Evolutionarily new sequences expressed in tumors

Background  

Earlier we suggested the concept of the positive evolutionary role of tumors. According to this concept, tumors provide conditions for the expression of evolutionarily new and/or sleeping genes in their cells. Thus, tumors are considered as evolutionary proving ground or reservoir of expression. To support this concept we have previously characterized in silico and experimentally a new class of human tumor-related transcribed sequences.     

Changes in immune status in patients with infectious endocarditis in surgical treatment involving artificial blood circulation

In 98.2% patients with infectious endocarditis, admitted to the hospital for surgical treatment, the moderate immune deficiency state is revealed with the cell link of immunity depression and phagocytic function of neutrophils insufficiency, which become aggravated after operative intervention performance, especially using artificial blood circulation. The cell link of immunity depression, the B-lymphocytes function inhibition are preserved during 6 months after the operation.     

Papillomavirus infection in healthy women from St.Petersburg

The study was aimed to evaluate the features of human papillomavirus (HPV) infection in healthy female inhabitants of St. Petersburg. 309 attendants of gynecological clinics were recruited for the screening. All participants were of reproductive age and were lacking the clinical or morphological symptoms of HPV-related diseases. PCR revealed HPV-specific sequences in 90 (29%) women. HPV type distribution was similar to the one in USA and Europe. HPV-positivity did not correlate with age of females, age at sexual debut, or total life-long duration of sexual activity. However, HPV were overrepresented among women reporting excessive number of contraceptive abortions. The data imply that an establishment of large-scale HPV-testing in Russia could be a desirable component of preventive anti-cancer programs.     

Enhancement of the therapeutic effect of sarcolysine by arterial hypotension in sarcoma 45 trials

Arterial hypotension was found to potentiate antitumor effect of sarcolysin on transplantable sarcoma 45 of rats. Induction of hypotension as modifying factor of chemotherapy of cancer is discussed.     

The small G-protein RalA stimulates metastasis of transformed cells

RAS oncogenes play a critical role in oncogenic transformation and metastases formation. Here we show that Ha-ras greatly stimulates spontaneous metastatic activity of transformed cells through the Ras/RalGDS/RalA intracellular signaling pathway. Introduction of RalA alone leads to a drastic increase of metastatic activity of transformed cells. We demonstrate that metastatic ability of cells could be dramatically enhanced by RalA stimulation or, conversely, hampered by RalA suppression. Furthermore, we found that during in vivo selection cells acquire high metastatic properties as a result of endogenous RalA activation. The ability of RalA to induce metastasis was demonstrated in spontaneously transformed as well as in virus transformed fibroblasts.     

Kinase-addiction and bi-phasic sensitivity-resistance of Bcr-Abl- and Raf-1-expressing cells to imatinib and geldanamycin

By activating anti-apoptotic factors (e.g., Hsp70, Raf-1, Bcl-xL), Bcr-Abl blocks apoptotic pathways at multiple levels, thus rendering leukemia cells resistant to chemotherapeutic agents such as doxorubicin (DOX). In Bcr-Abl-transfected HL60 (HL/Bcr-Abl) cells, procaspase-9 was increased and partially processed. The Bcr-Abl inhibitor imatinib (Gleevec, STI-571) released the apoptotic stream. Also, HL/Bcr-Abl cells were hyper-sensitive to geldanamycin (GA), which depletes Bcr-Abl and Raf-1. Raf-1 and Bcr-Abl-transfected FDC-P1 hematopoietic cells were selectively sensitive to GA and imatinib, respectively. Remarkably, cell clones with high levels of Bcr-Abl that could not be depleted by GA were relatively resistant to both GA and imatinib. GA and flavopiridol sensitized such resistant cells to imatinib. These data suggest bi-phasic sensitivity to mechanism-based therapeutic agents. Although Bcr-Abl renders cells hyper-sensitive, an excess of Bcr-Abl results in resistance (due to the remaining activity). We discuss therapeutic approaches to overcome bi-phasic resistance to mechanisms-based agents.