Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases.

Significant advances in timely diagnosis and modern antitumor therapy have led to a considerable increase in the survival rate of cancer patients. On the other hand, the incidence of cardiovascular (CV) diseases and their complications is increasingly growing, including due to side effects of anticancer drugs. CV complications are the most common cause of non-oncological death of cancer patients. The development of polychemotherapy-induced arterial hypertension (AH) is closely associated with the use of certain groups of drugs, for example, inhibitors of vascular endothelial growth factor (iVEGF). Such AH is generally dose-dependent and reversible after interruption or termination of treatment. However, systemic AH, regardless of its genesis, is one of the key risk factors for many CV events (myocardial infarction, stroke, heart failure, arrhythmias) and kidney disease. Therefore, thorough blood pressure monitoring and its timely and adequate correction if needed are indicated when using certain groups of chemotherapy drugs. This article describes a clinical follow-up of a patient with induced AH associated with the iVEGF antitumor therapy for advanced uterine cancer with a rapid development of left ventricular myocardial dysfunction.

Diabetic macular edema (DME) is a degenerative disease of the macular area in diabetes mellitus and can lead to vision loss, disability, and significantly reduced quality of life. Faricimab is the only bispecific antibody for DME therapy that targets two pathogenic pathways (Ang-2 and VEGF-A).

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice.

Intravitreal injection (IVI) of anti-angiogenic drugs is one of the most common therapeutic procedures in ophthalmology. In recent years, a new non-contact study method has been developed - anterior segment optical coherence tomography (AS-OCT), which allows the formation of three-dimensional images of the lens and provides more detailed information about its structure and morphology.

This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs.

To investigate the antitumor effects of human placenta hydrolysate (HPH) peptides on three hormone-dependent human cell lines: prostate adenocarcinoma, breast carcinoma, and ovarian cancer by metabolic analysis of cell cultures.

Intravitreal injections (IVI) of vascular endothelial growth factor (VEGF) inhibitors are actively used in the treatment of various ophthalmic pathologies. In addition to the pronounced therapeutic effect of anti-VEGF drugs described in the literature, a number of data on adverse effects associated with the use of IVI, including from the lens, have now been accumulated. Prevention of possible side effects of this type of treatment requires further investigation.

Chemoinduced polyneuropathy (CIPNP) is a common side-effect of chemotherapy, significantly impairing quality of life in patients treated for cancer. Platinum preparations are the most commonly used chemotherapeutic agents used in the treatment of ovarian, testicular, breast, lung and colon cancers. Clinical examination reveals restrictions on the motor, sensory and autonomic functions of the upper and lower extremities, which occur at different stages of antitumor treatment, seriously complicating the treatment of the underlying disease. Pain and sensory disturbances may persist for months or even years after chemotherapy is completed. Thus, CIPNP is a major problem because it is impossible to predict which patients will develop neurological symptoms, to estimate their timing of manifestation, which can occur at any time during the course of chemotherapy, there is no early indication to reduce the dose of the cytotoxic drug, and there are no drugs that effectively prevent or alleviate the course of neuropathy. This review focuses on neurotoxicity with the use of platinum drugs, including the frequency of occurrence, risk factors, cumulative doses, various pathogenetic mechanisms for the development of CIPNP, clinical features and variants of the neurophysiological picture.

Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1 EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.

Determining the role of vascular endothelial growth factor (VEGF) in the pathogenesis of intraocular neovascularization prompted the development of anti-VEGF therapy. In general, these intravitreal injections (IVI) are considered relatively safe. One of the side effects that can occur after IVI of anti-VEGF agents is ocular hypertension, it can be acute or persistent. Numerous studies investigating the prevention of ophthalmic hypertension have been carried out in connection with the proven risk of short-term intraocular pressure (IOP) elevation after anti-VEGF injections. Scientific literature describes several methods of preventing intraocular pressure spikes after IVI: prophylactic medications, anterior chamber paracentesis, scleral decompression. Despite the significant number of publications, there is no universal consensus on the necessity of prevention measures for IVI of anti-VEGF drugs since the clinical benefits of slightly reducing the short-term IOP spikes remain unclear. This literature review analyzes the prospects of preventing ocular hypertension after IVI of anti-VEGF agents.

Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) for the treatment of age-related macular degeneration with choroidal neovascularization have become much more popular nowadays. Anti-VEGF therapy is generally well-tolerated; however, one of its possible side effects is ocular hypertension - elevation of intraocular pressure (IOP) above the accepted norm, but without structural and functional changes in the retina and optic nerve common for glaucoma. The average duration of IOP elevation is 30 to 60 minutes, but it can increase when the patient has primary open-angle glaucoma (POAG). There is currently no uniform understanding of the pathogenesis of elevated IOP after IVI, as well as the effect of IOP fluctuations on the functional prognosis and the condition of the ocular tunics. This review considers the main causes and mechanisms of IOP elevation after IVI, analyzes recent publications on the consequences of ocular hypertension for the neurosensory part of the retina and the optic nerve, and examines the conditions for transition of IOP fluctuations into clinically significant ocular hypertension or POAG.

Rehabilitation therapy is considered as an actual and complex system of knowledge, in which the main task is the development and implementation of new methods of rehabilitation. In present time, the most perspective rehabilitation program is utilizing virtual reality. A report was made with the utilization of rehabilitation therapy with virtual reality in a child with chemotherapy-induced neurological disorders in acute lymphoblastic leukemia. The child performed a set of exercises using fully immersive virtual reality. Over the course of rehabilitation positive dynamics was observed, namely increased muscle strength in the injured limb from 3 to 5 scores according to the Medical Research Council Weakness Scale. There was improved balance on the Berg Balance Scale from 35 to 42. In addition, there were increased range of active movements, partly restored biomechanics of gait with increased velocity by 2 times. According to the results of testing the psycho-emotional state using the Luscher color test and the graphic technique «Cactus» by M.A. Panfilova, self-esteem, the desire to succeed and independence were improved, the level of auto-aggression was decreased. The results show that rehabilitation using fully immersive virtual reality is probably a perspective tool in addition to traditional rehabilitation. It improves the neurological and psycho-emotional state, raises motivation of patients, which, in turn, helps to increase the effectiveness of rehabilitation therapy and speeds up the rehabilitation process.

Treatment of malignant neoplasms often requires the use of combinations of chemotherapeutic agents. However, in order to select combinations that are effective against specific tumor cells, it is necessary to understand the mechanisms of action of the drugs that make up the combination. Bacillus pumilus ribonuclease (binase) is considered as an adjuvant antitumor agent, and the sensitivity of malignant cells to the apoptogenic effect of binase depends on the presence of certain oncogenes. In the acute myelogenous leukemia cell line Kasumi-1, binase blocks the proliferation pathway mediated by the mutant tyrosine kinase KIT, which, as shown in our work, activates an alternative proliferation pathway through AKT kinase. In Kasumi-1 cells, binase in combination with an Akt1/2 inhibitor induces apoptosis, and their toxic effects add up: the Akt1/2 inhibitor blocks the binase-induced pathway after suppression of the KIT-dependent pathway. Thus, a combination of binase and AKT kinase inhibitors can effectively block various pathways of tumor cell proliferation and be used for their elimination.

Human cytomegalovirus (HCMV) DNA and proteins are often detected in malignant tumors, warranting studies of the role that HCMV plays in carcinogenesis and tumor progression. HCMV proteins were shown to regulate the key processes involved in tumorigenesis. While HCMV as an oncogenic factor just came into focus, its ability to promote tumor progression is generally recognized. The review discusses the viral factors and cell molecular pathways that affect the resistance of cancer cells to therapy. CMV inhibits apoptosis of tumor cells, that not only promotes tumor progression, but also reduces the sensitivity of cells to antitumor therapy. Autophagy was found to facilitate either cell survival or cell death in different tumor cells. In leukemia cells, HCMV induces a "protective" autophagy that suppresses apoptosis. Viral factors that mediate drug resistance and their interactions with key cell death pathways are necessary to further investigate in order to develop agents that can restore the tumor sensitivity to anticancer drugs.

Increased expression levels of the Oct-1 transcription factor is considered to be one of the key markers of poor cancer prognosis. In addition to the ubiquitous Oct-1A isoform, which is found in all cells, there also exists a tissue-specific Oct-1L isoform, which is expressed in hematopoietic cells. Oct-1L increases cell resistance to different stresses and also regulates the expression of genes controlling differentiation of hematopoietic and immune system cells. The tissue-specific Oct-1L isoform levels are significantly increased in the B-cell lymphoblastoma Namalwa and Raji lines and the T-cell lymphoblastoma Jurkat line compared to normal B and T cells. Apparently, aberrant Oct-1L overexpression not only enhances stress resistance but also leads to the disruption of developmental pathways in the cells promoting their malignant transformation. We report here that targeted suppression of the tissue-specific Oct-1L isoform expression reduces the proliferation rate of Namalwa B-lymphoblastic Burkitt's lymphoma cells, significantly increases cell death rate under hypoxic conditions, and makes cells more sensitive to chemotherapeutic agents such as docetaxel and doxorubicin. These results indicate that targeted therapy aimed at the suppression of the Oct-1 isoforms with increased expression levels in tumor cells rather than the total Oct-1, thus avoiding the traumatic effects of total Oct-1 knockdown, may be promising. Selective suppression of Oct-1 isoforms is a promising strategy in the treatment of lymphoid tumors and may contribute to mitigating the disease course and increasing survival rates in cancer patients.

To analyze the short-term efficacy and safety of Brolucizumab in the treatment of patients with neovascular age-related macular degeneration (nAMD).

When administering anti-VEGF therapy for neovascular age-related macular degeneration (nAMD), it is necessary to take into account the fact that treatment outcomes - in addition to factors associated with the disease itself - may be affected by progressive concomitant conditions (for example, macular atrophy) and possible adverse events (AEs). The latter can be divided into two large groups: non-inflammatory and inflammatory. Intraocular inflammation (IOI) is a rare but potentially dangerous AE of anti-VEGF therapy, which can include endophthalmitis, early sterile inflammation and retinal vasculitis. Raising awareness about inflammatory AEs is becoming even more important due to the sheer number of intravitreal injections performed, as well as the frequency of cases of IOI when using new anti-VEGF drugs. The new anti-VEGF drug Brolucizumab is associated with the development of retinal vasculitis, which is considered a type III and IV hypersensitivity reaction (involving cellular and humoral immune responses, respectively). The article presents an overview of publications on the mechanisms, clinical manifestations, differentiation, and methods of treatment of various types of IOI.

To improve the therapeutic properties of the antitumor agent Sarcolysin, we have previously developed and characterized a dosage form representing its ester conjugate with decanol embedded in ultra-small phospholipid nanoparticles less than 30 nm in size ("Sarcolysin-NP"). The effect of the resulting composition was investigated in vivo in comparison with the free substance of sarcolysin. The composition intravenous administration to mice showed an improvement in the pharmacokinetic parameters of sarcolysin associated with its initial higher (by 22%) level in the blood and prolonged circulation, which was also observed in mice with P388 tumor. In mice with three types of tumors - lymphocytic leukemia P388, lymphocytic leukemia L1210, and adenocarcinoma of the mammary gland Ca755 - administration of two doses of sarcolysin over a period of 7 days showed its predominant antitumor effect. The maximum tumor growth inhibition was noted for lymphocytic leukemia L1210 and adenocarcinoma of the mouse mammary gland Ca755 (at a dose of Sarcolysin-NP - 8,4 mg/kg), which was higher in comparison with free substance by more than 24% and 17%, respectively. Differences in the life span of the treated animals were revealed significantly at a dose of 10 mg/kg and amounted to 25% and 17,4% for lymphocytic leukemia P388 and L1210, respectively, and 11% for adenocarcinoma Ca755. In an experiment on rats, acute toxicity of Sarcolysin-NP administered intravenously showed that an average LD50 value 2-3 times exceeded a similar parameter for commercial preparations of free sarcolysin (Melphalan and Alkeran), which indicates its lower toxicity.

The article presents and analyzes functional results of intravitreal application of two angiogenesis inhibitors of Ranibizumab and Aflibercept in treatment of diabetic macular edema. The positive results were obtained after triple administration of preparation with monthly intervals.