Based on the prediction of biological activity spectra for several secondary metabolites of medicinal plants using the PASS computer program and validation in vitro of the predictions results the priority direction of the pharmaceutical composition Phytoladaptogene (PLA) development was determined. PLA is a complex of structurally diverse small organic compounds including biologically active substances of phytoadaptogenes (ginsenosides from Panax ginseng, rhodionin from Rhodiola rosea and others) compiled considering previously developed pharmaceutical compositions. Two variants of the pharmaceutical composition were studied: - the major and minor variants included 22 and 13 compounds, respectively. The probability of activity exceeds the probability of inactivity for 1400 out of 1945 pharmacological effects and mechanisms predicted by PASS for the major variant of PLA. The wide range of predicted activities is mainly due to the low structural similarity of constituent compounds. An in silico prediction indicates the possibilities of antitumor properties against bladder, stomach, colon, ovarian and cervical cancers both for minor and major PLA compositions. It was found that the highest probability values of activity were predicted for three mechanisms: apoptosis agonist, caspase-3 stimulant, and transcription factor NF-κB inhibitor. According to the PharmaExpert program they are associated with the antitumor effect against bladder cancer. Experimental validation was using the human bladder cancer cell line RT-112. The results of the MTT test have shown that the cytotoxicity of the major PLA variant is higher than that of the minor PLA variant. In vitro experiments performed using two methods (double staining with annexin V and propidium iodide and detection of active caspase-3 in cells) confirmed that the death of bladder cancer cells occurred via the apoptotic mechanism. The data obtained correspond to the results of the prediction and indicate advantages of the major PLA composition. Thus, PLA can become the basis for the development of a drug with the antitumor activity against bladder cancer. The antitumor activity predicted by PASS for other cancers may be the subject of further studies.

Anti-angiogenic anticancer drugs that block the vascular endothelial growth factor signaling pathway can cause renal damage. Assessment of the risk of nephrotoxicity allows developing optimal treatment approaches and ensuring the relative safety of therapy.

Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death protein 1 (PD-1) or its ligand (PD-L1), are a new generation of immuno-oncological drugs that to date have demonstrated efficacy in a number of malignancies. The mechanism of ICT inhibitors action consist in the potentiation of the immune response by eliminating the tumor cells inhibitory effect on the T-lymphocytes activation. However, excessive immune system activation can cause the development of a special class of immune-related adverse events (irAEs) involved a wide variety of organs and systems, including the kidneys. Despite the fact that immuno-mediated kidney injury caused by ICI therapy develops quite rarely, it can be serious and determine the patient's prognosis, which necessitates early diagnosis and timely start of treatment. In this regard, awareness of the manifestations of ICI-associated renal irAEs is particularly relevant not only for oncologists and for nephrologists, but for doctors of other specialties. In this review, we elucidated the main variants of immuno-mediated kidney injury caused by ICI therapy, discussed possible predictors and mechanisms of their development, and considers the general principles of diagnosis and management of patients according to the severity of irAEs.

Antiangiogenic therapy with inhibitors of vascular endothelial growth factor (anti-VEGF) has not only fundamentally changed the treatment outcomes of vasoproliferative eye diseases, but also became the most common ophthalmic surgical manipulation. At the same time, in 36-48% of bilateral lesions there is a need to perform injections in both eyes, making relevant the issues of safety and prevention of severe complications that threaten irreversible loss of visual function. The article reviews the results of randomized clinical trials and real clinical practice, analyzes the incidence and causes of its most dangerous complication - endophthalmitis, characterizes the clinical course depending on the type of drug used, and considers the possibility of reducing the risk of this complication occurring. Special attention is paid to the safety profile of a new VEGF inhibitor - brolucizumab - which has received registration for the treatment of neovascular age-related macular degeneration (nAMD). Specialists dealing with retinal pathologies acknowledge the need to monitor the state of the anterior and posterior parts of the eye in order to detect the signs of intraocular inflammation as quickly and early as possible. Drug efficacy, treatment regimen, duration of action and safety are the main characteristics that should determine the personalized approach in each clinical case.

Neoangiogenesis is a basic factor for most physiological as well as pathological processes i.e. tumor metastases. The most important is vascular endothelium growth factor (VEGF) and its receptors (VEGFR1/2) in angiogenesis processes. Nowadays antiangiogenic agents (which inhibit VEGF like bevacizumab neither VEGFR2 like ramucirumab) are widely used in very different chemotherapeutic regimens in clinical oncology. The signalling pathway VEGF-VEGFR plays a crucial role in supporting of adequate kidney function. Appearance of antiangiogenic drugs led to adverse nephrotoxic effects: arterial hypertension, proteinuria, rarely nephrotic syndrome, and kidney dysfunction. Various hystological variants of nephropathy are described, however, in most cases, signs of thrombotic microangiopathy of the renal vessels are noted. This literature review discusses mechanisms, clinical and morphological aspects of nephropathy associated with antiangiogenic drugs.

To determine the effect of intraperitoneal chemotherapy (IPC) with mitomycin C on expression of intraperitoneal cancer cells markers in patients with T4 colon cancer.

Cyclic hydroxamic acids based on quinazoline-4(3H)-one and dihydroquinazoline-4(1H)-one have been synthesized. The antioxidant and iron-chelating properties of these compounds, their effect on the activity of the histone deacetylase enzyme, and their cytotoxic effect on cells of various tumor lines have been investigated. We have identified two compounds-hits, which exhibit the multipharmacological type of the antineoplastic activity. Their cytotoxic effect on cells of human lung carcinoma A549 and breast adenocarcinoma MCF-7 is obviously associated with their ability to modulate the level of reactive oxygen species and to chelate Fe(II) ions, as well as to inhibit the metalloenzymes, histone deacetylases, involved in the epigenetic regulation of tumor genesis. Thus, the synthesized hydroxamic acids may be considered as a promising basis for creating potential oncolytics.

Sorafenib has been used in acute myeloid leukemias with FLT3-ITD mutation improving the outcomes. However the high incidence of treatment - emergent adverse event may be associated with treatment using sorafenib with cytotoxic chemotherapy. We have reported a case of severe thyroiditis in patient with a relapse of acute myelomonocytic leukemia.

Melanoma is one of the most aggressive tumors and is accompanied by the induction of local and systemic inflammatory responses. Combinations of chemotherapeutic agents with immunotherapy are therefore commonly used for melanoma treatment. A B16 melanoma model was used to study the tumor suppressive, immunostimulating, and hepatotoxic effects of a combination of a small double-stranded immunostimulatory RNA (isRNA) with 3'-trinucleotide overhangs and the cytotoxic drug dacarbazine compared with respective monotherapies. The drugs efficiently suppressed the tumor growth and acted synergistically. Histological and immunohistochemical examinations of tumor nodes showed that the combination of isRNA and dacarbazine significantly decreased mitotic activity and more efficiently increased apoptosis in tumor tissue as compared with either monotherapy. Regardless of the treatment regimen, signs of immune activation were observed in the spleen, including an increase in the number and diameter of lymphoid follicles and the volume density of the white pulp. Destructive changes were detected in the livers of nontreated animals with B16 melanoma. Administration of isRNA in combination with dacarbazine did not cause any additional damage to liver parenchyma, while stimulating regenerative processes in hepatic tissue of tumor-bearing animals.

Retrospective analysis of patients with periampullary tumors undergoing pancreatoduodenectomy.

Migration of cancer cells from the primary tumor site to nearby tissues is the starting point of the metastatic process. The invasive properties of cells are especially important for carcinomas, since tumor cells need to overcome the basement membrane and go beyond its boundaries to the underlying tissues. Substances that reduce the invasive ability of malignant cells are promising as antimetastatic agents. In the present work, the possibility of inhibiting the ability of different cancer cell lines to migrate under the influence of the Bacillus pumilus ribonuclease (binase) was analyzed using the scratch-wound assay. It was established that binase at non-toxic concentrations (10 μg/mL) reliably suppressed the migratory ability of HuTu 80 human duodenum adenocarcinoma cells incubated with RNase for 48-72 h. The antimetastatic potential of binase is confirmed by molecular modeling data demonstrating the ability of binase to inhibit cellular metalloproteinases that determine the migration of tumor cells.

The article compares the course of age-related macular degeneration in elderly patients in three groups after complex therapy (intravitreal administration of angiogenesis blockers and photodynamic therapy). 339 case histories of persons with an average age of 75,6±9,7 years were analyzed (p<0,05). A slight decrease in the area of pathological autofluorescence and retinal thickness according to optical coherence tomography was revealed in all three groups of increased visual acuity. The best effect of combination therapy was observed in the first six months, no further positive dynamics was observed. Thus, timely diagnosis and complex therapy slows down and sometimes stops the progression of age-related macular degeneration and vision loss.

Cardiovascular diseases and malignancies are leading causes of mortality in the world. Two categories of advanced age patients with cancer are observed in clinical practice. These are patients with cardiovascular diseases as comorbidities and patients with cardiovascular diseases as a complications of targeted therapy for cancer. Cardiac toxicity of chemotherapeutic drugs results myocardial dysfunction, occurrence or progression of heart valve disease, coronary artery disease, arterial hypertension and thromboembolism. A patient who underwent aortic valve replacement and coronary artery bypass surgery is discussed in the article. Aortic valve disease and coronary artery disease were complications of targeted radio- and chemotherapy for sigmoid colon cancer followed by lung and liver metastases. Questions of timely diagnosis and treatment of advanced age patients in multi-field surgical clinic are also analyzed.

To improve short- and long-term outcomes of locally advanced pancreatic body-tail cancer followed by major vessels invasion.

The review considers properties of the type II anti-Mullerian hormone receptor (mullerian inhibiting substance receptor type II, MISRII), a transmembrane sensor with its own serine/threonine protein kinase activity, triggering apoptosis of the Mullerian ducts in mammalian embryogenesis and providing formation of the male type reproductive system. According to recent data, MISRII overexpression in the postnatal period is found in cells of a number of ovarian, mammary gland, and prostate tumors, and anti-Mullerian hormone (AMH) has a pro-apoptotic effect on MISRII-positive tumor cells. This fact makes MISRII a potential target for targeted anti-cancer therapy. Treatment based on targeting MISRII seems to be a much more effective alternative to the traditional one and will significantly reduce the drug dose. However, the mechanism of MISRII-AMH interaction is still poorly understood, so the development of new anticancer drugs is complicated. The review analyzes MISRII molecular structure and expression levels in various tissues and cell lines, as well as current understanding of the AMH binding mechanisms and data on the possibility of using MISRII as a target for the action of AMH-based antineoplastic drugs.

To estimate cardiotoxicity of targeted therapy of breast cancer by the results of methods of investigation, which are used in routine clinical practice.

To standardize surgical care for malignant colonic obstruction.

Oncological diseases are the main causes of death in the world. Modern treatment of cancer patients contributes to an increase in survival rate due to strong chemotherapeutic drugs, the use of which is accompanied by toxic effects on cardiomyocytes. The main manifestations of cardiotoxicity are left ventricular dysfunction, myocardial ischemia, thromboembolic complications, chronic heart failure. As a result, the risk of cardiovascular mortality may be higher than the risk of death from the tumor process. An important task of oncologists and cardiologists is the early diagnosis of cardiotoxic complications in order to start treatment in time and reduce mortality from cardiovascular pathology in cancer patients.

Patients with cancer have high risk of cardiovascular complications. They may be caused by tumor and cancer therapy. The possible approaches to the prevention of cardiotoxicity are discussed in this article: risk factors assessment, laboratory and instrumental diagnostics, non-pharmacological and pharmacological interventions.

Development and use of new anticancer drugs has resulted in the improving of 5‑year survival rates in patients with cancer. However, many of the modern chemotherapies are associated with cardiovascular toxicities that increases cardiovascular risk in cancer patients, including hypertension, heart failure, thrombosis and thromboembolism, cardiomyopathy, and arrhythmias. These side effects limitation restrict treatment options and farther perspectives. With increasing use of modern chemotherapies and prolongation of the cancer patients survival, the incidence of cardiovascular disease in this patient population will continue to increase. Accordingly, careful assessment and management of cardiovascular risk factors in cancer patients by oncologists and cardiologists working together is essential for optimal care.