Caveolin-1 has a complex role in prostate cancer and has been suggested to be a potential biomarker and therapeutic target. As mature caveolin-1 resides in caveolae, invaginated lipid raft domains at the plasma membrane, caveolae have been suggested as a tumor-promoting signaling platform in prostate cancer. However, caveola formation requires both caveolin-1 and cavin-1 (also known as PTRF; polymerase I and transcript release factor). Here, we examined the expression of cavin-1 in prostate epithelia and stroma using tissue microarray including normal, non-malignant and malignant prostate tissues. We found that caveolin-1 was induced without the presence of cavin-1 in advanced prostate carcinoma, an expression pattern mirrored in the PC-3 cell line. In contrast, normal prostate epithelia expressed neither caveolin-1 nor cavin-1, while prostate stroma highly expressed both caveolin-1 and cavin-1. Utilizing PC-3 cells as a suitable model for caveolin-1-positive advanced prostate cancer, we found that cavin-1 expression in PC-3 cells inhibits anchorage-independent growth, and reduces in vivo tumor growth and metastasis in an orthotopic prostate cancer xenograft mouse model. The expression of α-smooth muscle actin in stroma along with interleukin-6 (IL-6) in cancer cells was also decreased in tumors of mice bearing PC-3-cavin-1 tumor cells. To determine whether cavin-1 acts by neutralizing caveolin-1, we expressed cavin-1 in caveolin-1-negative prostate cancer LNCaP and 22Rv1 cells. Caveolin-1 but not cavin-1 expression increased anchorage-independent growth in LNCaP and 22Rv1 cells. Cavin-1 co-expression reversed caveolin-1 effects in caveolin-1-positive LNCaP cells. Taken together, these results suggest that caveolin-1 in advanced prostate cancer is present outside of caveolae, because of the lack of cavin-1 expression. Cavin-1 expression attenuates the effects of non-caveolar caveolin-1 microdomains partly via reduced IL-6 microenvironmental function. With circulating caveolin-1 as a potential biomarker for advanced prostate cancer, identification of the molecular pathways affected by cavin-1 could provide novel therapeutic targets.

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5–2.5 nm. The host-guest association constant K a was 1,639 M−1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.

The increasing burden of obesity worldwide and its effect on cardiovascular disease (CVD) risk is an opportunity for evaluation of preventive approaches. Both obesity and CVD have a genetic background and polymorphisms within genes which enhance expression of variant proteins that influence CVD in obesity. Genome‐based prediction may therefore be a feasible strategy, but the identification of genetically driven risk factors for CVD manifesting as clinically recognized phenotypes is a major challenge. Clusters of such risk factors include hyperglycaemia, hypertension, ectopic liver fat, and inflammation. All involve multiple genetic pathways having complex interactions with variable environmental influences. The factors that make significant contributions to CVD risk include altered carbohydrate homeostasis, ectopic deposition of fat in muscle and liver, and inflammation, with contributions from the gut microbiome. A futuristic model depends on harnessing the predictive power of plausible genetic variants, phenotype reversibility, and effective therapeutic choices based on genotype–phenotype interactions. Inverting disease phenotypes into ideal cardiovascular health metrics could improve genetic and epigenetic assessment, and form the basis of a future model for risk detection and early intervention.

Background Coronavirus disease 2019 (COVID‐19) has impacted cancer care globally. The aim of this study is to analyze the impact of COVID‐19 on cancer healthcare from the perspective of patients with cancer. Methods A cross‐sectional survey was conducted between June 19, 2020, to August 7, 2020, using a questionnaire designed by patients awaiting cancer surgery. We examined the impact of COVID‐19 on five domains (financial status, healthcare access, stress, anxiety, and depression) and their relationship with various patient‐related variables. Factors likely to determine the influence of COVID‐19 on patient care were analyzed. Results A significant adverse impact was noted in all five domains (p =  < 0.05), with the maximal impact felt in the domain of financial status followed by healthcare access. Patients with income levels of INR < 35 K (adjusted odds ratio [AOR] = 1.61, p < 0.05), and 35K‐ 100 K (AOR = 1.96, p < 0.05), married patients (AOR = 3.30, p < 0.05), and rural patients (AOR = 2.82, p < 0.05) experienced the most adverse COVID‐19‐related impact. Conclusion Delivering quality cancer care in low to middle‐income countries is a challenge even in normal times. During this pandemic, deficiencies in this fragile healthcare delivery system were exacerbated. Identification of vulnerable groups of patients and strategic utilization of available resources becomes even more important during global catastrophes, such as the current COVID‐19 pandemic. Further work is required in these avenues to not only address the current pandemic but also any potential future crises.