The Potential Role for Immunotherapy in Biochemically Recurrent Prostate Cancer.
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ABSTRACT:
SUBMITTER: Bilusic M
PROVIDER: S-EPMC8177734 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prostate cancer (PCa) is the second most common solid tumor type in men with high mortality rates. This study specifically aimed at identification of molecular biomarkers of PCa showing clinically aggressive course of the disease. Transcriptome analysis of PCa cases with biochemical progression (BCR) and No-BCR cases was performed with human gene expression microarrays. Expression levels of the selected genes were validated by real-time PCR in two independent cohorts of PCa cases (N = 55 and N = 53) and non-cancerous control tissues (NPT; N = 12). Comparison of gene expression profile of BCR and No-BCR cases revealed significant changes in expression levels of 455 genes, and the vast majority of the genes were down-regulated in the recurrent PCa. Quantitative evaluation of gene expression levels identified down-regulation of MT1E and GPR52 expression and up-regulation of EZH2 as the specific biomarkers of PCa progression, but only MT1E expression retained the independent prognostic value in a multivariate model. Aberrant methylation of the two fragments of MT1E promoter was frequent (71% and 60%) in PCa tissues as compared to NPT (p < 0.001) and was significantly associated with decreased expression in one of the PCa cohorts (p < 0.050). In conclusion, the data of our study suggest epigenetic inactivation of MT1E expression as the specific feature of PCa showing the tendency to progress.
2017-05-01 | GSE89317 | GEO
Project description:It is of paramount importance to unravel the molecular mechanisms underlying PCa progression to develop novel diagnostic and therapeutic approaches. MicroRNA (miRNA) profiling through microarrays is an invaluable tool to identify a miRNA signature, which is required to determine the general and specific expression alterations between distinct types of tissues. In this study, it is aimed to compare the miRNA profile of recurrent and non-recurrent prostate tumor tissues to explore a possible involvement of miRNAs in PCa progression.
2014-07-10 | E-GEOD-55323 | biostudies-arrayexpress
Project description:It is of paramount importance to unravel the molecular mechanisms underlying PCa progression to develop novel diagnostic and therapeutic approaches. MicroRNA (miRNA) profiling through microarrays is an invaluable tool to identify a miRNA signature, which is required to determine the general and specific expression alterations between distinct types of tissues.
2014-07-10 | GSE55323 | GEO
Project description:BACKGROUND:Plant derivatives have been studied as therapies for prostate cancer based on their purported anti-inflammatory and antioxidant properties and low toxicities. The acai berry is an example of a plant rich in phytochemicals, which may slow the growth of prostate cancer. METHODS:This was a phase II, Simon 2-stage clinical trial in patients with biochemically recurrent prostate cancer with a primary endpoint of prostate-specific antigen (PSA) response. Patients were asymptomatic, with a rising PSA of at least 0.2 ng/mL, and were treated with twice daily intake of Acai Juice Product until PSA progression, with a primary endpoint of PSA response. RESULTS:Twenty-one patients were enrolled in the first stage of the trial. One of those patients had a PSA response within the study time period. The PSA doubling time was lengthened in 71% of patients (95% confidence interval = 48% to 89%) on the trial, and in a small number of responders, this was sustained over an extended time. CONCLUSIONS:This study did not meet its primary endpoint of 50% PSA response. Nevertheless, the overall tolerability and effects on PSA stabilization warrant further exploration in a biochemically recurrent population.
| S-EPMC6247557 | biostudies-literature
Project description:We retrospectively explored changes in immunological parameters in men with biochemically recurrent prostate cancer treated with either 5 or 25 mg of lenalidomide in a randomized phase 2 trial, and determined whether those changes correlated with disease progression.Cytokine levels were compared for each patient at baseline and after 6 months of treatment with lenalidomide. Regression models for correlated data were used to assess associations of cytokine levels with lenalidomide treatment effect. Estimates were obtained using generalized estimating equations. Changes in circulating anti-prostate antibodies were evaluated using a high-throughput immunoblot technique.Treatment with lenalidomide was associated with global changes in immunoreactivity to a number of prostate-associated antigens, as well as with changes in circulating levels of the T(H) 2 cytokines IL-4, IL-5, IL-10, and IL-13. Disease progression in treated patients was associated with an increase in circulating IL-8 levels, while IL-8 levels decreased significantly in non-progressors.Lenalidomide demonstrates immunomodulatory properties in patients with biochemically recurrent prostate cancer. The induction of novel anti-prostate antibodies is a potential mechanism for lenalidomide response. Changes in serum IL-8 levels may serve as a potential biomarker in treated patients. These hypotheses require formal testing in future prospective trials.
| S-EPMC3248613 | biostudies-literature
Project description:PurposeRadiolabeled Prostate-Specific Membrane Antigen (PSMA) PET/CT is the current standard-of-care for lesion detection in patients with biochemically recurrent (BCR) prostate cancer (PCa). However, rigorous verification of detected lesions is not always performed in routine clinical practice. To aid future 18F-radiolabeled PSMA PET/CT interpretation, we aimed to identify clinical/imaging characteristics that increase the likelihood that a PSMA-avid lesion is malignant.Materials and methods262 patients with BCR, who underwent 18F-DCFPyL PSMA PET/CT, were retrospectively analyzed. The malignant nature of 18F-DCFPyL PET-detected lesions was verified through any of the following metrics: (1) positive histopathological examination; (2) additional positive imaging; (3) a ≥50% decrease in Prostate-Specific Antigen (PSA) following irradiation of the lesion(s).ResultsIn 226/262 PET scans (86.3%) at least one lesion suspicious for recurrent PCa was detected ('positive scan'). In 84/226 positive scans (37.2%), at least one independent verification metric was available. PSMA PET-detected lesions were most often confirmed to be malignant (PCa) in the presence of a CT-substrate (96.5% vs. 55.6% without CT-substrate), with SUVpeak ≥3.5 (91.4% vs. 60.0% with SUVpeak<3.5), in patients with a PSA-level ≥2.0 ng/mL (83.7% vs. 65.7% in patients with PSA <2.0ng/mL) and in patients with >2 PET-positive lesions (94.1% vs. 64.2% in patients with 1-2 PET-positive lesions; p<0.001-0.03).ConclusionsIn this study, the clinical verification of 18F-DCFPyL PET-positive lesions in patients with BCR was performed. Diagnostic certainty of PET-detected lesions increases in the presence of characteristic abnormalities on CT, when SUVpeak is ≥3.5, when PSA-levels exceed 2.0 ng/mL or in patients with more than two PET-positive lesions.
| S-EPMC7537873 | biostudies-literature
Project description:Despite local therapy with curative intent, approximately 30% of men suffer from biochemical relapse. Though some of these PSA relapses are not life threatening, many men eventually progress to metastatic disease and die of prostate cancer. Local therapy is an option for some men, but many have progression of disease following local salvage attempts. One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed. Androgen deprivation therapy is a cornerstone of therapy in the salvage setting. While subsets may benefit in terms of delay in time to metastatic disease and/or death, research is ongoing to improve salvage systemic therapy. Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers. While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing. Salvage therapy and imaging modalities in this setting are briefly reviewed, and the rationale for PSMA-based systemic salvage radioimmunotherapy is described.
| S-EPMC3368159 | biostudies-literature
Project description:Among men treated with prostatectomy or radiation therapy for localized prostate cancer, the state of an increasing prostate-specific antigen (PSA) level is known as biochemical recurrence (BCR). BCR can be predictive of the development of subsequent distant metastases and ultimately death, but BCR often predates other signs of clinical progression by several years. Although patients may be concerned about their rising PSA levels, physicians attempting to address patient anxiety must inform them that BCR is not typically associated with imminent death from disease, and that the natural history of biochemical progression may be prolonged. Misinterpretation of the significance of early changes in PSA may cause patients to receive androgen deprivation therapy (ADT) prematurely, especially in settings where the disease is unlikely to impact survival. In addition, knowledge of the morbidities associated with ADT (hot flashes, impotence, sarcopenia, metabolic syndrome, bone loss, and increased risk of vascular disease) has accelerated the search for alternative treatment options for these patients. Clinical trials investigating when and how to best use and supplement hormonal therapies in this patient population are under way, as are trials of novel nonhormonal targeted agents, immunotherapies, natural products, and other pharmaceuticals that have been approved by the US Food and Drug Administration (FDA) for other indications. This review will summarize the acceptable standards of care for the management of biochemically recurrent prostate cancer, and will also outline some novel experimental approaches for the treatment of this disease state.
| S-EPMC3624708 | biostudies-literature
Project description:Men with biochemical recurrence (BCR) of prostate cancer are typically observed or treated with androgen-deprivation therapy. Non-hormonal, non-toxic treatments to slow the rise of PSA are desirable. We studied a combination herbal supplement, Prostate Health Cocktail (PHC), in prostate cancer cell lines and in a population of men with BCR.PC3, LAPC3 and LNCaP cells were incubated with increasing concentrations of PHC suspension. Men previously treated for prostate cancer with surgery, radiation or both with rising PSA but no radiographic metastases were treated with three capsules of PHC daily; the primary end point was 50% PSA decline. Circulating tumor cells (CTCs) were identified using parylene membrane filters.PHC showed a strong dose-dependent anti-proliferative effect in androgen-sensitive and independent cell lines in vitro and suppression of androgen receptor expression. Forty eligible patients were enrolled in the clinical trial. Median baseline PSA was 2.8 ng ml(-1) (1.1-84.1) and 15 men (38%) had a PSA decline on study (1-55% reduction); 25 (62%) had rising PSA on study. The median duration of PSA stability was 6.4 months. Two patients had grade 2/3 transaminitis; the only other grade 2 toxicities were hyperglycemia, hypercalcemia and flatulence. There were no significant changes in testosterone or dihydrotestosterone. CTCs were identified in 19 men (47%).Although the primary end point was not met, PHC was well tolerated and was associated with PSA declines and stabilization in a significant number of patients. We believe this is the first report of detecting CTCs in men with BCR prostate cancer. Randomized studies are needed to better define the effect of PHC in men with BCR.
| S-EPMC4234307 | biostudies-literature
Project description:Predicting biochemical recurrence of prostate cancer is imperative for initiating early treatment, which can improve the outcome of cancer treatment. However, because of inter- and intrareader variability in interpretation of F-18 fluciclovine positron emission tomography/computed tomography (PET/CT), it is difficult to reliably discern between necrotic tissue owing to radiation therapy and tumor tissue. Our goal is to develop a computational methodology using Haralick texture analysis that can be used as an adjunct tool to improve and standardize the interpretation of F-18 fluciclovine PET/CT to identify biochemical recurrence of prostate cancer. Four main textural features were chosen by variable selection procedure using least absolute shrinkage and selection operator logistic regression and bootstrapping, and then included as predictors in subsequent logistic ridge regression model for prediction (n = 28). Age at prostatectomy, prostate-specific antigen (PSA) level before the PET/CT imaging, and number of days between the prostate-specific antigen measurement and PET/CT imaging were also included in the prediction model. The overfitting-corrected area under the curve and Brier score of the proposed model were 0.94 (95% CI: 0.81, 1.00) and 0.12 (95% CI: 0.03, 0.23), respectively. Compared with a model with textural features (TI model) and that with only clinical information (CI model), the proposed model achieved 2% and 32% increase in AUC and 8% and 48% reduction in Brier score, respectively. Combining Haralick textural features based on the PET/CT imaging data with clinical information shows a high potential of enhanced prediction of the biochemical recurrence of prostate cancer.
| S-EPMC7442090 | biostudies-literature