PVRIG is Expressed on Stem-Like T Cells in Dendritic Cell-Rich Niches in Tumors and Its Blockade May Induce Immune Infiltration in Non-Inflamed Tumors.

Cancers that are poorly immune infiltrated pose a substantial challenge, with current immunotherapies yielding limited clinical success. Stem-like memory T cells (TSCM) have been identified as a subgroup of T cells that possess strong proliferative capacity and that can expand and differentiate following interactions with dendritic cells (DCs). In this study, we explored the pattern of expression of a recently discovered inhibitory receptor poliovirus receptor-related immunoglobulin domain protein (PVRIG) and its ligand, poliovirus receptor-related ligand 2 (PVRL2), in the human tumor microenvironment.

Real-World Experience with Targeted Therapy in BRAF Mutant Advanced Melanoma Patients: Results from a Multicenter Retrospective Observational Study Advanced Melanoma in Russia (Experience) (ADMIRE).

Clinical trials of targeted therapy (TT) and immunotherapy (IT) for highly aggressive advanced melanoma have shown marked improvements in response and survival rates. However, real-world data on treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma are ultimately scarce. The study was designed as an observational retrospective chart review study, which included 382 patients with advanced BRAF V600 mutant melanoma, who received TT in a real-world setting and were not involved in clinical trials.

Clinical and immunological characteristics of sarcomas patients with clonogenic tumors.

Tumorigenesis is related to the generation of heterogeneous tumor cell population, which is the result of genetic and epigenetic alterations followed by clonal selections and subsequent expansion. In basic studies genetic, histological and morphological diversity of different clones within a patient's neoplasm and specifics of their interrelation with patient's immune system are investigated mostly on the models of tumors of epithelial origin. Mesenchymal tumors such as soft tissue and bone-derived sarcomas (STBS) have been poorly studied in this regard.

Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma.

Lessons Learned: Melatonin did not increase the efficacy of systemic chemotherapy in melanoma. Metformin did not increase the efficacy of systemic chemotherapy in melanoma.

Background: Current data support the possibility of antitumor activity of melatonin and metformin.

An Open-Label Study of the Safety and Efficacy of Tag-7 Gene-Modified Tumor Cells-Based Vaccine in Patients with Locally Advanced or Metastatic Malignant Melanoma or Renal Cell Cancer.

Lessons Learned: This study showed that carefully selected patients with locally advanced and metastatic forms of malignant melanoma and renal cell carcinoma could potentially have long-term disease control with a tag-7 gene-modified tumor cells-based vaccine. Randomized clinical trials in patients whose tumors produce low amounts of immunosuppressive factors are needed to confirm this hypothesis in both the adjuvant and metastatic settings.

Background: Immunotherapy may produce long-lasting effects on survival and toxicity.

Cancer/testis antigens expression during cultivation of melanoma and soft tissue sarcoma cells.

Background: Autologous dendritic cells (DC) loaded with tumor-associated antigens (TAAs) are a promising approach for anticancer immunotherapy. Polyantigen lysates appear to be an excellent source of TAAs for loading onto the patient's dendritic cells. Cancer/testis antigens (CTA) are expressed by a wide range of tumors, but are minimally expressed on normal tissues, and could serve as a universal target for immunotherapy.

ILDR2 Is a Novel B7-like Protein That Negatively Regulates T Cell Responses.

The B7-like protein family members play critical immunomodulatory roles and constitute attractive targets for the development of novel therapies for human diseases. We identified Ig-like domain-containing receptor (ILDR)2 as a novel B7-like protein with robust T cell inhibitory activity, expressed in immune cells and in immune-privileged and inflamed tissues. A fusion protein, consisting of ILDR2 extracellular domain with an Fc fragment, that binds to a putative counterpart on activated T cells showed a beneficial effect in the collagen-induced arthritis model and abrogated the production of proinflammatory cytokines and chemokines in autologous synovial-like cocultures of macrophages and cytokine-stimulated T cells.

ILDR2-Fc Is a Novel Regulator of Immune Homeostasis and Inducer of Antigen-Specific Immune Tolerance.

ILDR2 is a member of the Ig superfamily, which is implicated in tricellular tight junctions, and has a putative role in pancreatic islet health and survival. We recently found a novel role for ILDR2 in delivering inhibitory signals to T cells. In this article, we show that short-term treatment with ILDR2-Fc results in long-term durable beneficial effects in the relapsing-remitting experimental autoimmune encephalomyelitis and NOD type 1 diabetes models.

[Diabetic ketoacidosis with mild hyperglycemia associated with the use of canagliflozin. Report of one case with type 1 diabetes].

Diabetic ketoacidosis with mild hyperglycemia is a major complication of sodium-glucose cotransporter 2 inhibitors. Although its use is not approved for patients with type 1 diabetes mellitus, the drug is often prescribed with the hope of optimizing metabolic control. We report a 20 years old female with hypothyroidism and type 1 diabetes consulting for vomiting and abdominal pain.

[Modern methods of immunotherapy for metastatic melanoma].

Over the past five years drug therapy of disseminated melanoma took a giant step forward. In clinical practice there are several fundamentally new classes of drugs: inhibitors of the individual components of MAPK-signaling pathway and modulators of a work of immunological synapse (inhibitor of CTLA4 ipilimumab, inhibitors of PD1 nivolyumab and pem- brolizumab).Here are presented features of the mechanism of action of new immunotherapeutic agents, the review of results of their clinical use, the description of the main treatment- related adverse events.

[Modeling of the impact of chemotherapeutic agents on primary cultures of metastatic soft tissue sarcomas in the automated analytical system CELL-IQ].

This work presents results of long-term phase-contrast microscopy research of proliferative potential of soft tissue sarcomas utilizing live-cell imaging technology Cell-IQ (Chip-Man Technologies Ltd, Finland). It was found that the machine vision technology allowed to obtained sufficient body of evidence about high-quality and quantitative changes of proliferative activity of the cells soft tissue sarcoma cultivated in static conditions. The present study demonstrates that modeling in time interval of maximum proliferative activity of soft tissue sarcoma cells increases information efficacy and reliability of the analysis of dividing cells patterns using Cell-IQ technology.

[The first results of assessment of clinical efficacy of melatonin and metformin in patients with disseminated skin melanoma receiving dacarbazine as first-line systemic therapy].

The aim of the study was to assess efficacy and safety of combined therapy with dacarbazine and melatonin or metformin in comparison with dacarbazine alone in the 1st line of therapy of cutaneous melanoma. Thirty-six patients with disseminated melanoma, therapy naïve, were included between March 2014 and December 2015. Patients received DTIC 1000 mg/m2 in day 1 of 28-day cycle either as monotherapy (group 1) or in combination with melatonin 3 mg PO daily (group 2) or metformin 850 mg 2 times a day PO daily (group 3).

Vemurafenib-induced progression of breast cancer: a case report and review of the literature.

Vemurafenib, a specific inhibitor of mutated BRAF kinase, may activate wild-type BRAF and therefore induce squamous cell skin carcinomas in patients treated for melanoma. All vemurafenib clinical trials excluded patients with multiple primary malignant tumors; therefore, the action of this drug on concurrent BRAF wild-type malignancies remains insufficiently studied. We observed a patient, who was administered vemurafenib for BRAF mutation-containing melanoma, but experienced immediate relapse of previously controlled breast cancer disease.

[CYTOREDUCTIVE NEPHRECTOMY IN METASTATIC RENAL CELL CANCER].

The role of cytoreductive nephrectomy in the current era of targeted therapy remains unknown. Two prospective randomized phase III trials (CARMENA and SURTIME) are now opened to evaluate the efficacy of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma. So far it is not well known who will and who will not benefit from such surgery.

[Modern methods of molecular targeted therapy for disseminated melanoma].

Significant changes occurred in drug therapy for disseminated melanoma during the last 5 years. New classes of pharmaceuticals appeared in daily clinical practice: inhibitors of MAPK pathway components (BRAF inhibitors vemurafenib and dabrafenib, MEK--inhibitors trametinib and cobimetinib) and immune checkpoint inhibitors that modulate immunologic synapse activity. This article presents information about MAPK pathway inhibitors, their mechanism of action and clinical trials experience including specific related adverse events.

[Treatment of patients with disseminated testicular germ cell tumors].

Testicular germ cell tumors are rare diseases of young age with high sensitive to cytostatic therapy. Their complex treatment should be based on prognostic factors and individual properties of disease. It includes chemotherapy followed by cytoreductive surgery of residual lesions according to international standards and guidelines.

[Systemic therapy of soft tissue sarcomas].

Soft tissue sarcomas (STS) comprise a heterogeneous group of rare malignancies from mesenchymal tissues. The biology of STS causes high aggressiveness, poor prognosis due to early development of distant metastases and limited chemotherapeutic options due to tumor resistance. The paper considers the current principles of chemotherapy for early and metastatic disease.

[Efferent therapy in the treatment of solid tumors].

Endogenous intoxication and immune insufficiency accompany neoplastic process. Complex therapy for cancer worsens these pathologic conditions by its adverse effects (AE) and thus complicates treatment. Efferent therapy can provide continuity of antineoplastic therapy with normalization of hemostasis and decreasing the rate of AE and their intensity.

Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician's and patient's perspectives.

High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (AHSCT) is a promising approach to treatment of multiple sclerosis (MS) patients. In this paper, we present the long-term outcomes of a prospective single-center study with the analysis of the safety and efficacy of HDIT + AHSCT with reduced-intensity BEAM-like conditioning regimen in 99 MS patients: mean age-35 years old; male/female-39/60; median Expanded Disability Status Scale (EDSS) = 3.5; 43 relapsing/remitting MS, 56 progressive MS.

[Pharmacoeconomic analysis of gefitinib therapy in patients with non-cell cell lung cancer].

We performed a treatment efficacy analysis for non-small cell lung cancer (NSCLC) patients' population with EGFR mutation aimed at optimization of pharmacoeconomic factors. The employment of gefitinib leads to an increase in patients' life expectancy for a median of 1.05 years.

[Phase II clinical trial of autologous dendritic cell vaccine with immunologic adjuvant in cutaneous melanoma patients].

This paper describes the clinical results and immunologic changes in cutaneous melanoma patients receiving active specific immunotherapy with autologous dendritic cell vaccine (DCV) in combination with cyclophosphamide used as immunologic adjuvant. Twenty eight patients with morphologically verified stage III-IV cutaneous melanoma receiving therapy in N. N.

Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis.

High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (AHSCT) is a new and promising approach to multiple sclerosis (MS) treatment. In this article, we present the results of a prospective phase II open-label single-center study with the analysis of the safety and efficacy of high-dose immunosuppressive therapy+AHSCT with reduced-intensity conditioning regimen in 95 patients with different types of MS. The patients underwent early, conventional, and salvage/late transplantation.

[Plasma fructosamine to evaluate metabolic control among women with gestational diabetes].

Background: Metabolic control of diabetic pregnant women is assessed using glycated hemoglobin (HbAlc) levels and fasting blood sugar. Another glycated protein, namely fructosamine, can be an indicator of average glucose levels during the last three weeks.

Aim: To evaluate plasma fructosamine as an indicator of glycemic control in women with gestational diabetes.

[Transplantation of hemopoietic stem cells in autoimmune diseases].

Transplantation of stem hemopoietic cells is a new trend in the treatment of some autoimmune diseases.Large international trials made in the last 12 years in the USA, Europe, Russia, China were devoted to evaluation of efficacy of this method. Basing on the results of these trials, experts of the Russian Cooperative Cell Therapy Group and N.