Vaccination of Advanced Prostate Cancer Patients with PSCA and PSA Peptide-Loaded Dendritic Cells Induces Cellular Immune Responses That Correlate with Superior Overall Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2394-2394
Author(s):  
Anna K. Kaskel ◽  
Robert Zeiser ◽  
Rosa Jochim ◽  
Wolfgang Schultze-Seemann ◽  
Cornelius Waller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Specific Antigen ◽  
Hepatitis B Vaccination ◽  
Complete Disappearance ◽  
Psa Kinetics ◽  
Duration Of Response ◽  
Prostate Cancers

Abstract Prostate stem cell antigen (PSCA) and prostate-specific antigen (PSA) are overexpressed in most prostate cancers. PSCA- and PSA-derived, HLA-A2 binding peptides are specific targets for T cell responses in vitro. A phase I/II trial was performed to demonstrate feasibility, safety, and induction of antigen-specific immunity by vaccination with dendritic cells (DC) presenting PSCA and PSA peptides in patients with hormone- and chemotherapy-refractory prostate cancer. Patients received four vaccinations with median of 2.7x10e7 peptide-loaded mature DC s.c. in biweekly intervals. Twelve patients completed vaccination without relevant toxicities. Six patients had stable disease (SD) after four vaccinations. One patient had a complete disappearance of lymphadenopathy by ultrasound despite rising PSA. Regarding PSA kinetics, in one patient, the log PSA slope became negative after treatment, and three patients had significant decreases in the log PSA slopes. However, duration of response was short, with a median time to progression of 65 days (12–223). Four patients with SD and one progressor developed a positive DTH after the 4th vaccination. With a median survival of all patients of 13.4 months, DTH-positivity was associated with significantly superior survival (22 vs. 8 months, p=0.003). HLA tetramer analysis detected high frequencies of peptide-specific T cells after two vaccinations in one patient who was also the sole responder to concomitant hepatitis B vaccination as an indicator of immune competence and survived 27 months after start of vaccination. Taken together, vaccination with PSA/PSCA peptide-loaded, autologous DCs may induce cellular responses primarily in immunocompetent patients which were associated with superior outcome. The retardation of PSA kinetics upon vaccination suggest a causal influence of the treatment on the natural course of the disease. Testing of DC-based vaccination is warranted for patients at earlier stages of prostate cancer.

Correlation Between Testosterone and PSA Kinetics in Metastatic Prostate Cancer Patients Treated With Diverse Chemical Castrations

2014 ◽  
Vol 9 (5) ◽  
pp. 430-434 ◽  
Author(s):  
Leonardo O. Reis ◽  
Fernandes Denardi ◽  
Eliney F. Faria ◽  
Elcio Dias Silva
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Linear Correlation ◽  
Specific Antigen ◽  
Rank Correlation ◽  
Total Testosterone ◽  
Psa Kinetics ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Group 2

To assess total testosterone and prostatic-specific antigen (PSA) kinetics among diverse chemical castrations, advanced-stage prostate cancer patients were randomized into three groups of 20: Group 1, Leuprolide 3.75 mg; Group 2, Leuprolide 7.5 mg; and Group 3, Goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients’ levels of serum total testosterone and PSA were evaluated at two time periods: before the treatment and 3 months after the treatment. Spearman’s rank correlation coefficient was utilized to verify the hypothesis of linear correlation between total testosterone and PSA levels. At the beginning the patients’ age, stage, grade, PSA, and total testosterone were similar within the three groups, with median age 72, 70, and 70 years in Groups 1, 2, and 3, respectively. Three months after the treatment, patients who received Leuprolide 7.5 mg presented significantly lower median total testosterone levels compared with Goserelin 3.6 mg and Leuprolide 3.75 mg (9.5 ng/dL vs. 20.0 ng/dL vs. 30.0 ng/dL, respectively; p = .0072), while those who received Goserelin 3.6 mg presented significantly lower PSA levels compared with Leuprolide 7.5 mg and Leuprolide 3.75 mg (0.67 vs. 1.86 vs. 2.57, respectively; p = .0067). There was no linear correlation between total testosterone and PSA levels. Overall, regarding castration levels of total testosterone, 28.77% of patients did not obtain levels ≤50 ng/dL and 47.80% did not obtain levels ≤20 ng/dL. There was no correlation between total testosterone and PSA kinetics and no equivalence among different pharmacological castrations.

In vitro propagated dendritic cells from prostate cancer patients as a component of prostate cancer immunotherapy

The Prostate ◽  
1995 ◽  
Vol 27 (2) ◽  
pp. 63-69 ◽  
Author(s):  
Benjamin Tjoa ◽  
Sheila Erickson ◽  
Robert Barren ◽  
Haakon Ragde ◽  
Gerald Kenny ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dendritic Cells ◽  
Cancer Immunotherapy ◽  
Cancer Patients

scholarly journals Clinical diagnosis of prostate cancer using digital rectal examination and prostate-specific antigen tests: a systematic review and meta-analysis of sensitivity and specificity

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Nelson C. Okpua ◽  
Simon I. Okekpa ◽  
Stanley Njaka ◽  
Augusta N. Emeh
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Sensitivity And Specificity ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Antigen Test ◽  
Rectal Examination ◽  
Prostate Specific Antigen Test ◽  
Prostate Cancers ◽  
Antigen Tests

Abstract Background Being diagnosed with cancer, irrespective of type initiates a serious psychological concern. The increasing rate of detection of indolent prostate cancers is a source of worry to public health. Digital rectal examination and prostate-specific antigen tests are the commonly used prostate cancer screening tests. Understanding the diagnostic accuracies of these tests may provide clearer pictures of their characteristics and values in prostate cancer diagnosis. This review compared the sensitivities and specificities of digital rectal examination and prostate-specific antigen test in detection of clinically important prostate cancers using studies from wider population. Main body We conducted literature search in PubMed, Medline, Science Direct, Wiley Online, CINAHL, Scopus, AJOL and Google Scholar, using key words and Boolean operators. Studies comparing the sensitivity and specificity of digital rectal examination and prostate-specific antigen tests in men 40 years and above, using biopsy as reference standard were retrieved. Data were extracted and analysed using Review manager (RevMan 5.3) statistical software. The overall quality of the studies was good, and heterogeneity was observed across the studies. The result comparatively shows that prostate-specific antigen test has higher sensitivity (P < 0.00001, RR 0.74, CI 0.67–0.83) and specificity (P < 0.00001, RR 1.81, CI 1.54–2.12) in the detection of prostate cancers than digital rectal examination. Conclusion Prostate-specific antigen test has higher sensitivity and specificity in detecting prostate cancers from men of multiple ethnic origins. However, combination of prostate-specific antigen test and standardized digital rectal examination procedure, along with patients history, may improve the accuracy and minimize over-diagnoses of indolent prostate cancers.

scholarly journals Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients

2005 ◽  
Vol 93 (7) ◽  
pp. 749-756 ◽  
Author(s):  
L J Mu ◽  
J A Kyte ◽  
G Kvalheim ◽  
S Aamdal ◽  
S Dueland ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dendritic Cells ◽  
Cancer Patients

scholarly journals Recruitment of β-Catenin by Wild-Type or Mutant Androgen Receptors Correlates with Ligand-Stimulated Growth of Prostate Cancer Cells

2004 ◽  
Vol 18 (10) ◽  
pp. 2388-2401 ◽  
Author(s):  
David Masiello ◽  
Shao-Yong Chen ◽  
Youyuan Xu ◽  
Manon C. Verhoeven ◽  
Eunis Choi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Nuclear Receptor ◽  
Specific Antigen ◽  
Prostate Cancer Cells ◽  
Prostate Cell ◽  
Nuclear Receptor Corepressor ◽  
Prostate Cancers

Abstract Prostate cancers respond to treatments that suppress androgen receptor (AR) function, with bicalutamide, flutamide, and cyproterone acetate (CPA) being AR antagonists in clinical use. As CPA has substantial agonist activity, it was examined to identify AR coactivator/corepressor interactions that may mediate androgen-stimulated prostate cancer growth. The CPA-liganded AR was coactivated by steroid receptor coactivator-1 (SRC-1) but did not mediate N-C terminal interactions or recruit β-catenin, indicating a nonagonist conformation. Nonetheless, CPA did not enhance AR interaction with nuclear receptor corepressor, whereas the AR antagonist RU486 (mifepristone) strongly stimulated AR-nuclear receptor corepressor binding. The role of coactivators was further assessed with a T877A AR mutation, found in LNCaP prostate cancer cells, which converts hydroxyflutamide (HF, the active flutamide metabolite) into an agonist that stimulates LNCaP cell growth. The HF and CPA-liganded T877A ARs were coactivated by SRC-1, but only the HF-liganded T877A AR was coactivated by β-catenin. L-39, a novel AR antagonist that transcriptionally activates the T877A AR, but still inhibits LNCaP growth, similarly mediated recruitment of SRC-1 and not β-catenin. In contrast, β-catenin coactivated a bicalutamide-responsive mutant AR (W741C) isolated from a bicalutamide-stimulated LNCaP subline, further implicating β-catenin recruitment in AR-stimulated growth. Androgen-stimulated prostate-specific antigen gene expression in LNCaP cells could be modulated by β-catenin, and endogenous c-myc expression was repressed by dihydrotestosterone, but not CPA. These results indicate that interactions between AR and β-catenin contribute to prostate cell growth in vivo, although specific growth promoting genes positively regulated by AR recruitment of β-catenin remain to be identified.

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