Asian Pacific Journal of Cancer Prevention

Franca-Botelho, Aline Do Carmo;Ferreira, Marina Carvalho;Franca, Juliana Luzia;Franca, Eduardo Luzia;Honorio-Franca, Adenilda Cristina 5327

https://doi.org/10.7314/APJCP.2012.13.11.5327 PDF KSCI

In this review, we describe the patterns of known immunological components in breast milk and examine the relationship between breastfeeding and reduced risk of breast cancer. The top risk factors for breast cancer are a woman's age and family history, specifically having a first-degree relative with breast cancer. Women that have a history of breastfeeding have been shown to have reduced rates of breast cancer. Although the specific cause has not been elucidated, previous studies have suggested that breastfeeding reduces the risk of breast cancer primarily through two mechanisms: the differentiation of breast tissue and reduction in the lifetime number of ovulatory cycles. In this context, one of the primary components of human milk that is postulated to affect cancer risk is alpha-lactalbumin. Tumour cell death can be induced by HAMLET (a human milk complex of alpha-lactalbumin and oleic acid). HAMLET induces apoptosis only in tumour cells, while normal differentiated cells are resistant to its effects. Therefore, HAMLET may provide safe and effective protection against the development of breast cancer. Mothers should be encouraged to breastfeed their babies because the complex components of human milk secretion make it an ideal food source for babies and clinical evidence has shown that there is a lower risk of breast cancer in women who breastfed their babies.

Wu, Xia-Yu;Lu, Lin 5333

https://doi.org/10.7314/APJCP.2012.13.11.5333 PDF KSCI

Vitamin B6 functions as a coenzyme in >140 enzymatic reactions involved in the metabolism of amino acids, carbohydrates, neurotransmitters, and lipids. It comprises a group of three related 3-hydroxy-2-methyl-pyrimidine derivatives: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM) and their phosphorylated derivatives [pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP)], In the folate metabolism pathway, PLP is a cofactor for the mitochondrial and cytoplasmic isozymes of serine hydroxymethyltransferase (SHMT2 and SHMT1), the P-protein of the glycine cleavage system, cystathionine ${\beta}$-synthase (CBS) and ${\gamma}$-cystathionase, and betaine hydroxymethyltransferase (BHMT), all of which contribute to homocysteine metabolism either through folate-mediated one-carbon metabolism or the transsulfuration pathway. Folate cofactors carry and chemically activate single carbons for the synthesis of purines, thymidylate and methionine. So the evidence indicates that vitamin B6 plays an important role in maintenance of the genome, epigenetic stability and homocysteine metabolism. This article focuses on studies of strand breaks, micronuclei, or chromosomal aberrations regarding protective effects of vitamin B6, and probes whether it is folate-mediated one-carbon metabolism or the transsulfuration pathway for vitamin B6 which plays critical roles in prevention of cancer and cardiovascular disease.

Yin, Pei-Hao;Liu, Xuan;Qiu, Yan-Yan;Cai, Jian-Feng;Qin, Jian-Min;Zhu, Hui-Rong;Li, Qi 5339

https://doi.org/10.7314/APJCP.2012.13.11.5339 PDF KSCI

The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.

Yu, Shu-Dong;Liu, Fen-Ye;Wang, Qi-Rong 5345

https://doi.org/10.7314/APJCP.2012.13.11.5345 PDF KSCI

Radiotherapy is an important part of modern cancer management for many malignancies, and enhancing the radiosensitivity of tumor cells is critical for effective cancer therapies. The Notch signaling pathway plays a key role in regulation of numerous fundamental cellular processes. Further, there is accumulating evidence that dysregulated Notch activity is involved in the genesis of many human cancers. As such, Notch inhibitors are attractive therapeutic agents, although as for other anticancer agents, they exhibit significant and potential side effects. Thus, Notch inhibitors may be best used in combination with other agents or therapy. Herein, we describe evidence supporting the use of Notch inhibitors as novel and potent radiosensitizers in cancer therapy.

Kuppala, Manohar Babu;Syed, Sunayana Begum;Bandaru, Srinivas;Varre, Sreedevi;Akka, Jyothy;Mundulru, Hema Prasad 5353

https://doi.org/10.7314/APJCP.2012.13.11.5353 PDF KSCI

Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

Zhang, Er-Ying;Tang, Xu-Dong 5363

https://doi.org/10.7314/APJCP.2012.13.11.5363 PDF KSCI

High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-$1{\alpha}$, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling pathways in lung cancer. This article provides an overview of experiment data on HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.

Muttappallymyalil, Jayakumary;Divakaran, Binoo;Thomas, Teena;Sreedharan, Jayadevan;Haran, Jeesha C.;Thanzeel, Mohammed 5371

https://doi.org/10.7314/APJCP.2012.13.11.5371 PDF KSCI

The present study was conducted to assess the prevalence and type of tobacco use among adolescents and also the reasons for the initiation of tobacco use amongst them. It was conducted in ten randomly selected schools in the Kannur district of Kerala state, India. A total of 3,000 school children participated. The study observed an overall prevalence of 5.5%. The prevalence observed among boys was 12% and none of the girls were tobacco users. Association between father's and friend's tobacco habits were observed.

Zhang, Zhi-Hua;Yang, Lin-Sheng;Huang, Fen;Hao, Jia-Hu;Su, Pu-Yu;Sun, Ye-Huan 5375

https://doi.org/10.7314/APJCP.2012.13.11.5375 PDF KSCI

Introduction: Published studies on the association between Nijmegen breakage syndrome 1(NBS1) gene polymorphisms and breast cancer risk have been inconclusive, and a meta-analysis was therefore performed for clarification. Methods: Eligible articles were identified by a search of MEDLINE and EMBASE bibliographic databases for the period up to March 2012. The presence of between-study heterogeneity was investigated using the chi-square-based Cochran's Q statistic test. When there was statistical heterogeneity, the random effects model was chosen; otherwise, fixed effects estimates were reported as an alternative approach. Results: A total of 11 eligible articles (14 case-control studies) were identified, nine case-control studies were for the 657del5 mutation (7,534 breast cancer cases, 14,034 controls) and five case-control studies were for the I171V mutation (3,273 breast cancer cases, 4,004 controls). Our analysis results indicated that the 657del5 mutation was associated with breast cancer risk (carriers vs. non-carriers: pooled OR =2.63, 95% CI: 1.76-3.93), whereas the I171V mutation was not (carriers vs. non-carriers: pooled OR =1.52, 95% CI: 0.70-3.28). Conclusion: The present meta-analysis suggests that the 657del5 gene mutation in the NBS1 gene plays a role in breast cancer risk, while the I171V mutation does not exert a significant influence.

Mohammad-Alizadeh, Amir Houshang;Ghobakhlou, Mehdi;Shalmani, Hamid Mohaghegh;Zali, Mohammad Reza 5381

https://doi.org/10.7314/APJCP.2012.13.11.5381 PDF KSCI

Background and Aim: Cholangiocarcinoma (CCA) is an uncommon malignancy of the bile duct, occurring in nearly 2 out of 100,000 people. It is a type of adenocarcinoma that originates in the mucous glands of the epithelium, or surface layers of the bile ducts. The aim of this study was to evaluate the clinical features, diagnostic results and factors associated with survival, morbidity and mortalityof cholangiocarcinoma cases in Iranian patients. Method: In this retrospective study the hospital medical records of 283 patients with a primary or final diagnosis of cholangiocarcinoma who had been admitted to gastroenterology ward of our hospital from 2004 to 2011 were retrospectively reviewed. Results: 283 patients (180 male, 63%, and 103 female, 38.6%) with a mean age of $59.7{\pm}14.4$ years were studied. The most frequent symptoms were painless jaundice (190, 66.9%), abdominal pain (77, 27%), pruritus 133 (46.8%) and weight loss (169, 59.5%). The most frequent associated risk factors and diseases were as follows: gallstones (72, 25.4%), diabetes (70, 24.6%), HBV infection (52 (18.3%), HCV infection 43 (15%), primary sclerosing cholangitis (16, 5.6%) and smoking (120, 42.3%). The most frequent type of cholangiocarcinoma in ERCP and MRCP was hilar. The mean survival time was $7.42{\pm}5.76$ months. Conclusion: The mean survival time in our study was lower than one year. Moreover the most frequent risk factors and associated diseases were smoking, gallstones and diabetes. Painless jaundice, abdominal pain and weight loss were the most clinical features related to cholangiocarcinoma. Additionally survival time did not correlate with risk factors, associated diseases and clinical presentations, but was linked to biliary metallic stenting and surgery.

Amoui, Mahasti;Akbari, Mohammad Esmail;Tajeddini, Araam;Nafisi, Nahid;Raziei, Ghasem;Modares, Seyed Mahdi;Hashemi, Mohammad 5385

https://doi.org/10.7314/APJCP.2012.13.11.5385 PDF KSCI

Introduction: Sentinel lymph node biopsy (SLNB) is a precise procedure for lymphatic staging in early breast cancer. In a valid SLNB procedure, axillary lymph node dissection (ALND) can be omitted in nodenegative cases without compromising patient safety. In this study, detection rate, accuracy and false negative rate of SLNB for breast cancer was evaluated in a setting with simple modified conventional pathology facilities without any serial sectioning or immunohistochemistry. Material and Medthod: Patients with confirmed breast cancer were enrolled in the study. SLNB and ALND were performed in all cases. Lymph node metastasis was evaluated in SLN and in nodes removed by ALND to determine the false negative rate. Pathologic assessment was carried out only by modified conventional technique with only 3 sections. Detection rate was determined either by lymphoscintigraphy or during surgery. Results: 78 patients with 79 breast units were evaluated. SLN was detected in 75 of 79 cases (95%) in lymphoscintigraphy and 76 of 79 cases (96%) during surgery. SLN metastases was detected in 30 of 75 (40%) cases either in SLNB and ALND groups. Accuracy of SLNB method for detecting LN metastases was 92%. False negative rate was 3 of 30 of positive cases: 10%. In 7 of 10 cases with axillary lymphadenopathy, LN metastastates was detected. Conclusion: SLNB is recommended for patients with various tumor sizes without palpable lymph nodes. In modified conventional pathologic examination of SLNs, at least macrometastases and some micrometastases could be detected similar to ALND. Consequently, ALND could be omitted in node-negative cases with removal of all palpable LNs. We conclude that SLNB, as one of the most important developments in breast cancer surgery, could be expanded even in areas without sophisticated pathology facilities.

Inandiklioglu, Nihal;Yilmaz, Sema;Demirhan, Osman;Erdogan, seyda;Tanyeli, Atila 5391

https://doi.org/10.7314/APJCP.2012.13.11.5391 PDF KSCI

Background: Neuroblastoma (NB), like most human cancers, is characterized by genomic instability, manifested at the chromosomal level as allelic gain, loss or rearrangement. Genetics methods, as well as conventional and molecular cytogenetics may provide valuable clues for the identification of target loci and successful search for major genes in neuroblastoma. We aimed to investigate AURKA and MYCN gene rearrangements and the chromosomal aberrations (CAs) to determine the prognosis of neuroblastoma. Methods: We performed cytogenetic analysis by G-banding in 25 cases [11 girls (44%) and 14 boys (66%)] and in 25 controls. Fluorescence in situ hybridization (FISH) with AURKA and MYCN gene probes was also used on interphase nuclei to screen for alterations. Results: Some 18.4% of patient cells exhibited CAs., with a significant difference between patient and control groups in the frequencies (P<0.0001). Some 72% of the cells had structural aberrations, and only 28% had numerical chnages in patients. Structural aberrations consisted of deletions, translocations, breaks and fragility in various chromosomes, 84% and 52% of the patients having deletions and translocations, respectively. Among these expressed CAs, there was a higher frequency at 1q21, 1q32, 2q21, 2q31, 2p24, 4q31, 9q11, 9q22, 13q14, 14q11.2, 14q24, and 15q22 in patients. 32% of the patients had chromosome breaks, most frequently in chromosomes 1, 2, 3, 4, 5, 8, 9, 11, 12, 19 and X. The number of cells with breaks and the genomic damage frequencies were higher in patients (p<0.001). Aneuploidies in chromosomes X, 22, 3, 17 and 18 were most frequently observed. Numerical chromosome abnormalities were distinctive in 10.7% of sex chromosomes. Fragile sites were observed in 16% of our patients. Conclusion: Our data confirmed that there is a close correlation between amplification of the two genes, amplification of MYCN possibly contributing significantly to the oncogenic properties of AURKA. The high frequencies of chromosomal aberrations and amplifications of AURKA and MYCN genes indicate prognostic value in children with neuroblastomas and may point to contributing factors in their development.

Motawi, Tarek M.K.;Zakhary, Nadia I.;Salman, Tarek M.;Tadros, Samer A. 5399

https://doi.org/10.7314/APJCP.2012.13.11.5399 PDF KSCI

Aims and Background: Human leukocyte antigen-G and interleukin-2 receptor play pivotal roles in the proliferation of lymphocytes, and thus generation of immune responses. Their overexpression has been evidenced in different malignant hematopoietic diseases. This study aimed to validate serum soluble human leukocyte antigen-G (sHLA-G) and serum soluble interleukin-2 receptor (sIL-2R) as an additional tool for the diagnosis and follow up of acute lymphoblastic leukemia (ALL). Subjects and Methods: Both markers were determined by ELISA in the serum of 33 ALL pediatric patients before treatment and after intensification phase of chemotherapy as well as in the serum of 14 healthy donors that were selected as a control group. Results: ALL patients showed abnormal CBC and high serum lactate dehydrogenase, which were improved after chemotherapy. Also, there was a non-significant increase in serum sHLA-G in ALL patients compared with the control group. However, after chemotherapy, sHLA-G was increased significantly compared with before treatment. On the other hand, serum sIL-2R in ALL patients was increased significantly compared with the control group. After chemotherapy, sIL-2R decreased significantly compared with before treatment. Conclusions: From these results it could be suggested that measurement of serum sHLA-G might be helpful in diagnosis of ALL, while sIL-2R might be useful in diagnosis and follow-up of ALL in pediatric patients.

Hassan, Zeinab Korany;Al-Olayan, Ebtisam M. 5405

https://doi.org/10.7314/APJCP.2012.13.11.5405 PDF KSCI

Curcumin (CM), a biphenyl compound, possesses anti-inflammatory, antioxidant and antimicrobial activity. MicroRNAs (miRNAs) are small noncoding RNAs which regulate gene expression and the molecular mechanisms of several biological processes. Liver fibrosis is a major cause of hepatic dysfunction and cancer and there are few effective therapies emphasizing the need for new approaches to control. The present study was conducted to investigate the effect of curcumin (CM) on liver fibrosis through modulating the expression level of miRNAs (199 and 200), the main miRNAs associated with liver fibrosis. Induction of liver fibrosis by carbon tetrachloride ($CCL_4$) was confirmed by histopathological examination. Mice were divided into 3 groups: group 1 were i.p injected with 10% $CCL_4$ twice weekly for 4 weeks and then once a week for the next 4 weeks followed by 4 weeks with olive oil only. Group 2 were i.p injected with 10% $CCL_4$ twice weekly for 4 weeks and then once a week for the next 4 weeks followed by curcumin (5 mg/mouse/day) once daily for the next 4 weeks. The third group was injected with olive oil. The expression level of miR-199 and miR-200 and some of their targeted genes were measured by real time PCR. miRNA (199 and 200) levels were significantly elevated in liver fibrotic tissues compared to control groups. Curcumin was significantly returned the expression levels of mir-199 and -200 with their associated target gene nearly to their normal levels. This is the first study that highlighted the effect of curcumin on liver fibrosis through regulation of miRNAs.

Geng, Chuan-Ying;Liu, Nian;Yang, Guang-Zhong;Liu, Ai-Jun;Leng, Yun;Wang, Hui-Juan;Li, Li-Hong;Wu, Yin;Li, Yan-Chen;Chen, Wen-Ming 5409

https://doi.org/10.7314/APJCP.2012.13.11.5409 PDF KSCI

At present, multiple myeloma (MM) remains an incurable disease and cologenic cells may be responsible for disease relapse. It has been proposed that CD20+/CD138- NCI-H929 cells could be hallmarks of MM clonogenic cells. Here, the immunology phenotype of NCI-H929 cells is described. Only a small population of CD20+/CD138- cells (<1%) was found in the NCI-H929 cell line, but CD20+/CD138- cells were not detected. We found that CD20+/CD138+ cells were able to exhibit cologenic capacity by colony formation assay and continuous passage culture. Proteins were analyzed by 1D-SDS-PAGE and TMT based quantitative differential liquid chromatography tandem mass spectrometry (LC-MS/MS). 1,082 non-redundant proteins were identified, 658 of which were differentially expressed with at least a 1.5-fold difference. 205 proteins in CD20+ cells were expressed at higher levels and 453 proteins were at lower levels compared with CD20- cells. Most proteins had catalytic and binding activity and mainly participated in metabolic processes, cell communication and molecular transport. These results proved that there are different biological features and protein expression profile between CD20+ and CD20- cells in the NCI-H929 cell line.

Lin, Jian-Ying;Wang, Ming-Sheng;Dong, Liang-Peng;Xu, Da-Wei;Wang, Ying;Li, Xue-Liang;Li, Xiu-Min 5415

https://doi.org/10.7314/APJCP.2012.13.11.5415 PDF KSCI

The aim of this study was to investigate QoL (quality of life) of patients with esophageal cancer in northern Henan province, China, and to accurate evaluate and reflect the relationship between patient characteristics and QoL. In the high risk area of esophageal cancer in the north of Henan province, 735 patients with esophageal cancer were investigated. The Eysenck personality questionnaire (EPQ) and QoL were analyzed by using the questionnaire of general situation, EPQ, QLQ-C30 and QLQ-OES18. The effects of personal character on the QoL of esophageal carcinoma patients were analyzed by SPSS 11.0 software. The QoL of esophageal cancer patients in Northern Henan region was significantly affected by character. The difference between choleric and type of melancholic temperament types was significant (P<0.01), also in OESEAT, OESTA, OESCO and OESSP (P<0.05). Differences in personal character can thus influence the quality of esophageal cancer patient lives.

Yang, Xiao-Fei;Sun, Ai-Ning;Yin, Jia;Cai, Cheng-Sen;Tian, Xiao-Peng;Qian, Jun;Chen, Su-Ning;Wu, De-Pei 5421

https://doi.org/10.7314/APJCP.2012.13.11.5421 PDF KSCI

A monosomal karyotype (MK), defined as ${\geq}2$ autosomal monosomies or a single monosomy in the presence of additional structural abnormalities, was recently identified as an independent prognostic factor conveying an extremely poor prognosis in patients with acute myeloid leukemia (AML). In the present study, after excluding patients with t(15;17), t(8;21), inv(16) and normal karyotypes, 324 AML patients with cytogenetic abnormalities were the main subject of analysis. The incidences of MK were 13% in patients aged 15 to 60 years and 18% in those between 15 and 88 years old. MK was much more prevalent among elderly patients (p < 0.001) and was significantly associated with the presence of -7, -5, del(5q), abn12p, abn17p, -18 or 18q-, -20 or 20q- and CK (for all p < 0.001 except for abn12p p=0.009), and +8 or +8q was less frequent in MK+ AML(p=0.007). No correlation was noted between monosomal karyotype and FAB subtype (p > 0.05); MK remained significantly associated with worse overall survival among patients with complex karyotype (p=0.032); A single autosomal monosomy contributed an additional negative effect in OS of patients with structural cytogenetic abnormalities (P=0.008). This report presents the prevalence, feature and prognostic impact of MK among a large series of Chinese AML patients from a single center for the first time.

Lin, Jia-Ying;Qin, Jin-Bao;Li, Xiao-Yan;Dong, Ping;Yin, Bing-De 5427

https://doi.org/10.7314/APJCP.2012.13.11.5427 PDF KSCI

Background and Purpose: Ovarian cancer is the leading cause of death among gynecologic cancers because of the lack of effective early detection methods. Accuracies of the human epididymis protein 4 (HE4) and mesothelin in detecting ovarian cancer have never been systematically assessed. The current systematic review aimed to tackle this issue. Methods: MEDLINE, EMBASE, and Cochrane databases were searched (September 1995-November 2011) for studies on the diagnostic performances of HE4 and mesothelin in differentiating ovarian cancer from other benign gynecologic diseases. QUADAS items were used to evaluate the qualities of the studies. Meta-DiSc software was used to handle data from the included studies and to examine heterogeneity. All included studies for diagnostic performance were combined with sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratios (DORs) with 95% confidence intervals (CIs), summary receiver operating characteristic (SROC) curves, and areas under the SROC curves (AUC). Results: A total of 18 studies and 3,865 patients were eligible for the final analysis. The pooled sensitivity estimates for HE4 (74.4%) were significantly higher than those for mesothelin (49.3%). The pooled specificity estimates for mesothelin (94.5%) were higher than those for HE4 (85.8%). The pooled DOR estimates for HE4 (26.22) were higher than those for mesothelin (24.01). The SROC curve for HE4 showed better diagnostic accuracy than that for mesothelin. The PLR and NLR of HE4 were 6.33 (95% CI: 3.58 to 11.18) and 0.27 (95% CI: 0.21 to 0.34), respectively. The PLR and NLR for mesothelin were 11.0 (95% CI: 6.21 to 19.59) and 0.51 (95% CI: 0.42 to 0.62), respectively. The combination of the two tumor markers or their combination with CA-125 increased sensitivity and specificity to different extents. Conclusion: The diagnostic accuracy of HE4 in differentiating ovarian cancer from other benign gynecologic diseases is better than that of soluble mesothelin-related protein. Combinations of two or more tumor markers show more sensitivity and specificity.

Zekri, Abdel-Rahman N.;Hassan, Zeinab K.;Bahnassy, Abeer A.;Sherif, Ghada M.;ELdahshan, Dina;Abouelhoda, Mohamed;Ali, Ahmed;Hafez, Mohamed M. 5433

https://doi.org/10.7314/APJCP.2012.13.11.5433 PDF KSCI

Background: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. Patients and Methods: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. Result: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein ($AFP{\geq}600$ IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. Conclusion: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.

Sun, Jie;Xiong, Ju;Zhen, Yan;Chen, Zhao-Lun;Zhang, Hua 5439

https://doi.org/10.7314/APJCP.2012.13.11.5439 PDF KSCI

Objective: To explore the correlation of human papillomavious (HPV) infection with expression of p53 and proliferating cell nuclear antigen (PCNA) in patients with different ethnicity in Xinjiang, China. Methods: 166 biopsy specimens from 83 laryngeal squamous cell carcinomas (LSCC), 63 laryngeal papillomas (LP), and 20 laryngeal inflammatory polyps (LIP) were included in this study. HPV infection was determined by polymerase chain reaction (PCR) using specific types of HPV primers. Expression of p53 and PCNA was assessed using immunohistostaining. Results: The frequency of HPV 6/11 was higher in LP (33.3%) than in LSCC (9.6%) (P<0.0005), whereas the frequency of HPV 16/18 was higher in LSCC (37.3 %) than in LP (6.3%) (P<0.0005). Patients of the Han ethnic group with LSCC had a higher infection rate with HPV 6/11 or HPV 6/11 and HPV 16/18 coinfection than those of Uygur and Kazak ethnicity (P<0.05). Overexpression of p53 and PCNA were higher in LSCC (62.7%, 57.8%) than in LP (38%, 33.3%) (P<0.005, and P<0.005, respectively). That of p53 was not associated with lymph-node metastases and clinical stages, but overexpression of PCNA closely correlated with clinical stage. Conclusions: These results strongly implicate HPV6/11 infection in the carcinogenesis of LSCC and LP, respectively. There was a higher coincidence of increased malignancy of laryngeal tumors with overexpression of p53 and PCNA. Overexpression of p53 may serve as an early risk marker for malignant transformation in HPV infected cells while the overexpression of PCNA may serve as a late marker for progression of LSCC.

Bidgoli, Sepideh Arbabi;Khorasani, Hoda;Keihan, Heideh;Sadeghipour, Alireza;Mehdizadeh, Abolfazl 5445

https://doi.org/10.7314/APJCP.2012.13.11.5445 PDF KSCI

Although benign uterine leiomyomata (LMA) is the most common reproductive tumor in premenopausal women, its etiology is largely unknown. We aimed in the present study to demonstrate the potential role of environmental factors with estrogenic activity in tumor etiology by focusing on the role of aryl hydrocarbon receptor (AhR) which mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This case-control study aimed to compare the interactions between AhR and lifestyle factors in a clinical setting for the first time among 138 newly diagnosed LMA patients and 138 normal controls who lived in Tehran and Mashhad, respectively, during the last 10 years. To conduct immunohistochemical studies using appropriate monoclonal antibodies, 30 cases were selected retrospectively from 2009-2011 from the pathology departments of two university hospitals in Tehran. Although the levels of sex steroid receptors were similar in adjacent myometrium and uterine leiomyomas of all cases, AhR was significantly overexpressed (p=0.034, OR=1.667) in uterine LMA and this overexpression was correlated with living in Tehran [(p=0.04, OR=16 (1.216-210.58)], smoking[P=0.04, OR=2.085 (1.29-3.371)], living near polycyclic aromative hydrocarbon producing companies [p=0.007, OR=2.22 (1.256-3.926)] and eating grilled meat [p=0.042, OR=1.28 (1.92-3.842)]. Our study contributes to the understanding of the effects of EDCs on AhR levels as well as women's health and points out possible risk factors for the development and growth of uterine LMA. It seems that the development of LMA could be the result of interactions between hormonal and environmental factors.

Ren, Yong-Qiang;Han, Ju-Qiang;Cao, Jian-Biao;Li, Shao-Xiang;Fan, Gong-Ren 5451

https://doi.org/10.7314/APJCP.2012.13.11.5451 PDF KSCI

Objective: The objective of this study was to evaluate the association of MDR1 gene polymorphisms with susceptibility to hepatocellular carcinoma (HCC). Methods: A total of 689 HCC patients and 680 cancer-free subjects were enrolled. Human MDR1 gene polymorphisms were investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Multiple logistic regression models were applied to estimate the association between MDR1 gene polymorphisms and susceptibility to HCC. Results: We detected a novel c.4125A>C polymorphism and our findings suggested that this variant was significantly associated with susceptibility to HCC. A significantly increased susceptibility to HCC was noted in the homozygote comparison (CC versus AA: OR=1.621, 95% CI 1.143-2.300, ${\chi}^2$=7.4095, P=0.0065), recessive model (CC versus AC+AA: OR=1.625, 95% CI 1.167-2.264, ${\chi}^2$=8.3544, P=0.0039) and allele contrast (C versus A: OR=1.185, 95% CI 1.011-1.389, ${\chi}^2$=4.4046, P=0.0358). However, no significant increase was observed in the heterozygote comparison (AC versus AA: OR=0.995, 95% CI 0.794-1.248, ${\chi}^2$=0.0017, P=0.9672) and dominant model (CC+AC versus AA: OR=1.106, 95% CI 0.894-1.369, ${\chi}^2$=0.8560, P=0.3549). Conclusions: These findings suggest that the c.4125A>C polymorphism of the MDR1 gene might contribute to susceptibility to HCC in the Chinese population. Further work will be necessary to clarify the relationship between the c.4125A>C polymorphism and susceptibility to HCC on larger populations of diverse ethnicity.

Wang, Ting-Ting;Wang, Shao-Kang;Huang, Gui-Ling;Sun, Gui-Ju 5455

https://doi.org/10.7314/APJCP.2012.13.11.5455 PDF KSCI

Luteolin is a plant flavonoid which exhibits anti-oxidative, anti-inflammatory and anti-tumor effects. However, the antiproliferative potential of luteolin is not fully understood. In this study, we investigated the effect of luteolin on cell cycling and apoptosis in human esophageal squamous carcinoma cell line Eca109 cells. MTT assays showed that luteolin had obvious cytotoxicity on Eca109 with an $IC_{50}$ of $70.7{\pm}1.72{\mu}M$ at 24h. Luteolin arrested cell cycle progression in the G0/G1 phase and prevented entry into S phase in a dose- and time-dependent manner. as assessed by FCM. Luteolin induced apoptosis of Eca109 cells was demonstrated by AO/EB staining assay and annexin V-FITC/PI staining. Moreover, luteolin downregulated the expression of cyclin D1, survivin and c-myc, and it also upregulated the expression of p53, in line with the fact that luteolin was able to inhibit Eca109 cell proliferation.

Afshar, Reza Malekpour;Mollaie, Hamid Reza 5463

https://doi.org/10.7314/APJCP.2012.13.11.5463 PDF KSCI

Hepatitis B virus (HBV) infection is contagious with transmissiobn vertically or horizontally by blood products and body secretions. Over 50% of Iranian carriers contracted the infection prenatally, making this the most likely route of transmission of HBV in Iran. To evaluate the resistance to adefovir (ADV) therapy in patients with chronic hepatitis B infection, a study was conducted on 70 patients (63 males and 7 females), who had received in first line lamivudine and second line adefovir. All were tested for the presence of hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), serum alanine amino transferase (ALT) level and HBV DNA load before and after treatment with ADV. In all samples, resistance to lamivudine and ADV was tested with real time PCR. Among seventy patients with chronic hepatitis B infection, 18 (25.7%) were resistant to LAM and 8 (11.4%) were resistant to ADV. Only one patient was negative for the presence of HBS-Ag (5.6%) and two were negative for HBe-Ag (11.1%). In this study we used a new method (ALLGIO probe assay) that has high sensitivity in detection of adefovir resistance mutants, which we recommend to other researchers. Mutant strains of the YMDD motif of HBV polymerase can be found in some patients under treatment with lamivudine and ADV. ADV has been demonstrated to be efficient in patients with lamivudine resistant HBV.

Awan, Tashfeen;Iqbal, Zafar;Aleem, Aamer;Sabir, Noreen;Absar, Muhammad;Rasool, Mahmood;Tahir, Ammara H.;Basit, Sulman;Khalid, Ahmad Mukhtar;Sabar, Muhammad Farooq;Asad, Sultan;Ali, Agha Shabbir;Mahmood, Amer;Akram, Muhammad;Saeed, Tariq;Saleem, Arsalan;Mohsin, Danish;Shah, Ijaz Hussain;Khalid, Muhammad;Asif, Muhammad;Haq, Riazul;Iqbal, Mudassar;Akhtar, Tanveer 5469

https://doi.org/10.7314/APJCP.2012.13.11.5469 PDF KSCI

Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

Keyhani, Elahe;Muhammadnejad, Ahad;Karimlou, Masoud 5477

https://doi.org/10.7314/APJCP.2012.13.11.5477 PDF KSCI

Background: The HER-2/neu gene is altered in 15-20% of breast cancer patients. Immunohistochemistry (IHC) is considered to be the most cost-effective method for HER-2 detection in many countries. Approximately 8,000 new cases of breast cancer are observed annually in Iran. The aims of this study were to conduct a systematic review of the literature on the rate of HER-2-positive breast cancer diagnosed by IHC in Iran. Methods: A systematic search of the medical literature using the Medline/PubMed, ISI and SID databases revealed articles published in the English and Persian languages evaluating HER-2-positive breast cancer in Iran. Results: From 22 studies, 3,033 patients were evaluated, of whom 1,350 were diagnosed as HER-2-positive by IHC HER-2 testing. The mean percentage of HER-2-positive patients was 44.5%, which is higher than that recorded in international statistics. Results of this meta-analysis showed a significant heterogeneity between ratios. There was a statistically significant difference between the results of pre- and post implementation of 2007 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline. IHC HER-2 testing has been performed in Iran for over 10 years. Similar to many other countries, before establishment of an infrastructure for IHC diagnostic tests, HER-2 testing was routinely performed in Iran. Our study showed that the statistics reported from Iran varied widely; for instance, the rate of HER-2-positive cases varied from 23.3% to 81.0%. Conclusions: Our results demonstrate that the lack of standardization and harmonization of this test have led to marked variations in breast cancer diagnosis in Iran.

Jung, Hyun-Suk;Kim, Yeol;Son, Jungsik;Jeon, Young-Jee;Seo, Hong-Gwan;Park, So-Hee;Huh, Bong Ryul 5483

https://doi.org/10.7314/APJCP.2012.13.11.5483 PDF KSCI

Background: Although nicotine dependence plays a role as a main barrier for smoking cessation, there is still a lack of solid evidence on the validity of biomarkers to determine nicotine dependence in clinical settings. This study aimed to investigate whether urinary cotinine levels could reflect the severity of nicotine dependence in active smokers. Materials and Methods: Data regarding general characteristics and smoking status was collected using a self-administered smoking questionnaire. The Fagerstr$\ddot{o}$m test for nicotine dependence (FTND) was used to determine nicotine dependence of the participants, and a total of 381 participants were classified into 3 groups of nicotine dependence: low (n=205, 53.8%), moderate (n=127, 33.3%), and high dependence groups (n=49, 12.9%). Stepwise multiple linear regression model and receiver operating characteristic (ROC) curves analyses were used to determine the validity of urinary cotinine for high nicotine dependence. Results: In correlation analysis, urinary cotinine levels increased with FTND score (r=0.567, P<0.001). ROC curves analysis showed that urinary cotinine levels predicted the high-dependence group with reasonable accuracy (optimal cut-off value=1,000 ng/mL; AUC=0.82; P<0.001; sensitivity=71.4%; specificity=74.4%). In stepwise multiple regression analysis, the total smoking period (${\beta}$=0.042, P=0.001) and urinary cotinine levels (${\beta}$=0.234, P<0.001) were positively associated with nicotine dependence, whereas an inverse association was observed between highest education levels (>16 years) and nicotine dependence (${\beta}$=-0.573, P=0.034). Conclusions: The results of this study support the validity of using urinary cotinine levels for assessment of nicotine dependence in active smokers.

Natphopsuk, Sitakan;Settheetham-Ishida, Wannapa;Sinawat, Supat;Pientong, Chamsai;Yuenyao, Pissamai;Ishida, Takafumi 5489

https://doi.org/10.7314/APJCP.2012.13.11.5489 PDF KSCI

Cervical cancer is a serious public health problem in Thailand. We investigated possible risk factors for cervical cancer including HPV infection, p53 polymorphism, smoking and reproductive history among women in Northeast Thailand using a case control study with 177 cases and age-matched controls. Among the HPV carriers, a significantly increased risk for cervical cancer with an OR of 36.97(p<0.001) and an adjusted OR of 38.07(p<0.001) were observed. Early age at first sexual exposure, and multiple sexual partners increased the risk of cervical cancer with ORs ranging between 1.73-2.78(p<0.05). The interval between menarche and first sexual intercourse <6 years resulted in a significant increase in the risk for cervical cancer with ORs ranging between 3.32-4.09 and the respective adjusted OR range for the 4-5 and 2-3 year-old groups were 4.09 and 2.92. A higher risk was observed among subjects whose partner had smoking habits, whether currently or formerly; with respective ORs of 3.36(P<0.001) and 2.17(p<0.05); and respective adjusted ORs of 2.90(p<0.05) and 3.55(p<0.05). Other smoking characteristics of the partners including smoking duration ${\geq}20$ years, number of cigarettes smokes ${\geq}20$ pack-years and exposure time of the subject to passive smoking ${\geq}5$ hrs per day were found to be statistically significant risks for cervical cancer with adjusted ORs of 3.75, 4.04 and 11.8, respectively. Our data suggest that the risk of cervical cancer in Thai women is substantially associated with smoking characteristics of the partner(s), the interval between menarche and first sexual intercourse as well as some other aspects of sexual behavior.

Ahmed, Hussain Gadelkarim 5497

https://doi.org/10.7314/APJCP.2012.13.11.5497 PDF KSCI

Objective: The aim of this study was to assess the level of cancer awareness after delivering educational programs by assessing the awareness in regard to the role of microbial infectious agents in the etiology of some cancers. Methodology: Data were collected during Cancer Awareness and Educational Programs which were conducted at various places such as schools, clubs, mosques and Government health centres. This survey included 200 participants. Results: Of the persons who responded to the question, whether some viruses, bacteria, parasites and fungi, can cause cancer, 111/134 (82.8%), 105/129 (81.4%), 102/124 (82.8%) and 95/122 (77.8%), respectively, answered yes. Conclusion: The level of cancer awareness is low amongst Sudanese northern state inhabitants even after delivering an educational program.

Kritpetcharat, Onanong;Wutichouy, Wiwat;Sirijaichingkul, Suchat;Kritpetcharat, Panutas 5501

https://doi.org/10.7314/APJCP.2012.13.11.5501 PDF KSCI

Cervical cancer is an important woman's health problems worldwide, especially in low socio-economic countries. The aim of this study was to compare the Pap smear screening results between Akha hill tribe and urban women who live in Chiang Rai province, Thailand. Screening was conducted for 1,100 Akha women and 1,100 urban women who came to have the Pap smear at Chiangrai Prachanukroh Hospital and 1 private cytology laboratory from January to June 2008. The demographic characteristics and factors related to abnormal Pap smears of these women were gathered using closed model questionnaires. Abnormal Pap smears were defined according to the Bethesda 2001 system. The results showed that the prevalence of abnormal Pap smears was 12.2% in Akha women and 4.5% in urban women. The highest prevalence of Pap abnormalities was found in the 41-50 years age group in both populations (4.5% in Akha and 1.7% in urban women). In both populations, abnormal Pap smears were found in <21 years age groups. From the questionnaires, the possible risk factors related to the higher prevalence of abnormal Pap smears in Akha women were early age at marriage (${\leq}17$ years), high frequency pregnacies and high parity and no/low education level. In conclusion, cervical cancer control by education and early detection by Pap smear screening is necessary for hill tribe women. More Pap smear screening service units should be set to improve the coverage for the risk group women who got married in young age, especial in ethnic groups.

Xie, Xiu-Zhen;Song, Kun;Cui, Baoxia;Jiang, Jie;Zhang, You-Zhong;Wang, Bo;Yang, Xing-Sheng;Kong, Bei-Hua 5505

https://doi.org/10.7314/APJCP.2012.13.11.5505 PDF KSCI

Objective: The aim of this retrospective study is to analyze the clinical and pathological factors related to the prognosis of Chinese patients with stage Ib to IIb cervical cancer. Methods and Results: 13 clinical pathological factors in 255 patients with stage Ib to IIb cervical cancer undergoing radical hysterectomy and systematic lymphadenectomy were analyzed to screen for factors related to prognosis. The cumulative 5-year survival of the 255 patients was 75.7%. The result of the univariate analysis suggested that clinical stage, cell differentiation, depth of cervical stromal invasion, parametrial tissue involvement, and lymph node metastasis were prognostic factors for patients with stage Ib to IIb cervical cancer (P<0.05). Compared with cases with involvement of iliac nodes, obturator nodes, or inguinal lymph nodes, cases with metastasis to the common iliac lymph nodes had a poorer prognosis (P<0.05). Cases with involvement of four or more lymph nodes had a poorer prognosis than those with involvement of three or fewer lymph nodes (P<0.05). Using multivariate Cox proportional hazards model regression analysis, non-squamous histological type, poor differentiation, parametrial tissue involvement, and outer 1/3 stromal invasion were found to be independently related to patients poor prognosis (P<0.05). Conclusion: Non-squamous histological type, poor cell differentiation, parametrial tissue involvement, and outer 1/3 stromal invasion are the independent poor prognostic factors for patients with stage Ib to IIb cervical cancer.

Jana, Debarshi;Das, Soumen;Sarkar, Diptendra Kumar;Mandal, Syamsundar;Maji, Abhiram;Mukhopadhyay, Madhumita 5511

https://doi.org/10.7314/APJCP.2012.13.11.5511 PDF KSCI

Introduction: The nuclear factor ${\kappa}B$ (NF-${\kappa}B$) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-${\kappa}B$ /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. Materials and Methods: In this hospital based study 57 breast cancer patients attending a Breast Clinic of a reputed institute of Eastern India were assessed for p65 protein expression in breast tumor tissue samples by Western blotting. ER, PR and HER-2/neu expression was determined by immunohistochemistry. Results: NF-${\kappa}B$/p65 was significantly associated with advanced stage, large tumor size (${\geq}5$ cm), high grade, negative ER, negative PR, and positive HER-2/neu. High NF-${\kappa}B$/p65 expression was more frequent in patients with a high NPI ($NPI{\geq}5.4$, 84.6%) compared with low NPI (<5.4, 44.4%) and this association was statistically significant (p = 0.002). Conclusion: NF-${\kappa}B$/p65 overexpression was associated with advanced stage, large tumor size, high grade, and high NPI which are poor prognostic factors linked to enhanced aggressiveness of the disease. NF-${\kappa}B$/p65 expression implies aggressive biological behavior of breast cancer and this study validates significant association of NF-${\kappa}B$ /p65 overexpression with negative estrogen and progesterone receptor status and overexpression of HER-2/neu oncoprotein. In our good clinical practice, patients with NF-${\kappa}B$ positive tumors need to be treated aggressively.

Wang, Xi-Wen;Xiong, Yun-Hui;Zen, Xiao-Qing;Lin, Hai-Bo;Liu, Qing-Yi 5517

https://doi.org/10.7314/APJCP.2012.13.11.5517 PDF KSCI

Purpose: To evaluate the diagnostic accuracy of ultrasonograph and fine-needle aspiration cytologic examination (USG-FNAC) in the staging of axillary lymph node metastasis in breast cancer patients.Methods: We conducted an electronic search of the literature addressing the performance of USG-FNAC in diagnosis of axillary lymph node metastasis in databases such as Pubmed, Medline, Embase, Ovid and Cochrane library. We introduced a series of diagnostic test indices to evaluate the performance of USG-FNAC by the random effect model (REM), including sensitivity, specificity, likelihood ratios, and diagnostic odds ratios and area under the curve (AUC). Results: A total of 20 studies including 1371 cases and 1289 controls were identified. The pooled sensitivity was determined to be 0.66 (95% CI 0.64-0.69), specificity 0.98 (95% CI 0.98-0.99), positive likelihood ratio 22.7 (95% CI 15.0-34.49), negative likelihood ratio 0.32 (95% CI 0.25-0.41), diagnostic OR 84.2 (95% CI 53.3-133.0). Due to the marginal threshold effect found in some indices of diagnostic validity, we used a summary SROC curve to aggregate data, and obtained a symmetrical curve with an AUC of 0.942. Conclusion: The results of this meta-analysis indicated that the USG-FNAC techniques have acceptable diagnostic validity indices and can be used for early staging of axillary lymph node in breast cancer patients.

Haghighat, S.;Akbari, M.E.;Ghaffari, S.;Yavari, P. 5525

https://doi.org/10.7314/APJCP.2012.13.11.5525 PDF KSCI

Introduction: Breast cancer is the most common cancer in women. Improvements of early diagnosis modalities have led to longer survival rates. This study aimed to determine the 5, 10 and 15 year mortality rates of breast cancer patients compared to the normal female population. Materials and Methods: The follow up data of a cohort of 615 breast cancer patients referred to Iranian Breast Cancer Research Center (BCRC) from 1986 to 1996 was considered as reference breast cancer dataset. The dataset was divided into 5 year age groups and the 5, 10 and 15 year probability of death for each group was estimated. The annual mortality rate of Iranian women was obtained from the Death Registry system. Standardized mortality ratios (SMRs) of breast cancer patients were calculated using the ratio of the mortality rate in breast cancer patients over the general female population. Results: The mean age of breast cancer patients at diagnosis time was 45.9 (${\pm}10.5$) years ranging from 24-74. A total of 73, 32 and 2 deaths were recorded at 5, 10 and 15 years, respectively, after diagnosis. The SMRs for breast cancer patients at 5, 10 and 15 year intervals after diagnosis were 6.74 (95% CI, 5.5-8.2), 6.55 (95%CI, 5-8.1) and 1.26 (95%CI, 0.65-2.9), respectively. Conclusion: Results showed that the observed mortality rate of breast cancer patients after 15 years from diagnosis was very similar to expected rates in general female population. This finding would be useful for clinicians and health policy makers to adopt a beneficial strategy to improve breast cancer survival. Further follow-up time with larger sample size and a pooled analysis of survival rates of different centres may shed more light on mortality patterns of breast cancer.

Zheng, Xiang-Yi;Zhang, Peng;Xie, Li-Ping;You, Qi-Han;Cai, Bo-Sen;Qin, Jie 5529

https://doi.org/10.7314/APJCP.2012.13.11.5529 PDF KSCI

Aim: To investigate the utility of prostate-specific antigen velocity (PSAV) and PSAV per initial volume (PSAVD) for early detection of prostate cancer (PCa) in Chinese men. Methods: Between January 2009 and June 2012, a total of 193 men (aged 49-84 years, median 67 years) with at least 2 transrectal ultrasonography (TRUS) procedures and concurrent serum PSA measurements underwent prostate biopsy because of suspicion of PCa. The total group were classified into PCa and non-PCa groups, and the variables of the two groups were compared. Univariate and multivariate analyses were used to investigate which variables were predictove. The diagnostic values of PSAV, PSAVD and prostate-specific antigen density (PSAD) were compared using receiver operating characteristic (ROC) analysis. Results: Prostate cancer was diagnosed in 44 (22.8%) of the 193 men. There were significant differences between the groups in last and initial prostate volumes determined by TRUS, initial age, last serum PSA levels, PSAV, PSAD and PSAVD. After adjusting for confounding factors, the odds ratios of PCa across the quartile of PSAVD were 1, 4.06, 10.6, and 18.9 (P for trend <0.001).The area under the ROC curves (AUCs) of PSAD (0.779) and PSAVD (0.776) were similar and both significantly greater than that of PSA (AUC 0.667). PSAVD was a significantly better indicator of PCa than PSAV (AUC 0.736). There was no statistical significant difference between the AUC of PSAV and that of last serum PSA level. The sensitivity and specificity of PSAVD at a cutoff of 0.023ng in participants with last serum PSA levels of 4.0ng/mL-10.0ng was 73.7% and 70.7%, respectively. Conclusions: The results of this study demonstrated PSAVD may be a useful tool in PCa detection, especially in those undergoing previous TRUS examination.

Jayaraman, Bhaskar;Valiathan, Gopalakrishnan Mohan;Jayakumar, Keerthivasan;Palaniyandi, Arunmozhi;Thenumgal, Siji Jacob;Ramanathan, Arvind 5535

https://doi.org/10.7314/APJCP.2012.13.11.5535 PDF KSCI

Background: There have been case reports of oral squamous cell carcinoma arising from gingival overgrowth induced by phenytoin - an antiepileptic drug. However, a detailed analysis for the presence of mutations in p53 and ras genes, which are the two most frequently mutated genes in cancers, in phenytoin induced gingival overgrowth tissues has hitherto not been performed. Methods: Cellular DNA isolated from twenty gingival overgrowth tissues collected from patients undergoing phenytoin therapy were amplified using primers for p53 (exons 5-8) and H-ras (exons 1-2) genes. The PCR amplicons were then gel purified and subjected to direct sequencing analysis to screen for mutations. Results: Direct sequencing of twenty samples of phenytoin induced gingival growth did not identify mutations in any of the exons of p53 and H-ras genes that were analyzed. Conclusion: Our result indicates that mutational alteration of p53 and H-ras genes is infrequent in phenytoin induced gingival growth, which thus suggests a non malignant nature of this pathology. The findings in the present study are clinically significant as a large number of epileptic patients are treated with phenytoin.

Al-Naggar, Redhwan A.;Jawad, Ammar A.;Bobryshev, Yuri V. 5539

https://doi.org/10.7314/APJCP.2012.13.11.5539 PDF KSCI

Objective: The smoking prevalence in Malaysia is high, especially among men and adolescents. This study aimed to determine the prevalence and associated factors towards cigarette smoking among school teachers in Malaysia. Methodology: This study was a school-based cross-sectional study conducted among 495 secondary school teachers. The questionnaire used in this study consisted of 29 questions categorized into two sections: socio-demographic characteristics and smoking behaviour. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) program 13.0. ANOVA; t-tests were used in univariate analysis; multiple linear regression was applied for multivariate analysis. Results: The majority of the participants were female (81.6%), in the age group ranged between 30-39 years (44%), Malay (90.1%), married (89.7%), degree holders (85.1%), with monthly income ranged between 3000-3999 Ringgit Malaysia (33.5%), from urban areas (94.7%), their specialty is social studies (33.9%) and with no family history of cancer (83.6%). The prevalence of smoking among school teachers in Malaysia was found to be 7.8%. Regarding reasons to start smoking among school teachers: the major reason was found to be relaxation (33.3%), followed by stress-relief (28.2%). Univariate analysis showed that sex, educational status, monthly income and residency were significantly associated with smoking among school teachers (p<0.001, p=0.004, p=0.031, p=0.010; respectively). Multivariate analysis showed that gender and marital status were significantly associated with smoking among school teachers (p<0.001, p=0.033; respectively). Conclusion: The prevalence of smoking among school teachers in Malaysia was found to be relatively low. Sex, marital status, educational status, monthly income and residency were significantly associated with smoking among school teachers.

Wang, Hsiu-Ho;Chung, Yu-Chu;Sun, Jia-Ling 5545

https://doi.org/10.7314/APJCP.2012.13.11.5545 PDF KSCI

Aims: The purpose of this study was to investigate the effects of a breast cancer screening educational program on women's knowledge and intention to seek breast cancer screening in Taiwan. Materials and Method: This study describes the knowledge and intention of breast cancer screening changes during the period pre and post group education. A pre-test and post-test were used in both the experimental and the control groups. A convenience sampling was used. Two structured questionnaires were used. Results: The mean knowledge of breast cancer screening scores (pre-test and post-test) of the experimental group participants were 12.6 and 14.0. Then the mean knowledge of breast cancer screening scores (pre-test and post-test) of the control group participants were 11.8 and 12.1. The mean intention of breast cancer screening scores (pre-test and post-test) of the experimental group participants were 11.4 and 13.5. And the mean intention of breast cancer screening scores (pre-test and post-test) of the control group participants were 11.6 and 12.4. An independent-t test was applied to examine the differences among the two groups, revealing that the average post-test knowledge score differ significantly between the two groups (t =4.18, p<.00); and the post-test intention also demonstrate a marked statistical difference (t = 2.07, p<.05). A paired-t test was applied to examine the differences of each group, revealing that the total average scores of the experimental group participants on the knowledge of breast cancer screening scale clearly differ statistically (t =-5.54, p<.00); and the pre-test and post-test intention testing also demonstrate a marked statistical difference (t =-7.70, p<.00). Conclusions: These findings are helpful in understanding the knowledge and intention of breast cancer screening changes during the period pre and post group education. It is expected that these results can offer a reference for clinical breast cancer prevention.

Uchino, Junji;Takayama, Koichi;Nakagaki, Noriaki;Shuo, Wang;Hisasue, Junko;Nakatom, Keita;Ohta, Keiichi;Hirano, Ryosuke;Tashiro, Naoki;Miiru, Izumi;Fujita, Masaki;Watanabe, Kentaro;Nakanishi, Yoichi 5551

https://doi.org/10.7314/APJCP.2012.13.11.5551 PDF KSCI

Cytological examination is widely used as a diagnostic tool because of the ease of collecting cells from the involved area. However, the diagnostic yield of cytological examination is unsatisfactory; the reasons include sampling error, poorly prepared samples, small numbers of malignant cells, and low grades of cellular atypia. In this study, we focused on the high infectivity of adenovirus towards epithelial cells and applied the luciferase-expressing adenoviral vector to a new cancer cell detection tool. In addition, adenoviral infectivity was enhanced by modifying viral fiber proteins. The sensitivity of the diagnostic tool was tested using the NCI-H1299 lung cancer cell line, and validated in body fluid samples from cancer patients with a variety of etiology. Results showed that the adenovirus efficiently transfected NCI-H1299 with high sensitivity. Only 10 cancer cells were sufficient for detection of luciferase signals. In body fluid samples, the adenovirus confirmed the diagnosis for malignant and benign cancer, but not in non-epithelial cell derived samples. This study provides proof-of-concept for a more reliable and sensitive diagnostic tool for epithelium-derived cancer.

Wang, Yu-Qian;Zhang, Hai-Hong;Liu, Chen-Lu;Xia, Qiu;Wu, Hui;Yu, Xiang-Hui;Kong, Wei 5557

https://doi.org/10.7314/APJCP.2012.13.11.5557 PDF KSCI

Aim: The aim of this study was to investigate the frequency and correlation between auto-antibodies to survivin and MUC1 variable number tandem repeats (VNTR) in colorectal cancer (CRC), which can provide valuable information for the design of immunotherapeutic vaccines for this disease. Methods: Enzyme-linked immunosorbent assays (ELISA) were used to examine the level of auto-antibodies against survivin and MUC1 VNTR in the serum of 135 CRC patients and 95 healthy volunteers. Results: Using mean absorbance + 2 standard deviations (SD) of the healthy samples as a cut-off value, the positive rates of survivin and MUC1 VNTR auto-antibodies in CRC were 31.1% and 18.5%, respectively. Altogether, the survivin and MUC1 VNTR positive samples accounted for 36.3% of the CRC patients, and 7.4% were positive for both. Conclusion: A significant positive correlation was found between levels of specific antibodies against survivin and MUC1 VNTR in the serum of CRC patients (r = 0.3652, P < 0.0001), suggesting that vaccines against both targets would elicit immune responses more effectively.

Raja, Uthandaraman Mahalinga;Gopal, Gopisetty;Rajkumar, Thangarajan 5563

https://doi.org/10.7314/APJCP.2012.13.11.5563 PDF KSCI

Based on our previous report on gastric cancer which documented ATP4A and ATP4B mRNA down-regulation in gastric tumors relative to normal gastric tissues, we hypothesized that epigenetic mechanisms could be responsible. ATP4A and ATP4B mRNA expression in gastric cancer cell lines AGS, SNU638 and NUGC-3 was examined using reverse transcriptase PCR (RT-PCR). AGS cells were treated with TSA or 5'-AzaDC and methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis were performed. MSP analysis was on DNA from paraffin embedded tissues sections and plasma. Expression analysis revealed downregulation of ATP4A and ATP4B genes in gastric cancer cell lines relative to normal gastric tissue, while treatment with 5'-AzaDC re-activated expression of both. Search for CpG islands in their putative promoter regions did not indicate CpG islands (CGI) but only further downstream in the bodies of the genes. Methylation specific PCR (MSP) in the exon1 of the ATP4B gene and exon7 in ATP4A indicated methylation in all the gastric cancer cell lines tested. MSP analysis in tumor tissue samples revealed methylation in the majority of tumor samples, 15/19, for ATP4B and 8/8 for ATP4A. There was concordance between ATP4B and ATP4A down-regulation and methylation status in the tumour samples tested. ATP4B methylation was detectable in cell free DNA from gastric cancer patient's plasma samples. Thus ATP4A and ATP4B down-regulation involves DNA methylation and methylated ATP4B DNA in plasma is a potential biomarker for gastric cancer.

Mao, Xing-Jiang;Wang, Geng-Fu;Chen, Zhi-Jun;Wang, Li-Na;Zhang, Jun-Biao;Wang, Hui-Ling 5569

https://doi.org/10.7314/APJCP.2012.13.11.5569 PDF KSCI

Objectives: To evaluate the clinical significance of HMGB1 expression in T-cell lymphoma. Methods: Immunohistochemical staining for HMGB1 and survivin was performed with specimens from 120 cases of T-cell lymphoma and 40 cases of reactive lymphoid hyperplasia with antibodies against human HMGB1 and survivin. Results: The expression of HMGB1 and survivin was significantly higher in tissues of T-cell lymphoma than in reactive lymphoid hyperplasia. Positive expression of HMGB1 and survivin was observed in 63.7% (65/102) and 61.8% (63/102) of T-cell lymphoma cases, respectively. While was associated with gender, age, and tumor location, significant correlations with malignancy and clinical stage were observed. Spearman rank correlation analysis revealed that the expression of HMGB1 and survivin was positively correlated in T-cell lymphomas (P<0.01). Conclusions: Expression of HMGB1 and survivin in T-cell lymphomas is significantly associated with malignancy and clinical stage, but not with gender, age and tumor location. Elevated expression of HMGB1 may be an important biomarker for the development and progression of T-cell lymphoma.

Wang, Yi;Tian, Wei-Xi;Ma, Xiao-Feng 5573

https://doi.org/10.7314/APJCP.2012.13.11.5573 PDF KSCI

Onions (Allium cepa L.) are widely used in the food industry for its nutritional and aromatic properties. Our studies showed that ethyl acetate extract of onion (EEO) had potent inhibitory effects on animal fatty acid synthase (FAS), and could induce apoptosis in FAS over-expressing human breast cancer MDA-MB-231 cells. Furthermore, this apoptosis was accompanied by reduction of intracellular FAS activity and could be rescued by 25 mM or 50 mM exogenous palmitic acids, the final product of FAS catalyzed synthesis. These results suggest that the apoptosis induced by EEO occurs via inhibition of FAS. We also found that EEO could suppress lipid accumulation during the differentiation of 3T3-L1 adipocytes, which was also related to its inhibition of intracellular FAS activity. Since obesity is closely related to breast cancer and obese patients are at elevated risk of developing various cancers, these findings suggested that onion might be useful for preventing obesity-related malignancy.

Liu, Guo-Bing;Qu, Yan-Juan;Liao, Mei-Yan;Hu, Hui-Juan;Yang, Gui-Fang;Zhou, Su-Jun 5581

https://doi.org/10.7314/APJCP.2012.13.11.5581 PDF KSCI

Objective: To explore the relationship between computed tomography (CT) manifestations of thymoma and its WHO pathological classification. Methods: One hundred and five histopathologically confirmed cases were collected for their pathological and CT characteristics and results were statistically compared between different pathological types of thymoma. Results: Tumor size, shape, necrosis or cystic change, capsule integrity, invasion to the adjacent tissue, lymphadenopathy, and the presence of pleural effusion were significantly different between different pathological types of thymomas (P<0.05). Type B2, B3 tumors and thymic carcinomas were greater in size than other types. More than 50% of type B3 tumors and thymic carcinomas had a tumor size greater than 10 cm. The shape of types A, AB, and B1 tumors were mostly round or oval, whereas 75% of type B3 tumors and 85% of thymic carcinomas were irregular in shape. Necrosis or cystic change occurred in 67% of type B3 thymomas and 57% of thymic carcinomas, respectively. The respective figures for capsule destruction were 83% and 100%. Increases in the degree of malignancy were associated with increases in the incidence of surrounding tissue invasion: 33%, 75%, and 81% in type B2, type B3, and thymic carcinomas, respectively. Pleural effusion occurred in 48% of thymic carcinomas, while calcification was observed mostly in type B thymomas. Conclusions: Different pathological types of thymic epithelial tumors have different CT manifestations. Distinctive CT features of thymomas may reflect their pathological types.

Gu, Ming;Li, Su-Yi;Huang, Xin-En;Lin, Yan;Cheng, Hong-Yan;Liu, Lin 5587

https://doi.org/10.7314/APJCP.2012.13.11.5587 PDF KSCI

Objective: This study was performed to evaluated the efficacy and safety of continuous infusional paclitaxel and 5-Fu as first-line chemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Methods: A total of 22 patients with advanced esophageal squamous cell cancer with no indications for surgery and radiation therapy, or recurrent patients were enrolled from October 2008 to November 2010. All were treated with PTX 20 $mg/m^2$ was administered through a 16 hours continuous intravenous infusion on days 1 to 3, 8 and 9. DDP 3.75 $mg/m^2$ was given on days 1 to 4 and 8 to 11, continuous infusional 5-FU over 24-hours on days 1 to 5 and 8 to 12 at a dose of 375 $mg/m^2$, and folacin 60 mg orally synchronized with 5-Fu. The treatment was repeated every 21 days for at least two cycles. Results: 22 cases of all enrolled patients could be evaluated for the effect of treatment: 2 cases were CR, 9 cases PR, 5 cases SD and 2 cases PD, giving an overall response rate of 68.2%(15/22). The median time to progression was 7.0 months. The adverse reactions related to chemotherapy were tolerable; the most common toxic effects were marrow depression, alopecia, and fatigue. Conclusion: Low-dose continuous infusional PTX over 16-hours and 5-fu over 24-hours is a promising regimen with good tolerability in treating patients with advanced esophageal squamous cell cancer.

Yavuzsen, T.;Karadibak, D.;Cehreli, R.;Dirioz, M. 5593

https://doi.org/10.7314/APJCP.2012.13.11.5593 PDF KSCI

Purpose: The aim of this study was to evaluate the effects of the group therapy on psychological symptoms and quality of life of patients with early stage breast cancer. Methods: This study was performed on 16 breast cancer patients who completed treatments. The total group therapy program involved a weekly session of 2-3 hours, for 16 weeks. The group therapy sessions were given to women in the oncology department by a clinical psychologist and also given training sections by the different professional teams. All the required assessments for the study were performed after and before 16 week group therapy intervention. Results: Initially we had taken 21 women but 16 participated in all therapy programs and submitted questionnaires. The mean age was 47.8 years. There were significant differences between before and after group therapy program. Anxiety, depression, and distress showed significant improvements. Hopelessness scale was detected at the border of significance. There was no change in sleep problems and quality of life. According to the analysis of correlation, considering the age factor and year of diagnosis, there was found no statistically significant relationship between anxiety, distress, depression, hopelessness, sleeplessness, and quality of life. Conclusions: This pilot study demonstrated that brief, predominantly group therapy is feasible for patients with breast cancer and, also it may be helpful to cope with emotional and physical distress.

Tong, Lin;Yang, Xue-Xi;Liu, Min-Feng;Yao, Guang-Yu;Dong, Jian-Yu;Ye, Chang-Sheng;Li, Ming 5599

https://doi.org/10.7314/APJCP.2012.13.11.5599 PDF KSCI

Background: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer treatment; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. Methods: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. Results: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.50%) in the KRAS gene (rs121913530, rs112445441), and nine (7.50%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.27%) of the 22 genotyping assays called mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. Conclusions: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.

Bhattacharjee, Biplab;Vijayasarathy, Sandhya;Karunakar, Prashantha;Chatterjee, Jhinuk 5605

https://doi.org/10.7314/APJCP.2012.13.11.5605 PDF KSCI

Background: In the last two decades, pioneering research on anti-tumour activity of saffron has shed light on the role of crocetin, picrocrocin and safranal, as broad spectrum anti-neoplastic agents. However, the exact mechanisms have yet to be elucidated. Identification and characterization of the targets of bioactive constituents will play an imperative role in demystifying the complex anti-neoplastic machinery. Methods: In the quest of potential target identification, a dual virtual screening approach utilizing two inverse screening systems, one predicated on idTarget and the other on PharmMapper was here employed. A set of target proteins associated with multiple forms of cancer and ranked by Fit Score and Binding energy were obtained from the two independent inverse screening platforms. The validity of the results was checked by meticulously analyzing the post-docking binding pose of the picrocrocin with Hsp90 alpha in AutoDock. Results: The docking pose reveals that electrostatic and hydrogen bonds play the key role in inter-molecular interactions in ligand binding. Picrocrocin binds to the Hsp90 alpha with a definite orientation appropriate for nucleophilic attacks by several electrical residues inside the Hsp90-alpha ATPase catalytic site. Conclusion: This study reveals functional information about the anti-tumor mechanism of saffron bioactive constituents. Also, a tractable set of anti-neoplastic targets for saffron has been generated in this study which can be further authenticated by in vivo and in vitro experiments.

Hamdani, Nissar Hussain;Qadri, Sumyra Khurshid;Aggarwalla, Ramesh;Bhartia, Vishnu Kumar;Chaudhuri, Sumit;Debakshi, Sanjay;Baig, Sarfaraz Jalil;Pal, N.K. 5613

https://doi.org/10.7314/APJCP.2012.13.11.5613 PDF KSCI

Gallbladder carcinoma (GBC) is the commonest cancer of the biliary tree and the most frequent cause of death from biliary malignancies. The incidence of GBC shows prominent geographic, age, race, and gender-related differences and is 4-7 times higher in patients with gallstones. This prompted us to study the clinicopathological aspects of the disease and the incidence of gallstones in gallbladder carcinoma patients, in this part of India. In this, combined retrospective (Jan 2004-March 2010) and prospective study (April 2010-Dec 2011) of eight years, 198 patients of gallbladder carcinoma (50 males and 148 females), (range 28-82 years; mean 55 years) were studied. Most of the patients were poor and presented with abdominal pain and mass, with abnormal lab parameters. Gallstones were present in 86% of patients. Surgical exploration was performed in 130, with gallbladder resection in 60 (including 7 incidental GBC). Adenocarcinoma (87.7%) was the commonest histological type. The study indicates that GBC is common in our scenario. It is a disease of elderly females, has a strong association with gallstones and every cholecystectomy specimen should be examined histopathologically.

Song, Wei;Jiang, Rui;Zhao, Chun-Ming 5619

https://doi.org/10.7314/APJCP.2012.13.11.5619 PDF KSCI

Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

Al-Naggar, Redhwan A.;Bobryshev, Yuri V. 5627

https://doi.org/10.7314/APJCP.2012.13.11.5627 PDF KSCI

Background: The aim of the study was to determine the prevalence of shisha smoking and associated factors among medical students in Malaysia. Materials and Methods: A cross-sectional study was conducted at the Management and Science University from December 2011 until March 2012. The questionnaire consisted of five sections including socio-demographic, social environment, knowledge about shisha, psychosocial factors, and personal shisha smoking behavior. Obtained data were analyzed using Statistical Package for the Social Sciences (SPSS 13). T-test was used to determine the relationships between shisha smoking and socio-demographic characteristic. Results: A total number of 300 medical students participated in this study. Mean age was $22.5{\pm}2.5$ years. The majority were female, Malay, single, from urban areas (67%, 54%, 97%, 73%; respectively). The prevalence of shisha smoking among medical students was found to be 20%. The study revealed that many students believed that shisha does not contains nicotine, carbon monoxide, does not lead to lung cancer, dental problems and does not lead to cardiovascular diseases (25%, 20.7%, 22.3%, 29%, 26.7%; respectively). Age and sex were found to be significantly associated with smoking shisha status among medical students (p=0.029, p<0.001; respectively). Furthermore, having parents, siblings and friends smokers of shisha were found to be significantly associated with shisha smoking status (p<0.001, p<0.001, p<0.001; respectively). Furthermore, family problems, problems with friends, financial problems and university life were found to significantly associated with shisha smoking status among medical students (p<0.001, p=0.002, p<0.001, p=0.002; respectively). Conclusions: There is a high prevalence of shisha smoking and a poor knowledge about its impact on health among medical students. More attention is needed to focus on medical education in this regard. The policies that are currently employed in order to reduce the cigarettes smoking should be applied to shisha smoking and shisha products.

Pei, Xin-Hong;Li, Hui-Xiang 5633

https://doi.org/10.7314/APJCP.2012.13.11.5633 PDF KSCI

Purpose: Breast cancer is an important cause of cancer-related death in women. Numerous studies have evaluated the association between the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and breast cancer risk. However, the specific association is still controversial rather than conclusive. Therefore, we performed a meta-analysis of related studies to address this controversy. Methods: PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between the I/D polymorphism in the ACE gene and susceptibility to breast cancer. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: 10 separate studies of 7 included articles with 10,888 subjects on the relation between the I/D polymorphism in the ACE gene and breast cancer were analyzed by meta-analysis, and our results showed no association between the I/D polymorphism in the ACE gene and breast cancer in total population and different populations. No publication bias was found in the present study. Conclusions: The ACE I/D polymorphism may not be associated with breast cancer risk. Further large and well-designed studies are needed to confirm this conclusion.

Pan, Xiong-Fei;Xie, Yao;Loh, Marie;Yang, Shu-Juan;Wen, Yuan-Yuan;Tian, Zhi;Huang, He;Lan, Hui;Chen, Feng;Soong, Richie;Yang, Chun-Xia 5637

https://doi.org/10.7314/APJCP.2012.13.11.5637 PDF KSCI

Objective: Gastric cancer (GC) is one of the most common malignancies and its mortality ranks third among all cancers in China. We previously noted that XRCC1 Arg194Trp was associated with GC risk in Western China in a study on XRCC1 Arg194Trp and ADPRT Val762Ala. We aimed to further explore the association of these polymorphisms with risk of the noncardia subtype. Methods: We enrolled 176 noncardia GC patients and 308 controls from four hospitals and a community between October 2010 and August 2011. Genotyping was performed in a 384-well plate format on the Sequenom MassARRAY platform. A self-designed questionnaire was utilized to collect epidemiological data from the subjects regarding demographic factors and potential risk factors. Results: Subjects were aged $56.8{\pm}11.8$ (mean ${\pm}$ standard deviation) and $57.6{\pm}11.1$ years in the case and control groups, respectively. Individuals carrying the XRCC1 Trp/Trp or Arg/Trp variant genotype were at significantly increased risk of noncardia GC (adjusted OR, 1.48; 95% CI, 1.00-2.17), after adjustment for family history of cancer, drinking, and smoking. The increased risk of XRCC1 Arg194Trp variant genotype was more pronounced among subjects below 60 years old (adjusted OR, 1.78; 95% CI, 1.07-2.96), compared to older individuals. ADPRT Val762Ala variants (Ala/Ala or Val/Ala) were not associated with noncardia GC (adjusted OR, 1.03; 95% CI, 0.69-1.54). Conclusions: Our study suggests that XRCC1 Arg194Trp is a genetic susceptibility factor for developing noncardia GC in Han Chinese in Western China. In particular, individuals with the XRCC1 Arg194Trp variant genotype are at increased risk for GC below 60 years old.

Ahmadi, Azadeh;Roudbari, Masoud;Gohari, Mahmood Reza;Hosseini, Bistoon 5643

https://doi.org/10.7314/APJCP.2012.13.11.5643 PDF KSCI

Background and Objectives: Increase of mortality rates of gastric cancer in Iran and the world in recent years reveal necessity of studies on this disease. Here, hazard function for gastric cancer patients was estimated using Wavelet and Kernel methods and some related factors were assessed. Materials and Methods: Ninety-five gastric cancer patients in Fayazbakhsh Hospital between 1996 and 2003 were studied. The effects of age of patients, gender, stage of disease and treatment method on patient's lifetime were assessed. For data analyses, survival analyses using Wavelet method and Log-rank test in R software were used. Results: Nearly 25.3% of patients were female. Fourteen percent had surgery treatment and the rest had treatment without surgery. Three fourths died and the rest were censored. Almost 9.5% of patients were in early stages of the disease, 53.7% in locally advance stage and 36.8% in metastatic stage. Hazard function estimation with the wavelet method showed significant difference for stages of disease (P<0.001) and did not reveal any significant difference for age, gender and treatment method. Conclusion: Only stage of disease had effects on hazard and most patients were diagnosed in late stages of disease, which is possibly one of the most reasons for high hazard rate and low survival. Therefore, it seems to be necessary a public education about symptoms of disease by media and regular tests and screening for early diagnosis.

Sharma, Anita;Pandey, Arvind;Sardana, Sarita;Sehgal, Ashok;Sharma, Joginder K. 5647

https://doi.org/10.7314/APJCP.2012.13.11.5647 PDF KSCI

The glutathione S-transferases (GSTs) are involved in the metabolism of many xenobiotics, including an array of environmental carcinogens, pollutants, and drugs. Genetic polymorphisms in these genes may lead to inter-individual variation in susceptibility to various diseases. In the present study, GSTM1 and GSTT1 polymorphisms were analysed using a multiplex polymerase chain reaction in 500 normal individuals from Delhi. The frequency of individuals with GSTM1 and GSTT1 null genotypes were 168 (33.6%) and 62 (12.4%) respectively, and 54(10.8%) were having homozygous null genotype for both the genes GSTM1 and GSTT1simultaneously. The studied population was compared with reported frequencies from other neighbouring state populations, as well as with those from other ethnic groups; Europeans, Blacks, and Asians. The prevalence of homozygous null GSTM1 genotype is significantly higher in Caucasians and Asians as compared to Indian population. The frequency of GSTT1 homozygous null genotypes is also significantly higher in blacks and Asians. We believe that due to large number of individuals in this study, our results are reliable estimates of the frequencies of the GSTM1, GSTT1 in Delhi. It would provide a basic database for future clinical and genetic studies pertaining to susceptibility and inconsistency in the response and/or toxicity to drugs known to be the substrates for GSTs.

Ding, Ming-Xia;Wang, Hai-Feng;Wang, Jian-Song;Zhan, Hui;Zuo, Yi-Gang;Yang, De-Lin;Liu, Jing-Yu;Wang, Wei;Ke, Chang-Xing;Yan, Ru-Ping 5653

https://doi.org/10.7314/APJCP.2012.13.11.5653 PDF KSCI

Objectives: To investigate the effect of glycopeptide-preferring polypeptide GalNAc transferase 1 (ppGalNAc T1 ) targeted RNA interference (RNAi) on the growth and migration of human bladder carcinoma EJ cells in vitro and in vivo. Methods: DNA microarray assays were performed to determine ppGalNAc Ts(ppGalNAc T1-9) expression in human bladder cancer and normal bladder tissues. We transfected the EJ bladder cancer cell line with well-designed ppGalNAc T1 siRNA. Boyden chamber and Wound healing assays were used to investigate changes of shppGalNAc T1-EJ cell migration. Proliferation of shppGalNAc T1-EJ cells in vitro was assessed using [3H]-thymidine incorporation assay and soft agar colony formation assays. Subcutaneous bladder tumors in BALB/c nude mice were induced by inoculation of shppGalNAc T1-EJ cells and after inoculation diameters of tumors were measured every 5 days to determine gross tumor volumes. Results: ppGalNAc T1 mRNA in bladder cancer tissues was 11.2-fold higher than in normal bladder tissues. When ppGalNAc T1 expression in EJ cells was knocked down through transfection by pSUPER-shppGalNAc T1 vector, markedly reduced incorporation of [3H]-thymidine into DNA of EJ cells was observed at all time points compared with the empty vector transfected control cells. However, ppGalNAc T1 knockdown did not significantly inhibited cell migration (only 12.3%). Silenced ppGalNAc T1 expression significantly inhibited subcutaneous tumor growth compared with the control groups injected with empty vector transfected control cells. At the end of observation course (40 days), the inhibitory rate of cancerous growth for ppGalNAc T1 knockdown was 52.5%. Conclusion: ppGalNAc T1 might be a potential novel marker for human bladder cancer. Although ppGalNAc T1 knockdown caused no remarkable change in cell migration, silenced expression significantly inhibited proliferation and tumor growth of the bladder cancer EJ cell line.

Liu, Fei;Pu, Xiao-Yun;Huang, Shao-Guang;Xiang, Gui-Ming;Jiang, Dong-Neng;Hou, Gou;Huang, Di-Nan 5659

https://doi.org/10.7314/APJCP.2012.13.11.5659 PDF KSCI

To investigate the expression of hPOT1 in the HeLa cell line and screen point mutations of hpot1 in different tumor tissues a two step osmotic method was used to extract nuclear proteins. EMSA was performed to determine the expression of hPOT1 in the HeLa cell line. PCR was also employed to amplify the exon14 sequence of the hpot1 gene in various of cancer tissues. A SV gel and PCR clean-up system was performed to enrich PCR products. DNAStar was used to analyse the exon14 sequence of the hpot1 gene. hPOT1 was expressed in the HeLa cell line and the signal was gradually enhanced as the amount of extracted nuclear proteins increased. The DNA fragment of exon14 of hpot1 was successfully amplified in the HeLa cell line and all cancer tissues, point mutations being observed in 2 out of 3 cases of endometrial cancer (66.7%) despite the hpot1 sequence being highly conserved. However, the sequence of hpot1 exon14 do not demonstrate point mutations in most cancer tissues. Since hPOT1 was expressed in HeLa cell and the probability of gene point variants was obviously higher in endometrial cancer than other cancers, it may be involved in the pathogenesis of gynecological cancers, especially in cervix and endometrium.

Wang, Kai;Peng, Hong-Ling;Li, Long-Kun 5665

https://doi.org/10.7314/APJCP.2012.13.11.5665 PDF KSCI

Background: The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has involvement in cancer pathogenesis, progression and metastasis. However, the prognostic value of VEGF in patients with prostate cancer remains controversial. Objectives: The aim of our study was to evaluate the prognostic value of VEGF in prostate cancer, and summarise the results of related research on VEGF. Methods: In accordance with an established search strategy, 11 studies with 1,529 patients were included in our meta-analysis. The correlation of VEGF-expression with overall survival and progression-free survival was evaluated by hazard ratio, either given or calculated. Results: The studies were categorized by introduction of the author, demographic data in each study, prostate cancer-relatived information, VEGF cut-off value, VEGF subtype, methods of hazard ratio (HR) estimation and its 95% confidence interval (CI). High VEGF-expression in prostate cancer is a poor prognostic factor with statistical significance for OS (HR=2.32, 95%CI: 1.40-3.24). However, high VEGF-expression showed no effect on poor PFS (HR=1.30, 95%CI: 0.88-1.72). Using Begg's, Egger's test and funnel plots, we confirmed lack of publication bias in our analysis. Conclusion: VEGF might be regarded as a prognostic maker for prostate cancer, as supported by our meta-analysis. To achieve a more definitive conclusion enabling the clinical use of VEGF in prostate cancer, we need more high-quality interventional original studies following agreed research approaches or standards.

Wang, Li-Guang;Su, Ben-Hua;Du, Jia-Jun 5671

https://doi.org/10.7314/APJCP.2012.13.11.5671 PDF KSCI

Objective: Arrestins act as mediators of G protein-coupled receptor (GPCR) desensitization and trafficking, also actin as a scaffold for many intracellular signaling network. The role that ${\beta}$-arrestin 1 plays in gastric cardiac adenocarcinoma (GCA) and its clinicopathologic significance are untouched. Methods: Fifty patients with gastric cardiac adenocarcinoma were retrospectively enrolled and ${\beta}$-arrestin 1 was detected using immunohistochemistry in tissue samples. Results: Nuclear expression of ${\beta}$-arrestin 1 was observed in 78% of GCA samples (39/50) and cytoplasmic expression in 70% (35/50). ${\beta}$-arrestin 1 could be found in both nucleus and cytoplasm of 54% GCA (27/50) or in either of them in 94% (47/50). ${\beta}$-arrestin 1 protein positivity in well/moderately differentiated carcinomas was significantly higher than that in poorly differentiated carcinomas (P=0.005). We found increased expression of ${\beta}$-arrestin 1 in cytoplasm was correlated with lymph nodal metastasis (P=0.002) and pathological lymph nodal staging (P=0.030). We also found ${\beta}$-arrestin 1 to be over-expressed in glandular epithelia cells of mucinous adenocarcinoma, a tumour type associated with an adverse outcome of gastric cardiac adenocarcinoma (P=0.022). Conclusion: ${\beta}$-arrestin 1 is over-expressed in the nucleus and/or cytoplasm of gastric cardiac adenocarcinoma. However, ${\beta}$-arrestin 1 has no relationship with the prognosis of gastric cardiac adenocarcinoma (P>0.05). Our data imply that ${\beta}$-arrestin 1 in cytoplasm may be involved in differentiation and metastasis of gastric cardiac adenocarcinoma.

Norouzinia, M.;Asadzadeh, H.;Shalmani, H. Mohaghegh;Al Dulaimi, D.;Zali, M.R. 5677

https://doi.org/10.7314/APJCP.2012.13.11.5677 PDF KSCI

Background and Aim: Gastric cancer is the second most common cancer worldwide. In this study the clinical and histological features of gastric cancer in the cardia and distal stomach were evaluated. Method: Proximal and distal gastric cancer diagnosed and treated in eight provinces of Iran from 2010-2011 were reviewed in all collected cases. The age standardized incident rates were calculated and tumor location and histological type were recorded. Results: The age-standardized incidence rate for the eight centers was 40.6 per 100,000 populations per year with an upper and lower range of 22.1 and 102.4 per 100,000 population per year. Thirty four percent of the tumors were located in the cardia, 3% in fundus, and 63% in the distal stomach. In 7 provinces the prevalence of distal tumors was significantly greater than proximal tumors (p=0.006). A significant relationship was observed between diffuse form of gastric cancer and distal gastric tumors (p=0.007) and between poor tumor differentiation and distal gastric tumors (p<0.001). Conclusions: the result of this study shows that distal gastric cancer is more common than proximal gastric cancer in Iran.

Utada, Mai;Ohno, Yuko;Shimizu, Sachiko;Hori, Megumi;Soda, Midori 5681

https://doi.org/10.7314/APJCP.2012.13.11.5681 PDF KSCI

Three kinds of survival rates are generally used depending on the purpose of the investigation: overall, cause-specific, and relative. The differences among these 3 survival rates are derived from their respective formulas; however, reports based on actual cancer registry data are few because of incomplete information and short follow-up duration recorded on cancer registration. The aim of this study was to numerically and visually compare these 3 survival rates on the basis of data from the Nagasaki Prefecture Cancer Registry. Subjects were patients diagnosed with cancer and registered in the registry between 1999 and 2003. We calculated the proportion of cause of death and 5-year survival rates. For lung, liver, or advanced stage cancers, the proportions of cancer-related death were high and the differences in survival rates were small. For prostate or early stage cancers, the proportions of death from other causes were high and the differences in survival rates were large. We concluded that the differences among the 3 survival rates increased when the proportion of death from other causes increased.

Arabaci, Zeynep;Ozsoy, Suheyla 5687

https://doi.org/10.7314/APJCP.2012.13.11.5687 PDF KSCI

Objective: The study was planned with the purpose of examining the attitude of women who have pap-smear test for the early diagnosis of cervical cancer, factors affecting their decisions and their feelings and experiences during this period. Materials and Methods: A phenomenological method was used. Data were collected between March 2012 and April 2012 using standard and purposive samplings from 17 women. A detailed interview with women were held in their houses and recorded. The data collection tool consisted of two parts, one of which is information form with 17 questions identifying sociodemographic and cervical cancer risk factors of women and the second part is made up of semi-structured interview form with 15 alternative questions taking literature and the pap-smear test into consideration. Collected data were put into a written document. Content analysis was held by loading the documents into NVIVO 8 Statistical Programme. Results: The study comprised themes such as cervical risk factor, decision of taking pap-smear test, taking pap-smear test, knowledge about pap-smear test, relieving factors during pap-smear test, obstructive factors during pap-smear test, gynecological examination and feelings of women during and after pap-smear test while waiting for the results. Conclusions: As women perceive gynaecological examinations differently from other examinations, they have different feelings in each process of the Pap smear test. Medical staff should advise women more clearly on the nature and advantages of the Pap-smear test.

Goto, Yasuyuki;Kato, Tsuyoshi;Ando, Takafumi;Goto, Hidemi;Hamajima, Nobuyuki 5691

https://doi.org/10.7314/APJCP.2012.13.11.5691 PDF KSCI

Ectopic expression of CDX2 in the stomach is closely associated with chronic Helicobacter pylori (H. pylori) infection and intestinal metaplasia. Whether CDX2 has tumor suppression or tumorigenesis potential remains to be elucidated. In this study, we investigated the association between the CDX2 G543C polymorphism (silent mutation) and the risk for H. pylori-induced gastric atrophy and cancer as well as H. pylori infection, using 454 Japanese subjects undergoing a health checkup and 202 gastric cancer patients. The frequency of the minor allele was the same as previously reported in China, but different from that reported in England. CDX2 G543C was not associated with risk of H. pylori infection, gastric atrophy, or gastric cancer, although the point estimate for non-cardiac differentiated gastric cancer as compared to controls with gastric atrophy was 2.22 (95%CI=0.17-29.4). In conclusion, our results indicate that the CDX2 G543C polymorphism is unlikely to affect the H. pylori infection-gastric atrophy-gastric cancer sequence.

Woo, Hee-Yeon;Park, Hyosoon;Kwon, Min-Jung;Chang, Yoosoo;Ryu, Seungho 5695

https://doi.org/10.7314/APJCP.2012.13.11.5695 PDF KSCI

We investigated the relationships between demographics, lifestyle characteristics, and serum total prostate specific antigen (PSA) concentration and examined the population-based distribution of total PSA by age among 2,246 Korean men with a median age of 45 years. We obtained data about demographic and lifestyle characteristics based on self-reporting using a quetionnaire. We also performed physical examinations, anthropometric measurements, and biochemical measurements. The PSA concentration increased with age and there was a significant difference in total PSA concentration between the age groups of 21-60 years and >60 years. Age >60 years, height ${\geq}1.8$ m, a low frequency of alcohol consumption, and taking nutritional supplements showed a significantly increased odds ratio for increased PSA when 3.0 ng/mL was chosen as the PSA cut-off level. Smoking status, BMI, percent body fat, diabetes mellitus, fatty liver, herbal medicine use, vitamin use, and diet were not significantly associated with total PSA regardless of the cut-off level. When interpreting a single PSA test, height, alcohol consumption, and nutritional supplement use should be considered, in addition to age.

Manoharan, S.;Singh, Arjun Kumar;Suresh, K.;Vasudevan, K.;Subhasini, R.;Baskaran, N. 5701

https://doi.org/10.7314/APJCP.2012.13.11.5701 PDF KSCI

The aim of the study was to investigate the chemopreventive potential of andrographolide in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors developed in the buccal pouch of golden Syrian hamsters at a 100% incidence on painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Marked abnormalities in the status of detoxification enzymes, lipid perxodiation and antioxidants were noticed in hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also restored the status of the above mentioned biomarkers. The present study thus demonstrates the chemopreventive potential of andrographolide in DMBA-induced hamster buccal pouch carcinogenesis, which is probably due to its antioxidant potential as well as modulating effect on xenobiotic metabolising enzymes during DMBA-induced oral carcinogenesis.

Mo, Na;Li, Zheng-Qian;Li, Jing;Cao, You-De 5709

https://doi.org/10.7314/APJCP.2012.13.11.5709 PDF KSCI

Objective: To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-${\beta}1$ (TGF-${\beta}1$) in MDA-MB-231 cells and potential mechanisms. Methods: Human breast cancer MDA-MB-231 cells were used with the CCK-8 assay to measure the cytotoxicity of curcumin. After treatment with 10 ng/ml TGF-${\beta}1$, with or without curcumin (${\leq}10{\mu}M$), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-${\beta}1$-stimulated MMP-9 and phosphorylation of Smad2, extracellular-regulated kinase (ERK), and p38 mitogen activated protein kinases (p38MAPK) were examined by Western blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Following treatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Western blotting and zymography were employed to examine MMP-9 expression and activity, respectively. Results: Low dose curcumin (${\leq}10{\mu}M$) did not show any obvious toxicity to the cells, while $0{\sim}10{\mu}mol/L$ caused a concentration-dependent reduction in cell invasion provoked by TGF-${\beta}1$. Curcumin also markedly inhibited TGF-${\beta}1$-regulated MMP-9 and activation of Smad2, ERK1/2 and p38 in a dose- and time-dependent manner. Additionally, PD98059, but not SB203580, showed a similar pattern of inhibition of MMP-9 expression. Conclusion: Curcumin inhibited TGF-${\beta}1$-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-${\beta}$/Smad and TGF-${\beta}$/ERK signaling.

Taskin, Salih;Dunder, Ilkkan;Erol, Ebru;Taskin, Elif Aylin;Kiremitci, Saba;Oztuna, Derya;Sertcelik, Ayse 5715

https://doi.org/10.7314/APJCP.2012.13.11.5715 PDF KSCI

The relation between cyclooxygenase enzymes and E-cadherin, along with the roles of these markers in the prediction of survival in optimally cytoreduced serous ovarian cancer patients was investigated. Individuals who underwent primary staging surgery and achieved optimal cytoreduction (largest residual tumor volume <1 cm) constituted the study population. Specimens of 32 cases were immunohistochemically examined for cyclooxygenase-1, cyclooxygenase-2, and E-cadherin. Two could not be evaluated for E-cadherin and cyclooxygenase-1. Overall, 14/30, 19/30, and 15/32 cases were positive for E-cadherin, cyclooxygenase-1, and cyclooxygenase-2, respectively. The expressions of E-cadherin and cyclooxygenase-2 were inversely correlated (p:0.02). E-cadherin expression was related with favorable survival (p<0.001). The relation between the expression of cyclooxygenase enzymes and poor survival did not reach statistical significance. On multivariate analysis, E-cadherin appeared as an independent prognostic factor for survival. In conclusion, E-cadherin expression is strongly linked with favorable survival. E-cadherin and cyclooxygenase 2 may interact with each other during the carcinogenesis-invasion process. Further studies clarifying the relation between E-cadherin and cyclooxygenase enzymes may lead to new preventive and therapeutic targets in ovarian cancer.

Gan, Yi;Li, Xiao-Rong;Chen, Dao-Jin;Wu, Jun-Hui 5721

https://doi.org/10.7314/APJCP.2012.13.11.5721 PDF KSCI

We conducted this study to detect associations between XRCC1 Arg399Gln and XPD Lys751Gln genotypes and survival of colorectal cancer patients treated with 5-FU/oxalipatin chemotherapy. We included 289 Chinese patients with advanced colorectal cancer, who had received 5-FU/oxalipatin chemotherapy as first-line treatment from January 2005 to January 2007. All patients were followed up till Nov. 2011. Genotyping for XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was based upon duplex polymerase-chain-reaction with the PCR-RFLP method. In our study, we found the XRCC1 399 Gln/Gln genotype to confer significantly higher rates of response to chemotherapy when compared to the Arg/Arg genotype [OR (95% CI)= 2.56(1.57-2.55)]. patients with the XPD 751 Gln/Gln genotype had significantly higher rates of response to chemotherapy [OR (95% CI)= 1.54(0.87-2.65)] and those with the XRCC1 399 Gln/Gln genotype had a longer average survival time and significantly lower risk of death than did those with the Arg/Arg genotype [HR (95% CI)= 0.66(0.36-0.95)]. Similarly, those carrying the XPD 751Gln/Gln genotype had 0.51-fold the risk of death of those with XPD 751Lys/Lys [HR (95% CI)= 0.51(0.33 -0.94)]. In conclusion, it is suggested that the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms should be routinely assessed to determine colorectal patients who are more likely to benefit from 5-FU/oxalipatin chemotherapy.

Luo, Yong;Wang, Fan;Chen, Lv-An;Chen, Xiao-Wei;Chen, Zhi-Jun;Liu, Ping-Fei;Li, Fen-Fen;Li, Cai-Yan;Liang, Wu 5725

https://doi.org/10.7314/APJCP.2012.13.11.5725 PDF KSCI

Growing evidence shows that deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of gene chnages controlling circadian rhythm in glioma cells have not been explored. Using real time polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, cry1 and cry2, in 69 gliomas. In this study, out of 69 gliomas, 38 were cry1-positive, and 51 were cry2-positive. The expression levels of cry1 and cry2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of cry1 and cry 2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was non-significant (P>0.05) but there was a difference in the intensity of immunoactivity for cry 2 between high-grade gliomas and low-grade gliomas (r=-0.384, P=0.021). In this study, we found that the expression of cry1 and cry2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in cry1 and cry2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.

Baseskioglu, Barbaros;Duman, Berna Bozkurt;Kara, I. Oguz;Can, Cavit;Yildirim, Mustafa;Acikalin, Mustafa 5729

https://doi.org/10.7314/APJCP.2012.13.11.5729 PDF KSCI

Background and Objectives: This study aimed to present the clinicopathological characteristics and treatment of patients with bladder carcinoma with sarcomatoid differentiation at our institution. Methods: Between 1995-2009, 950 patients were followed-up for bladder carcinoma. Among them, 14 patients with sarcomatoid carcinoma were retrospectively reviewed, and their clinical, pathological features and treatment were recorded. Results: Median age of the patients was 65 years (range: 41-86 years), 12 (86%) being male and 2 (14%) female. All the patients presented with hematuria and 11 (88%) had a history of smoking. The tumor growth pattern was solid in 10 patients, papillary in 2, and mixed in 2. In all, 5 of the patients had urothelial carcinoma with sarcomatoid differentiation and 9 were diagnosed with sarcomatoid carcinoma. Five patients underwent radical cystectomy with ileal conduit surgery, 2 patients refused cystectomy, and 8 patients underwent re-TUR. Following diagnosis, 12 of the patients died in mean 10.7 months (range: 1-48 months). Conclusion: Urothelial carcinomas with sarcomatoid features are aggressive and are usually at advanced stage at the time of diagnosis. The outcomes of multimodal treatment are not satisfactory. Significant findings of the present study are that early diagnosis positively affect survival and that gemcitabine and cisplatin in combination can positively affect survival.

Berk, Serdar;Dogan, Omer Tamer;Kilickap, Saadettin;Epozturk, Kursat;Akkurt, Ibrahim;Seyfikli, Zehra 5735

https://doi.org/10.7314/APJCP.2012.13.11.5735 PDF KSCI

Background: Malignant mesothelioma (MM) is an insidious tumor with poor prognosis, arising from mesothelial surfaces such as pleura, peritoneum and pericardium. We here aimed to evaluate the demographic, clinical, and radiological features of patients with MM followed in our center as well as their survival. Methods: The study included 228 patients (131 male, 97 female) who were followed up in our institution between 1993 and 2010 with the diagnosis of MM. Results: The mean age was 59.1 years in men and 58.7 years in women and the sex ratio was 1.4:1 in favor of males. Environmental asbestos exposure was present in 86% of the patients for a mean duration of $40{\pm}20$ years (range: 3-70). Pleural effusion and thoracic/abdominal pain were the most common presenting signs and symptoms (70.2% and 57.8%, respectively). One hundred-thirteen (66%) patients were treated with platinum-based combination chemotherapy (PBCT) plus supportive care (SC) and 67 (34%) patients received SC alone. The median follow-up time was 10.0 months. The median overall survival was significantly improved with PBCT plus SC compared to SC alone (11.4 vs. 5.1 months; p=0.005). The 6, 12, 18, and 24-month survival rates were significantly improved with PBCT plus SC compared to SC alone (72%, 43%, 19%, and 2% vs. 49%, 31%, 11%, and 1%). Conclusion: The survival of patients with MM improved in patients treated with PBCT. The survival advantage continued 12- and 24-month after the initial time of combination chemotherapy.

Kilic, Diclehan;Yalman, Deniz;Aksu, Gorkem;Atasoy, Beste M.;Igdem, Sefik;Dincbas, Fazilet O.;Yalcin, Suayib 5741

https://doi.org/10.7314/APJCP.2012.13.11.5741 PDF KSCI

Aim: Although preoperative chemoradiatherapy (CRT) has proven its benefits in terms of decreased toxicity, there is still a considerable amount of cases that do not receive postoperative CRT. Oncologists at different geographic locations still need to know the long-term effects of this treatment in order to manage patients successfully. The current paper reports on long-term quality of life (QOL) and late side effects after adjuvant CRT in rectal cancer patients from 5 centers in Anatolia. Methods: Rectal cancer patients treated with postoperative CRT with minimum 1-year follow-up and were in complete remission, were evaluated according to RTOG and LENT-SOMA scales. They were also asked to complete Turkish version of EORTC QLQ-C30 questionnaire and the CR-38 module. Each center participated with the required clinical data. Results: Two hundred and thirty patients with median age of 55 years participated and completed the study. Median follow-up time was 5 years. All patients received RT concomitant with chemotherapy. Common parameters that both increased functional health scales and yielded better symptom scores were long term interval after treatment and sphincter-saving surgery. In addition, surgery type and follow-up time were determined to be predictors of QOL scores and late toxicity grade. Conclusion: Postoperative CRT was found to have a great impact on the long term QOL and side effects in rectal cancer survivors. The factors that adversely affect these are abdominoperineal resection and shorter interval. The findings may encourage life-long follow-up and cooperation with patients, which should be mentioned during the initial counseling.

Liang, Zhong-Guo;Zhu, Xiao-Dong;Zhou, Zhi-Rui;Qu, Song;Du, You-Qin;Jiang, Yan-Ming 5747

https://doi.org/10.7314/APJCP.2012.13.11.5747 PDF KSCI

Purpose: The main objective of the present study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. Randomized controlled trials (RCTs) that compared concurrent chemoradiotherapy followed by adjuvant chemotherapy with concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma were included. Meta-analysis was performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Five studies were included. Risk ratios of 1.02 (95%CI 0.89-1.15), 0.93 (95%CI 0.72-1.21), 1.07 (95%CI 0.87-1.32), 0.95 (95%CI 0.80-1.13) were observed for 3 years overall survival, 5 years failure-free survival, 5 years locoregional failure-free survival and 5 years distant metastasis failure-free survival. There were no treatment-related deaths in both groups of five studies. Hematologic and gastrointestinal toxicity were the most significant for patients during adjuvant chemotherapy. The level of evidence was low. Conclusion: Compared with concurrent chemoradiotherapy alone, concurrent chemotherapy followed by adjuvant chemotherapy did not improve prognosis. More toxicity was found during adjuvant chemotherapy.

Manoharan, S.;Palanimuthu, D.;Baskaran, N.;Silvan, S. 5753

https://doi.org/10.7314/APJCP.2012.13.11.5753 PDF KSCI

Apoptosis, also known as cell suicide or programmed cell death, removes unwanted and genetically damaged cells from the body. Evasion of apoptosis is one of the major characteristic features of rapidly proliferating tumor cells. Chemopreventive agents inhibit or suppress tumor formation through apoptotic induction in target tissues. The aim of the present study was to investigate the pro-apoptotic potential of lupeol during 7,12-dimethylbenz(a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA three times a week for 14 weeks in the buccal pouches of golden Syrian hamsters resulted in oral squamous cell carcinoma. The expression pattern of apoptotic markers was analyzed using immunohistochemistry (p53, Bcl-2, Bax) and ELISA reader (caspase 3 and 9). In the present study, 100% tumor formation with defects in apoptotic markerexpression pattern was noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50mg/kg bw completely prevented the formation oral tumors as well as decreased the expression p53 and Bcl-2, while increasing the expression of Bax and the activities of caspase 3 and 9. The present study thus indicated that lupeol might inhibit DMBA-induced oral tumor formation through its pro-apoptotic potential in golden Syrian hamsters.

Sangrajrang, Suleeporn;Chokvanitphong, Vanida;Sumetchotimaytha, Wutti;Khuhaprema, Thiravud 5759

https://doi.org/10.7314/APJCP.2012.13.11.5759 PDF KSCI

The objective of the study was to evaluate the efficacy of a health check-up program among Thai people at the National Cancer Institute in the years 2008-2009. The program included history taking, physical examination, chest X-ray, EKG, and laboratory tests. A total of 28,240 women and 9,665 men were included in the study, with mean ages of 44.5 and 46.9 years, respectively. The study showed that obesity, as assessed by a BMI over 25.0 kg/m2, in men and women was present in 41.4% and 30%, respectively. Biochemical study revealed that anemia was prevalent in 21.6% of men and 20.1% of women. High plasma glucose level (>115 mg/dL), cholesterol level (>200 mg/dL), triglyceride level (>190 mg/dL) in men was 13.8%, 63.8%, 22.6% and 7.7%, 61.1%, 8.9% in women. Hepatitis B virus infection was found 7.5% in men and 4.1% in women. In this study, 177 new cancer cases were detected, of which 35 were breast, 19 were cervical and 26 were colorectal, most of these cancers being detected at early stage. In addition, precancerous states was also found including 718 cases of benign and 99 cases of adenoma in situ. In conclusion, an annual check up may detect abnormalities that have no obvious clinical symptoms of disease. Early detection of asymptomatic neoplasms and precursor lesions should contribute to a prompt provision of treatment and further decline of death from cancer.

Marakala, Vijaya;Malathi, M.;Shivashankara, A.R. 5763

https://doi.org/10.7314/APJCP.2012.13.11.5763 PDF KSCI

Background: This study was conducted to determine levels of lipid peroxidation and antioxidant vitamin status in patients with oral cavity and oropharyngeal cancer. Methods: The study group consisted of a total number of 80 subjects between the age 40-68 years, 40 with clinically and histopathologically proved cases of oral cavity and oropharyngeal cancer and 40 normal healthy, age and sex matched volunteers as controls. Levels of lipid peroxidation products as malondialdehyde (MDA) and antioxidant vitamins as vitamin A and vitamin C were estimated and compared between the two groups. Results: There was a statistical significant difference in the mean MDA, plasma vitamin A and vitamin C in the oral and oropharyngeal cancer patients compared with the healthy controls (p<0.0001). Conclusions: Lipid peroxidation (MDA) is higher and plasma antioxidant vitamins like vitamin A and vitamin C were lower in oral cavity and oropharyngeal cancer patients than healthy controls.

Rezaianzadeh, Abbas;Talei, Abdolrasoul;Rajaeefard, Abdereza;Hasanzadeh, Jafar;Tabatabai, Hamidreza;Tahmasebi, Sedigheh;Mousavizadeh, Ali 5767

https://doi.org/10.7314/APJCP.2012.13.11.5767 PDF KSCI

Introduction: Identification of simple and measurable prognostic factors is an important issue in treatment evaluation of breast cancer. The present study was conducted to evaluate the prognostic role of vascular invasion in lymph node negative breast cancer patients. Methods: in a retrospective design, we analyzed the recorded profiles of the 1,640 patients treated in the breast cancer department of Motahari clinic affiliated to Shiraz University of Medical Sciences, Shiraz, Iran, from January 1999 to December 2012. Overall and adjusted survivals were evaluated by the Cox proportional hazard model. All the hypotheses were considered two-sided and a p-value of 0.05 or less was considered as statistically significant. Results: Mean age in lymph node negative and positive patients was 50.0 and 49.8 respectively. In lymph node negative patients, the number of nodes, tumor size, lymphatic invasion, vascular invasion, progesterone receptor, and nuclear grade were significant predictors. In lymph node and lymphatic negative patients, vascular invasion also played a significant prognostic role in the survival which was not evident in lymph node negative patients with lymphatic invasion. Discussion: The results of our large cohort study, with long term follow up and using multivariate Cox proportional model and comparative design showed a significant prognostic role of vascular invasion in early breast cancer patients. Vascular invasion as an independent prognostic factor in lymph node negative invasive breast cancer.

Mittal, Ankush;Gupta, Satrudhan Pd;Sathian, Brijesh;Sreedharan, Jayadevan;Poudel, Bibek;Yadav, Shambhu Kumar;Pandeya, Dipendra Raj 5773

https://doi.org/10.7314/APJCP.2012.13.11.5773 PDF KSCI

Objective: To assess the diagnostic and prognostic value of AFP and des-gamma-carboxyprothrombin (DCP) in combination and alone for hepatocellular carcinoma. Materials and Methods: A case control study carried out in the Department of Biochemistry of Manipal College of Medical Sciences, Pokhara, Nepal between $1^{st}$ January 2010 and $31^{st}$ December 2011. The variables collected were age, gender, BMI, total proteins, albumin, AST, ALT, total bilirubin, DCP, AFP. Approval for the study was obtained from the institutional research ethical committee. Estimation of AFP was performed by ELISA reader for all cases. Analysis was done using descriptive statistics and confidence interval (CI). The data was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. Results:The mean age of HCC cases was $53.6{\pm}14.93$ yrs. The percentage of females was less than males in both cases (23%) and controls (29%). The specificity of DCP reached 100% when its values was equal or greater than 150 (MAU/ml) for 0, 3, 6, 9, 12 months preceding the diagnosis of HCC. Similarly, the specificity for AFP was also nearly 100% when its value was equal or greater than 200 ng/ml 0, 3, 6, 9, 12 months earlier to the finding of HCC. The specificity of DCP (${\geq}40MAU/mL$) and AFP(${\geq}20$ ng/mL) in combination was 93%, 97%, 95%, 96%, 97% in respect to 0, 3, 6, 9, 12 months prior to the diagnosis of HCC. Conclusion: The combination of both DCP and AFP will improve the finding of initial HCC and the sensitivity of these markers was utmost at the time of HCC identification and noticeably lesser at former time points.

Pan, Feng;Tian, Jing;Ji, Chu-Shu;He, Yi-Fu;Han, Xing-Hua;Wang, Yong;Du, Jian-Ping;Jiang, Feng-Shou;Zhang, Ying;Pan, Yue-Yin;Hu, Bing 5777

https://doi.org/10.7314/APJCP.2012.13.11.5777 PDF KSCI

Published data on the associations between tumor necrosis factor-alpha (TNF-${\alpha}$) promoter -308G>A and -238G>A polymorphisms and cervical cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Data were collected from MEDLINE and PubMed databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a fixed/random effect model. 13 separate studies including 3294 cases and 3468 controls were involved in the meta-analysis. We found no association between TNF-${\alpha}$-308G>A polymorphism and cervical cancer in overall population. In subgroup analysis, significantly elevated risks were found in Caucasian population (A vs. G: OR = 1.43, 95% CI = 1.00-2.03; AA vs. GG: OR = 2.09, 95% CI = 1.34-3.25; Recessive model: OR = 2.09, 95% CI = 1.35-3.25) and African population (GA vs. GG: OR = 1.53, 95% CI = 1.02-2.30). An association of TNF-${\alpha}$-238G>A polymorphism with cervical cancer was found (A vs. G: OR = 0.61, 95% CI = 0.47-0.78; GA vs. GG: OR = 0.59, 95% CI = 0.45-0.77; Dominant model: OR = 0.59, 95% CI = 0.46-0.77). When stratified by ethnicity, similar association was observed in Caucasian population (A vs. G: OR = 0.62, 95% CI = 0.46-0.84; GA vs. GG: OR = 0.59, 95% CI = 0.43-0.82; Dominant model: OR = 0.60, 95% CI = 0.44-0.83). In summary, this meta-analysis suggests that TNF-${\alpha}$-238A allele significantly decreased the cervical cancer risk, and the TNF-${\alpha}$-308G>A polymorphism is associated with the susceptibility to cervical cancer in Caucasian and African population.

Nugroho, Agung Endro;Hermawan, Adam;Nastiti, Kunti;Suven, Suven;Elisa, Pritha;Hadibarata, Tony;Meiyanto, Edy 5785

https://doi.org/10.7314/APJCP.2012.13.11.5785 PDF KSCI

The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

Tan, Foo Lan;Loh, Siew Yim;Su, TinTin;Veloo, V.W.;Ng, Lee Luan 5791

https://doi.org/10.7314/APJCP.2012.13.11.5791 PDF KSCI

Introduction: Return-to-work (RTW) can be a problematic occupational issue with detrimental impact on the quality of life of previously-employed breast cancer survivors. This study explored barriers and facilitators encountered during the RTW process in the area of cancer survivorship. Materials and Methods: Six focus groups were conducted using a semi-structured interview guide on 40 informants (employed multiethnic survivors). Survivors were stratified into three groups for successfully RTW, and another three groups of survivors who were unable to return to work. Each of the three groups was ethnically homogeneous. Thematic analysis using a constant comparative approach was aided by in vivo software. Results: Participants shared numerous barriers and facilitators which directly or interactively affect RTW. Key barriers were physical-psychological after-effects of treatment, fear of potential environment hazards, high physical job demand, intrusive negative thoughts and overprotective family. Key facilitators were social support, employer support, and regard for financial independence. Across ethnic groups, the main facilitators were financial-independence (for Chinese), and socialisation opportunity (for Malay). A key barrier was after-effects of treatment, expressed across all ethnic groups. Conclusions: Numerous barriers were identified in the non-RTW survivors. Health professionals and especially occupational therapists should be consulted to assist the increasing survivors by providing occupational rehabilitation to enhance RTW amongst employed survivors. Future research to identify prognostic factors can guide clinical efforts to restore cancer survivors to their desired level/type of occupational functioning for productivity and wellbeing.

Zhang, Hai;Huang, Chang-Jun;Tian, Yuan;Wang, Yu-Ping;Han, Ze-Guang;Li, Xiang-Cheng 5799

https://doi.org/10.7314/APJCP.2012.13.11.5799 PDF KSCI

Family with sequence similarity 189, member B (FAM189B), alias COTE1, a putative oncogene selected by microarray, for the first time was here found to be significantly up-regulated in hepatocellular carcinoma (HCC) specimens and HCC cell lines. mRNA expression of COTE1 in HCC samples and cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR, while protein expression of COTE1 in HCC tissues was assessed by immunohistochemistry. In addition, invasion of HCC cells was observed after overexpressing or silencing COTE1. In the total of 48 paired HCC specimens, compared with the adjacent non-cancer tissues, the expression of COTE1 was up-regulated in 31 (p<0.01). In HCC cell lines, COTE1 expression was significantly higher than in normal human adult liver (p<0.01). Overexpression of COTE1 enhanced HCC-derived LM6 and MHCC-L cellular invasion in vitro. In contrast, COTE1 knockdown via RNAi markedly suppressed these phenotypes, as documented in LM3 and MHCC-H HCC cells. Mechanistic analyses indicated that COTE1 could physically associate with WW domain oxidoreductase (WWOX), a tumor suppressor. COTE1 may be closely correlated with invasion of hepatocellular carcinoma (HCC) cells and thus may serve as an effective target for gene therapy.

Peerawong, Thanarpan;Phungrassami, Temsak;Pruegsanusak, Kovit;Sangthong, Rassamee 5805

https://doi.org/10.7314/APJCP.2012.13.11.5805 PDF KSCI

Aims: The study aimed to compare treatment compliance and nutritional outcomes in nasopharyngeal carcinoma (NPC) patients during chemoradiation. Methods: Clinical information of patients with NPC that underwent chemoradiation during 2004-2009 were retrieved from the hospital database and retrospectively reviewed. Patients were categorised into a prophylactic percutaneous endoscopic gastrostomy (PPEG) group and a non-PPEG group. Clinical information including treatment compliance, weight, haematological and renal toxicity was compared. Results: A total of 219 patients were reviewed and categorised into PPEG (n=77) and non-PPEG (n=142). Significant differences in absolute percentage weight loss between groups were found from the $3^{rd}$ cycle of chemotherapy. There were 24.2, 20.3 and 24.8% in the third, the fourth and the fifth cycles of chemotherapy, respectively. Migration of grade 2 to grade 3 weight loss was obviously seen in the $3^{rd}$ cycle as well. A significant difference of grade 3 or more hypokalemia was found with values of 14.3% and 50% in the PPEG and non-PPEG groups, respectively. Other toxicity parameters and treatment compliance were not different between the groups. Conclusions: Use of PPEG resulted in decreased severe weight loss, reduced migration from grade 2 to grade 3 weight loss and reduced hypokalaemia. However, benefits in treatment compliance could not be detected. So consideration of PPEG in NPC patients requires care.

Zargaran, Massoumeh;Eshghyar, Nosratollah;Baghaei, Fahimeh;Moghimbeigi, Abbas 5811

https://doi.org/10.7314/APJCP.2012.13.11.5811 PDF KSCI

Background: Non-invasive oral verrucous carcinoma (OVC) and invasive well-differentiated oral squamous cell carcinoma (OSCC) have similar histopathologic findings but different biological behavior. These two malignancies must be correctly differentiated by pathologists. The aim of this study was to determine immunohistochemical (IHC) expression of Ki67 in OVC and well-differentiated OSCC. Methods: Expression of Ki67 was evaluated by IHC in 15 cases of epithelial hyperplasia with no dysplasia (A group), 15 cases of OVC (B group), 12 cases of microinvasive OSCC(C group) and 15 cases of well-differentiated OSCC (D group). Results: There was a significant difference in Ki67 expression based on pattern distribution of immunostaining positive cells, with quantitative and semi-quantitative analyses, among the four groups ; also, between A group and each of the other three groups (P=0.0001). But there was no significant difference between B and C, C and D, and B and D groups (P>0.05). Conclusions: The three evaluation methods of Ki67 expression showed Ki67 (Mib-1) is not a good immunohistochemical marker to assess invasion status and differentiate OVC from well-differentiated OSCC; also, it cannot be used as a diagnostic tool to distinguish between variants of OSCC with similar grade.

Sun, Zhen-Feng;Zhang, Jia;Xu, Hong-Ming;Wang, Guo-Liang;Dong, Pin 5817

https://doi.org/10.7314/APJCP.2012.13.11.5817 PDF KSCI

Background/Aims: Glutathione S-transferase M1 (GSTM1) is a multifunctional enzyme that plays a critical role in the detoxification of varieties of carcinogenic metabolites. Many studies have been conducted to investigate the association between GSTM1 polymorphism and nasopharyngeal cancer (NPC) risk, but the findings among those studies are inconsistent. To assess this relationship more precisely, we performed a meta-analysis of all available studies on the subject. Methods: Case-control studies were identified by searching Pubmed, Embase, ISI Web of Science, and Wanfang databases through September 6, 2012. We used the pooled odds ratio (OR) with its corresponding 95% confidence interval (95%CI) to evaluate the association of GSTM1 polymorphism with NPC susceptibility. Subgroup analyses by pathological types, sex and smoking status were performed to further identify the association. Results: Overall, 11 published studies with 1,513 cases and 2,802 controls were finally included into this meta-analysis according to the inclusion criteria. Meta-analysis of total studies showed that the null genotype of GSTM1 was significantly associated with increased risk of NPC, when comparing with the non-null genotype (OR=1.51, 95%CI=1.33-1.72, POR<0.001). The association was still statistically significant in subgroup analysis of patients with nasopharyngeal squamous cell carcinoma (OR=1.73, 95%CI=1.24-2.42, POR=0.001). Males with the null genotype of GSTM1 were more likely to subject to NPC than females. In addition, the association between the null genotype of GSTM1 and NPC risk was strongest in individuals with exposure to smoking. Sensitivity analysis by sequential omission of any individual studies one at a time further demonstrated the significant association. Conclusions: The findings suggest that the null genotype of GSTM1 is a risk factor for NPC, and there is a gene-smoking interaction in this association.

Erbil, Nulufer;Bolukbas, Nurgul 5823

https://doi.org/10.7314/APJCP.2012.13.11.5823 PDF KSCI

Background: Breast cancer (BC) is one of the most common cancer affecting women worldwide. Although a great deal of progress has been made in the health sciences, early diagnosis, and increasing community awareness, breast cancer remains a life-threatening illness. In order to reduce this threat, breast cancer screening needs to be implemented in all communities where possible. Objective: The purpose of this study was to examine health beliefs, attitudes and behaviors about breast cancer and breast self-examination of Turkish women. Methods: Data were collected from a sample of 656 women, using an adapted Turkish version of Champion's Health Belief Model Scale (CHBMS), between January and May 2011, in Ordu province of Turkey. Results: The results showed that 67.7% of women had knowledge about and 55.8% performed BSE, however 60.6% of those who indicated they practiced BSE reported they did so at irregular intervals. CHBMS subscales scores of women according to women's age, education level, occupation, family income and education level of the women's mothers, family history of breast cancer, friend and an acquaintance with breast cancer, knowledge about breast cancer, BSE and mammography were significantly different. Conclusion: Knowledge of women about the risks and benefits of early detection of breast cancer positively affect their health beliefs, attitudes, and behaviors. Health care professionals can develop effective breast health programs and can help women to gain good health behavior and to maintain health.

Pereira, Ana;Garmendia, Maria Luisa;Alvarado, Maria Elena;Albala, Cecilia 5829

https://doi.org/10.7314/APJCP.2012.13.11.5829 PDF KSCI

Background: Breast cancer is the most common cancer in women worldwide. Although different metabolic factors have been implicated in breast cancer development, the relationship between hypertension and breast cancer has not been elucidated. Aim: To evaluate hypertension as a risk factor for breast cancer in Chilean women of low and middle socio-economic status. Methods: We conducted an age-matched (1:1) case-control study in 3 hospitals in Santiago, Chile. Breast cancer cases (n=170) were histopathologically confirmed. Controls had been classified as Breast Imaging Reporting and Data System I (negative) or II (benign findings) within 6 months of recruitment. Blood pressure was measured using a mercury sphygmomanometer and standardized procedures. We used 2 hypertension cut-off points: blood pressures of ${\geq}140/90$ mmHg and ${\geq}130/85$ mmHg. Fasting insulin and glucose levels were assessed, and anthropometric, sociodemographic, and behavioral information were collected. Odds ratios and 95% confidence intervals were estimated for the entire sample and restricted to postmenopausal women using multivariable conditional logistic regression models. Results: Hypertension (${\geq}140/90$ mmHg) was significantly higher in cases (37.1%) than controls (17.1%) for the entire sample and in postmenopausal pairs (44.0% compared to 23.8%). In crude and adjusted models, hypertensive women had a 4-fold increased risk of breast cancer (adjusted odds ratio: 4.2; 95% confidence interval: 1.8; 9.6) compared to non-hypertensive women in the entire sample. We found a similar association in the postmenopausal group (adjusted odds ratio: 2.8; 95% confidence interval: 1.1; 7.4). A significant effect was also observed when hypertension was defined as blood pressure of ${\geq}130/85$ mmHg. Conclusion: A significant association was found between hypertension and breast cancer over the entire sample and when restricted to postmenopausal women. Hypertension is highly prevalent in Latin America and may be a modifiable risk factor for breast cancer; therefore, a small association between hypertension and breast cancer may have broad implications.

Dinc, Ayten 5835

https://doi.org/10.7314/APJCP.2012.13.11.5835 PDF KSCI

Objective: Cervix cancer is one of the most common gynecological cancer types that cause cancer deaths among women. This study was planned based on a descriptive method in order to evaluate the results of PAP smear screening during pregnancy for prevention of cancer. Materials and Methods: The research involved 110 pregnant women registered at the Obstetrics and Gynecology Polyclinic of Bagcilar Training and Research Hospital and 86 non-pregnant women of the same ages as a control group. As criteria for acceptance were conditions such as not being in coitus within the last 48 hours, not using vaginal ovule, and not performing vaginal lavage. A survey consisting of 33 questions was conducted and the results were processed using Bethesda. Results: The average ages were $27.1{\pm}4.70$ for the pregnant women and $28.8{\pm}4.24$ for the control group. 60.7% of cases had previously heard of a PAP smear test, 49% were aware of why PAP smear tests were conducted, 26.4% of pregnant participants and 27.3% of non-pregnant participants had previously undergone a smear test. In this study, smear results of all cases were 95.4% sufficient. 18.2% of pregnant cases had an infection, 54.5% had reactive cellular change, and 0.9% had atypical squamous cells of undetermined significance (ASC-US). 16.3% of non-pregnant cases had an infection, 58.1% had reactive cellular change, 3.5% had atypical squamous cells of undetermined significance (ASC-US), and 1.2% had low-grade squamous intraepithelial lesions (LGSIL). Conclusion: PAP smear test is a good opportunity to identify pre-invasive lesions in early phases of pregnancy.

Dilshad, Ahmad;Abulkhair, Omalkhair;Nemenqani, Dalal;Tamimi, Waleed 5839

https://doi.org/10.7314/APJCP.2012.13.11.5839 PDF KSCI

Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer. Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables. Nigella sativa has been shown to possess anti-carcinogenic activity, inhibiting growth of several cancer cell lines in vitro. However, the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood. Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of $2.5-5{\mu}g/mL$ (P<0.05). Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h. Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.

Hamedeyazdan, Sanaz;Fathiazad, Fatemeh;Sharifi, Simin;Nazemiyeh, Hossein 5843

https://doi.org/10.7314/APJCP.2012.13.11.5843 PDF KSCI

Aim: Developing antitumor drugs from natural products is receiving increasing interest worldwide due to limitations and side effects of therapy strategies for the second leading cause of disease related mortality, cancer. Methods: The antiproliferative activity of a methanolic extract from the aerial parts of Marrubium persicum extract was assessed with the MCF-7 breast cancer cell line using the MTT test for cell viability and cytotoxicity indices. In addition, antioxidant properties of the extract were evaluated by measuring its ability to scavenge free DPPH radicals. Moreover, the total phenolic and flavonoid content of the extract was determined based on Folin-Ciocalteu and colorimetric aluminum chloride methods. Results: The findings of the study for the antiproliferative activity of the methanolic extract of M. persicum showed that growth of MCF-7 cells was inhibited by the extract in a dose and time dependent manner, where a gradual increase of cytotoxicity effect has been achieved setting out on 200 ${\mu}g/mL$ concentration of the plant extract. The antioxidant assay revealed that the extract was a strong scavenger of DPPH radicals with an $RC_{50}$ value of 52 ${\mu}g/mL$. The total phenolic and flavonoids content of the plant extract was 409.3 mg gallic acid equivalent and 168.9 mg quercetin equivalent per 100g of dry plant material. Conclusion: Overall, M. persicum possesses potential antiproliferative and antioxidant activities on the malignant MCF-7 cell line that could be attributed to the high content of phenolics and flavonoids, and therefore warrants further exploration.

Shirinbayan, Vahid;Roshan, Valiollah Dabidi 5849

https://doi.org/10.7314/APJCP.2012.13.11.5849 PDF KSCI

Objective: The purpose of this study was to determine pretreatment effects of moderate-term endurance training before the various dosages (10 and $20{_{mg.kg}}^{-1}$) of DOX on a heat shock protein ($HSP_{70kda}$) and cardiotoxicity in heart tissue. Methods: Forty-eight male rats were randomly assigned to nontraining (NT) and training (T) groups and three subgroups; $DOX{_{10mg.kg}}^{-1}$ and $DOX{_{20mg.kg}}^{-1}$ and saline treatment. The training program included treadmill running between 25-39 min/day and 15-17 m/min, 5 days/wk for 3 wk. Result: DOX administration, in particularly with $20{_{mg.kg}}^{-1}$, caused up-regulation of oxidants and cardiac damage (MDA, CK, CPK-MB and CK/CPK-MB) and down-regulation of cardioprotection ($HSP_{70}$, SOD) markers, as compared to NT+saline group. Pretreatment effect of treadmill running endurance exercise in the presence of DOX with $10{_{mg.kg}}^{-1}$ caused a significant increase in $HSP_{70}$, SOD and a significant decrease in MDA and insignificant decrease in CK, CPK-MB and CK/CPK-MB, in comparison $T+DOX_{10}$ with $NT+DOX_{10}$ group. However, there was no significant difference between $T+DOX{_{10mg.kg}}^{-1}$ and $T+DOX{_{20mg.kg}}^{-1}$ in the aforesaid markers. Conclusion: Dox-induced cardiotoxicity is related to oxidative stress. Our study suggests that pretreatment with endurance exercise may be considered as a potentially useful strategy to improve myocardial tolerance against single dose DOX-induced oxidative damage.

Barchana, Micha;Margaliot, Menahem;Liphshitz, Irena 5857

https://doi.org/10.7314/APJCP.2012.13.11.5857 PDF KSCI

Introduction: Mobile phones are in extensive use worldwide and concerns regarding their role in tumor formation were raised. Over the years multiple studies were published in order to investigate this issue using several approaches. The current study looks at secular trends of brain gliomas (low and high grade) incidence and changes in tumor's laterality over 30 years in a population extensively using this technology with a possible correlation to the spread of use of mobile phones. Materials and Methods: All brain gliomas that were diagnosed from 1980-2009 were included and subdivided into two groups - low and high grade. Secular and periodic time trend analyses of incidence rates and changes in laterality were performed. Preferred side of head using mobile phones was assessed with a questionnaire in a sample of adult individuals. Results: A decrease in incidence of low grade giomas (LGG) that correlated with introduction of mobile technology was found from 2.57, 2.34 and 2.79 for every 100,000 in the period 1980 to the end of 1994 to 1.72, 1.82 and 1.57, respectively, over the last three 5-years periods (1995-2009). High-grade glioma incidences increased significantly from 1980-2009 but in the period after mobile phones were introduced (1994-2009) a lower, non significant, rate of increase was observed in males and a lower one (significant) in females. A shift towards left sided tumor location for all adult gliomas combined and separately for LGG and HGG was noted from 1995 onward. The shift was more marked for those who were diagnosed in ages 20-49 (p=0.03). Conclusions: We found a statistically significant decrease in LGG's over 30-years period that correlates with introducing of mobile phones technology and a shift in laterality towards left-sided tumors, the latter occurred in both low and high-grade gliomas.

Ghafouri-Fard, Soudeh;Abdollahi, Davood Zare;Omrani, Mirdavood;Azizi, Faezeh 5865

https://doi.org/10.7314/APJCP.2012.13.11.5865 PDF KSCI

RHOXF1 has been shown to be expressed in embryonic stem cells, adult germline stem cells and some cancer lines. It has been proposed as a candidate gene to encode transcription factors regulating downstream genes in the human testis with antiapoptotic effects. Its expression in cancer cell lines has implied a similar role in the process of tumorigenesis. The human breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in DMEM medium and transfected with a pGFP-V-RS plasmid bearing an RHOXF1 specific shRNA. Quantitative real-time RT-PCR was performed for RHOXF1, CASP8, BCL2 and HPRT genes. Decreased RHOXF1 expression was confirmed in cells after transfection. shRNA knock down of RHOXF1 resulted in significantly decreased BCL2 expression in both cell lines but no change in CASP8 expression. shRNA targeting RHOXF1 was shown to specifically mediate RHOXF1 gene silencing, so RHOXF1 can mediate transcriptional activation of the BCL2 in cancers and may render tumor cells resistant to apoptotic cell death induced by anticancer therapy. shRNA mediated knock down of RHOXF1 can be effective in induction of apoptotic pathway in cancer cells via BCL2 downregulation, so it can have potential therapeutic utility for human breast cancer.

Hansa, Jagadish;Kannan, Ravi;Ghosh, Sankar Kumar 5871

https://doi.org/10.7314/APJCP.2012.13.11.5871 PDF KSCI

Around 1.35 million people of worldwide suffer from breast cancer each year, whereas in India, 1 in every 17 women develops the disease. Mutations of the Breast Cancer 1 (BRCA1) gene account for the majority of breast/ovarian cancer families. The purpose of study was to provide a prevalence of BRCA1 germline mutations in the North-East Indian population. In relation to the personal and family history with the breast cancer, we found mutations in 6.25% and 12.5% respectively. Three mutations, 185DelAG, 1014DelGT and 3889DelAG, were observed in our North-East Indian patients in exons 2 and 11, resulting in truncation of the BRCA1 protein by forming stop codons individually at amino acid positions 39, 303 and 1265. Our results point to a necessity for an extensive mutation screening study of high risk breast cancer cases in our North-East Indian population, which will provide better decisive medical and surgical preventive options.

Canbay, Emel;Kurnaz, Ozlem;Canbay, Bahar;Bugra, Dursun;Cakmakoglu, Bedia;Bulut, Turker;Yamaner, Sumer;Sokucu, Necmettin;Buyukuncu, Yilmaz;Yilmaz-Aydogan, Hulya 5875

https://doi.org/10.7314/APJCP.2012.13.11.5875 PDF KSCI

Background: Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) is a ligand dependent transcription factor involved in various processes, including carcinogenesis. We aimed to investigate any possible association of the $PPAR{\gamma}$ Pro12Ala (rs1801282) polymorphism with risk of developing gastric cancer (GC). Patients and Methods: A hospital based case control study was designed covering 50 patients with GC and 120 healthy controls. The frequencies of $PPAR{\gamma}$ Pro12Ala (rs1801282) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The Ala12 allele of the $PPAR{\gamma}$ Pro12Ala G gene was associated with a 1.95 fold increased risk of GC development (p: 0.022; 95% CI: 1.58-2.40). Subgroup analyses showed that the same allele was also associated with metastasis (p: 0.000; OR:4.09; 95%CI:2.273-7.368) and differentiation (p: 0.004; OR:1.95; 95%CI:1.335-2.875) in patients with GC. Conclusion: This study suggests that the $PPAR{\gamma}$ Pro12Ala G (Ala12) allele might be associated with development, differentiation and metastatic process of GC in the Turkish population. Further studies conducted in larger study groups and in different ethnic populations will be needed to clarify the exact role of the $PPAR{\gamma}$ Pro12Ala polymorphism in GC.

Kotepui, Manas;Thawornkuno, Charin;Chavalitshewinkoon-Petmitr, Porntip;Punyarit, Phaibul;Petmitr, Songsak 5879

https://doi.org/10.7314/APJCP.2012.13.11.5879 PDF KSCI

Breast cancer is the leading cause of cancer deaths among women worldwide, including Thailand. In the present study, the differential mRNA expression of SVEP1, LPHN3, KLB, ITGA7, SEMA3G, TNS1 and MMP13 genes was examined in breast cancer using quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR). Among these genes, increased LPHN3 and MMP13 mRNA expression levels correlated with axillary-node metastasis (P=0.02). Multiple logistic regression analysis revealed that LPHN3 and MMP13 mRNA expression is significantly associated with axillary node status in breast cancer (P=0.04).

Yang, Li-Min;Li, Xiu-Hua;Bao, Cui-Fen 5883

https://doi.org/10.7314/APJCP.2012.13.11.5883 PDF KSCI

Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the response of GSTP1, ERCC1 and ERCC2 to chemotherapy among osteosarcoma patients, and the role of these genes on the prognosis of osteosarcoma. 187 patients with osteosarcoma were administered with methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine treatment. GSTP1, ERCC1 and ERCC2 polymorphism was genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.25). Individuals with ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated test of GSTP1 and ERCC2 Lys751Gln polymorphisms might be a candidate pharmacogenomic factors to be explored in the future to identify the osteosarcoma patients who might benefit from chemotherapy.

Manjamalai, A.;Kumar, M.J. Mahesh;Grace, V.M. Berlin 5887

https://doi.org/10.7314/APJCP.2012.13.11.5887 PDF KSCI

Background: To determine the effect of essential oil obtained from a traditionally used medicinal plant Tridax procumbens L, on lung metastasis developed by B16F-10 melanoma cells in C57BL/6 mice. Materials and Methods: Parameters studied were toxicity, lung tumor nodule count, histopathological features, tumor directed capillary vessel formation, apoptosis and expression levels of $P^{53}$ and caspase-3 proteins. Results: In vitro the MTT assay showed cytotoxicity was found to be high as 70.2% of cancer cell death within 24hrs for $50{\mu}g$. In vivo oil treatment significantly inhibited tumor nodule formation by 71.7% when compared with untreated mice. Formation of tumor directed new blood vessels was also found to be inhibited to about 39.5%. TUNEL assays also demonstrated a significant increase in the number of apoptotic positive cells after the treatment. $P^{53}$ and caspase-3 expression was also found to be greater in the essential oil treated group than the normal and cancer group. Conclusions: The present investigation showed significant effects of the essential oil of Tridax procumbens L in preventing lung metastasis by B16F-10 cell line in C57BL/6 mice. Its specific preventive effect on tumor directed angiogenesis and inducing effect on apoptosis warrant further studies at the molecular level to validate the significance of Tridax procumbens L for anticancer therapy.

Xiao, Jiang-Wei;Chen, Jia-Hui;Ren, Ming-Yang;Tian, Xiao-Bing;Wang, Chong-Shu 5897

https://doi.org/10.7314/APJCP.2012.13.11.5897 PDF KSCI

The aim of the study was to clarify the role of gastrokine 1 in the process of formation and development of gastric cancer. The expression of gastrokine 1 in gastric cancer and corresponding non-cancerous gastric tissues of 52 gastric cancer patients was assessed with the real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry. We also analyzed the relationship between the expression level and clinicopathological characteristics. Gastrokine 1 gene and protein expression in gastric cancer tissues was in both cases significantly lower than in corresponding non-cancerous gastric tissues (both P<0.01), but no significant relationship was found with clinicopathological parameters including tumor location, depth of invasion, differentiation, lymph node metastasis, stage, gender, age and carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) level in peripheral blood preoperation of patients (P>0.05, respectively). Furthermore, gastrokine 1 gene expression was markedly lower in gastric cancer tissues of Helicobacter pylori (HP)-positive patients than negative ones (P<0.05). The result of the study showed that gastrokine 1 might play a significant role in the process of formation and development of gastric cancer as an anti-oncogene. Its effect might be weakened by HP infection.

Hu, Li-Xia;Du, Ying-Ying;Zhang, Ying;Pan, Yue-Yin 5903

https://doi.org/10.7314/APJCP.2012.13.11.5903 PDF KSCI

Objective: The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. Methods: Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. Results: MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI<1). In addition, the combination of exemestane and aspirin exhibited a synergistic inhibition of cell proliferation, significantly arrested the cell cycle in the $G_0/G_1$ phase and produced a stronger inhibitory effect on COX-1 and Bcl-2 expression than control or individual drug treatment. Conclusion: These results indicate that the combination of exemestane and aspirin might become a useful method to the treatment of hormone-dependent breast cancer. The combination of the two inhibitors significantly increased the response as compared to single agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer.

Guo, Cun-Li;Yang, Hai-Chao;Yang, Xiu-Hua;Cheng, Wen;Dong, Tian-Xiu;Zhu, Wen-Jing;Xu, Zheng;Zhao, Liang 5909

https://doi.org/10.7314/APJCP.2012.13.11.5909 PDF KSCI

Aims: We aimed to analyze the phenotype of tumor-infiltrating lymphocytes (TILs) and non-tumor infiltrating lymphocytes (NILs) in HCC and non-tumor tissues, and evaluate relationships between changes in these cells and the prognosis of HCC. Methods: Lymphocytes were isolated from HCC and corresponding non-tumor tissues and tested by flow cytometry. For comparison, clinical parameters were analyzed. Results: Compared with the non-tumor tissue, tumor tissue had a lower intensity of NK, NKT andCD8+T cell infiltration. TILs had higher intensity of CD4+CD25+Foxp3+regulatory T cell (Treg cells) infiltration compared with that in NILs. The prevalence of Treg cells was associated with fewer CD8 + T lymphocytes in the HCC immune microenvironment. The frequencies of NK cells and CD8+T cells in TILs of HCC patients with metastasis less than 12 months were lower than those without metastasis. However, the frequency of Treg cells was higher than those without metastasis. Conclusion: These results suggest that the frequencies of CD8+T, NK and NKT cells as well as Treg cells in the tumor tissue of HCC are significantly associated with patient survival, and could be applied as predictive indicators for HCC prognosis.

Sendur, Mehmet Ali Nahit;Aksoy, Sercan;Ozdemir, Nuriye Yildirim;Zengin, Nurullah;Altundag, Kadri 5915

https://doi.org/10.7314/APJCP.2012.13.11.5915 PDF KSCI

Human epidermal growth factor receptor (HER) 2 overexpression, observed in 20-25 percent of invasive breast cancers, is well known to be associated with a more aggressive phenotype and poor prognosis, with resistance to certain chemotherapeutic agents. The majority of patients with metastatic breast cancer who initially respond to trastuzumab, demonstrate disease progression within 1 year of treatment initiation. Furthermore, lack of response in some patients and relapse during the course of therapy, continue to challenge researchers and clinicians. A better understanding of the fundamental mechanisms of trastuzumab action is required so that new therapies directed at HER2 can be developed. We present here findings for mechanisms, both of Trastuzumab action and clinical resistance or escape.

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