A5103180528- Prostate Cancer Treatment and Research
- Cancer, Hypoxia, and Metabolism
- Hormonal and reproductive studies
- Bipolar Disorder and Treatment
- Mental Health Research Topics
- Mental Health Treatment and Access
- Sexual Differentiation and Disorders
- Cancer, Lipids, and Metabolism
- Estrogen and related hormone effects
- Cancer-related molecular mechanisms research
- Tryptophan and brain disorders
- Child and Adolescent Psychosocial and Emotional Development
- Mental Health via Writing
- Epigenetics and DNA Methylation
- Pharmacogenetics and Drug Metabolism
- Ubiquitin and proteasome pathways
- Adipose Tissue and Metabolism
- Psychological and Temporal Perspectives Research
- High Altitude and Hypoxia
- Digestive system and related health
- Birth, Development, and Health
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Eicosanoids and Hypertension Pharmacology
- Schizophrenia research and treatment
- Electrolyte and hormonal disorders
Barwon Health
2024-2025
Deakin University
2024-2025
Florey Institute of Neuroscience and Mental Health
2024-2025
The University of Melbourne
2024-2025
Orygen Youth Health
2025
Orygen
2024
The Royal Melbourne Hospital
2024
Cleveland Clinic Lerner College of Medicine
2021-2024
Cerner (United States)
2023
Cleveland Clinic
2022-2023
Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in leads to derepression of retroelements (REs) followed by a double-stranded RNA (dsRNA)-stimulated interferon response blocks tumor growth. A forward genetic approach identified H3K9 trimethylation (H3K9me3) as an essential epigenetic adaptation antiandrogens, which enabled transcriptional silencing REs otherwise stimulate signaling and glucocorticoid receptor...
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...
Progression of prostate cancer depends on androgen receptor, which is usually activated by androgens. Therefore, a mainstay treatment deprivation therapy. Unfortunately, despite initial response, resistance nearly always develops, and disease progresses to castration-resistant (CRPC), remains driven non-gonadal androgens synthesized in tissues. 3β-Hydroxysteroid dehydrogenase/Δ5-->4 isomerase 1 (3βHSD1) catalyzes the rate-limiting step synthesis. However, how 3βHSD1, especially...
Abstract Background The depressive phase of bipolar disorder lasts longer than the manic and poses highest risk due to its negative impact on quality life mental health, peak in suicide attempts. Unfortunately, current therapies for are far more efficacious mania depression, suggesting an urgent need new improved depression. literature suggests chronic presence low-grade peripheral central inflammation is a key pathophysiology In particular, Angiotensin II Type I receptor (AT1R)...
Abstract Background Major depressive disorder (MDD) is a pervasive mental health condition with substantial global disease burden. Anhedonia core symptom of MDD and has been associated poorer prognosis suboptimal treatment response [1–3], however, the prevalence anhedonia its impact on related quality life outcomes not well-understood. There paucity data burden in Asia Pacific (APAC) [4–6], this potentially due to typically being managed distinctly from [4,5]. This study aims provide an...
Bipolar disorder (BD) is increasingly recognized as a with both mitochondrial dysfunction and heightened inflammatory reactivity, yet their contribution to neuronal activity remains unclear. To address these gaps, this study utilizes iPSC-derived cerebral organoids (COs) from BD patients healthy controls model disease-specific metabolic in physiologically relevant system. COs exhibited impairment, dysregulated function, increased nod-leucine rich repeat pyrin domain containing protein 3...
ABSTRACT Aim Anhedonia is a key symptom of major depressive disorder (MDD), however, its burden in patients with MDD not well understood. We aimed to assess the impact anhedonia on health‐related quality life (HRQoL), health‐care resource utilization (HRU), and work productivity subjects (MDD‐ANH) compared without ANH (MDD non‐ANH). Methods A cross‐sectional web‐based survey was conducted across six countries/territories. Adult participants were categorized as MDD‐ANH, non‐ANH, General...
Inhibiting H6PD restores prostate cancer response to AR antagonists by normalizing glucocorticoid metabolism in mouse xenograft models.
Abstract Androgen deprivation therapy suppresses tumor androgen receptor (AR) signaling by depleting circulating testosterone and is a mainstay treatment for advanced prostate cancer. Despite initial response, castration-resistant cancer nearly always develops remains driven primarily the axis. Here we investigated how changes in oxygenation affect synthesis. In cells, chronic hypoxia coupled to reoxygenation resulted efficient metabolism of precursors produce androgens activate AR. Hypoxia...
Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy an adrenal-permissive HSD3B1 (1245C) allele, which increases levels 3β-hydroxysteroid dehydrogenase (3βHSD1) and promotes intracellular androgen biosynthesis. Germline inheritance the adrenally permissive allele confers worse outcomes in PCa. We investigated whether drives resistance to combined deprivation radiotherapy. Adrenally 3βHSD1 enhanced radiotherapy PCa cell lines xenograft models engineered mimic human...
Androgens regulate broad physiologic and pathologic processes, including external genitalia development, prostate cancer progression, anti-inflammatory effects in both asthma. In cancer, several lines of evidence have implicated dietary endogenous fatty acids cell invasion, angiogenesis, treatment resistance. However, the role steroidogenesis mechanisms by which alterations this pathway occur are not well understood. Here, we show that, a panel tested, arachidonic acid its specific...
Most people with mental health problems do not seek help, delays of even decades in seeking professional help. Lack engagement services can lead to poor outcomes and functional impairment. However, few effective interventions have been identified improve help-seeking adults, those that exist are widely implemented deliver public impact. Co-designing lived experience ill-health other relevant stakeholders is critical increase the likelihood uptake these programs.
<title>Abstract</title> Psycho-linguistic theory postulates that linguistic features expressed in individuals’ communications may be valid indicators of their mental health. This trial aimed to examine the validity and reliability markers depressive anxiety symptoms adults. Using a randomised cross over design, 218 adults provided eight different types text data varying frequencies emotional valance including SMS data, social media posts, personal expressive essays, letters friend....
Abstract Background The rate of suicide attempts by patients with bipolar disorder is high. In addition to patient and country specific factors, environmental factors may contribute suicidal behavior. Sunlight has multiple diverse impacts on human physiology Solar insolation defined as the electromagnetic energy from sun striking a surface area earth. We previously found that large change in solar between minimum maximum monthly values was associated an increased risk I disorder. Methods...
144 Background: Kinase inhibitors have been ineffective in prostate cancer and no known role androgen biosynthesis. Inheritance of the adrenal-permissive HSD3B1(1245C) allele encodes a 3βHSD1 enzyme missense that up-regulates rate-limiting step biosynthesis from non-gonadal precursor steroids confers poor clinical outcomes castration-resistant (CRPC). About half all men with inherit HSD3B1 allele. Multiple studies demonstrate inheritance more rapid progression on ADT others also suggest...
<div>Abstract<p>Androgen deprivation therapy suppresses tumor androgen receptor (AR) signaling by depleting circulating testosterone and is a mainstay treatment for advanced prostate cancer. Despite initial response, castration-resistant cancer nearly always develops remains driven primarily the axis. Here we investigated how changes in oxygenation affect synthesis. In cells, chronic hypoxia coupled to reoxygenation resulted efficient metabolism of precursors produce androgens...
Supplementary Data from Hypoxia-Reoxygenation Couples 3βHSD1 Enzyme and Cofactor Upregulation to Facilitate Androgen Biosynthesis Hormone Therapy Resistance in Prostate Cancer
Supplementary Data from Hypoxia-Reoxygenation Couples 3βHSD1 Enzyme and Cofactor Upregulation to Facilitate Androgen Biosynthesis Hormone Therapy Resistance in Prostate Cancer
Supplementary Data from Hypoxia-Reoxygenation Couples 3βHSD1 Enzyme and Cofactor Upregulation to Facilitate Androgen Biosynthesis Hormone Therapy Resistance in Prostate Cancer
Supplementary Data from Hypoxia-Reoxygenation Couples 3βHSD1 Enzyme and Cofactor Upregulation to Facilitate Androgen Biosynthesis Hormone Therapy Resistance in Prostate Cancer
Abstract Background: Prostate cancer is the second leading cause of cancer-related death in men United States and dependent on androgens androgen receptor (AR) activation. Androgen deprivation therapy (ADT) mainstay treatment, but it as well next-generation treatments eventually fail. Disease then progresses castration-resistant prostate (CRPC), which driven by reactivation androgen-AR axis. 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) catalyzes rate-limiting step for potent synthesis from...