RESUMEN
Clear cell renal cell carcinoma (ccRCC) is a common urologic malignancy. Understanding of the transcriptional regulation of oncogenes and tumor suppressor genes involved is critical for the development of the treatments for renal tumors. Using ccRCC subdivision of the TCGA dataset, we identified NR0B2 encoding orphan nuclear receptor as a tumor suppressor candidate in renal tissue. In independent cohort of primary renal tumors, quantitative PCR experiments confirmed significant suppression of NR0B2 mRNA in 86% of ccRCC samples studied. In 80% of these cases, we detected the hypermethylation of the NR0B2 pro-moter region. These results suggest that NR0B2 is a tumor suppressor gene in ccRCC, and that the hypermethylation of promoter region is the main mechanism of its downregulation.
Asunto(s)
Carcinoma de Células Renales/metabolismo , Metilación de ADN , ADN de Neoplasias/metabolismo , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/metabolismo , Regiones Promotoras Genéticas , Receptores Citoplasmáticos y Nucleares/biosíntesis , Proteínas Supresoras de Tumor/biosíntesis , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , ADN de Neoplasias/genética , Femenino , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
The ex vivo maintenance and expansion of hematopoietic stem cells and early progenitors is necessary for the successful treatment of hematopoietic and immune diseases. Multiple attempts to improve the expansion of hematopoietic stem cells (HSCs) by their cultivation in the presence of growth factor cocktails have so far failed. Novel approaches aimed at conserving the earliest precursors in their undifferentiated state are needed. These approaches should take into account local regulatory factors that are present in the HSC microenvironment and the three-dimensional architecture of their niche. In the present study, we compared the effects of two Notch ligands, i.e., Jagged1 and DLL1, on murine and human hematopoiesis in vitro. Our observations indicate that the stromal expression of Notch ligands increases the production of both the total and phenotypically early murine and human hematopoietic cells in the co-culture. On one hand, this study demonstrates the similarity of effects of stromal expression of Notch ligands on murine and human hematopoiesis in vitro. On the other hand, our study revealed a number of cell type and ligand-specific variations that are systematically described below. It seems that the effects of SCF cytokine addition on murine hematopoiesis in vitro depend on the stromal context and are oppositely directed for Jagged1 and DLL1.
Asunto(s)
Hematopoyesis/fisiología , Células Madre Hematopoyéticas/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteína Jagged-1/metabolismo , Animales , Proteínas de Unión al Calcio , Células Madre Hematopoyéticas/citología , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Proteína Jagged-1/genética , Ratones , Células 3T3 NIH , Factor de Células Madre/genética , Factor de Células Madre/metabolismo , Células del Estroma/citología , Células del Estroma/metabolismoRESUMEN
The study revealed the key role of serine protease hepsin activity in transition of in situ prostate adenocarcinoma into the metastasizing form. Inhibition of hepsin activity suppresses the invasive growth of the tumor. Hepsin is an convenient target for pharmacological agents, so the study of its inhibitory mechanisms is a promising avenue in drug development. Assay of proteolytic activity in various tumor cell lines in vitro showed that this activity in prostate adenocarcinoma cells significantly surpasses proteolytic activity in other examined tumor cell lines. Selective cytotoxic action of anthralin, an inhibitor of hepsin activity, on human adenocarcinoma cells was demonstrated in comparison with other tumor cell lines.
Asunto(s)
Adenocarcinoma/metabolismo , Antralina/farmacología , Neoplasias de la Próstata/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Masculino , Serina Endopeptidasas/metabolismoRESUMEN
A recombinant hepsin-producing strain of Escherichia coli was obtained and the conditions for hepsin expression in a bacterial system were optimized. To study the physicochemical properties of the enzyme, a procedure for purification of active recombinant hepsin using metal-chelate affinity chromatography and ion-exchange chromatography was developed. The interaction of recombinant hepsin with various peptide substrates is characterized. The dose-dependent inhibition of the recombinant hepsin enzyme activity by anthralin in vitro and an increase in the hepsin enzymatic activity in the presence of resveratrol were revealed.
Asunto(s)
Escherichia coli/genética , Serina Endopeptidasas/química , Serina Endopeptidasas/aislamiento & purificación , Antralina/farmacología , Línea Celular Tumoral , Escherichia coli/metabolismo , Expresión Génica , Humanos , Cinética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Resveratrol , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Inhibidores de Serina Proteinasa/farmacología , Estilbenos/farmacología , Especificidad por SustratoRESUMEN
Hardphase ELISA was used to compare the blood sera of patients with malignant skin lymphomas and HIV infection and of healthy volunteers for autoimmune antibodies to CD4. Antibodies to CD4 were not detected in the volunteers (30 sera) and in the patients with malignant skin lymphomas (52 patients with different disease stages). The antibodies were found in 4 of 11 HIV cases.
Asunto(s)
Autoanticuerpos/sangre , Antígenos CD4/inmunología , Infecciones por VIH/inmunología , Linfoma Cutáneo de Células T/inmunología , Neoplasias Cutáneas/inmunología , Adulto , Anciano , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , SueroRESUMEN
Molecular physiology is a new interdisciplinary field of knowledge that looks into how complicated biological systems function. The living cell is a relatively simple, but at the same time very sophisticated biological system. After the sequencing of the human genome, molecular physiology has endeavored to investigate the systems of cellular interactions at a completely new level based on knowledge of the spatial organization and functions of receptors, their ligands, and protein-protein interactions. In recent years, the achievements in molecular physiology have centered on the study of sensor reception mechanisms and intercellular data transfer, as well as the immune system physiology, amongst other processes.
RESUMEN
The concentrations of tumor necrosis factor-alpha, interleukin-1beta, interleukin-2, interleukin-4, and the content of antibodies to H1 histone fraction in peripheral blood lymphocytes, epidermis, and serum were evaluated in patients with mycosis fungoides. It was found that as the disease progresses, cytokine synthesis is switched from Th1 to Th2 class and production of proinflammatory cytokines increases, which indirectly promotes the development of the autoimmune reaction.
Asunto(s)
Interleucinas/metabolismo , Micosis Fungoide/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Estudios de Casos y Controles , HumanosRESUMEN
Disorders in restructuring of T-cell receptor gamma-chain in DNA from skin biopsy specimens and peripheral blood lymphocyte of patients with malignant skin lymphomas at different stages of the disease were detected by PCR. Nucleotide sequences of monoclonal T-cell receptors were determined. The study showed that DNA sequences from the skin and lymphocytes did not coincide in some cases.