Snail transcription factor can induce epithelial-mesenchymal transition (EMT), associated with decreased cell adhesion-associated molecules like E-cadherin, increased mesenchymal markers like vimentin, leading to increased motility, invasion and metastasis. Muscadine grape skin extract (MSKE) has been shown to inhibit prostate cancer cell growth and induce apoptosis without affecting normal prostate epithelial cells. We investigated novel molecular mechanisms by which Snail promotes EMT in prostate cancer cells via Reactive Oxygen Species (ROS) and whether it can be antagonized by MSKE.
Objective: Cancer imposes higher burden on men. Sex differences in healthcare utilization may contribute to this problem. We compared healthcare utilization among adults with and without a history of cancer as measured by having at least one physician visit within the previous 12 months. Material and methods: We analyzed data from 7,229 responders (weighted population size=211,722,892) enrolled in the 2007 Health Information and National Trends Survey (HINTS), a nationally representative sample of non-institutionalized adults in the United States. We used survey weights in all analyses and variance estimation procedures to account for the complex survey design and used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Study participants consisted of 2808 (48.6%) males and 4421 (51.4%) females. Overall, men were less likely to have seen a physician within the previous 12 months (OR=0.39; 95% CI: 0.31-0.48) regardless of their cancer status. Cancer survivors were more likely to visit a physician within the previous 12 months (OR=2.01; 95% CI: 1.28-3.19) regardless of sex. When stratified by personal history of cancer, men without a history of cancer were less likely to visit a physician (OR=0.38; 95% CI: 0.30-0.47) whereas men with a history of cancer were as likely to have seen a physician in the previous 12 months as women with similar cancer status (OR=1.24; 95% CI: 0.44-3.45). Conclusion: Men increase their healthcare utilization to that of women only after they receive diagnosis of cancer. Targeted interventions to promote utilization of preventive care services by men are needed to reduce the burden of chronic illnesses including cancer among men. Cite this article as: Burnside C, Hudson T, Williams C, Lawson W, Laiyemo AO. Sex differences in the use of healthcare services among US adults with and without a cancer diagnosis. Turk J Urol 2018; 44: 298-302.
Challenges to docetaxel use in prostate cancer treatment include several resistance mechanisms as well as toxicity. To overcome these challenges and to improve the therapeutic efficacy in heterogeneous prostate cancer, the use of multiple agents that can destroy different subpopulations of the tumor is required. Brusatol, a multitarget inhibitor, has been shown to exhibit potent anticancer activity and play an important role in drug response and chemoresistance. Thus, the combination of brusatol and docetaxel in a nanoparticle platform for the treatment of prostate cancer is expected to produce synergistic effects. In this study, we reported the development of polymeric nanoparticles for the delivery of brusatol and docetaxel in the treatment of prostate cancer. The one-factor-at-a-time method was used to screen for formulation and process variables that impacted particle size. Subsequently, factors that had modifiable effects on particle size were evaluated using a 24 full factorial statistical experimental design followed by the optimization of drug loading. The optimization of blank nanoparticles gave a formulation with a mean size of 169.1 nm ± 4.8 nm, in agreement with the predicted size of 168.333 nm. Transmission electron microscopy showed smooth spherical nanoparticles. The drug release profile showed that the encapsulated drugs were released over 24 h. Combination index data showed a synergistic interaction between the drugs. Cell cycle analysis and the evaluation of caspase activity showed differences in PC-3 and LNCaP prostate cancer cell responses to the agents. Additionally, immunoblots showed differences in survivin expression in LNCaP cells after treatment with the different agents and formulations for 24 h and 72 h. Therefore, the nanoparticles are potentially suitable for the treatment of advanced prostate cancer.
Previously we demonstrated that muscadine grape skin extract (MSKE), a natural product, significantly inhibited androgen-responsive prostate cancer cell growth by inducing apoptosis through the targeting of survival pathways. However, the therapeutic effect of MSKE on more aggressive androgen-independent prostate cancer remains unknown. This study examined the effects of MSKE treatment in metastatic prostate cancer using complementary PC-3 cells and xenograft model. MSKE significantly inhibited PC-3 human prostate cancer cell tumor growth in vitro and in vivo. The growth-inhibitory effect of MSKE appeared to be through the induction of cell-cycle arrest. This induction was accompanied by a reduction in the protein expression of Hsp40 and cell-cycle regulation proteins, cyclin D1 and NF-kBp65. In addition, MSKE induced p21 expression independent of wild-type p53 induced protein expression. Moreover, we demonstrate that MSKE significantly inhibited cell migration in PC-3 prostate cancer cells. Overall, these results demonstrate that MSKE inhibits prostate tumor growth and migration, and induces cell-cycle arrest by targeting Hsp40 and proteins involved in cell-cycle regulation and proliferation. This suggests that MSKE may also be explored either as a neo-adjuvant or therapeutic for castration resistant prostate cancer.
A review of literature on the expression of Annexin 2 in cancer has shown that there is very limited research work on the association of this protein with breast cancer aggressiveness in African Americans. In the present study, TMA breast tissues from African American women were stained with Annexin 2 antibody to determine the association between the molecular subtypes and Annexin 2 protein expression. An annotated case series of 135 breast cancer tissues archived from 2000 to 2010 was acquired from the Howard University Tumor Registry. The association between ANX2 expression and survival by molecular subtypes Luminal A, Luminal B, HER2, and Triple Negative (TN) was assessed using Multinomial regression, chi-square analysis, and Kaplan-Meir graphs (Stata 11). Our findings show a marked association between ANX2 protein expression in Luminal B and HER2 subtypes unadjusted and when adjusted for age. Borderline differences in tumor grade were found in TN only.Univariately, age (<50, 50 + years) and metastases were highly significant for overall survival, disease-free survival and recurrence-free survival. Stage, tumor size, and nodal involvement were of borderline or greater significance for overall and disease-free survival. ANX2 expression was not significant. Kaplan Meier tests of ANX2 showed significant separation of overall survival by ANX2 protein expression in all breast tumor subtypes. In multivariate analyses comparing TN to Luminal A, ANX2 was not important while controlling for age and grade. ANX2 might be a biomarker of aggressiveness and a relevant candidate biomarker in high risk African American women with Luminal B and HER2 breast cancer.