Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795 percent (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Synergistic cytotoxicity and apoptosis induced in human cholangiocarcinoma cell lines by a combined treatment with tumor necrosis factor-alpha (TNF-alpha) and triptolide.

Cholangiocarcinoma is known to be relatively resistant to chemotherapy. One alternative approach is to use a combination of an immunomodulating agent with an anticancer drug. Here we studied the synergistic actions of TNF-alpha and triptolide (a diterpene epoxide prepared from Tripterygium wilfordii), previously shown to have antitumor activity against hamster cholangiocarcinoma (CCA) cells. Three human CCA cell lines (HuCCA-1, HubCCA-1, KKU-100 cell lines) were subjected to a combined treatment of TNF-alpha (0.1-10 ng/ml) and triptolide (5-50 ng/ml) for 24 hours in microculture plates. The combination of TNF-alpha and triptolide had a significantly increased cytotoxic activity over that of triptolide alone (p < 0.05). Under the same conditions, TNF-alpha by itself was not cytotoxic to these cell lines. Similarly, the combined treatment could also accelerate apoptotic cell death in all three human cholangiocarcinoma cell lines. The combined treatment of TNF-alpha at 10 ng/ml and triptolide at 50 ng/ml for 6-10 hours achieved a percentage of apoptotic cells shown by DAPI staining of 18-65%, compared to only 6-20% apoptotic cells for triptolide alone. Analyzing the possible mechanisms of the combined treatment, we found by Western blot that at 6 hours, there was a poly (ADP-ribose) polymerase (PARP) cleavage which was not detectable by the treatment of either TNF-alpha or triptolide alone. The cleavage of PARP was inhibited when the cells were pretreated with the enzyme inhibitor AC-DEVD-CMK, suggesting that apoptosis induced by the combination of TNF-alpha and triptolide involved activation of caspase 3. These results indicate that apoptosis of human cholangiocarcinoma cell lines as induced by a combination of TNF-alpha and triptolide is mediated through caspase 3 activation.

The relevance of crossmatch and HLA compatibility in liver transplantation

Encontra-se bem definido o papel dos aloanticorpos HLA no desencadeamento da rejeicao hiperaguda nos transplantes renais. Nos casos dos transplantes hepaticos, assim como nos transplantes cardiacos, permanece controverso o papel de anticorpos pre-formados na sobrevida do enxerto. Realizamos neste estudo extensa revisao da literatura medica recente publicada pelos grandes centros mundiais transplantadores de figado a respeito da importancia do crossmatch e da compatibilidade HLA nos resultados precoces e tardios do transplante de figado. Ainda longe da unanimidade, a compatibilidade imunologica HLA parece exercer influencias nos desempenhos precoce e tardio dos enxertos hepaticos, apesar do avanco dos imunossupressores. Entretanto a baixa incidencia de paciente transplantados com altos titulos de testes de crossmatch positivos, nao altera a sobrevida global das casuisticas analisadas, sendo controversa sua utilizacao como metodo de selecao frente aos custos de seu emprego, mas nao excluindo seu valor como auxiliar na orientacao da imunossupressao precoce e tardia destes pacientes

Quimiosensibilidad in vitro, en cánceres de cavidad oral y orofaringe, en medio líquido / Chemosensivity in vitro, in oral and oropharyngeal canceres, in liquid medium

La mayoría de ensayos in vitro para realizar pruebas de quimiosensibilidad se han desarrollado utilizando metodología relativamente compleja, sin la obtención de resultados favorables. Desarrollamos una prueba de quimiosensibilidad, in vitro, para cánceres humanos y la aplicamos en 8 biopsias de tumores de cabeza y cuello, cultivándolas por medio de la técnica de explante primario en medio líquido, y agregando distintos fármacos (Actinomivins D, Adriamicina, Bleomicina, Cisplatino, 5-Fluoruracilo, Metotrexate, Mitomicina C, Vinblastina y Vicristina) a concentraciones variadas. Se observó un 100 por ciento de eficacia de proliferación celular en ausencia de fármacos, así como una inhibición diferente que dependía de la droga citotóxica empleada. Algunos explantes fueron altamente inhibidos mientras que otros resultaron muy resistentes, esta variabilidad de respuesta se obtuvo en distintos explantes aún cuando se utilizaba el mismo fármaco. Metrotexate demostró tener una alta selectividad inhibitoria para los explantes de crecimiento rápido, mientras que Bleomicina, a dosis bajas, para los de crecimientos lento.