A5054138427- Prostate Cancer Treatment and Research
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- S100 Proteins and Annexins
- Telomeres, Telomerase, and Senescence
- Cancer, Stress, Anesthesia, and Immune Response
- RNA Interference and Gene Delivery
- Tissue Engineering and Regenerative Medicine
- Advanced biosensing and bioanalysis techniques
- Neonatal Respiratory Health Research
- TGF-β signaling in diseases
- Bone health and treatments
- Hippo pathway signaling and YAP/TAZ
- Receptor Mechanisms and Signaling
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Cancer, Hypoxia, and Metabolism
- Connective Tissue Growth Factor Research
- Cancer, Lipids, and Metabolism
- bioluminescence and chemiluminescence research
- PI3K/AKT/mTOR signaling in cancer
- Inhalation and Respiratory Drug Delivery
- Nanoplatforms for cancer theranostics
- Heterotopic Ossification and Related Conditions
- FOXO transcription factor regulation
Ellison Institute of Technology
2023
Larry Ellison Foundation
2023
University of Southern California
2011-2021
Cedars-Sinai Medical Center
2014
Medical College of Wisconsin
2014
Bipar
2014
University of California, Los Angeles
2008-2013
USC Norris Comprehensive Cancer Center
2012
Nara Medical University
2008
Kindai University
2008
Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades neurotransmitters and dietary amines. Despite the association between MAOA PCa, it is unclear how promotes PCa progression. Here, we found functions to induce epithelial-to-mesenchymal transition (EMT) stabilize transcription factor HIF1α, which mediates hypoxia through an elevation ROS, thus enhancing growth, invasiveness,...
GRP78/BiP has recently emerged as a novel biomarker for aggressive prostate cancer. Here, we report that homozygous deletion of Grp78 specifically in mouse epithelium suppresses tumorigenesis without affecting postnatal development and growth. Mouse prostates with double conditional knockout Pten exhibit normal histology cytology, contrast to the invasive adenocarcinoma inactivation. AKT activation null is inhibited by deletion, corresponding suppression phosphorylation GRP78 knockdown...
Abstract Signals originating from cancer-associated fibroblasts (CAF) may positively regulate proliferation and tumorigenicity in prostate cancer. In this study, we investigated whether CAFs the biology of cancer stem cells (CSC) by using a conditional Pten deletion mouse model adenocarcinoma to isolate both CAF cultures CSC-enriched cell fractions tumors. CSCs that were isolated possessed self-renewal, spheroid-forming, multipotential differentiation activities tissue culture, segregating...
Annexin A1 (AnxA1), a phospholipid-binding protein and regulator of glucocorticoid-induced inflammatory signaling, has implications in cancer. Here, role for AnxA1 prostate adenocarcinoma was determined using primary cultures tumor cell line (cE1), all derived from the conditional Pten deletion mouse model secretion by prostate-derived cancer-associated fibroblasts (CAF) significantly higher than normal (NPF). Prostate cells were sorted to enrich epithelial subpopulations based on...
Tumor cells are inherently heterogeneous and often exhibit diminished adhesion, resulting in the shedding of tumor into circulation to form circulating (CTCs). A fraction these live CTCs with potential metastatic colonization whereas others at various stages apoptosis making them likely be less relevant understanding disease. Isolation characterization may augment information yielded by standard enumeration help physicians more accurately establish diagnosis, choose therapy, monitor...
Background Monoamine oxidase A (MAOA) is best known for its role in neuro‐transmitter regulation. inhibitors are used to treat atypical depression. MAOA highly expressed high grade prostate cancer and modulates tumorigenesis progression cancer. Here, we investigated the potential of (MAOAIs) relation androgen receptor (AR) pathway resistance antiandrogen treatment Methods We examined expression effect MAOI AR‐targeted treatments using LNCaP, C4‐2B, 22Rv1 human cell lines. MAOA, AR‐full...
The application of Cre/loxP technology has resulted in a new generation conditional mouse models prostate cancer. Here, we describe the improvement Pten deletion model adenocarcinoma by combining it with either luciferase or enhanced green fluorescent protein reporter line. In these models, recombination mechanism that inactivates alleles also activates gene. model, growth primary cancer can be followed noninvasively bioluminescence imaging (BLI). Surgical castration tumor-bearing animals...
Abstract Two commonly occurring genetic aberrations of human prostate cancer [i.e., overexpression a mitogenic polypeptide (fibroblast growth factor 8, isoform b or FGF8b) and loss function PTEN tumor suppressor] were recapitulated into new combinatorial mouse model. This model harboring the Fgf8b transgene haploinsufficiency in Pten, both epithelium–specific manner, yielded prostatic adenocarcinoma with readily detectable lymph node metastases, whereas single models each defects shown...
Abstract We examined the effect of extracellular bone morphogenetic protein (BMP) 2 and 7, which are up-regulated in prostate adenocarcinomas conditional Pten deletion mouse model, on primary cultures cancer-associated fibroblasts (CAF) derived from these tumors. In CAF, we show that BMP2 or BMP7, but not transforming growth factor β-1, can strikingly stimulate secretion stromal cell–derived factor-1 (SDF-1), also known as CXCL12. The CAF cells express type I II BMP receptors well receptor...
Prostate cancer (PCa) is the second-leading cause of cancer-related mortality, after lung cancer, in men from developed countries. In its early stages, primary tumor growth dependent on androgens, thus generally can be controlled by androgen deprivation therapy (ADT). Eventually however, disease progresses to castration-resistant prostate (CRPC), a lethal form need more effective treatments. G-protein coupled receptors (GPCRs) comprise large clan cell surface proteins that have been...
Androgen receptor (AR) regulation pathways are essential for supporting the growth and survival of prostate cancer cells. Recently, sub-populations cells have been identified with stem cell features associated emergence treatment-resistant cancer. Here, we explored function AR in cancer-associated fibroblasts (CAFs) relative to cell-associated characteristics. CAFs were isolated from murine cPten-/-L model cultured human epithelial (hPCa) A murine-specific antisense oligonucleotide (ASO) was...
Background Despite its initial positive response to hormone ablation therapy, prostate cancers invariably recur in more aggressive, treatment resistant forms. The lack of our understanding underlying genetic alterations for the transition from androgen-dependent (AD) ADI cancer growth hampers ability develop target-driven therapeutic strategies efficient cancer. Methodology/Principal Findings By screening a library activated human kinases, we have identified TPL2, encoding serine/threonine...
We previously established a role for cancer-associated fibroblasts (CAF) in enhancing the self-renewal and differentiation potentials of putative prostate cancer stem cells (CSC). Our published work focused on androgen-dependent (ADPC) using conditional Pten deletion mouse model. Employing same model, we now describe interaction CAF CSC castration-resistant (CRPC). isolated from ADPC (ADPCAF) CRPC (CRPCAF) were compared terms their ability to support organoid formation tumor initiation by...
Monoamine oxidases (MAOA/MAOB) are enzymes known for their role in neurotransmitter regulation the central nervous system (CNS). Irreversible and non-selective MAO inhibitors (MAOi's) were first class of antidepressants, thus subsequent work on drugs such as selective MAOA inhibitor clorgyline has focussed selectivity increased CNS penetration. is highly expressed high grade metastatic prostate cancer with a proposed effect growth, recurrence, drug resistance. A Phase II Clinical Trial...
Abstract Monoamine oxidases (MAOs) degrade a number of biogenic and dietary amines, including monoamine neurotransmitters, play an essential role in many biological processes. Neurotransmitters related neural events have been shown to participate the development, differentiation, maintenance diverse tissues organs by regulating specialized cellular function morphological structures innervated such as prostate. Here we show that mice lacking both MAO isoforms, MAOA MAOB, exhibit smaller...
The inhibitor of apoptosis protein survivin is expressed in most cancers. Using the conditional PTEN deletion mouse model, we previously reported that levels increase with prostate tumor growth. Here evaluated functional role First, demonstrated mice lacking gene epithelium were fertile and had normal growth development. We then serially, from about 10–56 weeks age, histopathologic changes combined mono- or bi-allelic deletion. While within this time period animals wild-type monoallelic...
Abstract Telomerase plays a critical role in cancer, prompting the pursuit of various telomerase-based therapeutic strategies. One such strategy, telomerase interference, exploits high activity cancer cells and reprograms to encode “toxic” telomeres. To date, interference has been tested human xenografted into mice, an approach that does not recapitulate spontaneous malignancy offers few insights about host toxicities, because is targeted mouse host. address these limitations, we designed...