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Current Oncology (Toronto, Ont.) Sep 2023A recent approach to radiotherapy for prostate cancer is the administration of high doses of radiation to the prostate while minimizing the risk of side effects. Thus,... (Review)
Review
A recent approach to radiotherapy for prostate cancer is the administration of high doses of radiation to the prostate while minimizing the risk of side effects. Thus, image-guided radiotherapy utilizes advanced imaging techniques and is a feasible strategy for increasing the radiation dose. New radioactive particles are another approach to achieving high doses and safe procedures. Prostate brachytherapy is currently considered as a combination therapy. Spacers are useful to protect adjacent organs, specifically the rectum, from excessive radiation exposure.
Topics: Male; Humans; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Prostatic Neoplasms; Prostate; Rectum
PubMed: 37754502
DOI: 10.3390/curroncol30090587 -
Computerized Medical Imaging and... Jul 2023In healthcare, a growing number of physicians and support staff are striving to facilitate personalized radiotherapy regimens for patients with prostate cancer. This is... (Review)
Review
In healthcare, a growing number of physicians and support staff are striving to facilitate personalized radiotherapy regimens for patients with prostate cancer. This is because individual patient biology is unique, and employing a single approach for all is inefficient. A crucial step for customizing radiotherapy planning and gaining fundamental information about the disease, is the identification and delineation of targeted structures. However, accurate biomedical image segmentation is time-consuming, requires considerable experience and is prone to observer variability. In the past decade, the use of deep learning models has significantly increased in the field of medical image segmentation. At present, a vast number of anatomical structures can be demarcated on a clinician's level with deep learning models. These models would not only unload work, but they can offer unbiased characterization of the disease. The main architectures used in segmentation are the U-Net and its variants, that exhibit outstanding performances. However, reproducing results or directly comparing methods is often limited by closed source of data and the large heterogeneity among medical images. With this in mind, our intention is to provide a reliable source for assessing deep learning models. As an example, we chose the challenging task of delineating the prostate gland in multi-modal images. First, this paper provides a comprehensive review of current state-of-the-art convolutional neural networks for 3D prostate segmentation. Second, utilizing public and in-house CT and MR datasets of varying properties, we created a framework for an objective comparison of automatic prostate segmentation algorithms. The framework was used for rigorous evaluations of the models, highlighting their strengths and weaknesses.
Topics: Male; Humans; Prostate; Benchmarking; Neural Networks, Computer; Algorithms; Prostatic Neoplasms; Image Processing, Computer-Assisted
PubMed: 37201475
DOI: 10.1016/j.compmedimag.2023.102241 -
International Braz J Urol : Official... 2024
Topics: Male; Humans; Prostate; Prostatitis; Tuberculosis, Male Genital
PubMed: 37624660
DOI: 10.1590/S1677-5538.IBJU.2023.0299 -
Scientific Reports Jul 2023Molecular targeted therapy using poly (ADP-ribose) polymerase inhibitors has improved survival in patients with castration-resistant prostate cancer (CRPC). However,...
Molecular targeted therapy using poly (ADP-ribose) polymerase inhibitors has improved survival in patients with castration-resistant prostate cancer (CRPC). However, this approach is only effective in patients with specific genetic mutations, and additional drug discovery targeting epigenetic modulators is required. Here, we evaluated the involvement of the transcriptional coregulator ESS2 in prostate cancer. ESS2-knockdown PC3 cells dramatically inhibited proliferation in tumor xenografts in nude mice. Microarray analysis revealed that ESS2 regulated mRNA levels of chromodomain helicase DNA binding protein 1 (CHD1)-related genes and other cancer-related genes, such as PPAR-γ, WNT5A, and TGF-β, in prostate cancer. ESS2 knockdown reduced nuclear factor (NF)-κB/CHD1 recruitment and histone H3K36me3 levels on the promoters of target genes (TNF and CCL2). In addition, we found that the transcriptional activities of NF-κB, NFAT and SMAD2/3 were enhanced by ESS2. Tamoxifen-inducible Ess2-knockout mice showed delayed prostate development with hypoplasia and disruption of luminal cells in the ventral prostate. Overall, these findings identified ESS2 acts as a transcriptional coregulator in prostate cancer and ESS2 can be novel epigenetic therapeutic target for CRPC.
Topics: Male; Animals; Mice; Humans; Prostate; Prostatic Neoplasms, Castration-Resistant; Mice, Nude; Cell Line, Tumor; DNA-Binding Proteins; NF-kappa B; Neoplastic Processes; Poly(ADP-ribose) Polymerase Inhibitors; Cell Proliferation
PubMed: 37524814
DOI: 10.1038/s41598-023-39626-0 -
Cell Communication and Signaling : CCS Mar 2024Prostatitis is a highly prevalent condition that seriously affects men's physical and mental health. Although epidemiological investigations have provided evidence of a...
PURPOSE
Prostatitis is a highly prevalent condition that seriously affects men's physical and mental health. Although epidemiological investigations have provided evidence of a correlation between insufficient sleep and prostatitis, the pathogenesis of prostatitis remains unclear. We sought to identify the underlying mechanism involved and identify a promising therapeutic target.
METHODS
Sleep deprivation (SD) was utilized to establish a mouse model of insufficient sleep in a special device. Prostatitis was observed at different time points post-SD. The degree of prostatitis was evaluated by pathological section and behavioural tests. Using immunofluorescence, western blot, and proteomic analyses, the underlying mechanism of SD-related prostatitis was investigated, and the development and therapeutic target of prostatitis were elucidated.
RESULTS
SD, as an initial pathological trigger, resulted in a reduction in dihydrotestosterone and melatonin levels. Proteomic analysis revealed that the cGAS-STING pathway may play a significant role in inducing prostatitis. The subsequent results illustrated that the dual reduction in dihydrotestosterone and melatonin led to an accumulation of reactive oxygen species and the release of mitochondrial DNA (mt-DNA). The accumulation of mt-DNA activated the cGAS-STING pathway, which recruited inflammatory cells into the prostatic stroma through the secretion of interferon-β. Consequently, an inflammatory microenvironment was formed, ultimately promoting the development of prostatitis. Notably, mice with SD-induced prostatitis gradually recovered to a normal state within 7 days of recovery sleep. However, after being subjected to SD again, these mice tended to have a more pronounced manifestation of prostatitis within a shorter timeframe, which suggested that prostatitis is prone to relapse.
CONCLUSIONS
The cGAS-STING pathway activated by dual deficiency of dihydrotestosterone and melatonin plays a comprehensive inflammatory role in SD-related prostatitis. This research provides valuable insights into the pathogenesis, therapeutic targets, and prevention strategies of prostatitis.
Topics: Humans; Male; Animals; Mice; Sleep Deprivation; Dihydrotestosterone; Melatonin; Prostatitis; Proteomics; Sleep; DNA, Mitochondrial; Nucleotidyltransferases
PubMed: 38491517
DOI: 10.1186/s12964-024-01554-5 -
Genes Jul 2023Prostate cancer (PC) is polygenic disease involving many genes, and more importantly a host of gene-gene interactions, including transcriptional factors. The gene is a...
Prostate cancer (PC) is polygenic disease involving many genes, and more importantly a host of gene-gene interactions, including transcriptional factors. The gene is a transcriptional target of numerous oncoproteins, and its dysregulation can contribute to tumor progression by abnormal activation of targeted oncogenes. Using data from the Cancer Genome Atlas, we tested the possible involvement of in PC progression. A multi-dimensional scaling (MDS) model was applied to clarify the association of expression with other key genes, such as , , ( and ), , and . An increased expression was associated with higher PC grades and with a worse prognosis. It was also positively related to , , and . Moreover, MDS showed the central role of in influencing the other target genes by its central location on the map. Our study is the first to show a link between expression and other genes involved in PC progression, suggesting a novel role for in PC progression. This network between and through may have an important role in PC progression, as suggested by the association between high expression and unfavorable prognosis in our analysis.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Oncogenes; Epistasis, Genetic; Multifactorial Inheritance; Intracellular Signaling Peptides and Proteins
PubMed: 37628609
DOI: 10.3390/genes14081558 -
Development (Cambridge, England) Jul 2023The reactivation of developmental genes and pathways during adulthood may contribute to pathogenesis of diseases such as prostate cancer. Analysis of the mechanistic...
The reactivation of developmental genes and pathways during adulthood may contribute to pathogenesis of diseases such as prostate cancer. Analysis of the mechanistic links between development and disease could be exploited to identify signalling pathways leading to disease in the prostate. However, the mechanisms underpinning prostate development require further characterisation to interrogate fully the link between development and disease. Previously, our group developed methods to produce prostate organoids using induced pluripotent stem cells (iPSCs). Here, we show that human iPSCs can be differentiated into prostate organoids using neonatal rat seminal vesicle mesenchyme in vitro. The organoids can be used to study prostate development or modified to study prostate cancer. We also elucidated molecular drivers of prostate induction through RNA-sequencing analyses of the rat urogenital sinus and neonatal seminal vesicles. We identified candidate drivers of prostate development evident in the inductive mesenchyme and epithelium involved with prostate specification. Our top candidates included Spx, Trib3, Snai1, Snai2, Nrg2 and Lrp4. This work lays the foundations for further interrogation of the reactivation of developmental genes in adulthood, leading to prostate disease.
Topics: Male; Humans; Rats; Animals; Prostate; Rodentia; Urogenital System; Prostatic Neoplasms; Cell Differentiation; Organoids; Induced Pluripotent Stem Cells
PubMed: 37376888
DOI: 10.1242/dev.201328 -
Cell Genomics Mar 2024The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor...
The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Mutation; Genomics; Evolution, Molecular
PubMed: 38428419
DOI: 10.1016/j.xgen.2024.100511 -
Cell Communication and Signaling : CCS Sep 2023Adipose tissue has gained attention due to its potential paracrine role. Periprostatic adipose tissue surrounds the prostate and the prostatic urethra, and it is an...
BACKGROUND
Adipose tissue has gained attention due to its potential paracrine role. Periprostatic adipose tissue surrounds the prostate and the prostatic urethra, and it is an essential player in prostate cancer progression. Since obesity is directly related to human tumor progression, and adipose tissue depots are one of the significant components of the tumor microenvironment, the molecular mediators of the communication between adipocytes and epithelial cells are in the spotlight. Although periprostatic white adipose tissue contributes to prostate cancer progression, brown adipose tissue (BAT), which has beneficial effects in metabolic pathologies, has been scarcely investigated concerning cancer progression. Given that adipose tissue is a target of androgen signaling, the actual role of androgen removal on the periprostatic adipose tissue was the aim of this work.
METHODS
Surgical castration of the transgenic adenocarcinoma of the mouse prostate (TRAMP) was employed. By histology examination and software analysis, WAT and BAT tissue was quantified. 3T3-like adipocytes were used to study the role of Casodex® in modifying adipocyte differentiation and to investigate the function of the secretome of adipocytes on the proliferation of androgen-dependent and independent prostate cancer cells. Finally, the role of cell communication was assayed by TRAMP-C1 xenograft implanted in the presence of 3T3-like adipocytes.
RESULTS
Androgen removal increases brown/beige adipose tissue in the fat immediately surrounding the prostate glands of TRAMP mice, concomitant with an adjustment of the metabolism. Castration increases body temperature, respiratory exchange rate, and energy expenditure. Also, in vitro, it is described that blocking androgen signaling by Casodex® increases the uncoupling protein 1 (UCP1) marker in 3T3-like adipocytes. Finally, the effect of brown/beige adipocyte secretome was studied on the proliferation of prostate cancer cells in vivo and in vitro. The secretome of brown/beige adipocytes reduces the proliferation of prostate cancer cells mediated partly by the secretion of extracellular vesicles.
CONCLUSIONS
Consequently, we concluded that hampering androgen signaling plays a crucial role in the browning of the periprostatic adipose tissue. Also, the presence of brown adipocytes exhibits the opposite effect to that of white adipocytes in vitro regulating processes that govern the mechanisms of cell proliferation of prostate cancer cells. And finally, promoting the browning of adipose tissue in the periprostatic adipose tissue might be a way to handle prostate cancer cell progression. Video Abstract.
Topics: Male; Humans; Mice; Animals; Prostate; Androgens; Tumor Microenvironment; Castration; Prostatic Neoplasms
PubMed: 37770940
DOI: 10.1186/s12964-023-01294-y -
Computer Methods and Programs in... Sep 2023With emerging evidence to improve prostate cancer (PCa) screening, multiparametric magnetic prostate imaging is becoming an essential noninvasive component of the...
BACKGROUND AND OBJECTIVE
With emerging evidence to improve prostate cancer (PCa) screening, multiparametric magnetic prostate imaging is becoming an essential noninvasive component of the diagnostic routine. Computer-aided diagnostic (CAD) tools powered by deep learning can help radiologists interpret multiple volumetric images. In this work, our objective was to examine promising methods recently proposed in the multigrade prostate cancer detection task and to suggest practical considerations regarding model training in this context.
METHODS
We collected 1647 fine-grained biopsy-confirmed findings, including Gleason scores and prostatitis, to form a training dataset. In our experimental framework for lesion detection, all models utilized 3D nnU-Net architecture that accounts for anisotropy in the MRI data. First, we explore an optimal range of b-values for diffusion-weighted imaging (DWI) modality and its effect on the detection of clinically significant prostate cancer (csPCa) and prostatitis using deep learning, as the optimal range is not yet clearly defined in this domain. Next, we propose a simulated multimodal shift as a data augmentation technique to compensate for the multimodal shift present in the data. Third, we study the effect of incorporating the prostatitis class alongside cancer-related findings at three different granularities of the prostate cancer class (coarse, medium, and fine) and its impact on the detection rate of the target csPCa. Furthermore, ordinal and one-hot encoded (OHE) output formulations were tested.
RESULTS
An optimal model configuration with fine class granularity (prostatitis included) and OHE has scored the lesion-wise partial Free-Response Receiver Operating Characteristic (FROC) area under the curve (AUC) of 1.94 (CI 95%: 1.76-2.11) and patient-wise ROC AUC of 0.874 (CI 95%: 0.793-0.938) in the detection of csPCa. Inclusion of the auxiliary prostatitis class has demonstrated a stable relative improvement in specificity at a false positive rate (FPR) of 1.0 per patient, with an increase of 3%, 7%, and 4% for coarse, medium, and fine class granularities.
CONCLUSIONS
This paper examines several configurations for model training in the biparametric MRI setup and proposes optimal value ranges. It also shows that the fine-grained class configuration, including prostatitis, is beneficial for detecting csPCa. The ability to detect prostatitis in all low-risk cancer lesions suggests the potential to improve the quality of the early diagnosis of prostate diseases. It also implies an improved interpretability of the results by the radiologist.
Topics: Male; Humans; Prostatitis; Prostatic Neoplasms; Magnetic Resonance Imaging; Prostate; Diffusion Magnetic Resonance Imaging; Retrospective Studies
PubMed: 37271051
DOI: 10.1016/j.cmpb.2023.107624