Gravgaardvang6134

Prostate cancers are reliant on androgens for growth and survival. Clinicians and researchers are looking for potent treatments for the resistant forms of prostate cancer; however, a handful of small molecules used in the treatment of castration-resistant prostate cancer have not shown potent effects owing to the mutations in the AR (Androgen Receptor). We used SBF-1, a well-characterized antitumor agent with potent cytotoxic effects against different kinds of cancers and investigated its effect on human prostate cancer. SBF-1 substantially inhibited the proliferation, induced apoptosis, and caused cell cycle arrest in LNCaP and PC3/AR+ prostate cancer cell lines. SBF-1 inhibited the activation of the IGF-1-PNCA pathway, as demonstrated by decreased expression of IGF-1 (insulin-like growth factor 1), proliferating cell nuclear antigen (PCNA), and its downstream Bcl-2 protein. Using microscale thermophoresis (MST) and isothermal titration calorimetry (ITC) assays, we observed a direct binding of SBF-1 to the AR. SBF-1 binds to the AR-DBD (DNA-binding domain) and blocks the transcription of its target gene. SBF-1 demonstrated a potent antitumor effect in vivo; it inhibited AR signaling and suppressed tumor growth in animals. Our study suggests that SBF-1 is an inhibitor of the AR and might be used in the treatment of prostate cancer.Infantile hemangioma is the most common vascular tumor of childhood. It is characterized by clinical expansion of endothelial cells and promoted by angiogenic factors. Luteolin is a flavonoid compound that carries anti-cancer and anti-angiogenesis properties. The study aimed to investigate the effect of luteolin in treating infantile hemangioma. We first tested the effect of luteolin on cell proliferative potential and VEGFA expression in hemangioma-derived stem cells (HemSCs). We then examined the efficacy of systemic application of luteolin in a murine hemangioma model. We then identified the downstream factor regulated by luteolin in HemSCs and validated its causative relationship with knock-down method in both in vitro and in vivo models. We also investigated the protein expression change of this targeting factor in proliferating hemangiomas. Luteolin inhibited HemSC growth and suppressed VEGF-A expression in a dose-dependent manner. Luteolin inhibited microvessel formation and de novo vasculogenesis in the murine model. FZD6 was induced by luteolin and exerted the anti-angiogenesis effect in our tumor models. Lastly, FZD6 level was repressed in the clinical tissues of human proliferating hemangiomas. Luteolin is a promising new agent to treat infantile hemangioma. Targeting the Wnt pathway may represent a potential therapeutic strategic to inhibit angiogenesis in proliferating hemangiomas.Background Gemcitabine plus cisplatin is regarded as the standard first-line therapy for patients with advanced biliary tract cancer (BTC); however, no standard chemotherapy has yet been recommended after treatment failure. Modified FOLFIRINOX (mFOLFIRINOX) appears to be a better-tolerated regimen, which leads to improved survival in metastatic pancreatic cancer that has histological and molecular similarities with BTC. We assessed the efficacy and safety of mFOLFIRINOX as salvage therapy in advanced BTC patients who were refractory to previous chemotherapy. Methods A total of 15 consecutive patients with documented unresectable locally advanced or metastatic BCT who received the mFOLFIRINOX regimen were included in the study. Patients were intravenously administrated with oxaliplatin (65 mg/m2), leucovorin (400 mg/m2), irinotecan (150 mg/m2), and continuous infusion of fluorouracil (2400 mg/m2) over 46 h. The objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were recorded. Results At least three cycles of mFOLFIRINOX regimen were delivered to 15 patients with a median number of 6.0 cycles (IQR 5.5-11.0). The median duration of treatment was 3.8 months (IQR 2.9-8.5). Four patients (26.7%) achieved an ORR, and 12 patients (80.0%) had a DCR. The median PFS and OS were 6.7 months (95%CI 2.3-11.1) and 13.2 months (95%CI 7.3-19.1), respectively. Five patients (33.3%) had treatment-related grade 3/4 AEs. The most common grade 3/4 AE was neutropenia (n = 3, 20.0%), while there was no occurrence of febrile neutropenia. Conclusion Treatment with mFOLFIRINOX has promising efficacy and favorable tolerance as salvage therapy in patients with refractory advanced BCT.Sexual communication with partners informs risk assessment and sexual practices. We evaluated participant, partner, and network factors associated with communication about condom use and HIV serostatus and explored their relationships with condomless anal intercourse (CAI) among 446 men who have sex with men (MSM) and 122 transgender women (TW) in Lima, Peru. Generalized estimating equations assessed contextual influences on communication and practices with recent sexual partners. More frequent HIV communication was reported by MSM who identified as heterosexual, compared to bisexual or gay; characterized partnerships as stable, compared to casual, anonymous, or commercial; or discussed HIV/STIs with close social contacts (p  less then  0.05). TW in concurrent partnerships discussed condom use more frequently than those in monogamous relationships (p  less then  0.05). Condom use discussions and alcohol use among MSM were associated with CAI (p  less then  0.05). Findings highlight complexity in sexual decision-making and call for further study of conversation content and practices to inform HIV prevention messaging.Although many students benefit from evidence-based reading comprehension interventions, not all students will exhibit adequate response. Moderation analysis provides a statistical approach to examine for whom and under what conditions interventions are most effective. Conducted within a parent project, which investigated the effects of an inferential reading comprehension intervention, the current study examined factors related to the deployment of students' attention as well as language status that might be associated with differential response to intervention. Sixty-six struggling middle school readers were randomly assigned to a computerized version of the intervention, a teacher-led version, or business-as-usual (BaU) control instruction. The influence of language status (i.e., English Learner status) and pre-intervention levels of mind-wandering, anxiety, and mindset on the effects of the inferential reading comprehension intervention were examined. There were no moderator effects for the teacher-led group compared to the BaU control. Conversely, anxiety, mind-wandering, and language status moderated the effects of the computer-led intervention for some reading and inference-making outcomes. The computer-led intervention was associated with improved inference-making for students with higher levels of self-reported anxiety and mind-wandering. In contrast, the computer-led intervention was less beneficial than BaU instruction for English learners. Findings are discussed with respect to how these factors might be relevant for interpreting the effects of interventions for struggling middle school readers in general, and for English learners in particular. The findings also point to the importance of considering the characteristics of both student and instructional features in the creation and testing of reading comprehension interventions.Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis. Graphical Abstract.Increasing evidence suggests that diabetes also targets lung tissues resulting in structural and physiological abnormalities. The present study evaluated the impact of pristine C60 fullerene (C60) against diabetes-induced lung damage for the first time. The objective was to evaluate the impacts of Curcumin (Cur), C60 and C60 fullerene+Curcumin (C60 + Cur) combination on oxidative stress (MDA, GSH, CAT, GST, Retinol, α-tocopherol), apoptosis (Caspase-3, Bcl-2), cholesterol and fatty acid profile (160,180,181,182, 224, 226) against changes in the lung tissue of diabetic rats. Streptozotocin (STZ) was used for inducing diabetes with Cur, C60 and C60 + Cur combination administered for eight weeks to treat diabetic and control rats. Increased oxidative stress, apoptosis and significant changes in cell structure were observed in the lung tissues of diabetic rats. The combination of Cur, C60 and C60 + Cur reduced oxidative stress in the lung tissue of diabetic rats while increasing the antioxidant defense capacity of the tissue, exhibiting tissue protective properties against apoptosis. The diabetic rats displayed favorable properties against lipotoxicity-induced tissue damage due to the increase in the fatty acid and cholesterol levels in lung tissue. It was observed that Cur, C60 and C60 + Cur combination displays protective effects against hyperglycemia induced oxidative damage to lung tissue. Oxidative stress, prevention of lipid and cholesterol accumulation, and weakening of lung apoptosis may be associated with these effects.

Gains in cancer detection and treatment have meant that more patients are now living with both cancer and other chronic health conditions, which may become burdensome. We used the Patient Experience with Treatment and Self-Management (PETS) framework to study challenges in self-management and its impact on health among survivors of women's cancers who are caring for other chronic health conditions.

Applicability of the PETSdomains among survivors of women's cancers with comorbidities was assessed in focus groups to create the study survey. find more Women surviving primary breast, cervical, ovarian, or endometrial/uterine cancer treated between 6 months and 3 years prior at two large healthcare systems in Virginia were mailed study invitation letters to complete a telephone-based survey. The survey included questions on cancer treatment history, comorbid conditions prior to cancer, treatment and self-management experiences, health literacy, financial security, and items on self-management activities, self-management difficulties and self-management impact (i.