Differential involvement of glutathione S‐transferase mu 1 and multidrug resistance protein 1 in melanoma acquired resistance to vinca alkaloids

On account of its extreme intrinsic resistance to apoptosis and of its strong ability to become chemoresistant after a primary response to drugs, malignant melanoma (MM) is still a therapeutic challenge. We previously showed that glutathione S‐transferase mu 1 (GSTM1) acts in synergy with multidrug resistance protein 1 (MRP1) to protect GSTM1‐transfected human CAL1 melanoma cells from toxic effects of vincristine (VCR). Herein, we investigated the role of these proteins in the acquired resistance of CAL1 cells to vinca alkaloids (VAs). Resistant lines were established by continuous exposure (>1 year) of parental CAL1‐wt cells to VCR, vindesine (VDS), or vinorelbine (VRB): CAL1R‐VCR, CAL1R‐VDS, CAL1R‐VRB, respectively. All resistant lines displayed more than 10‐fold increase in resistance to their selection VA, and specifically expressed GSTM1. Suggesting a direct interaction between this protein and VAs, each VA specifically decreased the GSTM1‐mediated glutathione conjugation activity in cell lysates. Curcumin (GSTM1 inhibitor), BSO (glutathione synthesis inhibitor), and MK571 (MRP1 inhibitor) considerably reversed the acquired resistance to VCR and VDS, but not to VRB. Microarray data analysis revealed similar gene expression patterns of CAL1R‐VCR and CAL1R‐VDS, and a distinct one for CAL1R‐VRB. These data suggest a differential involvement of GSTM1 and MRP1 in acquired resistance to VAs. A coordinated expression and activity of GSTM1 and MRP1 is required to protect CAL1 cells from VCR and VDS, while the simple expression of GSTM1 is sufficient, possibly by a direct drug/protein interaction, to confer resistance against VRB.     

Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence,progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.     

Yakima Valley Farm Workers Clinic oral health transformation project

The Yakima Valley Farm Workers Clinic (YVFWC) is one of the largest community health centers in the country with clinics throughout south-central Washington and northern Oregon. Its dental program consists of 14 dental clinics providing general and specialty services to the low-income populations it serves. Modeling itself after the YVFWC medical managed care program; the Dental program recently added value-based metrics to its dental practice after Oregon offered a value-based dental reimbursement plan in 2019. This is the first-step YVFWC's dental program that has taken to prepare for value-based reimbursement and transform its dental practice in order to reduce the disease burden in its patient population. The purpose of this article is to describe the processes YVFWC undertook to prepare itself for the new reimbursement model, which included the development of metrics, a metric validation process, a clinical dashboard, and a method for improving metrics. It also outlines its medical/dental integration improvement brought about by embedding hygienists into the medical primary care teams.     

Magnetic detection of sentinel nodes in oral squamous cell carcinoma by means of superparamagnetic iron oxide contrast

The aim was to evaluate sentinel node detection capacity by means of a magnetic probe in 11 patients with oral squamous cell carcinoma at stages T1-T2 received submucosal injections of a superparamagnetic iron oxide contrast agent (SPIO). A magnetic probe was used for sentinel node biopsy. The use of SPIO and magnetic probes in the early stages of oral cancer may offer an alternative to conventional radioisotope techniques and/or elective neck dissection.