Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refractory and metastatic breast cancers. We leverage matched PDXs and PDX-derived organoids (PDxO) for drug screening that is feasible and cost-effective with in vivo validation. Moreover, we demonstrate the feasibility of using these models for precision oncology in real time with clinical care in a case of triple-negative breast cancer (TNBC) with early metastatic recurrence. Our results uncovered a Food and Drug Administration (FDA)-approved drug with high efficacy against the models. Treatment with this therapy resulted in a complete response for the individual and a progression-free survival (PFS) period more than three times longer than their previous therapies. This work provides valuable methods and resources for functional precision medicine and drug development for human breast cancer.
Background Research indicates that dispositional mindfulness is associated with positive psychological functioning. Although this disposition has been linked with beneficial outcomes in the broader mental health literature, less is known about dispositional mindfulness in cancer survivors and how it may be linked with indices of psychological and physical health relevant to cancer survivorship. Methods We conducted a multivariate path analysis of data from a heterogeneous sample of cancer patients (N = 97) to test the Mindfulness-to-Meaning Theory, an extended process model of emotion regulation linking dispositional mindfulness with cancer-related quality of life via positive psychological processes. Results We found that patients endorsing higher levels of dispositional mindfulness were more likely to pay attention to positive experiences (β = .56), a tendency which was associated with positive reappraisal of stressful life events (β = .51). Patients who engaged in more frequent positive reappraisal had a greater sense of meaning in life (β = .43) and tended to savor rewarding or life affirming events (β = .50). In turn, those who engaged in high levels of savoring had better quality of life (β = .33) and suffered less from emotional distress (β = −.54). Conclusions Findings provide support for the Mindfulness-to-Meaning Theory, and help explicate the processes by which mindfulness promotes psychological flourishing in the face of cancer.
Capecitabine is used to treat advanced breast and gastrointestinal malignancies. A single case of encephalopathy and three cases of peripheral neuropathy are the only neurotoxicities reported. The authors report five additional cases of capecitabine-induced multifocal leukoencephalopathy.
Owing to the rare, yet serious nature of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), the authors would like to describe our experience with 41 pediatric patients to contribute to the current clinical understanding of the disease. From records at a single institution, 41 patients ≤18 years of age with a diagnosis of SJS or TEN were retrospectively identified. Data were obtained from the hospital's medical record, and a variety of variables were collected, including causative agent, percentage of total body surface area (%TBSA) slough, ocular involvement, medical treatment, operative procedures, time to wound closure, ventilator days, intensive care unit length of stay, and associated hospital mortality. Of the pediatric TEN patients included, the mean epidermal sloughing was 39.7 ± 26% TBSA. The presumptive inciting agent was a medication in 90% of cases. Mycoplasma pneumoniae was implicated in two cases (5%). The average time between onset of symptoms and burn intensive care unit admission was 3.6 ± 2.0 days. Acutely, 73% of patients exhibited ocular involvement, 90% needed supplemental enteral nutritional support, and 51% required mechanical ventilation. On average, subjects spent 19.9 ± 13.9 days in the intensive care unit. While acute mortality was 0%, 100% of patients still experienced long-term complications and 30% required follow-up procedures. When compared to current literature, the outcomes of our patients were similar to that of pediatric TEN at other institutions. While acute mortality is typically better within the pediatric population, patients still experience a significant level of morbidity and have serious long-term sequelae.
Introduction: The primary aims of this Stage I pilot randomized controlled trial were to establish the feasibility of integrating exercise and nutrition counseling with Mindfulness-Oriented Recovery Enhancement (MORE), a novel intervention that unites training in mindfulness, reappraisal, and savoring skills to target mechanisms underpinning appetitive dysregulation a pathogenic process that contributes to obesity among cancer survivors; to identify potential therapeutic mechanisms of the MORE intervention; and to obtain effect sizes to power a subsequent Stage II trial. Methods: Female overweight and obese cancer survivors (N = 51; mean age = 57.92 ± 10.04; 88% breast cancer history; 96% white) were randomized to one of two 10-week study treatment conditions: ( a ) exercise and nutrition counseling or ( b ) exercise and nutrition counseling plus the MORE intervention. Trial feasibility was assessed via recruitment and retention metrics. Measures of therapeutic mechanisms included self-reported interoceptive awareness, maladaptive eating behaviors, and savoring, as well as natural reward responsiveness and food attentional bias, which were evaluated as psychophysiological mechanisms. Results: Feasibility was demonstrated by 82% of participants who initiated MORE receiving a full dose of the intervention. Linear mixed models revealed that the addition of MORE led to significantly greater increases in indices of interoceptive awareness, savoring, and natural reward responsiveness, and, significantly greater decreases in external eating behaviors and food attentional bias—the latter of which was significantly associated with decreases in waist-to-hip ratio. Path analysis demonstrated that the effect of MORE on reducing food attentional bias was mediated by increased zygomatic electromyographic activation during attention to natural rewards. Conclusions and Implications: MORE may target appetitive dysregulatory mechanisms implicated in obesity by promoting interoceptive awareness and restructuring reward responsiveness.
The NCCN Guidelines for Palliative Care provide interdisciplinary recommendations on palliative care for patients with cancer. The NCCN Guidelines are intended to provide guidance to the primary oncology team on the integration of palliative care into oncology. The NCCN Palliative Care Panel's recommendations seek to ensure that each patient experiences the best quality of life possible throughout the illness trajectory. Accordingly, the NCCN Guidelines outline best practices for screening, assessment, palliative care interventions, reassessment, and after-death care.
Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members’ clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel’s recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.