Small cell prostate cancer

This study discusses the synthesis and use of a new library of spirooxindole-benzimidazole compounds as inhibitors of the signal transducer and activator of p53, a protein involved in regulating cell growth and cancer prevention. The text includes the scientific details of the [3 + 2] cycloaddition (32CA) reaction between azomethine ylide 7a and ethylene 3a within the framework of Molecular Electron Density Theory. The mechanism of the 32CA reaction proceeds through a two-stage one-step process, with emphasis on the highly asynchronous transition state structure...

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) for the treatment of oligometastatic disease can improve survival and delay the requirement for systemic therapy. The benefits of SABR in oligoprogressive disease are less well-defined. Here, we evaluate the available evidence investigating the efficacy of SABR in the treatment of oligoprogressive disease. METHODS: A systematic review was carried out following PRISMA guidelines. Medline and Embase databases were searched using the terms "stereotactic radiotherapy" OR "SABR" OR "Stereotactic Ablative Body Radiotherapy" OR "SBRT" OR "SRT" AND "oligoprogression" in May 2022, June 2023, and February 2024...

Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers comprised of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of PGC-1α, a potent regulator of mitochondrial oxidative phosphorylation (OXPHOS), across several SCNC types. PGC-1α correlated tightly with increased expression of the lineage marker ASCL1 through a positive feedback mechanism...

Genome instability is a hallmark of cancer and are driven by mutations in oncogenes and tumor suppressor genes. Despite successes seen with select targeted therapeutics, this type of personalized medicine is only beneficial for a small subpopulation of cancer patients who have one of a few actionable genetic changes. Most tumors also contain hundreds of passenger mutations that offered no fitness advantage or disadvantage during tumor evolution. Mutations in known pharmacogenetic (PGx) loci for which germline variants encode variability in drug response can cause somatically acquired drug sensitivity...

UNLABELLED: Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)--a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival...

Objective: To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC. Methods: In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients)...

The androgen receptor (AR) and estrogen receptor alpha (ERα) are steroid receptor transcription factors with critical roles in the development and progression of prostate and breast cancers. Advances in the understanding of mechanisms underlying the ligand-dependent activation of these transcription factors have contributed to the development of small molecule inhibitors that block AR and ERα actions. These inhibitors include competitive antagonists and degraders that directly bind the ligand binding domains of these receptors, luteinizing hormone releasing hormone (LHRH) analogs that suppress gonadal synthesis of testosterone or estrogen, and drugs that block specific enzymes required for biosynthesis of testosterone or estrogen...

In contemporary oncologic diagnostics, molecular imaging modalities are pivotal for precise local and metastatic staging. Recent studies identified fibroblast activation protein as a promising target for molecular imaging across various malignancies. Therefore, we aimed to systematically evaluate the current literature on the utility of fibroblast activation protein inhibitor (FAPI) PET/CT for staging patients with genitourinary malignancies. Methods: A systematic Embase and Medline search was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) process, on August 1, 2023...

Cigarette smoke changes the genomic and epigenomic imprint of cells. In this study, we investigated the biological consequences of extended cigarette smoke exposure on dental pulp stem cells (DPSCs) and the potential roles of miRNAs. DPSCs were treated with various doses of cigarette smoke condensate (CSC) for up to six weeks. Cell proliferation, survival, migration, and differentiation were evaluated. Cytokine and miRNA expression were profiled. The results showed that extended exposure to CSC significantly impaired the regenerative capacity of the DPSCs...

BACKGROUND: HER3 (ErbB3), a member of the human epidermal growth factor receptor family, is frequently overexpressed in various cancers. Multiple HER3-targeting antibodies and antibody-drug conjugates (ADCs) were developed for the solid tumor treatment, however none of HER3-targeting agent has been approved for tumor therapy yet. We developed DB-1310, a HER3 ADC composed of a novel humanized anti-HER3 monoclonal antibody covalently linked to a proprietary DNA topoisomerase I inhibitor payload (P1021), and evaluate the efficacy and safety of DB-1310 in preclinical models...

Homologous recombination (HR) related gene alterations are present in a significant subset of prostate, breast, ovarian, pancreatic, lung and colon cancers rendering these tumors as potential responders to specific DNA damaging agents. A small molecule acylfulvene prodrug, LP-184, metabolizes to an active compound by the oxidoreductase activity of enzyme Prostaglandin Reductase 1 (PTGR1), which is frequently elevated in multiple solid tumor types. Prior work demonstrated that cancer cell lines deficient in a spectrum of (DNA damage repair) DDR pathway genes show increased susceptibility to LP-184...

Ferroptosis is a form of regulatory cell death that relies on iron and reactive oxygen species (ROS) to inhibit tumors. The present study aimed to investigate whether icariin-curcumol could be a novel ferroptosis inducer in tumor inhibition. Various concentrations of icariin-curcumol were used to stimulate prostate cell lines (RWPE-2, PC-3, VCAP and DU145). Small interfering negative control (si-NC) and si-nuclear factor erythroid 2-related factor 2 (Nrf2) were used to transfect DU145 cells. Cell viability was determined by using cell counting kit-8...

Previously, we designed the EuK-based PSMA ligand BQ0413 with an maE3 chelator for labeling with technetium-99m. It showed efficient tumor targeting, but our preclinical data and preliminary clinical results indicated that the renal excretion levels need to be decreased. We hypothesized that this could be achieved by a decrease in the ligand's total negative charge, achieved by substituting negatively charged glutamate residues in the chelator with glycine. The purpose of this study was to evaluate the tumor targeting and biodistribution of two new PSMA inhibitors, BQ0411 and BQ0412, compared to BQ0413...

Transthyretin binders have previously been used to improve the pharmacokinetic properties of small-molecule drug conjugates and could, thus, be utilized for radiopharmaceuticals as an alternative to the widely explored "albumin binder concept". In this study, a novel PSMA ligand modified with a transthyretin-binding entity (TB-01) was synthesized and labeled with lutetium-177 to obtain [177 Lu]Lu-PSMA-TB-01. A high and specific uptake of [177 Lu]Lu-PSMA-TB-01 was found in PSMA-positive PC-3 PIP cells (69 ± 3% after 4 h incubation), while uptake in PSMA-negative PC-3 flu cells was negligible (<1%)...

BACKGROUND: Prostate cancer (PCa) is the second-leading cause of cancer mortalities in the United States and is the most commonly diagnosed malignancy in men. While androgen deprivation therapy (ADT) is the first-line treatment option to initial responses, most PCa patients invariably develop castration-resistant PCa (CRPC). Therefore, novel and effective treatment strategies are needed. The goal of this study was to evaluate the anticancer effects of the combination of two small molecule inhibitors, SZL-P1-41 (SKP2 inhibitor) and PBIT (KDM5B inhibitor), on PCa suppression and to delineate the underlying molecular mechanisms...

Multiple cancer cell types are found in prostate tumors. They are either luminal-like adenocarcinoma or less luminal-like and more stem-like non-adenocarcinoma and small cell carcinoma. These types are lineage related through differentiation. Loss of cancer differentiation from luminal-like to stem-like is mediated by the activation of stem cell transcription factors (scTF) such as LIN28A, NANOG, POU5F1 and SOX2. scTF expression leads to down-regulation of β2-microglobulin (B2M). Thus, cancer cells can change from the <mml:math xmlns:mml="https://www...

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA...

Prostate cancer is the most prevalent malignancy in men. While diagnostic and therapeutic interventions have substantially improved in recent years, disease relapse, treatment resistance, and metastasis remain significant contributors to prostate cancer-related mortality. Therefore, novel therapeutic approaches are needed. Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway which plays an essential role in cholesterol homeostasis...

The translocator protein 18-kDa (TSPO) is a mitochondrial membrane protein that is previously identified as the peripheral benzodiazepine receptor (PBR). Furthermore, it plays a significant role in a diverse range of biochemical processes, including steroidogenesis, mitochondrial cholesterol transport, cell survival and death, cell proliferation, and carcinogenesis. Several investigations also reported its roles in various types of cancers, including colorectal, brain, breast, prostate, and lung cancers, as well as melanoma...

BACKGROUND: Chronic inflammation is associated with various malignant tumors. Bacterial lipopolysaccharides (LPSs) play a significant part in the event and development of prostate cancer. Dishevelled segment polarity protein 3 ( DVL3 ) is a shared component of the Wnt/β-catenin and Notch signaling pathways, which are involved in tumor progression, chemoresistance, and maintenance of stem cell-like properties. According to reports, prostatic cancer cell invasion and proliferation are mediated by toll-like receptor 4 ( TLR4 )...