A5026535772- Prostate Cancer Treatment and Research
- Hormonal and reproductive studies
- Cancer, Lipids, and Metabolism
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Sexual Differentiation and Disorders
- Hormonal Regulation and Hypertension
- Pharmacogenetics and Drug Metabolism
- Prostate Cancer Diagnosis and Treatment
- Steroid Chemistry and Biochemistry
- Radiopharmaceutical Chemistry and Applications
- Asthma and respiratory diseases
- Adrenal Hormones and Disorders
- Ubiquitin and proteasome pathways
- Cholesterol and Lipid Metabolism
- Radiation Therapy and Dosimetry
- Cancer, Stress, Anesthesia, and Immune Response
- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Assays
- Mass Spectrometry Techniques and Applications
- Salivary Gland Disorders and Functions
University of Miami
2025
Sylvester Comprehensive Cancer Center
2025
Cleveland Clinic
2016-2024
Cleveland Clinic Lerner College of Medicine
2015-2023
Cerner (United States)
2023
Cleveland State University
2016-2017
Prostate cancer is driven by androgen stimulation of the receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that glucocorticoid (GR) upregulated in this context, stimulating expression AR-target genes permit continued growth despite blockade. However, countering mechanism administration GR antagonists problematic because essential for life. We show enzalutamide treatment human models...
After androgen deprivation, prostate cancer frequently becomes castration resistant (CRPC), with intratumoral production from extragonadal precursors that activate the receptor pathway. 3β-Hydroxysteroid dehydrogenase-1 (3βHSD1) is rate-limiting enzyme for synthesis, which together lead to CRPC. Here, we show cancer-associated fibroblasts (CAFs) increased epithelial 3βHSD1 expression, induced activated receptor, and Unbiased metabolomics revealed CAF-secreted glucosamine specifically 3βHSD1....
Prostate cancer is highly dependent on androgens and the androgen receptor (AR). Hormonal therapies inhibit gonadal testosterone production, block extragonadal biosynthesis, or directly antagonize AR. Resistance to medical castration occurs as castration-resistant prostate (CRPC) driven by reactivation of androgen-AR axis. 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) serves rate-limiting step for potent synthesis from precursors, thereby stimulating CRPC. Genetic evidence in men demonstrates...
BACKGROUND. A common germline variant in HSD3B1(1245A>C) encodes for a hyperactive 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) missense that increases metabolic flux from extragonadal precursor steroids to DHT synthesis prostate cancer. Enabling of by HSD3B1(1245C) predicts more rapid clinical resistance castration and sensitivity androgen inhibition. thus appears define subgroup patients who benefit blocking androgens. However, abiraterone, which is administered block androgens, steroidal...
Significance Although resistance to glucocorticoids is a major clinical problem, the underlying mechanisms are unknown. It known that glucocorticoid use can suppress adrenal androgen production. In population studies, animal models, and cell culture experiments, androgens associated with several benefits in asthma, but neither glucocorticoid-resistant asthma nor genetic determinants of responsiveness have been studied humans. A missense-encoding variant HSD3B1 regulate conversion from...
Abstract Purpose: Germline variation in solute carrier organic anion (SLCO) genes influences cellular steroid uptake and is associated with prostate cancer outcomes. We hypothesized that, due to its steroidal structure, the CYP17A inhibitor abiraterone may undergo transport by SLCO-encoded transporters that SLCO gene influence intracellular levels Experimental Design: Steroid were measured serum tissue from 58 men localized a clinical trial of LHRH agonist plus acetate prednisone for 24...
Inhibiting H6PD restores prostate cancer response to AR antagonists by normalizing glucocorticoid metabolism in mouse xenograft models.
230 Background: DHEA, testosterone (T) and androstenedione (AD) are adrenal androgens that can drive CRPC. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) has 2 common missense-encoding germline variants: the more active adrenal-permissive allele less adrenal-restrictive associated with greater lesser non-gonadal androgen biosynthesis from DHEA. A single (1245C) is sufficient to confer rapid development of CRPC homozygous inheritance (about 7-10% men) most monogenic link...
246 Background: Serum androgen levels are prognostic in mCRPC and genetic variation metabolism may drive these effects. OATPs, encoded by genes of the solute carrier organic anion (SLCO) family, govern uptake steroids. We hypothesize differential outcomes on ARPI therapy. A secondary analysis was contribution race to prevalence outcome with variants. Methods: A031201 a randomized phase 3 trial progressive Prostate Cancer Working Group 2 (PCWG2) criteria. Patients (pts) were 1:1 enzalutamide...
Abstract Introduction: Androgen deprivation therapy (ADT) significantly alters metabolism in prostate cancer patients. Serum metabolomics are the gold standard for studying these effects; however, saliva offers a non-invasive alternative biomarker assessment. This study evaluates impact of ADT on serum and metabolites correlation between two matrices. By evaluating as potential surrogate serum, this work explores its application analysis chronic risk factors within community health programs....
Steroid hormones and their respective nuclear receptors are essential mediators in numerous physiologic pathophysiologic processes, ranging from regulation of metabolism, immune function, reproductive processes to the development hormone-dependent cancers such as those breast prostate. Because steroids must enter cells before activating receptors, understanding mechanisms by which cellular uptake occurs is critical, yet a clear these has been elusive. It generally assumed that...
3βHSD1 enzymatic activity is essential for synthesis of potent androgens from adrenal precursor steroids in prostate cancer. A germline variant HSD3B1, the gene that encodes 3βHSD1, a stable enzyme, regulates androgen dependence, and predictive biomarker poor clinical outcomes after gonadal testosterone deprivation therapy. However, little known about HSD3B1 transcriptional regulation. Generally, it thought intratumoral upregulated deprivation, enabling development castration-resistant Given...
Since their discovery ~70 years ago, glucocorticoids (GC) have been widely used to elicit a systemic anti-inflammatory response, and currently play major role in the treatment of asthma other inflammatory diseases (1). However, unresponsiveness GC some individuals is limitation asthma, mechanisms underlying this clinical entity are not fully elucidated Indeed, severe generally defined as that remains symptomatic despite high-dose inhaled and/or therapy. GCs inhibit production adrenal...
BACKGROUNDGenerally, clinical assessment of gonadal testosterone (T) in human physiology is determined using concentrations measured peripheral blood. Prostatic T exposure similarly thought to be from exposure. Despite the fact that androgens drive prostate cancer, has had no role evaluation or treatment men with localized cancer.METHODSTo assess local androgen delivery we obtained blood (periprostatic) prostatic dorsal venous complex 266 undergoing radical prostatectomy July 2014 August...
325 Background: Abi, a potent inhibitor of 17α-hydroxylase/17,20-lyase (CYP17A1), is an oral treatment option for metastatic PCa in castration-resistant and -sensitive settings. Abi converted to ∆ 4 , 3-keto-abi (D4A) by 3β-hydroxysteroid dehydrogenase (3βHSD). D4A further metabolized multiple downstream steroidal metabolites including 3-keto-5α-Abi (5αA), which androgen receptor (AR) agonist might affect response and/or resistance Abi. The common HSD3B1(1245C) germline variant encodes 3βHSD...
Abstract Background : Abiraterone (ABI), a steroidal CYP17A1 inhibitor, blocks the DHT synthesis from adrenal precursor steroids in castration resistant prostate cancer (mCRPC) patients. ABI is converted by 3β-hydroxysteroid dehydrogenase (HSD3B) into D4-abiraterone (D4-ABI). In previous preclinical study, D4-ABI was shown to block multiple steroidogenic enzymes and antagonize androgen receptor. Besides, it appeared more active than itself (Li Z et al. Nature 2015). However, contribution of...