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1.
CA Cancer J Clin ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39207229

RESUMEN

Older adults with cancer heterogeneously experience health care, treatment, and symptoms. Geriatric assessment (GA) offers a comprehensive evaluation of an older individual's health status and can predict cancer-related outcomes in individuals with solid tumors and those with hematologic malignancies. In the last decade, randomized controlled trials have demonstrated the benefits of GA and GA management (GAM), which uses GA information to provide tailored intervention strategies to address GA impairments (e.g., implementing physical therapy for impaired physical function). Multiple phase 3 clinical trials in older adults with solid tumors and hematologic malignancies have demonstrated that GAM improves treatment completion, quality of life, communication, and advance care planning while reducing treatment-related toxicity, falls, and polypharmacy. Nonetheless, implementation and uptake of GAM remain challenging. Various strategies have been proposed, including the use of GA screening tools, to identify patients most likely to benefit from GAM, the systematic engagement of the oncology workforce in the delivery of GAM, and the integration of technologies like telemedicine and mobile health to enhance the availability of GA and GAM interventions. Health inequities in minoritized groups persist, and systematic GA implementation has the potential to capture social determinants of health that are relevant to equitable care. Caregivers play an important role in cancer care and experience burden themselves. GA can guide dyadic supportive care interventions, ultimately helping both patients and caregivers achieve optimal health.

2.
Proc Natl Acad Sci U S A ; 119(40): e2204828119, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36161942

RESUMEN

Biased G protein-coupled receptor (GPCR) ligands, which preferentially activate G protein or ß-arrestin signaling pathways, are leading to the development of drugs with superior efficacy and reduced side effects in heart disease, pain management, and neuropsychiatric disorders. Although GPCRs are implicated in the pathophysiology of Alzheimer's disease (AD), biased GPCR signaling is a largely unexplored area of investigation in AD. Our previous work demonstrated that GPR3-mediated ß-arrestin signaling modulates amyloid-ß (Aß) generation in vitro and that Gpr3 deficiency ameliorates Aß pathology in vivo. However, Gpr3-deficient mice display several adverse phenotypes, including elevated anxiety-like behavior, reduced fertility, and memory impairment, which are potentially associated with impaired G protein signaling. Here, we generated a G protein-biased GPR3 mouse model to investigate the physiological and pathophysiological consequences of selective elimination of GPR3-mediated ß-arrestin signaling in vivo. In contrast to Gpr3-deficient mice, G protein-biased GPR3 mice do not display elevated anxiety levels, reduced fertility, or cognitive impairment. We further determined that G protein-biased signaling reduces soluble Aß levels and leads to a decrease in the area and compaction of amyloid plaques in the preclinical AppNL-G-F AD mouse model. The changes in amyloid pathology are accompanied by robust microglial and astrocytic hypertrophy, which suggest a protective glial response that may limit amyloid plaque development in G protein-biased GPR3 AD mice. Collectively, these studies indicate that GPR3-mediated G protein and ß-arrestin signaling produce discrete and separable effects and provide proof of concept for the development of safer GPCR-targeting therapeutics with more directed pharmacological action for AD.


Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Modelos Animales de Enfermedad , Proteínas de Unión al GTP/metabolismo , Ratones , Ratones Transgénicos , Placa Amiloide/patología , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestinas/metabolismo
3.
BMC Cancer ; 23(1): 917, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37770838

RESUMEN

BACKGROUND: Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults. METHODS: This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study. RESULTS: Twenty-seven older adult survivors from rural areas completed open-ended semi-structured interviews. The mean age was 73.4 (SD = 5.0). Most participants were non-Hispanic White (96.3%), female (59.3%), married (63.0%), and had up to a high school education (51.9%). Rural older survivors reported a general lack of awareness of survivorship care plans, communication challenges with healthcare team, transportation challenges, financial toxicity, psychological challenges, and diet and physical challenges. Rural older survivors recommend the provision of nutritional advice referral to exercise programs, and social support groups and for their healthcare providers to discuss their survivorship plan with them. CONCLUSIONS: Although study participants reported similar survivorship challenges as urban older adult survivors, additional challenges reported regarding transportation and consideration of farm animals have not been previously reported. Heightened awareness of the survivorship needs of rural older adults may result in better survivorship care for this population.


Asunto(s)
Supervivientes de Cáncer , Neoplasias , Humanos , Femenino , Anciano , Supervivientes de Cáncer/psicología , Sobrevivientes , Supervivencia , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias/psicología , Oncología Médica
4.
J Rural Health ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847392

RESUMEN

BACKGROUND: Currently, 64% of cancer survivors are aged 65+. Older cancer survivors have unique complications after chemotherapy and are often excluded from cancer clinical trials. Although there is research on barriers to clinical trial participation of older adult cancer survivors, to date no research has explored barriers to clinical trial participation unique to rural older adult cancer survivors. METHODS: This study is a secondary qualitative analysis from a study exploring survivorship challenges of rural older adults. Eligible participants were rural residents over age 65 who have completed curative-intent chemotherapy in the past 12 months. Participants (n = 27) completed open-ended semi-structured interviews that included questions on barriers to clinical trial participation. Transcripts were coded independently by two coders using thematic analysis. We have adhered to the standards for reporting qualitative research. FINDINGS: Participants reported a variety of barriers that included limited knowledge and fear about clinical trials, transportation challenges, their physicians not informing them of clinical trials, and thinking they are too old to participate in clinical trials. However, participants also reported facilitators to participating in clinical trials, including acknowledging benefits to their own health and society, and understanding the importance of clinical trials. CONCLUSION: Rural older cancer survivors face numerous interpersonal, intrapersonal, and organizational barriers to clinical trial participation. Aging- and location-sensitive interventions that focus on patients, their caregivers, and health care providers may lead to improved participation of rural older adult survivors into clinical trials.

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