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The review presents the data on the specifics of mechanism of action, classification, and clinical manifestations of neurotoxicity effect. The most significant features of specific side effects when using taxanes in different treatment regimens, including cumulative doses, are considered. The proven methods of treatment and prevention of neuropathy caused by anticancer drugs are discussed.

Methionine dependence of malignant cells is one of the cancer hallmarks. It is well described that methionine deprivation drives cancer cells death, both in vitro and in vivo. Methionine gamma-lyase (MGL) isolated from different species or obtained by genetic engineering can be used for effective methionine depletion. In this work, we show that MGL S3, a genetically engineered protein comprised of MGL from Clostridium sporogenesis fused to epidermal growth factor (EGF)-like peptide, reduces, in vitro, the number of cancer cells of four different origins—neuroblastoma, lung, breast, and colon cancer. We reveal that MGL S3 is more toxic for neuroblastoma SH-SY5Y and lung cancer H1299 cells compared to MGL tetani, and causes cell death by the induction of apoptosis. In addition, the observed death of cells treated with MGL S3 is accompanied by the prominent downregulation of ERK activity. By the analysis of transcriptomic data of more than 1500 cancer cell lines and patient samples, we show that the high expression of four genes from the methionine metabolism pathway (AHCY, CBS, DNMT3A, and MTAP) is associated with poor prognosis for breast cancer and neuroblastoma patients. Additionally, cells of these origins are characterized by a high correlation between EGFR dependency and DNMT3A/CBS expression. Finally, we demonstrate the ability of MGL S3 to enhance the sensitivity of H1299 cells to EGFR inhibition with gefitinib.

Introduction/Background In our study, we evaluated the long-term results of neoadjuvant dose-dense platinum-based chemotherapy in patients with locally advanced cervical cancer FIGO IB2, IIB stage. Methodology A cohort of 119 consecutive patients with median age of 43 (range 27–68) years was studied. All patients had verified locally-advanced (cT1B2Nx,0M0; cT2BNx,0M0) cervical cancer and received 3 dose-dense intravenous neoadjuvant AP (cisplatin 75 mg/m2, doxorubicin 35 mg/m2; n=75) or TP (cisplatin 60 mg/m2 and paclitaxel 60 mg/m2; n=30) chemotherapy cycles. Results The median follow-up was 28 (4 - 48) months for AP and 17 (3 - 30) months for TP group, accordingly. The overall survival rates in FIGO IB2 stage for AP and TP groups were 100%. For FIGO IIB stage the overall survival rate in AP group was 94%, in TP group - 97%. The disease-free survival rate in FIGO IB2 stage for AP group was 78%, for TP group - 100%. For FIGO IIB stage the disease-free survival rate in the AP group was 87%, in TP group - 100%. Conclusion The dose-intensive chemotherapy is an effective treatment modality for locally-advanced cervical cancer and may be a feasible alternative for standard treatment approach. It deserves further study in larger patient cohort with evaluation of the long-term results.

The retrospective dynamics of land use in the Kemerovo region since the Soviet period is presented in the study. The survey of views of the scientific community regarding the development of reclamation of lands allocated to industry was conducted. The statistics are reflected: areas of lands disturbed by the activities of open pits and mines in the mining region; the number of land law violations; land retirement. A technique is presented for determining the potential use of disturbed lands for agriculture in order to identify their suitability or unsuitability for reclamation; its algorithm including seven consecutive stages is presented. Indicators that contribute to maximizing income from each plot suitable for long-term agricultural reclamation were selected.

ObjectivesCisplatin and mitomycin C exert high activity towards BRCA1-deficient cells. This study aimed to evaluate the efficacy of a combination of these drugs in hereditary BRCA1-associated ovarian cancer (OC).MethodsTwelve OC patients, who could not be treated by primary debulking surgery owing to extensive tumor spread, were given neoadjuvant cisplatin (100 mg/m2) and mitomycin C (10 mg/m2) every 4 weeks for 3 (n = 9), 2 (n = 2), or 4 (n = 1) cycles.ResultsThe decrease of tumor burden and complete surgical cytoreduction were achieved in all patients. Pathologic complete response, defined as the absence of tumor cells in surgically removed tissues, was observed in 2 (17%) of 12 cases. Retrospective analysis of 62 OC in BRCA1 mutation carriers subjected to conventional neoadjuvant chemotherapy schemes revealed 36 objective tumor responses (58%) and 37 instances (60%) of complete cytoreductive surgery; however, none of these patients demonstrated pathologic complete response.ConclusionsThe combination of cisplatin plus mitomycin C showed promising results in BRCA1-driven OC and therefore deserves further clinical evaluation.

The article presents the world experience of cytoreductive surgery for ovarian cancer (OC) according to literature data and also estimates the thirteen-year experience of the Oncogynecology Department of the N.N. Petrov National Medical Research Center of Oncology in the treatment of OC patients. Materials and methods: In order to analyze the results of treatment for thirteen years it is proposed a comparative evaluation of results of primary and interval cytoreductive operations in 213 patients with OC. For this purpose all patients depending on the start of treatment were divided into two groups: a group of patients with an advanced OC where treatment started with neoadjuvant chemotherapy and a group of patients with an advanced OC where primary cytoreductive surgery was performed at the start of treatment. In these groups the long-term results of treatment were studied: platinum-free interval and life expectancy. Results: When studying the effect of a number of neoadjuvant chemotherapy courses on long-term results of treatment it was established that the best results for platinum-free interval were obtained in a 3-course group of neoadjuvant chemotherapy - platinum-free interval was 9.6 months compared to 6.9 and 4.7 months in groups of 4 and> 5 courses although the differences in the groups did not reach statistically significant rates (p = 0.337). The increase in a number of postoperative chemotherapy courses in our study also statistically was unreliable and had a negative effect on survival: patients from the neoadjuvant chemotherapy group with> 3 courses of postoperative chemotherapy had 9.6 months versus 11.7 months in patients with 3 courses p = 0.787); life expectancy was 35.6 months compared to 30.9 months respectively (p = 0.968). The same tendency was also observed in patients from the primary cytoreduction group: in the group of patients with> 3 courses of postoperative chemotherapy platinum-free interval was 10.2 months compared to 16.3 months in patients with 3 courses (p = 0.312); life expectancy was 54.4 months compared with 48.7 months respectively (p = 0.435). The Kaplan-Meier survival estimation revealed a statistically significant improvement in life expectancy index for patients from the primary cytore-duction group (median survival time 53.7 months, 95 % CI 41.9-73.6 months) compared to patients in the neoadjuvant chemotherapy group (median life expectancy 33.0 months, 95 % CI 20.6-42.0 months, p

To study the role of retroperitoneal lymphadenectomy in epithelial ovarian cancer (OC) the work was divided into two parts. In the first part for a retrospective analysis 852 patients with stage I-IV OC, who were treated from January 2000 to January 2014, were selected to investigate the localization of the first relapse of the disease. In the second part, prospective from August 2016 to April 2017, in 28 patients with stage I-IV OC the surgical stage of the combined treatment was supplemented by iliac-pelvic and para-aortic lymphadenectomy; in this group the results of surgical staging were studied. The incidence of isolated recurrence in para-aortic lymph nodes in the group of early OC was 3/28 (11%), in pelvic 2/28 (7%), whereas in the group of advanced OC - in para-aortic lymph nodes 9/24 (37%), in iliac-pelvic 10/24 (42%), combined in pelvic and para-aortic lymph nodes 5/24 (21%). In the prospective group the lesion of pelvic and para-aortic lymph nodes was observed in 2/28 (7%) of patients with the presumed I stage of the disease and in 2/28 (7%) with the presumed stage II, which resulted in re-staging of the disease. In 2 cases the clinical IA and IB stages were re-staged to IIIA and this required 6 courses of chemotherapy. In 2/28 (7%) patients metastases to para-aortic lymph nodes were detected in the absence of pelvic lesions.

In 24 patients (mean age 48 years) with locally advanced cervical cancer there were studied the efficacy and toxicity of 3 cycles of neoadjuvant dose-intensive chemotherapy with cisplatin (75 mg/m2) and doxorubicin (35 mg/m2) administered intravenously on the first day of a two- week cycle with the support of colony-stimulating factors. An important criterion for the inclusion in this study of patients with locally advanced cervical cancer (T1b2-2bN0-1M0) was the absence of infiltration of the anterior parameters according to the gynecological examination and MRI studies. An objective response to treatment was registered in 72.7 % of cases. Progression of the disease was not detected in any case. Conducting neoadjuvant drug therapy allowed performing radical surgical intervention in 95.4 % of patients. The pathomorphlogical response of tumor of varying severity was 40.9 %. In 9.1 % complete clinical regression of tumor was confirmed by a complete pathomor-phological response (CR). The dose-intensive regimen of chemotherapy did not lead to a significant increase of complications on the drug and surgical stages. An analysis showed that dose-intensive neoadjuvant chemotherapy is a highly effective method in treatment for locally advanced cervical cancer.

Results of numerous retrospective studies have confirmed that the degree of cytoreduction and the size of the residual tumor after the primary surgery are the most important factors affecting overall life expectancy as well as the time to progression in patients with ovarian cancer (OC). The article presents the immediate results of the first 16 extensive cytoreductive surgeries in advanced OC performed at the Oncogynecology Department of the N.N. Petrov National Medical Research Center of Oncology.