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The Prostate Jun 2021Hedgehog (Hh) signaling promotes castration-resistant prostate cancer by supporting androgen-independent prostate cancer cell development and growth; however, its role...
PURPOSE
Hedgehog (Hh) signaling promotes castration-resistant prostate cancer by supporting androgen-independent prostate cancer cell development and growth; however, its role in neuroendocrine prostate cancer (NEPC) has not yet been explored. In this study, we assessed the expression of key genes involved in Hh signaling in prostate cancer and investigated the potential role of smoothened (SMO) in the pathogenesis of NEPC.
METHODS
Six public datasets, each containing cases of prostate adenocarcinoma (AdPC) and NEPC, were analyzed to compare the differential messenger RNA (mRNA) expression of six classic Hh signaling genes. The SMO, synaptophysin, chromogranin A (CHGA) and androgen receptor (AR) proteins were evaluated in human tissues from 5 cases of NEPC, 2 cases of AdPC mixed with NEPC, 2 cases of AdPC with neuroendocrine differentiation and 22 cases of high-grade AdPC as determined by an immunohistochemistry assay. Gene set enrichment analysis (GSEA) was performed to identify relevant genetic signatures associated with SMO expression based on the public datasets. Stable SMO-knockdown LNCaP and C4-2B cells were established with a lentiviral system, and the expression of SMO, Gli1, AR, prostate-specific antigen (PSA), and REST was assessed by real-time polymerase chain reaction and western blot. Secreted PSA in the conditioned medium was assessed by ELISA. Gli1 was ectopically expressed performed by the transfection of Gli1 complementary DNA into SMO-knockdown LNCaP cells, and western blot was used to assess of AR and PSA expression.
RESULTS
The mRNA level of SMO was dramatically downregulated in NEPC samples compared with AdPC samples in all 6 public datasets. SMO protein loss was observed in 100% of NEPC samples but in only 9% (2 of 22) of high-grade AdPC samples. GSEA results showed that SMO loss was closely correlated with AR signaling activity. Stable SMO knockdown significantly attenuated AR signaling activity and suppressed AR expression, while Gli1 overexpression partially reversed the inhibitory effects of SMO knockdown on AR signaling activity and AR expression in LNCaP and C4-2B cells.
CONCLUSION
These results demonstrate that SMO loss is a characteristic of NEPC and that detecting SMO by IHC could aid pathologists in NEPC diagnosis. SMO loss may promote NEPC pathogenesis by modulating AR signaling.
Topics: Adenocarcinoma; Carcinoma, Neuroendocrine; Cells, Cultured; Chromogranin A; Down-Regulation; Gene Expression Profiling; Gene Knockdown Techniques; Hedgehog Proteins; Humans; Immunohistochemistry; Male; Prostate; Prostatic Neoplasms; RNA, Messenger; Receptors, Androgen; Signal Transduction; Smoothened Receptor; Synaptophysin
PubMed: 33955576
DOI: 10.1002/pros.24122 -
Journal of Comparative Pathology Aug 2019The terminology applied to canine prostatic epithelial lesions, especially carcinomas, is currently not standardized and this hampers the ability of pathologists to... (Review)
Review
The terminology applied to canine prostatic epithelial lesions, especially carcinomas, is currently not standardized and this hampers the ability of pathologists to study the biological and clinical significance of these lesions. The aim of this review is to present the essential histomorphological diagnostic attributes of a wide spectrum of prostatic epithelial lesions in dogs. In addition to the traditionally recognized prostatic hyperplasia, hormonal atrophy, prostatitis, squamous metaplasia, adenocarcinoma and transitional cell (urothelial) carcinoma, new entities are described and discussed in order to provide veterinary pathologists with a basic atlas of common histological lesions of the canine prostate that is comprehensive and easy to use.
Topics: Animals; Dog Diseases; Dogs; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Terminology as Topic
PubMed: 31540623
DOI: 10.1016/j.jcpa.2019.07.005 -
Cancer Causes & Control : CCC Mar 2023Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We...
PURPOSE
Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We investigated MS and PC diagnosis in black and white men undergoing prostate biopsy in an equal access healthcare system. We hypothesized MS would be linked with aggressive PC, regardless of race.
METHODS
Among men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, medical record data abstraction of diagnosis or treatment for hypertension (≥ 130/85 mmHg), dyslipidemia (HDL < 40 mg/dL), hypertriglyceridemia (≥ 150 mg/dL), diabetes, hyperglycemia (fasting glucose ≥ 100 ml/dL), and central obesity (waist circumference ≥ 40 inches) were done. Biopsy grade group (GG) was categorized as low (GG1) or high (GG2-5). Multinomial logistic regression was used to examine MS (3-5 components) vs. no MS (0-2 components) and diagnosis of high grade and low grade vs. no PC, adjusting for potential confounders. Interactions between race and MS were also tested.
RESULTS
Of 1,051 men (57% black), 532 (51%) had MS. Men with MS were older, more likely to be non-black, and had a larger prostate volume (all p ≤ 0.011). On multivariable analysis, MS was associated with high-grade PC (OR = 1.73, 95% CI 1.21-2.48, p = 0.003), but not overall PC (OR = 1.17, 95% CI 0.88-1.57, p = 0.29) or low grade (OR = 0.87, 95% CI 0.62-1.21, p = 0.39). Results were similar in black and non-black men (all p-interactions > 0.25).
CONCLUSION
Our data suggest that metabolic dysregulation advances an aggressive PC diagnosis in both black and non-black men. If confirmed, prevention of MS could reduce the risk of developing aggressive PC, including black men at higher risk of PC mortality.
Topics: Male; Humans; Prostate; Metabolic Syndrome; Prostatic Neoplasms; Prostate-Specific Antigen; Obesity
PubMed: 36450931
DOI: 10.1007/s10552-022-01649-9 -
Radiology. Imaging Cancer Jul 2023
Topics: Male; Humans; Prostate; Prostatic Neoplasms; Gallium Isotopes; Adenocarcinoma
PubMed: 37449916
DOI: 10.1148/rycan.230037 -
International Journal of Molecular... Nov 2021The link between the microbiome and cancer has led researchers to search for a potential probe for intracellular targeting of bacteria and cancer. Herein, we developed...
The link between the microbiome and cancer has led researchers to search for a potential probe for intracellular targeting of bacteria and cancer. Herein, we developed near infrared-emitting ternary AgInSe/ZnS quantum dots (QDs) for dual bacterial and cancer imaging. Briefly, water-soluble AgInSe/ZnS QDs were synthesized in a commercial kitchen pressure cooker. The as-synthesized QDs exhibited a spherical shape with a particle diameter of 4.5 ± 0.5 nm, and they were brightly fluorescent with a photoluminescence maximum at 705 nm. The QDs showed low toxicity against mouse mammary carcinoma (FM3A-Luc), mouse colon carcinoma (C26), malignant fibrous histiocytoma-like (KM-Luc/GFP) and prostate cancer cells, a greater number of accumulations in , and good cellular uptake in prostate cancer cells. This work is an excellent step towards using ternary QDs for diagnostic and guided therapy for prostate cancer.
Topics: Animals; Cell Line, Tumor; Colonic Neoplasms; Female; Histiocytoma, Malignant Fibrous; Humans; Indium; Male; Mammary Neoplasms, Animal; Mice; Prostatic Neoplasms; Prostatitis; Quantum Dots; Selenium; Silver; Staphylococcus aureus; Sulfides; Water; Zinc Compounds
PubMed: 34830396
DOI: 10.3390/ijms222212514 -
Prostate Cancer and Prostatic Diseases Feb 2022Binding of F-DCFPyL at prostate cancer (PC) cells increases over time. The dual-phase protocol may be helpful in separating benign lesions from malignant ones associated...
OBJECTIVE
Binding of F-DCFPyL at prostate cancer (PC) cells increases over time. The dual-phase protocol may be helpful in separating benign lesions from malignant ones associated with prostate cancer. The purpose of this study was to retrospectively analyze the incremental diagnostic value of F-DCFPyL dual-time imaging in patients with prostate cancer.
METHOD
114 prostate-related malignant lesions and 43 benign lesions in 38 patients with prostate cancer were retrospectively analyzed. Maximum standardized uptake value (SUVmax) for benign and prostate-related malignant lesions were calculated at min 60 and min 120 of PET/CT imaging. In order to calculate SUV ratio, the SUVmax of left gluteus maximus was measured at the same time. The difference of SUVmax metrics and SUV ratio between malignant and benign lesions was statistically analyzed, the cut-off value of ROC curve was calculated, and the diagnostic efficacy of SUVmax index and SUV ratio at two time points was compared.
RESULTS
SUVmax metrics and SUV ratio of early and delayed imaging of PC-related malignant lesions were significantly higher than those of benign lesions (p < 0.05). In terms of individual indicators, the highest accuracy and sensitivity was in the delayed SUV ratio (89.2% and 94.7%), the best specificity was in the early SUVmax (93.0%). When the individual and combined indicators were compared together, the SUV ratio in the delay period still showed the best diagnostic sensitivity and accuracy, and the best specificity were SUVmax early and ▵SUVmax, SUVmax early and RI.
CONCLUSIONS
Uptake of F-DCFPyL increased over time in prostate-associated malignant lesions compared with benign tissue. For single-phase imaging, 2-hour (delayed) imaging has better diagnostic performance. However, the dual-phase imaging (1 and 2 h) are helpful in the differential diagnosis of prostate-associated malignant lesions and benign lesions.
Topics: Carcinoma; Fluorodeoxyglucose F18; Humans; Male; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostate; Prostatic Neoplasms; Radiopharmaceuticals; Retrospective Studies
PubMed: 35422099
DOI: 10.1038/s41391-022-00534-5 -
International Journal of Molecular... Jan 2023Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct...
Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment. Plasma exosomes were isolated from CRPC (n = 10), NSCLC (n = 14), and healthy controls (n = 10) using three different methods: size exclusion chromatography (SEC), lectin binding, and T-cell immunoglobulin domain and mucin domain-containing protein 4 (TIM4) binding. Molecular profiles were determined by mass spectrometry of extracted exosome fractions. Enrichment analysis of uniquely detected molecules was performed for each method with MetaboAnalyst. The exosome enrichment index (EEI) scores methods based on top differential molecules between patient groups. The lipidomic analysis detected 949 lipids using exosomes from SEC, followed by 246 from lectin binding and 226 from TIM4 binding. The detectable metabolites showed SEC identifying 191 while lectin binding and TIM4 binding identified 100 and 107, respectively. When comparing uniquely detected molecules, different methods showed preferential enrichment of different sets of molecules with SEC enriching the greatest diversity. Compared to controls, SEC identified 28 lipids showing significant difference in NSCLC, while only 1 metabolite in NSCLC and 5 metabolites in CRPC were considered statistically significant (FDR < 0.1). Neither lectin-binding- nor TIM4-binding-derived exosome lipids or metabolites demonstrated significant differences between patient groups. We observed the highest EEI from SEC in lipids (NSCLC: 871.33) which was also noted in metabolites. These results support that the size exclusion method of exosome extraction implemented by SBI captures more heterogeneous exosome populations. In contrast, lectin-binding and TIM4-binding methods bind surface glycans or phosphatidylserine moieties of the exosomes. Overall, these findings suggest that specific isolation methods select subpopulations which may significantly impact cancer biomarker discovery.
Topics: Male; Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Exosomes; Lipidomics; Prostate; Prostatic Neoplasms, Castration-Resistant; Metabolome; Lipids; Lectins
PubMed: 36768152
DOI: 10.3390/ijms24031830 -
Medicine Mar 2023Colon carcinoma is the most common type of cancer, and a leading cause of cancer-related death. Clinically, the most common sites of metastases from colon carcinoma are... (Review)
Review
RATIONALE
Colon carcinoma is the most common type of cancer, and a leading cause of cancer-related death. Clinically, the most common sites of metastases from colon carcinoma are the liver, lungs, peritoneum, and lymph nodes, while the incidence of metastases to the prostate is low. There are few relevant studies on colon carcinoma, most of them being case reports.
PATIENT CONCERNS
A 76-year-old man treated with radical resection of right colon carcinoma due to primary poorly differentiated adenocarcinoma of the cecum. Postoperative pathological examination suggested that he had cancer at the junction of the ascending colon and the cecum. He had received adjuvant chemotherapy after surgery. One year later, he received transurethral plasma resection of the prostate due to urinary system discomfort. Postoperative pathological immunohistochemistry suggested prostate metastasis of colorectal carcinoma, and he received individualized treatment, but this produced no clear survival benefit.
DIAGNOSES
Ascending colon cecal junction carcinoma with prostate metastasis.
INTERVENTIONS
Radical resection, chemotherapy, anti-androgen therapy, surgery to relieve primary lesion obstruction symptoms, and local radiotherapy of the prostate.
OUTCOMES
At present, clinical cases of colon carcinoma with prostate metastasis are rare. By sharing a rare case of ascending colon cecal junction carcinoma with prostate metastasis and reviewing the relevant literature, this paper explores and optimizes the clinical treatment of colon carcinoma with prostate metastasis.
Topics: Male; Humans; Aged; Colon, Ascending; Prostate; Prostatic Neoplasms; Colonic Neoplasms; Carcinoma; Cecal Neoplasms
PubMed: 36930066
DOI: 10.1097/MD.0000000000033308 -
Current Oncology (Toronto, Ont.) Mar 2022Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in... (Review)
Review
Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in the literature. Data on treatment options are scarce. The aim of our work was to retrospectively review the published reports. Thirty-three case reports or case series were analyzed (106 patients in total). Pathological features, management, and follow-up information were evaluated. Despite the relatively low level of evidence given the unavoidable lack of prospective trials for such a rare prostate tumor, the following considerations were made: prostate ACC/BCC is an aggressive tumor often presenting with locally advanced disease and incidental diagnosis occurs during transurethral resection of the prostate for urinary obstructive symptoms. Prostate-specific antigen was not a reliable marker for diagnosis nor follow-up. Adequate staging with Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) should be performed before treatment and during follow-up, while there is no evidence for the use of Positron Emission Tomography (PET). Radical surgery with negative margins and possibly adjuvant radiotherapy appear to be the treatments of choice. The response to androgen deprivation therapy was poor. Currently, there is no evidence of the use of truly effective systemic therapies.
Topics: Androgen Antagonists; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Humans; Male; Prostate; Prostatic Neoplasms; Retrospective Studies; Skin Neoplasms; Transurethral Resection of Prostate
PubMed: 35323352
DOI: 10.3390/curroncol29030152 -
The Oncologist Dec 2022Challenges with sequencing tissue samples from patients with prostate cancer have been reported in clinical trials. To assess the success rate of comprehensive genomic...
Challenges with sequencing tissue samples from patients with prostate cancer have been reported in clinical trials. To assess the success rate of comprehensive genomic profiling (CGP) for prostate cancer patients, we analyzed a real-world cohort who underwent sequencing of their prostate tissue sample as well as a subset of patients with a reflex liquid biopsy. Overall, a significant majority (82%) of tissue prostate carcinoma samples yielded reportable CGP results. Of those samples that were unsuccessful, most (75%) were inadequate samples that did not meet pre-established criteria to advance into sequencing. For cases where liquid CGP was performed if tissue CGP was unsuccessful, mutations that were likely attributable to prostate carcinoma were observed in most cases and all cases were successful in generating a report. These results suggest that, for CGP testing, prostate cancer tissue is a reasonable matrix type and that liquid samples can be effectively used as an alternative to tissue.
Topics: Humans; Male; Prostate; Prostatic Neoplasms; Carcinoma
PubMed: 36069892
DOI: 10.1093/oncolo/oyac181