Aim. The evaluation of the clinical relevance of disseminated tumor cells (DTCs) in bone marrow (BM) of patients with gastric cancer (GC) and their association with primary tumor hypoxia. Patients and Methods. 89 resected specimens were used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography. Results. DTCs were detected in 51.4% of GC patients with M0. There was significant correlation between frequency of DTCs in BM and level of tumor hypoxia (P < 0.024). DTCs presence was accompanied with Flt-1 positivity of BM. The correlation between DTCs and tumor VEGF expression in patients with M0 was shown (P < 0.0248). Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients with M0 (P < 0.05). Overall survival (OS) of patients with M0 and DTCs was shorter than that of patients without DTCs (patients in both groups were operated only) (P = 0.0497). Conclusion. Appearance of DTCs correlates with hypoxia level in primary tumors. Detection of DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using.

The VEGF- (bevacizumab) and EGFR- (cetuximab and panitumumab) targeting monoclonal antibodies have become integral components of the first-line treatment strategies for patients with metastatic colorectal cancer (mCRC). Increasingly combination chemotherapy, with or without a targeted agent, is being used to facilitate curative liver resection and improve survival rates in patients with initially unresectable but potentially resectable mCRC. Currently, the only selective marker for the treatment of patients with mCRC is tumor RAS mutational status. BRAF status is a strong prognostic indicator. Medical and clinical oncologists from Central Asia, Russia, the Middle East, Africa and Turkey reviewed data for the use of targeted agents in the treatment of patients with mCRC and have formed recommendations for the biological of choice first-line for patients with mCRC.

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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.

Summary. Malignancy may be characterized as a state formed in the setting of specific tumor-host relationships at the molecular and cellular microenvironment levels. R.E. Kavetsky and his collaborators distinctly outlined the concept of tumor-host interaction. Tumor is a complicated biological system closely connected with the organism, where it arises and develops. Tumor cells are in the environment of different factors that form tumor microenvironment playing an active role in the disease progression. There are two types of tumor microenvironment: the metabolic microenvironment mediated by factors of tumor microphysiology (blood flow, vascular permeability, oxygenation, extracellular рН, interstitial fluid pressure, etc.) and the cellular-molecular microenvironment comprising interactions between tumor cells and non-tumor cells and the factors of the stromal compartment. Factors of tumor microphysio­logy can modify the interaction between tumor cells and surrounding non-tumor cells and molecular components and they form the tumor profile that influences the pressure of tumor on the host. The review presents the data concerning the role of metabolic microenvironment of tumor cells from the point of tumor-host interaction in order to employ these parameters to working out the methods of diagnosis and prognosis of disease outcome in patients with gastric cancer. Special attention has been paid to hypoxia as a key factor of metabolic microenvironment that positively affects tumor progression, stimulating its aggressiveness, metastasis and resistance to therapy and is regarded as a factor of unfavorable prognosis. It was shown that there is possible clinical relevance of tumor classification based on the level of tumor oxygenation that may be advantageous for selection of patients for individualized therapy that may give the hope for enhancement of treatment efficacy.