A5044212915- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- TGF-β signaling in diseases
- Hormonal and reproductive studies
- Effects and risks of endocrine disrupting chemicals
- Sperm and Testicular Function
- Cell Adhesion Molecules Research
- Reproductive System and Pregnancy
- Cancer, Lipids, and Metabolism
- Glioma Diagnosis and Treatment
- Pluripotent Stem Cells Research
- Sexual Differentiation and Disorders
- PARP inhibition in cancer therapy
- Xenotransplantation and immune response
- Tissue Engineering and Regenerative Medicine
- Proteoglycans and glycosaminoglycans research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Prostate Cancer Diagnosis and Treatment
- Selenium in Biological Systems
- DNA Repair Mechanisms
- Reproductive Biology and Fertility
- Liver physiology and pathology
- FOXO transcription factor regulation
University of Glasgow
2019-2024
University of Cincinnati
2011-2016
Monash University
2013
Oncology Hematology Care
2013
ARUP Laboratories (United States)
2012
University of Utah
2012
Vanderbilt University
2012
University of Rochester Medical Center
2007-2012
University of Cincinnati Medical Center
2012
University of Rochester
2009-2010
Abstract The present study explores the mechanisms by which human prostatic carcinoma-associated fibroblasts (CAF) induce tumorigenesis in initiated but nonmalignant epithelial cells (BPH-1). CAF express elevated levels of both transforming growth factor-β1 (TGF-β1) and stromal cell–derived factor-1 (SDF-1/CXCL12). TGF-β inhibits BPH-1 vitro, was found to be necessary for tumorigenic response CAF. This counterintuitive result suggested that signaling system involved other processes relating...
Estrogen action is dependent upon the presence of specific ligand-activated receptors in target tissues. The aim present experiments was to compare spatial and temporal pattern expression estrogen receptor β (ERβ) with that ERα full thickness endometrial samples (from superficial basal zone) obtained from both women rhesus macaques. Immunohistochemical localization antibodies revealed ERβ were expressed nuclei glands stroma. Consistent previous studies, declined stroma functionalis during...
The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib potentiated radiation and temozolomide (TMZ) chemotherapy in preclinical glioblastoma models but brain penetration was poor. Clinically, PARP inhibitors exacerbate the hematological side effects of TMZ. OPARATIC trial conducted to measure recurrent by assess safety tolerability its combination with
Background: Patients with glioblastoma who are elderly or have poor performance status (PS) experience particularly clinical outcomes. At the time of study initiation, these patients were treated short-course radiotherapy (40 Gy in 15 fractions). Olaparib is an oral inhibitor DNA repair enzyme poly(ADP-ribose) polymerase (PARP) that well tolerated as a single agent but exacerbates acute radiation toxicity extracranial sites. Preclinical data predicted PARP inhibitors would enhance...
Estrogens and androgens are essential for the maturation of ovarian follicle normal fertility in female. We have used antibodies specific both forms estrogen receptor (alpha [ERα] beta [ERβ]) androgen (AR) to investigate pattern expression ovaries obtained from women a New World primate, Common marmoset (Callthrix jacchus). On Western blots, three directed against different peptides within human ERβ all recognized recombinant (h) but did not bind hERα. The protein was extracted ovary...
ABSTRACT: This study evaluated whether androgen action is altered in rats treated neonatally with diethylstilbestrol (DES) at a dose that induced reproductive tract abnormalities. Rats were on alternate days 2–12 10 μg DES and studied Day 18. DES‐induced abnormalities included 70% reduction testis weight, distension overgrowth of the rete, epithelial height efferent ducts, underdevelopment epididymal duct epithelium, vas deferens, convolution extra‐epididymal vas. In DES‐treated rats,...
Abstract BACKGROUND Hormonal therapy is effective for advanced prostate cancer (PC) but the disease often recurs and becomes hormone‐refractory. It hypothesized that a subpopulation of cells, is, stem cells (CSCs), survives hormonal leads to tumor recurrence. CD44 expression was shown identify with CSC features. PC contains secretory type epithelial minor population neuroendocrine cells. Neuroendocrine do not express androgen receptor are quiescent, features associated CSCs. The purpose...
Abstract Transforming growth factor-β (TGF-β) is a pleiotropic factor with actions that are dependent on circumstances, including dose, target cell type, and context. TGF-β can elicit both growth-promoting growth-suppressive activities. In normal tissues, generally acts to restrict maintain differentiation. However, during tumorigenesis, changes in expression cellular responses promote tumorigenesis. The present study examines the effects of nontumorigenic human prostatic epithelial line...
It has been postulated that prostatic carcinogenesis is androgen dependent and androgens mediate their effects primarily through epithelial cells; however, definitive proof of hormone action in prostate cancer (PRCA) progression lacking. Here we demonstrate genetic loss function experiments PRCA dependency occurs via stromal receptors (AR) but not AR. Utilizing tissue recombination models carcinogenesis, AR was evaluated by surgical castration or deletion. Loss prevented malignant...
Determining the source of regenerated luminal epithelial cells in adult prostate during androgen deprivation and replacement will provide insights into origin cancer their fate therapy. Prostate stem layer have been suggested to give rise epithelium. However, extent cell participation regrowth is not clear. In this report, using prostate-specific antigen-CreER(T2)-based genetic lineage marking/tracing mice, preexisting were shown be a prostate. Prostatic could survive capable proliferating...
The biosynthesis of oestrogens from androgens is catalysed by the aromatase complex, an essential component which cytochrome P450 (P450 arom) protein. Expression a functional arom for normal fertility in males and females sequence protein highly conserved. We have raised new monoclonal antibody against conserved peptide validated it on fixed tissue sections rat, common marmoset (Callthrix jacchus) human. was used successfully Western analysis specifically reacted with 55 kDa microsomal...
Glyceollins, a group of novel phytoalexins isolated from activated soy, have recently been demonstrated to be antiestrogens that bind the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. Our previous publications focused specifically on inhibition formation growth by glyceollin mixture, which contains three isomers (I, II, III). Here, we show mixture is also effective as potential antiestrogenic, therapeutic agent prevents estrogen-stimulated tumorigenesis displays...
This randomized clinical trial explores whether hormone intensification at start of androgen deprivation therapy alters selection receptor ( AR ) gene alterations within the body and/or enhancer region.
The vast majority of clinical small molecule multi-kinase inhibitors (mKI) report abject failures in targeting cancers with high stem cell contents like high-grade glioma and colorectal cancers. FDA-approved mKIs to date ablate receptor tyrosine kinase signaling but do not target the paradoxical WNT which is a key survival driver for self-renewing cancer cells. pathway enhances plasticity triggers relapse highly heterogenous tumours. Using de novo synthesis structure-activity-relationship...
An epididymis-specific, secretory glutathione peroxidase (GPX5) has been proposed previously to play a role in protecting mammalian sperm membranes from the deleterious effects of lipid peroxidation, which, if not contained, can lead reduced fertilizing capacity. Here we report cDNA cloning human GPX5 and show that majority transcripts contain 118 nt frame-shifting deletion, arising, most likely, inappropriate excision exon 3 during processing. Antisera raised against recombinant...
This study in rats sought to 1) characterize immunoexpression of estrogen receptor α (ERα) and ERβ the efferent ducts, epididymis, vas deferens during postnatal development; 2) establish whether ER expression changed after neonatal treatment with diethylstilbestrol (DES); 3) determine changes coincided abnormal epididymal/vas development. Rats were administered 10μ g DES or vehicle on days 2, 4, 6, 8, 10, 12 sampled 18, 25, 35, 90+. At all ages, ERα was immunoexpressed intensely ducts. On...
Abstract The cyclin D1 oncogene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates Rb protein promotes progression through G1 to S phase cell cycle. Several prostate cancer lines subset primary samples have increased expression. However, relationship between expression tumor has yet be clearly characterized. This study examined effects manipulating in either human prostatic epithelial or stromal cells using tissue recombination model. data showed...
Abstract Prostate cancer stem cells (CSC) are implicated in tumor initiation, progression, metastasis, and the development of therapeutic-resistant disease. It is well known that bulk prostate express androgen receptor (AR) androgens required for growth, emergence castration-resistant In contrast, small subpopulation self-renewing CSCs exhibits an AR-negative (AR−) signature. The mechanisms underlying absence AR unknown. Using CSC-like cell models isolated from clinical biopsy tissues, we...
We have sought to develop a new in vivo model of prostate carcinogenesis using human prostatic epithelial cell cultures. Human cancers frequently display DNA amplification the 8q24 amplicon, which leads an increase copy number c-MYC gene, finding that suggests role for carcinogenesis. In addition overexpression transgenic mouse models results carcinogenesis.We took advantage ability retroviruses integrate foreign into epithelium (huPrE) generate lines overexpress protooncogene. These cells...
The primary induced isoflavones in soybean, the glyceollins, have been shown to be potent estrogen antagonists vitro and vivo. discovery of glyceollins' ability inhibit cancer cell proliferation has led analysis estrogenic activities other isoflavones. In this study, we investigated a novel isoflavone, glycinol, precursor glyceollin that is produced elicited soy. Sensitive specific bioassays were used determine glycinol exhibits activity. Estrogen-based reporter assays performed, displayed...
Bisphenol A (BPA) is an endocrine disrupting chemical that ubiquitous in wild and built environments. Due to variability study design, the disruptive effects of BPA have proven difficult experimentally replicate. This was designed assess actions dietary exposure, while carefully controlling for known confounders. Parental CD1 mice were acclimated defined diet containing (0.03, 0.3, 3, 30, or 300 ppm) 17α-ethinyl estradiol (EE; 0.0001, 0.001, 0.01 bred produce progeny (F1) maintained through...