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Search results for: Androgen Receptor

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#34314871   2021/07/24 To Up

Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study).

In the last years, many studies have highlighted the hypothesis that diabetes and hyperglycemia could be relevant for prostate cancer (PC) development and progression. We aimed to identify the prognostic value of tissue expression of androgen receptor (AR), Prostate-Specific Membrane Antigen (PSMA), Ki-67, insulin receptors (IR)  α and β, insulin growth factor-1 (IGF-1) receptor, in patients with PC and to evaluate their association with diabetes. We retrospectively collected data from 360 patients who underwent radical prostatectomy for PC or surgery for benign prostatic hyperplasia (BPH), between 2010 and 2020. We constructed tissue microarray for immunohistochemistry (IHC) analysis. In the final cohort (76 BPH and 284 PC), 57 (15.8%) patients had diabetes, 17 (22.37%) in BPH and 40 (14.08%) in PC (p=0.08). IR-α was more expressed in patients with PC compared to the BPH Group (95.96% vs. 4.04%; p<0.01). We found that AR was associated with increased risk of International Society of Urological Pathology (ISUP) score ≥4 (OR: 2.2; p<0.05), higher association with Ki-67 (OR: 2.2; p<0.05) and IR-α (OR: 5.7; p<0.05); IGF-1 receptor was associated with PSMA (OR: 2.8; p<0.05), Ki-67 (OR: 3.5; p<0.05) and IR-β (OR: 5.1; p<0.05). Finally, IGF-1 receptor was predictive of ISUP ≥ 4 (OR: 16.5; p=0.017) in patients with PC and diabetes. In the present study we highlighted how prostate cancer patients have a different protein expression in the tissue. This expression, and in particular that relating to IGF-1R, is associated with greater tumor aggressiveness in those patients with diabetes. We suppose that these results are attributable to an alteration of the insulin signal which therefore determines a greater mitogenic activity that can influence tumor progression.
Giuseppe Broggi, Arturo Lo Giudice, Marina Di Mauro, Elisabetta Pricoco, Eliana Piombino, Matteo Ferro, Rosario Caltabiano, Giuseppe Morgia, Giorgio Ivan Russo

1272 related Products with: Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study).



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#34314764   2021/07/24 To Up

α-Methylacyl-CoA racemase: a useful immunohistochemical marker of breast carcinoma with apocrine differentiation.

Carcinoma with apocrine differentiation is an androgen receptor (AR)-positive subset of triple-negative breast carcinomas. In addition to carcinoma with apocrine differentiation, other AR-positive triple-negative breast carcinomas occur, albeit less frequently. We found that α-methylacyl-CoA racemase (AMACR), also known as P504S, is overexpressed in carcinoma with apocrine differentiation and non-neoplastic apocrine metaplasia. We aimed to evaluate AMACR as a possible marker of carcinoma with apocrine differentiation. We immunohistochemically examined the expression of AMACR in carcinoma with apocrine differentiation and non-apocrine carcinomas and compared it with that of gross cystic disease fluid protein-15 (GCDFP-15). In total, 212 breast carcinomas were evaluated: 39 carcinomas with apocrine differentiation, 28 ductal carcinomas in situ with apocrine morphology (ADCIS), and 145 non-apocrine breast carcinomas. AMACR was expressed in 38 out of 39 (97.4%) carcinomas with apocrine differentiation and in 27 out of 28 (96.4%) ADCIS, consistent with the expression of GCDFP-15. However, in non-apocrine carcinomas, AMACR expression was observed in 32 out of 145 (22.0%) lesions, whereas GCDFP-15 expression was observed in 91 out of 145 (62.7%) lesions. For carcinoma with apocrine differentiation, AMACR was as sensitive as GCDFP-15 (both 97.1%) but more specific (77.9% vs. 37.2%). In selected cases, AMACR mRNA levels were quantitatively determined relative to that of TATA-binding protein mRNA, and they comprised 5.23, 1.33, and 0.60 for carcinomas with apocrine differentiation, non-apocrine carcinomas, and normal breast tissue, respectively. CONCLUSION: Our findings demonstrate that AMACR expression may be utilized for differentiating carcinoma with apocrine differentiation from non-apocrine carcinomas and indicate that AMACR is a more sensitive carcinoma with apocrine differentiation marker than GCDFP-15.
Harumi Nakamura, Yoji Kukita, Kei Kunimasa, Nobuyoshi Kittaka, Hirotaka Kusama, Takahiro Nakayama, Yasuhiro Tamaki, Ryoko Sugiura, Hidemitsu Yasuda, Masanori Hashimoto, Takashi Yamamoto, Fumio Imamura, Sin-Ichi Nakatsuka

1603 related Products with: α-Methylacyl-CoA racemase: a useful immunohistochemical marker of breast carcinoma with apocrine differentiation.



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#34313171   // To Up

The Role of Androgen Receptor Splicing Variant 7 in Predicting the Prognosis of Metastatic Castration-Resistant Prostate Cancer: Systematic Review and Meta-Analysis.

The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer (mCRPC) under different treatment options (chemotherapy, hormone therapy).
Rui-Ji Liu, Qiang Hu, Shu-Ying Li, Wei-Pu Mao, Bin Xu, Ming Chen

1101 related Products with: The Role of Androgen Receptor Splicing Variant 7 in Predicting the Prognosis of Metastatic Castration-Resistant Prostate Cancer: Systematic Review and Meta-Analysis.

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#34312180   2021/07/26 To Up

RNA splicing factors SRRM3 and SRRM4 distinguish molecular phenotypes of castration-resistant neuroendocrine prostate cancer.

Neuroendocrine (NE) differentiation in metastatic castration-resistant prostate cancer (mCRPC) is an increasingly common clinical feature arising from cellular plasticity. We recently characterized two mCRPC phenotypes with NE features: androgen receptor (AR)-positive NE-positive amphicrine prostate cancer (AMPC) and AR-negative small cell or neuroendocrine prostate cancer (SCNPC). Here, we interrogated the regulation of RE1-silencing transcription factor (REST), a transcriptional repressor of neuronal genes, and elucidated molecular programs driving AMPC and SCNPC biology. Analysis of prostate cancer (PC) cell lines, mCRPC specimens, and LuCaP patient-derived xenograft models detected alternative splicing of REST to REST4 and attenuated REST repressor activity in AMPC and SCNPC. The REST locus was also hypermethylated and REST expression was reduced in SCNPC. While serine/arginine repetitive matrix protein 4 (SRRM4) was previously implicated in alternative splicing of REST in mCRPC, we detected SRRM3 expression in REST4-positive, SRRM4-negative AMPC and SCNPC. In CRPC cell lines, SRRM3 induced alternative splicing of REST to REST4 and exacerbated the expression of REST-repressed genes. Furthermore, SRRM3 and SRRM4 expression defined molecular subsets of AMPC and SCNPC across species and tumor types. Two AMPC phenotypes and three SCNPC phenotypes were characterized, denoted either by REST attenuation and ASCL1 activity or by progressive activation of neuronal transcription factor programs, respectively. These results nominate SRRM3 as the principal REST splicing factor expressed in early NE differentiation and provide a framework to molecularly classify diverse NE phenotypes in mCRPC.
Mark P Labrecque, Lisha G Brown, Ilsa M Coleman, Bryce Lakely, Nicholas J Brady, John K Lee, Holly M Nguyen, Dapei Li, Brian Hanratty, Michael C Haffner, David S Rickman, Lawrence D True, Daniel W Lin, Hung-Ming Lam, Joshi J Alumkal, Eva Corey, Peter S Nelson, Colm Morrissey

2984 related Products with: RNA splicing factors SRRM3 and SRRM4 distinguish molecular phenotypes of castration-resistant neuroendocrine prostate cancer.



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#34311541   2021/04/01 To Up

Emerging impact of quercetin in the treatment of prostate cancer.

Quercetin is a flavonoid agent detected in fruits and vegetables with anti-inflammatory, antioxidant, and anticancer effects. This flavonoid can suppress cell cycle transition and induce apoptosis in neoplastic cells. Therapeutic effects of quercetin have been assessed in diverse cancers including prostate cancer through the establishment of in vitro and in vivo experiments. Moreover, this agent might prevent the initiation of this type of cancer as it indirectly blocks the activity of promoters of two important genes in the pathogenesis of prostate cancer i.e. androgen receptor (AR) and prostate specific antigen (PSA). Several in vitro investigations have identified the differential influence of quercetin on normal prostate cells versus neoplastic cells, emphasizing its specific cytotoxic effects on cancerous cells. The most appreciated route of quercetin effect on prostate cancer cells is the detachment of Bax from Bcl-xL and the stimulation of caspase families. Besides, quercetin might enhance the effects of other therapeutic options against prostate cancer. For instance, a combination of TNF-related apoptosis-inducing ligand (TRAIL) and quercetin has been recommended as a novel modality for the treatment of prostate cancer. These kinds of strategies might overcome resistance to apoptosis in cancer cells. In the current paper, we summarize the recent data about the preventive and therapeutic influences of quercetin in prostate cancer.
Soudeh Ghafouri-Fard, Farnaz Aghazadeh Shabestari, Saba Vaezi, Atefe Abak, Hamed Shoorei, Arash Karimi, Mohammad Taheri, Abbas Basiri

2560 related Products with: Emerging impact of quercetin in the treatment of prostate cancer.



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#34297060   2021/07/23 To Up

Androgen-dependent and DNA binding-independent association of androgen receptor with chromatic regions coding androgen-induced non-coding RNAs.

Androgen induces the binding of its receptor (AR) to androgen-responsive elements (AREs), while genome-wide studies showed that most androgen-induced AR binding sites on chromatin were unrelated to AREs. Enhancer RNAs (eRNAs), a class of non-coding RNAs(ncRNAs), are transcribed from super-enhancers (SEs), and trigger the formation of large ribonucleoprotein (RNP) condensates of transcription factors. By in silico search, an SE is found to be located on the locus of KLK3 that encodes prostate specific antigen (PSA). On the KLK3 SE, androgen-induced expression of ncRNAs was detected and designated as KLK3eRNAs in LNCaP cells, and androgen-induced association of AR and FOXA1 on the KLK3eRNA coding regions was detected. Such androgen-induced association of an AR mutant lacking DNA binding activity on the KLK3eRNA coding regions was undetectable on an exogenous ARE. Thus, the present findings suggest a molecular basis of androgen-induced association of AR with chromatin on ARE-unrelated sequences.
Takahiro Sawada, Koichi Nishimura, Jinichi Mori, Yoshiaki Kanemoto, Alexander Kouzmenko, Rei Amano, Akira Hayakawa, Suguru Tokiwa, Hiroaki Shimmura, Shigeaki Kato

1194 related Products with: Androgen-dependent and DNA binding-independent association of androgen receptor with chromatic regions coding androgen-induced non-coding RNAs.

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#34296344   2021/07/23 To Up

Activation of C-C motif chemokine receptor 2 modulates testicular macrophages number, steroidogenesis, and spermatogenesis progression.

The monocyte chemoattractant protein 1 (MCP-1) belongs to the CC chemokine family and acts in the recruitment of C-C motif chemokine receptor 2 (CCR2)-positive immune cell types to inflammation sites. In testis, the MCP-1/CCR2 axis has been associated with the macrophage population's functional regulation, which presents significant functions supporting germ cell development. In this context, herein, we aimed to investigate the role of the chemokine receptor CCR2 in mice testicular environment and its impact on male sperm production. Using adult transgenic mice strain that had the CCR2 gene replaced by a red fluorescent protein gene, we showed a stage-dependent expression of CCR2 in type B spermatogonia and early primary spermatocytes. Several parameters related to sperm production were reduced in the absence of CCR2 protein, such as Sertoli cell efficiency, meiotic index, and overall yield of spermatogenesis. Daily sperm production decreased by almost 40%, and several damages in the seminiferous tubules were observed. Significant reduction in the expression of important genes related to the Sertoli cell function (Cnx43, Vim, Ocln, Spna2) and meiosis initiation (Stra8, Pcna, Prdm9, Msh5) occurred in comparison to controls. Also, the number of macrophages significantly decreased in the absence of CCR2 protein, along with a disturbance in Leydig cell steroidogenic activity. In summary, our results show that the non-activation of the MCP-1/CCR2 axis disturbs the testicular homeostasis, interfering in macrophage population, meiosis initiation, blood-testis barrier function, and androgen synthesis, leading to the malfunction of seminiferous tubules, decreased testosterone levels, defective sperm production, and lower fertility index.
A F A Figueiredo, N T Wnuk, C P Vieira, M F F Gonçalves, M R G Brener, A B Diniz, M M Antunes, H M Castro-Oliveira, G B Menezes, G M J Costa

2465 related Products with: Activation of C-C motif chemokine receptor 2 modulates testicular macrophages number, steroidogenesis, and spermatogenesis progression.

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#34296282   2021/07/23 To Up

Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer.

Randomized trials showed the survival benefits of the combined use of androgen receptor axis-targeted agents with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer (mHSPC), regardless of the risk. However, treating patients with low-risk mHSPC with such intensive treatment is still debatable.
Shunsuke Tsuzuki, Shota Kawano, Wataru Fukuokaya, Keiichiro Mori, Hideomi Nishikawa, Kojiro Tashiro, Daisuke Watanabe, Taizo Uchimoto, Kazuki Nishimura, Yusuke Yano, Masaya Murakami, Yusuke Koike, Kenichi Hata, Haruhisa Koide, Jun Miki, Hirokazu Abe, Hiroki Yamada, Takehito Naruoka, Shingo Sugaya, Takahiro Kimura, Masayuki Tomita, Hiroshi Nakajo, Shin Egawa

1940 related Products with: Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer.



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#34294894   2021/07/22 To Up

Arming androgen receptors to oppose oncogenic estrogen receptor activity in breast cancer.

Most breast cancers are driven by oncogenic activity of the estrogen receptor alpha (ER). Resistance to ER target therapies is the major cause of breast cancer death. Recently, there has been renewed interest in targeting the androgen receptor (AR) to treat ER-driven breast cancers. Herein, we discuss evidence for an AR agonist, not antagonist, treatment strategy.
Theresa E Hickey, Amy R Dwyer, Wayne D Tilley

1324 related Products with: Arming androgen receptors to oppose oncogenic estrogen receptor activity in breast cancer.

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#34310983   2021/07/23 To Up

Prognostic value of androgen receptor expression and molecular alterations in metastatic triple negative or low hormone receptor breast carcinomas.

Metastatic breast carcinomas (BCs) with phenotype of triple negative (TNBC) or low hormonal receptor levels [estrogen receptor (ER)/progesterone receptor (PR) < 10% and HER2-] are mainly treated with cytotoxic chemotherapy. Targeting androgen receptor (AR) pathway may represent a potential new therapeutic strategy in such group of BCs. We evaluated AR expression by immunohistochemistry and genetic alterations by next generation sequencing. Among 114 metastatic BCs, 37 (32.5%) cases showed AR expression and 77 (67.5%) were lack of AR expression. Statistical analysis revealed that AR expression is associated with older age, lobular carcinoma, positive ER and positive PR in primary tumors, and lymph node metastasis. Patients with AR-positive tumors had significantly longer metastatic intervals and overall survivals. In addition, AR-positive tumors had significantly higher rate of PI3CA mutation. Our results demonstrated that AR expression has prognostic value in this subgroup of metastatic BCs and tumors with AR expression had different molecular alterations compared to those without AR expression.
Tiansheng Shen, Lai Wei, Xiaoxian Li, Anil V Parwani, Zaibo Li

1825 related Products with: Prognostic value of androgen receptor expression and molecular alterations in metastatic triple negative or low hormone receptor breast carcinomas.

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