Caloric Restriction Impairs Regulatory T cells Within the Tumor Microenvironment After Radiation and Primes Effector T cells.

Outcomes for triple negative breast cancer (TNBC) are poor and may be improved by increasing CD8 tumor infiltrating lymphocytes (TIL) to augment antitumor immunity. Radiation (RT) can promote immunogenic cell death with increased antitumor T cell activity but also stimulates suppressive regulatory T cells (Tregs). Because metabolic alterations affect immune homeostasis and prior studies show caloric restriction (CR) combined with RT improves preclinical TNBC outcomes, we hypothesized that CR augments RT, in part, by altering intratumoral immunity.

Combining Radiation and Immune Checkpoint Blockade in the Treatment of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality worldwide. Current treatment options, even though potentially curative, have many limitations including a high rate of complications. Over the past few years immune checkpoint inhibitors (ICI) targeting cytotoxic lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have changed treatment paradigms in many malignancies and are currently under investigation in HNSCC as well.

[Surgical treatment of portal hypertension: the state of art].

The article highlights modern approaches to the treatment of portal hypertension. The differential tactics is based on the type of portal hypertension, functional liver state, urgency of the situation and severity of blood loss, localization and stage of varices, concomitant diseases, etc. The role of miniinvasive methods is stressed.

[The modification of the M.D. Patsiora's operation by portal hypertension].

The direct transcutaneous transhepatic portography was performed in 85 patients with hystologically confirmed liver cirrhosis, portal hypertension and varices of the esophagus and stomach. It was found out, that the left gastric vein partakes the varicous transformation in 100% of cases. The least had an isolated division in 27% of the studied patients.

[Pathogenesis of esophageal and gastric varicose veins formation in patients with liver cirrhosis].

Research Objective: studying the features of the collateral venous blood flow and the basic ways of the formation of gastroesophageal varices in patients with cirrhosis and portal hypertension.

Methods: The following analysis is based on the interpretation of results from percutaneous transhepatic splenoportography in 85 patients. It has been established that in all 85 patients the left gastric vein plays a key role in the formation of gastroesophageal varices.

Optimization and validation of a robust human T-cell culture method for monitoring phenotypic and polyfunctional antigen-specific CD4 and CD8 T-cell responses.

Background Aims: Monitoring cellular immune responses is one prerequisite for the rational development of cancer vaccines.

Methods: We describe an extensive effort to optimize and validate quantitatively an in vitro T-cell culture method by determining the phenotype and function of both CD4(+) and CD8(+) T cells, including measurement of the phenotype markers CCR7, CD45RA, CD28 and CD27 and the functional markers interferon (IFN)-gamma, interleukin (IL)-2, macrophage inflammatory protein (MIP)-1beta, tumor necrosis factor (TNF)-alpha and CD107a.

Results: Autologous peripheral blood mononuclear cells (PBMC) were potent stimulators that expanded antigen (Ag)-specific CD8(+) T cells during short-term culture with the addition of IL-2 and IL-15 cytokines.

Safety and immunogenicity of a human and mouse gp100 DNA vaccine in a phase I trial of patients with melanoma.

A differentiation antigen commonly expressed on melanoma cells, gp100 is the target of infiltrating T cells. We conducted a phase I randomized cross-over trial of melanoma patients with either xenogeneic (mouse) or human gp100 plasmid DNA injected intramuscularly at three dosages (100, 500 or 1,500 microg) every three weeks for three doses. After the first three injections, patients were then immunized three times with gp100 from the other species.

CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit.

Blockade of inhibitory signals mediated by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to enhance T cell responses and induce durable clinical responses in patients with metastatic melanoma. The functional impact of anti-CTLA-4 therapy on human immune responses is still unclear. To explore this, we analyzed immune-related adverse events and immune responses in metastatic melanoma patients treated with ipilimumab, a fully human anti-CTLA-4 monoclonal antibody.

Phase I/II study of GM-CSF DNA as an adjuvant for a multipeptide cancer vaccine in patients with advanced melanoma.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances immune responses by inducing proliferation, maturation, and migration of dendritic cells (DCs) as well as expansion and differentiation of B and T lymphocytes. The potency of DNA vaccines can be enhanced by the addition of DNA encoding cytokines, acting as molecular adjuvants. We conducted a phase I/II trial of human GM-CSF DNA in conjunction with a multipeptide vaccine (gp100 and tyrosinase) in stage III/IV melanoma patients.

CD8+ T-cell-dependent immunity following xenogeneic DNA immunization against CD20 in a tumor challenge model of B-cell lymphoma.

The CD20 B-cell differentiation antigen is an attractive target for immunotherapy of B-cell lymphomas. In an experimental lymphoma model, BALB/c mice were immunized with mouse or human CD20 cDNA (mCD20 and hCD20, respectively) or their extracellular domains (minigenes). IFNgamma secretion by CD8+ T cells against CD20 was detected in mice vaccinated with hCD20 or human minigene, indicating that hCD20-primed CD8+ T cells recognize syngeneic CD20.

[Enteral detoxication in patients with liver cirrhosis and bleeding from the esophageal and gastric varices ].

A new method of enteral detoxication with the use of both well-known medicines ("Normase", "Sorbit") and new medicine-"Rafinosa" is described. Clinical effectiveness (normalization of neurological status) of these medicines correlates with normalization of blood amino acids unbalance, decrease of the catabolic processes and accumulation of toxic products of nitrogenous metabolism. All the above medicines (Italian made "Normase", "Sorbit" and Russian made "Rafinosa") are equally important for clinical practice.

[Several factors in the pathogenesis of hepatic failure in patients with liver cirrhosis and bleeding from esophageal and gastric varicose veins].

Bleeding in patients with liver cirrhosis leads to the activation of catabolic processes, accumulation of end products of nitrogen metabolism and pronounced imbalance of blood plasma amino acids. There is a correlation between the changes observed and disorders in neurological status. The authors hold that increased catabolism, pronounced imbalance of blood plasma amino acids and elevated blood ammonia level are the leading factors affecting the onset of hepatic encephalopathy.

[Diagnosis of dilated cardiomyopathy using patient blood serum and myocardial tissue culture].

Based on a study of the interaction of the sera from healthy persons (20), patients with coronary disease (20), rheumatic heart disease (20), myocarditis (20), congestive dilated cardiomyopathy (48) it was established that the sera from dilated cardiomyopathy patients exert an inhibitory effect on the contraction of chick embryo myocardial explants in experiments in vitro. Three grades of the inhibitory effect were detected, depending on the patient's status gravity. The sera from healthy persons and patients with the enumerated cardiovascular diseases failed to produce such an effect.

[Mechanical jaundice in cholangitis].

The peripheral lymph of the leg and venous blood from donor volunteers were compared. The lymph was found to issue at a higher rate in the active period of the day (from 9 a. m.

[Correlations between various cardiometric and functional parameters in dilated cardiomyopathy and alcoholic lesion of the heart (data of roentgenological and echocardiographic studies)].

Volumetric changes of the heart and its left ventricle, as well as myocardial contractility were assessed in 50 patients with dilatation cardiomyopathy (DCMP) and 16 patients with acute alcoholic heart damage (AHD), on the basis of roentgenologic (cardiac shape and volume, left ventricular and aortic pulsation, respiratory volumetric variations, pulmonary circulation) and echocardiographic (end-diastolic size and volume, systolic increment of posterior wall thickness, ejection fraction and left-ventricular shortening) data. Both DCMP and acute AHD were shown to be associated with total enlargement of the heart, diffuse impairment of myocardial contractility, considerably depressed left ventricular pumping function, early congestion in the systemic circulation network coupled with minor roentgenologic signs of congestion in pulmonary circulation.