BJcuL, a lectin purified from Bothrops jararacussu venom, induces apoptosis in human gastric carcinoma cells accompanied by inhibition of cell adhesion and actin cytoskeleton disassembly

We show that BJcuL, a lectin purified from Bothrops jararacussu venom, exerts cytotoxic effects to gastric carcinoma cells MKN45 and AGS. This effect was due to the direct interaction with specific glycans on the cells surface and was observed by cell viability decrease, disorganization of actin filaments and apoptosis. In addition, BJcuL was able to reduce tumor cell adhesion to matrigel, what was inhibited by specific carbohydrate or partially inhibited when cells were pre-incubated with matrigel. Our results suggest that BJcuL was able to promote apoptosis in both tumor cells lines and therefore has a prospect for potential use in cancer therapy. (C) 2011 Elsevier Ltd. All rights reserved.

Identification of protein expression signatures in gastric carcinomas using clustering analysis

Background and Aim: The identification of gastric carcinomas (GC) has traditionally been based on histomorphology. Recently, DNA microarrays have successfully been used to identify tumors through clustering of the expression profiles. Random forest clustering is widely used for tissue microarrays and other immunohistochemical data, because it handles highly-skewed tumor marker expressions well, and weighs the contribution of each marker according to its relatedness with other tumor markers. In the present study, we e identified biologically- and clinically-meaningful groups of GC by hierarchical clustering analysis of immunohistochemical protein expression. Methods: We selected 28 proteins (p16, p27, p21, cyclin D1, cyclin A, cyclin B1, pRb, p53, c-met, c-erbB-2, vascular endothelial growth factor, transforming growth factor [TGF]-beta I, TGF-beta II, MutS homolog-2, bcl-2, bax, bak, bcl-x, adenomatous polyposis coli, clathrin, E-cadherin, beta-catenin, mucin (MUC) 1, MUC2, MUC5AC, MUC6, matrix metalloproteinase [ MMP]-2, and MMP-9) to be investigated by immunohistochemistry in 482 GC. The analyses of the data were done using a random forest-clustering method. Results: Proteins related to cell cycle, growth factor, cell motility, cell adhesion, apoptosis, and matrix remodeling were highly expressed in GC. We identified protein expressions associated with poor survival in diffuse-type GC. Conclusions: Based on the expression analysis of 28 proteins, we identified two groups of GC that could not be explained by any clinicopathological variables, and a subgroup of long-surviving diffuse-type GC patients with a distinct molecular profile. These results provide not only a new molecular basis for understanding the biological properties of GC, but also better prediction of survival than the classic pathological grouping.

Adjuvant chemoradiotherapy after d2-lymphadenectomy for gastric cancer: the role of n-ratio in patient selection. results of a single cancer center

Background: Adjuvant chemoradiotherapy is part of a multimodality treatment approach in order to improve survival outcomes after surgery for gastric cancer. The aims of this study are to describe the results of gastrectomy and adjuvant chemoradiotherapy in patients treated in a single institution, and to identify prognostic factors that could determine which individuals would benefit from this treatment. Methods: This retrospective study included patients with pathologically confirmed gastric adenocarcinoma who underwent surgical treatment with curative intent in a single cancer center in Brazil, between 1998 and 2008. Among 327 patients treated in this period, 142 were selected. Exclusion criteria were distant metastatic disease (M1), T1N0 tumors, different multimodality treatments and tumors of the gastric stump. Another 10 individuals were lost to follow-up and there were 3 postoperative deaths. The role of several clinical and pathological variables as prognostic factors was determined. Results: D2-lymphadenectomy was performed in 90.8% of the patients, who had 5-year overall and disease-free survival of 58.9% and 55.7%. The interaction of N-category and N-ratio, extended resection and perineural invasion were independent prognostic factors for overall and disease-free survival. Adjuvant chemoradiotherapy was not associated with a significant improvement in survival. Patients with node-positive disease had improved survival with adjuvant chemoradiotherapy, especially when we grouped patients with N1 and N2 tumors and a higher N-ratio. These individuals had worse disease-free (30.3% vs. 48.9%) and overall survival (30.9% vs. 71.4%). Conclusion: N-category and N-ratio interaction, perineural invasion and extended resections were prognostic factors for survival in gastric cancer patients treated with D2-lymphadenectomy, but adjuvant chemoradiotherapy was not. There may be some benefit with this treatment in patients with node-positive disease and higher N-ratio.

Clinical implication of 14-3-3 epsilon expression in gastric cancer

AIM: To evaluate for the first time the protein and mRNA expression of 14-3-3 epsilon in gastric carcinogenesis. METHODS: 14-3-3 epsilon protein expression was determined by western blotting, and mRNA expression was examined by real-time quantitative RT-PCR in gastric tumors and their matched non-neoplastic gastric tissue samples. RESULTS: Authors observed a significant reduction of 14-3-3 epsilon protein expression in gastric cancer (GC) samples compared to their matched non-neoplastic tissue, Reduced levels of 14-3-3 epsilon were also associated with diffuse-type GC and early-onset of this pathology. Our data suggest that reduced 14-3-3 epsilon may have a role in gastric carcinogenesis process. CONCLUSION: Our results reveal that the reduced 14-3-3 epsilon expression in GC and investigation of 14-3-3 epsilon interaction partners may help to elucidate the carcinogenesis process. (C) 2012 Baishideng. All rights reserved.

Pharmacokinetics of Photogem Using Fluorescence Spectroscopy in Dimethylhydrazine-Induced Murine Colorectal Carcinoma

This study aimed to investigate the pharmacokinetics of a hematoporphyrin derivative in colonic tumors induced by dimethylhydrazine and adjacent normal colon in Wistar rats using an in vivo fluorescence spectroscopy technique. In conventional clinical application of photodynamic therapy, the interval between photosensitizer (PS) administration and lesion illumination is often standardized without taking into account variations due to the type or localization of the tumor and intrinsic differences in the microcirculation and vascular permeability of each target organ. The analysis of the fluorescence spectra was based on the intensity of porphyrin emission band centered at around 620nm in normal colon and colon tumors. The photosensitizer fluorescence intensity rapidly grew for carcinoma and normal colon, reaching the maximum values 1 and 3 hours after PS injection, respectively. Data presented here allow us to verify that the best compromise between selectivity and drug concentration for colon carcinoma in rats took place in the interval between 1 to 4 h after PS injection.

FGFR4 Profile as a Prognostic Marker in Squamous Cell Carcinoma of the Mouth and Oropharynx

Background: Fibroblast growth factor receptor 4 (FGFR4) is a member of a receptor tyrosine kinase family of enzymes involved in cell cycle control and proliferation. A common single nucleotide polymorphism (SNP) Gly388Arg variant has been associated with increased tumor cell motility and progression of breast cancer, head and neck cancer and soft tissue sarcomas. The present study evaluated the prognostic significance of FGFR4 in oral and oropharynx carcinomas, finding an association of FGFR4 expression and Gly388Arg genotype with tumor onset and prognosis. Patients and Methods: DNA from peripheral blood of 122 patients with oral and oropharyngeal squamous cell carcinomas was used to determine FGFR4 genotype by PCR-RFLP. Protein expression was assessed by immunohistochemistry (IHC) on paraffin-embedded tissue microarrays. Results: Presence of allele Arg388 was associated with lymphatic embolization and with disease related premature death. In addition, FGFR4 low expression was related with lymph node positivity and premature relapse of disease, as well as disease related death. Conclusion: Our results propose FGFR4 profile, measured by the Gly388Arg genotype and expression, as a novel marker of prognosis in squamous cell carcinoma of the mouth and oropharynx.