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. Prospective univariate analyses (n = 75) determined that completion of a pre-pharmacy biochemistry course is not associated with pharmacy student performance. However, performance on a biochemistry competency test was associated with performance in Biochemistry and Cell&Molecular Biology (p = 0.002). Furthermore, post-hoc analyses determined that pre-pharmacy cumulative chemistry GPA correlates with performance in both the Biochemistry and Cell&Molecular Biology and Medicinal Chemistry foundational science courses (p = 0.002 and p = 0.04, respectively) and can predict first year GPA (p = 0.002). The combined data indicate that further assessment of the impact of pre-pharmacy competency in biochemistry and chemistry on pharmacy student success is warranted

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. Proliferation, clonogenic, and apoptosis assays confirmed that Obatoclax can decrease cell proliferation and promote apoptosis in a dose-dependent manner. Combination treatment experiments identified Obatoclax + cisplatin as the most effective treatment. Immunoprecipitation and Western analyses indicate that, in addition to being able to inhibit Bcl-2 and Bcl-xL, Obatoclax can also decrease cyclin D1 and Cdk4/6 expression levels. This has not previously been reported. The combined data demonstrate that Obatoclax can inhibit cell proliferation, promote apoptosis, and significantly enhance the effectiveness of cisplatin in MI-BC cells via mechanisms that likely involve the inhibition of both pro-survival molecules and cell cycle regulators

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. Proliferation, clonogenic, and apoptosis assays confirmed that Obatoclax can decrease cell proliferation and promote apoptosis in a dose-dependent manner. Combination treatment experiments identified Obatoclax + cisplatin as the most effective treatment. Immunoprecipitation and Western analyses indicate that, in addition to being able to inhibit Bcl-2 and Bcl-xL, Obatoclax can also decrease cyclin D1 and Cdk4/6 expression levels. This has not previously been reported. The combined data demonstrate that Obatoclax can inhibit cell proliferation, promote apoptosis, and significantly enhance the effectiveness of cisplatin in MI-BC cells via mechanisms that likely involve the inhibition of both pro-survival molecules and cell cycle regulators

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

Abstract 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). Expression levels of 5 miRNA associated with TCC pathophysiology (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) were assessed by quantitative real-time PCR. Results Statistical analyses using ranked ANOVA identified significant differences in miR-103b and miR-16 levels between urine samples from LUTD and TCC patients (miR-103b, p = 0.002; and miR-16, p = 0.016). No statistically significant differences in miRNA levels were observed between blood samples from LUTD versus TCC patients. Expression levels of miR-34a trended with miR-16, let-7c, and miR-103b levels in individual normal urine samples, however, this coordination was completely lost in TCC urine samples. In contrast, co-ordination of miR-34a, miR-16, let-7c, and miR-103b expression levels was maintained in blood samples from TCC patients. Conclusions Our combined data indicate a potential role for miR-103b and miR-16 as diagnostic urine biomarkers for TCC, and that further investigation of miR-103b and miR-16 in the dysregulation of coordinated miRNA expression in bladder carcinogenesis is warranted

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

PurposeConventional 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. This review focuses on the underlying molecular pathways that lead to urothelial carcinoma resistance to EGFR family inhibitors.Materials and methodsWe performed a PubMed® search for peer reviewed literature on bladder cancer development, EGFR family expression, clinical trials of EGFR family inhibitors and molecular bypass pathways. Research articles deemed to be relevant were examined and a summary of original data was created. Meta-analysis of expression profiles was also performed for each EGFR family member based on data sets accessible via Oncomine®.ResultsMany clinical trials using inhibitors of EGFR family RTKs have been done or are under way. Those that have concluded with results published to date do not show an added benefit over standard of care chemotherapy in an adjuvant or second line setting. However, a neoadjuvant study using erlotinib before radical cystectomy demonstrated promising results.ConclusionsClinical and preclinical studies show that for reasons not currently clear prior treatment with chemotherapeutic agents rendered patients with urothelial carcinoma with muscle invasive bladder cancer resistant to EGFR family inhibitors as well. However, EGFR family inhibitors may be of use in patients with no prior chemotherapy in whom EGFR or ERBB2 is over expressed

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

SUMMARY 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. Here, we describe the effects of conditional expression of a mutant Tp53 (Tp53R270H; equivalent to the human hotspot mutant R273H) in the prostate epithelium of mice. Heterozygous “Tp53LSL-R270H/+” [129S4(Trp53tm3Tyj)] and “Nkx3.1-Cre” [129S(Nkx3-1tm3(cre)Mms)] mice with prostate-specific expression of the Tp53R270H mutation (p53R270H/+ Nkx3.1-Cre mice) were bred onto an FVB/N background via speed congenesis to produce strain FVB.129S4(Trp53tm3Tyj/wt); FVB.129S(Nkx3-1tm3(cre)Mms/wt) and littermate genotype negative control mice. These mutant mice had significantly increased incidences of prostatic intraepithelial neoplasia (PIN) lesions, and these appeared earlier, compared with the Nkx3.1 haploinsufficient (Nkx3.1-Cre het) littermate mice, which did not express the Tp53 mutation. PIN lesions in these mice showed consistent progression and some developed into invasive adenocarcinoma with a high grade, sarcomatoid or epithelial-mesenchymal transition (EMT) phenotype. PIN lesions were similar to those seen in PTEN conditional knockout mice, with evidence of AKT activation concomitant with neoplastic proliferation. However, the invasive tumor phenotype is rarely seen in previously described mouse models of prostatic neoplasia. These data indicate that the Tp53R270H mutation plays a role in CaP initiation. This finding has not previously been reported. Further characterization of this model, particularly in a setting of androgen deprivation, should allow further insight into the mechanisms by which the Tp53R270H mutation mediates CaP progression

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

Background and objectiveMultiple 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; Azadirachta indica), commonly used throughout Southeast Asia for the prevention and treatment of a wide array of diseases including cancer. To date, there are more than 130 biologically active compounds that have been isolated from the Neem tree including azadirachtin, nimbolinin, nimbin, nimbidin, nimbidol, which have demonstrated a wide range of biological activities including anti-microbial, anti-fertility, anti-inflammatory, anti-arthritic, hepatoprotective, anti-diabetic, anti-ulcer, and anti-cancer effects. Very few scientific reports focus on the benefits of Neem in PCa, even though this herb has been used to prevent the disease and its progression for years in complementary and alternative medicine.MethodsWe used the search engines like PubMed, InCommon and Google using the key words: "Neem", "Cancer", "Prostate Cancer" and related words to find the information and data within the time frame from 1980-2022 for our article study.Key content and findingsHere, we provide an overview of Neem extracts and phytochemical derivatives with a focus on their known potential and ability to inhibit specific cellular signaling pathways and processes which drive PCa incidence and progression.ConclusionsThe information presented here indicate that Neem and its derivatives have a therapeutic potential for the treatment of PCa when used as a single agent or in combination with conventional chemotherapeutics