Development of a Bladder Cancer-on-a-Chip Model to Assess Bladder Cancer Cell Invasiveness.

We have developed a bladder cancer-on-a-chip model which supports the 3D growth of cells and can be used to assess and quantify bladder cancer cell invasiveness in a physiologically appropriate environment. Three bladder cancer cell lines (T24, J82, and RT4) were resuspended in 50% Matrigel and grown within a multi-channel organ-on-a-chip system. The ability of live cells to invade across into an adjacent 50% Matrigel-only channel was assessed over a 2-day period.

Impact of high-stakes exams, incentives, and preparation on student performance: Insights from the pharmacy curriculum outcomes assessment.

Introduction: Efforts to ensure success of pharmacy students in passing pharmacy standardized exams require substantial investments. Engaging students effectively can be a challenge when there are no consequences for non-participation or poor performance. This study examined how engagement reinforcement, including high-stake exam requirements, instructional strategies, and incentives, impacted student performance on the Pharmacy Curriculum Outcomes Assessment (PCOA).

A pharmacist-led community-based survey study: Determining the impact of the Covid-19 pandemic on actionable factors associated with worse cancer outcomes and cancer health disparities.

Purpose: The goals of this cross-sectional community-based survey study were to assess the impact of the Covid-19 pandemic on actionable factors which are known to contribute to worse cancer outcomes, and to determine whether race and ethnicity-based differences exist.

Methods: A survey study which captured demographic information and changes in cancer outcomes-related factors since the start of the Covid-19 pandemic, was conducted at a public Covid-19 vaccination clinic over a period of 10 days during March 2021. Surveys were administered in multiple languages.

Effectiveness of an Advanced Naloxone Training, Simulation, and Assessment of Second-Year Pharmacy Students.

Opioid overdoses continue to be one of the most urgent public health priorities. In 2020, reported overdose deaths in the United States reached a high of over 93,000 cases. As the COVID-19 pandemic and opioid crisis continues to be addressed, life-saving agents must be more widely accessible to those with a high overdose risk.

Exploring the therapeutic potential of Neem () for the treatment of prostate cancer: a literature review.

Background And Objective: Multiple studies have demonstrated the medical potency of plant extracts and specific phytochemicals as therapeutics for prostate cancer (PCa) patients. Of note, the Neem plant known for its role as an antibiotic and anti-inflammatory is underexplored with an untapped potential for further development. This review focuses on extracts and phytochemicals derived from the Neem tree (Latin name; ), commonly used throughout Southeast Asia for the prevention and treatment of a wide array of diseases including cancer.

COVID-19-Driven Improvements and Innovations in Pharmacy Education: A Scoping Review.

The COVID-19 pandemic led to many colleges of pharmacy having to make major changes relating to their infrastructure and delivery of their curriculum within a very short time frame, including the transition of many components to an online setting. This scoping review sought to summarize what is known about the impact of COVID-19 on pharmacy education and the effectiveness of adaptation strategies which were put in place. PubMed, Web of Science, OVID Medline, and MedEdPortal were searched to identify pharmacy education-related articles published since the beginning of the COVID-19 pandemic.

Use of RNA-Seq and a Transgenic Mouse Model to Identify Genes Which May Contribute to Mutant p53-Driven Prostate Cancer Initiation.

We previously demonstrated that the mutation can drive prostate cancer (CaP) initiation using the FVB.129S4 (Trp53); FVB.129S (Nkx3-1) genetically engineered mouse model (GEM).

Use of Team-Based Learning Pedagogy to Prepare for a Pharmacy School Accreditation Self-Study.

Ensuring adequate engagement and preparation of all stakeholders in an accreditation self-study can be challenging for many reasons, including lack of motivation and inadequate understanding of expectations and procedures. The goal of this exploratory study was to determine whether using team-based learning (TBL) pedagogy to deliver an accreditation preparation workshop could effectively prepare and engage participants. A Likert-scale questionnaire was administered to workshop attendees ( = 52) to determine whether they found TBL-based training helpful and whether it promoted engagement.

Androgen Receptor-Mediated Nuclear Transport of NRDP1 in Prostate Cancer Cells Is Associated with Worse Patient Outcomes.

To our knowledge, our group is the first to demonstrate that NRDP1 is located in the nucleus as well as the cytoplasm of CaP cells. Subcellular fractionation, immunohistochemistry, and immunofluorescence analysis combined with confocal microscopy were used to validate this finding. Subcellular fractionation followed by western blot analysis revealed a strong association between AR and NRDP1 localization when AR expression and/or cellular localization was manipulated via treatment with R1881, AR-specific siRNA, or enzalutamide.

Use of Concept Mapping to Identify Expectations of Pharmacy Students Selecting Elective Courses.

The objective of this study was to demonstrate the use of concept mapping as a method for analyzing pharmacy students' qualitative perceptions of their expectations of elective courses and to thus help guide delivery methods and course content. A survey containing demographic, Likert scale, and open-ended questions was administered to second-year pharmacy students prior to the start of elective courses and an innovative methodology, concept mapping, was used to identify major themes relating to student expectations. The association between preferred class delivery method (online versus in person) with student gender and English-as-a-second-language status (ESL) was also assessed.

Use of End-of-Class Quizzes to Promote Pharmacy Student Self-Reflection, Motivate Students to Improve Study Habits, and to Improve Performance on Summative Examinations.

Underperforming students are often unaware of deficiencies requiring improvement until after poor performance on summative exams. The goal of the current study was to determine whether inclusion of individual end-of-class formative quizzes, which comprise of higher level Bloom's questions, could encourage students to reflect on and address deficiencies and improve academic performance. Ninety-seven out of 123 first-year pharmacy students (79%) enrolled in a Biochemistry and Cell & Molecular Biology course participated in a single-blinded, randomized, controlled, crossover study.

Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells.

Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines; GCP can inhibit intracrine androgen synthesis in CaP cells. UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels ( < 0.

Impact of Completion of a Pre-Pharmacy Biochemistry Course and Competency Levels in Pre-Pharmacy Courses on Pharmacy Student Performance.

Poor performance in foundational science courses, which are usually taken during the first or second year of pharmacy school, can have several negative consequences including increases in student drop-out rates and increases in the number of dismissals and remediating students. The primary goal of the current study was to determine whether completion of a pre-pharmacy biochemistry course and/or performance on a biochemistry competency test (administered at the beginning of the pharmacy program) are associated with pharmacy student performance in foundational science courses and overall academic performance. A secondary goal was to determine whether performance in pre-pharmacy courses and/or student demographics are associated with pharmacy student performance.

Obatoclax, a BH3 Mimetic, Enhances Cisplatin-Induced Apoptosis and Decreases the Clonogenicity of Muscle Invasive Bladder Cancer Cells via Mechanisms That Involve the Inhibition of Pro-Survival Molecules as Well as Cell Cycle Regulators.

Several studies by our group and others have determined that expression levels of Bcl-2 and/or Bcl-xL, pro-survival molecules which are associated with chemoresistance, are elevated in patients with muscle invasive bladder cancer (MI-BC). The goal of this study was to determine whether combining Obatoclax, a BH3 mimetic which inhibits pro-survival Bcl-2 family members, can improve responses to cisplatin chemotherapy, the standard of care treatment for MI-BC. Three MI-BC cell lines (T24, TCCSuP, 5637) were treated with Obatoclax alone or in combination with cisplatin and/or pre-miR-34a, a molecule which we have previously shown to inhibit MI-BC cell proliferation via decreasing Cdk6 expression.

XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies.

Treatment options for high grade urothelial cancers are limited and have remained largely unchanged for several decades. Selinexor (KPT-330), a first in class small molecule that inhibits the nuclear export protein XPO1, has shown efficacy as a single agent treatment for numerous different malignancies, but its efficacy in limiting bladder malignancies has not been tested. In this study we assessed selinexor-dependent cytotoxicity in several bladder tumor cells and report that selinexor effectively reduced XPO1 expression and limited cell viability in a dose dependent manner.

MicroRNA profiling of dogs with transitional cell carcinoma of the bladder using blood and urine samples.

Background: Early signs of canine transitional cell carcinoma (TCC) are frequently assumed to be caused by other lower urinary tract diseases (LUTD) such as urinary tract infections, resulting in late diagnosis of TCC which could be fatal. The development of a non-invasive clinical test for TCC could dramatically reduce mortality. To determine whether microRNAs (miRNAs) can be used as non-invasive diagnostic biomarkers, we assessed miRNA expression in blood and/or urine from dogs with clinically normal bladders (n = 28), LUTD (n = 25), and TCC (n = 17).

Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy.

The identification and development of biomarkers which predict response of muscle invasive bladder cancer (MIBC) patients to neoadjuvant chemotherapy would likely increase usage of this treatment option and thereby improve patient survival rates. MiRNA array and qRT-PCR validation was used to identify miRNA which are associated with response to neoadjuvant chemotherapy. RNA was extracted from a total of 41 archival, fully annotated, MIBC patient diagnostic biopsies (20 chemo-responders and 21 non-responders (response is defined as > 5 year survival rate and being pT0 post-chemotherapy)).

Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer.

We report herein the development, functional and molecular characterization of an isogenic, paired bladder cancer cell culture model system for studying platinum drug resistance. The 5637 human bladder cancer cell line was cultured over ten months with stepwise increases in oxaliplatin concentration to generate a drug resistant 5637R sub cell line. The MTT assay was used to measure the cytotoxicity of several bladder cancer drugs.

The role of EGFR family inhibitors in muscle invasive bladder cancer: a review of clinical data and molecular evidence.

Purpose: Conventional platinum based chemotherapy for advanced urothelial carcinoma is plagued by common resistance to this regimen. Several studies implicate the EGFR family of RTKs in urothelial carcinoma progression and chemoresistance. Many groups have investigated the effects of inhibitors of this family in patients with urothelial carcinoma.

Expression of microRNAs in urinary bladder samples obtained from dogs with grossly normal bladders, inflammatory bladder disease, or transitional cell carcinoma.

Objective: To determine expression of microRNA (miRNA) in urinary bladder samples obtained from dogs with grossly normal urinary bladders, inflammatory bladder disease, or transitional cell carcinoma (TCC) and in cells of established canine TCC cell lines.

Sample: Samples of grossly normal bladders (n = 4) and bladders from dogs with inflammatory bladder disease (13) or TCC (18), and cells of 5 established canine TCC cell lines.

Procedures: Expression of 5 miRNAs (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) that target p53, Rb, or Bcl-2 protein pathways was determined for bladder samples and cells via quantitative real-time PCR assay.

Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization.

As prostate cancer (CaP) is regulated by androgen receptor (AR) activity, metastatic CaP is treated with androgen deprivation therapy (ADT). Despite initial response, patients on ADT eventually progress to castration-resistant CaP (CRPC), which is currently incurable. We previously showed that cleavage of the 280 kDa structural protein Filamin A (FlnA) to a 90 kDa fragment, and nuclear localization of the cleaved product, sensitized CRPC cells to ADT.

Initiation of prostate cancer in mice by Tp53R270H: evidence for an alternative molecular progression.

Tp53 mutations are common in human prostate cancer (CaP), occurring with a frequency of ∼30% and ∼70% in localized and metastatic disease, respectively. In vitro studies have determined several common mutations of Tp53 that have specific gain-of-function properties in addition to loss of function, including the ability to promote castration-resistant (CR) growth of CaP cells in some contexts. To date, a lack of suitable mouse models has prohibited investigation of the role played by Tp53 mutations in mediating CaP progression in vivo.

Dual EGFR/HER2 inhibition sensitizes prostate cancer cells to androgen withdrawal by suppressing ErbB3.

Purpose: Patients with recurrent prostate cancer are commonly treated with androgen withdrawal therapy (AWT); however, almost all patients eventually progress to castration resistant prostate cancer (CRPC), indicating failure of AWT to eliminate androgen-sensitive prostate cancer. The overall goal of these studies is to determine whether dual inhibition of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER2 would prolong the effectiveness of this treatment in prostate cancer.

Experimental Design: We used androgen-dependent LNCaP cells and its CRPC sublines LNCaP-AI and C4-2.

Dual blockade of PKA and NF-κB inhibits H2 relaxin-mediated castrate-resistant growth of prostate cancer sublines and induces apoptosis.

We previously demonstrated that H2 relaxin (RLN2) facilitates castrate-resistant (CR) growth of prostate cancer (CaP) cells through PI3K/Akt/β-catenin-mediated activation of the androgen receptor (AR) pathway. As inhibition of this pathway caused only ~50% reduction in CR growth, the goal of the current study was to identify additional RLN2-activated pathways that contribute to CR growth. Next-generation sequencing-based transcriptome and gene ontology analyses comparing LNCaP stably transfected with RLN2 versus LNCaP-vector identified differential expression of genes associated with cell proliferation (12.

MiR-34a chemosensitizes bladder cancer cells to cisplatin treatment regardless of p53-Rb pathway status.

MiR-34a is a downstream effector of p53 that has been shown to target several molecules associated with cell cycle and cell survival pathways. As alterations in these pathways are frequent in muscle invasive transitional cell carcinoma of the bladder (MI-TCC), for example mutation or loss of p53 and Rb, the goal of this study was to determine whether manipulation of miR-34a expression levels could abrogate the effect of these alterations and sensitize bladder cancer cells to chemotherapy. We demonstrate that transfection of T24, TCCSUP and 5637 with pre-miR-34a followed by cisplatin treatment results in a dramatic reduction in clonogenic potential and induction of senescence compared to treatment with cisplatin alone.