Asian Pacific Journal of Cancer Prevention

Senthilkumar, Chinnu Sugavanam;Sah, Nand Kishore;Ganesh, Narayanan 2429

https://doi.org/10.7314/APJCP.2012.13.6.2429 PDF KSCI

Methyl isocyanate may have a role in cancer etiology, although the link is unclear. There is evidence in the literature that it can induce cancer in animals but the carcinogenic potency is weak. Pheochromocytoma of adrenal medulla and acinar cell tumors of pancreas have been observed in methyl isocyanate exposed animals. Conversely, emerging data from population-based epidemiological studies are contradictory since there is no evidence of such cancers in methyl isocyanate exposed humans. Recently, we reported a high prevalence of breast and lung cancers in such a population in Bhopal. In vitro findings appearing in the latest scientific literature suggest that genomic instability is caused by methyl isocyanate analogs in lung, colon, kidney, ovary epithelial cells, and that hepatocytes may undergo oncogenic transformation, have obvious implications. The conflicting information prompted us to present this update over the last three decades on methyl isocyanate-induced cancers after an extensive literature search using PubMed. While the pertinent literature remains limited, with a scarcity of strong laboratory analyses and field-epidemiological investigations, our succinct review of animal and human epidemiological data including in vitro evidences, should hopefully provide more insight to researchers, toxicologists, and public health professionals concerned with validation of the carcinogenicity of methyl isocyanate in humans.

Zhang, Yao-Yao;Chen, Bin;Ding, Yan-Qing 2437

https://doi.org/10.7314/APJCP.2012.13.6.2437 PDF KSCI

Tumor metastasis remains the principal cause of treatment failure and poor prognosis in patients with colorectal cancer. It is a multistage process which includes proteolysis, motility and migration of cells, proliferation in a new site, and neoangiogenesis. A crucial step in the process of intra- and extra-vasation is the activation of proteolytic enzymes capable of degrading the extracellular matrix (ECM). In this stage, urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs) are necessary. Micrometastases need the presence of growth factor and vascular growth factor so that they can form macrometastasis. In addition, cell adhesion molecules (CAMs) and guanine nucleotide exchange factors (GEFs) play important roles in the progression of colorectal cancer and metastatic migration. Further elucidation of the mechanisms of how these molecules contribute will aid in the identification of diagnostic and prognostic markers as well as therapeutic targets for patients with colorectal metastasis.

Ramachandran, Puthucode Venkatakrishnan;Ignacimuthu, Savarimuthu 2445

https://doi.org/10.7314/APJCP.2012.13.6.2445 PDF KSCI

RNA interference has created a breakthrough in gene silencing technology and there is now much debate on the successful usage of RNAi based methods in treating a number of debilitating diseases. Cancer is often regarded as a result of mutations in genomic DNA resulting in faulty gene expression. The occurrence of cancer can also be influenced by epigenetic irregularities in the chromatin structure which leads to alterations and mutations in DNA resulting in cancer cell formation. A number of therapeutic approaches have been put forth to treat cancer. Anti cancer therapy often involves chemotherapy targeting all the cells in common, whereby both cancer cells as well as normal cells get affected. Hence RNAi technology has potential to be a better therapeutic agent as it is possible to deactivate molecular targets like specific mutant genes. This review highlights the successful use of RNAi inducers against different types of cancer, thereby paving the way for specific therapeutic medicines.

Demirbag, Birsel Canan 2453

https://doi.org/10.7314/APJCP.2012.13.6.2458 PDF KSCI

Background: The healthcare needs of cancer patients are complex and persons involved in their caregiving process are faced with many issues that need to be addressed. The entire family and particularly the person taking on responsibility for patient care develop expectations from healthcare professionals, especially nurses. Objective: The study was conducted to evaluate the impact of a home education program provided to caregivers of cancer patients on the level of their perceived social support and problems in caregiving. Interventions/Methods: The caregivers of thirty seven cancer patients of 2,400 registered people in a family center were given an educational program in this descriptive and cross-sectional study twice a week for a month during the period of March 2011 - April 2011. Results: Of all caregivers, 56.8% were between the ages 36-40, 94.5% were female, 91.9% had received no education on caregiving, 81.0% stated that they mostly felt physically and mentally inadequate in their caregiving. Perceived Social Support from the family indicated a significant difference at $8.05{\pm}4.38$ before and $11.7{\pm}4.97$ after the education. A comparison of the mean scores of caregivers on emotional issues before and after the education revealed the following: spiritual distress scores were $2.54{\pm}0.69$ before and $2.44{\pm}0.43$ after the education; hopelessness scores, $2.24{\pm}0.59$ before and $2.23{\pm}0.38$ after the education; ineffective individual coping was $3.89{\pm}1.42$ before and $2.45{\pm}0.59$ after the education; competing needs in decision-making were $3.54{\pm}0.69$ before and $2.10{\pm}1.24$ after the education; depressive feeling were $3.01{\pm}1.53$ before and $2.02{\pm}0.99$ after the education (p<0.05). Conclusions: Positive effects of home education on levels of perceived social support and caregiving problems of caregivers of cancer patients were observed. Home educational programs for caregivers of cancer patients are important for both better understanding of the requirements of their patients and themselves.

Zhang, Zeng-Li;Sun, Jing;Dong, Jia-Yi;Tian, Hai-Lin;Xue, Lian;Qin, Li-Qiang;Tong, Jian 2459

https://doi.org/10.7314/APJCP.2012.13.6.2459 PDF KSCI

Background: Numbers of epidemiological studies assessing residential radon exposure and risk of lung cancer have yielded inconsistent results. Methods: We therefore performed a meta-analysis of relevant published case-control studies searched in the PubMed database through July 2011 to examine the association. The combined odds ratio (OR) were calculated using fixed- or random-effects models. Subgroup and dose-response analyses were also performed. Results: We identified 22 case-control studies of residential radon and lung cancer risk involving 13,380 cases and 21,102 controls. The combined OR of lung cancer for the highest with the lowest exposure was 1.29 (95% CI 1.10-1.51). Dose-response analysis showed that every 100 Bq/$m^3$ increment in residential radon exposure was associated with a significant 7% increase in lung cancer risk. Subgroup analysis displayed a more pronounced association in the studies conducted in Europe. Studies restricted to female or non-smokers demonstrated weakened associations between exposure and lung cancer. Conclusions: This meta-analysis provides new evidence supporting the conclusion that residential exposure to radon can significantly increase the risk of lung cancer in a dose-response manner.

Azrif, Muhammad;Leong, Yu Kong;Aslan, Nik Muhammad;Fong, Kua Voon;Ismail, Fuad 2467

https://doi.org/10.7314/APJCP.2012.13.6.2467 PDF KSCI

Introduction: Although bleomycin/etoposide/cisplatinum (BEP) chemotherapy is established as the standard treatment for germ cell tumours, it requires significant experience in administration and toxicity management to maintain optimal dose intensity. A retrospective review of 30 patients was conducted at UKMMC to study treatment outcomes. Methods & Materials: Patients with GCTs and treated with at least two cycles of BEP chemotherapy between January 2003 and Oct 2009 were eligible for this study. Patients received 4-6 cycles of bleomycin 30,000IU IV D1, D8 & D15 and either etoposide $100mg/m^2$ IV D1-D5 and cisplatin $20mg/m^2$ IV D1-D5 (5 day BEP regimen) or etoposide $165mg/m^2$ D1-D3 and cisplatin $50mg/m^2$ D1-3 (3 day BEP regimen) every three weeks per cycle. All patients received prophylactic granulocyte colony-stimulating factor (GCSF) from days 6 to 10 of each cycle. The overall response rates, 2 year progression-free survival and overall survival of the whole cohort were assessed. Results: Thirty patients fulfilled the inclusion criteria. Non-seminomatous GCTs comprised 93.3% of cases and gonadal and mediastinal primary sites were the most common. Sixty percent were classified as IGCCCG poor risk disease. Median follow-up was 26.6 months. The overall response rate (CR+PR) was 70%. The two year PFS and OS were 70% and 66%. There was a significant difference in terms of the overall response rate (85% vs 40%, p = 0.03) and in PFS (94.7% vs 50%, p = 0.003) between gonadal and extragonadal primary sites. Conclusion: It is possible to achieve outcomes similar to those in international clinical trials with close monitoring and good supportive care of patients undergoing BEP chemotherapy. There is a strong argument for patients with IGCCCG poor prognosis disease to be treated in specialist tertiary centres to optimize treatment outcomes.

Zaman, Maseeh Uz;Fatima, Nosheen;Sajjad, Zafar;Akhtar, Jaweed;Islam, Najmul;Masood, Qamar;Ahmed, Asma 2473

https://doi.org/10.7314/APJCP.2012.13.6.2473 PDF KSCI

Background: In papillary and follicular thyroid cancers (PTC, FTC), nodal and distant metastasis are generally considered important determinants of recurrence and survival, respectively. However, there is no consensus about the threshold primary tumour size (PTS) for these determinants. The aim of this study was to assess size relationships for developing nodal, pulmonary, bone and overall distant metastases. Methods: This prospective study covered 139 (93 females and 46 males) consecutive biopsy proven patients with PTC (114/139, mean age $41.0{\pm}15.7$ years, M: F, 35%:65%) and FTC (25/139, mean age $39.2{\pm}14.3$ years, M: F: 24%:76%). Results: Average primary tumor size was $23.4{\pm}11.1$ mm and $26.5{\pm}13.1$ mm for PTC and FTC respectively (p value=0.223). Nodal metastasis was found more common in PTC than FTC (49% vs 28%, p value <0.05), whereas overall distant metastasis was approximately the same (13% and 24%, p value=0.277); however, bone metastasis was significantly higher in FTC than PTC (24% vs 5%, p value <0.05). Cumulative risk for nodal and distant metastases for FTC and PTC starts at PTS <20 mm and may indicate an unusual aggressive tumor behavior in the studied population. Highest cumulative risk for nodal and pulmonary metastases in PTC and for bone metastasis in FTC was found to be ${\geq}50$ mm PTS. Conclusion: We conclude that a PTS of <20 mm may indicate an unusual aggressive tumor behavior with highest cumulative risk for nodal and pulmonary metastases in PTC and for bone metastasis in FTC with a cutoff of ${\geq}50$ mm.

Laishram, Rajesh Singh;Kipgen, Paokai;Laishram, Sharmila;Khuraijam, Sucheta;Sharma, Durlav Chandra 2477

https://doi.org/10.7314/APJCP.2012.13.6.2477 PDF KSCI

Objective: To study the histomorphological pattern of urothelial tumors of the urinary bladder in Manipur and to evaluate whether any correlation exists between tumor grade and muscle invasion. Methods: A 10 year retrospective study of all consecutive cases diagnosed in the Department of Pathology RIMS - Imphal, between $1^{st}$ January 2001 to $31^{st}$ December 2010. Results: The study included 26 cases of transitional cell tumors of urinary bladder. The male to female ratio was 1.5:1 and the ages ranged from 38 years to 73 years (medians of 60 and 64 years, respectively). Of the total, 14 (53.9%) cases were low grade, 9 (34.6%) were high grade, 2 (7.7%) were papillomas and 1 (3.9%) was a papillary urothelial neoplasm of low malignant potential (PUNLMP). Pathological staging showed that 14 (53.9%) of the cases were stage PTa, four (15.4%) PT1, and eight (30.9%) PT2. Some 18.2% of low grade tumors and 75% of high grade tumors were invasive to the detrusor muscle layer. Conclusion: Bladder cancer is an uncommon disease, transitional tumors being the only histological type observed. It was more common in males than females, with peak incidence in seventh decade. Most of the tumors were non-invasive (PTa) and invasion to the detrusor muscle layer was seen in more than half of the high grade tumors. There is a definite correlation between advancing tumor grade and muscle invasion.

Zhong, Chen;Li, Kai-Nan;Bi, Jing-Wang;Wang, Bao-Cheng 2481

https://doi.org/10.7314/APJCP.2012.13.6.2481 PDF KSCI

Aim: The risk factors mostly strongly associated with gastric cancer are gastric bacteria Helicobacter pylori and diet. Using a case-control study among residents in Jinan, we examined the association between the salt taste and gastric cancer according to H. pylori infection, smoking and histological type as well as tumor site. Methods: This population-based case-control study included 207 cases and 410 controls. Data on potential risk factors of gastric cancer were obtained by interview of cases and controls with a questionnaire, salt taste preference was measured for all subjects, and IgG antibodies to H. pylori were applied to assess infection. Risk measures were determined using unconditional logistic regression. Results: The proportions of salt taste at intervals of 1.8-7.2 g/L and ${\geq}7.2$ g/L were significantly higher in cases than controls, with ORs of 1.56 (1.23-3.64) and 2.03 (2.12-4.11), respectively, subjects with high salt intake having an elevated risk for gastric cancer when infected with H. pylori. Significant modification by smoking and tumor site was observed across the different measures of salt intake, the highest salt taste showed higher cancer risk in ever smokers or with non-cardia cancers. Conclusion: Our study supports the view that high intake of sodium is an important dietary risk factor for gastric cancer, with a synergistic effect found between salt and H.pylori and smoking, dependent on the tumor site.

Ye, Qi-Fa;Zhang, Yi-Chuan;Peng, Xiao-Qing;Long, Zhi;Ming, Ying-Zi;He, Le-Ye 2485

https://doi.org/10.7314/APJCP.2012.13.6.2485 PDF KSCI

Purpose: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. Methods: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of $p21^{waf1/cip1}$ and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. Results: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased $p21^{waf1/cip1}$ expression and decreased Akt expression and activation in PC-3 cells. Conclusion: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.

Cheng, Zhe;Wang, Wei;Dai, Ling-Ling;Kang, Yan 2491

https://doi.org/10.7314/APJCP.2012.13.6.2491 PDF KSCI

The current study was performed to assess any association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of lung cancer in Henan province. This case-control study involved94 patients with newly histological confirmed lung cancer and 78 healthy controls. Genotyping was achieved with peripheral blood lymphocytes DNA and association of the polymorphism with risk of lung cancer was estimated by unconditional logistic regression analysis. The frequencies of the MTHFR 667TT genotype were 37.2% in cases compared with 23.1% in controls (${\chi}^2$ = 4.008, P = 0.045). Individuals with the 667CC/CT genotype displayed a significantly reduced risk of lung cancer compared with those with the TT genotypes [adjusted odds ratio (OR), 0.506; 95% confidence interval (95% CI), 0.258 - 0.991]. The C667T polymorphism might have a significant effect on the occurrence of lung cancer in Henan province.

Huang, Tian-Ren;Zhang, Si-Wei;Chen, Wan-Qing;Deng, Wei;Zhang, Chun-Yan;Zhou, Xin-Juan;Zhai, Ri-Hong 2495

https://doi.org/10.7314/APJCP.2012.13.6.2495 PDF KSCI

Nasopharyngeal carcinoma (NPC) is a disease with distinct ethnic and geographic distribution. The incidence of NPC in Chinese residing in Asia has declined over the last few decades, but NPC mortality trends in the entire Chinese population over time have not been systematically evaluated. In this study, we examined NPC mortality at the national level in China between 1973-2005. Mortality rates were derived from the databases of national retrospective surveys on cancer mortality conducted in the periods of 1973-1975, 1990-1992, and 2004-2005, respectively. NPC was classified according to the International classification of diseases. Age-adjusted mortality rates were calculated by direct standardization according to the world standard population. Trends in rates were evaluated by age, gender, geographic areas, and socioeconomic status. From 1973 to 2005, there was a general trend of decrease in NPC mortality in China, with higher rates in the south on a downward trend in the north. The age-standardized NPC mortality rates were 2.60 per 100,000 in 1973-1975, 1.94 per 100,000 in 1990-1992, and 1.30 per 100,000 in 2004-2005, respectively. The trend was similar in both men and women, in both urban and rural areas, but the declining rates in females were more remarkable than in males. The mortality rates were higher for the age groups above 50 years than those less than 50 years of age, both showing downward trend over 30-year period. In summary, the overall NPC mortality has consistently decreased in China over the past three decades, particularly in women and in old adults.

Zhang, Zhao-Yang;Dong, Jia-Hong;Chen, Yong-Wei;Wang, Xian-Qiang;Li, Chong-Hui;Wang, Jian;Wang, Guo-Qiang;Li, Hai-Lin;Wang, Xue-Dong 2503

https://doi.org/10.7314/APJCP.2012.13.6.2503 PDF KSCI

Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

Wang, Rui-Tao;Xu, Xin-Sen;Liu, Jun;Liu, Chang 2511

https://doi.org/10.7314/APJCP.2012.13.6.2511 PDF KSCI

Objective: To evaluate the prognostic factors of gallbladder carcinoma. Methods: Presentation, operative data, complications, and survival outcome were examined for 132 gallbladder carcinoma patients who underwent gallbladder surgery in our unit during 2002-2007, and follow-up results were obtained from every patient for univariate and multivariate survival analysis. Results: The univariate analysis showed that gallbladder lesion history, tumor cell differentiation, Nevin staging, preoperative lymph node metastasis and the surgical approach significantly correlated with the prognosis of the patients (p<0.05). The results of the multivariate analysis (Cox regression) showed that gallbladder lesion history, Nevin staging and the surgical approach were independent predicators with relative risks of 6.9, 4.4, 2.8, respectively (p=0.002, 0.003, 0.008). Conclusion: Gallbladder lesion history, Nevin staging and the surgical approach are independent prognostic factors for gallbladder carcinoma, a rapidly fatal disease. Therefore, early diagnosis, anti-infective therapy and radical surgery are greatly needed to improve the prognosis of gallbladder carcinoma.

Ng, Keng Lim;Htun, Thi Ha;Dublin, Norman;Ong, Teng Aik;Razack, Azad Hassan 2515

https://doi.org/10.7314/APJCP.2012.13.6.2515 PDF KSCI

Aim: To study the causes and significance of both microscopic and macroscopic haematuria in adult patients and assess possible relevance to early detection of urological cancers. Methods: 417 patients presenting with haematuria were assessed in our Urology Unit. Following confirmation of haematuria, these patients were subjected to imaging techniques and flexible cystoscopy. Parameters analysed included clinical characteristics, imaging results, flexible cystoscopy findings, time delay to diagnoses and eventual treatment and final diagnoses of all cases. Results: 390 haematuria cases were analysed from 417 consecutive patients with haematuria. After 27 cases were excluded as they had previous history, 245 microscopic and 145 macroscopic. Age range was 17 to 95 years old with predominance of 152 females to 239 males. The racial distribution included 180 Chinese, 100 Indians,95 Malays and 15 other races. The final diagnoses were benign prostatic hyperplasia (22.6%), no cause found (22.3%), other causes (18.7%), urolithiasis (11.5%), urinary tract infection UTI (10.8%), non specific cystitis (10.3%), bladder tumours (2.8%) and other genitourinary tumours (1%). 11 new cases (2.8%) of bladder cancers were diagnosed, with a mean age of 59 years. Only 3 of 245 (1.2%) patients with microscopic haematuria had newly diagnosed bladder tumour compared with 8 of 145 (5.5%) patients with frank haematuria (p=0.016). Mean time taken from onset of symptoms to diagnosis of bladder cancer was 53.3 days with definitive treatment (TURBT) in 20.1 days from diagnosis. Conclusion:- This study has highlighted the common causes of haematuria in our local setting. We recommend that full and appropriate investigations be carried out on patients with frank haematuria especially those above 50 years old in order to provide earlier detection and prompt management of bladder diseases especially tumours.

Yang, Xue-Xi;Li, Fen-Xia;Zhou, Cui-Ping;Hu, Ni-Ya;Wu, Ying-Shong;Li, Ming 2519

https://doi.org/10.7314/APJCP.2012.13.6.2519 PDF KSCI

Objective: Data from a recent genome-wide association studiesy of gastric cancer (GC) and oesophageal squamous cell carcinoma in Chinese living in the Taihang Mountains of north-central China suggest that 1q22 and 10q23 are susceptibility-associated regions for GC. However, this has not been confirmed in southern Chinese populations. The aim of this study was to investigate whether these polymorphisms at 1q22 and 10q23 are associated with the risk of GC in a southern Chinese population. Methods: We selected seven top significant associated single nucleotide polymorphisms (SNPs) at 1q22 and 10q23 and conducted a population-based case-control study in a southern Chinese population. Genotypes were determined using MassARRAYTM system (Sequenome, San Diego, CA). Results: Two SNPs at 1q22, rs4072037 and rs4460629, were significantly associated with a reduced risk of GC, best fitting the dominant genetic model. Logistic regression models adjusted for age and sex showed that rs4072037 AG and GG (OR=0.64, P=0.017, compared with AA) and rs4460629 CT and TT (OR=0.54, P=0.0016, compared with TT) significantly reduced the risk of GC. However, no significant results for the five SNPs at 10q23 were obtained in this study. Conclusion: These outcomes indicate that 1q22 is associated with GC susceptibility in this southern Chinese population, while an association for the locus at 10q23 was not confirmed.

Osmani, Asif Husain;Ansari, Tayyaba Zehra;Masood, Nehal;Ahmed, Bilal 2523

https://doi.org/10.7314/APJCP.2012.13.6.2523 PDF KSCI

Introduction: Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy and improvement in absolute neutrophil count (ANC) has been linked directly to improved outcome. Evaluation of granulocyte colony stimulating factors (GCSFs) for treatment has shown reduced incidences of episodes of prolonged neutropenia and protracted hospitalization. To determine absolute neutrophil counts with GCSF in febrile neutropenic cancer patients admitted to a tertiary care centre and to co-relate the improvement in ANC with mortality and hospital discharge. Methods: A prospective cross sectional study was carried at an oncology ward at Aga Khan University hospital from January 2010 to June 2011. All adult patients who were admitted and treated with GCSF for chemotherapy induced febrile neutropenia were included. Multivariable regression was conducted to identify the factors related with poor outcomes. Results: A total of 131 patients with febrile neutropenia were identified with mean age of 43.2 (18-85) years, 79 (60%) being ${\leq}50$. Seventy-five (57%) had solid tumors and 56 (43%) hematological malignancies, including lymphoma. Fifty seven (43.5%) had an ANC less 100 cells/$mm^3$, 34 (26%) one between 100-300 cells/$mm^3$ and 40 (31%) an ANC greater than 300 cells/$mm^3$. Thirty (23%) patients showed ANC recovery in 1-3 days, and 74(56%) within 4-7 days. Thirteen (10%) patients showed no recovery. The overall mortality was 18 (13.7%) patients. The mean time for ANC recovery seen in hematological malignancies was 6.34 days whereas for solid tumors it was 4.88 days. Patients with ANC <100 cells/$mm^3$ were more likely to die than patients with ANC >300 cells/$mm^3$ by a factor of 4.3. Similarly patients >50 years of age were 2.7 times more likely to die than younger patients. Conclusion: Our study demonstrated that use of GCSF, in addition to intravenous antibiotics, in treatment of patients with chemotherapy induced febrile neutropenia accelerates neutrophil recovery, and shortens antibiotic therapy and hospitalization. We propose to risk classify the patients at the time of admission to evaluate the cost effectiveness of this approach in a resource constrained setup.

Wang, Jin-Sheng;Ji, Ai-Fang;Wan, Hong-Jun;Lu, Ya-Li;Yang, Jian-Zhou;Ma, Li-Li;Wang, Yong-Jin;Wei, Wu 2527

https://doi.org/10.7314/APJCP.2012.13.6.2527 PDF KSCI

Objectives: The aim of the present study was to explore mechanisms underlying the effects of down-regulating ${\beta}$-catenin expression on esophageal carcinoma (EC) cells. Methods: Cell cycle distribution and apoptosis were determined using flow cytometry and annexin V apoptosis assay, respectively. Transmission electron microscopy (TEM) was used to examine changes in ultrastructure, while expression of cyclin D1 protein and mRNA was detected by western blot and real-time PCR. Proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) 1-2 were evaluated by Western blot analysis. PCNA labeling index (LI) was determined by immunocytochemistry. Results: Compared with pGen-3-con transfected and Eca-109 cells, the percentage of G0/G1-phase pGen-3-CTNNB1 transfected cells was obviously increased (P<0.05), with no significant difference among the three groups with regard to apoptosis (P>0.05). pGen-3-CTNNB1 transfected cells exhibited obvious decrease in cyclin D1 mRNA and protein expression (P<0.05) and the ultrastructure of Eca-109 cells underwent a significant change after being transfected with pGen-3-CTNNB1, suggesting that down-regulating ${\beta}$-catenin expression can promote the differentiation and maturation. The expression of PCNA and the ERKI/2 phosphorylation state were also down-regulated in pGen-3-CTNNB1 transfected cells (P<0.05). At the same time, the PCNA labeling index was decreased accordingly (P<0.05). Conclusion: Inhibition of EC Eca-109 cellproliferation by down-regulating ${\beta}$-catenin expression could improve cell ultrastructure by mediating blockade in G0/G1 through inhibiting cyclin D1, PCNA and the MAPK pathway (p-ERK1/2).

Hamizah, Sulaiman;Roslida, A.H.;Fezah, O.;Tan, K.L.;Tor, Y.S.;Tan, C.I. 2533

https://doi.org/10.7314/APJCP.2012.13.6.2533 PDF KSCI

Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(${\alpha}$)anthracene (DMBA 100ug/100ul acetone) and promotion by repeated application of croton oil (1% in acetone/twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in theAMLE-treated group. Interestingly, At 100 and 300 mg/kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.

Cheng, Chun-Xia;Xue, Min;Li, Kai;Li, Wu-Sheng 2541

https://doi.org/10.7314/APJCP.2012.13.6.2541 PDF KSCI

Objective: To investigate any association between XRCC1 and XRCC3 polymorphisms and outcome of platinum-based chemotherapy in ovarian cancer patients. Methods: With a prospective study design was cases were consecutively collected from January 2005 to January 2007. All 310 included patients were followed-up until the end of January 2010. Genotyping of XRCC1 and XRCC3 polymorphisms was conducted by TaqMan Gene Expression assays. Results: A total of 191 patients died during follow-up. Our study showed a lower survival rate in XRCC1 399 Arg/Arg genotype than Gln/Gln, with a significant increased risk of death (HR=1.69, 95%CI=1.07-2.78). Similarly, those carrying XRCC3 Thr/Thr genotype had a increased risk as compare to the Met/Met genotype, with a HR (95% CI) of 1.90 (1.12-3.41). There was no significant association between XRCC1 Arg194Trp and XRCC1Arg280His gene polymorphisms and ovarian cancer death. Conclusion: Our study demonstrates that polymorphisms in DNA repair genes have roles in the susceptibility and survival of ovarian cancer patients.

Ansari, Walid El;Labeeb, Shokria;Kotb, Safaa;Yousafzai, Mohammad T.;El-Houfey, Amira;Stock, Christiane 2547

https://doi.org/10.7314/APJCP.2012.13.6.2547 PDF KSCI

Objectives: Smoking among university students represents a formidable and global public health challenge. We assessed the associations between socio-demographic, health and wellbeing variables as independent variables, with daily smoking, attempts to quit smoking, and agreement with smoking ban as dependent variables. Methods: A sample of 3258 undergraduate students from eleven faculties at Assiut University, Assiut, Egypt, completed a general health questionnaire. Results: Overall daily or occasional smoking in last three months prior to the survey was about 9% (8% occasional and 1% daily smokers), and smoking was generally more prevalent among males (male=17%, female=0.6%, P < 0.001). After adjustment for confounders, not having normal BMI and having a mother who completed at least bachelor's degree education was positively associated with daily smoking, and conversely, no history of illicit drug use was a protective factor. About 76% of smokers had attempted to quit smoking within the last 12 months prior to the survey. Although a large proportion of students agreed/strongly agreed with the banning of smoking at university altogether (87%), such agreement was less likely among smokers. Conclusion: There is need for implementation of non-smoking policies on university premises, as well as regular up-to-date information on, and the periodic/yearly monitoring of tobacco use by university students employing standardised data collection instruments and reference periods. In addition, it would be valuable to develop campus-based educational/ awareness campaigns designed to counteract tobacco advertisement directed towards young people in Middle East countries. Otherwise, the danger could be that the current relatively low smoking prevalence among university students may escalate in the future.

Nazlican, Ersin;Akbaba, Muhsin;Okyay, R. Azim 2557

https://doi.org/10.7314/APJCP.2012.13.6.2557 PDF KSCI

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females in Turkey. The main problems experienced by women with breast cancer are physical losses, emotional distress and degradation in family, work and social roles. The purpose of this cross-sectional retrospective study was to investigate the socio-demographical characteristics and depressive symptoms of 125 newly diagnosed cases with breast cancer reported to cancer control department of Hatay provincial health directorate in 2011. To evaluate the depressive symptoms the Beck Depression Inventory (BDI) was used. All 125 cases who participated in the study were female. The mean age was $49.2{\pm}11.9$. The mean BDI score of the cases was $17.5{\pm}10.6$. The number of cases whose BDI scores were 17 and above was 65 (52.0%), and the number of cases whose BDI scores were under 17 was 60 (48.0%). The most striking finding in our study was that only 4 of the cases were receiving psychological help and support. The rate of depression was found high in our study and psychological support is a must for patients with a life threatening disease such as cancer.

Sharma, Veena;Paliwal, Ritu;Janmeda, Pracheta;Sharma, Shatruhan 2563

https://doi.org/10.7314/APJCP.2012.13.6.2563 PDF KSCI

Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of Moringa oleifera as a hepatoprotective and an antioxidant against 7, 12-dimethylbenz[a]anthracene induced hepatocellular damage. Single oral administration of DMBA (15 mg/kg) to mice resulted in significantly (p<0.001) depleted levels of xenobiotic enzymes like, cytochrome P450 and b5. DMBA induced oxidative stress was confirmed by decreased levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) in the liver tissue. The status of hepatic aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) which is indicative of hepatocellular damage were also found to be decreased in DMBA administered mice. Pretreatment with the Moringa oleifera (200 and 400 mg/kg) orally for 14 days significantly reversed the DMBA induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that Moringa oleifera exhibits good hepatoprotective and antioxidant potential against DMBA induced hepatocellular damage in mice that might be due to decreased free radical generation.

Hasan, Hathama Razooki;Mathkor, Thikra Hasan;Al-Habal, Mohammed Hasan 2571

https://doi.org/10.7314/APJCP.2012.13.6.2571 PDF KSCI

Breast cancer is the first of the most common ten cancers in Iraq. Its etiology is multifactorial, oxidative stress and lipid peroxidation being suggested to play important roles in carcinogenesis. The purpose of this study was to investigate the oxidant-antioxidant status in breast cancer patients, by measuring SOD isoenzyme activities (total SOD, CuZn-SOD, Mn-SOD and EC-SOD) in plasma and breast tumors, and by estimating thiobarbituric reactive substances (TBRS) in tissue homogenates. General increase in total SOD activity was observed in plasma and tissue samples of breast tumors, greater in the malignant when compared to benign group (p<0.05). Mn-SOD showed a significant decrease in tissue malignant samples (p<0.05), and insignificant decrease in plasma malignant samples compared with control and benign samples. Plasma EC-SOD activity in both patient benign and malignant breast tumors demonstrated 3.5% and 22.8% increase, respectively. However, there was a decrease in tissue EC-SOD activity in malignant breast tumors when compared with benign. A similar tendency was noted for TBRS. We suggest that elevated total SOD might reflect a response to oxidative stress, and then may predict a state of excess reactive oxygen species in the carcinogenesis process. If there is proteolytic removal of the heparin binding domain, EC-SOD will lose its affinity for the extracellular matrix and diffuse out of the tissue. This will result in a decreased EC-SOD activity, thus leading to an increase in the steady-state concentration of $O^{2-}$ in this domain, and increase in EC-SOD activity in the extracellular fluid. This might explain the results recorded here concerning the decrease in tissue EC-SOD activity and increase in plasma of breast cancer patients.

Han, Bao-Lin;Xu, Xiang-Ying;Zhang, Chun-Zhi;Wu, Jian-Juan;Han, Chun-Feng;Wang, Hui;Wang, Xuan;Wang, Guang-Shun;Yang, Shu-Juan;Xie, Yao 2577

https://doi.org/10.7314/APJCP.2012.13.6.2577 PDF KSCI

Objective: To conduct a meta-analysis to investigate the value of EBV DNA in diagnosis of nasopharyngeal cancer (NPC) in Asian populations, and provide important evidence for screening. Methods: Prospective or respective case-control or cohort studies regarding the detection role of EBV DNA for NPC were included in our study. We conducted a comprehensive literature search in PubMed, EMBASE, and the Chinese Biomedical Database (CBM database between January 1980 and March 2012. Results: A total of 18 studies with 1492 NPC cases and 2641 health controls were included. Almost of the included studies were conducted in China, and only one other conducted in Thailand. The overall results demonstrated that the pooled sensitivity, specificity, positive likelihood (+LR) and negative likelihood (-LR) were 0.73 (0.71-0.75), 0.89 (0.88-0.90), 8.84 (5.65-13.84) and 0.19(0.11-0.32), respectively. The overall EBV DNA detection showed the largest area of 0.932 under the summary receiver operator curve (SROC). The accuracy of detection by plasma for NPC (0.86) was higher than in serum (0.81), with largest areas under the SROC of 0.97 and 0.91, respectively. Conclusion: Our results demonstrated the EBV DNA detection in plasma or serum has high sensitivity and specificity in diagnosis of NPC, especially in Chinese populations with a high risk of cancer.

Zhang, Zhen-Yong;Tian, Xin;Wu, Rong;Liang, Yuan;Jin, Xue-Ying 2583

https://doi.org/10.7314/APJCP.2012.13.6.2583 PDF KSCI

Aim: There is increasing evidence that ERCC1 and XPD have roles in response to chemotherapy among patients with NSCLC, but the results are conflicting. Therefore, we conducted the present prospective study in a Chinese population. Methods: A total of 632 primary NSCLC patients were included, followed-up from May 2006 to May 2011. Polymorphisms were detected by real time PCR with TaqMan probse, using genomic DNA extracted from peripheral blood samples. The Cox regression model was used to analyze the hazard ratios (HR) for ERCC1 and XPD. Results: The median time of follow-up was 31.6 months. Our results showed the ERCC1 118 T/T(HR=1.65, 95% CI=1.17-2.43) and XPD 751 Gln/Gln genotypes (HR=1.52, 95%CI=1.04-2.08) were associated with an increased risk of death from NSCLC. Moreover, the ERCC118 T allele and XPD 751 Gln allele genotypes had a more higher risk of death from NSCLC among both ex-smokers and current smokers. Conclusion: In summary, ERCC1 and XPD gene polymorphisms might provide better prognostic predictive information for NSCLC patients in Chinese populations, with smoking possibly interacting with the genotypes.

Paul, Proma;LaMontagne, D. Scott;Le, Nga Thi 2587

https://doi.org/10.7314/APJCP.2012.13.6.2587 PDF KSCI

Background: Limited human papillomavirus (HPV) related knowledge might be a barrier to future vaccine acceptance. From 2008-2010, PATH conducted an HPV vaccination demonstration project in partnership with the government immunization program in Vietnam, which included awareness campaigns prior to vaccination. Objective: To assess and compare knowledge and attitudes about cervical cancer and HPV vaccines between mothers and daughters, and whether knowledge was associated with vaccination status. Methods: We analyzed HPV-related knowledge and attitude data from mother-daughter paired responses to a cross-sectional household survey. After parents completed the survey, daughters were asked the same questions. We calculated the frequency of responses for each question and devised a scaled composite measure for knowledge. Results: Participants believed they had received enough information about cervical cancer and HPV vaccines and it was sufficient to make a decision about vaccination. Fifty percent of the participants knew HPV causes cervical cancer and 80% knew the HPV vaccine prevented cervical cancer. Mothers had more knowledge about cervical cancer and HPV infection (p<0.01), compared to daughters, who had more vaccine specific knowledge (p<0.01). However, the total mean knowledge score was similar for the groups. Girls not fully vaccinated had a lower mean knowledge score than fully vaccinated girls (p<0.001). Conclusions: Our results suggest that the purpose of the HPV vaccine was clearly messaged; however, some misconceptions about cervical cancer and HPV still exist. Limited knowledge about the magnitude of cervical cancer, HPV as a cause of cervical cancer, and HPV vaccines may have contributed to incomplete vaccination.

Li, Fang;Zhong, Mei-Zuo;Li, Jian-Huang;Liu, Wei;Li, Bin 2593

https://doi.org/10.7314/APJCP.2012.13.6.2593 PDF KSCI

Aims: A case-control study of 300 gastric cancer patients and 300 controls was conducted to investigate whether the polymorphisms rs2294008 in PSCA and rs2070803 in MUC1 might be associated with risk of gastric cancer in a Chinese population. Methods: Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY platform. Results: The data showed that the rs2294008 TT genotype increased gastric cancer risk to an adjusted odds ratio (OR) of 2.26 (95%CI 1.25-4.07), TC to 1.72 (95%CI 1.23-2.42) and TC/TT to 1.81 (95% CI 1.31-2.50), while the rs2070803 GA genotype was associated with a decrease in risk to an adjusted OR of 0.42 (95% CI 0.28-0.62) and rs2070803 GA / AA to 0.46 (95% CI 0.32-0.67). Further stratification analysis revealed that rs2294008 in PSCA consistently increased risk of both intestinal and diffuse-type gastric cancers. The effect of rs2070803 in MUC1 was noteworthily also consistent with both subtypes. Conclusions: Our study suggested rs2294008 in the PSCA gene to be associated with increased risk of gastric cancer and rs2070803 in MUC1 to play a protective role in a Chinese population.

Zhang, Wei-Bing;Zhang, Jun-Hong;Pan, Zheng-Qi;Yang, Qi-Sheng;Liu, Bo 2597

https://doi.org/10.7314/APJCP.2012.13.6.2597 PDF KSCI

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062 controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statistical relationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094; CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343; Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observe the homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of the polymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants' residential region: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asian studies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P < 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90], P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P < 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76], P < 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginal significance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphism against prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI = [0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI = [0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomena should be viewed with the consideration of folate metabolism profile and different gene background as well as living habits of different populations, and more relevant studies should be conducted to confirm our hypothesis and provide a comprehensive and clear picture concerning this topic.

Lu, Min;Sun, Luhaoran;Yang, Jing;Li, Yue-Yao 2605

https://doi.org/10.7314/APJCP.2012.13.6.2605 PDF KSCI

Background: Studies investigating the association of 2R/3R polymorphism in the thymidylate synthase 5'-untranslated enhanced region (TSER) and colorectal cancer (CRC) risk have reported conflicting results. Thus, a meta-analysis was performed to summarize the data on the potential association. Methods: Pubmed, Embase and CBM databases were searched for all available studies. Links between the TSER 2R/3R polymorphism and CRC risk were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Results: Seven case-control studies with a total of 2723 cases and 4030 controls were included in this meta-analysis. The results showed that the 3R variant of TSER 2R/3R polymorphism contributes to CRC risk in two comparison models (OR 3R vs. 2R =1.10, 95%CI 1.02-1.18, P = 0.015; OR Homozygote comparison model = 1.22 1.04-1.43, 95%CI 1.04-1.43, P = 0.012). Subgroup analyses by ethnicity further demonstrated a contribution in Caucasians with three comparison models (OR 3R vs. 2R = 1.10, 95%CI 1.02-1.19, P = 0.015; OR Homozygote comparison model = 1.21, 95%CI 1.03-1.41, P = 0.019; OR Recessive comparison model = 1.18, 95%CI 1.05-1.33, P = 0.008). However, the association in the Asian population was still uncertain due to the limited data (all P values were more than 0.05). Conclusions: Our meta-analysis suggests that the 3R variant of Thymidylate synthase 5'-untranslated enhanced region 2R/3R polymorphism contributes to gastric cancer risk in the Caucasian population, while any association in Asian populations needs further study.

Binnal, A.;Rajesh, G.;Denny, C.;Ahmed, J. 2611

https://doi.org/10.7314/APJCP.2012.13.6.2611 PDF KSCI

Introduction: To curb the ever growing menace of tobacco and its ill effects, it is essential to prevent its usage. Dental professionals' contributions can be invaluable in this venture. Objectives: To assess Indian dental graduates' knowledge, attitude and practices towards tobacco cessation; perceived effectiveness in pursuing tobacco cessation activities; perception of factors that interfere in tobacco cessation as barriers; and willingness to participate in tobacco cessation. Further, to determine associations among the aforementioned variables. Methodology: All house surgeons in Manipal College of Dental Sciences, Manipal University, Mangalore were included in the study. A structured, pre-tested and self-administered questionnaire was employed to assess participants' knowledge, attitude, behavior, perceived effectiveness, perceived barriers and willingness to participate in tobacco cessation. Information regarding respondents' age, gender and residence was collected. Results: A total of 100 out of 103 respondents participated in the study. Mean knowledge, attitude, behavior, perceived effectiveness, perceived barrier scores were $17.6{\pm}2.53$ (73.2%), $72.1{\pm}6.59$ (90.2%), $28.3{\pm}5.12$ (67.4%), $13.3{\pm}5.36$ (53.16%) and $35.0{\pm}3.79$ (89.8%) respectively. Overall, 97% respondents were willing to participate in tobacco cessation activities. Correlation analysis revealed that knowledge was associated with attitude (r=0.36, p=0.00) and perceived barriers (r=0.34, p=0.00) and behavior was associated with perceived barriers (r=0.22, p=0.03). Conclusions: Respondents reported high knowledge and attitude scores, along with high perceived barriers scores and willingness to participate in tobacco cessation activities. Present study highlights the need for a more meaningful involvement of dental professionals in tobacco cessation and has policy implications for curriculum changes regarding the same.

Chansaenroj, Jira;Theamboonlers, Apiradee;Junyangdikul, Pairoj;Supiyaphan, Pakpoom;Poovorawan, Yong 2619

https://doi.org/10.7314/APJCP.2012.13.6.2619 PDF KSCI

The prevalence of human papillomavirus genotypes differs in various target organs. HPV16 is the most prevalent genotype in the cervix while genotypes 6 and 11 are highly prevalent in skin and aero-digestive tract infections. In this study HPV11 positive specimens were selected from cervix, larynx and lung biopsy tissue to analyze the whole genome by PCR and direct sequencing. Five HPV11 whole genomes were characterized, consisting of two cervical specimens, two laryngeal specimens and one lung specimen. The results showed high homology of HPV11 in these organs. Phylogenetic analysis showed that all HPV11 derived from various organs belonged to the same lineage. Molecular characterization and functional studies can further our understanding of virulence, expression or transmission. Additional studies on functional protein expression at different organ sites will also contribute to our knowledge of HPV infection in various organs.

Alizadeh, Ali Mohammad;Roshandel, Gholamreza;Roudbarmohammadi, Shahla;Roudbary, Maryam;Sohanaki, Hamid;Ghiasian, Seyed Amir;Taherkhani, Amir;Semnani, Shahryar;Aghasi, Maryam 2625

https://doi.org/10.7314/APJCP.2012.13.6.2625 PDF KSCI

Introduction: Fumonisin B1 (FB1) is a toxic and carcinogenic mycotoxin produced in cereals due to fungal infection. This study was conducted to determine FB1 contamination of rice and corn samples and its relationship with the rate of esophageal cancer (EC) in a high risk area in northeastern Iran. Methods: In total, 66 rice and 66 corn samples were collected from 22 geographical subdivisions of Golestan province of Iran. The levels of FB1 were measured for each subdivision by thin layer and high pressure liquid chromatographies. The mean level of FB1 and the proportions of FB1 contaminated samples were compared between low and high EC-risk areas of the province. Results: The mean of FB1 levels in corn and rice samples were 223.64 and 21.59 ${\mu}g/g$, respectively. FB1 contamination was found in 50% and 40.9% of corn and rice samples, respectively. FB1 level was significantly higher in rice samples obtained from high EC-risk area (43.8 ${\mu}g/g$) than those obtained from low risk area (8.93 ${\mu}g/g$) (p-value=0.01). The proportion of FB1 contaminated rice samples was also significantly greater in high (75%) than low (21.4%) EC-risk areas (p-value=0.02). Conclusion: We found high levels of FB1 contamination in corn and rice samples from Golestan province of Iran, with a significant positive relationship between FB1 contamination in rice and the risk of EC. Therefore, fumonisin contamination in commonly used staple foods, especially rice, may be considered as a potential risk factor for EC in this high risk region.

Rai, Avdhesh K.;Freddy, Allen J.;Banerjee, Atanu;Kurkalang, Sillarine;Rangad, Gordon M.;Islam, Mohammad;Nongrum, Henry B.;Dkhar, Hughbert;Chatterjee, Anupam 2629

https://doi.org/10.7314/APJCP.2012.13.6.2629 PDF KSCI

Background: Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes. Methods: A panel of dinucelotide polymorphic markers were chosen for loss of heterozygosity studies in 93 samples of which 34 were collected from patients with only RBN-chewing habit. Promoter hypermethylation was also investigated. Results: Loss in microsatellite markers D9S1748 and D9S1749, located close to exon $1{\beta}$ of CDKN2A/ARF gene at 9p21, was noted in 40% ESCC samples with the habit of RBN-chewing alone. Involvement of a novel site in the 9p23 region was also observed. Promoter hypermethylation of CDKN2A gene in the samples with the habit of only RBN-chewing alone was significantly higher (p=0.01) than Rb1 gene, also from the samples having the habit of use both RBN and tobacco (p=0.047). Conclusions: The data indicate that the disruption of 9p21 where CDKN2A gene resides, is the most frequent critical genetic event in RBN-associated carcinogenesis. The involvement of 9p23 as well as 13q14.2 could be required in later stages in RBN-mediated carcinogenesis.

Pan, Zhao-Jun;Huang, Wei-Jia;Zou, Zi-Hao;Gao, Xing-Cheng 2635

https://doi.org/10.7314/APJCP.2012.13.6.2635 PDF KSCI

Background: Many studies have investigated the association between glutathione S-transferase T 1 (GSTT1) null genotype and risk of prostate cancer, but the impact of GSTT1 null genotype in Asians is still unclear owing to inconsistencies across results. Thie present meta-analysis aimed to quantify the strength of the association between GSTT1 null genotype and risk of prostate cancer. Methods: We searched the PubMed, Embase and Wangfang databases for studies of associations between the GSTT1 null genotype and risk of prostate cancer in Asians and estimated summary odds ratio (OR) with their 95% confidence interval (95% CI). Results: A total of 11 case-control studies with 3,118 subjects were included in this meta-analysis, which showed the GSTT1 null genotype to be significantly associated with increased risk of prostate cancer in Asians (random-effects OR = 1.49, 95% CI 1.15-1.92, P = 0.002), also after adjustment for heterogeneity (fixed-effects OR = 1.45, 95% CI 1.23-1.70, P < 0.001). No evidence of publication bias was observed. Conclusions: This meta-analysis of available data suggested the GSTT1 null genotype does contribute to increased risk of prostate cancer in Asians.

Roshanaei, Ghodratollah;Ghannad, Masoud Sabouri;Safari, Maliheh;Sadighi, Sanambar 2639

https://doi.org/10.7314/APJCP.2012.13.6.2639 PDF KSCI

Background: The patterns of gastric cancer recurrence vary across societies. We designed the current study in an attempt to evaluate and reveal the outbreak of the recurrence patterns of gastric cancer and also prediction of time to recurrence and its effected factors in Iran. Materials and Methods: This research was performed from March 2003 to February 2007. Demographic characteristics, clinical and pathological diagnosis and classification including pathologic stage, tumor grade, tumor site and tumor size in of patients with GC recurrent were collected from patients' data files. To evaluate of factors affected on the relapse of the GC patients, gender, age at diagnosis, treatment type and Hgb were included in the research. Data were analyzed using Kaplan-Meier and logistic regression models. Results: After treatment, 82 patients suffered recurrence, 42, 33 and 17 by the ends of first, second and third years. The mean ( SD) and median ( IQR) time to recurrence in patients with GC were 25.5 (20.6-30.1) and 21.5 (15.6-27.1) months, respectively. The results of multivariate analysis logistic regression showed that only pathologic stage, tumor grade and tumor site significantly affected the recurrence. Conclusions: We found that pathologic stage, tumor grade and tumor site significantly affect on the recurrence of GC which has a high positive prognostic value and might be functional for better follow-up and selecting the patients at risk. We also showed time to recurrence to be an important factor for follow-up of patients.

Pandey, Saumya;Mishra, Malvika;Chandrawati, Chandrawati 2643

https://doi.org/10.7314/APJCP.2012.13.6.2643 PDF KSCI

Objectives: Human papillomavirus (HPV) is the major etiological agent of cervical cancer, a leading cause of morbidity and mortality in women worldwide. Screening strategies for reducing the burden of HPV-mediated carcinogenesis are emerging as an effective means for cervical cancer control and prevention in developing countries. Our study, therefore, aimed to identify HPV infection status in North Indian women during random population screening. Methodology: Cervical/vaginal exfoliated cells and/or Pap smear specimens were collected from 890 women of North Indian ethnicity residing in Lucknow and adjoining areas, during random population screening from June 2009-March 2012. HPV viral loads in clinical specimens were determined by the Hybrid Capture (hc)-2 HPV DNA assay, and subsequently, positive/negative/borderline HPV status was calculated. Results: The HPV incidence in the present study was 11.7%. 751 out of a total of 890 women (84.4%) participating in our HPV screening program were HPV negative (HPV -), 104 (11.7%) tested positive (HPV +) while 35 (3.9%) showed borderline (HPV $^*$) infection status. Furthermore, in the HPV + subjects (N=104), 18 (17.3%) showed strong positivity. We observed that HPV positivity tends to increase with age in North Indian women; the higher the viral load with increasing age, higher is the susceptibility to HPV-mediated cervical cancer. Conclusions: HPV viral load/genotyping may help in identifying women at risk of developing cervical cancer. However, cost-effective HPV screening protocols with a wider population coverage are warranted so as to reduce the burden of cervical cancer in women worldwide in the vaccine-era.

Bandala, Cindy;Floriano-Sanchez, E.;Cardenas-Rodriguez, N.;Lopez-Cruz, J.;Lara-Padilla, E. 2647

https://doi.org/10.7314/APJCP.2012.13.6.2647 PDF KSCI

Involvement of cytochrome P450 genes (CYPs) in breast cancer (BCa) may differ between populations, with expression patterns affected by tumorigenesis. This may have an important role in the metabolism of anticancer drugs and in the progression of cancer. The aim of this study was to determine the mRNA expression patterns of four cytochrome P450 genes (CYP2W1, 3A5, 4F11 and 8A1) in Mexican women with breast cancer. Real-time PCR analyses were conducted on 32 sets of human breast tumors and adjacent non-tumor tissues, as well as 20 normal breast tissues. Expression levels were tested for association with clinical and pathological data of patients. We found higher gene expression of CYP2W1, CYP3A5, CYP4F11 in BCa than in adjacent tissues and only low in normal mammary glands in our Mexican population while CYP8A1 was only expressed in BCa and adjacent tissues. We found that Ki67 protein expression was associated with clinicopathological features as well as with CYP2W1, CYP4F11 and CYP8A1 but not with CYP3A5. The results indicated that breast cancer tissues may be better able to metabolize carcinogens and other xenobiotics to active species than normal or adjacent non-tumor tissues.

Kim, Dong-Woo;Oh, Se-Young;Kwon, Sung-Ok;Kim, Jeong-Seon 2655

https://doi.org/10.7314/APJCP.2012.13.6.2655 PDF KSCI

Validation of a food frequency questionnaire (FFQ) utilising a short-term measurement method is challenging when the reference method does not accurately reflect the usual food intake. In addition, food group intake that is not consumed on daily basis is more critical when episodically consumed foods are related and compared. To overcome these challenges, several statistical approaches have been developed to determine usual food intake distributions. The Multiple Source Method (MSM) can calculate the usual food intake by combining the frequency questions of an FFQ with the short-term food intake amount data. In this study, we applied the MSM to estimate the usual food group intake and evaluate the validity of an FFQ with a group of 333 Korean children (aged 3-6 y) who completed two 24-hour recalls (24HR) and one FFQ in 2010. After adjusting the data using the MSM procedure, the true rate of non-consumption for all food groups was less than 1% except for the beans group. The median Spearman correlation coefficients against FFQ of the mean of 2-d 24HRs data and the MSM-adjusted data were 0.20 (range: 0.11 to 0.40) and 0.35 (range: 0.14 to 0.60), respectively. The weighted kappa values against FFQ ranged from 0.08 to 0.25 for the mean of 2-d 24HRs data and from 0.10 to 0.41 for the MSM-adjusted data. For most food groups, the MSM-adjusted data showed relatively stronger correlations against FFQ than raw 2-d 24HRs data, from 0.03 (beverages) to 0.34 (mushrooms). The results of this study indicated that the application of the MSM, which was a better estimate of the usual intake, could be worth considering in FFQ validation studies among Korean children.

Jayakrishnan, R.;Mathew, Aleyamma;Lekshmi, Kamala;Sebastian, Paul;Finne, Patrik;Uutela, Antti 2663

https://doi.org/10.7314/APJCP.2012.13.6.2663 PDF KSCI

Objectives: An attempt was made to understand the nicotine dependence of smokers selected for an ongoing smoking cessation intervention programme in rural Kerala, India. Methods: Data were collected from resident males in the age group of 18 to 60 years from 4 randomly allocated community development blocks of rural Thiruvananthapuram district (2 intervention and 2 control groups). Trained accredited social health activist workers were utilised to collect data from all groups through face to face interview. Nicotine dependence among participants was assessed by means of the six-item Fagerstrom Test for Nicotine Dependence (FTND) translated into the local language. The internal consistency of FTND was computed using Cronbach's alpha coefficient. Criterion validity (concurrent) was assessed by correlations of nicotine dependence scores with age at initiation of smoking and cumulative smoking volume in pack-years. Results: Among the 928 smokers identified, 474 subjects were in the intervention area (mean age = 44.6 years, SD = 9.66 years) and 454 in the control area (mean age = 44.5 years, SD = 10.30 years). The overall FTND score among current daily smokers was 5.04 (SD: 5.05). FTND scores in the control and intervention areas were 4.75 (SD: 2.57) and 4.92 (SD: 2.51) respectively. The FTND scores increased with age and decreased with higher literacy and socioeconomic status. The average FTND score was high among smokers using both bidi and cigarettes (mean 6.10, SD 2.17). Internal consistency analysis yielded a Cronbach's alpha coefficient of 0.70 in a subsample of 150 subjects, a moderate result. The association of the scale was strongest, with the number of pack-years smoked (rho = 0.677, p < 0.001). Conclusion: A moderate level of nicotine dependence was observed among smokers in the current study. Tobacco cessation strategies could be made more cost effective and productive if a baseline assessment of nicotine dependence is completed before any intervention.

Hong, Guo-Bin;Zhou, Jing-Xing;Sun, Hua-Bin;Li, Chun-Yang;Song, Li-Qing 2669

https://doi.org/10.7314/APJCP.2012.13.6.2669 PDF KSCI

Purpose: Pancreatic carcinoma is one of the most malignant tumors of the alimentary system, with relatively high incidence rates. The purpose of this study was to assess the efficacy and safety of two regimens for advanced pancreatic carcinoma: continuous transarterial infusion versus systemic venous chemotherapy with gemcitabine and 5-fluorouracil. Methods: Of the 48 patients with advanced pancreatic carcinoma receiving chemotherapy with gemcitabine and 5-fluorouracil, 24 received the selective transarterial infusion, and 24 the systemic chemotherapy. For the continuous transarterial infusion group (experimental group), all patients received gemcitabine 1000 mg/$m^2$, given by 30-minute transarterial infusion, on day 1 of a 4-week cycle for 2 cycles, and a dose of 600 mg/$m^2$ 5-fluorouracil was infused on days 1~5 of a 4-week cycle for 2 cycles. For the systemic venous group (control group), gemcitabine and 5-fluorouracil were infused through a peripheral vein, a dose of 1000 mg/$m^2$ gemcitabine being administrated over 30 min on days 1 and 8 of a 4-week cycle for 2 cycles, and a dose of 600 mg/$m^2$ 5-fluorouracil was infused on days 1~5 of a 4-week cycle for 2 cycles. The effectiveness and safety were evaluated after 2 cyclesaccording to WHO criteria. Results:The objective effective rate in transarterial group was 33.3% versus 25% in the systemic group, the difference not being significant (P=0.626). Clinical benefit rates(CBR) in the transarterial and systemic groups were 83.3% and 58.3%, respectively (P=0.014). The means and medians for survival time in transarterial group were higher than those of the systemic group (P < 0.005). at the same time, the adverse effects did not significantly differ between the two groups (P > 0.05). Conclusion: Continuous transarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate and survival time of patients with advanced pancreatic carcinoma, compared with systemic venous chemotherapy. Since adverse effects were limited in the transarterial group, the regimen of continuous transarterial infusion chemotherapy can be used more extensively in clinical practice. A CT and MRI conventional sequence can be used for efficacy evaluation after chemotherapy in pancreatic carcinoma.

Sabokbar, Tayebeh;Khajeh, Elias;Taghdiri, Foad;Peyghambari, Vahideh;Shirkoohi, Reza 2675

https://doi.org/10.7314/APJCP.2012.13.6.2675 PDF KSCI

Introduction: Annually a considerable number of people die because of breast cancer, a common disease among women also in Iran. Identifying risk factors and susceptible people can lead to prevention or at least early diagnosis. Among susceptibility risks, 5-10% of patients have a family history predisposing factor which can influence the risk of incidence among the family. Having a registry program can be a more practical way to screen high risk families for preventive planning. Method: Based on inclusion criteria, a questionnaire was prepared and after a pilot study on a small number of patients, actual data were collected on 400 patients and processed in SPSS 16.0. Results: Totally, 28.2%of the patients were younger than 40 years old and 36.8% had the included criteria for familial breast cancer (FBC). 102 patient's samples could be compared for receptor presentation. Similar to other studies, the number of triple negative breast cancers increased as the age decreased. Conclusion: The high percentage of patients with FBC among 400 cases in this study demonstrates that in order to design an infrastructural diagnostic protocol and screening of patients with FBC, a precise survey related to frequency and founder mutations of FBC is needed nationwide.

Cheng, Tao;Zhang, Jian-Guo;Cheng, Yuan-He;Gao, Zhong-Wei;Ren, Xiao-Qiang 2681

https://doi.org/10.7314/APJCP.2012.13.6.2681 PDF KSCI

Objectives: This study focused on PTEN and Livin expression and associations with malignancy in human renal clear cell carcinomas (RCCC). Methods: PTEN and Livin expression was assessed in 100 RCCC tissue samples, 50 paracarcinoma cases, and 20 normal renal tissue samples using the immunohistochemical Streptavidin proxidase (SP) method. The relationships between binding and corresponding biological characteristics, such as histological grade, lymph node metastases, and clinical stages were analyzed. Results: Positive PTEN expression in RCCC was significantly lower than in renal tissue adjacent to carcinoma tissue and normal renal tissue (P<0.01). Livin expression in the renal tissue adjacent to the carcinoma and normal renal tissues exhibited only low levels, whereas overall Livin expression in RCCC was statistically significant (P<0.01). In RCCC, PTEN expression rate gradually decreased with an increase in clinical stage, whereas that of Livin increased to statistically significant levels (P<0.01), PTEN and Livin levels being negatively correlated (r=-0.395, P<0.01). Conclusions: PTEN and Livin are important in RCCC development. The two factors combined are expected to provide indices for estimating RCCC malignancy and progression levels, as well as references for RCCC diagnosis and treatment.

Zeng, Xian-Tao;Xiong, Ping-An;Wang, Fen;Li, Chun-Yi;Yao, Juan;Guo, Yi 2687

https://doi.org/10.7314/APJCP.2012.13.6.2687 PDF KSCI

Objective: Passive smoking has been considered as a risk factor of many cancers. To examine whether it might also pose a risk for cervical cancer, we performed a meta-analysis based on published case-control studies. Methods: We searched the PubMed database and references of included studies up to February 10th, 2012 for relevant studies. After two authors independently assessed the methodological quality and extracted data, a meta-analysis was conducted using CMA v2 software. Publication bias was evaluated by funnel plot, using Egger's and Begg's tests. Results: Finally 11 eligible studies yielded, involving 3,230 cases and 2,982 controls. The results showed that women who never smoke but exposed to smoking experience a 73% increase in risk of cervical cancer compared with non-exposed women (OR = 1.73, 95% CI = 1.35 - 2.21, p<0.001). Subgroup and sensitivity analyses indicated this result to be robust. Moderate publication bias was detected by visualing funnel plot, Egger's and Begg's tests. Conclusion: Based on currently available evidence, the findings of this meta-analysis suggests that passive smoking significantly and independently increases the risk of cervical cancer.

Azadeh, Safaee;Reza, Fatemi Seyed;Sara, Ashtari;Mohsen, Vahedi;Bijan, Moghimi-Dehkordi;Zali, Zali Reza 2695

https://doi.org/10.7314/APJCP.2012.13.6.2695 PDF KSCI

Introduction: Design and implementation of screening programs in each country must be based on epidemiological data. Despite the relatively high incidence of CRC, there is no nationwide comprehensive program for screening in Iran. This study was designed to investigate national CRC data and help to determine guidelines for screening. Methods: Incidence data used in this study were obtained from Iranian annual of National Cancer Registration report. Age standardized rates (ASR)were calculated using world standard population and were categorized by age, sex, anatomic subsite and morphology of tumor. Data were analyzed using SPSS.V.13 and Open Source Epidemiologic Statistics for Public Health software (OpenEpi v.2.3.1). Results: A quarter of cases were less than 50 years of age. The majority of tumors were detected in the colon. The overall ASR in the four years period was 38.0 per 100000 and was higher for men compared women (P<0.05). Incidence rate of colorectal cancer increased with age. Conclusion: Results of present study indicated that incidence of colorectal cancer is relatively high in Iran. Incidence of CRC in people under 50 years and in rectum were reported higher than other countries that related etiologic factors should be investigate in further studies. According to the increasing of ASR after age 50 years, it seems that onset of screening at age 50 would be appropriate.

Li, Li-Ping;Cheng, Wei-Bo;Li, Hong;Li, Wen;Yang, Hui;Wen, Ding-Hou;Tang, Yue-Di 2699

https://doi.org/10.7314/APJCP.2012.13.6.2699 PDF KSCI

The functional significance of the proteasome activator $REG{\gamma}$ in the regulation of cell proliferation and apoptosis has been recognized. However, pathological contributions to tumor development remain to be elucidated. Both oncogenic proteins and tumor suppressors are targeted by $REG{\gamma}$ for proteasomal degradation. It has been proposed that the role of the $REG{\gamma}$ in the pathogenesis of cancer is cell- and context-specific. In this study, we aimed to explore the potential involvement of $REG{\gamma}$ in laryngeal carcinomas, comparing protein expression in tumor and adjacent tissues by immunohistochemical staining and Western blot analysis. We also characterized the correlation between the expression of $REG{\gamma}$ and the previously identified substrates p53 and p21. We showed that $REG{\gamma}$ was abnormally highly expressed in cancer tissues. Statistical analysis revealed that there was a positive relationship between the level of $REG{\gamma}$ and the expression of p53 and p21. Our study suggests that $REG{\gamma}$ overexpression can facilitate the growth of laryngeal cancer cells.

Zhang, Shai-Lin;Mao, Ning-Fang;Sun, Jun-Ying;Shi, Zhi-Cai;Wang, Bing;Sun, Yong-Jian 2705

https://doi.org/10.7314/APJCP.2012.13.6.2705 PDF KSCI

Objective: To evaluate the predictive value of glutathione S-transferase (GST) gene polymorphisms for the prognosis of osteosarcoma patients receiving chemotherapy. Methods: A total of 159 patients were included in our study between January 2005 and December 2007., with follow-up until January 2012. Genotyping was based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. Results: At the time of diagnosis, 15.4% of the patients presented with metastasis, while 22.3% developed metastasis during follow-up. At the time of final analysis on January 2012, the median follow-up was 45.5 months. Patients with null GSTM1 and GSTT1 had a higher event free survival rate than non-null genotype, but no significant association was found between the two genotypes and prognosis of osteosarcoma. Individuals with GSTP1 Val/Val genotype tended to live shorter than with the IIe/IIe genotype, and we found a significantly higher risk of death from osteosarcoma (adjusted HR=2.35, 95% CI=1.13-4.85). Conclusion: The GSTP1 gene polymorphism may have an important role in the prognosis of osteosarcoma patients with chemotherapy. Further analyses with larger samples and more genes encoding metabolizing and DNA repair enzymes are warranted.

Lee, Ho-Sun;Pyo, Myoung-Yun;Yang, Mi-Hi 2711

https://doi.org/10.7314/APJCP.2012.13.6.2711 PDF KSCI

Background: Bisphenol A (BPA), an endocrine disrupting chemical, has been suspected to pose carcinogenic risks. However, likely mechanisms are obscure and there are difficulties to estimating its real significance for cancer development. Methods: We therefore studied BPA-induced proteomic alterations in immune organs of ICR mice offspring that were prenatally exposed to BPA (15 and 300 mg/L of drinking water). We performed 2D-gel analyses of samples, considering differences in spleen, exposure levels, sex, and ages. Results: From proteomic analyses, we found various proteins were up- or down-regulated by BPA. Among them, SET, a putative oncogene and inhibitor of phosphatase 2A, was significantly down-regulated in a BPA dose-dependent manner. We also confirmed down-regulation of SET in western blot and real time PCR analyses. From gene network analysis, SET is predicted to communicate with other genes including CYP17, which is involved in biosynthesis and metabolism of sex-hormones. Conclusions: This study provided evidence that SET can be applied as a new biomarker for prenatal BPA exposure and suggests a potential new mechanism of action in that BPA may disrupt CYP17 via SET.

Samah, Asnarulkhadi Abu;Ahmadian, Maryam 2717

https://doi.org/10.7314/APJCP.2012.13.6.2717 PDF KSCI

Background: The rates of breast cancer have increased over the past two decades, and this raises concern about physical, psychological and social well-being of women with breast cancer. Further, few women really want to do breast cancer screening. We here investigated the socio-demographic correlates of mammography participation among 400 asymptomatic Iranian women aged between 35 and 69. Methods: A cross-sectional survey was conducted at the four outpatient clinics of general hospitals in Tehran during the period from July through October, 2009. Bi-variate analyses and multi-variate binary logistic regression were employed to find the socio-demographic predictors of mammography utilization among participants. Results: The rate of mammography participation was 21.5% and relatively high because of access to general hospital services. More women who had undergone mammography were graduates from university or college, had full-time or part-time employment, were insured whether public or private, reported a positive family history of breast cancer, and were in the middle income level (all P<0.01).The largest number of participating women was in the age range of 41 to 50 years. The results of multivariate logistic regression further showed that education (95%CI: 0.131-0.622), monthly income (95%CI: 0.038-0.945), and family history of breast cancer (95%CI: 1.97-9.28) were significantly associated (all P<0.05) with mammography participation. Conclusions: The most important issue for a successful screening program is participation. Using a random sample, this study found that the potential predictor variables of mammography participation included a higher education level, a middle income level, and a positive family history of breast cancer for Iranian women, after adjusting for all other demographic variables in the model.

Chang, Hoo-Sun;Park, Eun-Cheol;Chung, Woo-Jin;Nam, Chung-Mo;Choi, Kui-Son;Cho, Eun;Cho, Woo-Hyun 2721

https://doi.org/10.7314/APJCP.2012.13.6.2721 PDF KSCI

Background: There are limited data evaluating the cost-effectiveness of gastric cancer screening using endoscopy or upper gastrointestinal x-ray in the general population. Objective: To evaluate the cost-effectiveness of population-based screening for gastric cancer in South Korea by decision analysis. Methods: A time-dependent Markov model for gastric cancer was constructed for healthy adults 30 years of age and older, and a deterministic sensitivity analysis was performed. Cost-utility analysis with multiple strategies was conducted to compare the costs and effects of 13 different screening alternatives with respect to the following eligibility criteria: age at the beginning of screening, screening interval, and screening method. The main outcome measurement was the incremental cost-effectiveness ratio. Results: The results revealed that annual endoscopic screening from ages 50-80 was the most cost-effective for the male population. In the females, biennial endoscopy screening from ages 50-80 was calculated as the most cost-effective strategy among the 12 screening alternatives. The most cost-effective screening strategy may be adjustable according to the screening costs and the distribution of cancer stage at screening. The limitation was that effectiveness data were obtained from published sources. Conclusions: Using the threshold of $19,162 per quality-adjusted life year on the basis of the Korean gross domestic product (2008), as suggested by the World Health Organization, endoscopic gastric cancer screening starting at the age of 50 years was highly cost-effective in the Korean population. The national recommendation for gastric cancer screening should consider the starting age of screening, the screening interval, and the screening modality.

Kumar, D.R. Naveen;George, V. Cijo;Suresh, P.K.;Kumar, R. Ashok 2729

https://doi.org/10.7314/APJCP.2012.13.6.2729 PDF KSCI

Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects. Oroxylum indicum (L.) Vent. is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties. In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA-MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay. All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells. PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells. Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects. Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity. Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy.

Liu, Ying;Jiang, Qiu-Ying;Xin, Tao;Cai, Li;Zhao, Chang-Hong 2735

https://doi.org/10.7314/APJCP.2012.13.6.2735 PDF KSCI

Background: Our objective was to clarify the clinical and biological characteristics of basal-like breast cancer (BLBC) and non-basal-like breast cancer (TN3BKE) in Heilongjiang. Methods: We examined, by immunohistochemistry, expression of biological markers cytokeratin (CK) 5/6 and epidermal growth factor receptor (EGFR) and B cell specific moloney murine leukemia virus integration site 1( Bmi-1) in triple-negative breast cancer (TNBC). We studied the correlation between BLBC and several factors related to tumor progression, along with its prognostic value. Results: In the 229 cases of operable TNBC, BLBC was detected in 178 (77.7%) and TN3BKE- in 51 (22.2%). There was no significant difference in clinicopathological factors between them, However, BLBC was significantly associated with Bmi-1 expression (P=0.000) and shorter disease-free survival (DFS) (P = 0.045) and overall survival (OS) (P = 0.041). Conclusions: Compared with the non-basal group, patients with BLBC have a high expression of Bmi-1 and a poor prognosis.

Zhan, Yun-Hong;Liu, Jing;Qu, Xiu-Juan;Hou, Ke-Zuo;Wang, Ke-Feng;Liu, Yun-Peng;Wu, Bin 2739

https://doi.org/10.7314/APJCP.2012.13.6.2739 PDF KSCI

Background: Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. ${\beta}$-Elemene, a promising anticancer drug extracted from a traditional Chinese medicine, has been shown to be effective against various tumors. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated. Methods: Human RCC 786-0 cells were treated with different concentrations of ${\beta}$-elemene, and cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by western blotting. Autophagy was evaluated by transmission electron microscopy. Results: ${\beta}$-Elemene inhibited the viability of 786-0 cells in a dose- and time-dependent manner. The anti-tumor effect was associated with induction of apoptosis. Further study showed that ${\beta}$-elemene inhibited the MAPK/ERK as well as PI3K/Akt/mTOR signalling pathways. Moreover, robust autophagy was observed in cells treated with ${\beta}$-elemene. Combined treatment of ${\beta}$-elemene with autophagy inhibitors 3-methyladenine or chlorochine significantly enhanced the anti-tumor effects. Conclusions: Our data provide first evidence that ${\beta}$-elemene can inhibit the proliferation of RCC 786-0 cells by inducing apoptosis as well as protective autophagy. The anti-tumor effect was associated with the inhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathway. Inhibition of autophagy might be a useful way to enhance the anti-tumor effect of ${\beta}$-elemene on 786-0 cells.

Song, Nan;Chen, Gang;Zhang, Peng;Liu, Ming;He, Wen-Xin;Jiang, Ge-Ning 2745

https://doi.org/10.7314/APJCP.2012.13.6.2745 PDF KSCI

Aims: To study KIT (CD117) expression in thymic epithelial tumors in China, and investigate diagnostic and clinical significance. Material and Methods: Thymic epithelial tumors (TETs) from 102 patients (3 type A, 29 type AB, 5 type B1, 22 type B2, 29 typeB3 and 16 thymic carcinomas) were examined. Immunohistochemical staining with an antic-kit monoclonal antibody was performed on a tissue microarray. Relationships between KIT positive expression and the TET clinical characteristics (WHO histologic classification and Masaoka stage system) were analysed. Results: The KIT positive expression rate was significantly higher in thymic carcinoma (60%, 9/16) than in thymoma (8%, 7/86), a strong correlation being found with the WHO classification, but not the Masaoka tumor stage. The overall survival for patients with KIT positive lesions was significantly worse. Conclusions: KIT is a good molecule marker to differentially diagnose thymic carcinoma from thymoma, while also serving as a predictor of prognosis for TETs. Further research into KIT mutations in Chinese TETs should be conducted to assess the efficacy of targeted therapy.

Eng, Tan Chai;Yaakup, Hayati;Shah, Shamsul Azhar;Jaffar, Aida;Omar, Khairani 2749

https://doi.org/10.7314/APJCP.2012.13.6.2749 PDF KSCI

Background: Breaking bad news to cancer patients is a delicate and challenging task for most doctors. Better understanding of patients' preferences in breaking bad news can guide doctors in performing this task. Objectives: This study aimed to describe the preferences of Malaysian cancer patients regarding the communication of bad news. Methodology: This was a cross-sectional study conducted in the Oncology clinic of a tertiary teaching hospital. Two hundred adult cancer patients were recruited via purposive quota sampling. They were required to complete the Malay language version of the Measure of Patients' Preferences (MPP-BM) with minimal researcher assistance. Their responses were analysed using descriptive statistics. Association between demographic characteristics and domain scores were tested using non-parametric statistical tests. Results: Nine items were rated by the patients as essential: "Doctor is honest about the severity of my condition", "Doctor describing my treatment options in detail", "Doctor telling me best treatment options", Doctor letting me know all of the different treatment options", "Doctor being up to date on research on my type of cancer", "Doctor telling me news directly", "Being given detailed info about results of medical tests", "Being told in person", and "Having doctor offer hope about my condition". All these items had median scores of 5/5 (IQR:4-5). The median scores for the three domains were: "Content and Facilitation" 74/85, "Emotional Support" 23/30 and "Structural and Informational Support" 31/40. Ethnicity was found to be significantly associated with scores for "Content and Facilitation" and "Emotional Support". Educational status was significantly associated with scores for "Structural and Informational Support". Conclusion: Malaysian cancer patients appreciate the ability of the doctor to provide adequate information using good communication skills during the process of breaking bad news. Provision of emotional support, structural support and informational support were also highly appreciated.

Shilpa, P.N.;Sivaramakrishnan, V.;Devaraj, S. Niranjali 2753

https://doi.org/10.7314/APJCP.2012.13.6.2753 PDF KSCI

Rubia cordifolia Linn, which belongs to the Rubiaceae family, is a well-known herb used in Ayurvedic medicine. In the present study, we investigated the influence of a methanolic extract (RC) on the induction of apoptosis in HEp-2 (human laryngeal carcinoma) cell line, as evidenced by cytotoxicity, morphological changes and modification in the levels of pro-oxidants. Inhibition of cell proliferation and lactate dehydrogenase (LDH) release increased in a time and dose-dependent manner. Further, reduced glutathione (GSH), glutathione transferase (GST) and protein levels decreased and lipid peroxidation increased significantly on RC treatment in a dose dependent manner when compared to controls. Based on the results we determined the optimal dose as 30mg/ ml and the apoptotic effect of RC extract (30 mg/ml) on HEp-2 cells was confirmed by fluorescent microscopy and transmission electron microscopy (TEM) based on morphological and ultrastructural changes. RC extract suppressed the proliferation of HEp-2 oral cancer cells inducing apoptotic cell death in vitro. These results point to potential of RC extract as an agent for the treatment of laryngeal squamous cell carcinoma.

Lin, Ying;Shao, Nan;Zhang, Yun-Jian;Wu, Zhuang-Hong;Li, Zhi-Bin;Ren, Ze-Fang;Wang, Shen-Ming 2759

https://doi.org/10.7314/APJCP.2012.13.6.2759 PDF KSCI

Objectives: Compared with Western countries, the incidence rates for breast cancer in China are still low. However, breast cancer appears to be hitting Chinese women at a much younger age, with a peak between 40 and 50 years. Furthermore, breast tumors of Asian women have molecular and genetic characteristics that are different from those of Caucasian women. Methods: A community-based study was designed to evaluate the relationship between lifestyles and breast cancer risk in Chinese women residing in Guangzhou. 16,314 subjects completed the questionnaire. Potential confounding factors included sociodemographic characteristics. Results: 33 individuals reported a history of breast cancer, yielding a prevalence rate of 202.3/100000. Associations between subjects' demographic and breast cancer risk factors were assessed. Breast cancer is associated with family history of breast cancer, X-rays received, benign breast disease and hyperlipoidemia or hypercholesteremia with elevated odds ratios. Conclusions: Family history of breast cancer, X-ray received benign breast disease and hyperlipoidemia or hypercholesteremia were significantly associated with risk of breast cancer and may havepotential for breast cancer risk assessment.

Saraydin, Serpil Unver;Tuncer, Ersin;Tepe, Bektas;Karadayi, Sule;Ozer, Hatice;Sen, Metin;Karadayi, Kursat;Inan, Deniz;Elagoz, Sahande;Polat, Zubeyde;Duman, Mustafa;Turan, Mustafa 2765

https://doi.org/10.7314/APJCP.2012.13.6.2765 PDF KSCI

Background: There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. Here we investigated the antiproliferative properties of Melissa officinalis (MO) from Turkey on breast cancer. Methods: MO extracts were studied for cytotoxicity against breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). In vitro apoptosis studies were performed by annexin V staining and flow cytometry analyses. Immunohistochemistry for Ki-67 and caspase 7 in the tumoral tissue sections of DMBA-induced mammary tumors in rats was also performed, along with TUNEL assays to detect apoptotic cells. In vivo anticancer activity testing was carried out with reference to inhibition of growth of DMBA induced mammary tumors in rats. Results: MO showed cytotoxicity against three cancer cell lines, inducing increase in Annexin-positive cells. Expression of caspase-7 protein and TUNEL positive cells were much higher in rats treated by MO, compared with the untreated control group, while expression of Ki-67 was decreased. Furthermore, in vivo studies showed that mean tumor volume inhibition ratio in MO treated group was 40% compared with the untreated rats. Conclusion: These results indicated that MO extrcts have antitumoral potential against breast cancer.

Kucukzeybek, Yuksel;Dirican, Ahmet;Erten, Cigdem;Somali, Isil;Can, Alper;Demir, Lutfiye;Bayoglu, Ibrahim Vedat;Akyol, Murat;Medeni, Murat;Tarhan, Mustafa Oktay 2771

https://doi.org/10.7314/APJCP.2012.13.6.2771 PDF KSCI

Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

Sreelatha, S.;Dinesh, E.;Uma, C. 2775

https://doi.org/10.7314/APJCP.2012.13.6.2775 PDF KSCI

In recent years there has been a substantial increase in the use of functional foods for disease control. Fruits and vegetables produce phytochemicals such as flavonoids and antioxidants which can lower oxidative stress and reduce the risk of chronic ailments like cancer. The aim of the present study was to investigate the antioxidant capacity and the possible protective effects of Amaranthus paniculatus leaves on the antioxidant defense system in Ehrlich's ascites carcinoma (EAC)-treated mice. Oral administration of the leaf extract at different doses caused a significant decrease in tumor volume, viable cell count and tumor weight and elevated the life span of EAC bearing mice. It also showed an improved antioxidant potential as evidenced by a significant increase in the cellular antioxidant defense system such as catalase, superoxide dismutase and reduced glutathione and also significantly reduced the levels of TBARS. The levels of RBC, hemoglobin and lymphocyte count were altered in EAC bearing mice and were reverted back to near normal levels after the treatment with the leaf extracts. Their adequate content of total phenolics and flavonoids, DPPH scavenging activity which further suggests that the extracts exert a significant protection against oxidative stress conditions.

Seth, Tulika;Kotwal, Atul;Thakur, Rakesh Kumar;Ganguly, K.K. 2781

https://doi.org/10.7314/APJCP.2012.13.6.2781 PDF KSCI

Assessment of perceptions of the community, the determinants and development of their behavior regarding common malignancies, helps in establishing evidence-based activities for prevention and early diagnosis of cancer. However information on this important aspect is lacking in our country. Qualitative methods were here used to obtain information through in depth interviews and Focus Group Discussions (FGDs) with all categories of identified stakeholders. Most were unaware of the activities of the cancer control program. Even the providers were not fully conversant. All respondents mentioned lack of diagnostic and treatment facilities in government, primary and secondary level facilities. Perceptions of different categories of stakeholders regarding why many community members did not attend screening camps and other services reflect the determinants of community behavior, acting independently as well as in combination. The cancer control program was thought to be restricted only to some private facilities and overcrowded government tertiary care facilities where the visits were time consuming. Almost all the facilities were considered curative oriented. Issues of supervision, monitoring and feedback were inadequately addressed by providers who were inadequately trained in many program activities. The program lacked effective planning, coordination and appropriate implementation at the grass roots level in Delhi. Social mobilization was grossly inadequate, as most of the community members were unaware of the existence of the program. Misconceptions about the risk factors, signs and symptoms, diagnosis, and treatment were common amongst community members as well as many of the providers. Thus the national cancer control program in our country needs further community participation and social mobilization. Accessibility, availability, acceptability and affordability of various preventive, curative and rehabilitative activities, as well as intersectoral coordination, training, supervision and monitoring of program activities, all need to be addressed to ensure the success of this important public health program.

Chen, Da-Qing;Yao, Dong-Xiao;Zhao, Hong-Yang;Yang, Shu-Juan 2791

https://doi.org/10.7314/APJCP.2012.13.6.2791 PDF KSCI

Aims: We conducted a case-control study in a Chinese population to clarify the association between polymorphisms in ERCC1 and XPD and susceptibility and survival of glioma. Methods: A total of 393 cases and 410 controls were selected from March 2007 to December 2011. Genotyping of ERCC1 and XPD was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. All analyses were performed using the STATA statistical package. Results: Polymorphisms in ERCC1 118C/T, ERCC1 8092C/A and XPD Asp312Asn showed no statistically significant difference between glioma cases and controls. However, individuals with the XPD 751Gln/Gln genotype had an increased risk of developing glioma compared with those with the Lys/Lys genotype (adjusted OR=1.64, 95% CI: 1.06-2.89). The ERCC1 118T/T genotype was associated with significantly higher median survival than the ERCC1 C/C genotype (HR=0.67, 95%CI=0.35-0.96). In addition, individuals with XPD 751Gln/Gln had a lower median survival time than XPD Lys/Lys carriers (HR=0.54, 95%CI=0.37-0.93). Conclusion: In conclusion, we observed that the XPD 751Gln/Gln genotype is associated with glioma susceptibility, and ERCC1 118 T/T and XPD 751Gln/Gln genotypes confer a significantly better prognosis.

Ren, Hui;Li, Jun;Liu, Jing-Jing;Guo, Hui-Ling;Jiang, Tao 2795

https://doi.org/10.7314/APJCP.2012.13.6.2795 PDF KSCI

Objective: This study is conducted to evaluate the effects of anti-HER-2${\times}$anti-CD3 bi-specific antibodies(BsAb) on HER-2/neuover-expressing human colorectal carcinoma cells. Methods: Growth was assessed by MTT assays after exposure of HCT-116 cells to Herceptin, anti-CD3 and BsAb antibodies. Immunocytochemistry was applied to test the HER-2 level of HCT-116. In a nude mouse model, HER-2${\times}$CD3 BsAb was combined with effector cells (peripheral blood lymph cells from normal human being) for observations on in Vivo growth of tumors. Results: Compared with the control group, using effector cells combined with anti-CD3 McAb, Herceptin or HER2${\times}$CD3 BsAb, tumor cell growth in vitro and in vivo was significantly inhibited (P<0.05), most remarkably in the HER2${\times}$CD3 BsAb case. The growth of xenografts with HER2${\times}$CD3 BsAb combined with effector cells was also significantly inhibited when compared with the anti-CD3 McAb or Herceptin groups (P<0.05). Conclusion: HER-2/neu might be a useful target for immunotherapy in colorectal carcinoma, anti-HER2${\times}$anti-CD3 BsAb exerting clear anti-tumor effects.

Wang, De-Lin;Lan, Jian-Hua;Chen, Liang;Huang, Biao;Li, Zeng;Zhao, Xiu-Min;Ma, Qiang;Sheng, Xia;Li, Wen-Bin;Tang, Wei-Xue 2799

https://doi.org/10.7314/APJCP.2012.13.6.2799 PDF KSCI

The aim of this study was to elucidate the role of the integrin-linked kinase (ILK) gene in development of human bladder transitional cell carcinoma (BTCC). Expression of ILK protein and ILK mRNA in 56 cases of human BTCC tissue and in 30 cases of adjacent normal bladder tissue was detected by immunohistochemistry S-P and reverse transcription polymerase chain reaction (RT-PCR), respectively. Four specific miRNA RNAi vectors targeting human ILK were synthesized and transfected into BIU-87 cells by liposome to obtain stable expression cell strains. The influence of ILK on proliferation of BTCC was detected by MTT, FCM on athymic mouse tumorigenesis. The positive rate of ILK protein in BTCC tissue (53.6%) was much higher than adjacent normal bladder tissue (10.0%) (p<0.05). Similarly, expression of ILK mRNA in BTCC tissue ($0.540{\pm}0.083$) was significantly higher than in adjacent normal bladder tissue ($0.492{\pm}0.070$) (p<0.05). MTT showed that the proliferation ability of miRNA-ILK transfected group was clearly decreased (p<0.05), the cell cycle being arrested in G0/G1-S, an tumorigenesis in vivo was also significantly reduced (p<0.05). ILK gene transcription and protein expression may be involved in the development of BTCC, so that ILK might be the new marker for early diagnosis and the new target for gene treatment.

Zhou, Shi-Xiang;Li, Feng-Sheng;Qiao, Yu-Lei;Zhang, Xue-Qing;Wang, Zhi-Dong 2807

https://doi.org/10.7314/APJCP.2012.13.6.2807 PDF KSCI

The purpose of this study was to examine the effect of a Toll-like receptor 5 (TLR5) agonist, CBLB502, on the growth and radiosensitivity of A549 lung cancer cells in vivo. Expression of myeloid differentiation factor 88 (MyD88) or TLR5 was stably knocked down in human lung cancer cells (A549) using lentivirus expressing short hairpin RNA targeting human MyD88 or TLR5. Lack of MyD88 or TLR5 expression enhanced tumor growth in mouse xenografts of A549 lung cancer cells. CBLB502 inhibited the growth of A549 lung cancer cells, not A549-MyD88-KD cells in vivo in the murine xenograft model. Our results showed that the inhibition of A549 by CBLB502 in vivo was realized through regulating the expression of neutrophil recruiting cytokines and neutrophil infiltration. Finally, we found that activation of TLR5 signaling did not affect the radiosensitivity of tumors in vivo.

Wang, Song;Shu, Jie-Zhi;Cai, Yi;Bao, Zheng;Liang, Qing-Mo 2813

https://doi.org/10.7314/APJCP.2012.13.6.2813 PDF KSCI

Background: Considerable evidence suggests that metadherin (MTDH) is a potentially crucial mediator of tumor malignancy and an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk. Inhibition of MTDH expression by RNA interference has been shown in several previous research, but silencing MTDH expression by microRNA (miRNA) interference in breast cancer has not been established. In the present study, we investigated the role of MTDH-miRNA in down-regulation of proliferation, motility and migration of breast carcinoma cells. Methods: Expression vectors of recombinant plasmids expressing artificial MTDH miRNA were constructed and transfected to knockdown MTDH expression in MDA-MB-231 breast cancer cells. Expression of MTDH mRNA and protein was detected by RT-PCR and Western blot, respectively. MTT assays were conducted to determine proliferation, and wound healing assays and transwell migration experiments for cell motility and migration. Results: Transfection of recombinant a plasmid of pcDNA-MTDH-miR-4 significantly suppressed the MTDH mRNA and protein levels more than 69% in MDA-MB-231 breast cancer cells. This knockdown significantly inhibited proliferation, motility and migration as compared with controls. Conclusions: MTDH-miRNA may play an important role in down-regulating proliferation, motility and migration in breast cancer cells, and should be considered as a potential small molecule inhibitor therapeutic targeting strategy for the future.

Chu, De-Jie;Guo, Shui-Gen;Pan, Chun-Feng;Wang, Jing;Du, Yong;Lu, Xu-Feng;Yu, Zhu-Yuan 2819

https://doi.org/10.7314/APJCP.2012.13.6.2819 PDF KSCI

Objective: To assess induction effects of Chlamydia pneumoniae (Cpn) on lung cancer in rats. Methods: A lung cancer animal model was developed through repeated intratracheal injection of Cpn (TW-183) into the lungs of rats, with or without exposure to benzo(a)pyrene (Bp). Cpn antibodies (Cpn-IgA, -IgG, and -IgM) in serum were measured by microimmunofluorescence. Cpn-DNA or Cpn-Ag of rat lung cancer was detected through polymerase chain reaction or enzyme-linked immunosorbent assay. Results: The prevalence of Cpn infection was 72.9% (35/48) in the Cpn group and 76.7% (33/43) in the Cpn plus benzo(a)pyrene (Bp) group, with incidences of lung carcinomas in the two groups of 14.6% (7/48) and 44.2% (19/43), respectively (P-values 0.001 and <0.000 compared with normal controls). Conclusions: A rat model of lung carcinoma induced by Cpn infection was successfully established in the laboratory for future studies on the treatment, prevention, and mechanisms of the disease.

Sun, Jian-Jun;Jing, Wei;Ni, Yan-Yan;Yuan, Xiao-Jian;Zhou, Hai-Hua;Fan, Yue-Zu 2823

https://doi.org/10.7314/APJCP.2012.13.6.2823 PDF KSCI

Objective: To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. Method: On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Results: Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenograpfts in-situ than in the negative control group(both P<0.01). Moreover, the expression of VEGF-C, VEGF-D and VEGFR-3 proteins and mRNAs were significantly higher in xenografts in-situ (both P<0.01), in conformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. Conclusions: In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

Kilickap, Saadettin;Arslan, Cagatay;Rama, Dorina;Yalcin, Suayib 2829

https://doi.org/10.7314/APJCP.2012.13.6.2829 PDF KSCI

Background: This study aimed to research the awareness of screening colonoscopy (SC) among patients with colorectal cancer (CRC) and their relatives. Methodology: A questionnaire form including information and behavior about colonoscopic screening for CRCs of patients and their first-degree relatives (FDRs) was prepared. Results: A total of 406 CRC patients were enrolled into the study, with 1534 FDRs (siblings n: 1381 and parents n: 153). Positive family history for CRC was found in 12% of the study population. Previous SC was performed in 11% of patients with CRC. Mean age of the patients whose FDRs underwent SC was lower than the patients whose FDRs did not (52 vs 57 years; p<0,001). The frequency of SC in FDRs was 64% in patients diagnosed CRC under 35 years of age. Persons having a positive family history of CRC had SC more often (51 vs 22%, p<0,001). FDRs of patients having a higher educational level and income had SC more frequently. Conclusions: When screening for CRC is planned, elderly subjects, those with family history for CRC, and those with low educational and lower income should be given esspecial attention in order that they be convinced to undergo screening for CRC.

Baygi, Modjtaba Emadi;Nikpour, Parvaneh 2833

https://doi.org/10.7314/APJCP.2012.13.6.2833 PDF KSCI

Aim: Gastric cancer is the third most frequent cause of cancer mortality worldwide. In Iran, it is one of the leading causes at the national level. Localized at chromosome 8q22, the human MTDH gene has been reported to be over-expressed in a spectrum of malignancies. However, since there is a lack of data concerning with expression in gastric cancer at the transcriptional level, in this study we evaluated MTDH expression in Iranian cases. Methods: Totally, thirty paired gastric samples were examined by quantitative real-time RT-PCR. Results: Although the mRNA expression was significantly elevated in 46.6% of the examined tumor tissues; its expression was low in others (36.6%). Moreover, there was only a marginal statistical difference between the MTDH gene expression of all tumor specimens compared to their paired non-tumor ones and no statistically significant association with the grades and types of the tumors. Conclusion: Taken together, our results demonstrated that expression of MTDH at the transcriptional level may be increased in gastric cancer tissue samples but with considerable heterogeneity. Due to this, it may have the potential to be used as a target for diagnostic/therapeutic purposes only in a subset of patients.

Guo, Yan;Wang, Gan;Gao, Wen-Wei;Cheng, Shi-Wen;Wang, Ren;Ju, Shi-Ming;Cao, He-Li;Tian, Heng-Li 2837

https://doi.org/10.7314/APJCP.2012.13.6.2837 PDF KSCI

We investigated whether IFN-${\beta}$ inhibits the growth of human malignant glioma and induces glioma cell apoptosis using the human IFN-${\beta}$ gene transfected into glioma cells. A eukaryonic expression vector ($pSV2IFN{\beta}$) for IFN-${\beta}$ was transfected into the glioma cell line SHG44 using liposome transfection. Stable transfection and IFN-${\beta}$ expression were confirmed using an enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was also assessed by Hoechst staining and electron microscopy. In vivo experiments were used to establish a SHG44 glioma model in nude mice. Liposomes containing the human IFN-${\beta}$ gene were injected into the SHG44 glioma of nude mice to observe glioma growth and calculate tumor size. Fas expression was evaluated using immunohistochemistry. The IFN-${\beta}$ gene was successfully transfected and expressed in the SHG44 glioma cells in vitro. A significant difference in the number of apoptotic cells was observed between transfected and non-transfected cells. Glioma growth in nude mice was inhibited in vivo, with significant induction of apoptosis. Fas expression was also elevated. The IFN-${\beta}$ gene induces apoptosis in glioma cells, possibly through upregulation of Fas. The IFN-${\beta}$ gene modulation in the Fas pathway and apoptosis in glioma cells may be important for the treatment of gliomas.

Ma, Hong-Bo;Huang, Tao;Han, Feng;Chen, Wei-Yu 2841

https://doi.org/10.7314/APJCP.2012.13.6.2841 PDF KSCI

Background: Many studies have investigated the association between the MDM2 promoter SNP309 T/G polymorphism and liver cancer risk, but inconsistencies make drawwing definitive conclusions difficult. Methods: We therefore searched main databases for articles relating MDM2 SNP309 T/G polymorphism to risk of liver cancer in humans and estimated summary odds ratio (OR) with 95% confidence intervals (95% CI) to assess the possible association in a meta-analysis. Results: The main analysis revealed no significant heterogeneity, and the pooled ORs of fixed-effects were all significant (for G versus T, OR = 1.59, 95% CI 1.42-1.78; for GG versus TT, OR = 2.45, 95% CI 1.93-3.12; for GT versus TT, OR = 1.70, 95% CI 1.38-2.09; for GG versus GT, OR = 1.49, 95% CI 1.24-1.79; for GG and GT versus TT, OR = 1.95, 95% CI 1.61-2.38; for GG versus TT and GT, OR = 1.73, 95% CI 1.46-2.07). Subgroup analyses by ethnicity and sensitivity analyses both showed associations to remain significant. Conclusion: The present meta-analysis of available data showed a significant association between the MDM2 SNP309 T/G polymorphism and liver cancer risk, the MDM2 SNP309 G allele contributing to increased risk in both Asians and Caucasians in a graded, dose-dependent fashion.

Huang, Tao;Gong, Wei-Hua;Li, Xiu-Cheng;Zou, Chun-Ping;Jiang, Guang-Jian;Li, Xu-Hui;Qian, Hao 2847

https://doi.org/10.7314/APJCP.2012.13.6.2847 PDF KSCI

Purpose: To study the killing effects on osteosarcoma cells of cinobufacini and cisplatin in combination and the related mechanisms so as to explore the chemotherapeutic method with integrated traditional Chinese and Western medicines. Methods: Cinobufacini and cisplatin were applied to OS732 cells singly or jointly and survival rates were measured by MTT assay. Changes in cellular shape were observed with inverted phase contrast and fluorescence microscopy and apoptosis rates were analyzed with flow cytometry (FCM). Immunocytochemistry were used to examine the Fas expression of OS732 cells. Results: The combination of cinobufacini and cisplatin had the effect of up-regulating Fas expression and inducing apoptosis. The survival rate of combined application of 100 ${\mu}g/ml$ cinobufacini and 1 ${\mu}g/ml$ cisplatin on OS-732 cells was significantly lower than with either of the agents alone (p<0.01). Changes in cellular shape and apoptotic rates also indicated the apoptosis-inducing effects of combined application were much enhanced. Conclusion: The combination of cinobufacini and cisplatin demonstrated strong killing effects on OS-732 cells which might be related to up-regulation of Fas expression.

Guo, Xiao-Tong;Wang, Jun-Feng;Zhang, Lin-You;Xu, Guang-Quan 2853

https://doi.org/10.7314/APJCP.2012.13.6.2853 PDF KSCI

Background: Previous studies assessing associations between matrix metalloproteinase 2 (MMP-2) polymorphisms and lung cancer risk reported conflicting results. A meta-analysis was therefore performed to derive a more precise estimation. Method: Case-control studies assessing associations between MMP-2 C735T and C1306T polymorphisms and lung cancer risk were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Results: 7 studies with a total of 3,189 lung cancer cases and 3,013 controls were finally included into this meta-analysis. Overall, the MMP-2 C735T polymorphism was associated with lung cancer risk under the homozygote model (CC versus TT: OR =1.44, 95% CI = 1.03-2.02, $I^2$ = 0%), while the MMP-2 C1306T polymorphism also associated demonstrated links with all four models (all P values less than 0.05). Subgroup analyses by race suggested obvious associations between MMP-2 C735T and C1306T polymorphisms and lung cancer risk in Asians but not in Caucasians. There was no evidence for publication bias. Conclusion: Currently available evidence supports teh conclusion that MMP-2 C735T and C1306T polymorphisms influence susceptibility to lung cancer in Asians.

Norsa'adah, Bachok;Nur-Zafira, Azemi;Knight, Aishah 2857

https://doi.org/10.7314/APJCP.2012.13.6.2857 PDF KSCI

Pancreatic cancer is usually detected late and has a high mortality rate. Since little is known about this cancer in Malaysia, a review of all cases admitted to Universiti Sains Malaysia Hospital was conducted to identify the epidemiological distribution and assess survival. A list of pancreatic cancer patients in 2001-2008 was obtained from the Hospital Record Department. Only cases confirmed by radio-imaging or histo-pathology examination were included. We excluded those with incomplete medical records. Kaplan-Meier and Cox proportional hazard approaches were used for data analysis. Only 56 cases were included with a mean (SD) age of 49.6 (16.0) years, with 60.7% males and 82.1% of Malay ethnicity. Previous history included cholelithiasis in 23.2%, diabetes mellitus in 16.1%, previous laparotomy in 10.7%, chronic pancreatitis in 7.1%, alcohol drinking in 5.4% and positive family history in 3.6%. The common presenting history included 67.9% loss of appetite, 66.1% loss of weight, 58.9% jaundice and 46.4% abdominal pain. Tumour staging was: 21.5% stage l, 17.8% stage ll, 3.6% stage lll and 57.1% stage lV. The median (95% CI) survival time was 3.4 (0.5, 6.3) months and significant prognostic factors were duration of symptoms (HR 0.97; 95% CI: 0.95, 0.99; p value 0.013), ascites (HR 2.64; 95% CI: 1.28, 5.44; p value 0.008) and Whipple surgery (HR 4.20; 95% CI: 2.27, 7.76; p value <0.001). The history of presenting complaints was short and the majority presented at late stages of the disease, thus the median survival time was very poor.

Cheng, Wei-Hong;Kao, Chen-Yi;Hung, Yu-Shin;Su, Po-Jung;Hsieh, Chia-Hsun;Chen, Jen-Shi;Wang, Hung-Ming;Chou, Wen-Chi 2861

https://doi.org/10.7314/APJCP.2012.13.6.2861 PDF KSCI

Background: The aim of our study was to assess the practical utility of the palliative prognostic index (PPI) as a prognostic tool used by nurse specialists in a hospice consultation setting in Taiwan. Methods: In total, 623 terminal cancer patients under hospice consultation care from one medical center in northern Taiwan were enrolled between January 1 and June 30, 2011. PPI was assessed by a nurse specialist at first hospice consultation and patients categorized into groups by prognosis (good, intermediate, poor). Patient survival was analyzed retrospectively to determine significance of between-group differences. Results: By PPI sum score, 37.2% of patients were in the good prognosis group, 18% in the intermediate prognosis group and 44.8% in the poor prognosis group. The death rates were 56%, 81.2% and 89.6% and median survivals were 76, 18 and 7 days, respectively. The hazard ratio was 0.19 (95% confidence interval [CI] 0.10-0.24, p<0.001) for the poor versus good prognosis group and 0.54 (95% CI 0.43-0.69, p<0.001) for the poor versus intermediate prognosis group. The sensitivity and specificity for the poor prognosis group was 66% and 71%; the positive predictive value and negative predictive value were 81% and 52%, respectively, to predict patient death within 21 days (area under the curve of the receiver operating characteristic was 0.68). Conclusions: Assessment by PPI can accurately predict survival of terminal cancer patients receiving hospice consultation care. PPI is a simple tool and can be administered by nurse members of hospice consultation teams.

Zhang, Qing-Hui;Yao, Yong-Liang;Gu, Tao;Gu, Jin-Hua;Chen, Ling;Liu, Yun 2867

https://doi.org/10.7314/APJCP.2012.13.6.2867 PDF KSCI

Background: Multiple studies have reported associations between the PSCA rs2294008 C > T polymorphism and GC, but susceptibility has proven inconsistent. Therefore, we estimates the relationship between the rs2294008 C > T polymorphism and GC by meta-analysis. Methods: PubMed, Embase and Web of Science databases were searched and nine independent case-control studies were included in this meta-analysis. Crude ORs with 95% CIs were extracted according to the Mantal-Haenszel method and pooled to assess the strength of the association. Results: We observed that the PSCA rs2294008 C > T polymorphism was significantly correlated with GC risk when all studies were pooled into the meta-analysis. Further subgroup analysis showed the polymorphism to be linked with diffuse and noncardia GC in the allele contrast model, homozygote codominant model, dominant model, and recessive model. However, no connection was apparent for intestinal and cardia GC. In the stratified analysis by ethnicity, significant associations were observed in Asians for the recessive model. Interestingly, the relationship was particularly significant in the Chinese population. Conclusions: Our findings suggest that the PSCA rs2294008 C > T polymorphism is a risk factor for GC, especially in diffuse and noncardia GC and in Chinese.

Zhao, Xue;Sun, Xian;Li, Xiao-Li 2873

https://doi.org/10.7314/APJCP.2012.13.6.2873 PDF KSCI

Objective: To determine STAT3, P-STAT3, and VEGF-C expression levels in small cell lung cancers (SCLCs), and discuss their role and clinical significance in SCLC development. Method: Immunohistochemical methods were applied to 128 cases of SCLC and 40 cases of adjacent normal tissue. Results: The expression levels of STAT3, P-STAT3, and VEGF-C were higher in SCLC than in normal tissue (P<0.05). Pairwise comparisons showed positive correlations with lymph node metastasis, clinical stage, and tumor size (P<0.05). The expression levels were also related with the overall survival rates. Conclusion: STAT3 and VEGF-C play important roles in the development of SCLC, and might be expected to become new targets for SCLC treatment.

Ronco, Alvaro L.;Stefani, Eduardo De;Deneo-Pellegrini, Hugo 2879

https://doi.org/10.7314/APJCP.2012.13.6.2879 PDF KSCI

In order to thoroughly analyze risk factors of breast cancer (BC) in premenopausal Uruguayan women, a case-control study was carried out at the Pereira Rossell Women's Hospital, Montevideo, where 253 incident BC cases and 497 frequency-matched healthy controls were interviewed on menstrual and reproductive story, were administered a short food frequency questionnaire and undertook a series of body measurements necessary to calculate body composition and somatotype. Odds ratio (OR) coefficients were taken as estimates of relative risk derived from unconditional logistic regression. Among the classical risk factors, only the family history of BC in first degree relatives was significantly associated with risk of premenopausal BC (OR=2.20, 95% CI 1.33-3.62). Interestingly, this risk factor was found to be stronger in women of ages >40 (OR=4.05, 95% CI 2.10-7.81), late menarche (OR= 2.39, 95% CI 1.18-4.85), early age for their first delivery (OR=3.02, 95% CI 1.26-7.22), short time between menarche and first delivery (OR=3.22, 95% CI 1.29-8.07), and with high parity (OR=4.10, 95% CI 1.79-9.36), although heterogeneity was detected only for age and parity. High consumption of red meat was positively associated with the disease risk (OR=2.20, 95% CI 1.35-3.60), in the same way as fried foods (OR=1.79, 95% CI 1.12-2.84). Conversely, a high intake of plant foods displayed a protective effect (OR=0.41, 95% CI 0.26-0.65). Except for hypertension (OR=1.55, 95% CI 1.03-2.35), none of the analyzed components of metabolic syndrome were associated to BC risk. Particular increases of risk for premenopausal BC were found for family history in first degree relatives in certain subsets derived from the menstrual-reproductive history. Preventive strategies could broaden their scope if new studies confirm the present results, in view of the limited prevention measures that premenopausal BC currently has.

Soydinc, Hilal Oguz;Duranyildiz, Derya;Guney, Nese;Derin, Duygu;Yasasever, Vildan 2887

https://doi.org/10.7314/APJCP.2012.13.6.2887 PDF KSCI

Malignant tumors have a capacity to degrade the extracellular matrix by controlled proteolysis. One system involved in these processes is the urokinase-type plasminogen activator (uPA) system. uPAR levels are elevated in tumors from several types of cancer. Our study was planned to investigate serum and urine levels of uPAR in breast cancer patients (n=180) and healthy controls (n=60) by ELISA. Serum (p<0.001) and urine (p<0.001) uPAR values in the patients were both significantly elevated. High serum and urine levels of uPAR can be used as diagnostic tools in lymph node positive patients.

Sardari, Yasaman;Pardis, Soheil;Tadbir, Azadeh Andisheh;Ashraf, Mohammad Javad;Fattahi, Mohammad Javad;Ebrahimi, Hooman;Purshahidi, Sara;Khademi, Bijan;Hamzavi, Marzieh 2891

https://doi.org/10.7314/APJCP.2012.13.6.2891 PDF KSCI

Background: HER2/neu, a member of EGFR family, is over expressed in some tumors. The purpose of this study was to determine the salivary level and tissue expression of HER2/neu in patients with head and neck squamous cell carcinoma (HNSCC) and any correlation with clinicopathologic parameters. Methods: An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the salivary level and immunohistochemistry (IHC) to assess tissue expression of HER2/neu in 28 patients with HNSCC and 25 healthy controls. Results: The salivary levels of HER2/neu in HNSCC patients was not significantly higher than in the healthy controls (p>0.005). There was no apparent correlation in salivary HER2/neu level with clinicopathological features such as age, sex, grade, tumor size and nodal status. All HNSCC specimens were positive (membranous or/and cytoplasmic) for HER2/neu, except one sample. Only one HNSCC specimen was stained in cytoplasm purely. All control specimens were membranous and cytoplasmic positive for HER2/neu. There was a significant difference between cytoplasmic staining in case and control groups (p-value<0.05). Conclusion: In our cases, no overexpression of HER2/neu was observed. Thus, our findings suggested that the use of Her-2 as a salivary marker of HNSCC cannot be recommended.

Zhong, Dong;Ran, Jian-Hua;Tang, Wen-Yuan;Zhang, Xiao-Dong;Tan, Yun;Chen, Gui-Jie;Li, Xiao-Song;Yan, Yi 2897

https://doi.org/10.7314/APJCP.2012.13.6.2897 PDF KSCI

Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin. Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (FAK) and JNK in CHG-5 and CHG-hS cells. The migration ability of CHG-hS cells was significantly higher than that of CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925 sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 site was not changed. Phosphorylated Src, JNK and Akt levels in CHG-hS cells were also significantly upregulated. Phosphorylation of JNK and Akt were abolished by the specific inhibitors SP600125 and LY294002, respectively, and the migration ability of CHG-hS cells was decreased, indicating that the JNK and PI3K/Akt pathways play important roles in regulating mda-9/syntenin-induced human brain glioma migration. Our results indicate Mda-9/syntenin overexpression could activate FAK-JNK and FAK-Akt signaling and then enhance the migration capacity of human brain glioma cells.

Zhang, Qiong-Wen;Liu, Lei;Chen, Ru;Wei, Yu-Quan;Li, Ping;Shi, Hua-Shan;Zhao, Yu-Wei 2903

https://doi.org/10.7314/APJCP.2012.13.6.2903 PDF KSCI

Background: Matrix metalloproteinase-9 (MMP-9) is associated with disruption of basement membranes of blood vessels and promotion of metastasis through the lymphatics. However, its prognostic value for survival in patients with gastric cancer remains controversial. Method: We therefore conducted a meta-analysis of the published literature in order to clarify the impact of MMP-9. Clinical studies were selected for further analysis if they provided an independent assessment of MMP-9 in gastric cancer and reported analysis of survival data according to MMP-9 expression. Results: A total of 11 studies, covering 1700 patients, were included for meta-analysis. A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combined HR suggested that a positive MMP-9 expression had an impact on overall survival: 1.25 (95% confidence interval 1.11-1.40) in all eligible studies; 1.13 (1.06-1.20) in 8 studies detecting MMP-9 by immunohistochemistry; 1.36 (1.12-1.65) in 7 studies from Asia. Only one study for DFS showed a significant impact on disease free survival (HR 1.73, 95%CI 1.27-2.34). Conclusions: Our findings suggested that MMP-9 protein expression might be a factor for a poor prognosis in patients with gastric cancer. However, the association was rather weak, so that more prospective studies should further explore the prognostic impact of MMP-9 mRNA and correlations between MMP-9 and clinicopathological characteristics.

Altinbas, Mustafa;Kalender, Mehmet Emin;Oven, Basak;Sevinc, Alper;Karaca, Halit;Kaplan, M. Ali;Alici, Suleyman;Arpaci, Erkan;Yildiz, Ramazan;Uncu, Dogan;Camci, Celalettin;Gumus, Mahmut 2909

https://doi.org/10.7314/APJCP.2012.13.6.2909 PDF KSCI

Aim: To evaluate efficacy and tolerability of topotecan treatment for recurrent small cell lung carcinoma. Patients and Methods: A total of 62 patients were evaluated retrospectively. Statistical analysis was performed using GraphPad Instat (version 3.05). Results: DFifty five of patients (89%) were male and 7 (11%) were female. Median age was $56.7{\pm}9.3$ (34-75). Forty eight of patients (80%) were extensive stage (ES) at the time of diagnosis. Fifty of the patients (80.6 Medical Oncology Clinic) were given median 5.36 cycles of cisplatin-etoposide (2-8 cycles). Time to recurrence was $15.6{\pm}6.13$ weeks in patients with limited stage (LS) and $6.3{\pm}3.82$ weeks in extensive stage (ES) (p<0.0001). Overall survival was $14.0{\pm}6.08$ months in ES and $17.9{\pm}6.88$ months in LS. The difference between two groups was statistically meaningful (p=0.0447). The overall survival of the patients was $14.8{\pm}6.43$ months (4.5-40 months). In terms of survival, there was no difference between males and females (p=0.1171). In 17 (27%) patients who were refractory to topotecan or in whom progression occurred other chemotherapies were used. Conclusion: Small cell lung cancer is chemosensitive, but recurrences occur in short time. Other chemotherapy regimens are used in progression. Topotecan is one of them. Patients who were young and in whom recurrences occur late had given better response to topotecan. Because of the retrospective nature of the study, we couldn't reach the records exactly and consequently, rate and duration of response couldn't be calculated. In recurrent SCLC topotecan is one of the treatment choices. But both hematological and non hematological side effects should be taken into consideration.

Kim, Young-Mi;Ati, Abigael;Kols, Adrienne;Lambe, Fransisca Maria;Soetikno, Djoko;Wysong, Megan;Tergas, Ana Isabel;Rajbhandari, Presha;Lu, Enriquito 2913

https://doi.org/10.7314/APJCP.2012.13.6.2913 PDF KSCI

Introduction: The impact of cervical cancer prevention programs depends on persuading women to go for screening and, if needed, treatment. As part of an evaluation of a pilot project in Indonesia, qualitative research was conducted to explore the factors that influence women's decisions regarding screening and treatment and to generate practical recommendations to increase service coverage and reduce loss to follow up. Methods: Research was conducted at 7 of the 17 public health centers in Karawang District that implemented the pilot project. Interviews and focus group discussions were held with 20 women, 20 husbands, 10 doctors, 18 midwives, 3 district health officials, and 16 advocacy team members. Results: Free services and mobile outreach events encouraged women to go for screening, along with promotional efforts by community health workers, advocacy teams, and the mass media. Knowledge and perceptions were the most important barriers to screening: women were not aware of cervical cancer risks, did not know the disease was treatable, and were fatalistic. Factors facilitating treatment were social support from husbands, relatives, and friends and the encouragement and role modeling of health workers. Barriers to prompt treatment included limited access to services and the requirement for husband's consent for cryotherapy. Conclusion: As cervical cancer prevention services are scaled up throughout Indonesia, the findings suggest three strategies to expand screening coverage and ensure prompt treatment: strengthening community mobilization and advocacy activities, modifying the service delivery model to encourage a single visit approach to screening and treatment, and working to gain men's support.

Jo, Angela M.;Maxwell, Annette E.;Choi, Sun-Hye;Bastani, Roshan 2923

https://doi.org/10.7314/APJCP.2012.13.6.2923 PDF KSCI

Background: Little is known about interest in faith-based health promotion programs among Asian American populations. Among the Christian denominations, the Seventh-day Adventist (SDA) church is known to place a strong doctrinal emphasis on health. Objectives: To understand appropriate ways to develop and implement health promotion programs and to conduct research among Korean American SDAs. Methods: We collaborated with the North American Division of Korean SDA Churches which sponsors annual week-long religious retreats for their church members. We developed and administered a 10-page questionnaire at their 2009 retreat in order to assess socio-demographic and church characteristics, religiosity, perceived relationship between health and religion, and interest and preferences for church-based health promotion programs. Results: Overall, 223 participants completed our survey (123 in Korean and 100 in English). The sample consisted of regular churchgoers who were involved in a variety of helping activities, and many holding leadership positions in their home churches. The vast majority was interested in receiving health information at church (80%) in the form of seminars, cooking classes and workshops (50-60%). Fewer respondents were interested in support groups (27%). Some interests and preferences differed between English and Korean language groups. Conclusion: Korean American SDA church retreat participants from a large geographic area are very interested in receiving health information and promoting health at their churches and can potentially serve as "agents of influence" in their respective communities.

Dugandzija, Tihomir;Mikov, Marica Miladinov;Rajcevic, Smiljana;Kacavenda, Dragana;Malenkovic, Goran;Ristic, Mioljub 2931

https://doi.org/10.7314/APJCP.2012.13.6.2931 PDF KSCI

Background: The epidemiological situation regarding cervical carcinoma in Serbia is rather unfavorable and one of contributing factors is the insufficient interest of women concerning the risk factors responsible for occurrence of this disease. The aim of this study was to determine the sources of relevant information for women Methods: An anonymous questionnaire was used for questioning of patients, students and women undergoing systematic examinations. There were 600 women in total in 2006, 2009 and 2010, and the data were statistically processed by the ${\chi}^2$ test with Yates correction and the Fisher test. Results: When observed for certain groups of tested women, and summed up for all three periods, there was a statistically significant difference for the answer "without any knowledge" (p=0.0001). When observed for certain years and summed up for all three tested groups, there was a statistically significant difference in answers regarding the source of information, the "doctor" (p=0.0011), "media" (p=0.0349) and "encyclopedia-internet" (p=0.0136). Conclusion: The media are a dominant source of information for women on risk factors for cervical cancer. The significance of the Internet increased during the three observed periods, while the students considered themselves least informed of all concerning risk factors.

Basu, Kaustuv;Mukherjee, Joydeep;Law, Sujata;Chaudhuri, Samaresh 2935

https://doi.org/10.7314/APJCP.2012.13.6.2935 PDF KSCI

Biological response modifiers (BRMs) can alter interactions between the immune system and cancer cells to boost, direct, or restore the body's ability to fight disease. Mice with ethylnitrosourea- (ENU) induced leukemia were here used to monitor the therapeutic efficacy of lipopolysaccaride (LPS), Bacillus Calmette Guerin (BCG) and sheep erythrocytes (SRBC). Flow cytometry based CD34+ positivity analysis, clonogenicity, proliferation and ultrastructure studies using scanning electron microscopy (SEM) of stem cells in ENU induced animals with and without BRMs treatment were performed. BRMs improved the stem-stromal relationship structurally and functionally and might have potential for use as an adjunct in human stem cell therapy.

Chaudhuri, Suhnrita;Acharya, Sagar;Chatterjee, Sirshendu;Kumar, Pankaj;Singh, Manoj Kumar;Bhattacharya, Debanjan;Basu, Anjan Kumar;Dasgupta, Shyamal;Flora, S.J.S.;Chaudhuri, Swapna 2943

https://doi.org/10.7314/APJCP.2012.13.6.2943 PDF KSCI

Arsenic exposure is a serious health hazard worldwide. We have previously established that it may result in immune suppression by upregulating Th2 cytokines while downregulating Th1 cytokines and causing lymphocytic death. Treatment modalities for arsenic poisoning have mainly been restricted to the use of chelating agents in the past. Only recently have combination therapies using a chelating agent in conjunction with other compounds such as anti-oxidants, micronutrients and various plant products, been introduced. In the present study, we used T11TS, a novel immune potentiating glycopeptide alone and in combination with the sulfhydryl-containing chelator, mono-iso-amyl-dimarcaptosuccinic acid (MiADMSA) as a therapeutic regimen to combat arsenic toxicity in a mouse model. Results indicated that Th1 cytokines such as TNF-${\alpha}$, $IFN{\gamma}$, IL12 and the Th2 cytokines such as IL4, IL6, IL10 which were respectively downregulated and upregulated following arsenic induction were more efficiently restored to their near normal levels by T11TS alone in comparison with the combined regimen. Similar results were obtained with the apoptotic proteins studied, FasL, BAX, BCL2 and the caspases 3, 8 and 9, where again T11TS proved more potent than in combination with MiADMSA in preventing lymphocyte death. The results thus indicate that T11TS alone is more efficient in immune re-establishment after arsenic exposureas compared to combination therapy with T11TS+MiADMSA.

Khabaz, Mohamad Nidal 2949

https://doi.org/10.7314/APJCP.2012.13.6.2949 PDF KSCI

The glutathione S transferase (GST) family is a major part of cellular defense mechanisms against endogenous and exogenous substances, many of which have carcinogenic potential. Alteration in the expression level or structure of the glutathione-S-transferase (GST) enzymes may lead to inadequate detoxification of potential carcinogens and consequently contribute to cancer development. A member of the glutathione-S-transferase (GST) family, GSTP1, is an attractive candidate for involvement in susceptibility to carcinogen-associated colorectal cancer. An $Ag{\rightarrow}G$ transition in exon 5 resulting in an Ile105Val amino acid substitution has been identified which alters catalytic efficiency. The present study investigated the possible impact of Ile105Val GSTP1 polymorphism on susceptibility to colorectal cancer. in Jordan We examined 90 tissue samples previously diagnosed with colorectal carcinoma, and 56 non-cancerous colon tissues. DNA was extracted from paraffin embedded tissues and the status of the GSTP1 polymorphism was determined using a polymerase chain reaction restriction fragment length polymorphism (RFLP) method. No statistically significant differences were found between colorectal cancer cases and controls for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. The glutathione S-transferase polymorphism was not associated with risk in colorectal cancer cases in Jordan stratified by age, sex, site, grade or tumor stage. In conclusion, the GSTP1 Ile105Val polymorphism is unlikely to affect the risk of colorectal cancer.

Rohani-Rasaf, Marzieh;Moradi-Lakeh, Maziar;Ramezani, Rashid;Asadi-Lari, Mohsen 2955

https://doi.org/10.7314/APJCP.2012.13.6.2955 PDF KSCI

Background: Health disparities exist among and within countries, while developing and low income countries suffer more. The aim of this study was to quantify cancer disparities with regard to socioeconomic position (SEP) in 22 districts of Tehran, Iran. Method: According to the national cancer registry, 7599 new cancer cases were recorded within 22 districts of Tehran in 2008. Based on combined data from census and a population-based health equity study (Urban HEART), socioeconomic position (SEP) was calculated for each district. Index of disparity, absolute and relative concentration indices (ACI & RCI) were used for measuring disparities in cancer incidence. Results: The overall cancer age standardised rate (ASR) was 117.2 per 100,000 individuals (120.4 for men and 113.5 for women). Maximum ASR in both genders was seen in districts 6, 3, 1 and 2. Breast, colorectal, stomach, skin and prostate were the most common cancers. Districts with higher SEP had higher ASR (r=0.9, p<0.001). Positive ACI and RCI indicated that cancer cases accumulated in districts with high SEP. Female disparity was greater than for men in all measures. Breast, colorectal, prostate and bladder ASR ascended across SEP groups. Negative ACI and RCI in cervical and skin cancers in women indicate their aggregation in lower SEP groups. Breast cancer had the highest absolute disparities measure. Conclusion: This report provides an appropriate guide and new evidence on disparities across geographical, demographic and particular SEP groups. Higher ASR in specific districts warrants further research to investigate the background predisposing factors.

Balamuralikrishnan, Balasubramanian;Balachandar, Vellingiri;Kumar, Shanmugam Suresh;Stalin, Nattan;Varsha, Prakash;Devi, Subramaniam Mohana;Arun, Meyyazhagan;Manikantan, Pappuswamy;Venkatesan, Chinnakulandhai;Sasikala, Keshavarao;Dharwadkar, Shahnaz N. 2961

https://doi.org/10.7314/APJCP.2012.13.6.2961 PDF KSCI

Extremely low frequency electro magnetic fields (EMFs) have been classified as possibly carcinogenic to humans by the International Agency for Research on Cancer. An increased number of chromosomal alterations in peripheral lymphocytes are correlated with elevated incidence of cancer. The aim of the present study was to assess occupationally induced chromosomal damage in EMF workers exposed to low levels of radiation. We used conventional metaphase chromosome aberration (CA) analysis and the micronucleus (MN) assay as biological indicators of non ionizing radiation exposure. In the present study totally 70 subjects were selected including 50 exposed and 20 controls. Informed written consent was obtained from all participants and the study was performed in accordance with the Declaration of Helsinki and the approval of the local ethical committee. A higher degree of CA and MN was observed in exposed subjects compared to controls, the frequency of CA being significantly enhanced with long years of exposure (P<0.05). Moreover increase in CA and MN with age was noted in both exposed subjects and controls, but was significantly greater in the former. The results of this study demonstrated that a significant induction of cytogenetic damage in peripheral lymphocytes of workers occupationally exposed to EMFs in electric transformer and distribution stations. In conclusion, our findings suggest that EMFs possess genotoxic capability, as measured by CA and MN assays; CA analysis appeared more sensitive than other cytogenetic end-points. It can be concluded that chronic occupational exposure to EMFs may lead to an increased risk of genetic damage among electrical workers.

Yuan, Shao-Fei;Chen, Wen-Jun;Zhu, Lin-Jia;Zheng, Wei-E.;Chen, Hua;Xiong, Jian-Ping 2967

https://doi.org/10.7314/APJCP.2012.13.6.2967 PDF KSCI

Objective: To explore whether monoclonal antibodies against stathmin and the chemotherapuetic agent paclitaxel have synergenic effects in inhibiting growth and inducing apoptosis in human QG-56 cells. Methods: QG-56 cells were treated with monoclonal antibodies against stathmin or paclitaxel alone or in combination, with untreated cells used as controls. After 24, 48, 72 and 96 hours the cell growth condition was observed under an inverted microscope and inhibition was studied by MTT assay; apoptosis was analyzed by flow cytometry. Results: The populations decreased and cell shape and size changed after the various treatments. Monoclonal antibodies against stathmin and paclitaxel used alone or incombination inhibited the proliferation of QG-56 cells, especially in combination with synergism (P<0.05). Combined treatment also resulted in a significantly higher apoptosis rate than in the other groups (P<0.05). Conclusions: Monoclonal antibodies against stathmin and paclitaxel used alone or in combination can inhibit proliferation of QG-56 cells and induce apoptosis when applied together. The observed synergistic effects may have important implications for clinical application.

Madjd, Zahra;Ramezani, Babak;Molanae, Saadat;Asadi-Lari, Mohsen 2973

https://doi.org/10.7314/APJCP.2012.13.6.2973 PDF KSCI

Background: Cancer stem cells (CSC) have been described in a variety of malignancies, including breast carcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breast cancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressing ALDH1. Methods: We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status. Results: Comparing the results for both ALDH1 and BRCA1 expression showed a significant inverse association between the two, indicating that reduced BRCA1 was more often seen in breast cancer cells expressing ALDH1 (p-value = 0.044). A total of 24/110 (22%) of tumours displayed the ALDH1 + / BRCA1 -/low phenotype, which showed a trend for a relation with a high grade (p-value= 0.056). Cytoplasmic expression of ALDH1 was not correlated with tumour characteristics. Conclusion: Taken together, our findings suggest that increased ALDH1 is inversely correlated with decreased BRCA1 in a series of unselected breast carcinomas. Therefore, ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate.

Kalalinia, Fatemeh;Elahian, Fatemeh;Hassani, Mitra;Kasaeeian, Jamal;Behravan, Javad 2979

https://doi.org/10.7314/APJCP.2012.13.6.2979 PDF KSCI

Recent studies have indicated a link between levels of cyclooxygenase-2 (COX-2) and development of the multidrug resistance (MDR) phenotype. The ATP-binding cassette sub-family G member 2 (ABCG2) is a major MDR-related transporter protein that is frequently overexpressed in cancer patients. In this study, we aimed to evaluate any positive correlation between COX-2 and ABCG2 gene expression using the COX-2 inducer 12-O-tetradecanoylphorbol-13-acetate (TPA) in human breast cancer cell lines. ABCG2 mRNA and protein expression was studied using real-time RT-PCR and flow cytometry, respectively. A significant increase of COX-2 mRNA expression (up to 11-fold by 4 h) was induced by TPA in MDA-MB-231 cells, this induction effect being lower in MCF-7 cells. TPA caused a considerable increase up to 9-fold in ABCG2 mRNA expression in parental MCF-7 cells, while it caused a small enhancement in ABCG2 expression up to 67 % by 4 h followed by a time-dependent decrease in ABCG2 mRNA expression in MDA-MB-231 cells. TPA treatment resulted in a slight increase of ABCG2 protein expression in MCF-7 cells, while a time-dependent decrease in ABCG2 protein expression was occurred in MDA-MB-231 cells. In conclusion, based on the observed effects of TPA in MDA-Mb-231 cells, it is proposed that TPA up-regulates ABCG2 expression in the drug sensitive MCF-7 breast cancer cell line through COX-2 unrelated pathways.

Dogan, Erkan;Yalcin, Suayib;Koca, Dogan;Olmez, Aydemir 2985

https://doi.org/10.7314/APJCP.2012.13.6.2985 PDF KSCI

Background: Hepatocellular carcinoma (HCC), the main malignant tumor of the liver, is very common and highly lethal. The aim of this study was to determine its clinicopathologic characteristics and risk factors in Turkey. Materials and methods: In this study, patients who were diagnosed as suffering from HCC in the period between August 2004 and December 2011 were evaluated retrospectively. Results: A total of 98 patients were included, with a median age 61 (range: 16 to 82). Seventy nine (80.6%) were male 59 (60.2%) were infected with hepatitis B virus (HBV) and 15 (15.3%) with HCV, another 15 (15.3%) being alcohol abusers. Seventy two (73.5%) were at advanced stage and 54 (55.1%) had elevated serum alpha-fetoprotein (AFP). Surgery, chemoembolization, systemic chemotherapy and application of the tyrosine kinase inhibitor sorafenib were the major treatment options. Conclusions: According to our findings HCC is mostly diagnosed in advanced stage and age, being five times more common in males than females. Main risk factors of HCC are HBV infection, HCV infection and alcohol abuse. Elevation in AFP may facilitate early diagnosis of HCC in high risk groups.

Thulaseedharan, Jissa V.;Malila, Nea;Hakama, Matti;Esmy, Pulikottil O.;Cheriyan, Mary;Swaminathan, Rajaraman;Muwonge, Richard;Sankaranarayanan, Rengaswami 2991

https://doi.org/10.7314/APJCP.2012.13.6.2991 PDF KSCI

Background: India shows some of the highest rates of cervical cancer worldwide, and more than 70% of the population is living in rural villages. Prospective cohort studies to determine the risk factors for cervical cancer are very rare from low and medium resource countries. The aim of this study was to quantify the effect of risk factors related to cervical cancer in a rural setting in South India. Material and methods: Sociodemographic and reproductive potential risk factors for cervical cancer were studied using the data from a cohort of 30,958 women who constituted the unscreened control group in a randomised screening trial in Dindigul district, Tamilnadu, India. The analysis was accomplished with the Cox proportional hazard regression model. Results: Women of increasing age (HR=2.4; 95% CI: 1.6, 3.8 in 50-59 vs 30-39), having many pregnancies (HR=7.1; 1.0, 52 in 4+ vs 0) and no education (HR=0.6; 0.2, 0.7 in high vs none) were found to be at significantly increased risk of cervical cancer. Conclusion: This cohort study gives very strong evidence to say that education is the fundamental factor among the sociodemographic and reproductive determinants of cervical cancer in low resource settings. Public awareness through education and improvements in living standards can play an important role in reducing the high incidence of cervical cancer in India. These findings further stress the importance of formulating public health policies aimed at increasing awareness and implementation of cervical cancer screening programmes.

Sarkar, Madhutandra;Konar, Hiralal;Raut, D.K. 2997

https://doi.org/10.7314/APJCP.2012.13.6.2997 PDF KSCI

Background: This cross-sectional observational study was undertaken to identify the epidemiological characteristics of patients with gynecological malignancies in India, in relation to gynecological cancer risk. Methods: In the gynecology out-patient clinic of a tertiary care hospital in Kolkata, India, the patients with suggestive symptoms of gynecological malignancies were screened. One hundred thirteen patients with histopathologically confirmed gynecological malignancies were interviewed. Results: More than two-thirds of the cases (69.0%) occurred in the age range of 35-64 years and the same proportion of patients was from rural areas. Almost all the patients were "ever-married" (96.5%). More than half (54.9%) were illiterate/just literate. Nearly two-thirds (64.6%) were parity 3 or higher. Among the 18 patients with history of multiple sexual partners of the husband, 94.4% (17) were suffering from cervical malignancy, along with all the 3 patients with history of STD syndromes (sexually transmitted diseases) of their husbands. No one had given a history of condom use by her husband. Most of the patients (91.1%) used old / reused cloth pieces during menstruation. Conclusions: There is a need to increase awareness among women and the broader community about different epidemiological factors that may be responsible for increased risk of gynecological malignancies.

Hagiwara, Tadashi;Mukaisho, Ken-Ichi;Nakayama, Takahisa;Sugihara, Hiroyuki;Hattori, Takanori 3005

https://doi.org/10.7314/APJCP.2012.13.6.3005 PDF KSCI

Feng, Ren-Nan;Liu, Gui-You;Wang, Cheng;Sun, Chang-Hao;Li, Ying 3007

https://doi.org/10.7314/APJCP.2012.13.6.3007 PDF KSCI

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