Search results for: Androgen Receptor (Phospho-Ser213) Antibody
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Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR's prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients' prognosis.
2812 related Products with: Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.Breast cancer tissue arra Breast cancer and normal Breast cancer tissue arra Breast cancer tissue arra Breast cancer tissue arra Middle advanced stage bre Breast cancer tissue arra Breast cancer test tissue High density (188 cases 2 Breast cancer tissue arra Breast cancer tissue arra Breast cancer and matched
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Phenotypic Profiling of Circulating Tumor Cells in Metastatic Prostate Cancer Patients Using Nanoparticle-Mediated Ranking.The analysis of circulating tumor cells (CTCs) provides a means to collect information about the evolving properties of a tumor during cancer progression and treatment. For patients with metastatic prostate cancer, noninvasive serial measurements of bloodborne cells may provide a means to tailor therapeutic decisions based on an individual patient's response. Here, we used a high-sensitivity profiling approach to monitor CTCs in patients with metastatic castrate-resistant prostate cancer (mCRPC) undergoing treatment with abiraterone and enzalutamide, two drugs used to treat advanced prostate cancer. The capture and profiling approach uses antibody-functionalized magnetic nanoparticles to sort cells according to protein expression levels. CTCs are tagged with magnetic nanoparticles conjugated to an antibody specific for the epithelial cell adhesion molecule (EpCAM) and sorted into four zones of a microfluidic device based on EpCAM expression levels. Our approach was compared to the FDA-cleared CellSearch method, and we demonstrate significantly higher capture efficiency of low-EpCAM cells compared to the commercial method. The nanoparticle-based approach detected CTCs from 86% of patients at baseline, compared to CellSearch which only detected CTCs from 60% of patients. Patients were stratified as prostate specific antigen (PSA) progressive versus responsive based on clinically acceptable definitions, and it was observed that patients with a limited response to therapy had elevated levels of androgen receptor variant 7 (ARV7) and the mesenchymal marker, N-cadherin, expressed on their CTCs. In addition, these CTCs exhibited lower EpCAM expression. The results highlight features of CTCs associated with disease progression on abiraterone or enzalutamide, including mesenchymal phenotypes and increased expression levels of ARV7. The use of a high-sensitivity method to capture and profile CTCs provides more informative data concerning the phenotypic properties of these cells as patients undergo treatment relative to an FDA-cleared method.
1696 related Products with: Phenotypic Profiling of Circulating Tumor Cells in Metastatic Prostate Cancer Patients Using Nanoparticle-Mediated Ranking.Prostate cancer tissue ar Lung cancer tissue array Prostate cancer tissue ar Breast cancer and matched Prostate cancer test tiss Prostate cancer, PIN (pro Prostate cancer tissue ar Mid advanced stage kidney Prostate cancer tissue ar Prostate cancer and norma Prostate cancer, hyperpla Prostate cancer, hyperpla
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Preclinical efficacy of hK2 targeted [Lu]hu11B6 for prostate cancer theranostics.Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The humanized IgG1 antibody hu11B6 internalizes into prostate and prostate cancer (PCa) cells by binding to the catalytic cleft of human kallikrein 2 (hK2), a prostate specific enzyme governed by the AR-pathway. In a previous study, hu11B6 conjugated with Actinium-225 (Ac), a high linear energy transfer (LET) radionuclide, was shown to generate an AR-upregulation driven feed-forward mechanism that is believed to enhance therapeutic efficacy. We assessed the efficacy of hu11B6 labeled with a low LET beta-emitter, Lutetium-177 (Lu) and investigated whether similar tumor killing and AR-enhancement is produced. Moreover, single-photon emission computed tomography (SPECT) imaging of Lu is quantitatively accurate and can be used to perform treatment planning. [Lu]hu11B6 therefore has significant potential as a theranostic agent. : Subcutaneous PCa xenografts (LNCaP s.c.) were grown in male mice. Biokinetics at 4-336 h post injection and uptake as a function of the amount of hu11B6 injected at 72 h were studied. Over a 30 to 120-day treatment period the therapeutic efficacy of different activities of [Lu]hu11B6 were assessed by volumetric tumor measurements, blood cell counts, molecular analysis of the tumor as well as SPECT/CT imaging. Organ specific mean absorbed doses were calculated, using a MIRD-scheme, based on biokinetic data and rodent specific S-factors from a modified MOBY phantom. Tumor tissues of treated xenografts were immunohistochemically (IHC) stained for Ki-67 (proliferation) and AR, SA-β-gal activity (senescence) and analyzed by digital autoradiography (DAR). : Organ-to-blood and tumor-to-blood ratios were independent of hu11B6 specific activity except for the highest amount of antibody (150 µg). Tumor accumulation of [Lu]hu11B6 peaked at 168 h with a specific uptake of 29 ± 9.1 percent injected activity per gram (%IA/g) and low accumulation in normal organs except in the submandibular gland (15 ± 4.5 %IA/g), attributed to a cross-reaction with mice kallikreins in this organ, was seen. However, SPECT imaging with therapeutic amounts of [Lu]hu11B6 revealed no peak in tumor accumulation at 7 d, probably due to cellular retention of Lu and decreasing tumor volumes. For [Lu]hu11B6 treated mice, tumor decrements of up to 4/5 of the initial tumor volume and reversible myelotoxicity with a nadir at 12 d were observed after a single injection. Tumor volume reduction correlated with injected activity and the absorbed dose. IHC revealed retained expression of AR throughout treatment and that Ki-67 staining reached a nadir at 9-14 d which coincided with high SA- β-gal activity (14 d). Quantification of nuclei staining showed that Ki-67 expression correlated negatively with activity uptake. AR expression levels in cells surviving therapy compared to previous timepoints and to controls at 30 d were significantly increased (p = 0.017). : This study shows that hu11B6 labeled with the low LET beta-emitting radionuclide Lu can deliver therapeutic absorbed doses to prostate cancer xenografts with transient hematological side-effects. The tumor response correlated with the absorbed dose both on a macro and a small scale dosimetric level. Analysis of AR staining showed that AR protein levels increased late in the study suggesting a therapeutic mechanism, a feed forward mechanism coupled to AR driven response to DNA damage or clonal lineage selection, similar to that reported in high LET alpha-particle therapy using Ac labeled hu11B6, however emerging at a later timepoint.
2065 related Products with: Preclinical efficacy of hK2 targeted [Lu]hu11B6 for prostate cancer theranostics.Top 4 types of cancer (co High density (208 core) p Multiple prostate cancer Prostate cancer and hyper Prostate cancer, adjacent Prostate cancer tissue ar Top 4 types of cancer (co High density prostate can Prostate cancer tissue ar Prostate cancer test tiss Prostate cancer tissue ar Prostate cancer and norma
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Human placental androgen receptor variants: Potential regulators of male fetal growth.Numerous studies show that males have increased intrauterine growth compared to females, and that pregnancy complications may further these growth differences, but the regulatory mechanisms underlying these differences remain unknown. We propose that these growth outcomes may be due to sex-specific differences in androgen sensitivity - giving rise to altered growth signalling pathways - mediated by the differential expression of placental androgen receptor (AR) variants.
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Apocrine epithelial-myoepithelial carcinoma of the parotid gland with concurrent oncocytic change: a novel variant.Epithelial-myoepithelial carcinoma (EMCa) is a rare, low-grade, malignant salivary gland tumor. Here, we report an unusual case of an EMCa with extensive apocrine and oncocytic changes. The tumor occurred in the left parotid gland of a 68-year-old male. Histologically, the tumor was characterized by a biphasic arrangement of luminal ductal cells and abluminal polygonal myoepithelial cells, with prominent apocrine differentiation in the luminal layer and dense eosinophilic cytoplasm in both components. Immunohistochemically, the ductal epithelial component was positive for cytokeratin 7, androgen receptor, gross cystic disease fluid protein 15, and human epidermal growth factor receptor 2, and both components were diffusely positive for anti-mitochondria antibody and phosphotungstic acid-hematoxylin. EMCa with apocrine differentiation or oncocytic change is an uncommon variant. To the best of our knowledge, this report describes the first case of these 2 variants coexisting in EMCa tumor cells to be reported in the English-language literature. Awareness of the histopathologic features of EMCa is necessary to avoid making an incorrect diagnosis.
1964 related Products with: Apocrine epithelial-myoepithelial carcinoma of the parotid gland with concurrent oncocytic change: a novel variant.Parotid gland disease spe Breast carcinoma (combina Colon and rectum carcinom Lung carcinoma progressio Thyroid carcinoma (multi Colon carcinoma (multi ti Non small cell lung carci Penile (penis) carcinoma Alkaline Phospatase (ALP) Multiple head and neck sq Cervical carcinoma tissue Lung large cell carcinoma
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Consideration of breast cancer subtype in targeting the androgen receptor.The androgen receptor (AR) is a drug target in breast cancer, and AR-targeted therapies have induced tumor responses in breast cancer patients. In this review, we summarized the role of AR in breast cancer based on preclinical and clinical data. Response to AR-targeted therapies in unselected breast cancer populations is relatively low. Preclinical and clinical data show that AR antagonists might have a role in estrogen receptor (ER)-negative/AR-positive tumors. The prognostic value of AR for patients remains uncertain due to the use of various antibodies and cut-off values for immunohistochemical assessment. To get more insight into the role of AR in breast cancer, we additionally performed a retrospective pooled analysis to determine the prognostic value of the AR using mRNA profiles of 7270 primary breast tumors. Our analysis shows that a higher AR mRNA level is associated with improved disease outcome in patients with ER-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, but with worse disease outcome in HER2-positive subgroups. In conclusion, next to AR expression, incorporation of additional tumor characteristics will potentially make AR targeting a more valuable therapeutic strategy in breast cancer.
1895 related Products with: Consideration of breast cancer subtype in targeting the androgen receptor.Late stage breast cancer Breast cancer tissue arra Advanced breast cancer an High density breast cance High density (188 cases 2 Breast cancer tissue arra Breast cancer tissue arra Breast cancer and matched Breast cancer, carcinoma Breast disease spectrum t Breast cancer test tissue Breast cancer tissue arra
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Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis.Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies and presents chemoresistance after chemotherapy treatment. Androgen receptor (AR) has been known to participate in proliferation. Yet the mechanisms of the resistance of this drug and its linkage to the AR remains unclear.
1405 related Products with: Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis.Androgen Receptor , Mouse Androgen Receptor Antibod Anti-Androgen Receptor pr Goat Anti-Human TEM8 Anth Rabbit Anti-Human Androge Androgen Receptor (Phosph Dog Receptor-binding canc Rat Toll Like Receptor 2( Goat Anti-Human Androgen Rabbit Anti-Human Toll-Li Androgen Receptor Ab-1 An Androgen Receptor Antibod
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The gonadotropin-inhibitory hormone system of fish: The case of sea bass (Dicentrarchus labrax).Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide belonging to the RFamide peptide family that was first discovered in quail by Tsutsui and co-workers in the year 2000. Since then, different GnIH orthologues have been identified in all vertebrate groups, from agnathans to mammals. These GnIH genes synthesize peptide precursors that encompass two to four C-terminal LPXRFamide peptides. Functional and behavioral studies carried out in birds and mammals have demonstrated a clear inhibitory role of GnIH on GnRH and gonadotropin synthesis and secretion as well as on aggressive and sexual behavior. However, the effects of Gnih orthologues in reproduction remain controversial in fish with both stimulatory and inhibitory actions being reported. In this paper, we will review the main findings obtained in our laboratory on the Gnih system of the European sea bass, Dicentrarchus labrax. The sea bass gnih gene encodes two putative Gnih peptides (sbGnih1 and sbGnih2), and is expressed in the olfactory bulbs/telencephalon, diencephalon, midbrain tegmentum, rostral rhombencephalon, retina and testis. The immunohistochemical study performed using specific antibodies developed in our laboratory revealed Gnih-immunoreactive (ir) perikarya in the same central areas and Gnih-ir fibers that profusely innervated the brain and pituitary of sea bass. Moreover, in vivo studies revealed the inhibitory role of centrally- and peripherally-administered Gnih in the reproductive axis of male sea bass, by acting at the brain (on gnrh and kisspeptin expression), pituitary (on gnrh receptors and gonadotropin synthesis and release) and gonadal (on androgen secretion and gametogenesis) levels. Our results have revealed the existence of a functional Gnih system in sea bass, and have provided evidence of the differential actions of the two Gnih peptides on the reproductive axis of this species, the main inhibitory role in the brain and pituitary being exerted by the sbGnih2 peptide. Recent studies developed in our laboratory also suggest that Gnih might be involved in the transduction of photoperiod and temperature information to the reproductive axis, as well as in the modulation of daily and seasonal rhythmic processes in sea bass.
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Nimotuzumab inhibits epithelial-mesenchymal transition in prostate cancer by targeting the Akt/YB-1/AR axis.Nimotuzumab is a humanized anti-EGF monoclonal antibody that has been approved for treating different cancers. However, few studies have examined its therapeutic potential in prostate cancer (PC), a most common and highly aggressive malignancy among male population. We used both LNCaP, and PC3 and PC3-AR (androgen receptor) cells as the model system and assessed the effects of nimotuzumab on epithelial-mesenchymal transition (EMT) in vitro and in vivo. The EMT makers were detected by immunohistochemistry, qRT-PCR and Western blot. MTT, wound healing assay, and transwell assay were used to measure cell viability, migration, and invasion, respectively. For mechanistic understanding, we evaluated the significance of Akt/Y-box binding protein-1 (YB-1)/AR axis in nimotuzumab-induced EMT by overexpressing AR, activating Akt using SC79, and/or downregulating YB-1 using siRNA. Nimotuzumab suppressed the xenograft growth from both LNCaP and PC3 cells in vivo, which was associated with reduced EMT. Consistently, nimotuzumab inhibited proliferation, cell-cycle progression, EMT, and migration/invasion, but stimulated apoptosis of both LNCaP and PC3-AR cells in vitro. On the molecular level, nimotuzumab inactivated Akt and YB-1 and reduced the expression of AR. Boosting AR expression in LNCaP and PC3-AR cells antagonized the action of nimotuzumab, at least partially restored EMT, and enhanced the migration/invasion. We also found that Akt was essential for controlling YB-1 activation, and both critical for regulating the levels of AR and EMT-related biomarkers. In this study, we presented our novel findings that by targeting the Akt/YB-1/AR axis, nimotuzumab significantly inhibited EMT of PC cells. Considering that EMT is a critical mechanism contributing to the metastatic spread of cancer cells, nimotuzumab may become a promising therapy for alleviating the malignant progression of PC. © 2019 IUBMB Life, 1-14, 2019.
2314 related Products with: Nimotuzumab inhibits epithelial-mesenchymal transition in prostate cancer by targeting the Akt/YB-1/AR axis.Prostate cancer tissue ar Prostate cancer, hyperpla Prostate cancer tissue ar Multiple prostate cancer Prostate cancer and hyper Prostate cancer test tiss Prostate cancer tissue ar Prostate cancer tissue ar Prostate cancer and norma Prostate cancer tissue ar Prostate cancer test tiss Prostate cancer, PIN (pro
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Combination of phospholipase Cε knockdown with GANT61 sensitizes castration‑resistant prostate cancer cells to enzalutamide by suppressing the androgen receptor signaling pathway.Castration‑resistant prostate cancer (CRPC) is a major challenge in the treatment of prostate cancer (PCa). Phospholipase Cε (PLCε), an oncogene, has been found to be involved in the carcinogenesis, tumor proliferation and migration of several types of cancer. The effects, however, of PLCε on CRPC remains unclear. In the present study, the expression of PLCε and glioma‑associated homolog (Gli)‑1/Gli‑2 in benign prostatic hyperplasia (BPH), PCa and CRPC tissues and cells was investigated, and the correlations between PLCε and Gli‑1/Gli‑2 in CRPC tissues and cell lines were further explored. In addition, the effect of PLCε on cell proliferation and invasion was assessed in CRPC cell lines, and the sensitivity of EN‑R and 22RV1 cells to enzalutamide following the downregulation of PLCε expression was determined using lentivirus‑mediated shPLCε and/or treatment with specific Gli inhibitor GANT61. It was found that the PLCε expression was excessively upregulated in the majority of CRPC tissues, and PLCε positivity was linked to poor progression‑free survival (PFS) and overall survival (OS) in patients with PCa. Furthermore, PLCε knockdown significantly suppressed CRPC cell proliferation and invasion. Of note, it was found that PLCε knockdown increased the sensitivity of CRPC cells to enzalutamide in vitro by suppressing androgen receptor (AR) activities via the non‑canonical Hedgehog/Gli‑2 and p‑STAT3 signaling pathways. PLCε knockdown was shown to increase the sensitivity of CRPC cell xenografts to enzalutamide in vivo. Finally, the combination of PLCε knockdown with GANT61 significantly sensitized CRPC cells to enzalutamide. Collectively, the results of the present study suggest that PLCε is a potential therapeutic target for CRPC.
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