RESUMEN
Palliative care is provided by an interdisciplinary team, including physicians, advanced practice providers, nurses, social workers, chaplains, and other disciplines based on need. Music therapists and art therapists are becoming increasingly available to palliative care teams and are advancing the diverse and unique clinical services available to effectively meet the holistic needs of patients with serious illnesses and their families. This article provides a concrete exploration of clinical music therapy and art therapy within palliative care and hospice paradigms, with discussion of therapists' training and expertise, therapeutic approaches within the setting of interprofessional team-based care, and discussion of evidence-based symptom management and outcomes supporting the inclusion of music and art therapies within medical education and clinical employment.
Asunto(s)
Arteterapia , Cuidados Paliativos al Final de la Vida , Enfermería de Cuidados Paliativos al Final de la Vida , Musicoterapia , Humanos , Cuidados PaliativosRESUMEN
Primary tumors often give rise to disseminated tumor cells (DTC's), which acquire full malignancy after invading distant site(s). Thus, DTC's may be a productive target for preventing prostate cancer metastasis progression. Our prior research showed that PHSCN peptide (Ac-PHSCN-NH2) targets activated α5ß1 integrin to prevent invasion and metastasis in preclinical adenocarcinoma models, and disease progression in Phase I clinical trial. Here, we report that D-stereoisomer replacement of histidine and cysteine in PHSCN produces a highly potent derivative, Ac-PhScN-NH2 (PhScN). PhScN was 27,000- to 150,000-fold more potent as an inhibitor of basement membrane invasion by DU 145 and PC-3 prostate cancer cells. A large increase in invasion-inhibitory potency occurred after covalent modification of the sulfhydryl group in PHSCN to prevent disulfide bond formation; while the potency of covalently modified PhScN was not significantly increased. Thus PhScN and PHSCN invasion inhibition occurs by a noncovalent mechanism. These peptides also displayed similar cell surface binding dissociation constants (Kd), and competed for the same site. Consistent with its increased invasion-inhibitory potency, PhScN was also a highly potent inhibitor of lung extravasation and colonization in athymic nude mice: it was several hundred- or several thousand-fold more potent than PHSCN at blocking extravasation by PC-3 or DU 145 cells, and 111,000- or 379,000-fold more potent at inhibiting lung colonization, respectively. Furthermore, systemic 5 mg/kg PhScN monotherapy was sufficient to cause complete regression of established, intramuscular DU 145 tumors. PhScN thus represents a potent new family of therapeutic agents targeting metastasis by DTC's to prevent parallel progression in prostate cancer.
Asunto(s)
Adenocarcinoma/prevención & control , Aminoácidos/farmacología , Integrina alfa5beta1/antagonistas & inhibidores , Neoplasias Pulmonares/prevención & control , Fragmentos de Péptidos/farmacología , Neoplasias de la Próstata/prevención & control , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Desnudos , Invasividad Neoplásica , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Anticoagulantes/uso terapéutico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Suplementos Dietéticos , Vitamina K/farmacología , Warfarina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/farmacología , Trastornos de la Coagulación Sanguínea/sangre , Estabilidad de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vitamina K/administración & dosificación , Vitamina K/sangre , Warfarina/farmacologíaRESUMEN
We demonstrate a general approach for metabolic engineering of biocatalytic systems comprising the uses of a chemostat for strain improvement and radioisotopic tracers for the quantification of pathway fluxes. Flux determination allows the identification of target pathways for modification as validated by subsequent overexpression of the corresponding gene. We demonstrate this method in the indene bioconversion network of Rhodococcus modified for the overproduction of 1,2-indandiol, a key precursor for the AIDS drug Crixivan.