[Treatment of recurrent retroperitoneal myxolipoma]. / Opyt lecheniya retsidiviruyushchei zabryushinnoi miksolipomy.

The problem of retroperitoneal neoplasm management is still relevant despite certain achievements in diagnosis, anesthetic care and surgical techniques. These patients often admit to specialized hospitals with a widespread malignant process and/or complications due to no specific symptoms. Resection is preferred for malignant inorganic retroperitoneal tumors. A feature of these neoplasms is frequent local relapses, which seriously limit the possibility of redo surgery. The authors report successful surgical treatment of recurrent malignant inorganic retroperitoneal myxolipoma with giant baseline dimensions.

Relationship of intracellular proteolysis with CAP1 and cofilin1 in non-small-cell lung cancer.

The main cause of death in non-small-cell lung cancer (NSCLC) is tumor progression, in which metastasis and invasion play an important role. The metastatic cascade is marked by a change in morphological, biological, biochemical and functional characteristics, including the acquisition of cellular mobility. The migration activity of tumor cells determines the work of actin-binding proteins that cause their functional partners CAP1 and cofilin. Of interest is the study of the regulation of working tandem CAP1/cofilin in NSCLC. The mechanism that regulates the level of proteins in cells is proteolysis, carried out by proteasomes and calpains. Therefore, the aim of this study was to estimate the expression of CAP1/CFL1 mRNA and their protein level in NSCLC tissues, and to analyze the possible mechanisms of their regulation by the proteasome and calpain systems. Samples of NSCLC and histological unchanged lung tissue were used (n = 42). The CAP1 and CFL1 mRNA expressions were determined by real-time PCR, the contents of proteins encoded by them were determined by Western blotting, and the activity of proteasomes and calpains by the fluorimetric method. There was an increase in the expression of mRNA and protein levels of CAP1 and cofilin in the tumor tissue compared with the unchanged lung tissue. The expression of mRNA and the level of CAP1 in tumor tissue increased during growth of the primary tumor. The cofilin level in the tumor tissue decreases against the background of increased expression of its mRNA. At the same time, during tumor growth, the activity of proteasomes and calpains increased. A negative regression relationships between the activity of proteasomes and the levels of CAP1 and cofilin, as well as the activity of calpains and the level of cofilin, were found. It can be assumed that proteasomes and calpains are involved in the degradation of CAP1 and cofilin. The data obtained suggest the importance of CAP1, cofilin and proteolytic systems in the tumor transformation and lymphogenous metastasis.

AKT/mTOR Signal Cascade and Expression of PD-1, PD-L1, and PD-L2 in Gastric Cancer.

The peculiarities of gastric cancer development associated with the expression levels of components of the AKT/mTOR signaling cascade and PD, PD-L1, PD-L2 have not yet been identified. We revealed the fundamental changes in the expression AKT/mTOR and PD receptors and their ligands associated with dissemination of gastric cancer. An increase in the mRNA level of all components of this cascade was demonstrated. The expression of mTOR and AKT decreased against the background of enhanced expression of PTEN phosphatase. The increase in the expression of PD-1 receptors and PD-L1 and PD-L2 ligands was most pronounced in patients with distant metastases.

[Increases in mRNA and Protein Levels of the Genes for the Actin-Binding Proteins Profilin, Fascin, and Ezrin Promote Metastasis in Non-Small Cell Lung Cancer].

The actin-binding proteins profilin, fascin, and ezrin were tested for involvement in metastasis of non-small cell lung cancer (NSCLC). The levels of the PFN1, FSCN1, and EZR mRNAs and respective proteins were determined by real-time PCR and Western blotting; tumor and adjacent normal lung tissue samples were obtained from 46 NSCLC patients. Patients with lymphatic metastasis had higher expression levels of the profilin, fascin, and ezrin mRNAs and the profilin and fascin proteins. Both mRNA and protein expression levels increased in patients with distant metastasis. The molecules may serve as predictors to evaluate the prognosis in NSCLC.

Beta-Catenin in Non-Small Cells Lung Cancer and Its Association with Proteasomes.

We analyzed the content of ß-catenin fractions and activity and content of proteasomes in the tissues of patients with non-small cells lung cancer. The content of ß-catenin fractions was elevated and proteasome-dependent proteolysis in the tumor tissue was enhanced in comparison with the corresponding unchanged lung tissue. A negative regression relationship of caspase-like activity of proteasomes and a positive correlation between the content of proteasomes and both fractions of ß-catenin were found. We hypothesize that proteasomes are involved in the degradation of ß-catenin due to caspase-like activity.

Adenylate Cyclase-Associated Protein 1 and Cofilin in Progression of Non-Small Cell Lung Cancer.

We studied the expression of mRNA and the level of CAP1 (adenylate cyclase-associated protein 1) and cofilin proteins in the tissues of patients with non-small cell lung cancer. The expression of mRNA and the level of CAP1 in tumor tissue increased during growth of the primary tumor and its metastasis. It was shown that with the growth of the primary tumor, the content of cofilin in the tumor tissue decreases against the background of increased expression of its mRNA; in regional metastasis, the content of cofilin and expression of the corresponding mRNA increased. It was found that increased content of the studied proteins in the tumor tissue increased the risk of metastasis.

Functioning of Proteasomes in Lymphogenic Metastasizing of Non-Small-Cell Lung Cancer.

Chymotrypsin- and caspase-like activities and expression of the total proteasome pool subunits (α1α2α3α5α6α7) were studied in patients with non-small-cell lung cancer. Proteasome activities were higher in the primary tumors and lymphogenic metastases than in corresponding adjacent lung tissue. The content of α1α2α3α5α6α7 subunits decreased in metastases and remained unchanged in primary tumor tissue. The development of metastatic process in non-small-cell lung cancer was associated with nonlinear changes in proteasome activities and content in primary tumor tissue and lymphogenic metastases.

[Results of surgical and combined treatment of non-small cell lung cancer].

AIM: To study the results of surgical and combined treatment of non-small cell lung cancer stage III using preoperative chemotherapy and intraoperative radiotherapy. MATERIAL AND METHODS: The study included 152 patients with non-small cell lung cancer stage III. Overall and recurrence-free 5-year survival were 20.4% and 14.3% respectively. These values were significantly higher in case of combined treatment consisting of radical surgery and intraoperative radiotherapy (29.2% and 18.7% respectively, p<0.05). RESULTS: The best results were obtained in case of preoperative chemotherapy with paclitaxel/carboplatin, radical surgery and intraoperative radiotherapy on background of radiosensitization with cisplatin. Overall and recurrence-free 5-year survival were 47.9% and 41.7% respectively (p<0.05). Incidence of postoperative complications and mortality rate did not significantly differ between surgical and combined treatment (p>0.05).

[Chemoradiotherapy in combination with local hyperthermia for patients with non-small cell lung cancer].

Short-term treatment outcomes for 15 patients with stage IB-III non-small cell lung cancer (NSCLC) were present- ed. The patients were treated with thermochemoradiothrapy (TCRT). Hyperfractionated radiation therapy at a total dose of 40 Gy (1.3 Gy/fraction, twice daily, 5 days per week) was given concurrently with 2 courses of chemotherapy with pa- clitaxel (175 mg/m², i.v, on day 1) and carboplatin (AUC 6, i.v, on day 1). Ten sessions of local hyperthermia were deliv- ered using the Celsius TCS electro-hyperthermia system. Local hyperthermia was administered twice a week, 2 hours before radiotherapy or immediately after administration of chemotherapeutic agents, for 45-60 min at 41-43 °C. The overall, histologically confirmed, response rate was 93% with 3 (20%) patients achieving a complete response and 11 (73.3%) with a partial response. Stable disease was seen in 1 case (6.7%). No disease progression was found. Chemoradiotherapy and local hyperthermia were well tolerated. Twelve (88%) patients underwent radical surgery (RO): 8 (66.7%) lobectomy and 4 (33.3%) pneumonectomy (TCRT as an option of preoperative treatment). There were no postoperative complications and deaths. Radiation therapy was continued up to the total dose of 60-66 Gy in 3 cases (inoperable patients), and the number of local hyperthermia sessions was increased to 12-14 (TCRT alone). During the follow-up period of 12-14 months, no evidence of disease progression was observed. A prelimi- nary analysis of data obtained indicate that TCRT for patients with NSCLC is well tolerated, results in tumor regression, expand the indications for surgical treatment and demonstrates the encouraging results.

Age-related function of tumor suppressor gene TP53:contribution to cancer risk and progression.

AIM: To examine the influence of combined genotypes of TP53 (exon 4, intron 3, intron 6) and XRCC1 (codon 10) on lung cancer age of onset. METHODS: TP53 polymorphisms in codon 72 of exon 4 (Arg72Pro), in intron 3 (16 bp duplication), in intron 6 (G/A transition) and XRCC1 polymorphism in codon 10 (Arg399Gln) were analyzed in blood cells of 177 lung cancer patients and 196 healthy donors with Restriction Fragment Lenth Polymorphism PCR. RESULTS: We showed that combination of TP53 variant genotypes and XRCC1 variant genotype is associated with the increased lung cancer risk in younger, but not elderly, smokers. In contrast, wild allele combination increases lung cancer risk for individuals over the age of 60. CONCLUSION: Our data confirm antagonistic pleiotropy hypothesis indicating that p53 protects the organism against cancer early in life, but promoting aging phenotype, including late life cancer in older persons.