Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PC). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP). Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and <2 years follow-up. TCLo was the number of locations with positive cores at diagnosis (DBx) and CBx. TCLo density was TCLo / prostate volume (PV). CP was progression to any active treatment while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical pathology. Independent predictors of time to CP or GP were estimated with Cox regression. Kaplan-Meier analysis compared progression-free survival curves between TCLo density groups. Test characteristics of TCLo were explored with receiver operating characteristic (ROC) curves. Results: We included 181 patients who had CBx between 2012-2015, and met inclusion criteria. The mean age of patients was 62.58 years (SD=7.13) and median follow-up was 60.9 months (IQR=23.4). A high TCLo density score (>0.05) was independently associated with time to CP (HR 4.70, 95% CI: 2.62-8.42, p<0.001), and GP (HR 3.85, 95% CI: 1.91-7.73, p<0.001). ROC curves showed TCLo density has greater area under the curve than number of positive cores at CBx in predicting progression. Conclusion: TCLo density is able to stratify patients on AS for risk of CP and GP. With further validation, it could be added to the decision-making algorithm in AS for low-risk localized PC.

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A Phase I Feasibility Study of an Intraprostatic Prostate-Specific Antigen–Based Vaccine in Patients with Prostate Cancer with Local Failure After Radiation Therapy or Clinical Progression on Androgen-Deprivation Therapy in the Absence of Local Definitive Therapy

Clinical Genitourinary Cancer ◽

10.3816/cgc.2006.n.024 ◽

2006 ◽

Vol 5 (1) ◽

pp. 89-92 ◽

Cited By ~ 4

Author(s):

Jean-Baptiste Lattouf ◽

Philip M. Arlen ◽

Peter A. Pinto ◽

James L. Gulley

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Phase I ◽

Prostate Specific Antigen ◽

Androgen Deprivation Therapy ◽

Feasibility Study ◽

Specific Antigen ◽

Local Failure ◽

Clinical Progression ◽

Definitive Therapy

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Validation of the decipher genomic classifier (GC) in SAKK 09/10: A phase III randomized trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy (RP).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5010 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5010-5010

Author(s):

Alan Dal Pra ◽

Pirus Ghadjar ◽

Stefanie Hayoz ◽

Daniel Eidelberg Spratt ◽

Vinnie YT Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Controlled Trial ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Risk Groups ◽

Phase Iii ◽

Clinical Progression ◽

Clinical Value ◽

Prognostic Utility ◽

The Impact

5010 Background: GC has been shown to independently prognosticate outcomes in prostate cancer. Herein, we validate the GC in a European randomized phase III trial of dose escalated SRT after RP. Methods: SAKK 09/10 (NCT01272050) randomized 350 patients with biochemical recurrence after RP to 64Gy vs 70Gy. No patients received androgen deprivation therapy (ADT) or pelvic nodal radiotherapy. A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. RP samples were centrally reviewed for the highest-grade tumor and those passing quality control (QC) were run on a clinical-grade whole-transcriptome assay to obtain the GC score (0 to 1; < 0.45, 0.45-0.6, > 0.6 for low-, intermediate-, and high, respectively). The primary aim of this study was to validate the GC for the prediction of freedom from biochemical progression (FFBP) using Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, PSA at randomization, and randomization arm. The secondary aims were to evaluate the association of GC with clinical progression-free survival (CPFS) and use of salvage ADT. Results: Of 233 patients with tissue available, 226 passed QC and were included for analysis. The final GC cohort was a representative sample of the overall cohort, with a median follow-up of 6.3 years (IQR 6.0-7.2). GC score (continuous per 0.1 unit, score 0-1) was independently associated with FFBP (HR 1.14 [95% CI 1.03-1.25], p = 0.009). Higher GC scores were independently associated with CPFS, use of salvage ADT, and rapid biochemical failure ( < 18 months after SRT). High- vs. low/intermediate-GC showed a HR of 2.22 ([95% CI 1.37-3.58], p = 0.001) for FFBP, 2.29 ([95% CI 1.32-3.98], p = 0.003) for CPFS, and 2.99 ([95% CI 1.50-5.95], p = 0.002) for use of salvage ADT. Patients with high-GC had 5-year FFBP of 45% [95% CI 32-59] vs 71% [95% CI 64-78] in low-intermediate GC. Similar estimates for GC risk groups were observed in the 64Gy vs 70Gy in GC high (5-year FFBP of 51% [95% CI 32-70] vs 39% [95% CI 20-59]) and in low-intermediate GC (75% [95% CI 65-84] vs 69% [95% CI 59-78]). Conclusions: This study represents the first contemporary randomized controlled trial in patients with recurrent prostate cancer treated with early SRT without ADT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and radiotherapy dose, patients with a high-GC were more than twice as likely than a lower GC score to experience biochemical and clinical progression and receive salvage ADT. This data confirms the clinical value of Decipher GC for tailoring treatment in the postoperative salvage setting.

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Induction of cell death in prostate cancer cells by escopoletin, a promising treatment strategy

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i3.23095 ◽

2015 ◽

Vol 10 (3) ◽

pp. 500 ◽

Cited By ~ 1

Author(s):

Da Chen ◽

Xiao-Yi Zhang ◽

Fa-Zhu Zheng ◽

Hai-Tao Wang ◽

Jian-Liang Cai ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Death ◽

Antioxidant Activities ◽

Apoptotic Cell ◽

Annexin V ◽

Cycle Arrest ◽

Anti Cancer ◽

Enhanced Expression ◽

Promising Treatment ◽

Du145 Cells

<p>Escopoletin, a phenolic compound belonging to anthocyanin family shows promising antioxidant activities. In the present study, anti-cancer effects of escopoletin treatment in DU145 cells were investigated. The sulphorhodamine-B staining and annexin V and propidium iodide were respectively used for the analysis of cell viability and death. The results revealed a significantly higher cytotoxicity by escopoletin that caused cell death in DU145 cells. Escopoletin treatment in DU145 cells markedly inhibited cell growth through non-apoptotic cell death and induced significant reactive oxygen species (ROS) production. It also induced G1 cell cycle arrest and cyclin D1 accumulation through the enhanced expression of p21. However, the effect of escopoletin on DU145 cells was reversed by pretreatment with glutathione antioxidant. This suggests that escopoletin induced generation of ROS is responsible for the increased cytotoxicity in DU145 cells. Thus, escopoletin exhibits potential therapeutic efficacy for the treatment of prostate cancer.</p><p> </p>

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Characterization of the oncogenic function of centromere protein F in hepatocellular carcinoma

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2013.06.021 ◽

2013 ◽

Vol 436 (4) ◽

pp. 711-718 ◽

Cited By ~ 28

Author(s):

Yongdong Dai ◽

Lulu Liu ◽

Tingting Zeng ◽

Ying-Hui Zhu ◽

Jiangchao Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Centromere Protein ◽

Protein F ◽

Oncogenic Function

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Phase II Randomized Study of Vaccine Treatment of Advanced Prostate Cancer (E7897): A Trial of the Eastern Cooperative Oncology Group

Journal of Clinical Oncology ◽

10.1200/jco.2004.08.083 ◽

2004 ◽

Vol 22 (11) ◽

pp. 2122-2132 ◽

Cited By ~ 167

Author(s):

Howard L. Kaufman ◽

Wei Wang ◽

Judith Manola ◽

Robert S. DiPaola ◽

Yoo-Joung Ko ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trial ◽

T Cell ◽

Phase Ii ◽

Eastern Cooperative Oncology Group ◽

T Cell Responses ◽

Oncology Group ◽

Clinical Progression ◽

Cell Responses ◽

Antibody Titers

Purpose A phase II clinical trial was conducted to evaluate the feasibility and tolerability of a prime/boost vaccine strategy using vaccinia virus and fowlpox virus expressing human prostate-specific antigen (PSA) in patients with biochemical progression after local therapy for prostate cancer. The induction of PSA-specific immunity was also evaluated. Patients and Methods A randomized clinical trial was conducted by the Eastern Cooperative Oncology group and 64 eligible patients were randomly assigned to receive four vaccinations with fowlpox-PSA (rF-PSA), three rF-PSA vaccines followed by one vaccinia-PSA (rV-PSA) vaccine, or one rV-PSA vaccine followed by three rF-PSA vaccines. The major end point was PSA response at 6 months, and immune monitoring included measurements of anti-PSA and anti-vaccinia antibody titers and PSA-specific T-cell responses. Results The prime/boost schedule was well tolerated with few adverse events. Of the eligible patients, 45.3% of men remained free of PSA progression at 19.1 months and 78.1% demonstrated clinical progression-free survival. There was a trend favoring the treatment group that received a priming dose of rV-PSA. Although no significant increases in anti-PSA antibody titers were detected, 46% of patients demonstrated an increase in PSA-reactive T-cells. Conclusion Therapy with poxviruses expressing PSA and delivered in a prime/boost regimen was feasible and associated with minimal toxicity in the cooperative group setting. A significant proportion of men remained free of PSA and clinical progression after 19 months follow-up, and nearly half demonstrated an increase in PSA-specific T-cell responses. Phase III studies are needed to define the role of vaccination in men with prostate cancer or those who are at risk for the disease.

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