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Rinsho Ketsueki ; 60(9): 1243-1256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31597850


Multiple myeloma is a malignant plasma cell neoplasm that is incurable despite significant progress in treatment over the past several decades. The incorporation of novel agents and combinations into the MM treatment paradigm has resulted in improved survival and tolerability, as well as deeper responses including achieving a minimal residual disease negative state. The addition of new treatment options and combinations has added complexity in treatment selection for myeloma patients. The current strategy for newly diagnosed myeloma involves induction, consolidation, and maintenance therapy. However, nearly all myeloma patients will develop refractory disease. This highlights the need for more effective therapies targeting the myeloma cells and their microenvironment. In this article, we summarize current management of transplant eligible and ineligible newly diagnosed patients in both the upfront and relapsed refractory setting, highlighting risk adapted strategies. We also summarize emerging therapies, such as immune and targeted approaches, as well as drugs with novel mechanisms of action. Emerging strategies offer individualized treatment options and may ultimately offer the possibility of a cure for myeloma patients.

Mieloma Múltiplo/terapia , Gerenciamento Clínico , Humanos , Imunoterapia , Terapia de Alvo Molecular , Microambiente Tumoral
Oncologist ; 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30341175


BACKGROUND: Oncology clinicians often struggle with managing medications and vaccinations in older adults with cancer. We sought to demonstrate the feasibility and preliminary efficacy of integrating pharmacists into the care of older adults with cancer to enhance medication management and vaccination administration. METHODS: We randomly assigned patients aged ≥65 years with breast, gastrointestinal, or lung cancer receiving first-line chemotherapy to the pharmacy intervention or usual care. Patients assigned to the intervention met with a pharmacist once during their second or third chemotherapy infusion. We obtained information about patients' medications and vaccinations via patient report and from the electronic health record (EHR) at baseline and week 4. We determined the number of discrepant (difference between patient report and EHR) and potentially inappropriate (Beers Criteria assessed by nonintervention pharmacists blinded to group assignment) medications. We defined the intervention as feasible if >75% of patients enrolled in the study and received the pharmacist visit. RESULTS: From January 17, 2017, to October 27, 2017, we enrolled and randomized 60 patients (80.1% of patients approached). Among those assigned to the intervention, 96.6% received the pharmacist visit. At week 4, intervention patients had higher rates of acquiring vaccinations for pneumonia (27.6% vs. 0.0%, p = .002) and influenza (27.6% vs. 0.0%, p = .002) compared with usual care. Intervention patients had fewer discrepant (5.82 vs. 8.07, p = .094) and potentially inappropriate (3.46 vs. 4.80, p = .069) medications at week 4, although differences were not significant. CONCLUSION: Integrating pharmacists into the care of older adults with cancer is feasible with encouraging preliminary efficacy for enhancing medication management and improving vaccination rates. IMPLICATIONS FOR PRACTICE: Results of this study showed the feasibility, acceptability, and preliminary efficacy of an intervention integrating pharmacists into the care of older adults with cancer. Notably, patients assigned to the intervention had fewer discrepant medications and were more likely to acquire vaccinations for pneumonia and influenza. Importantly, this work represents the first randomized controlled trial involving the integration of pharmacists into the outpatient oncologic care of older adults with cancer. In the future, a larger randomized trial is needed to demonstrate the efficacy of this care model to enhance medication management and improve vaccination outcomes for older patients with cancer.

PLoS Genet ; 2(5): e74, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16710447


In Caenorhabditis elegans, vulval cell-fate specification involves the activities of multiple signal transduction and regulatory pathways that include a receptor tyrosine kinase/Ras/mitogen-activated protein kinase pathway and synthetic multivulva (SynMuv) pathways. Many genes in the SynMuv pathways encode transcription factors including the homologs of mammalian Rb, E2F, and components of the nucleosome-remodeling deacetylase complex. To further elucidate the functions of the SynMuv genes, we performed a genome-wide RNA interference (RNAi) screen to search for genes that antagonize the SynMuv gene activities. Among those that displayed a varying degree of suppression of the SynMuv phenotype, 32 genes are potentially involved in chromatin remodeling (called SynMuv suppressor genes herein). Genetic mutations of two representative genes (zfp-1 and mes-4) were used to further characterize their positive roles in vulval induction and relationships with Ras function. Our analysis revealed antagonistic roles of the SynMuv suppressor genes and the SynMuv B genes in germline-soma distinction, RNAi, somatic transgene silencing, and tissue specific expression of pgl-1 and the lag-2/Delta genes. The opposite roles of these SynMuv B and SynMuv suppressor genes on transcriptional regulation were confirmed in somatic transgene silencing. We also report the identifications of ten new genes in the RNAi pathway and six new genes in germline silencing. Among the ten new RNAi genes, three encode homologs of proteins involved in both protein degradation and chromatin remodeling. Our findings suggest that multiple chromatin remodeling complexes are involved in regulating the expression of specific genes that play critical roles in developmental decisions.

Regulação da Expressão Gênica no Desenvolvimento , Mutação , Proteína do Retinoblastoma/metabolismo , Animais , Caenorhabditis elegans , Linhagem da Célula , Cromatina/metabolismo , Inativação Gênica , Genoma , Humanos , Modelos Genéticos , Fenótipo , Interferência de RNA , Transgenes