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Journal of Molecular Medicine (Berlin,... Oct 2023The transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family... (Review)
Review
The transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family transcription factors that act as pioneering transcription factors which facilitate the opening of heterochromatin and the subsequent binding of other transcription factors to induce gene expression from previously inaccessible regions of the genome. Although GATA2 is essential for hematopoiesis and lymphangiogenesis, it is also expressed in other tissues such as the lung, prostate gland, gastrointestinal tract, central nervous system, placenta, fetal liver, and fetal heart. Gene or transcriptional abnormalities of GATA2 causes or predisposes patients to several diseases including the hematological cancers acute myeloid leukemia and acute lymphoblastic leukemia, the primary immunodeficiency MonoMAC syndrome, and to cancers of the lung, prostate, uterus, kidney, breast, gastric tract, and ovaries. Recent data has also linked GATA2 expression and mutations to responses to infectious diseases including SARS-CoV-2 and Pneumocystis carinii pneumonia, and to inflammatory disorders such as atherosclerosis. In this article we review the role of GATA2 in the etiology and progression of these various diseases.
PubMed: 37624387
DOI: 10.1007/s00109-023-02359-8 -
European Urology Focus Nov 2023In an increasingly ageing transplant population, timely management of benign prostatic obstruction (BPO) is key to preventing complications that result in graft... (Review)
Review
CONTEXT
In an increasingly ageing transplant population, timely management of benign prostatic obstruction (BPO) is key to preventing complications that result in graft dysfunction or compromise survival.
OBJECTIVE
To evaluate benefits/harms of BPO treatments in transplant patients by reviewing current literature.
EVIDENCE ACQUISITION
A computerised bibliographic search of Medline, Embase, and Cochrane databases was performed for studies reporting outcomes on BPO treatments in transplanted patients.
EVIDENCE SYNTHESIS
A total of 5021 renal transplants (RTs) performed between 1990 and 2016 were evaluated. BPO incidence was 1.61 per 1000 population per year. Overall, 264 men underwent intervention. The mean age was 58.4 yr (27-73 yr). In all, 169 patients underwent surgery (n = 114 transurethral resection of the prostate [TURP]/n = 55 transurethral incision of the prostate [TUIP]) and 95 were treated with an un-named alpha-blocker (n = 46) or doxazosin (n = 49). There was no correlation between prostate volume and treatment modality (mean prostate size = 26 cc in the surgical group where reported and 48 cc in the medical group). The mean follow-up was 31.2 mo (2-192 mo). The time from RT to BPO treatment was reported in six studies (mean: 15.4 mo, range: 0-156 mo). The time on dialysis before RT was recorded in only three studies (mean: 47.3 mo, range: 0-288 mo). There was a mean improvement in creatinine after intervention from 2.17 to 1.77 mg/dl. A total of 157 men showed an improvement in the International Prostate Symptom Score (from 18.26 to 6.89), and there was a significant reduction in postvoid residual volume in 199 (mean fall 90.6 ml). Flow improved by a mean of 10 ml/s following intervention in 199 patients. Complications included acute urinary retention (4.1%), urinary tract infections (8.4%), bladder neck contracture (2.2%), and urethral strictures (6.9%). The mean reoperation rate was 1.4%.
CONCLUSIONS
Current literature is heterogeneous and of low-level evidence. Despite this, alpha-blockers, TUIP, and TURP showed a beneficial increase in the peak urinary flow and reduced symptoms in transplants patients with BPO. Improvement in the mean graft creatinine was noted after intervention. Complications were under-reported. A multicentre comparative cohort study is needed to draw firm conclusions about the ideal treatment for BPO in RT patients.
PATIENT SUMMARY
In this report, we looked at the outcomes for transplant patients undergoing medical or surgical management of benign prostatic obstruction. Although the literature was very heterogeneous, we found that medical management and surgery with transurethral resection/incision of the prostate are beneficial for improving urinary flow and bothersome symptoms. We conclude that further prospective studies are required for better clarity about timing and modality of intervention in transplant patients.
Topics: Male; Humans; Middle Aged; Transurethral Resection of Prostate; Prostatic Hyperplasia; Prostate; Urinary Retention; Urinary Bladder Neck Obstruction
PubMed: 37596113
DOI: 10.1016/j.euf.2023.05.001 -
Therapeutic Advances in Urology 2023Transperineal laser ablation (TPLA) of the prostate is a new, minimally invasive technique for benign prostatic hyperplasia (BPH) with promising effectiveness and safety... (Review)
Review
INTRODUCTION
Transperineal laser ablation (TPLA) of the prostate is a new, minimally invasive technique for benign prostatic hyperplasia (BPH) with promising effectiveness and safety outcomes. This systematic review aims to provide an update of existing literature.
METHODS
A literature review was performed in Pubmed/MEDLINE, Embase, Cochrane Library, and clinicaltrials.gov from January 2000 up to April 2023. Data extraction and risk of bias were performed independently by three authors.
RESULTS
A total of 11 studies were included, among which 9 were observational, 1 randomized controlled trial, 1 animal study, while 2 of them were comparative (1 with prostatic artery embolization and 1 with transurethral resection of the prostate). Functional outcomes were improved in the majority of studies both for objective (maximum flow rate and post-void residual) and subjective outcomes (improvement of International Prostate Symptom Score and quality of life). Complication rates ranged between 1.9% and 2.3% for hematuria, 3.7% and 36.3% for dysuria, 1.9% and 19% for acute urinary retention, 0.6% and 9.1% for orchitis/urinary tract infections, and 0.6% and 4.8% for prostatic abscess formation. Regarding sexual function, >95% of patients retained their ejaculation while erectile function was maintained or improved.
CONCLUSION
TPLA of the prostate is an innovative, minimally invasive technique for managing patients with BPH. Existing studies indicate an effective technique in reducing International Prostate Symptom Score and quality of life scores, post-void residual reduction, and increase in Qmax, albeit the measured improvements in terms of Qmax are not equal to transurethral resection of the prostate. Although sexual function is maintained, the mean catheterization time is 7 days, and no long-term data are available for most patients.
PubMed: 37745187
DOI: 10.1177/17562872231198634 -
JAMA Network Open Oct 2023Technical advances in treatment of prostate cancer and a better understanding of prostate cancer biology have allowed for hypofractionated treatment courses using a...
IMPORTANCE
Technical advances in treatment of prostate cancer and a better understanding of prostate cancer biology have allowed for hypofractionated treatment courses using a higher dose per fraction. Use of ultrahypofractionated stereotactic body radiotherapy (SBRT) has also been characterized.
OBJECTIVE
To characterize US national trends of different RT fractionation schemes across risk groups of prostate cancer.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used data collected by the National Cancer Database (NCDB) to characterize the fractionation regimens used for 302 035 patients diagnosed as having prostate cancer from January 1, 2004, to December 31, 2020, who underwent definitive RT. The analysis was performed between February 1 and April 30, 2023.
EXPOSURE
Stereotactic body RT or ultrahypofractionation, defined as 5 or fewer fractions of external beam RT (EBRT), moderate hypofractionation, defined as 20 to 28 fractions of EBRT, or conventional fractionation, defined as all remaining EBRT fractionation schemes.
MAIN OUTCOMES AND MEASURES
Temporal trends and clinical and sociodemographic factors associated with SBRT, moderate hypofractionation, and conventional fractionation use.
RESULTS
A total of 302 035 men receiving EBRT for localized prostate cancer between 2004 and 2020 were identified (40.1% aged 60-69 years). Black patients comprised 17.6% of this cohort; White patients, 77.9%; and other races and ethnicities, 4.5%. Patients with low-risk disease comprised 17.5% of the cohort; favorable intermediate-risk disease, 23.5%; unfavorable intermediate-risk disease, 23.9%; and high-risk disease, 35.1%. Treatment consisted of conventional fractionation for 81.2%, moderate hypofractionation for 12.9%, and SBRT for 6.0%. The rate of increase over time in patients receiving SBRT compared with conventional fractionation was higher (adjusted odds ratio [AOR] for 2005 vs 2004, 3.18 [95% CI, 2.04-4.94; P < .001]; AOR for 2020 vs 2004, 264.69 [95% CI, 179.33-390.68; P < .001]) than the rate of increase in patients receiving moderate hypofractionation compared with conventional fractionation (AOR for 2005 vs 2004, 1.05 [95% CI, 0.98-1.12; P = .19]; AOR for 2020 vs 2004, 4.41 [95% CI, 4.15-4.69; P < .001]). Compared with White patients, Black patients were less likely to receive SBRT compared with conventional fractionation or moderate hypofractionation (AOR for conventional fractionation, 0.84 [95% CI, 0.80-0.89; P < .001]; AOR for moderate hypofractionation, 0.77 [95% CI, 0.72-0.81; P < .001]). Compared with 2019, patients treated with all fractionation regimens declined in 2020 by 24.4%.
CONCLUSIONS AND RELEVANCE
In this hospital-based cohort study of patients with prostate cancer treated with definitive EBRT, use of moderate hypofractionation and SBRT regimens for definitive prostate cancer treatment has increased from 2004 to 2020. Despite this increasing trend, findings suggest potential health care disparities for Black patients receiving EBRT for localized prostate cancer. The number of patients treated with EBRT in the year 2020 decreased, coinciding with official onset of the COVID-19 pandemic in March 2020.
Topics: Male; Humans; Cohort Studies; Pandemics; Retrospective Studies; COVID-19; Prostatic Neoplasms
PubMed: 37815829
DOI: 10.1001/jamanetworkopen.2023.37165 -
Biomolecules Nov 2023Prostate cancer (PCa) is a complex disease and the cause of one of the highest cancer-related mortalities in men worldwide. Annually, more than 1.2 million new cases are... (Review)
Review
Prostate cancer (PCa) is a complex disease and the cause of one of the highest cancer-related mortalities in men worldwide. Annually, more than 1.2 million new cases are diagnosed globally, accounting for 7% of newly diagnosed cancers in men. Programmed cell death (PCD) plays an essential role in removing infected, functionally dispensable, or potentially neoplastic cells. Apoptosis is the canonical form of PCD with no inflammatory responses elicited, and the close relationship between apoptosis and PCa has been well studied. Necroptosis and pyroptosis are two lytic forms of PCD that result in the release of intracellular contents, which induce inflammatory responses. An increasing number of studies have confirmed that necroptosis and pyroptosis are also closely related to the occurrence and progression of PCa. Recently, a novel form of PCD named PANoptosis, which is a combination of apoptosis, necroptosis, and pyroptosis, revealed the attached connection among them and may be a promising target for PCa. Apoptosis, necroptosis, pyroptosis, and PANoptosis are good examples to better understand the mechanism underlying PCD in PCa. This review aims to summarize the emerging roles and therapeutic potential of apoptosis, necroptosis, pyroptosis, and PANoptosis in PCa.
Topics: Male; Humans; Pyroptosis; Caspases; Necroptosis; Apoptosis; Prostatic Neoplasms
PubMed: 38136586
DOI: 10.3390/biom13121715 -
The American Journal of Tropical... Dec 2023Prostatic abscess is a common manifestation of melioidosis in men, but the characteristics of female genitourinary melioidosis are incompletely defined. There were 453...
Prostatic abscess is a common manifestation of melioidosis in men, but the characteristics of female genitourinary melioidosis are incompletely defined. There were 453 cases of melioidosis in Far North Queensland, tropical Australia, between January 1998 and April 2023; genitourinary involvement was less common in women than in men (13/140 [9%] versus 76/313 [24%], odds ratio [95% confidence interval]: 0.32 [0.17-0.60], P = 0.0004). In 11 of these 13 (85%) women, other organs were also affected. The two women with disease involving only the genitourinary tract had underlying anatomical abnormalities: one had an ovarian malignancy, the only case to involve the female reproductive system in the cohort, while the other had a urethral diverticulum. In 3 of 13 (23%) women, genitourinary involvement was identified only with computed tomography, emphasizing the importance of early imaging of patients with melioidosis to identify unexpected foci of disease and to inform the optimal duration of antibiotic therapy.
Topics: Male; Humans; Female; Melioidosis; Australia; Queensland; Prostatic Diseases; Tomography, X-Ray Computed; Burkholderia pseudomallei
PubMed: 37955316
DOI: 10.4269/ajtmh.23-0350 -
Heliyon Oct 2023Growing evidence suggests an association between Mycoplasma infections and the development and progression of prostate cancer (PCa). In this study, we report that...
Growing evidence suggests an association between Mycoplasma infections and the development and progression of prostate cancer (PCa). In this study, we report that chronic and persistent infection induced robust TNF-α secretion from PCa cells. TNF-α secreted from -infected PCa cells subsequently led to activation of the NF-κB pathway. Chronic infection induced gene expression of pro-inflammatory cytokines and chemokines in a NF-κB-dependent manner and promoted cell proliferation, migration, and invasion in PCa cells. The elimination of in PCa cells significantly blocked TNF-α secretion, gene expression of cytokines and chemokines, migration, and invasion in PCa cells, suggesting -induced TNF-α plays an important role to promote malignant transformation of PCa. Furthermore, second mitochondria-derived activator of caspases (SMAC) mimetics potentiated caspase activation and cell death in -infected PCa by antagonizing inhibitor of apoptosis proteins (IAPs) activity. Tissue microarray analysis indicated that TNF-α is co-expressed in infected human patient tissues. Findings from this study advance our understanding of the mycoplasma-oncogenesis process and suggest the potential for new approaches for preventions, diagnosis, and therapeutic approaches against prostate cancers.
PubMed: 37867861
DOI: 10.1016/j.heliyon.2023.e20655 -
Parasite Immunology Aug 2023Toll-like receptors (TLRs) and inflammasomes belong to the pattern recognition receptors (PRRs) of innate immunity identifying conserved compounds produced by pathogens... (Review)
Review
Toll-like receptors (TLRs) and inflammasomes belong to the pattern recognition receptors (PRRs) of innate immunity identifying conserved compounds produced by pathogens or discharged by injured cells. Different cell subsets in the human urogenital system, such as epithelial cells and infiltrating leukocytes, express different kinds of TLRs (such as TLR2, TLR3, TLR4, TLR5 and TLR9) as well as inflammasomes (such as NLRP3, NLRC4 and AIM2). Various types of the Trichomonas vaginalis-derived components such as glycosyl-phosphatidylinositol (GPI), T. vaginalis virus (TVV), Lipophosphoglycan (LPG) and flagellin can be recognized by TLR2, TLR3, TLR4 and TLR5, respectively, leading to the production of proinflammatory cytokines and chemokines in the cervicovaginal mucosa. The T. vaginalis-induced inflammasomes can lead to pyroptosis as well as the release of IL-1β and IL-18 promoting innate and adaptive immune responses. The PRR-mediated responses to T. vaginalis may contribute to the induction of protective immune responses, local inflammation, promotion of co-infections, or even the development of malignancies, for example, prostate cancer. The protective or pathogenic roles of the TLRs and inflammasomes during trichomoniasis are highlighted in this review. A better understanding of PRR-mediated responses provides invaluable insights to develop effective immunotherapeutic strategies against T. vaginalis infection.
Topics: Male; Humans; Inflammasomes; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptor 3; Toll-Like Receptor 5; Toll-Like Receptors; Trichomonas Infections
PubMed: 37338019
DOI: 10.1111/pim.13000 -
Frontiers in Immunology 2023Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present... (Meta-Analysis)
Meta-Analysis Review
Immunotherapy has revolutionized the treatment paradigm of many cancers, however, its effectiveness in prostate cancer patients is still under question. In the present systematic review and meta-analysis, we sought for assessing the efficacy and safety of Immune checkpoint inhibitors (ICIs) in patients with prostate cancer. PubMed, Scopus, Web of Science, and EMBASE databases were searched on Aguste 19, 2022. Thirty five studies met the eligibility criteria. The median overall survival (mOS) of all treatments was 14.1 months, with the longest and shortest mOS was seen among patients who received anti-CTLA-4 monotherapy and anti-PD-1/PD-L1+anti-CTLA-4 regimen at 24.9 and 9.2 months, respectively. Noteworthy, all types of adverse events had the lowest incidence in the anti-PD-1/PD-L1 monotherapy group. Considering the ICI monotherapy regimens, we found that fatigue, diarrhea, and infusion reaction had the highest incidence rates. Future studies evaluating the efficacy and safety of novel combination therapies with ICIs are warranted.
Topics: Male; Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Prostatic Neoplasms; Combined Modality Therapy; Databases, Factual
PubMed: 38022569
DOI: 10.3389/fimmu.2023.1181051 -
Xenobiotica; the Fate of Foreign... May 2024Prostate inflammation is often treated with drugs which are ineffective. Antibacterial agents fail to reach the prostate epithelium, and the blood-prostate barrier (BPB)...
Prostate inflammation is often treated with drugs which are ineffective. Antibacterial agents fail to reach the prostate epithelium, and the blood-prostate barrier (BPB) may affect the drug transport process. Factors affecting drug efficacy remain unclear.Rats were categorised into groups A and B, corresponding to adulthood and puberty, respectively. Group C included the model of chronic prostate infection. Dialysates of levofloxacin and cefradine were collected from the prostate gland and jugular vein and evaluated. Pharmacokinetic analysis was conducted.The free concentrations of antimicrobials in the prostate and plasma samples of all groups peaked at 20 min, then gradually decreased. The mean AUCprostate/AUCplasma ratio in the levofloxacin group were 0.86, 0.53, and 0.95, and the mean values of AUCprostate/AUCplasma ratio were 0.85, 0.63, and 0.97. The corresponding values in the cefradine group were 0.67, 0.30 and 0.84, and 0.66, 0.31, and 0.85, respectively. The mean values in group B were lower than those in group A, and those in group C were higher than those in group B.The maturity of the prostate may affect the ability of the drug to cross the BPB. Infection may disrupt the BPB, affecting drug permeability.
Topics: Male; Animals; Prostate; Rats; Levofloxacin; Anti-Bacterial Agents
PubMed: 38634734
DOI: 10.1080/00498254.2024.2343892