HIF-1--a big chapter in the cancer tale.

Approximately 1.0-1.5% of the genome is transcriptionally regulated by hypoxia, and hypoxia-inducible factor (HIF)-1α is the transcription factor modulating many of these genes. Cancer cells are able to survive hypoxic environments and hypoxia itself can activate adaptive cellular responses that contribute to tumor progression. Many HIF-1α-mediated biological effects are beneficial for tumor progression, including metabolic shift toward glycolysis, inhibition of fatty acid ß-oxidation, production of cellular reactive oxygen species and altering expression of tumor suppressor genes. HIF-1 promotes selective mitochondrial autophagy, resistance to T cell mediated lysis of cancer cells, induction of pluripotent cancer stem cells, epithelial-mesenchymal and epithelial-mesenchymal-endothelial transitions beneficial for tumor growth and progression, loss of E-cadherin. HIF-1 also induces production of signal molecules and cytokines by carcinoma-associated fibroblasts and upregulation of certain microRNAs important for cancer progression. This minireview focuses on the HIF-1 promoting role in tumor initiation and progression and HIF-1 targeting. HIF-1 pathway downregulation seems to be promising in future cancer treatment.

Soluble P-selectin glycoprotein ligand - a possible new target in ulcerative colitis.

BACKGROUND: The main characteristic of active inflammatory bowel disease (IBD) is the neutrophil infiltration into the intestinal lamina propria, where neutrophils usually do not reside. Selectins are cell surface glycoproteins responsible for binding the leukocytes to vascular cells and their extravasation into the surrounding tissue. They show high affinity to P-selectin glycoprotein ligand-1 (PSGL-1) receptors. PSGL-1 is expressed on the surface of all leukocytes and they mediate the rolling of neutrophils on P-selectin. Soluble PSGL-1 acts competitively with cellular PSGL in many physiological and pathological processes.The aim of our study was to compare serum sPSGL-1 concentration in the blood of patients with ulcerative colitis (UC) and healthy control subjects. METHODS: Serum concentrations of sPSGL-1 were measured in 20 patients with UC and 20 control subjects. Two-layer immunoenzyme procedure (ELISA) was used. RESULTS: The mean (± standard deviation) serum concentrations of sPSGL-1 in patients with UC and controls were 349.97±75.40 U/mL and 284.39±52.40 U/mL, respectively (p=0.003). CONCLUSION: In the present study, we showed that patients with UC had significantly higher sPSGL-1 blood values in comparison with healthy subjects. A short-term blockade with anti-PSGL-1 antibodies could block the transport of neutrophils and decrease UC activity. Thus it could possibly be employed in a new therapeutic approach to the treatment of UC (Fig. 1, Ref. 25).

[Early detection of colorectal carcinoma using the Hemdetect Test]. / Prilog ranom otkrivanju kolorektalnog karcinoma Hemdetect testom.

Cellular immunity was examined by two methods in vitro: absolute number T and B lymphocytes (E.T. and E.A.C. rosettes) and by the lymphocyte transformation test, in 280 patients with psoriasis (83.5% with psoriasis vulgaris and 16.5% with other forms of psoriasis). No statistically significant changes were found in comparison with the control group.