Emerging roles of cohesin-STAG2 in cancer.

Cohesin, a crucial regulator of genome organisation, plays a fundamental role in maintaining chromatin architecture as well as gene expression. Among its subunits, STAG2 stands out because of its frequent deleterious mutations in various cancer types, such as bladder cancer and melanoma. Loss of STAG2 function leads to significant alterations in chromatin structure, disrupts transcriptional regulation, and impairs DNA repair pathways.

Rifaximin stimulates nitrogen detoxification by PXR-independent mechanisms in human small intestinal organoids.

Background And Aims: Recurrent hepatic encephalopathy (HE) is characterized by hyperammonaemia in combination with neuropsychiatric abnormalities and is treated with lactulose and rifaximin. Rifaximin is a pregnane X receptor (PXR) agonist with low systemic and high intestinal bioavailability. The mechanisms by which it alleviates HE are unclear.

Targeting glutamine metabolism and autophagy: the combination for prostate cancer radiosensitization.

Radiotherapy is one of the curative mainstays of prostate cancer; however, its efficacy is often diminished by tumor radioresistance. Depending on the stage of disease, tumors can relapse in approximately 50% of patients with prostate cancer after radiotherapy. Nevertheless, the mechanisms that drive tumor cell survival are not fully characterized, and reliable molecular prognostic markers of prostate cancer radioresistance are missing.

GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy.

Radiotherapy is one of the curative treatment options for localized prostate cancer (PCa). The curative potential of radiotherapy is mediated by irradiation-induced oxidative stress and DNA damage in tumor cells. However, PCa radiocurability can be impeded by tumor resistance mechanisms and normal tissue toxicity.

Splice variants of metabolic nuclear receptors: Relevance for metabolic disease and therapeutic targeting.

Metabolic nuclear receptors are ligand-activated transcription factors which control a wide range of metabolic processes and signaling pathways in response to nutrients and xenobiotics. Targeting these NRs is at the forefront of our endeavours to generate novel treatment options for diabetes, metabolic syndrome and fatty liver disease. Numerous splice variants have been described for these metabolic receptors.

Metabolic Targeting of Cancer Stem Cells.

Most human tumors possess a high heterogeneity resulting from both clonal evolution and cell differentiation program. The process of cell differentiation is initiated from a population of cancer stem cells (CSCs), which are enriched in tumor-regenerating and tumor-propagating activities and responsible for tumor maintenance and regrowth after treatment. Intrinsic resistance to conventional therapies, as well as a high degree of phenotypic plasticity, makes CSCs hard-to-target tumor cell population.

Interplay between MycN and c-Myc regulates radioresistance and cancer stem cell phenotype in neuroblastoma upon glutamine deprivation.

Targeting glutamine metabolism has emerged as a potential therapeutic strategy for Myc overexpressing cancer cells. Myc proteins contribute to an aggressive neuroblastoma phenotype. Radiotherapy is one of the treatment modalities for high-risk neuroblastoma patients.

[Problems of general surgery in clinical transplantology and cardiac surgery].

The authors have analyzed results of operative treatment of 128 patients with terminal chronic renal failure (59) and cardiac pathology (69) associated with general surgical diseases (cholelithiasis, abdominal hernias, ulcer disease, malignant tumors etc). The authors recommend the indications, terms and character of operative measures be defined individually.

[Treatment of patients with general surgical diseases after open-heart operations with cardiopulmonary bypass].

Experience in surgical treatment of 69 patients suffering from coronary heart disease and valve pathology in combination with various general surgical diseases was summarized. Two methods of surgical correction were studied: combined one and staged one. Up-to-date technologies such as endoscopic surgery, tension free hernioplasty, and artificial materials were used during the procedures.

[Adequacy of prescribing the disaggregants in vascular pathology of the eye fundus and in primary open-angle glaucoma].

The functional activity of blood platelets was studied in 936 patients with vascular pathology of the eye fundus (central chorioretinal dystrophy--CCRD; preproliferative diabetic retinopathy--PPDR; proliferative diabetic retinopathy--PDR; hypertensive retinopathy--HP; thrombosis of retinal veins--TRV; and primary open angle glaucoma--POAG) by using 2 methods: the routine one, which does not expose the real process of platelets' aggregation in the blood bed, and a method, which is closer to the conditions in vivo. The non-physiological ("tube"-based) methods of determination of platelets' aggregation overstate almost 3-fold the share (%) of patients needing disaggregants. The disaggregation therapy is indicated in 28% of cases; it is more often prescribed for patients with TRV (52.

[The content of D-dimer in peripheral blood as observed studied in thrombohemorrhagic lesions of the retina].

The content of D-dimer in peripheral blood was studied in thrombohemorrhagic lesions of the retina. 60 patients with retinal pathology of the retina, i.e.

[Treatment of patients with proliferative diabetic retinopathy and serotonin insufficiency].

30 patients (19--female and 11--male) with proliferative diabetic retinopathy (DR) were examined. The age of patients and of the controls ranged from 25 to 72 years. The duration of diabetes mellitus amounted on the average to 16.

[Significance of serotonin in the pathogenesis of diabetic retinopathy and central chorioretinal dystrophy].

A total of 147 patients with preproliferative and proliferative diabetic retinopathy (DR), with the exudative hemorrhagic and nonexudative stages (93 females and 54 males), were consulted at Helmholtz Institute of Ophthalmic Diseases in 1997-2001. Control group consisted of 39 healthy subjects aged 25-76 years. The group of patients with preproliferative DR consisted of 27 patients with compensated diabetes mellitus.

[Thrombocytopathies and their role in the development of hemorrhagic syndrome in vascular diseases of the fundus oculi].

Examinations of 407 patients with angiological disorders of the fundus oculi (diabetic retinopathy, retinal vein thrombosis, central chorioretinal dystrophy, retinal angiitis) revealed relapsing hemorrhagic syndrome in 40% (170) patients. No thrombocytopenia was revealed in any of the patients, which suggests qualitative impairment of platelets in such patients. Evaluation of the platelet aggregation coefficient (PAC) using thrombin aggregation inducers and adenosine diphosphate disodium revealed a statistically significant decrease of PAC for one or both aggregants in all 170 patients with the hemorrhagic syndrome, which indicated platelet dysfunction.

[Effect of therapy with blood component (activated autoplasma) on blood glutathione level in patients with vascular abnormalities on the fundus oculi].

Thirty-three patients with central chorioretinal dystrophy, 18 with proliferative diabetic retinopathy, and 15 controls without ocular diseases were examined. All patients were treated by blood components. The treatment started with activation of blood plasma platelets.

[Effects of activated autoplasma on platelet aggregation in patients with vascular diseases of the fundus oculi].

Activated autoplasma (AAP) was used in the treatment of patients with central chorioretinal dystrophy and diabetic retinopathy. The therapeutic effect of AAP injected intrabulbarly and its effect on platelet aggregation in the peripheral blood after intramuscular and intravenous injections were assessed. Intravenous AAP was found to exert a manifest disaggregating effect, whereas intramuscular injections did not affect platelet aggregation.

[Hemocomponent therapy of central involution chorioretinal dystrophy].

Hemocomponent therapy was used in 181 patients (347 eyes) with central chorioretinal dystrophy. Activated autoplasma possessing a marked resorptive effect, consisting in resorption of hemorrhages and exudations on the fundus oculi, was used. Vision acuity improved in 75% of examined eyes by an average of 0.

[Results of the use of vasoactive preparation pikamilon in pigmented retinal abiotrophy].

Eighty patients with pigmented retinal abiotrophy (PRA) and 20 controls were examined. The perfusion pressure and arteriovenous coefficient are markedly reduced in patients with stages 1-2 PRA, in comparison with controls. Deterioration of the visual function in patients with stages 3-4 PRA vs.

[Perfusion pressure in ocular vessels of patients with open-angle glaucoma].

Perfusion pressure in ophthalmic vessels was measured by computer-aided ophthalmodynamography in health, stenoses of the internal carotid artery, and open-angle glaucoma. A total of 70 subjects were examined. Stenoses of the internal carotid artery are associated with a noticeable reduction of perfusion pressure on the side of stenosis.

[Clinical significance of the determination of several hemostatic parameters in the lacrimal fluid of patients with vascular diseases of the retina].

Clinicolaboratory studies of 92 patients with vascular diseases of the retina (retinal vein thrombosis, central chorioretinal dystrophy, retinal hypertensive angiosclerosis) were carried out to assess hemorheologic parameters (platelet and red cell aggregation coefficients, blood viscosity). In parallel with this, lacrimal fluid was analyzed for hemostatic parameters, plasminogen and antithrombin III. A marked increase of plasminogen and antithrombin III levels was found in the lacrimal fluid of patients with retinal vein thrombosis, this increase correlating with pathologic shifts in the studied rheologic characteristics.

[Results of the use of ticlid in the treatment of patients with post-thrombotic retinopathy].

Presents 22 case histories of patients with postthrombotic retinopathy (n = 20) and fresh thrombosis (n = 2), treated with ticlid, a new drug. Demonstrates the disaggregating and antithrombotic effects of the drug, a positive time course of microcirculatory changes in the fundus oculi and improvement of blood rheology.

[Results of phlebo-destruction surgery and blood rheology indicators in patients with central chorioretinal dystrophy].

Hemorheologic parameters were analyzed in 34 patients with central chorioretinal dystrophy and the effects of these parameters on the outcome of phlebodestruction studied. Blood viscosity and red cell aggregation coefficient were found increased in such patients. Phlebodestruction was found ineffective in the patients with significant disturbances of blood rheology.

[Prospects of intraoperative dynamic cholangio-manometry by tensor detectors with graphic recording of pressure function].

Intraoperative cholangio-manometry with a miniature tensor sensor and graphic recording of the results were conducted to study the function of the major duodenal papilla in 53 patients. A periodical activity of the ampulla of the papilla was revealed, which was characterized by certain values of the peak and basal pressure, and duration of contraction and relaxation periods. The numerical values and the pattern of the pressure curve differed in patients with obstructive cholecystitis, biliary pancreatitis, and a concrement incarcerated in the ampulla of the papilla.