scholarly journals Comparative proteome analysis identified CD44 as a possible serum marker for docetaxel resistance in castration‐resistant prostate cancer

2021 ◽  
Author(s):  
Dávid Keresztes ◽  
Anita Csizmarik ◽  
Nikolett Nagy ◽  
Orsolya Módos ◽  
Tamás Fazekas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proteome Analysis ◽  
Serum Marker ◽  
Castration Resistant Prostate Cancer ◽  
Docetaxel Resistance ◽  
Castration Resistant

EGFR mediates docetaxel resistance in human castration-resistant prostate cancer through the Akt-dependent expression of ABCB1 (MDR1)

2014 ◽  
Vol 89 (4) ◽  
pp. 591-605 ◽  
Author(s):  
Tzyh-Chyuan Hour ◽  
Shiu-Dong Chung ◽  
Wang-Yi Kang ◽  
Ying-Chu Lin ◽  
Shu-Ju Chuang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Docetaxel Resistance ◽  
Castration Resistant

Evaluation of Docetaxel-Sensitive and Docetaxel-Resistant Proteomes in PC-3 Cells

2015 ◽  
Vol 95 (1) ◽  
pp. 114-119 ◽  
Author(s):  
Shulu Zu ◽  
Weiming Ma ◽  
Pan Xiao ◽  
Yazhou Cui ◽  
Tianjia Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Polyacrylamide Gel Electrophoresis ◽  
Acquired Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Ionization Time ◽  
Flight Mass Spectrometry ◽  
Docetaxel Resistance ◽  
Castration Resistant ◽  
Glucose Regulated Protein

Objectives: Docetaxel was the first drug with proven survival benefit in men with castration-resistant prostate cancer. Acquired resistance to docetaxel precedes fatality in castration-resistant prostate cancer. The aims of this study were to evaluate docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells, and to investigate the molecular mechanism of docetaxel-resistant PC-3 cells. Methods: Docetaxel-resistant PC-3 cells were developed by docetaxel dose escalation. The global profiling of the protein expression was investigated in docetaxel-sensitive and docetaxel-resistant proteomes in PC-3 cells using 2-dimensional polyacrylamide gel electrophoresis/matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: Forty-nine differential proteins were found in docetaxel-resistant PC-3 cells in comparison with docetaxel-sensitive PC-3 cells. Expression in 29 proteins was upregulated, whereas expression in 20 proteins was downregulated. ATP synthase and galectin-1 were involved in the formation of tumor vessels; calreticulin, cathepsin D, and cofilin were involved in tumor metastasis, and GRP78 (78-kDa glucose-regulated protein) and microtubule-associated protein-6 were involved in drug resistance of tumor. Conclusion: It is suggested that a proteomic expression difference exists between docetaxel-sensitive and docetaxel-resistant PC-3 cells, which would be helpful for further understanding the molecular mechanisms of docetaxel resistance in PC-3 cells.

scholarly journals Identification of Docetaxel Resistance Genes in Castration-Resistant Prostate Cancer

2011 ◽  
Vol 11 (2) ◽  
pp. 329-339 ◽  
Author(s):  
Mercedes Marín-Aguilera ◽  
Jordi Codony-Servat ◽  
Susana G. Kalko ◽  
Pedro L. Fernández ◽  
Raquel Bermudo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Resistance Genes ◽  
Castration Resistant Prostate Cancer ◽  
Docetaxel Resistance ◽  
Castration Resistant

Novel biomarker of specific castration-resistant prostate cancer (CRPC) by exploring the proteome analysis.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 247-247 ◽  
Author(s):  
Hiroji Uemura ◽  
Noriaki Arakawa ◽  
Yusuke Itoh ◽  
Takashi Kawahara ◽  
Yasuhide Miyoshi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Proteome Analysis ◽  
Human Prostate ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Prostate Hyperplasia ◽  
Castration Resistant ◽  
Significant Difference ◽  
Prostate Cancers

247 Background: It is well known that prostate specific antigen (PSA) level has no reliable correlation with pathological malignancy of prostate cancer and is not a predictor for the development of castration resistant prostate cancer (CRPC). The aim of this study is to explore novel biomarkers to predict the development of CRPC by using proteomics from secreted proteins from human prostate cancer cells. Methods: The proteins secreted from 6 prostate cancers in culture medium were analyzed and compared with 8 other cancer cells including renal and urothelial cancers using LTQ Orbitrap mass spectrometer. With the focus on high tissue specificity, the candidate biomarker proteins were then identified through analysis of gene expressions in proteins common to human prostate cancers by real time qPCR. Next, a system to measure the identified mouse monoclonal antibodies against the focused proteins was established. Finally, serum levels of these proteins from 33 patients with benign prostate hyperplasia (BPH), 31 with untreated prostate cancer (PCa) and 35 with CRPC, were measured. Results: The proteome analysis identified 12 candidates of secreted cell membrane proteins as new biomarkers. The proteome analysis indicated that not only matured GDF15, but pro-peptide as well as fragments (GDDP) are released from prostate cancer cells. Patients’ serum was analyzed for matured and pro-peptide GDF15 using ELISA and immunoprecipitation-MRM mass spectrometry. The results showed that the serum level of GDDP-1, one of the processing forms of GDDP, was significantly higher in CRPC than those in BPH and untreated PCa (P < 0.01). ROC analysis also showed that the AUC of GDDP-1(0.86) was higher than that of matured GDF15 (0.76). When the cutoff value of GDDP-1 was set at 4.0 ng/mL, there was a significant difference of overall survival (OS) in CRPC patients between those with more than 4.0 ng/mL compared to less than 4.0 ng/mL of GDDP-1, whereas there was no significant difference of OS measurable by PSA in CRPC patients. These data suggest that GDDP-1 may be a novel biomarker for CRPC. Conclusions: GDDP-1 shows potential as a novel biomarker for CRPC.

Nuclear factor-kappa B and interleukin-6 related docetaxel resistance in castration-resistant prostate cancer

The Prostate ◽  
2012 ◽  
Vol 73 (5) ◽  
pp. 512-521 ◽  
Author(s):  
Jordi Codony-Servat ◽  
Mercedes Marín-Aguilera ◽  
Laura Visa ◽  
Xabier García-Albéniz ◽  
Estela Pineda ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Interleukin 6 ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Castration Resistant Prostate Cancer ◽  
Nuclear Factor Kappa ◽  
Docetaxel Resistance ◽  
Castration Resistant

TMPRSS2-ERG in Blood and Docetaxel Resistance in Metastatic Castration-resistant Prostate Cancer

2016 ◽  
Vol 70 (5) ◽  
pp. 709-713 ◽  
Author(s):  
Òscar Reig ◽  
Mercedes Marín-Aguilera ◽  
Gemma Carrera ◽  
Natalia Jiménez ◽  
Laia Paré ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Docetaxel Resistance ◽  
Castration Resistant

Corrigendum re: “TMPRSS2-ERG in Blood and Docetaxel Resistance in Metastatic Castration-resistant Prostate Cancer” [Eur Urol 2016;70:709–13]

2017 ◽  
Vol 72 (2) ◽  
pp. e49
Author(s):  
Òscar Reig ◽  
Mercedes Marín-Aguilera ◽  
Gemma Carrera ◽  
Natalia Jiménez ◽  
Laia Paré ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Docetaxel Resistance ◽  
Castration Resistant

scholarly journals Identification of Key Genes and Molecular Mechanisms Associated With Docetaxel Resistance in Castration Resistant Prostate Cancer Based on Bioinformatics Analysis

2020 ◽  
Author(s):  
Yu Liu ◽  
Changpeng Hu ◽  
Qian Zhang ◽  
Wuyi Liu ◽  
Guobing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Castration Resistant Prostate Cancer ◽  
Mesenchymal Transition ◽  
Docetaxel Resistance ◽  
Castration Resistant ◽  
E2f Transcription Factor ◽  
Key Genes

Abstract BackgroundCastration resistant prostate cancer (CRPC) is one of the most common solid tumor with high mortality and limited therapeutic options, and docetaxel is the first-line chemotherapy for patients. However, the long-term use of docetaxel has limited its clinical applications. The aim of this study was to identify docetaxel-resistant key genes and molecular mechanisms. ResultsTUBB4A (Class IVa beta-tubulin), SRPX (Sushi repeat containing protein, X chromosome) and CSRP2 (Cysteine and glycine rich protein 2) were finally identified as the key genes tightly related to docetaxel resistance. TUBB4A and CSRP2 may participate in docetaxel resistance by E2F transcription factor and MYC proto-Oncogene in the process of cell cycle, and SRPX may participate in docetaxel resistance by epithelial–mesenchymal transition (EMT) and P53 pathway. ConclusionTUBB4A, SRPX and CSRP2 may be the key genes associated with docetaxel resistance, which could be prognostic biomarkers for docetaxel resistance in CRPC.

scholarly journals Successful Targeting of the Warburg Effect in Prostate Cancer by Glucose-Conjugated 1,4-Naphthoquinones

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1690 ◽  
Author(s):  
Sergey A. Dyshlovoy ◽  
Dmitry N. Pelageev ◽  
Jessica Hauschild ◽  
Ksenia L. Borisova ◽  
Moritz Kaune ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Warburg Effect ◽  
Proteome Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Current Standard ◽  
Normal Tissues ◽  
Castration Resistant ◽  
Glucose Conjugation ◽  
The Warburg Effect

Treatment of castration-resistant prostate cancer (CRPC) remains challenging due to the development of drug resistance. The Warburg effect describes the ability of cancer cells to consume larger amounts of glucose compared to normal tissues. We identified derivatives of natural 1,4-naphthoquinones to be active in CRPC and further synthetically modified them via glucose conjugation to increase selectivity by Warburg effect targeting. Mechanisms of action were examined by quantitative proteomics followed by bioinformatical analysis and target validation. Four synthesized molecules revealed the highest selectivity towards human CRPC cells, which correlated with higher GLUT-1 activity and expression. The compounds were able to induce pro-apoptotic signs and to inhibit the pro-survival processes and mechanisms of drug resistance (i.e., AR-signaling and autophagy). Proteome analysis suggested a disruption of the mitochondria/oxidative phosphorylation, which was validated by further functional analysis: thus, mitochondria depolarization, elevated levels of cytotoxic ROS, an increase of Bax/Bcl-2 ratio as well as release of mitochondrial AIF and cytochrome C to cytoplasm were observed. In conclusion, glucose-conjugated 1,4-naphthoquinones show potent activity and selectivity in human CRPC exerted via mitochondrial targeting. The compounds can overcome drug resistance against current standard therapies and suppress pro-survival mechanisms. This unique combination of properties makes them new promising candidates for the treatment of CRPC.

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