prophylactic chemotherapy for high risk hydatidiform moles could significantly decrease the incidence of malignancy. Thus, it is essential to discover a breakthrough to determine patients with high risk malignancy so that prophylactic chemotherapy can be started as soon as possible. Objectives: Development of a scoring system of risk factors as a predictor of hydatidiform mole malignant transformation. Materials and Methods: This research is a case control study with hydatidiform mole and choriocarcinoma patients as subjects. Multiple logistic regression was used to analyze the data. Odds ratios (OR), attributable at risk (AR : OR-1) and risk index ($ARx{\beta}$ ) were calculated for develoipment of a scoring system of malignancy risk. The optimal cut-off point was determined using receiver operating characteristic (ROC) curve. Results: This study analyzed 34 choriocarcinoma cases and 68 benign hydatidiform mole cases. Four factors significantly increased the risk of malignancy, namely age${\geq}35$ years old (OR:4.41, 95%CI:1.07-16.09, risk index 5); gestational age${\geq}$ 12weeks (OR:11.7, 95%CI:1.8-72.4, risk index 26); uterine size greater than the gestational age (OR:10.2, 95%CI:2.8-36.6, risk index 21); and histopathological grade II-III (OR:3.4, 95%CI:1.1-10.6, risk index 3). The lowest and the highest scores for the risk factors were zero and 55, respectively. The best cut-off point to decide high risk malignancy patients was${\geq}31$ . Conclusions: Malignant transformation of hydatidiform moles can be predicted using the risk scoring by analyzing the above four parameters. Score${\geq}31$ implies high risk patients so that prophylactic chemotherapy can be promptly administered for prevention. -
Park, So-Hyun;Park, Chan-Sung;Kim, Young-Il;Nam-Goong, Il-Seong;Kim, Yon-Seon;Lee, Jong-Cheol;Choi, Jung-Il;Park, Jeong-Woo;Kim, Eun-Sook 2447
Background: Human papillary thyroid carcinoma (PTC) is often associated with Hashimoto's thyroiditis (HT); their coexistence improves PTC prognosis. Osteopontin, a secreted glycoprotein, plays a role in cell survival, immunity, and tumor progression, its expression being associated with a poor prognosis and metastasis in several malignancies. Osteopontin overexpression correlates with aggressive clinicopathological features in PTC. Lymph node metastases and large tumor size positively correlate with osteopontin positivity. This study aimed to: (1) confirm osteopontin overexpression in human PTC samples; (2) compare osteopontin expression levels in PTC cases with and without HT; and (3) identify correlations between tumor aggressiveness and osteopontin expression levels. Materials and Methods: Plasma osteopontin was assessed in 45 patients with PTC, 22 patients with PTC and HT, and 24 healthy controls by enzyme-linked immunosorbent assay. Thyroid tissue osteopontin mRNA and protein levels were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively. Results: Plasma osteopontin levels were significantly higher in PTC patients than in healthy controls. Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone. In advanced disease stage cases, osteopontin mRNA and protein expression levels were lower in patients with PTC and HT than in those with PTC alone. However, the osteopontin expression level was not significantly associated with the TNM stage. Conclusions: Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone, suggesting that HT attenuates PTC aggressiveness through negative regulation of osteopontin expression. -
Zhao, Wen-Jing;Deng, Bo-Ya;Wang, Xue-Mei;Miao, Yuan;Wang, Jian-Nan 2453
Background: X-linked inhibitor of apoptosis protein (XIAP) associated factor 1 (XAF1) exhibits aberrantly low or absent expression in various human malignancies, closely associated with anti-apoptosis and overgrowth of cancer cells. However, limited attention has been directed towards the contribution of XAF1 to invasion, apoptosis, and cisplatin (DDP)-resistance of epithelial ovarian cancer (EOC) cells. This study aimed to evaluate the potential effects of XAF1 on invasion, cell cycle, apoptosis, and cisplatin-resistance by overexpressing XAF1 in SKOV-3 and SKOV-3/DDP cells. Methods and Results: The pEGFP-C1-XAF1 plasmid was transfected into SKOV-3 and SKOV-3/DDP cells, and the expression of XAF1 at both mRNA and protein levels was analyzed by reverse transcription-PCR and Western blotting. Overexpression of XAF1 suppressed XIAP expression in both SKOV-3 and SKOV-3/DDP cells. Transwell invasion assays demonstrated that XAF1 exerted a strong anti-invasive effect in XAF1-overexpressing cells. Moreover, flow cytometry analysis revealed that XAF1 overexpression arrested the cell cycle at G0/G1 phase, and cell apoptosis analysis showed that overexpression of XAF1 enhanced apoptosis of SKOV-3 and SKOV-3/DDP cells apparently by activating caspase-9 and caspase-3. Furthermore, MTT assay confirmed a dose-dependent inhibitory effect of cisplatin in the tested tumor cells, and overexpression of XAF1 increased the sensitivity of SKOV-3 and SKOV-3/DDP cells to cisplatin-mediated antiproliferative effects. Conclusions: In summary, our data indicated that overexpression of XAF1 could suppress XIAP expression, inhibit invasion, arrest cell cycle, promote apoptosis, and confer cisplatin-sensitivity in SKOV-3 and SKOV-3/DDP cells. Therefore, XAF1 may be further assessed as a potential target for the treatment of both cisplatin-resistant and non-resistant EOCs. -
Zhang, Zi-Chao;Zheng, Li-Qiang;Pan, Li-Jie;Guo, Jin-Xing;Yang, Guo-Shan 2459
Background: To investigate the expression and clinical significance of zinc finger protein 217 (ZNF217) in human colorectal carcinoma (CRC). Materials and Methods: The expression of ZNF217 in 60 CRC tissues and matched tumor adjacent tissues, collected between January 2013 and June 2014, was assessed immunohistochemically. The relationship between the expression of ZNF217 and clinicopathlogical features was analyzed by Pearson chi-square test. In addition, siRNA was used to down-regulate the expression of ZNF217 in CRC cells. The effects of ZNF217 for cell migration and invasion were measured by wound healing assay and transwell assay, respectively. Results: The expression level of ZNF217 was significantly higher in CRC tissues than in tumor adjacent tissues (p<0.05), positively correlating with tumor size, lymphatic metastasis and advanced TNM stage (p<0.05). Down-regulation of ZNF217 in CRC cells could significantly suppress cell migration and invasion. Conclusions: ZNF217 is overexpressed in colorectal carcinoma tissues and is associated with tumor malignant clinicopathological features. ZNF217 may promote CRC progression by inducing cell migration and invasion. -
Campbell, Ian;Scott, Nina;Seneviratne, Sanjeewa;Kollias, James;Walters, David;Taylor, Corey;Roder, David 2465
Background: The Quality Audit (BQA) program of the Breast Surgeons of Australia and New Zealand (NZ) collects data on early female breast cancer and its treatment. BQA data covered approximately half all early breast cancers diagnosed in NZ during roll-out of the BQA program in 1998-2010. Coverage increased progressively to about 80% by 2008. This is the biggest NZ breast cancer database outside the NZ Cancer Registry and it includes cancer and clinical management data not collected by the Registry. We used these BQA data to compare socio-demographic and cancer characteristics and survivals by ethnicity. Materials and Methods: BQA data for 1998-2010 diagnoses were linked to NZ death records using the National Health Index (NHI) for linking. Live cases were followed up to December$31^{st}$ 2010. Socio-demographic and invasive cancer characteristics and disease-specific survivals were compared by ethnicity. Results: Five-year survivals were 87% for Maori, 84% for Pacific, 91% for other NZ cases and 90% overall. This compared with the 86% survival reported for all female breast cases covered by the NZ Cancer Registry which also included more advanced stages. Patterns of survival by clinical risk factors accorded with patterns expected from the scientific literature. Compared with Other cases, Maori and Pacific women were younger, came from more deprived areas, and had larger cancers with more ductal and fewer lobular histology types. Their cancers were also less likely to have a triple negative phenotype. More of the Pacific women had vascular invasion. Maori women were more likely to reside in areas more remote from regional cancer centres, whereas Pacific women generally lived closer to these centres than Other NZ cases. Conclusions: NZ BQA data indicate previously unreported differences in breast cancer biology by ethnicity. Maori and Pacific women had reduced breast cancer survival compared with Other NZ women, after adjusting for socio-demographic and cancer characteristics. The potential contributions to survival differences of variations in service access, timeliness and quality of care, need to be examined, along with effects of comorbidity and biological factors. -
Esmatabadi, Mohammad Javad Dehghan;Farhangi, Baharak;Safari, Zahra;Kazerooni, Hanif;Shirzad, Hadi;Zolghadr, Fatemeh;Sadeghizadeh, Majid 2473
Colon cancer is one of the leading causes of cancer-associated death worldwide. The prognosis for advanced colorectal cancers remains dismal, mainly due to the propensity for metastatic progression. Accordingly, there is a need for effective anti-metastasis therapeutic agents. Since a great body of research has indicated anticancer effects for curcumin, we investigated the effects of dendrosomal curcumin (DNC) on cellular migration and adhesion of human SW480 cells and possible molecular mechanisms involved. Different methods were applied in this study including MTT, Scratch and adhesion assays as well as real-time PCR and transwell chamber assays. Based on the results obtained, DNC inhibits metastasis by decreasing Hef 1, Zeb 1 and Claudin 1 mRNA levels and can reduce SW480 cell proliferation with$IC_{50}$ values of 15.9, 11.6 and$7.64{\mu}M$ at 24, 48 and 72h post-treatment. Thus it might be considered as a safe formulation for therapeutic purpose in colorectal cancer cases. -
Matsumoto, Kazumasa;Mochizuki, Kohei;Hirayama, Takahiro;Ikeda, Masaomi;Nishi, Morihiro;Tabata, Ken-ichi;Okazaki, Miyoko;Fujita, Tetsuo;Taoka, Yoshinori;Iwamura, Masatsugu 2483
This study was conducted to evaluate the effectiveness of a combination of gemcitabine and nedaplatin therapy among patients with metastatic urothelial carcinoma previously treated with two lines of chemotherapy. Between February 2009 and August 2013, 30 patients were treated with gemcitabine and paclitaxel as a second-line chemotherapy. All had received a first-line chemotherapy consisting of methotrexate, vinblastine, doxorubicin and cisplatin. Ten patients who had measurable histologically proven advanced or metastatic urothelial carcinoma of the urinary bladder and upper urinary tract received gemcitabine$1,000mg/m^2$ on days 1, 8 and 15 and nedaplatin$70mg/m^2$ on day 2 as a third-line chemotherapy. Tumors were assessed by imaging every two cycles. The median number of treatment cycles was 3.5. One patient had partial response and three had stable disease. The disease-control rate was 40%, the median overall survival was 8.8 months and the median progression-free survival was 5.0 months. The median overall survival times for the first-line and second-line therapies were 29.1 and 13.9 months, respectively. Among disease-controlled patients (n=4), median overall survival was 14.2 months. Myelosuppression was the most common toxicity. There were no therapy-related deaths. Gemcitabine and nedaplatin chemotherapy is a favorable third-line chemotherapeutic option for patients with metastatic urothelial carcinoma. Given the safety and benefit profile seen in this study, further prospective trials are warranted given the implications of our results with regard to strategic chemotherapy for patients with advanced or metastatic urothelial carcinoma. -
Long, Jin;Zhang, Zhong-Bo;Liu, Zhe;Xu, Yuan-Hong;Ge, Chun-Lin 2489
Background: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. Materials and Methods: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). Results: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial$Ca^{2+}$ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. Conclusions: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer. -
Chen, Qi;Lu, Hong-sheng;Gan, Mei-fu;Chen, Lan-xi;He, Kai;Fan, Guang-min;Cao, Xue-quan 2495
Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important serine/threonine protein kinase and a member of the MAPK family. MEKK3 can effectively activate the MEK/ERK signaling pathway and promote an autocrine growth loop critical for tumor genesis, cell proliferation, terminal differentiation, apoptosis and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3, pERK and FoxP3 in the renal clear cell carcinoma (RCCC). Protein expression was detected by tissue microarray and immunochemistry in 46 cases of RCCC and 28 control cases. Expression levels of CD3+,CD3+CD4+,CD3+CD8+,CD4+CD25+, CD4+CD25+ FoxP3+ were assessed by flow cytometry and analyzed for their association with pathological factors, correlation and prognosis in RCCC. Expression of MEKK3, pERK and FoxP3 was significantly up-regulated in RCCC as compared to control levels (p<0.01), associated with pathological grade (p<0.05)and clinical stage (p<0.05). CD4+CD25+ Foxp3+ Treg cells were also significantly increased in RCCC patients (p<0.05). Cox multivariate regression analysis showed that MEKK3, pERK expression and patholigical stage were independent prognostic factors in patients with RCCC (p<0.05). MEKK3 can be used as an important marker of early diagnosis and prognostic evaluation in RCCC. It may be associated with imbalance of anti-tumor immunity and overexpression of pERK. Expression of MEKK3 and pERK are significantly increased in RCCC, with protein expression and clinical stage acting as independent prognostic factors. -
Yasli, Gokben;Turhan, Ebru;Eser, Sultan;Tozun, Mustafa;Oguz, Murat;Alpay, Fatma 2501
Purpose: The present study was carried out to measure knowledge level and behavior of family health personnel (FHP) in Izmir on early diagnosis of breast and cervical cancers. Materials and Methods: The study population of this cross-sectional study was not selected. A questionnaire was applied to all FHP to measure knowledge level and behavior about cancer. The participation rate was 88%. Breast examination, mammography analysis, Papanicolaou smear applications were determined as dependent variables, and knowledge level about breast and cervical cancer, age, professional time as FHP as independent variables. Data were evaluated using definitive statistics, chi-square and logistic regression tests in SPSS software package for Windows 15.0. Results: A total of 970 family health personnel participated in the research. The age range was 20-45 years (82.4%). Mean age was$37.9{\pm}7.4$ . Response rate was 87.3%. Of the participants, 88.4% performed breast self-examination. Rate of performing mammography at least once was 24.1%. Rate of performing Pap-smear examination at least once was 61.0%. In logistic regression analyses, it was determined that people with knowledge on breast and cervical cancer were those performing breast self-examination, mammography and Pap-smear examinations (p<0.05. Conclusions: It is essential that the knowledge, behavior and manners of health providers on early diagnosis for cancer increases awareness in the general population and provides information on execution ofthe most effective methods for generating a healthy society. -
Lim, Seung Taek;Jeon, Ye Won;Suh, Young Jin 2507
Background: Serum vitamin D status can affect the prognosis of breast cancer patients. Our aim was to determine the association between alterations in the 25-hydroxyvitamin D [25(OH)D] status during follow-up and the prognosis of breast cancer patients. Additionally, we evaluated the association between the 25(OH)D status at the time of diagnosis and the prognosis using a detailed age and stage categorization. Materials and Methods: Four hundred and sixty-nine Korean breast cancer patients were included. We collected patient clinicopathological data, including their serum 25(OH)D concentration at diagnosis and at the annual follow-up until 4 years after diagnosis. The patients were divided according to their 25(OH)D status at diagnosis into a deficient (<20 ng/ml) and a non-deficient (${\geq}20ng/ml$ ) group. At follow-up, patients were categorized into the four following groups according to 25(OH)D status alterations: persistently deficient, improved, deteriorated and persistently non-deficient. Results: At diagnosis, 118 patients were classified into the deficient group and 351 into the non-deficient group. After a median follow-up period of$85.8{\pm}31.0$ months, the patients with advanced-stage disease or an older age in the non-deficient group showed a significantly better survival compared with the deficient group. Furthermore, at the 1-year follow-up of 25(OH)D status, the persistently non-deficient group and the improved group had better survival compared with the other two groups. Conclusions: Our results suggest that maintaining an optimal 25(OH)D status at diagnosis and during the 1-year follow-up period is important for improving breast cancer patient survival. -
Topan, Aysel;Ozturk, Ozlem;Eroglu, Hulya;Bahadir, Ozgur;Harma, Muge;Harma, Mehmet Ibrahim 2515
Purpose: To determine knowledge levels of working and student nurses about cervical cancer and prophylactic cancer vaccines. Materials and Methods: This study was performed on 259 nursing students in the Department of Nursing and 137 nurses working in Health Research and Practice Center, approved to participate in the study between April-June 2012. The study was performed universally without selecting a sample. A questionnaire that was prepared for evaluating participants' knowledge and attitudes about human papilloma virus (HPV) vaccine was distributed to the nurses and data obtained from the forms were transferred to SPSS 15.00 program and statistically analyzed. Results: It was found that 54.8% of the student nurses were between 21-24 years old and 13.1% of working students were between 25-28 years old. When student nurses and working nurses were compared in terms of their knowledge about the causes of cervical cancer, their ideas about prevention from cervical cancer with HPV vaccine, their ideas about possible risks of HPV vaccine and conservation ratios of HPV vaccine, it was observed that there were no statistically significant differences (p>0.05). When student nurses and working nurses were compared in terms of the information-source about HPV, ways of HPV contamination, awareness about people who are susceptible to HPV contamination and age of HPV vaccination, it was determined that there was a statistically significant difference (p<0.05). Conclusions: It was found that all nurses had some knowledge about cervical cancer and HPV vaccine, but this was not sufficient. Therefore; it is recommended to use verbal, written and visual communication tools intensively in order to have topics on cervical cancer, early diagnosis and prevention in bachelor and master programs for nurses, to inform society about cervical cancer and HPV vaccine for public health and to teach precautions for its prevention. -
Tian, Shi-Feng;Liu, Ai-Lian;Wang, He-Qing;Liu, Jing-Hong;Sun, Mei-Yu;Liu, Yi-Jun 2521
Objective: The purpose of this study was to evaluate computed tomography (CT) virtual non-contrast (VNC) spectral imaging for gastric carcinoma. Materials and Methods: Fifty-two patients with histologically proven gastric carcinomas underwent gemstone spectral imaging (GSI) including non-contrast and contrast-enhanced hepatic arterial, portal venous, and equilibrium phase acquisitions prior to surgery. VNC arterial phase (VNCa), VNC venous phase (VNCv), and VNC equilibrium phase (VNCe) images were obtained by subtracting iodine from iodine/water images. Images were analyzed with respect to image quality, gastric carcinoma-intragastric water contrast-to-noise ratio (CNR), gastric carcinoma-perigastric fat CNR, serosal invasion, and enlarged lymph nodes around the lesions. Results: Carcinoma-water CNR values were significantly higher in VNCa, VNCv, and VNCe images than in normal CT images (2.72, 2.60, 2.61, respectively, vs 2.35,$p{\leq}0.008$ ). Carcinoma-perigastric fat CNR values were significantly lower in VNCa, VNCv, and VNCe images than in normal CT images (7.63, 7.49, 7.32, respectively, vs 8.48, p< 0.001). There were no significant differences of carcinoma-water CNR and carcinoma-perigastric fat CNR among VNCa, VNCv, and VNCe images. There was no difference in the determination of invasion or enlarged lymph nodes between normal CT and VNCa images. Conclusions: VNC arterial phase images may be a surrogate for conventional non-contrast CT images in gastric carcinoma evaluation. -
Aktas, Binhan Kagan;Ozden, Cuneyt;Bulut, Suleyman;Tagci, Suleyman;Erbay, Guven;Gokkaya, Cevdet Serkan;Baykam, Mehmet Murat;Memis, Ali 2527
Background: The cancer of the prostate risk assessment (CAPRA) score has been defined to predict prostate cancer recurrence based on the pre-clinical data, then pathological data have also been incorporated. Thus, CAPRA post-surgical (CAPRA-S) score has been developed based on six criteria (prostate specific antigen (PSA) at diagnosis, pathological Gleason score, and information on surgical margin, seminal vesicle invasion, extracapsular extension and lymph node involvement) for the prediction of post-surgical recurrences. In the present study, biochemical recurrence (BCR)-free probabilities after open retropubic radical prostatectomy (RP) were evaluated by the CAPRA-S scoring system and its three-risk level model. Materials and Methods: CAPRA-S scores (0-12) of our 240 radical prostatectomies performed between January 2000-May 2011 were calculated. Patients were distributed into CAPRA-S score groups and also into three-risk groups as low, intermediate and high. BCR-free probabilities were assessed and compared using Kaplan-Meier analysis and Cox proportional hazards regression. Ability of CAPRA-S in BCR detection was evaluated by concordance index (c-index). Results: BCR was present in 41 of total 240 patients (17.1%) and the mean follow-up time was$51.7{\pm}33.0$ months. Mean BCR-free survival time was 98.3 months (95% CI: 92.3-104.2). Of the patients in low, intermediate and high risk groups, 5.4%, 22.0% and 58.8% had BCR, respectively and the difference among the three groups was significant (P = 0.0001). C-indices of CAPRA-S score and three-risk groups for detecting BCR-free probabilities in 5-yr were 0.87 and 0.81, respectively. Conclusions: Both CAPRA-S score and its three-risk level model well predicted BCR after RP with high c-index levels in our center. Therefore, it is a clinically reliable post-operative risk stratifier and disease recurrence predictor for prostate cancer. -
Son, Byung Ho;Dominici, Laura S;Aydogan, Fatih;Shulman, Lawrence N;Ahn, Sei Hyn;Cho, Ja Young;Coopey, Suzanne B;Kim, Sung Bae;Min, H Elise;Valero, Monica;Wang, Jiping;Caragacianu, Diana;Gong, Gyung-yub;Hevelone, Nathanael D;Baek, Seunghee;Golshan, Mehra 2531
Background: Breast cancer diagnosed in young women may be more aggressive, with higher rates of local and distant recurrence compared to the disease in older women. Epidemiologic evidence suggests that Korean women have a lower incidence of breast cancer than women in the United States, but that they present at a younger age than their American counterparts. We sought to compare risk factors and management of young women with breast cancer in Boston, Massachusetts (US) with those in Seoul, South Korea (KR). Materials and Methods: A retrospective review was performed of consecutive patients less than 35 years old with a diagnosis of breast cancer at academic cancer centers in the US and KR from 2000-2005. Patient data were obtained by chart review. Demographic, tumor and treatment characteristics were compared utilizing Pearson's chisquare or Wilcoxon rank-sum tests where appropriate. All differences were assessed as significant at the 0.05 level. Results: 205 patients from the US and 309 from KR were analyzed. Patients in US were more likely to have hormone receptor positive breast cancer, while patients in KR had a higher rate of triple negative lesions. Patients in US had a higher mean body mass index and more often reported use of birth control pills, while those in the KR were less likely to have a sentinel node procedure performed or to receive post mastectomy radiation. Conclusions: Patients under 35 diagnosed with breast cancer in the US and KR differ with respect to demographics, tumor characteristics and management. Although rates of breast conservation and mastectomy were similar, US patients were more likely to receive post mastectomy radiation. The lower use of sentinel node biopsy is explained by the later adoption of the technique in KR. Further evaluation is necessary to evaluate recurrence rates and survival in the setting of differing disease subtypes in these patients. -
Salamat, Faezeh;Semnani, Shahryar;Aboomardani, Maryam;Roshandel, Gholamreza 2537
Background: Nutrition transition is a global health problem, especially in developing countries. It is known as an important factor for development of different types of health conditions including cancers. Objectives: We aimed to assess the pattern of nutrition transition in a high-risk area for upper gastrointestinal cancers in Northern Iran during the last decade. Materials and Methods: This cross-sectional study was conducted on households of Golestan province, Iran. Data on household food consumption between 2001 and 2010 were obtained from the Statistical Center of Iran. The proportions of households with medium/high consumption of main foods were calculated for each year. Joint point software was used for assessing trends. Annual percent changes (APCs) and 95%CIs were calculated. Results: In total, 12,060 households were recruited. The APCs (95%CI) of the proportion of households medium/high consumption of cereals, vegetables, legumes, fish, dairy products and meats were -3.1 (-4.1 to -2.2), -2.9 (-3.8 to -2.1), -2.3 (-3.2 to -1.4), -2.8 (-3.3 to -2.4), -1.9 (-3.0 to -0.9) and 2.7 (1.2 to 4.3), respectively. Conclusions: We found significant increase in meat consumption among our population between 2001 and 2010. Our results also suggested significant decreasing trend in consumption of so-called healthy foods including, plant foods, fish, and dairy products. Regarding its correlation with health conditions including cancers, nutrition transition should be considered as a priority in health policy making in our region as well as other high-risk populations. It is recommended to conduct community level interventions to increase consumption of plant foods, fish, and dairy products. -
Xu, Chuan;Huang, Xin-En;Wang, Shu-Xiang;Lv, Peng-Hua;Sun, Ling;Wang, Fu-An 2543
Purpose: Percutaneous transhepatic biliary drainage (PTBD) is a form of palliative care for patients with malignant obstructive jaundice. We here compared the infection incidence between internal-external and external drainage for patients with malignant obstructive jaundice. Methods: Patients with malignant obstructive jaundice without infection before surgery receiving internal-external or external drainage from January 2008 to July 2014 were recruited. According to percutaneous transhepatic cholangiography (PTC), if the guide wire could pass through the occlusion and enter the duodenum, we recommended internal-external drainage, and external drainage biliary drainage was set up if the occlusion was not crossed. All patients with infection after procedure received a cultivation of blood and a bile bacteriological test. Results: Among 110 patients with malignant obstructive jaundice, 22 (52.4%) were diagnosed with infection after the procedure in the internal-external drainage group, whereas 19 (27.9%) patients were so affected in the external drainage group, the difference being significant (p<0.05). In 8 patients (36.3%) in the internal-external group infection was controlled, as compared to 12 (63.1%) in the external group (p< 0.05). The mortality rate for patients with infection not controlled in internal-external group in one month was 42.8%, while this rate in external group was 28.6% (p< 0.05). Conclusion: External drainage is a good choice, which could significantly reduce the chance of biliary infection caused by bacteria, and decrease the mortality rate at one month and improve the long-term prognosis. -
Vithana, PVS Chiranthika;Ariyaratne, MAY;Jayawardana, PL 2547
Purpose: The present study concerns the effectiveness of an educational intervention for improving knowledge, attitudes and practices (KAP) of breast cancer early detection among target group women (TGW) in the district of Gampaha, Sri Lanka. Materials and Methods: The study was a community-based intervention. Two medical officer of health areas in Gampaha district were selected using random sampling as intervention (IA) and control (CA). Public health midwives (PHMs) in the IA were exposed to the educational intervention first, conducted the same among the TGW through PHMs. KAP was assessed using an interviewer- administrated questionnaire among 260 TGW from each area selected using cluster sampling before and six months after the intervention. Results: The overall median scores for KAP among TGW in IG increased significantly from pre intervention level of 54% (IQR: 46-59%), 50% (IQR: 41-59%), and 0% (IQR: 0-20%) to post intervention level of 77% (IQR: 72-82%), 68% (IQR: 59- 76 %) and 40% (IQR: 20-60%) respectively. In CG, overall median scores for KAP remained almost the same at pre intervention 54% (IQR:44-59%), 50% (IQR:36-59%) and 0% (IQR: 0-20%) and post intervention 54% (IQR:46-59%), 50% (IQR:36-64%) and 0% (IQR: 0-20%) respectively. Conclusions: The educational intervention was found to be effective. -
Purpose: To investigate effects of the TESTIN (TES) gene on proliferation and migration of highly metastatic nasopharyngeal carcinoma cell line 5-8F and the related mechanisms. Materials and Methods: The target gene of human nasopharyngeal carcinoma cell line 5-8F was amplified by PCR and cloned into the empty plasmid pEGFP-N1 to construct a eukaryotic expression vector pEGFP-N1-TES. This was then transfected into 5-8F cells. MTT assays, flow cytometry and scratch wound tests were used to detect the proliferation and migration of transfected 5-8F cells. Results: A cell model with stable and high expression of TES gene was successfully established. MTT assays showed that the OD value of 5-8F/TES cells was markedly lower than that of 5-8F/GFP cells and 5-8F cells (p<0.05). Flow cytometry showed that the apoptosis rate of 5-8F/TES cells was prominently increased compared with 5-8F/GFP cells and 5-8F cells (p<0.05). In vitro scratch wound assays showed that, the width of the wound area of 5-8F/TES cells narrowed slightly, while the width of the wound area of 5-8F/ GFP cells and 5-8F cells narrowed sharply, suggesting that the TES overexpression could inhibit the migration ability. Conclusions: TES gene expression remarkably inhibits the proliferation of human nasopharyngeal carcinoma cell line 5-8F and reduces its migration in vitro. Thus, it may be a potential tumor suppressor gene for nasopharyngeal carcinoma.
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Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death worldwide. Our study aimed to reveal molecular mechanisms. Microarray data of GSE15471 (including 39 matching pairs of pancreatic tumor tissues and patient-matched normal tissues) was downloaded from Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) in PDAC tissues compared with normal tissues by limma package in R language. Then GO and KEGG pathway enrichment analyses were conducted with online DAVID. In addition, principal component analysis was performed and a protein-protein interaction network was constructed to study relationships between the DEGs through database STRING. A total of 532 DEGs were identified in the 38 PDAC tissues compared with 33 normal tissues. The results of principal component analysis of the top 20 DEGs could differentiate the PDAC tissues from normal tissues directly. In the PPI network, 8 of the 20 DEGs were all key genes of the collagen family. Additionally, FN1 (fibronectin 1) was also a hub node in the network. The genes of the collagen family as well as FN1 were significantly enriched in complement and coagulation cascades, ECM-receptor interaction and focal adhesion pathways. Our results suggest that genes of collagen family and FN1 may play an important role in PDAC progression. Meanwhile, these DEGs and enriched pathways, such as complement and coagulation cascades, ECM-receptor interaction and focal adhesion may be important molecular mechanisms involved in the development and progression of PDAC.
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Necroptosis, also known as "programmed necrosis", has emerged as a critical factor in a variety of pathological and physiological processes and is considered a cell type-specific tightly regulated process with mechanisms that may vary rather greatly due to the change of cell line. Here we used HT-29, a human colon cancer cell line, to establish a necroptosis model and elucidate associated mechanisms. We discovered that cobalt chloride, a reagent that could induce hypoxia-inducible
$factor-1{\alpha}(HIF1{\alpha})$ expression and therefore mimic the hypoxic microenvironment of tumor tissue in some aspects induces necroptosis in HT-29 cells when caspase activity is compromised. On the other hand, apoptosis appears to be the predominant death form when caspases are functioning normally. HT-29 cells demonstrated significantly increased RIPK1, RIPK3 and MLKL expression in response to cobalt chloride plus z-VAD treatment, which was accompanied by drastically increased$IL1{\alpha}$ and IL6 expression, substantiating the notion that necrosis can induce profound immune reactions. The RIPK1 kinase inhibitor necrostatin-1 and the ROS scavenger NAC each could prevent necrosis in HT-29 cells and the efficiency was enhanced by combined treatment. Thus by building up a necroptosis model in human colon cancer cells, we uncovered that mechanically RIP kinases collaborate with ROS during necrosis promoted by cobalt chloride plus z-VAD, which leads to inflammation. Necroptosis may present a new target for therapeutic intervention in cancer cells that are resistant to apoptotic cell death. -
Farooqi, Ammad Ahmad;Wang, Zhiqiang;Hasnain, Sidra;Attar, Rukset;Aslam, Ayesha;Mansoor, Qaisar;Ismail, Muhammad 2575
Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies. -
Ozaslan, Ersin;Aksoy, Asude;Gumusay, Ozge;Arpaci, Erkan;Berk, Veli 2581
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Arakawa, Ichiro;Murasawa, Hideki;Konno, Ryo 2583
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Tanoglu, Alpaslan;Karagoz, Ergenekon;Beyazit, Yavuz 2585