A new Prostate Cancer Surrogate Marker-Vimentin3?

Prostate cancer is one of the leading causes of death in men all over the world. Treatment options such as androgen ablation therapy and cytotoxic agents have many undesirable side effects, narrow therapeutic windows, or other limitations. In this research, we have explored the effects of paeonol on prostate cancer and its mechanism of action. Our results have shown that paeonol reduced the viability of prostate cancer cells in a dose-dependent manner. The wound-healing assay, a surrogate marker of tumor metastasis, showed that the relative wound width of 10 µM group was less than that of 50 µM paeonol-treated cells. Besides, the results of the transwell assay also showed that the number of migrated cells was significantly lower after treatment with 50 µM paeonol compared to the 10 µM group. The Western blot results showed that paeonol treatment induced a decrease in the mesenchymal markers (vimentin and N-cadherin), while the epithelial marker (E-cadherin) increased in a dose-dependent manner suggesting that paeonol effectively inhibits the epithelial-mesenchymal transformation in PC3 cells. Furthermore, the expression of STAT3 and p-STAT3 was also decreased after paeonol treatment, which indicated that the STAT3 signaling pathway was inhibited by paeonol. To conclude, the results summarized in this paper suggest that paeonol could be a potential candidate in the treatment of prostate cancer.

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Early alkaline phosphatase dynamics as biomarker of survival in metastatic castration-resistant prostate cancer patients treated with radium-223

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05283-6 ◽

2021 ◽

Author(s):

Maarten J. van der Doelen ◽

Agnes Stockhaus ◽

Yuanjun Ma ◽

Niven Mehra ◽

Jeffrey Yachnin ◽

...

Keyword(s):

Prostate Cancer ◽

Alkaline Phosphatase ◽

Confidence Interval ◽

Surrogate Marker ◽

Response Monitoring ◽

Castration Resistant Prostate Cancer ◽

Related Event ◽

Castration Resistant ◽

Radium 223 ◽

Skeletal Related Event

Abstract Purpose Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS). Methods This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate. Results A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5–15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73–3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients. Conclusion Early treatment–induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.

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Morphometric sum optical density as a surrogate marker for ploidy status in prostate cancer: an analysis in 180 biopsies using logistic regression and binary recursive partitioning

Virchows Archiv ◽

10.1007/s00428-006-0237-y ◽

2006 ◽

Vol 449 (3) ◽

pp. 302-307 ◽

Cited By ~ 6

Author(s):

Girish Venkataraman ◽

Vijayalakshmi Ananthanarayanan ◽

Gladell P. Paner ◽

Rui He ◽

Saeedeh Masoom ◽

...

Keyword(s):

Prostate Cancer ◽

Logistic Regression ◽

Optical Density ◽

Recursive Partitioning ◽

Surrogate Marker ◽

Ploidy Status

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Diverse Effects of Methylseleninic Acid on the Transcriptional Program of Human Prostate Cancer Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e03-07-0501 ◽

2004 ◽

Vol 15 (2) ◽

pp. 506-519 ◽

Cited By ~ 73

Author(s):

Hongjuan Zhao ◽

Michael L. Whitfield ◽

Tong Xu ◽

David Botstein ◽

James D. Brooks

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Specific Antigen ◽

Surrogate Marker ◽

Detoxification Enzymes ◽

Human Prostate ◽

Human Prostate Cancer ◽

Phase 2 ◽

Transcript Levels ◽

Methylseleninic Acid

Methylseleninic acid (MSA) has been shown to have potent anticancer activity and is an excellent compound for studying the anticancer effects of selenium in vitro. To gain insights into the effects of MSA in prostate cancer, we characterized the global transcriptional response of LNCaP, an androgen-sensitive human prostate cancer cell line, to MSA by using high-density cDNA microarrays. We identified 951 genes whose expression shows striking dose- and time-dependent changes in response to 3-30 μM MSA over the time course of 48 h. Transcript levels of many cell cycle-regulated genes change in response to MSA, suggesting that MSA inhibits proliferation. Consistent with these gene expression changes, cell proliferation, monitored by carboxyfluoroscein succinimidyl ester staining, was decreased after MSA treatment, and an accumulation of cells at G0/G1 phase was detected by flow cytometry. Surprisingly, MSA also modulated expression of many androgen-regulated genes, suppressed androgen receptor (AR) expression at both mRNA and protein level, and decreased levels of prostate specific antigen secreted into the medium. Low concentrations of MSA also induced significant increases in transcript levels of phase 2 detoxification enzymes and induced NADPH dehydrogenase, quinone 1 enzymatic activity, a surrogate marker of global phase 2 enzyme activity. Our results suggest that MSA may protect against prostate cancer by inhibiting cell proliferation, by modulating the expression of AR and AR-regulated genes and by inducing carcinogen defenses.

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Prostate-specific antigen (PSA) alone is not an appropriate surrogate marker of long-term therapeutic benefit in prostate cancer trials

European Journal of Cancer ◽

10.1016/j.ejca.2006.02.011 ◽

2006 ◽

Vol 42 (10) ◽

pp. 1344-1350 ◽

Cited By ~ 56

Author(s):

Laurence Collette ◽

Tomasz Burzykowski ◽

Fritz H. Schröder

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Surrogate Marker ◽

Therapeutic Benefit ◽

Cancer Trials

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Circulating tumor cells in prostate cancer: A potential surrogate marker of survival

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2011.05.004 ◽

2012 ◽

Vol 81 (3) ◽

pp. 241-256 ◽

Cited By ~ 46

Author(s):

Jérôme Doyen ◽

Catherine Alix-Panabières ◽

Paul Hofman ◽

Scott K. Parks ◽

Emmanuel Chamorey ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Surrogate Marker

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Correlation of circulating tumor cells (CTCs) and clinical biomarker endpoints in metastatic prostate cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15124 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15124-e15124

Author(s):

Robert J. Amato ◽

Vladislava O. Melnikova ◽

Yujian Zhang ◽

Wen Liu ◽

Yuan Wang ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Gleason Score ◽

Clinical Characteristics ◽

Metastatic Prostate Cancer ◽

Patient Survival ◽

Surrogate Marker ◽

Androgen Depletion

e15124 Background: Circulating tumor cells (CTCs) are found in human blood when cancers undergo metastatic dissemination, and CTCs have been reported as a surrogate marker for tumor response and linked to shorter survival in metastatic prostate cancer patients. This study assessed the use of CTCs as a continuous factor for clinical monitoring of prostate cancers patient in real time and evaluated the association between baseline CTC number, various clinical characteristics, and survival. Methods: CTCs were enumerated using the CellSearch FDA cleared CTC kit in 206 patients with metastatic prostate cancer. Variables including metastatic site, PSA, Gleason score, level of testosterone and androgen treatment were tested for association with CTC number. The probability of patient survival over time was estimated by the Kaplan-Meier method. Results: Baseline CTC numbers were strongly associated with survival (p<0.0001), with overall survival being significantly poorer in patients with ≥5 CTCs. Significantly higher CTC numbers were observed in patients with bone metastasis (mean=41.1 CTCs) compared to those with lymph node metastasis (mean=2.5 CTC, p=0.026). Analysis of the association between CTC counts and PSA level revealed a weak positive correlation between CTC number and PSA (Correlation coefficient r=0.269, Significance level p<0.001). CTC number further correlated with the Gleason score (p=0.009) and lower testosterone levels (p<0.0001). Patients with no androgen depletion had significantly lower numbers of CTCs (median=3.94) compared to those with androgen depletion (median=406, p<0.001). Conclusions: Baseline CTCs are predictive of patient survival and are significantly correlated with clinical characteristics in prostate cancer patients.Our study confirms previous findings that support the use of CTC levels as a prognostic biomarker for prostate cancer patients.

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