RESUMEN
CD44 is a complex family of molecules, associated with aggressive malignancies and cancer stem cells. However, the role of CD44 variants in tumor progression and treatment resistance is not clear. In this study, the expression of CD44 and its variants was assessed in head and neck squamous cell carcinomas (HNSCC). Furthermore, subpopulations of cells expressing high amounts of CD44 variants were identified and characterized, for e.g., cell cycle phase and radioresistance. Results revealed high and homogenous CD44 and CD44v7 expression in four cell lines and CD44v4 and CD44v6 in three cell lines. CD44v3 was highly expressed in two cell lines, whereas CD44v5, CD44v7/8, CD44v10, CD133, and CD24 demonstrated no or moderate expression. Moreover, a subpopulation of very high CD44v4 expression was identified, which is independent of cell phase, demonstrating increased proliferation and radioresistance. In cell starvation experiments designed to enrich for cancer stem cells, a large population with dramatically increased expression of CD44, CD44v3, CD44v6, and CD44v7 was formed. Expression was independent of cell phase, and cells demonstrated increased radioresistance and migration rate. Our results demonstrate that the heterogeneity of tumor cells has important clinical implications for the treatment of HNSCC and that some of the CD44 variants may be associated with increased radioresistance. Highly expressed CD44 variants could make interesting candidates for selective cancer targeting.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Receptores de Hialuranos/metabolismo , Línea Celular Tumoral , Separación Celular , Citometría de Flujo , Humanos , Isoformas de Proteínas , Tolerancia a Radiación/fisiologíaRESUMEN
Experience gained as a result of indirect endolymphatic chemotherapy of patients with tuberculosis of the skin, peripheral and mesenteric lymph nodes is presented. The above treatment is tolerated well by the patients and causes no local or general complications. The clinical effect is achieved 1-3 months earlier than with a traditional therapy which provides a significant drop in the inpatient period and the drug load. Incidence of exacerbations also becomes less. It is worthwhile to include lymphotropic chemotherapy into a complex of therapeutic measures both at the beginning of the treatment and in a torpid course of the disease.