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Physiological Research Dec 2021Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the... (Review)
Review
Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the activity of which is dependent on androgens. The important role of androgens is also evidenced by clinical observations that men in some age categories are infected by this novel coronavirus up to two times more frequently than women. In addition, men with androgenic alopecia tend to have more serious clinical courses, while men with androgen deprivation as a result of prostate cancer treatments tend to have milder courses. This is in line with the fact that preadolescent children are only rarely sickened with serious forms of SARS-CoV-2 infections. Even though these observations may be explained by other factors, many authors have hypothesized that lowered androgen levels and blocking their activity using anti-androgen medication may moderate the course of the viral infection in intermediately- to critically-affected cases. Clearly, it would be important for androgen deprivation to block not just gonadal androgens, but also adrenal androgens. On the other hand, low androgen levels are considered to be a risk factor for the course of SARS-CoV-2 infections, either because low androgen levels have a general effect on anabolic-catabolic equilibrium and energy metabolism, or because of the ability of testosterone to modify the immune system. It is not yet clear if infection with this novel coronavirus might induce hypogonadism, leading to undesirable side effects on male fertility.
Topics: Age Factors; Androgens; Animals; COVID-19; Female; Fertility; Gonadal Steroid Hormones; Host-Pathogen Interactions; Humans; Infertility, Male; Male; Risk Assessment; Risk Factors; SARS-CoV-2; Sex Characteristics; Sex Factors
PubMed: 34913348
DOI: 10.33549/physiolres.934724 -
Infection, Genetics and Evolution :... Mar 2021Members of Coronaviridae family have been the source of respiratory illnesses. The outbreak of SARS-CoV-2 that produced a severe lung disease in afflicted patients in... (Review)
Review
Members of Coronaviridae family have been the source of respiratory illnesses. The outbreak of SARS-CoV-2 that produced a severe lung disease in afflicted patients in China and other countries was the reason for the incredible attention paid toward this viral infection. It is known that SARS-CoV-2 is dependent on TMPRSS2 activity for entrance and subsequent infection of the host cells and TMPRSS2 is a host cell molecule that is important for the spread of viruses such as coronaviruses. Different factors can increase the risk of prostate cancer, including older age, a family history of the disease. Androgen receptor (AR) initiates a transcriptional cascade which plays a serious role in both normal and malignant prostate tissues. TMPRSS2 protein is highly expressed in prostate secretory epithelial cells, and its expression is dependent on androgen signals. One of the molecular signs of prostate cancer is TMPRSS2-ERG gene fusion. In TMPRSS2-ERG-positive prostate cancers different patterns of changed gene expression can be detected. The possible molecular relation between fusion positive prostate cancer patients and the increased risk of lethal respiratory viral infections especially SARS-CoV-2 can candidate TMPRSS2 as an attractive drug target. The studies show that some molecules such as nicotinamide, PARP1, ETS and IL-1R can be studied deeper in order to control SARS-CoV-2 infection especially in prostate cancer patients. This review attempts to investigate the possible relation between the gene expression pattern that is produced through TMPRSS2-ERG fusion positive prostate cancer and the possible influence of these fluctuations on the pathogenesis and development of viral infections such as SARS-CoV-2.
Topics: Aged; Angiotensin-Converting Enzyme 2; COVID-19; Dihydrotestosterone; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Male; Oncogene Proteins, Fusion; Prostatic Neoplasms; Receptors, Androgen; SARS-CoV-2; Serine Endopeptidases; Signal Transduction; Spike Glycoprotein, Coronavirus; Transcription, Genetic; Virus Internalization
PubMed: 33301988
DOI: 10.1016/j.meegid.2020.104669 -
Prostate Cancer and Prostatic Diseases Dec 2020A new coronavirus, named SARS-CoV-2, emerged in Wuhan city, China, in December 2019 causing atypical pneumonia and affecting multiple body organs. The rapidly increasing... (Review)
Review
A new coronavirus, named SARS-CoV-2, emerged in Wuhan city, China, in December 2019 causing atypical pneumonia and affecting multiple body organs. The rapidly increasing numbers of infected patients and deaths due to COVID-19 disease necessitated declaring it as a global pandemic. Efforts were combined since then to rapidly develop a treatment and/or a vaccine to combat the deadly virus. Drug repurposing approach has been pursued as a temporary management tactic to treat COVID-19 patients. However, reports about the efficacy of many of the used drugs had been controversial with a dire need to keep the ongoing efforts for rapid development of new treatments. Promising data came out pointing to a possible hidden liaison between prostate cancer (PCa) and COVID-19, where androgen-deprivation therapies (ADT) used in PCa had been shown to instigate a protective role against COVID-19. Delving into the possible mechanisms underlying the crosstalk between COVID-19 and PCa alludes a potential association between SARS-CoV-2 targets on host epithelial cells and PCa genetic aberrations and molecular signatures, including AR and TMPRSS2. The question remains: Can PCa treatments serve as potential therapeutic options for COVID-19 patients?
Topics: Androgen Antagonists; Betacoronavirus; COVID-19; China; Coronavirus Infections; Humans; Male; Pandemics; Pneumonia, Viral; Prostatic Neoplasms; SARS-CoV-2; Serine Endopeptidases
PubMed: 32709978
DOI: 10.1038/s41391-020-0262-y -
Hormone and Metabolic Research =... Dec 2022By the end of December 2019 new corona virus began to spread from Wuhan, China and caused a worldwide pandemic. COVID-19 deaths and prevalence represented sex discrepant... (Review)
Review
By the end of December 2019 new corona virus began to spread from Wuhan, China and caused a worldwide pandemic. COVID-19 deaths and prevalence represented sex discrepant patterns with higher rate of deaths and infection in males than females which could be justified by androgen-mediated mechanisms. This review aimed to assess the role of androgens in COVID-19 severity and mortality. Androgens increase expressions of Type II transmembrane Serine Protease (TMPRSS2) and Angiotensin Converting Enzyme 2 (ACE2), which both facilitate new corona virus entry into host cell and their expression is higher in young males than females. According to observational studies, prevalence of COVID-19 infections and deaths was more in androgenic alopecic patients than patients without androgenic alopecia. The COVID-19 mortality rates in aged men (>60 years) were substantially higher than aged females and even young males caused by high inflammatory activities such as cytokine storm due to hypogonadism in this population. Use of anti-androgen and TMPRSS2 inhibitor drugs considerably modified COVID-19 symptoms. Androgen deprivation therapy also improved COVID-19 symptoms in prostate cancer: overall the role of androgens in severity of COVID-19 and its associated mortality seemed to be very important. So, more studies in variety of populations are required to define the absolute role of androgens.
Topics: Humans; Male; Aged; Androgens; COVID-19; Androgen Antagonists; Prostatic Neoplasms; China
PubMed: 36195265
DOI: 10.1055/a-1954-5605 -
Parasites, Hosts and Diseases Feb 2023Trichomonas vaginalis is a flagellated protozoan that causes trichomoniasis, a common nonviral sexually transmitted infection. T. vaginalis infection is asymptomatic in... (Review)
Review
Trichomonas vaginalis is a flagellated protozoan that causes trichomoniasis, a common nonviral sexually transmitted infection. T. vaginalis infection is asymptomatic in most infected men but can lead to chronic infection. The inflammatory response to chronic T. vaginalis infection may contribute to prostatic diseases, such as prostatitis and benign prostatic hyperplasia (BPH); however, studies on the relationship between T. vaginalis infection and prostate diseases are scarce. In this review, we discuss evidence from our studies on the involvement of T. vaginalis in the pathogenesis of prostate diseases, such as prostatitis and BPH. Studies of prostatitis have demonstrated that the attachment of T. vaginalis trophozoite to prostate epithelial cells (PECs) induces inflammatory cytokine production and inflammatory cell migration, leading to prostatitis. T. vaginalis also causes pathological changes, such as inflammatory cell infiltration, acinar changes, interstitial fibrosis, and mast cell infiltration, in prostate tissues of infected rats. Thus, T. vaginalis is considered an infectious agent that triggers prostatitis. Meanwhile, studies of prostatic hyperplasia revealed that mast cells activated by T. vaginalis-infected prostate cells secreted inflammatory mediators, such as β-hexosaminidase and tryptase, which promoted proliferation of prostate stromal cell (PSC). Moreover, interleukin-6 produced by proliferating PSCs induced the multiplication of BPH-1 epithelial cells as a result of stromal-epithelial interaction, suggesting that the proliferation of T. vaginalis-infected prostate cells can be induced through crosstalk with mast cells. These collective findings suggest that T. vaginalis contributes to the progression of prostatitis and prostatic hyperplasia by creating an inflammatory microenvironment involving PECs and PSCs.
Topics: Male; Humans; Rats; Animals; Trichomonas vaginalis; Prostatitis; Prostatic Hyperplasia; Trichomonas Infections; Prostate
PubMed: 37170459
DOI: 10.3347/PHD.22160 -
Viruses Dec 2022COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of... (Review)
Review
COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre- or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.
Topics: Male; Humans; Female; COVID-19; SARS-CoV-2; Androgen Antagonists; Androgens; Pandemics; Peptidyl-Dipeptidase A; Antiviral Agents
PubMed: 36560732
DOI: 10.3390/v14122728 -
Mayo Clinic Proceedings Sep 2020Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has rapidly caused a global pandemic associated with a novel respiratory infection: coronavirus disease-19...
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has rapidly caused a global pandemic associated with a novel respiratory infection: coronavirus disease-19 (COVID-19). Angiotensin-converting enzyme-2 (ACE2) is necessary to facilitate SARS-CoV-2 infection, but-owing to its essential metabolic roles-it may be difficult to target it in therapies. Transmembrane protease serine 2 (TMPRSS2), which interacts with ACE2, may be a better candidate for targeted therapies. Using publicly available expression data, we show that both ACE2 and TMPRSS2 are expressed in many host tissues, including lung. The highest expression of ACE2 is found in the testes, whereas the prostate displays the highest expression of TMPRSS2. Given the increased severity of disease among older men with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in severity of disease. We show that expression levels of ACE2 and TMPRSS2 are overall comparable between men and women in multiple tissues, suggesting that differences in the expression levels of TMPRSS2 and ACE2 in the lung and other non-sex-specific tissues may not explain the gender disparities in severity of SARS CoV-2. However, given their instrumental roles for SARS-CoV-2 infection and their pleiotropic expression, targeting the activity and expression levels of TMPRSS2 is a rational approach to treat COVID-19.
Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; Coronavirus Infections; Female; Gene Expression; Gene Frequency; Humans; Lung; Male; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Serine Endopeptidases; Sex Factors
PubMed: 32861340
DOI: 10.1016/j.mayocp.2020.06.018 -
The Canadian Journal of Urology Aug 2021INTRODUCTION The relationship between circumcision and prostate cancer has been controversial. A recently published meta-analysis contradicted previous meta-analyses of... (Meta-Analysis)
Meta-Analysis
UNLABELLED
INTRODUCTION The relationship between circumcision and prostate cancer has been controversial. A recently published meta-analysis contradicted previous meta-analyses of male circumcision and prostate cancer risk. Our aim was to conduct a de novo meta-analysis and critically evaluate this recent paper published by Van Howe.
MATERIALS AND METHODS
We retrieved data from each of the 12 source studies Van Howe used, then performed a random effects meta-analysis of those data. We critically examined the data and other information in Van Howe's study.
RESULTS
Using the same values as Van Howe, we confirmed his finding of a positive association of circumcision with prostate cancer (random effects summary OR = 1.14; 95% CI 0.99, 1.31). However, our independent meta-analysis found a negative association of circumcision with prostate cancer (random effects summary OR= 0.87; 95% CI 0.76, 1.00; p = 0.05). The reason for this critical discrepancy was Van Howe's erroneous transposition of values for circumcised and uncircumcised men in his Table columns, leading to inversion of the result. We further critically evaluated a geographical analysis and cost analysis of circumcision and prostate cancer, as well as claims denying a role for sexually transmitted infections in prostate cancer etiology, finding these too to be misleading.
CONCLUSIONS
Van Howe's 2020 meta-analysis was based on erroneous data transposition leading to an inverted outcome. The journal concerned recently corrected his Table. Van Howe's claim of a positive association of circumcision with country-level-age standardized prostate cancer prevalence and his cost analysis were found to be questionable. Our meta-analysis showed that circumcision is associated with lower prostate cancer risk.
Topics: Circumcision, Male; Humans; Male; Prevalence; Prostate; Prostatic Neoplasms; Sexually Transmitted Diseases
PubMed: 34378513
DOI: No ID Found -
Endocrine-related Cancer Sep 2020The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral... (Review)
Review
The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral drugs and vaccines seeking to reduce its significant disease burden. Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. TMPRSS2 is an androgen-responsive gene and its fusion represents one of the most frequent alterations in prostate cancer. Androgen suppression by androgen deprivation therapy and androgen receptor signaling inhibitors form the foundation of prostate cancer treatment. In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.
Topics: Androgen Antagonists; Androgens; Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Hypothalamo-Hypophyseal System; Male; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Prostatic Neoplasms; SARS-CoV-2; Serine Endopeptidases
PubMed: 32508311
DOI: 10.1530/ERC-20-0165 -
BMJ Open May 2023Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of...
INTRODUCTION
Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of postbiopsy infection is increasing due to increasing antibiotic resistance of rectal flora. Single-centre studies suggest that a clean, percutaneous transperineal approach to prostate biopsy may have a lower risk of infection. To date, there is no high-level evidence comparing transperineal versus transrectal prostate biopsy. We hypothesise that transperineal versus transrectal prostate biopsy under local anaesthesia has a significantly lower risk of infection, similar pain/discomfort levels and comparable detection of non-low-grade prostate cancer.
METHODS AND ANALYSIS
We will perform a multicentre, prospective randomised clinical trial to compare transperineal versus transrectal prostate biopsy for elevated prostate-specific antigen in the first biopsy, prior negative biopsy and active surveillance biopsy setting. Prostate MRI will be performed prior to biopsy, and targeted biopsy will be conducted for suspicious MRI lesions in addition to systematic biopsy (12 cores). Approximately 1700 men will be recruited and randomised in a 1:1 ratio to transperineal versus transrectal biopsy. A streamlined design to collect data and to determine trial eligibility along with the two-stage consent process will be used to facilitate subject recruitment and retention. The primary outcome is postbiopsy infection, and secondary outcomes include other adverse events (bleeding, urinary retention), pain/discomfort/anxiety and critically, detection of non-low-grade (grade group ≥2) prostate cancer.
ETHICS AND DISSEMINATION
The Institutional Review Board of the Biomedical Research Alliance of New York approved the research protocol (protocol number #18-02-365, approved 20 April 2020). The results of the trial will be presented at scientific conferences and published in peer-reviewed medical journals.
TRIAL REGISTRATION NUMBER
NCT04815876.
Topics: Male; Humans; Prostate; Prospective Studies; Biopsy; Prostatic Neoplasms; Rectum; Image-Guided Biopsy; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37208135
DOI: 10.1136/bmjopen-2022-071191