Репозиторий Университета

© 2020 The Authors Background: Haemostatic activation and hypercoagulability are frequently observed in patients with metastatic colorectal cancer (mCRC), increase risk of venous thromboembolism (VTE) and have been implicated in tumour proliferation and progression. To date, the association of haemostatic biomarkers with oncologic outcomes including overall survival (OS), progression free survival (PFS) and disease control rate (DCR) is incompletely understood. Methods: Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, we conducted an exploratory analysis to investigate the association of six known biomarkers of haemostasis with oncologic outcomes in 99 patients with mCRC prior to chemotherapy initiation. Results: Patients with high levels of factor VIII activity (FVIII), D-dimer, prothrombin fragment 1 + 2 (F1 + 2) and fibrinogen (defined as levels >75th percentile) had significantly shorter median OS than patients with lower levels. Elevation of four biomarkers was associated with mortality in multivariable analysis, adjusting for age, sex, number of metastatic sites and VTE (hazard ratio [95% CI] for death per doubling of levels: FVIII: 2.06 [1.28–3.30]; sP-selectin: 1.55 [1.07–2.24]; D-dimer: 1.40 [1.18–1.65]; F1 + 2: 1.64 [1.10–2.46]). Patients with elevated levels had numerically shorter median PFS across all markers and disease control rate (DCR) was significantly smaller in those with high levels of FVIII and F1 + 2 (adjusted odds ratio [95% CI] for DCR per doubling of levels: 0.23 [0.09–0.62] and 0.36 [0.16–0.82]) compared to patients with lower levels. Conclusion: Specific elevated haemostatic biomarkers are associated with higher mortality and partially with worse response to chemotherapy in patients with mCRC.

© 2018 Vitebsk State Medical University. All rights reserved. Primary-multifocal malignant tumors hold a specific place in oncology. Present case report describes the combination of two neoplastic processes with different anatomic localization, the analogues to which have not been found either in the domestic literature or foreign sources. The article presents the case of a synchronous primary-multiple malignant neoplasm - malignant tumor from the membranes of the peripheral nerves of the nasal cavity with expansion into the right maxillary sinus, the cells of the ethmoidal sinus т2bN0M0 and moderately differentiated adenocarcinoma of the sigmoid colon т4аN0M0. Physical examination and positron emission tomography combined with the computed tomography confirmed a hypervascular tumor of the posterior cells of the ethmoidal sinus and a nasal cavity without hypermetabolism and the circular tumor of the sigmoid colon with hypermetabolism. Taking into account the primary-multiple character of the lesion and the clinic of intestinal obstruction, a tactic of the treatment was a combined surgery - the removal of the neoplasm of the nasal cavity with resection of the right maxillary sinus with microsurgical technique and a reconstructive-plastic component using a coronary access, laparotomy, resection of the sigmoid colon, lymphadenectomy. The chosen treatment allowed eliminating both of the tumors in a short time and moving on to a further stage of treatment. The patient is under the supervision, there is no recurrence of the disease at the moment.

© 2017 Wiley Periodicals, Inc. Colorectal cancer (CRC) has become the fourth leading cause of cancer-related death in the worldwide. It is urgent to find more effective therapeutic strategies for it. Reactive oxygen species (ROS) play multiple roles in normal cellular physiology processes. Thus, a certain level of ROS is essential to keep normal cellular function. However, the accumulation of ROS shows dual roles for cells, which is mainly dependent on the concentration of ROS, the origin of the cancer cell and the activated signaling pathways during tumor progression. In general, moderate level of ROS leads to cell damage, DNA mutation and inflammation, which promotes the initiation and development of cancer. Excessive high level of ROS induces cancer cell death, showing an anti-cancer role. ROS are commonly higher in CRC cells than their normal counterpart cells. Therefore, it is possible that ROS induce cell death in cancer cells while not affecting the normal cells, demonstrating lower side effects. Besides, ROS also play a role in tumor microenvironment and drug resistance. These multiple roles of ROS make them a promising therapeutic target for cancer. To explore potential ROS-target therapies against CRC, it is worth to comprehensively understanding the role of ROS in CRC and therapy. In this review, we mainly discuss the strategies of ROS in CRC therapy, including direct CRC cell target and indirect tumor environment target. In addition, the influences of ROS in drug resistance will also been discussed.

© 2018 Russian Academy of Medical Sciences. All Rights Reserved. Cancer immunotherapy represents a promising and rapidly developing approach for the treatment of oncological diseases. Among the methods of personalized adjuvant immunotherapy, neoantigenic peptide-based drugs have demonstrated substantial efficiency. These drugs are designed to target mutant proteins arising from somatic alterations in the genome of tumor cells and thus stimulate immune response against tumor tissues. The methods of individual screening for potentially immunogenic mutations are mostly based on next-generation exome sequencing of tumor samples, which is a complex and costly procedure for clinical application. Targeted gene sequencing panels limited to a certain set of genes represent a reasonable alternative to WES. Targeted sequencing is also more efficient when there is a low amount of the sample DNA available. We have estimated the potential efficiency of targeted oncological panels in terms of somatic neoantigen profiling in colorectal cancer (colon and rectal adenocarcinoma). The clinical practice of identification of frequent somatic variants does not provide enough data for designing an efficient personalized drug when applied to low and medium mutated cancers such as colorectal cancer. Our analysis of 11 commercially available panels containing different number of genes has shown that neither the larger size of a panel nor its initial customization for colorectal cancer provides a significantly better estimation of an individual somatic mutation profile. The optimal approach is to use the general-purpose medium-sized cancer panels (2300-11200 amplicons and/or 150-600 genes). These panels allow to detect a sufficient number of immunogenic epitopes (>3) per patient for over 30-50% of patients.

AIM: To determine optimal treatment strategy for acute malignant colonic obstruction. MATERIAL AND METHODS: 349 patients with acute malignant colonic obstruction were retrospectively analyzed for the period 2005-2017. All patients were divided into two groups depending on surgical approach. Surgical group comprised 259 patients, endoscopic group - 90 patients. Both groups were comparable by gender, age, level of intestinal obstruction and duration of the disease. However, morbidity and mortality rate were significantly different. RESULTS: In surgical group incidence of complications was 63.3%, mortality - 19.7%. In group of endoscopic stenting the same values were 8.9% and 6.7%, respectively. Significant differences of morbidity and mortality were observed between groups (p<0.05). CONCLUSION: Endoscopic stenting should be preferred over surgery to eliminate colonic obstruction in patients with acute malignant ileus.