Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer (PCa) is the second commonly diagnosed malignancy in men over the world. Although androgen deprivation therapy for advanced PCa patients has significantly improved their survival, the majority of these patients eventually develop castration-resistant prostate cancer (CRPC). Proscillaridin A (Pro A), a cardiac glycoside that is clinically used to treat various heart failure diseases, has been reported to have anticancer activity in several cancers. However, whether Pro A exerts an inhibitory effect on PCa progression remains unknown. In this study, we determined possible antitumor effects of Pro A on PCa cells and demonstrated the following: firstly, Pro A selectively inhibited androgen-independent PCa (including PC3 and DU145) cell growth and induced cell apoptosis in vitro; secondly, Pro A significantly decreased cell motility and invasion of androgen-independent PCa cells; thirdly, Pro A enhanced the sensitivity of PCa cells to docetaxel; fourthly, Pro A significantly inhibited the growth of PCa xenografts in vivo and patient-derived organoids (PDO). In addition, RNA-sequencing analysis revealed that the antitumor effects of Pro A on androgen-independent PCa appeared to be achieved via driving the activation of endoplasmic reticulum stress. The antitumor effects of Pro A could be ameliorated by reactive oxygen species scavenger and ER stress inhibitors. Therefore, these data suggest that Pro A may provide a potential therapeutic option for the treatment of PCa, particularly CRPC.
 ...
PMID:Proscillaridin A slows the prostate cancer progression through triggering the activation of endoplasmic reticulum stress. 3200 41

Cardiac amyloidosis (CA) is an important cause of restrictive cardiomyopathy and heart failure with preserved ejection fraction (HFpEF). At present, 3 bone-seeking tracers, 99mTc-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), 99mTc-pyrophosphate (99mTc-PYP), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP), have been evaluated for detecting CA, but they are not widely available. In contrast, methylene diphosphate (MDP) is widely available. However, only sporadic case reports have shown that MDP can accumulate in patients with CA. We report an 86-year-old man with multiple medical problems, including hypertension, hyperlipidemia, HFpEF, and a history of treated prostate cancer, who was referred for a 99mTc-MDP bone scan to rule out bone metastasis. The bone scan was negative for bone metastasis, but there was mild tracer accumulation in the heart, suggestive of CA. Subsequently, CA was diagnosed on 99mTc-PYP imaging. MDP may play a role comparable to other bone-seeking tracers in the diagnosis of CA and may be used as a noninvasive adjunct in the diagnosis of CA. Future research should compare MDP with other bone-seeking tracers for the diagnosis of CA. In addition, mechanistic studies on tracer binding to amyloid fibrils may help understand the pathophysiology of CA and facilitate the development of better and more specific tracers for CA.
 ...
PMID:Incidentally detected cardiac amyloidosis on 99mTc-MDP bone scintigraphy. 3228 Apr 3

The orphan nuclear receptor COUP-TFII is expressed at a low level in adult tissues, but its expression is increased and shown to promote progression of multiple diseases, including prostate cancer, heart failure, and muscular dystrophy. Suppression of COUP-TFII slows disease progression, making it an intriguing therapeutic target. Here, we identified a potent and specific COUP-TFII inhibitor through high-throughput screening. The inhibitor specifically suppressed COUP-TFII activity to regulate its target genes. Mechanistically, the inhibitor directly bound to the COUP-TFII ligand-binding domain and disrupted COUP-TFII interaction with transcription regulators, including FOXA1, thus repressing COUP-TFII activity on target gene regulation. Through blocking COUP-TFII's oncogenic activity in prostate cancer, the inhibitor efficiently exerted a potent antitumor effect in xenograft mouse models and patient-derived xenograft models. Our study identified a potent and specific COUP-TFII inhibitor that may be useful for the treatment of prostate cancer and possibly other diseases.
 ...
PMID:Small-molecule inhibitor targeting orphan nuclear receptor COUP-TFII for prostate cancer treatment. 3249 82

A 63-year-old man with a significantly high prostate-specific antigen level was diagnosed via pathology to have advanced prostate adenocarcinoma due to multiple lung metastases. He was then treated with androgen deprivation therapy (ADT) comprising bicalutamide and goserelin. Only after 6 months of stable disease, the cancer progressed and the drug was changed to abiraterone; however, no significant therapeutic effect was observed and the disease was considered as castration-resistant prostate cancer. The histopathologic analysis of the biopsied metastatic lymph node confirmed small-cell neuroendocrine carcinoma, and genetic testing revealed BRCA1 germ-line mutation. The oral PARP inhibitor olaparib was used and achieved a partial tumor response over a period of 2.5 months. Meanwhile, palliative radiotherapy was performed for pain control in the sacrococcygeal region with complete symptom relief. The combination chemotherapy strategy of etoposide and cisplatin was used after the failure of olaparib and achieved pain alleviation in the left leg. The patient received one cycle of this chemotherapy strategy and eventually died of a rapid tumor progression, respiratory failure, and heart failure on April 27, 2019.
 ...
PMID:Metastatic Castration-Resistant Prostate Cancer with Neuroendocrine Transformation and BRCA 1 Germ-Line Mutation: A Case Report and Literature Review. 3284 24

Neprilysin (NEP) is an integral membrane-bound metallopeptidase with a wide spectrum of substrates and physiological functions. It plays an important role in proteolytic processes in the kidney, cardiovascular regulation, immune response, cell proliferation, foetal development etc. It is an important neuropeptidase and amyloid-degrading enzyme which makes NEP a therapeutic target in Alzheimer's disease (AD). Moreover, it plays a preventive role in development of cancer, obesity and type-2 diabetes. Recently a role of NEP in COVID-19 pathogenesis has also been suggested. Despite intensive research into NEP structure and functions in different organisms, changes in its expression and regulation during brain development and ageing, especially in age-related pathologies, is still not fully understood. This prevents development of pharmacological treatments from various diseases in which NEP is implicated although recently a dual-acting drug sacubitril-valsartan (LCZ696) combining a NEP inhibitor and angiotensin receptor blocker has been approved for treatment of heart failure. Also, various natural compounds capable of upregulating NEP expression, including green tea (EGCG), have been proposed as a preventive medicine in prostate cancer and AD. This review summarizes the existing literature and our own research on the expression and activity of NEP in normal brain development, ageing and under pathological conditions.
 ...
PMID:Neprilysin expression and functions in development, ageing and disease. 3298 38


<< Previous 1 2 3 4 5 6