scholarly journals N-Myc Promotes Angiogenesis and Therapeutic Resistance of Prostate Cancer by TEM8

2021 ◽  
Author(s):  
MingFeng Li ◽  
LinNa Fang ◽  
LOUIS BOAFO KWANTWI ◽  
GuiFang He ◽  
WenWu Luo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Umbilical Vein ◽  
Underlying Mechanism ◽  
Therapeutic Resistance ◽  
Cancer Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Tubule Formation ◽  
R Language ◽  
Cancer Tissues

Abstract Although patients with early localized prostate cancer can achieve a longer survival, castration-resistant prostate cancer (CRPC) has gradually developed with the use of androgen deprivation therapy (ADT). N-Myc and TEM8 play an important role in the progression of several cancer types. However, the underlying mechanism of how N-Myc and TEM8 promote the progression of prostate cancer remains unclear. In this study, the expression of N-Myc and TEM8 were detected in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues by immunohistochemistry (IHC). To find the mechanism of prostate cancer resistance to treatment, LNCaP cell lines were maintained in RPMI 1640 medium supplemented with 10% Charcoal-stripped fetal Bovine Serum. Subsequently, R language software was used to verify our results. Tubule formation assay of human umbilical vein endothelial cell (HUVEC) was conducted to examine the effect of N-Myc and TEM8 overexpression on angiogenesis of prostate cancer cells.IHC results showed a positive correlation between the expression of N-Myc and TEM8 in prostate cancer tissues. Further analysis showed that N-Myc and TEM8 were associated with clinicopathological features and poor prognosis in prostate cancer patients. We found that the overexpression of N-Myc and TEM8 promotes proliferative ability and angiogenesis. Further, N-Myc and TEM8 overexpression was associated with therapeutic resistance. N-Myc promoted angiogenesis and therapeutic resistance in prostate cancer via TEM8. Hence, targeting N-Myc/TEM8 pathway in prostate cancer would be a novel therapeutic strategy to advance the treatment of prostate cancer patients.

scholarly journals N-Myc promotes angiogenesis and therapeutic resistance of prostate cancer by TEM8

2021 ◽  
Vol 38 (10) ◽  
Author(s):  
Mingfeng Li ◽  
Linna Fang ◽  
Louis Boafo Kwantwi ◽  
Guifang He ◽  
Wenwu Luo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Umbilical Vein ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Therapeutic Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Tubule Formation

AbstractAlthough patients with early localized prostate cancer can survive longer, castration-resistant prostate cancer (CRPC) has gradually emerged with the use of androgen deprivation therapy (ADT). N-Myc and TEM8 play a vital role in the progression of several cancer types. However, the underlying mechanism of how N-Myc and TEM8 promote the progression of prostate cancer remains unclear. In this study, the expression of N-Myc and TEM8 was detected in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues by immunohistochemistry (IHC). LNCaP cell lines were maintained in RPMI 1640 medium supplemented with 10% charcoal-stripped fetal bovine serum. Subsequently, R language software was used to verify our results. Tubule formation assay of human umbilical vein endothelial cell (HUVEC) was conducted to examine the effect of N-Myc and TEM8 overexpression on angiogenesis in prostate cancer cells. IHC results showed a positive correlation between the expression of N-Myc and TEM8 in prostate cancer tissues. Further analysis showed that N-Myc and TEM8 were associated with clinicopathological features and poor prognosis in prostate cancer patients. Moreover, the overexpression of N-Myc and TEM8 promoted proliferation of prostate cancer cells and angiogenesis. Additionally, N-Myc and TEM8 overexpression was associated with therapeutic resistance. We further found that N-Myc promoted angiogenesis and therapeutic resistance in prostate cancer via TEM8. Hence, targeting N-Myc/TEM8 pathway in prostate cancer would be a novel therapeutic strategy to enhance the treatment of prostate cancer patients.

scholarly journals Development of an Androgen Receptor Inhibitor Targeting the N-Terminal Domain of Androgen Receptor for Treatment of Castration Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3488
Author(s):  
Fuqiang Ban ◽  
Eric Leblanc ◽  
Ayse Derya Cavga ◽  
Chia-Chi Flora Huang ◽  
Mark R. Flory ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Splice Variants ◽  
Full Length ◽  
Cancer Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Terminal Domain ◽  
Castration Resistant ◽  
Coregulatory Proteins ◽  
Androgen Binding

Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castration-resistant prostate cancer. Resistance can occur when mutations in the androgen receptor (AR) render anti-androgen drugs ineffective or through the expression of constitutively active splice variants lacking the androgen binding domain entirely (e.g., ARV7). In this study, we are reporting the discovery of a novel AR-NTD covalent inhibitor 1-chloro-3-[(5-([(2S)-3-chloro-2-hydroxypropyl]amino)naphthalen-1-yl)amino]propan-2-ol (VPC-220010) targeting the AR-N-terminal Domain (AR-NTD). VPC-220010 inhibits AR-mediated transcription of full length and truncated variant ARV7, downregulates AR response genes, and selectively reduces the growth of both full-length AR- and truncated AR-dependent prostate cancer cell lines. We show that VPC-220010 disrupts interactions between AR and known coactivators and coregulatory proteins, such as CHD4, FOXA1, ZMIZ1, and several SWI/SNF complex proteins. Taken together, our data suggest that VPC-220010 is a promising small molecule that can be further optimized into effective AR-NTD inhibitor for the treatment of CRPC.

scholarly journals Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divya Bhagirath ◽  
Michael Liston ◽  
Theresa Akoto ◽  
Byron Lui ◽  
Barbara A. Bensing ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Neuroendocrine Differentiation ◽  
Extracellular Vesicle ◽  
Machine Learning Algorithms ◽  
Castration Resistant Prostate Cancer ◽  
Cellular Models ◽  
Non Invasive ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer

AbstractNeuroendocrine prostate cancer (NEPC), a highly aggressive variant of castration-resistant prostate cancer (CRPC), often emerges upon treatment with androgen pathway inhibitors, via neuroendocrine differentiation. Currently, NEPC diagnosis is challenging as available markers are not sufficiently specific. Our objective was to identify novel, extracellular vesicles (EV)-based biomarkers for diagnosing NEPC. Towards this, we performed small RNA next generation sequencing in serum EVs isolated from a cohort of CRPC patients with adenocarcinoma characteristics (CRPC-Adeno) vs CRPC-NE and identified significant dysregulation of 182 known and 4 novel miRNAs. We employed machine learning algorithms to develop an ‘EV-miRNA classifier’ that could robustly stratify ‘CRPC-NE’ from ‘CRPC-Adeno’. Examination of protein repertoire of exosomes from NEPC cellular models by mass spectrometry identified thrombospondin 1 (TSP1) as a specific biomarker. In view of our results, we propose that a miRNA panel and TSP1 can be used as novel, non-invasive tools to identify NEPC and guide treatment decisions. In conclusion, our study identifies for the first time, novel non-invasive exosomal/extracellular vesicle based biomarkers for detecting neuroendocrine differentiation in advanced castration resistant prostate cancer patients with important translational implications in clinical management of these patients that is currently extremely challenging.

Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation

The Prostate ◽  
2015 ◽  
Vol 76 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Sushil K. Badrising ◽  
Vincent van der Noort ◽  
Alfons J.M. van den Eertwegh ◽  
Paul Hamberg ◽  
Inge M. van Oort ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Prognostic Parameters ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Time Relation
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