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Int J Mol Sci ; 23(7)2022 Mar 26.
Article in English | MEDLINE | ID: covidwho-1785731


Oral Squamous Cell Carcinoma (OSCC) is the most common malignant cancer affecting the oral cavity. It is characterized by high morbidity and very few therapeutic options. Angiotensin (Ang)-(1-7) is a biologically active heptapeptide, generated predominantly from AngII (Ang-(1-8)) by the enzymatic activity of angiotensin-converting enzyme 2 (ACE 2). Previous studies have shown that Ang-(1-7) counterbalances AngII pro-tumorigenic actions in different pathophysiological settings, exhibiting antiproliferative and anti-angiogenic properties in cancer cells. However, the prevailing effects of Ang-(1-7) in the oral epithelium have not been established in vivo. Here, we used an inducible oral-specific mouse model, where the expression of a tamoxifen-inducible Cre recombinase (CreERtam), which is under the control of the cytokeratin 14 promoter (K14-CreERtam), induces the expression of the K-ras oncogenic variant KrasG12D (LSLK-rasG12D). These mice develop highly proliferative squamous papilloma in the oral cavity and hyperplasia exclusively in oral mucosa within one month after tamoxifen treatment. Ang-(1-7) treated mice showed a reduced papilloma development accompanied by a significant reduction in cell proliferation and a decrease in pS6 positivity, the most downstream target of the PI3K/Akt/mTOR signaling route in oral papilloma. These results suggest that Ang-(1-7) may be a novel therapeutic target for OSCC.

Carcinoma, Squamous Cell , Mouth Neoplasms , Papilloma , Papillomavirus Infections , Angiotensin I/pharmacology , Animals , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Mice , Mice, Transgenic , Mouth Neoplasms/drug therapy , Papilloma/drug therapy , Papilloma/pathology , Papilloma/prevention & control , Papillomavirus Infections/drug therapy , Peptide Fragments , Phosphatidylinositol 3-Kinases/metabolism , Tamoxifen/therapeutic use
J Obstet Gynaecol Can ; 42(3): 301-303, 2020 Mar.
Article in English | MEDLINE | ID: covidwho-1291550


Vulvovaginal atrophy (VVA) resulting from estrogen deprivation at menopause often results in distressing vaginal dryness and dyspareunia. Fewer than 25% of affected women seek help for this condition citing embarrassment, cultural values, an aging or unavailable partner and concerns about use of estrogens following the Women's Health Initiative. Available non-hormonal treatments, such as moisturizers, while affording some relief can be messy to apply and do not prevent disease progression. A new oral selective estrogen receptor modulator, ospemifene, has been found to have strong estrogenic activity in vaginal tissues without adverse estrogenic effects at other sites.

Atrophy/drug therapy , Menopause , Selective Estrogen Receptor Modulators/administration & dosage , Tamoxifen/analogs & derivatives , Vagina/drug effects , Vulva/drug effects , Aged , Atrophy/pathology , COVID-19/drug therapy , Dyspareunia/drug therapy , Female , Humans , Menopause/physiology , Middle Aged , Postmenopause , Selective Estrogen Receptor Modulators/therapeutic use , Tamoxifen/administration & dosage , Tamoxifen/therapeutic use , Vagina/pathology , Vulva/pathology
Cell Transplant ; 30: 963689721991477, 2021.
Article in English | MEDLINE | ID: covidwho-1058182


TRANSLATIONAL RELEVANCE: No prophylactic treatments for COVID-19 have been clearly proven and found. In this pandemic context, cancer patients constitute a particularly fragile population that would benefit the best from such treatments, a present unmet need. TMPRSS2 is essential for COVID-19 replication cycle and it is under androgen control. Estrogen and androgen receptor dependent cues converge on TMPRSS2 regulation through different mechanisms of action that can be blocked by the use of hormonal therapies. We believe that there is enough body of evidence to foresee a prophylactic use of hormonal therapies against COVID-19 and this hypothesis can be easily tested on cohorts of breast and prostate cancer patients who follow those regimens. In case of pandemic, if the protective effect of hormonal therapies will be proven on cancer patients, the use of specific hormonal therapies could be extended to other oncological groups and to healthy individuals to decrease the overall risk of infection by SARS-CoV-2.Given the COVID-19 coronavirus emergency, a special focus is needed on the impact of this rapidly spreading viral infection on cancer patients. Androgen receptor (AR) signaling in the transmembrane protease serine 2 (TMPRSS2) regulation is emerging as an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility. In our study, we analyzed AR and TMPRSS2 expression in 17,352 normal and 9,556 cancer tissues from public repositories and stratified data according to sex and age. The emerging picture is that some patient groups may be particularly susceptible to SARS-CoV-2 infection and may benefit from antiandrogen- or tamoxifen-based therapies. These findings are relevant to choose proper treatments in order to protect cancer patients from concomitant SARS-CoV-2 contagion and related symptoms and put forward the idea that hormonal therapies could be used as prophylactic agents against COVID-19.

Androgen Receptor Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/complications , COVID-19/complications , Estrogen Antagonists/therapeutic use , Prostatic Neoplasms/complications , Tamoxifen/therapeutic use , Androgen Receptor Antagonists/pharmacology , Antineoplastic Agents, Hormonal/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , COVID-19/drug therapy , COVID-19/metabolism , Drug Discovery , Estrogen Antagonists/pharmacology , Female , Humans , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Receptors, Androgen/analysis , Receptors, Androgen/metabolism , Serine Endopeptidases/analysis , Serine Endopeptidases/metabolism , Signal Transduction/drug effects , Tamoxifen/pharmacology