CANCER-ASSOCIATED ADIPOCYTES AND PROGNOSTIC VALUE OF PREOPERATIVE NEUTROPHIL-LYMPHOCYTE RATIO IN GASTRIC CANCER.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) turned out to be a routinely available marker capable to reflect the systemic inflammatory response created by a tumor. Gastric cancer (GC) grows in the anatomical vicinity of adipose tissue, which is also associated with low-grade inflammation. AIM: To investigate the usefulness of the combined use of preoperative NLR and density of intratumoral cancer-associated adipocytes (CAAs) for predicting the disease outcome in GC patients. MATERIALS AND METHODS: A total of 151 patients with GC were eligible for retrospective analysis between 2009 and 2015.NLR preoperative values were calculated. Perilipin expression in tumor tissue was examined immunohistochemically. RESULTS: Low preoperative NLR is the most reliable prognostic factor for the favorable outcome for patients with low density of intratumoral CAAs. Patients with a high density of CCAs are at high risk of lethal outcomes independently of the value of preoperative NLR. CONCLUSION: The results have clearly shown an association between preoperative NLR and the density of CAAs in the primary tumor of GC patients. The prognostic value of NLR is essentially modified by means of the individual density of intratumoral CAAs in GC patients.The elevated NLR could be of significant predictive potential for a negative prognosis for patients with tumors characterized by the high density of CAAs independently of BMI.

CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome.

AIM: To evaluate the association between the presence of CD8 and CD45RO T lymphocytes in bone marrow (BM), disseminated tumor cells (DTCs), tumor hypoxia and their impact on disease outcome. MATERIAL AND METHODS: 91 naïve gastric cancer (GC) patients were enrolled into the study. DTCs, CD8- and CD45RO-positive T lymphocytes in BM were detected using immunocytochemistry. All patients were thoroughly informed about the study that was approved by the local ethics committee. Statistical analyses were done using NCSS2000/PASS2000 and Prism, version 4.03 software packages. RESULTS: It was detected that 80.5 and 81.3% of patients had CD8- and CD45RO-positive T cells in BM, respectively. When DTCs were detected in BM, the number of patients with CD8-and CD45RO-positive T cells in BM were 86.1 and 84.4%, respectively. It was also determined that the number of patients with DTCs in BM with categories M0 and M1 and with CD8- and CD45RO-positive T cells in BM were 86.2 and 85.7%, 85.7 and 80.0%, respectively. The association between DTCs in BM and presence of CD8 and CD45RO T cells lymphocytes in BM was not found. At the same time it was shown the association between presence of CD8 and CD45RO T lymphocytes and survival. The presence of CD8- and CD45RO-positive T cells in BM were accompanied with significantly longer overall survival of patients compared to that of patients without CD8- and CD45RO-positive T cells in BM. CONCLUSION: Patients with the presence of CD8- and CD45RO-positive T cells in BM demonstrated better survival of GC patients than those with the absence of these cells in BM. It may be suggested that tumor cells in BM are controlled in a dormant state by T cells in BM, in particular by CD8-positive T cells.

Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival

INTRODUCTION: Hypoxia is a key feature of the microenvironment of cancer cells actively participating in tumour progression. Our study was aimed to evaluate the impact of hypoxia and hypoxia-associated factors on tumour progression and survival of patients with gastric cancer. MATERIAL AND METHODS: One hundred and five resected specimens were used. The level of tumour hypoxia was evaluated using (31)P NMR spectroscopy, CD68 (tumour-associated macrophages), CD34 (microvessel density, MVD) and VEGF expression, immunohistochemistry, MMP-2 and MMP-9 activity, zymography. Statistical analysis was conducted using Pearson's test, Kaplan-Meier survival analysis, log-rank test and Cox proportional hazards model. RESULTS: Intratumoral hypoxia level has been significantly correlated with VEGF expression, TAM number and total protease activity. The overall survival rate of patients with strong tumour hypoxia, high level of MVD, VEGF expression, TAM and MMP activity was significantly lower than that of the patients without the mentioned tumour characteristics. CONCLUSIONS: The hypoxia-associated signalling that is activated in tumours promotes tumour progression through the recruitment of macrophages, remodelling of extracellular matrix and neoangiogenesi (AU)

Helicobacter pylori infection of gastric cancer cells elevates the level of expression and activation of protein kinase D2.

AIM: To test the hypothesis, whether H. pylori infection may affect the level of PKD2 expression and/or activation in gastric cancer cells. METHODS: Studies were performed on AGS human gastric adenocarcinoma cell line, gastric tissues samples from 36 cases of different histological variants of gastric cancer. Immunohistochemical, cell and molecular biology, bacteriological and biochemical approaches have been used in this study. RESULTS: H. pylori 16S rRNA gene was detected in 97% cases of gastric tumors, and in 83% of cases csmall a, CyrillicgA gene was detected. In all tested adenocarcinoma samples cagA+ H. pylori was revealed. These cases were characterized by high level of PKD1/2 expression and autophosphorylation. In adenogenic cancer samples the presence of cagA- H. pylori was identified. Carcinoid and nondifferentiated gastric cancers contain H. pylori, with very low numbers of cagA+ copies. All cases of gastric tumors with cagA- H. pylori had very low levels of PKD1/2 autophosphorylation. AGS cell line infection with cagA- and cagA+ H. small er, Cyrillicylori resulted in elevation of PKD2 expression levels in 3.29 and 3.66 times respectively (p < 0.001). In cells infected by cag+ H. small er, Cyrillicylori the level of PKD2 transphosphorylation was 1.39 higher than in cells infected by cagA- H. pylori. For PKD2 autophosphorylation this difference was even higher - 3.27 times (p < 0.001). CONCLUSION: H. pylori infection enhanced the level of protein kinase D2 expression, trans- and autophosphorylation. The level of PKD2 autophosphorylation/activation was higher in AGS cell line inoculated of with cag+ H. pylori than in AGS cells with cagA- H. pylori. These suggest that H. pylori induces activation of PKD1/2 and could exploit PKD2 mediated signaling pathways that may contribute to the pathogenesis of gastric cancer.