Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 36

Publication Record

Connections

Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer: Contemporary Meta-Analyses.
Hu JR, Duncan MS, Morgans AK, Brown JD, Meijers WC, Freiberg MS, Salem JE, Beckman JA, Moslehi JJ
(2020) Arterioscler Thromb Vasc Biol 40: e55-e64
MeSH Terms: Androgen Antagonists, Antineoplastic Agents, Hormonal, Cardiotoxicity, Cardiovascular Diseases, Cardiovascular System, Humans, Male, Prostatic Neoplasms, Risk Assessment, Risk Factors, Treatment Outcome
Show Abstract · Added May 29, 2020
Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.
0 Communities
2 Members
0 Resources
11 MeSH Terms
Heart failure and atrial tachyarrhythmia on abiraterone: A pharmacovigilance study.
Bretagne M, Lebrun-Vignes B, Pariente A, Shaffer CM, Malouf GG, Dureau P, Potey C, Funck-Brentano C, Roden DM, Moslehi JJ, Salem JE
(2020) Arch Cardiovasc Dis 113: 9-21
MeSH Terms: Adverse Drug Reaction Reporting Systems, Aged, Aged, 80 and over, Androgen Antagonists, Androstenes, Antineoplastic Agents, Hormonal, Cardiotoxicity, Databases, Factual, Heart Failure, Humans, Male, Middle Aged, Pharmacovigilance, Phenylthiohydantoin, Prostatic Neoplasms, Retrospective Studies, Risk Assessment, Risk Factors, Tachycardia, Supraventricular, Time Factors
Show Abstract · Added November 12, 2019
BACKGROUND - Abiraterone and enzalutamide are recently-approved androgen deprivation therapies (ADTs) for metastatic prostate cancer, with unknown cardiac safety profiles. Abiraterone has a propensity to hypermineralocorticism on top of androgen deprivation, so might carry an additional risk for atrial tachyarrhythmia (AT) and heart failure (HF) compared with other ADTs.
AIM - To determine if abiraterone was associated with an increased proportion of AT and HF reports among all suspected adverse drug reactions (ADRs) reported in several pharmacovigilance databases compared with enzalutamide, other ADTs and all other drugs.
METHODS - In this observational retrospective pharmacovigilance study, we performed a disproportionality analysis of reports of suspected ADRs in men in the French pharmacovigilance database, the European pharmacovigilance database and the international pharmacovigilance database VigiBase, to evaluate the reporting odds ratios (RORs) of AT and HF for abiraterone compared with enzalutamide, other ADTs and all other drugs.
RESULTS - In the 5,759,781 ADR reports in men in VigiBase, 55,070 pertained to ADTs. The RORs for AT for abiraterone versus enzalutamide, other ADTs and all other drugs were 4.1 (95% confidence interval 3.1-5.3), 3.7 (3-4.5) and 3.2 (2.7-3.7), respectively (P<0.0001 for all). The corresponding RORs for HF were 2.5 (2-3), 1.5 (1.3-1.7) and 2 (1.7-2.3), respectively (P<0.0001 for all). These results were concordant with the French and European pharmacovigilance databases. Mean times to AT and HF onset were shorter with abiraterone (5.2±0.8 and 4.5±0.6 months, respectively) versus other ADTs (13.3±3.2 and 9.2±1.1 months, respectively) (both P<0.05). Cases on abiraterone versus other ADTs were more frequently associated with at least two ADR terms, including AT, HF, hypokalaemia, hypertension and oedema (13.6% vs 6%; P<0.0001). For abiraterone, age, but not dose, was associated with reporting of AT and HF versus any other ADR.
CONCLUSIONS - Compared with other ADTs, abiraterone was associated with higher reporting of AT and HF, associated with hypokalaemia, hypertension and oedema. These findings are consistent with the hypermineralocorticism induced by abiraterone, but not by other ADTs.
Copyright © 2019 Elsevier Masson SAS. All rights reserved.
0 Communities
2 Members
0 Resources
20 MeSH Terms
Hypogonadism as a Reversible Cause of Torsades de Pointes in Men.
Salem JE, Waintraub X, Courtillot C, Shaffer CM, Gandjbakhch E, Maupain C, Moslehi JJ, Badilini F, Haroche J, Gougis P, Fressart V, Glazer AM, Hidden-Lucet F, Touraine P, Lebrun-Vignes B, Roden DM, Bachelot A, Funck-Brentano C
(2018) Circulation 138: 110-113
MeSH Terms: Adverse Drug Reaction Reporting Systems, Aged, Aged, 80 and over, Androgen Antagonists, Biomarkers, Cross-Sectional Studies, Databases, Factual, Electronic Health Records, Heart Rate, Hormone Replacement Therapy, Humans, Hypogonadism, Male, Middle Aged, Paris, Pharmacovigilance, Prospective Studies, Risk Assessment, Risk Factors, Testosterone, Torsades de Pointes
Added October 1, 2018
0 Communities
2 Members
0 Resources
21 MeSH Terms
Activation of GRP/GRP-R signaling contributes to castration-resistant prostate cancer progression.
Qiao J, Grabowska MM, Forestier-Roman IS, Mirosevich J, Case TC, Chung DH, Cates JM, Matusik RJ, Manning HC, Jin R
(2016) Oncotarget 7: 61955-61969
MeSH Terms: Adenocarcinoma, Androgen Antagonists, Androgens, Antineoplastic Agents, Cell Line, Tumor, Disease Progression, Gastrin-Releasing Peptide, Gene Expression Regulation, Neoplastic, Genetic Variation, Humans, Male, Prostatic Neoplasms, Castration-Resistant, RNA Splicing, Receptors, Androgen, Receptors, Bombesin, Signal Transduction, Transcription, Genetic
Show Abstract · Added April 6, 2017
Numerous studies indicate that androgen receptor splice variants (ARVs) play a critical role in the development of castration-resistant prostate cancer (CRPC), including the resistance to the new generation of inhibitors of androgen receptor (AR) action. Previously, we demonstrated that activation of NF-κB signaling increases ARVs expression in prostate cancer (PC) cells, thereby promoting progression to CRPC. However, it is unclear how NF-κB signaling is activated in CRPC. In this study, we report that long-term treatment with anti-androgens increases a neuroendocrine (NE) hormone - gastrin-releasing peptide (GRP) and its receptor (GRP-R) expression in PC cells. In addition, activation of GRP/GRP-R signaling increases ARVs expression through activating NF-κB signaling. This results in an androgen-dependent tumor progressing to a castrate resistant tumor. The knock-down of AR-V7 restores sensitivity to antiandrogens of PC cells over-expressing the GRP/GRP-R signaling pathway. These findings strongly indicate that the axis of Androgen-Deprivation Therapy (ADT) induces GRP/GRP-R activity, activation NF-κB and increased levels of AR-V7 expression resulting in progression to CRPC. Both prostate adenocarcinoma and small cell NE prostate cancer express GRP-R. Since the GRP-R is clinically targetable by analogue-based approach, this provides a novel therapeutic approach to treat advanced CRPC.
0 Communities
3 Members
0 Resources
17 MeSH Terms
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.
Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L
(2016) Nat Rev Clin Oncol 13: 674-690
MeSH Terms: Androgen Antagonists, BRCA2 Protein, Biomarkers, Tumor, Clinical Trials as Topic, Female, Humans, Immune System, Immunotherapy, Mitogen-Activated Protein Kinases, Molecular Targeted Therapy, Mutation, Neoplastic Stem Cells, Phosphoinositide-3 Kinase Inhibitors, Poly(ADP-ribose) Polymerase Inhibitors, Prognosis, Triple Negative Breast Neoplasms, Ubiquitin-Protein Ligases
Show Abstract · Added April 6, 2017
Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) in both the early and advanced-stages of the disease. The lack of targeted therapies and the poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets to treat patients with these tumours. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', the presence of the androgen receptor, and several rare genomic alterations. Whether these alterations are molecular 'drivers', however, has not been clearly established. A subgroup of TNBCs shows a high degree of tumour-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. In this Review, we discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities derived from these data.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Cardiovascular Effects of Androgen Deprivation Therapy for the Treatment of Prostate Cancer: ABCDE Steps to Reduce Cardiovascular Disease in Patients With Prostate Cancer.
Bhatia N, Santos M, Jones LW, Beckman JA, Penson DF, Morgans AK, Moslehi J
(2016) Circulation 133: 537-41
MeSH Terms: Aged, Androgen Antagonists, Aspirin, Blood Pressure, Cardiovascular Diseases, Cholesterol, Diabetes Mellitus, Exercise, Humans, Male, Prostatic Neoplasms, Treatment Outcome
Added February 4, 2016
0 Communities
2 Members
0 Resources
12 MeSH Terms
Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial.
Penson DF, Armstrong AJ, Concepcion R, Agarwal N, Olsson C, Karsh L, Dunshee C, Wang F, Wu K, Krivoshik A, Phung D, Higano CS
(2016) J Clin Oncol 34: 2098-106
MeSH Terms: Adult, Aged, Androgen Antagonists, Anilides, Antineoplastic Agents, Double-Blind Method, Humans, Male, Middle Aged, Nitriles, Phenylthiohydantoin, Prostate-Specific Antigen, Prostatic Neoplasms, Castration-Resistant, Tosyl Compounds
Show Abstract · Added February 4, 2016
PURPOSE - Enzalutamide, a potent oral androgen receptor inhibitor, improves survival in men with metastatic castration-resistant prostate cancer (CRPC) before and after chemotherapy. Bicalutamide, a nonsteroidal antiandrogen, is widely used to treat men with nonmetastatic or metastatic CRPC. The efficacy and safety of these drugs were compared in this randomized, double-blind, phase II study of men with CRPC.
PATIENTS AND METHODS - A total of 396 men with nonmetastatic (n = 139) or metastatic (n = 257) CRPC were randomly assigned to enzalutamide 160 mg per day (n = 198) or bicalutamide 50 mg per day (n = 198). Androgen deprivation therapy was continued in both arms. The primary end point was progression-free survival (PFS).
RESULTS - Enzalutamide reduced the risk of progression or death by 76% compared with bicalutamide (hazard ratio [HR], 0.24; 95% CI, 0.18 to 0.32; P < .001). Median PFS was 19.4 months with enzalutamide versus 5.7 months with bicalutamide. Enzalutamide resulted in significant improvements in all key secondary end points: time to prostate-specific antigen progression (HR, 0.19; 95% CI, 0.14 to 0.26; P < .001); proportion of patients with a ≥ 50% prostate-specific antigen response (81% v 31%; P < .001); and radiographic PFS in metastatic patients (HR, 0.32; 95% CI, 0.21 to 0.50; P < .001). Beneficial effects with enzalutamide were observed in both nonmetastatic and metastatic subgroups. The observed adverse event profile was consistent with that from phase III enzalutamide trials.
CONCLUSION - Enzalutamide significantly reduced risk of prostate cancer progression or death compared with bicalutamide in patients with nonmetastatic or metastatic CRPC.
© 2016 by American Society of Clinical Oncology.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Cardiology Patient Page. ABCDE Steps for Heart and Vascular Wellness Following a Prostate Cancer Diagnosis.
Guan J, Khambhati J, Jones LW, Morgans A, Allaf M, Penson DF, Moslehi J
(2015) Circulation 132: e218-20
MeSH Terms: Adenocarcinoma, Androgen Antagonists, Androgens, Antineoplastic Agents, Hormonal, Cardiovascular Diseases, Comorbidity, Diabetes Mellitus, Diet, Disease Susceptibility, Exercise, Health Promotion, Humans, Hypercholesterolemia, Hypertension, Life Style, Male, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, Risk Factors, Smoking Cessation, Survivors
Added February 4, 2016
0 Communities
2 Members
0 Resources
21 MeSH Terms
Androgen deprivation therapy reversibly increases endothelium-dependent vasodilation in men with prostate cancer.
Nguyen PL, Jarolim P, Basaria S, Zuflacht JP, Milian J, Kadivar S, Graham PL, Hyatt A, Kantoff PW, Beckman JA
(2015) J Am Heart Assoc 4:
MeSH Terms: Aged, Androgen Antagonists, Anilides, Brachial Artery, Drug Therapy, Combination, Endothelium, Vascular, Humans, Leuprolide, Male, Nitriles, Prostatic Neoplasms, Tosyl Compounds, Vasodilation
Show Abstract · Added January 15, 2016
BACKGROUND - Androgen deprivation therapy (ADT) is a standard treatment for patients with aggressive prostate cancer. Although ADT improves survival, it increases the risk of diabetes. Emerging evidence suggests that ADT increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that ADT may impair endothelium-dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population.
METHODS AND RESULTS - We prospectively evaluated conduit artery endothelium-dependent and -independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66 ± 7 years; 25% with diabetes) with prostate cancer before and after 3 months of ADT. High-resolution B-mode ultrasound was used to assess flow-mediated (endothelium-dependent) and nitroglycerine-mediated (endothelium-independent) brachial artery vasodilation. ADT significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium-dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively; P=0.046, allometric P=0.037). Nitroglycerine-mediated vasodilation did not change from baseline (P>0.2). The subset of participants on ADT for 6 months returned for reevaluation at 1 year. In this group, endothelium-dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively; P=0.05).
CONCLUSIONS - In contrast to our expectation, ADT improved endothelium-dependent vasodilation and its cessation returned endothelium-dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation.
© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Inhibition of NF-kappa B signaling restores responsiveness of castrate-resistant prostate cancer cells to anti-androgen treatment by decreasing androgen receptor-variant expression.
Jin R, Yamashita H, Yu X, Wang J, Franco OE, Wang Y, Hayward SW, Matusik RJ
(2015) Oncogene 34: 3700-10
MeSH Terms: Androgen Antagonists, Anilides, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Boronic Acids, Bortezomib, Cell Line, Tumor, Humans, Male, NF-kappa B, Nitriles, Prostatic Neoplasms, Castration-Resistant, Pyrazines, Receptors, Androgen, Signal Transduction, Tosyl Compounds, Xenograft Model Antitumor Assays
Show Abstract · Added January 20, 2015
Androgen receptor splicing variants (ARVs) that lack the ligand-binding domain (LBD) are associated with the development of castration-resistant prostate cancer (CRPC), including resistance to the new generation of high-affinity anti-androgens. However, the mechanism by which ARV expression is regulated is not fully understood. In this study, we show that the activation of classical nuclear factor-kappa B (NF-κB) signaling increases the expression of ARVs in prostate cancer (PCa) cells and converts androgen-sensitive PCa cells to become androgen-insensitive, whereas downregulation of NF-κB signaling inhibits ARV expression and restores responsiveness of CRPC to anti-androgen therapy. In addition, we demonstrated that combination of anti-androgen with NF-κB-targeted therapy inhibits efficiently tumor growth of human CRPC xenografts. These results indicate that induction of ARVs by activated NF-κB signaling in PCa cells is a critical mechanism by which the PCa progresses to CRPC. This has important implications as it can prolong the survival of CRPC patients by restoring the tumors to once again respond to conventional androgen-deprivation therapy (ADT).
1 Communities
3 Members
0 Resources
17 MeSH Terms