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Investigational drugs for the treatment of cancer cachexia: a focus on phase I and phase II clinical trials.

: Cachexia is frequent in chronic diseases and especially during cancer development. Multiple definitions of cachexia have been proposed; it may be considered a multifactorial complex syndrome that presents with progressive unintentional weight loss and wasting of muscle mass and adipose tissue. : This article covers phase-I and phase-II clinical trials of investigational drugs for cancer cachexia. We performed a search on PubMed with keywords as cancer cachexia, phase-I/phase-II trial, drug, identifying articles relevant to this review. Studies were conducted using compounds, including anabolic agents such as ghrelin analogs, selective androgen receptor modulators, as well as anti-inflammatory drugs such as thalidomide, OHR, anti-interleukin antibody, cannabinoids, and omega-3 supplements. We also describe the mechanisms of action of these molecules and their phase-I and phase-II study design. The major outcomes were appetite stimulation, weight gain, improvement of muscle mass and function, modulation of inflammation, and quality of life. : The molecules discussed act on molecular pathways involved in cancer cachexia; they modulate appetite, anabolic effects, inflammation and direct interaction with muscle. Considering the multifactorial aspects of the cachexia syndrome, the combination of these drugs with metabolic and nutritional interventions may represent the most promising therapeutic approach to cancer cachexia.

2414 related Products with: Investigational drugs for the treatment of cancer cachexia: a focus on phase I and phase II clinical trials.

Soft tissue cancer test t Middle advanced stage sto Colon cancer test tissue Ovarian cancer tissue arr Rectum cancer tissue arra Kidney cancer test tissue Breast cancer test tissue Thymus cancer test tissue Ovary cancer survey tissu Stomach cancer tissue arr Breast cancer tissue arra Cervix cancer test tissue

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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.

1082 related Products with: Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

Breast cancer, carcinoma Late stage breast cancer 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 (IDC) tissu Breast disease spectrum t ER Immunohistochemistry c Breast cancer tissue arra

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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.

1195 related Products with: Phenotypic Profiling of Circulating Tumor Cells in Metastatic Prostate Cancer Patients Using Nanoparticle-Mediated Ranking.

Prostate cancer tissue ar Mid advanced stage kidney Prostate cancer, PIN (pro Prostate cancer, hyperpla Prostate cancer tissue ar Top 4 types of cancer (co Prostate cancer tissue ar Prostate cancer and norma Prostate cancer, hyperpla Prostate cancer tissue ar Prostate cancer test tiss Prostate cancer tissue ar

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Dihydrotestosterone Increases Cytotoxic Activity of Macrophages on Prostate Cancer Cells via TRAIL.

Although androgen deprivation therapy (ADT) and immunotherapy are potential treatment options in men with metastatic prostate cancer (CaP), androgen has conventionally been proposed to be a suppressor of the immune response. However, we herein report that DHT activates macrophages. When the murine macrophage cell line (RAW 264.7), human monocyte cell line (THP-1), and human peripheral blood monocytes were cultured with androgen-resistant CaP cell lines, DHT increased cytotoxicity of macrophages in a concentration-dependent manner. Further studies revealed that DHT induced M1 polarization and increased the expression levels of TNF-related apoptosis-inducing ligand (TRAIL) in macrophages and that this effect was abrogated when TRAIL was neutralized with a blocking antibody or small interfering RNA. Subsequent experiments demonstrated that induction of TRAIL expression was regulated by direct binding of androgen receptor to the TRAIL promoter region. Finally, an in vivo mouse study demonstrated that castration enhanced the growth of an androgen-resistant murine CaP tumor and that this protumorigenic effect of castration was blocked when macrophages were removed with clodronate liposomes. Collectively, these results demonstrate that DHT activates the cytotoxic activity of macrophages and suggest that immunotherapy may not be optimal when combined with ADT in CaP.

2822 related Products with: Dihydrotestosterone Increases Cytotoxic Activity of Macrophages on Prostate Cancer Cells via TRAIL.

Prostate cancer, PIN (pro Prostate cancer tissue ar MarkerGene™ Cellular Se Human Prostate Microvascu anti CD7 All T cells Reco Prostate cancer frozen ti anti Transferrin receptor Top 4 types of cancer (co High density (114 cases 2 Multiple prostate cancer Prostate cancer test tiss MarkerGene™ â Galactos

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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.

2342 related Products with: Preclinical efficacy of hK2 targeted [Lu]hu11B6 for prostate cancer theranostics.

High density prostate can Prostate cancer tissue ar Prostate cancer test tiss Prostate cancer tissue ar Prostate cancer and norma Prostate cancer tissue ar Top 4 types of cancer (co Multiple prostate cancer Prostate cancer test tiss Prostate cancer tissue ar Prostate cancer tissue ar Prostate cancer tissue ar

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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.

1976 related Products with: Human placental androgen receptor variants: Potential regulators of male fetal growth.

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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.

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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.

2553 related Products with: Consideration of breast cancer subtype in targeting the androgen receptor.

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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.

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Goat Anti-Human Androgen Rabbit Anti-Human Toll-Li Androgen Receptor Ab-1 An Androgen Receptor (Phosph Androgen Receptor (Phosph Androgen Receptor Antibod Androgen Receptor (Phosph Androgen Receptor (Ab 650 Androgen Receptor , Mouse Androgen Receptor Antibod Androgen Receptor Rabbit Anti-Human Androge

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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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Multiple organ tumor tiss FDA Standard Frozen Tissu Normal rat multiple organ Multiple organ cancer tis Tissue array of ovarian g Normal rat multiple organ Normal rat multiple organ MyGenie 96 Gradient Therm Recombinant Thermostable Thermostable TDG Kit *DIS Rabbit anti PKC theta (Ab Theophylline CAS Number [

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