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Open Veterinary Journal May 2024Canine prostatic carcinoma (cPC) is a urogenital tumour with a poor prognosis, for which no effective treatment has been established. Recently, it has been shown that...
BACKGROUND
Canine prostatic carcinoma (cPC) is a urogenital tumour with a poor prognosis, for which no effective treatment has been established. Recently, it has been shown that human epidermal growth factor receptor type 2 (HER2) is overexpressed in cPC cells; however, the efficacy of HER2-targeted therapy remains unclear.
AIM
Investigate the anti-tumour effect of lapatinib on HER2-positive cPC cell lines.
METHODS
Two cell lines (muPC and bePC) were established from two dogs with cPC and the effects of lapatinib treatment on cell proliferation, apoptosis, and HER2 downstream signalling were investigated. Furthermore, muPC was used to generate tumour-bearing mice, and the anti-tumour effects of lapatinib were examined .
RESULTS
Lapatinib treatment inhibited the proliferation and phosphorylation of Erk1/2 and Akt, which are downstream signals of HER2. Furthermore, the TUNEL assay showed that lapatinib induced apoptosis in both cell lines. The muPC-engrafted nude mouse model showed that lapatinib significantly inhibited tumour growth and increased the area of necrotic tumour tissue compared to the vehicle-treated groups.
CONCLUSION
Lapatinib exerts anti-tumour effects on cPC cells by inhibiting HER-2 signalling.
Topics: Lapatinib; Animals; Dogs; Male; Cell Line, Tumor; Dog Diseases; Prostatic Neoplasms; Antineoplastic Agents; Receptor, ErbB-2; Mice; Mice, Nude; Apoptosis; Cell Proliferation; Quinazolines
PubMed: 38938437
DOI: 10.5455/OVJ.2024.v14.i5.21 -
Journal of Translational Medicine Jun 2024Over the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast...
BACKGROUND
Over the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast tumors, in order to improve both outcome prediction and treatment decision-making. In this context, molecular signatures gained by main components of the tumor microenvironment, such as cancer-associated fibroblasts (CAFs), have been explored as prognostic and therapeutic tools. Nevertheless, a deeper understanding of the significance of CAFs-related gene signatures in breast and prostate cancers still remains to be disclosed.
METHODS
RNA sequencing technology (RNA-seq) was employed to profile and compare the transcriptome of CAFs isolated from patients affected by breast and prostate tumors. The differentially expressed genes (DEGs) characterizing breast and prostate CAFs were intersected with data from public datasets derived from bulk RNA-seq profiles of breast and prostate tumor patients. Pathway enrichment analyses allowed us to appreciate the biological significance of the DEGs. K-means clustering was applied to construct CAFs-related gene signatures specific for breast and prostate cancer and to stratify independent cohorts of patients into high and low gene expression clusters. Kaplan-Meier survival curves and log-rank tests were employed to predict differences in the outcome parameters of the clusters of patients. Decision-tree analysis was used to validate the clustering results and boosting calculations were then employed to improve the results obtained by the decision-tree algorithm.
RESULTS
Data obtained in breast CAFs allowed us to assess a signature that includes 8 genes (ITGA11, THBS1, FN1, EMP1, ITGA2, FYN, SPP1, and EMP2) belonging to pro-metastatic signaling routes, such as the focal adhesion pathway. Survival analyses indicated that the cluster of breast cancer patients showing a high expression of the aforementioned genes displays worse clinical outcomes. Next, we identified a prostate CAFs-related signature that includes 11 genes (IL13RA2, GDF7, IL33, CXCL1, TNFRSF19, CXCL6, LIFR, CXCL5, IL7, TSLP, and TNFSF15) associated with immune responses. A low expression of these genes was predictive of poor survival rates in prostate cancer patients. The results obtained were significantly validated through a two-step approach, based on unsupervised (clustering) and supervised (classification) learning techniques, showing a high prediction accuracy (≥ 90%) in independent RNA-seq cohorts.
CONCLUSION
We identified a huge heterogeneity in the transcriptional profile of CAFs derived from breast and prostate tumors. Of note, the two novel CAFs-related gene signatures might be considered as reliable prognostic indicators and valuable biomarkers for a better management of breast and prostate cancer patients.
Topics: Humans; Prostatic Neoplasms; Male; Breast Neoplasms; Female; Cancer-Associated Fibroblasts; Gene Expression Regulation, Neoplastic; Prognosis; Transcriptome; Gene Expression Profiling; Cluster Analysis; Treatment Outcome; Middle Aged; Kaplan-Meier Estimate
PubMed: 38937754
DOI: 10.1186/s12967-024-05413-2 -
Causal relationship between prostatic diseases and prostate cancer: a mendelian randomization study.BMC Cancer Jun 2024Although it is thought that prostatitis or benign prostatic hyperplasia (BPH) is related to prostate cancer (PCa), the underlying causal effects of these diseases are...
BACKGROUND
Although it is thought that prostatitis or benign prostatic hyperplasia (BPH) is related to prostate cancer (PCa), the underlying causal effects of these diseases are unclear.
METHODS
We assessed the causal relationship between prostatitis or BPH and PCa using a two-sample Mendelian randomization (MR) approach. The data utilized in this study were sourced from genome-wide association study. The association of genetic variants from cohorts of prostatitis or BPH and PCa patients was determined using inverse-variance weighted and MR Egger regression techniques. The direction of chance was determined using independent genetic variants with genome-wide significance (P < 5 × 10). The accuracy of the results was confirmed using sensitivity analyses.
RESULTS
MR analysis showed that BPH had a significant causal effect on PCa (Odds Ratio = 1.209, 95% Confidence Interval: 0.098-0.281, P = 5.079 × 10) while prostatitis had no significant causal effect on PCa (P > 0.05). Additionally, the pleiotropic test and leave-one-out analysis showed the two-sample MR analyses were valid and reliable.
CONCLUSIONS
This MR study supports that BPH has a positive causal effect on PCa, while genetically predicted prostatitis has no causal effect on PCa. Nonetheless, further studies should explore the underlying biochemical mechanism and potential therapeutic targets for the prevention of these diseases.
Topics: Humans; Male; Mendelian Randomization Analysis; Prostatic Neoplasms; Genome-Wide Association Study; Prostatic Hyperplasia; Prostatitis; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38937672
DOI: 10.1186/s12885-024-12551-9 -
Scientific Reports Jun 2024The prognostic significance of unconventional histology (UH) subtypes including intraductal carcinoma of the prostate (IDC-P), ductal adenocarcinoma, and cribriform...
The prognostic significance of unconventional histology (UH) subtypes including intraductal carcinoma of the prostate (IDC-P), ductal adenocarcinoma, and cribriform pattern has been investigated for prostate cancer (PCa). However, little is known about magnetic resonance imaging (MRI) features and the oncological impact of tumor localization in localized PCa with UH. Clinical data of 211 patients with acinar adenocarcinoma (conventional histology [CH]) and 82 patients with UH who underwent robotic-assisted radical prostatectomy (RARP) were reviewed. Patients with UH are more likely to be older and have higher Gleason grade group, higher Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score, and larger tumor volume (TV) than those with CH. Multivariate analysis identified the presence of UH as an independent prognostic factor for progression-free survival (PFS) (hazard ration (HR) 2.41, 95% confidence interval (CI) 0.22-0.79, P = 0.0073). No significant difference in PFS was seen regarding tumor localization (transition zone [TZ] or peripheral zone [PZ]) in patients with UH (P = 0.8949), whereas PZ cancer showed shorter PFS in patients with CH (P = 0.0174). PCa with UH was associated with higher progression than PCa with CH among resection margin (RM)-negative cases (P < 0.0001). Further, increased PI-RADS v2.1 score did not correlate with larger TV in UH (P = 0.991), whereas a significant difference in TV was observed in CH (P < 0.0001). The prognostic significance of UH tumor was independent of tumor localization, and shorter PFS was observed even in RM-negative cases, indicating an aggressive subtype with micro-metastatic potential. Furthermore, UH tumors are more likely to harbor a large TV despite PI-RADS v2.1 score ≤ 3. These findings will help optimal perioperative management for PCa with UH.
Topics: Humans; Male; Prostatectomy; Prostatic Neoplasms; Magnetic Resonance Imaging; Aged; Middle Aged; Neoplasm Grading; Prognosis; Retrospective Studies; Prostate; Robotic Surgical Procedures
PubMed: 38937563
DOI: 10.1038/s41598-024-65681-2 -
Prostate Cancer and Prostatic Diseases Jun 2024The use of systematic biopsies in addition to targeted biopsies is based on multiple studies showing that 15-20% of "clinically significant" cancers are missed on... (Review)
Review
INTRODUCTION
The use of systematic biopsies in addition to targeted biopsies is based on multiple studies showing that 15-20% of "clinically significant" cancers are missed on targeted biopsies. Concern about these 'missed' cancers drives many interventions. This includes systematic biopsies in men with negative imaging and in men having targeted biopsies, and drives a preference for total gland treatment in men who may be candidates for partial gland ablation. This article summarizes recent genomic and clinical data indicating that, despite "clinically significant" histology, MRI invisible lesions are genomically and clinically favorable. These studies have demonstrated that the genetic aberrations associated with cancer visibility are the same aberrations that drive cancer invasiveness and metastasis. Thus invisible cancers, even if undiagnosed at baseline, are in most cases indolent and pose little threat to the patient. The implications are that patients should be monitored with imaging rather than systematic biopsy, and subject to repeat targeted biopsy for evidence of MR progression. Patients prefer this strategy. It has many advantages in terms of reduced burden of care, cost, psychological benefits, and less diagnosis of insignificant cancer.
CONCLUSION
It is now appropriate to abandon systematic biopsies in most patients.
PubMed: 38937536
DOI: 10.1038/s41391-024-00849-5 -
Scientific Data Jun 2024Bone metastasis is an essential factor affecting the prognosis of prostate cancer (PCa), and circulating tumor cells (CTCs) are closely related to distant tumor...
Bone metastasis is an essential factor affecting the prognosis of prostate cancer (PCa), and circulating tumor cells (CTCs) are closely related to distant tumor metastasis. Here, the protein-protein interaction (PPI) networks and Cytoscape application were used to identify diagnostic markers for metastatic events in PCa. We screened ten hub genes, eight of which had area under the ROC curve (AUC) values > 0.85. Subsequently, we aim to develop a bone metastasis-related model relying on differentially expressed genes in CTCs for accurate risk stratification. We developed an integrative program based on machine learning algorithm combinations to construct reliable bone metastasis-related genes prognostic index (BMGPI). On the basis of BMGPI, we carefully evaluated the prognostic outcomes, functional status, tumor immune microenvironment, somatic mutation, copy number variation (CNV), response to immunotherapy and drug sensitivity in different subgroups. BMGPI was an independent risk factor for disease-free survival in PCa. The high risk group demonstrated poor survival as well as higher immune scores, higher tumor mutation burden (TMB), more frequent co-occurrence mutation, and worse efficacy of immunotherapy. This study highlights a new prognostic signature, the BMGPI. BMGPI is an independent predictor of prognosis in PCa patients and is closely associated with the immune microenvironment and the efficacy of immunotherapy.
Topics: Humans; Algorithms; Biomarkers, Tumor; Bone Neoplasms; Machine Learning; Neoplastic Cells, Circulating; Prognosis; Prostatic Neoplasms; Protein Interaction Maps; Tumor Microenvironment
PubMed: 38937469
DOI: 10.1038/s41597-024-03551-2 -
International Urology and Nephrology Jun 2024Acquired prostatic fistula (PF) was defined as a connection between the prostatic urethra and the rectum, symphysis, peritoneum, or ending freely in the periprostatic...
PURPOSE
Acquired prostatic fistula (PF) was defined as a connection between the prostatic urethra and the rectum, symphysis, peritoneum, or ending freely in the periprostatic area. This study aims to report our experience with PF presentation, diagnosis, and treatment.
METHODS
From January 2014 to February 2024, we retrospectively analyzed a prospectively maintained database from two urologic university hospitals to identify men with acquired PF. Diagnosis was based on post-intervention symptoms, including pneumaturia, fecaluria, rectal urine leakage, periprostatic inflammation or abscess, completed by radiological assessment using retrograde urethrogram, CT, or MRI. Standard cystoscopy and/or rectosigmoidoscopy assessed bladder and rectal integrity. Patients with post-prostatectomy fistulas were excluded.
RESULTS
Thirteen patients with a mean age of 66.54 ± 7.40 years were identified. The most commonly presenting symptoms were fecaluria/pneumaturia 54%, rectal urine leakage 31%, and recurrent urinary tract infection 31%. The mean time from the initial treatment to fistula development was 22.28 ± 20.53 months (0.1-59 months), and from diagnosis to repair was 3.5 ± 3 months (1-12 months). Cumulative closure rates (success rate) post-first and second attempts were 77% (10 patients) and 92% (12 patients), respectively; one patient declined definitive surgery, maintaining a persistent fistula after bladder drainage.
CONCLUSION
Clinical suspicion and detailed diagnosis are essential for formulating a tailored treatment plan for prostatic fistulas, which are successfully manageable in many patients. Complex cases benefit from a multidisciplinary approach, with individualized therapy based on etiology, severity, and recurrence of PF, facilitating effective closure.
PubMed: 38937414
DOI: 10.1007/s11255-024-04092-8 -
European Radiology Jun 2024To review the components of past and present active surveillance (AS) protocols, provide an overview of the current studies employing artificial intelligence (AI) in AS... (Review)
Review
OBJECTIVE
To review the components of past and present active surveillance (AS) protocols, provide an overview of the current studies employing artificial intelligence (AI) in AS of prostate cancer, discuss the current challenges of AI in AS, and offer recommendations for future research.
METHODS
Research studies on the topic of MRI-based AI were reviewed to summarize current possibilities and diagnostic accuracies for AI methods in the context of AS. Established guidelines were used to identify possibilities for future refinement using AI.
RESULTS
Preliminary results show the role of AI in a range of diagnostic tasks in AS populations, including the localization, follow-up, and prognostication of prostate cancer. Current evidence is insufficient to support a shift to AI-based AS, with studies being limited by small dataset sizes, heterogeneous inclusion and outcome definitions, or lacking appropriate benchmarks.
CONCLUSION
The AI-based integration of prostate MRI is a direction that promises substantial benefits for AS in the future, but evidence is currently insufficient to support implementation. Studies with standardized inclusion criteria and standardized progression definitions are needed to support this. The increasing inclusion of patients in AS protocols and the incorporation of MRI as a scheduled examination in AS protocols may help to alleviate these challenges in future studies.
CLINICAL RELEVANCE STATEMENT
This manuscript provides an overview of available evidence for the integration of prostate MRI and AI in active surveillance, addressing its potential for clinical optimizations in the context of established guidelines, while highlighting the main challenges for implementation.
KEY POINTS
Active surveillance is currently based on diagnostic tests such as PSA, biopsy, and imaging. Prostate MRI and AI demonstrate promising diagnostic accuracy across a variety of tasks, including the localization, follow-up and risk estimation in active surveillance cohorts. A transition to AI-based active surveillance is not currently realistic; larger studies using standardized inclusion criteria and outcomes are necessary to improve and validate existing evidence.
PubMed: 38937295
DOI: 10.1007/s00330-024-10869-3 -
BMJ Case Reports Jun 2024Giant bladder is a rare condition with varied definitions and causes. It can lead to complications such as urinary tract infections, retrograde urine reflux,...
Giant bladder is a rare condition with varied definitions and causes. It can lead to complications such as urinary tract infections, retrograde urine reflux, pyelonephritis, renal damage and occasionally vascular obstruction. In this case report, we present a man in his 70s with massive urinary retention >7 L and severe bilateral hydronephrosis. The patient underwent a successful Greenlight photovaporisation of the prostate to address underlying bladder outlet obstruction. The surgical procedure resulted in significant improvement in urinary function, enabling the patient to live catheter and infection free, and without renal damage. This case demonstrates that bladder outlet surgery can be useful in selected cases of giant bladder to avoid complications of chronic catheterisation or ongoing retention.
Topics: Humans; Male; Urinary Bladder Neck Obstruction; Urinary Retention; Aged; Urinary Bladder; Hydronephrosis; Urination; Recovery of Function; Prostatectomy; Treatment Outcome
PubMed: 38937265
DOI: 10.1136/bcr-2024-260123 -
Asian Journal of Surgery Jun 2024
PubMed: 38937233
DOI: 10.1016/j.asjsur.2024.06.038