RESUMO
The aryl hydrocarbon receptor (AhR) regulates Th17-polarized CD4+ T cell functions, but its role in HIV-1 replication/outgrowth remains unknown. Genetic (CRISPR-Cas9) and pharmacological inhibition reveal AhR as a barrier to HIV-1 replication in T cell receptor (TCR)-activated CD4+ T cells in vitro. In single-round vesicular stomatitis virus (VSV)-G-pseudotyped HIV-1 infection, AhR blockade increases the efficacy of early/late reverse transcription and subsequently facilitated integration/translation. Moreover, AhR blockade boosts viral outgrowth in CD4+ T cells of people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Finally, RNA sequencing reveals genes/pathways downregulated by AhR blockade in CD4+ T cells of ART-treated PLWH, including HIV-1 interactors and gut-homing molecules with AhR-responsive elements in their promoters. Among them, HIC1, a repressor of Tat-mediated HIV-1 transcription and a tissue-residency master regulator, is identified by chromatin immunoprecipitation as a direct AhR target. Thus, AhR governs a T cell transcriptional program controlling viral replication/outgrowth and tissue residency/recirculation, supporting the use of AhR inhibitors in "shock and kill" HIV-1 remission/cure strategies.
Assuntos
Infecções por HIV , HIV-1 , Receptores de Hidrocarboneto Arílico , Humanos , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/metabolismo , HIV-1/fisiologia , Receptores de Hidrocarboneto Arílico/genética , Células Th17 , Replicação ViralRESUMO
BACKGROUND/AIM: Surgery, which remains a conventional treatment of breast tumors, may induce the secretion of growth factors that support angiogenesis and wound healing. These factors are suspected to trigger carcinoma cell division and promote tumor relapse. We addressed this question by culturing breast cancer cell lines in the presence of wound fluid harvested after surgery. MATERIALS AND METHODS: Wound fluids were collected from patients who underwent either breast reconstruction, tumor resection, or tumor resection after neoadjuvant chemotherapy. MCF-7 (estrogen receptor (ER)+/progesterone receptor (PgR)+, HCC1937 (ER/PgR-, human epidermal growth factor receptor/neuralized (HER2/neu)-) and MCF-10A (used as a negative control) cell lines were grown in culture media supplemented with wound fluids. RESULTS: Wound fluids drained during the three categories of procedures significantly stimulated the proliferation of MCF-7 and HCC1937 cells in a similar manner. CONCLUSION: This stimulatory effect on tumor cell proliferation could be attenuated by therapeutic targeting against growth factors and inflammation processes in order to avoid tumor relapse.
Assuntos
Líquidos Corporais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Meios de Cultura , Drenagem , Feminino , Humanos , Células MCF-7 , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/cirurgia , Cicatrização/fisiologiaRESUMO
Socio-aesthetic care in oncology, a parenthesis in the patient's journey. Socio-aesthetics, which is an aspect of support care, is carried out within the hospital. The treatments given into the suggestion of paramedical teams or at the request of patients provide relief and well-being to women and men who are treated for cancer. Recourse to services of socio-esthetics at various stages of the cancer treatment helps avoid isolation, regain confidence in one's self image and prepare for life "after cancer".