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#34570375   2021/09/27 To Up

Endothelial dysfunction after androgen deprivation therapy and the possible underlying mechanisms.

Androgen deprivation therapy (ADT) is a key treatment modality in the management of prostate cancer (PCa), especially for patients with metastatic disease. Increasing evidences suggest that patients who received ADT have increased incidence of diabetes, myocardial infarction, stroke, and even mortality. It is important to understand the pathophysiological mechanisms on how ADT increases cardiovascular risk and induces cardiovascular events, which would provide important information for potential implementation of preventive measures.
Jeremy Yuen-Chun Teoh, Xiao-Yu Tian, Christine Yim-Ping Wong, Chi-Wai Lau, Chak-Kwong Cheng, Victor Wai-Lun Tang, Ronald Cheong-Kin Chan, Yu Huang, Chi-Fai Ng

1568 related Products with: Endothelial dysfunction after androgen deprivation therapy and the possible underlying mechanisms.

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#34568716   2021/09/16 To Up

Metastatic Castration-Resistant Prostate Cancer Remains Dependent on Oncogenic Drivers Found in Primary Tumors.

Metastatic prostate cancer is initially sensitive to androgen receptor inhibition, but eventually becomes castration-resistant prostate cancer (mCRPC). Early use of more intensive therapies targeting androgen receptor and other oncogenic drivers in treatment-naïve primary prostate cancer (PC) may be more effective than that in advanced mCRPC. However, analysis of primary tumors may not reveal targetable metastatic drivers that are subclonal in the primary tumor or acquired at metastatic sites.
David J Einstein, Seiji Arai, Carla Calagua, Fang Xie, Olga Voznesensky, Brian J Capaldo, Christina Luffman, Jonathan L Hecht, Steven P Balk, Adam G Sowalsky, Joshua W Russo

2915 related Products with: Metastatic Castration-Resistant Prostate Cancer Remains Dependent on Oncogenic Drivers Found in Primary Tumors.



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#34565686   2021/08/20 To Up

A First-in-Human Phase 1 Study of a Novel Selective Androgen Receptor Modulator (SARM), RAD140, in ER+/HER2- Metastatic Breast Cancer.

This first-in-human, phase 1 study aimed to characterize the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetic (PK) profile, and antitumor activity of RAD140, an oral selective androgen receptor (AR) modulator (SARM).
Patricia LoRusso, Erika Hamilton, Cynthia Ma, Neelima Vidula, Rebecca G Bagley, Steven Troy, Miriam Annett, Ziyang Yu, Maureen G Conlan, Amy Weise

2394 related Products with: A First-in-Human Phase 1 Study of a Novel Selective Androgen Receptor Modulator (SARM), RAD140, in ER+/HER2- Metastatic Breast Cancer.

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#34565331   2021/09/26 To Up

Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer.

Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC).
Yingying Lin, Xusheng Zhou, Wei Peng, Jing Wu, Xiufeng Wu, Yan Chen, Zhaolei Cui

2792 related Products with: Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer.



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#34562790   2021/09/10 To Up

Endocrine disruption in the sub Antarctic fish Patagonotothen tessellata (Perciformes, Notothenidae) from Beagle Channel associated to anthropogenic impact.

Situated in the sub-Antarctic region, Beagle Channel represents a unique marine ecosystem due to the connection between the Pacific and the Atlantic Oceans, and its proximity to the Antarctic Peninsula. Ushuaia city, the biggest settlement on the channel, exerts an increasing anthropogenic pressure by discharges of urban and industrial effluents. In the present work, we use Patagonotothen tessellata, one of the most abundant and widespread species in the channel, as a bioindicator species in order to evidence anthropic impact from Ushuaia Bay and surrounding areas. We first analyzed and characterized real time gene expression of androgen receptor, estrogen receptor and different forms of vitellogenin (VTG), under laboratory conditions. This was achieved by induction with estradiol of P. tessellata males. Then, the selected genes were used as biomarkers for an environmental biomonitoring study. Morphometric indices and circulating sex steroids (estradiol and testosterone) were also quantified in male fish collected from different sites. The qPCR analysis showed that vtgAb form is more inducible than vtgAa or vtgC forms after estrogen induction. The field survey revealed the up-regulation of vtgAb and the androgen receptor in fish from sites with higher anthropogenic influence. Sex steroids followed seasonal variations according to their reproductive cycle, with higher levels of estradiol and testosterone in winter and summer seasons. The use of biomarkers such as gene expression of VTG demonstrates that fish from Ushuaia Bay are likely to be exposed to endocrine disrupting compounds. To our knowledge, this research is the first attempt to assess the endocrine disruption associated to anthropic impact in a widespread fish of the Beagle Channel and contributes to a better understanding of the reproductive physiology of sub Antarctic ichthyofauna.
Maria Florencia Ferreira, Fabiana L Lo Nostro, Daniel A Fernández, Griselda Genovese

1139 related Products with: Endocrine disruption in the sub Antarctic fish Patagonotothen tessellata (Perciformes, Notothenidae) from Beagle Channel associated to anthropogenic impact.

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#34562481   2021/09/22 To Up

Impacts of endocrine-disrupting chemicals on prostate function and cancer.

Because of their historical mode of action, endocrine-disrupting chemicals (EDCs) are associated with sex-steroid receptors, namely the two estrogen receptors (ERα and ERβ) and the androgen receptor (AR). Broadly, EDCs can modulate sex-steroid receptor functions. They can also indirectly impact the androgen and estrogen pathways by influencing steroidogenesis, expression of AR or ERs, and their respective activity as transcription factors. Additionally, many of these chemicals have multiple cellular targets other than sex-steroid receptors, which results in a myriad of potential effects in humans. The current article reviews the association between prostate cancer and the endocrine-disrupting functions of four prominent EDC families: bisphenols, phthalates, phytoestrogens, and mycoestrogens. Results from both in vitro and in vivo models are included and discussed to better assess the molecular mechanisms by which EDCs can modify prostate biology. To overcome the heterogeneity of results published, we established common guidelines to properly study EDCs in the context of endocrine diseases. Firstly, the expression of sex-steroid receptors in the models used must be determined before testing. Then, in parallel to EDCs, pharmacological compounds acting as positive (agonists) and negative controls (antagonists) have to be employed. Finally, EDCs need to be used in a precise range of concentrations to modulate sex-steroid receptors and avoid off-target effects. By adequately integrating molecular endocrinology aspects in EDC studies and identifying their underlying molecular mechanisms, we will truly understand their impact on prostate cancer and distinguish those that favor the progression of the disease from those that slow down tumor development.
Aurélie Lacouture, Camille Lafront, Cindy Peillex, Martin Pelletier, Étienne Audet-Walsh

2421 related Products with: Impacts of endocrine-disrupting chemicals on prostate function and cancer.



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#34561463   2020/09/25 To Up

ARe we there yet? Understanding androgen receptor signaling in breast cancer.

The role of androgen receptor (AR) activation and expression is well understood in prostate cancer. In breast cancer, expression and activation of AR is increasingly recognized for its role in cancer development and its importance in promoting cell growth in the presence or absence of estrogen. As both prostate and breast cancers often share a reliance on nuclear hormone signaling, there is increasing appreciation of the overlap between activated cellular pathways in these cancers in response to androgen signaling. Targeting of the androgen receptor as a monotherapy or in combination with other conventional therapies has proven to be an effective clinical strategy for the treatment of patients with prostate cancer, and these therapeutic strategies are increasingly being investigated in breast cancer. This overlap suggests that targeting androgens and AR signaling in other cancer types may also be effective. This manuscript will review the role of AR in various cellular processes that promote tumorigenesis and metastasis, first in prostate cancer and then in breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of cancer, especially breast cancer.
Anna R Michmerhuizen, Daniel E Spratt, Lori J Pierce, Corey W Speers

2232 related Products with: ARe we there yet? Understanding androgen receptor signaling in breast cancer.



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#34559606   2021/08/31 To Up

A Common Endocrine Signature Marks the Convergent Evolution of an Elaborate Dance Display in Frogs.

AbstractUnrelated species often evolve similar phenotypic solutions to the same environmental problem, a phenomenon known as convergent evolution. But how do these common traits arise? We address this question from a physiological perspective by assessing how convergence of an elaborate gestural display in frogs (foot-flagging) is linked to changes in the androgenic hormone systems that underlie it. We show that the emergence of this rare display in unrelated anuran taxa is marked by a robust increase in the expression of androgen receptor (AR) messenger RNA in the musculature that actuates leg and foot movements, but we find no evidence of changes in the abundance of AR expression in these frogs' central nervous systems. Meanwhile, the magnitude of the evolutionary change in muscular AR and its association with the origin of foot-flagging differ among clades, suggesting that these variables evolve together in a mosaic fashion. Finally, while gestural displays do differ between species, variation in the complexity of a foot-flagging routine does not predict differences in muscular AR. Altogether, these findings suggest that androgen-muscle interactions provide a conduit for convergence in sexual display behavior, potentially providing a path of least resistance for the evolution of motor performance.
Nigel K Anderson, Eric R Schuppe, K V Gururaja, Lisa A Mangiamele, Juan Carlos Cusi Martinez, H Priti, Rudolf von May, Doris Preininger, Matthew J Fuxjager

1164 related Products with: A Common Endocrine Signature Marks the Convergent Evolution of an Elaborate Dance Display in Frogs.

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#34555425   2021/09/20 To Up

Androgens promote vascular endothelial cell proliferation through activation of a ZIP9-dependent inhibitory G protein/PI3K-Akt/Erk/cyclin D1 pathway.

While androgens have been reported to mediate cardiovascular endothelial cell proliferation, the potential involvement of membrane androgen receptors (mAR) has not been examined. Here we show ZIP9, a recently characterized mAR, mediates androgen-induced early proliferative events in human umbilical vein endothelial cells (HUVECs). Androgen treatment significantly increased cyclin D1 nuclear localization and proliferation, which were blocked by transfection with siRNA targeting ZIP9 but not the nuclear AR. Testosterone rapidly activated inhibitory G protein signaling, Erk, and Akt, and inhibition of these signaling members abrogated the ZIP9-mediated cyclin D1 and proliferative responses. Erk and Akt modulated cyclin D1 nuclear localization by upregulation of cyclin D1 mRNA and inhibition of GSK-3β activity, respectively. This is the first study to demonstrate a role for ZIP9 in HUVEC proliferation and indicates ZIP9 is a physiologically-relevant androgen receptor in the cardiovascular system that merits further study as a potential therapeutic target for treating cardiovascular disease.
Aubrey Converse, Peter Thomas

1369 related Products with: Androgens promote vascular endothelial cell proliferation through activation of a ZIP9-dependent inhibitory G protein/PI3K-Akt/Erk/cyclin D1 pathway.

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