• Journal of Gastric Cancer
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• v.17 no.1
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• pp.21-32
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• 2017

Purpose: Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. Materials and Methods: We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. Results: Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. Conclusions: EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resections, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.

• Biomedical Science Letters
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• v.11 no.4
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• pp.481-486
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• 2005

This study was performed to define roles of telomerase and apoptosis and their relationships with clinicopathologic characteristics in colorectal cancers. We performed TRAP (Telomeric Repeat Amplification Protoco1)-ELISA assay for telomerase activity and immunohistochemistry of active caspase-3 expression for apoptosis in 35 colorectal cancers. Increased telomerase activity was detected in $71.4\%$ (25/35) and average apoptotic index was 14.6 per 1000 tumor cells. Telomerase activity and caspase 3 expression had no significant association with clinicopathological characteristics, however, increased telomerase activity was more frequently found in progressed colorectal cancers. Although there is no definitive relation, low apoptotic index group was more frequent in cases with increased telomerase activity. These date indicate that telomerase might be involved in progression of colorectal cancers. We suggest that there is a need for further study to define the relationship between telomerase and apoptosis in colorectal cancers.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.117-125
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• 2015

Purpose: To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). Results: With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. Conclusion: ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT.

• Journal of Nutrition and Health
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• v.36 no.3
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• pp.280-286
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• 2003

Conjugated linoleic acid (CLA) consists of several geometric isomers of linoleic acid. CLA is found in foods derived from ruminants and exhibits strong anticarcinogenic effects in a variety of animal models. Matrix metalloproteinases (MMPs) play a key role in cancer progression. Specifically, MMP-2 and -9, which hydrolyze the basal membrane type IV collagen, are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. However, the effects of CLA on cancer cell motility and MMP expression and activity are not currently well known. Therefore, the present study examined whether CLA reduces the activity of MMP and cell motility in SW480 and SW620 cells, the human colon cancer cell lines. Gelatin zymography and Western blot analysis revealed that phorbol 12-myristate 13-acetate (PMA) induced the activity and protein expression of Mr 92,000 MMP-9 in both cell lines. To examine whether CLA inhibits the MMP activity, cells were incubated with 100 ngfmL PMA in the presence of various concentrations of CLA. PMA-induced MMP-9 activity was decreased by 20 $\mu$ M CLA in SW480 cells, and by 10 $\mu$ M and 20 $\mu$ M CLA in SW620 cells. Results from the Hoyden chamber assay showed that cell motility was increased by PMA and that PMA-induced cell motility was significantly decreased by 20 $\mu$ M CLA in SW480 cells. These results indicate that CLA may reduce the motility and MMP activity in human colon cancer cells.

• Journal of Ginseng Research
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• v.23 no.2 s.54
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• pp.99-104
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• 1999

The effects of ginseng and cinnamon extract alone or mixture on the various cancer cell lines in vitro have been examined. Human colon cancer cell line (HT-29), human rectal cancer cell line (HRT-18) and human hepatoma cell line (HepG2) were used for the experiment. When given separately, the proliferation of all cancer cell lines was inhibited in proportion to the concentration of ginseng or cinnamon extract, respectively. Based on the cytotoxic activity, mixture of ginseng and cinnamon extract demonstrated a synergistic inhibition of cancer cell growth. The progression of cell cycle from G1 to S phase was significantly inhibited by ginseng and cinnamon mixture in the HT-29 and HRT-18 cell lines.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9385-9390
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• 2014

Introduction: Human adiponectin (ApN) is a 30 kDa glycoprotein of 244-amino acids which is extensively produced by adipocytes. ApN acts via two receptors, namely adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Studies have shown the presence of Adipo-R1 and Adipo-R2 expression immunohistochemically in human colorectal cancers (CRCs). However, only a few studies exist which investigated effects of adiponectin receptor expression on CRC characteristics. Objectives: In the present study, we aimed to explore Adipo-R1/-R2 expression in human colorectal cancers and any association with clinicopathological characteristics and survival. Materials and Methods: The study enrolled 58 colorectal cancer patients with tumor resection and a control group of 30 subjects with normal colon mucosa. Results: Positivity for Adipo-R1/-R2 expression was significantly more common in the control group in comparison to the patient group (both p<0.001). There was no significant association between Adipo-R1/-R2 expression and clinicopathological characteristics including age, sex tumor location, pTNM stage, Duke's stage, metastasis, histological differentiation, perineural invasion, venous invasion sex, lymphatic invasion, cancer-related mortality, tumor size and recurrence. Adipo- R1/-R2 positivity was also not significantly linked to progression-free or overall survival [p values (0.871, 0.758) and (0.274, 0.232), respectively]. Conclusions: Although significantly reduced Adipo-R1/-R2 expression was found in colorectal cancer patients, it had no influence on survival.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8405-8410
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• 2016

Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) development. Recent studies demonstrated that single nucleotide polymorphisms (SNPs) rs2293152 in signal transducer and activator of transcription 3 (STAT3) and rs7574865 in signal transducer and activator of transcription 4 (STAT4) are associated with chronic hepatitis B (CHB)-related HCC in the Chinese population. We hypothesized that these polymorphisms might be related to HCC susceptibility in Thai population as well. Study subjects were divided into 3 groups consisting of CHB-related HCC (n=192), CHB without HCC (n=200) and healthy controls (n=190). The studied SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the distribution of different genotypes for both polymorphisms were in Hardy-Weinberg equilibrium (P>0.05). Our data demonstrated positive association of rs7574865 with HCC risk when compared to healthy controls under an additive model (GG versus TT: odds ratio (OR)=2.07, 95% confidence interval (CI)=1.06-4.03, P=0.033). This correlation remained significant under allelic and recessive models (OR=1.46, 95% CI=1.09-1.96, P=0.012 and OR=1.71, 95% CI=1.13-2.59, P=0.011, respectively). However, no significant association between rs2293152 and HCC development was observed. These data suggest that SNP rs7574865 in STAT4 might contribute to progression to HCC in the Thai population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4319-4323
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• 2014

Background: Phospholipase C epsilon 1 (PLCE1) encodes a member of the phospholipase family of proteins that play crucial roles in carcinogenesis and progression of several cancers including esophageal cancer (EC). In two large scale genome-wide association studies (GWAS) single nucleotide polymorphisms (SNP, rs2274223A>G, rs3765524C>T) in PLCE1 were identified as novel susceptibility loci of esophageal cancer (EC) in China. The aim of the present study was to investigate this finding in Kashmir Valley, a high risk area. Materials and Methods: We determined genotypes of three potentially functional SNPs (rs2274223A>G, rs3765524C>T and rs7922612C>T) of PLCE1 in 135 EC patients, and 195 age and gender matched controls in Kashmiri valley by PCR RFLP method. Risk for developing EC was estimated by binary logistic regression using SPSS. Results: The selected PLCE1 polymorphisms did not show independent association with EC. However, the $G_{2274223}T_{3765524}T_{7922612}$ haplotype was significantly associated with increased risk of EC (OR=2.92; 95% CI=1.30-6.54; p=0.009). Smoking and salted tea proved to be independent risk factors for EC. Conclusions: Genetic variations in PLCE1 modulate risk of EC in the high risk Kashmiri population.

• Journal of Gastric Cancer
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• v.3 no.3
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• pp.145-150
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• 2003

Purpose: The p53 tumor suppressor gene is believed to play a pivotal role in preventing the uncontrolled cellular growth characteristic of cancer. Mutation of the p53 gene represent one of the most common genetic alterations in human cancers, and the acquisition of such defects is strongly associated with tumor progression and metastasis. The aim of this study was to evaluate the relation between p53 immunoreactivity and the mutation of p53 gene in gastric adenocarcinoma obtained by laser capture microscope. Materials and Methods: Formalin fixed paraffin embedded tissue specimens were obtained from 20 patients who underwent surgery for gastric cancer. According to UICC TNM system, 3 of the cases were Ia, 2 cases II, 4 cases IIIa, 5 cases IIIb, and 6 cases IV. Results: Immunohistochemical staining revealed eight cases as negative (less than $10\%$), twelve cases as postive (more than $10\%$). The locations of mutations were as follows; 7 cases had point mutation at exon 4, and 3 cases point mutation at exon 8. There was no mutation at exon 5, 6, 7 and 9. The mutation was observed in 1 case out of 8 p53 oncoprotein negative cases, and 7 cases out of 12 p53 positive cases. The mutation was more common in p53 positive cases (P<0.05), However, there was no significant correlation between p53 mutation observed by DNA sequencing after laser capture microdissection and expression of p53 oncoprotein. Conclusion: These result suggest that he expression of p53 oncoprotein not to be related to the mutation of p53 gene at exons 4 through 9 in gastric cancer.

• Journal of Gastric Cancer
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• v.13 no.2
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• pp.111-116
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• 2013

Purpose: Chronic inflammation induces cancer and cancer induces local tissue damage with systemic inflammation. Therefore, the aim of this study is to investigate the potential relationship between the severity of inflammation and prognosis in cancer patients. Materials and Methods: This study enrolled 220 patients from January 2002 to December 2006 who underwent gastric surgery. We evaluated the relationship between preoperative inflammatory parameters (erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio) and other clinicopathological factors. Survival outcomes were compared according to the extent of inflammation. Results: Significant elevation of erythrocyte sedimentation rate was related with old age, increased neutrophil-to-lymphocyte ratio, decreased hemoglobin, increased carcinoembryonic antigen, increased tumor size and advanced TNM stage. Neutrophil-to-lymphocyte ratio was significantly correlated with old age, increased erythrocyte sedimentation rate and advanced TNM stage. In the univariate analysis, elevated erythrocyte sedimentation rate and increased neutrophil-to-lymphocyte ratio had significantly poorer survival than those without elevation (all P<0.05). However, the multivariate analysis failed to prove erythrocyte sedimentation rate and neutrophil-tolymphocyte ratio as independent prognostic factors. Conclusions: The elevation of erythrocyte sedimentation rate and neutrophil-to-lymphocyte ratio were correlated with poor prognosis in the univariate analysis and there was a strong correlation between inflammatory parameters (erythrocyte sedimentation rate and neutrophil- to-lymphocyte ratio) and tumor progression. Thus, erythrocyte sedimentation rate and neutrophil-to-lymphocyte ratio are considered useful as follow-up factors.