PPARγ, PTEN, and the Fight against Cancer

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor, which belongs to the family of nuclear hormone receptors. Recent in vitro studies have shown that PPARγ can regulate the transcription of phosphatase and tensin homolog on chromosome ten (PTEN), a known tumor suppressor. PTEN is a susceptibility gene for a number of disorders, including breast and thyroid cancer. Activation of PPARγ through agonists increases functional PTEN protein levels that subsequently induces apoptosis and inhibits cellular growth, which suggests that PPARγ may be a tumor suppressor. Indeed, several in vivo studies have demonstrated that genetic alterations of PPARγ can promote tumor progression. These results are supported by observations of the beneficial effects of PPARγ agonists in the in vivo cancer setting. These studies signify the importance of PPARγ and PTEN's interaction in cancer prevention

The role of nurses in the management of adverse events in patients receiving first-line Axitinib plus immuno-oncology agents for advanced renal cell carcinoma

The recent approval of first-line tyrosine kinase inhibitor plus immuno-oncology agent combination therapy for the treatment of advanced renal cell carcinoma offers substantially improved response rates and survival compared with the previous standard of care. This expansion of treatment options has also led to a greater range and complexity of potential treatment-related adverse events related to overlapping toxicities. The aim of this article is to discuss the management of common treatment-emergent adverse events (AEs) associated with axitinib plus immuno-oncology therapy, highlight the specific roles of oncology nurses in managing these events, and provide AE management resources to aid oncology nurses in their care of patients with advanced renal cell carcinoma

Cowden syndrome affected patients with pten promoter mutations demonstrate abnormal protein translation

Germline mutations of PTEN (phosphatase and tensin homolog deleted on chromosome 10) are associated with the multihamartomatous disorder Cowden syndrome (CS). Moreover, patients with CS with germline PTEN promoter mutations have aberrant PTEN protein expression and an increased frequency of breast cancer. Here, we examined the downstream effect of five PTEN promoter variants (-861G/T, -853C/G, -834C/T, -798G/C, and -764G/A) that are not within any known cis-acting regulatory elements. Clinically, all five of these patients have been given diagnoses of breast, thyroid, and/or endometrial cancer. We demonstrated that protein binding to the PTEN promoter (-893 to -755) was not altered in the five variants when compared with the wild-type (WT) promoter. However, reporter assays indicated that three of the variants (-861G/T, -853C/G, and -764G/A) demonstrated an 50% decrease in luciferase activity compared with the WT construct. PTEN messenger RNA (mRNA) levels were not altered in these variants, whereas secondary structure predictions indicated that different PTEN 5' untranslated region transcript-folding patterns exist in three variants, suggesting an inhibition of protein translation. This was confirmed by PTEN protein analysis. These data indicate that variants causing large mRNA secondary structure alterations result in an inhibition of protein translation and a decrease in PTEN protein expression. These data emphasize the importance of PTEN promoter nucleotide variations and their ability to lead to CS progression by a novel regulatory mechanism. Importantly, these patients have a high prevalence of breast, thyroid, and endometrial malignancies; thus, understanding of the mechanism of PTEN dysfunction in these patients will lead to more-sensitive molecular diagnostic and predictive testing and, ultimately, to rational targeted therapies to treat or prevent malignanc

Mobile Health Technology Is Here-But Are Hospice Informal Caregivers Receptive?

Mobile health applications (mHealth apps) represent a rapidly emerging technology that is being used to improve health-care delivery. In home hospice, informal caregivers play an essential role in attending to the day-to-day needs of their terminally ill loved ones. Using mHealth apps by caregivers in this setting could potentially improve the support provided to both patients and caregivers at the end of life (EoL). To explore informal caregivers' receptivity and concerns in using mHealth apps along with app features, caregivers perceived to be most useful in home hospice care. Eighty semistructured phone interviews were conducted with informal caregivers who received care from a nonprofit hospice organization. Study data were analyzed using content analysis, coding for themes of receptivity and interest. Sixty-two (78%) participants were receptive to using an mHealth app in home hospice care. Informal caregivers were interested in features that addressed: (1) communication to improve patient care (n = 44, 70%), (2) access to patient care information (n = 30, 48%), (3) education (n = 24, 39%), and (4) updates from health-care personnel and scheduling services (n = 10, 16%). A substantial majority of informal caregivers voiced receptivity to using mHealth apps and expressed interest in features that enhance communication and provide information to improve patient care. Although more research is needed to examine how to incorporate this technology into existing home hospice care, our study suggests that informal caregivers are likely to use this technology they feel will help enhance home-based EoL care delivery

Supplementary Figures S1-S6 from Integrative Analyses of Tumor and Peripheral Biomarkers in the Treatment of Advanced Renal Cell Carcinoma

Supplementary Figure S1 shows forest plots of PFS according to numbers of circulating cell populations in the overall trial population (both arms combined) at baseline. Supplementary Figure S2 shows forest plots of PFS with A+Ax or sunitinib according to cytokine, chemokine, or protein concentrations in peripheral blood at baseline and during treatment (cycle 2 day 1). Supplementary Figure S3 shows PFS according to metrics describing TCR repertoire change from baseline to cycle 2 day 1 with A+Ax vs sunitinib. Supplementary Figure S4 shows PFS according to updated mutation subgroup definitions and treatment group. Supplementary Figure S5 shows normalized numbers of total T cells in pretreatment tumors according to molecular subgroup. Supplementary Figure S6 shows peripheral T-cell receptor quantitation and clonality metrics at baseline and cycle 2 day 1 by mutation subgroup.</p