Flow cytometric analysis of the ERCC1, marker of DNA damage repair, in the tumor specimens embedded into paraffin blocks.

The differences in expression of ERCC1 were estimated between tumor specimens embedded into paraffin blocks and surgical biopsy specimens of non-small cell lung cancer as well as breast and ovarian cancers. Concordance or differences not higher than 20% were observed in 73% of the cases. The number of the cases with more significant differences in ERCC1 expression was less than 17%. The results show that ERCC1 detection in surgical biopsy specimens by flow cytometry is the more preferable method due to reduced preanalytical phase of the analysis.

[Surgical strategy for locally-advanced right-sided colonic cancer]. / Strategiia khirurgicheskogo lecheniia mestno-rasprostranennogo raka pravoi poloviny obodochnoi kishki.

AIM: To present early and remote surgical outcomes in patients with locally-advanced right-sided colonic cancer, invasion of pancreatic head and/or duodenal wall. MATERIAL AND METHODS: Early and remote surgical outcomes were analyzed in 27 patients who underwent gastropancreatoduodenectomy combined with right-sided hemicolectomy (ileotransversostomy extirpation) for locally-advanced right-sided colonic cancer. RESULTS: Mean time of surgery was 300 (240-460) minutes, intraoperative blood loss - 2000 (500-7200) ml. Postoperative complications were observed in 15 (55.6%) patients. 3 (11.1%) patients died in early postoperative period. Overall 1-, 3- and 5-year survival was 92.7%, 48% and 36,5% respectively. Median was 33 months. CONCLUSION: Advanced combined surgery for locally-advanced right-sided colonic cancer, invasion of pancreatic head and/or duodenal wall is associated with acceptable incidence of postoperative complications, early and long-term mortality.

Digoxin is a selective modifier increasing platinum drug anticancer activity.

Using the model of breast cancer Ehrlich ascites tumor in mice, we showed that a sigle intraperitoneal injection of cardiac glycoside digoxin 1 h before the intraperitoneal injection of cisplatin increased the anticancer effect of the cytostatic drug more than twice when recalculated for the dose. It is assumed that the modifying effect of digoxin is determined by the direct inhibition of glycolysis in tumor cells. Taking into account the design of the study, we consider promising the clinical evaluation of the effectiveness of digoxin as a modifier of cisplatin efficiency in intracavitary therapy of ascites cancers with pleural and abdominal dissenmination.

New Data on Molecular Targets of Tamoxifen Besides Estrogen Receptors, Their Clinical Significancy.

Tamoxifen is the first target agent with a high-end position in breast cancer therapy till now. In recent years experimental researches revealed new biological effects of tamoxifen on tumor cells. The present study continues the theme of the review published in 2012, where a plenty of tamoxifen effects besides interaction with estrogen receptors was discussed. Thus, there is described a wide range of the drug targets which are the key points of signal cascades activating the cell proliferation and determining the course of the growth of the cancer and its sensitivity to chemotherapy. Also clinical trials of tamoxifen based on existing of targets besides the estrogen receptors are reviewed. Furthermore, the data on the antiviral, antibacterial, antifungal and antiparasitic activities of tamoxifen are indicated.

[ERCC1 as a Marker of Ovarian Cancer Resistance to Platinum Drugs].

The review is concerned with the crucial marker of nucleotide excision repair ERCC1 and its contribution to platinum resistance of ovarian cancer. All the variants of the laboratory and clinical ERCC1 assessment in the ovarian cancer tissue (single nucleotide polymorphisms of the ERCC1 gene, levels of mRNA or protein) are considered. Data on the prognostic and predictive value of ERCC1 as a marker of the response to platinum-based therapy in ovarian cancer are systematized. The authors discuss the possible causes of heterogeneity of the results and emphasize the necessity of a unified and integrated approach to evaluation of ERCC1 in the tumor. The publications cited in the Search Engine Pub Med up to January 2015 were analyzed.

Surgical treatment of patients with kidney and bladder cancer in case of severe concomitant cardiovascular diseases.

It was operated 17 patients with kidney and bladder cancer against the background of severe concomitant coronary artery disease (52.9%), aortic aneurysm (35.3%) or combination of coronary artery disease with Leriche syndrome (5.9%) or hemodynamically significant stenosis of internal carotid artery (5.9%). Patients were operated for the period from 1998 to 2012. All patients were male at the age from 39 to 80 years (mean 62.1 years). The first stage of kidney cancer was diagnosed in 8 (53.3%) patients, the second stage - in 1 (6.7%) patient, the third stage - in 2 (13.3%) patients and the fourth stage was observed in 4 (26.7%) patients. Bladder cancer had 1 and 2 stages. Simultaneous operations were performed in 3 (17.6%) patients. 12 (70.6%) patients were operated consequentially. Surgery for kidney cancer was not done in 2 (11.8%) of 17 patients because of patient death after coronary bypass surgery or patient refusal of surgery after carotid arteries stenting. Intraoperative and postoperative complications have been developed in 9 (52.9%) of 17 patients. 2 (11.8%) patients died. The complications frequency and mortality after simultaneous operations were 25% (1 of 4) and 0. These parameters were 57.1% (8 of 14) and 14.3% respectively in case of consequent tactics. It was not observed myocardial infarction and aortic aneurysm rupture after surgeries for kidney and bladder cancer. Overall 1, 3, 5 - year survival of patients with kidney cancer and severe concomitant cardiovascular diseases was 100%, 73.3% and 52.4% respectively. It was concluded that surgical treatment of severe concomitant coronary artery disease and aortic aneurysm in patients with kidney and bladder cancer decreases risk of myocardial infarction and aortic aneurysm rupture in intraoperative and postoperative periods.

[Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

[Radical removal of a malignant mediastinum hemangioendothelioma with restoration of the main blood supply to the brain].

46 year old man appealed to the Cancer Research Center of RAMS in October 2012 with unverified anterior superior mediastinal tumor, which was diagnosed in 2010. Progressive compartment syndrome of the superior vena cava was observed. On examination: CT, MRI, angiography, histological and cytological examination of biopsy material did not allow to confirm the morphological structure of the tumor. Removal of the tumor with bifurcation of the brachiocephalic trunk prosthetics was performed. Immunohistochemical (IHC) study verified malignant hemangioendothelioma.

[Surgical treatment of patients with stomach cancer and severe concomitant cardio-vascular pathology].

51 patients with gastric cancer and severe concomitant ischemic heart disease (90.2%), valvular heart disease (5.9%), critical stenosis of the internal carotid artery (2%) or abdominal aortic aneurism (2%) were operated on during 1995-2011yy. Of them men were 41, women - 10; mean age was 65.1 years (51-82). The first stage of gastric cancer was diagnosed in 18 (35.3%) of patients, second, third and fourth in 12 (23.5%), 17 (33.3%) and 4 (7.8%), respectively. Radical tumor resection was achieved in 37 (72.5%), palliative operations were performed in 13 (25.5%) patients. 17.6% of patients were operated on stomach and vessels simultaneously. 82.4% received the stepwise treatment. Intra- and postoperative complications were registered in 47.1% (24 of 51 patients); of whom 5.9% (3 patients) ended lethally. Simultaneous operations showed the 55.6% complications and zero lethality rate, whereas stepwise treatment resulted in 45.2% complications and 7.1% lethality.

[Discordance of estrogen receptor status between primary and metastatic breast cancer--possible reasons and prognostic value].

The aim of the review was systematization of the data on discordance in expression of estrogen receptors between primary and metastatic breast cancer, different metastases and repeated analyses of the same tissue. The possible reasons for the phenomenon are discussed. The authors emphasize the need to analyze estrogen receptors in breast cancer metastases, regardless of the receptor status of the primary tumor, for predicting the course of the metastatic disease and providing an adequate treatment of the metastatic tumor in strict accordance with its receptor status during drug therapy. The works cited in the search engine Pub Med to May 2013 were analyzed.

[The surgical treatment of patients with lung cancer and severe cardiovascular disorders].

During the period of 1991--2010 yy 51 patients with lung cancrs were operated on the severe cardiovascular diseases (IHD -- 90%; critical carotid stenosis -- 6%; tricuspidal valve failure -- 2% and the combination of the IHD and aortic valve failure -- 2%). Lung cancer steged I in 17 (33.3%) patients, II in 15 (29.4%); III - in 16 (31.4%) and IV in 3 (5.9%) patients. 33 patients of 51 were radically operated on lung cancer, palliative resections were performed in 3; trial thoracotomies were performed in 2 patients. 8 (15.7%) patients were operated on simultaneously. The complicated postoperative period was registered in 22 (57.9%) patients of 38 with exitus lethalis in 2 cases. The complication rate after simultaneous operation was 62.5% with lethality of 12.5%, whereas by the consecutive operations the complication rate was 56.7% with lethality of 3.3%, Nevertheless, surgical correction of the severe concurrent cardiovascular pathology flares the range of operable patients with lung cancer.

[Heterotopic transplantation of non-immunogenic trachea populated with recipient bone marrow stromal cells].

Morphological changes in decellularized allogenic trachea populated with recipient bone marrow stromal (mesenchymal) stem cells and transplanted heterotopically, were examined in 30 C57Bl/6 and Balb/c mice of 22-25 g body mass. The research results have shown the insufficient efficacy of a transplant preparation mode by freezing and thawing method as in this case inflammatory reaction developed in the transplant area and its rejection took place. It was established that the mode of obtaining decellularized tracheal transplant by means of sodium perchlorate (NaClO4) treatment, proposed by the authors, unlike a freezing-thawing mode, allowed to efficiently remove immunocompetent cells that expressed MHC I and II markers. NaClO4 effect did not result in either chondrocyte damage or significant disturbance of tracheal cartilaginous and connective tissue structure in heterotopic transplants. Since transplant population with bone marrow stromal stem cells promoted connective tissue restoration, reduced the formation of granulations in anastomosis area and favored faster transplant epithelization, most promising method of trachea preparation for transplantation apparently seems to be the combination of immune cell removal from this organ by NaClO4 treatment with subsequent bone marrow stromal stem cell population of transplant obtained.

[Tamoxifen molecular targets different from estrogen receptors].

Experimental studies showing ever new biological effects of tamoxifen on tumor cells, both expressing and nonexpressing estrogen receptors, are providing a novel conception of the drug, likely well known at present. The review describes tamoxifen targets, whose blocking induces inhibition of tumor cell growth and angiogenesis, stimulation of the programmed cell death (apoptosis, autophagia and necrosis), inhibition of multiple drug resistance mechanism and inhibition of invasion and metastasizing. In all the events, the results of the tamoxifen interaction with the cells are prognostically favourable from the viewpoint of both the inhibition of the tumor growth and metastasizing and the susceptibility to the medicinal therapy, that is considered by some authors as an extremely important addition to the tamoxifen antiestrogenic effect. The strategy of long-term tamoxifen adjuvant therapy of breast cancer with positive status of the estrogen reseptors was developed by Craig V. Jordan as far back as in the seventies of the XXth century, however there are arguments allowing to consider it also useful for the treatment of other tumors. First of all it is the fact described lately in regard to expression of estrogen beta-reseptors in solid tumors of practically all known localization and histological types, that are also the targets of tamoxifen. Apart from estimation of estrogen receptors, it is believed by some authors that molecular and biological choice of patients is necessary with an account of expression of other cell targets of antiestrogen for complete realization of all the aspects of tamoxifen biological activity in long-term adjuvant therapy of malignant tumors of various localization.