Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and ...high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions.
Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed ...as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.
Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely ...used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, discomfort for the patient and high economic burden. Thus, there is an essential demand of non-invasive, sensitive, fast and inexpensive biomarkers for clinical management of BC patients. In this context, liquid biopsy represents a very promising tool that has been widely investigated over the last decade. Liquid biopsy will likely be at the basis of patient selection for precision medicine, both in terms of treatment choice and real-time monitoring of therapeutic effects. Several different urinary biomarkers have been proposed for liquid biopsy in BC, including DNA methylation and mutations, protein-based assays, non-coding RNAs and mRNA signatures. In this review, we summarized the state of the art on different available tests concerning their potential clinical applications for BC detection, prognosis, surveillance and response to therapy.
Abstract Background Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). Objective To study the impact of combination chemotherapy ...delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. Design, setting, and participants Individual patient-level data from phase 2 trials of salvage systemic therapy were used. Interventions Trials evaluating either single agents (paclitaxel or docetaxel) or combination chemotherapy (taxane plus one other chemotherapeutic agent or more) following prior platinum-based therapy were used. Outcome measurements and statistical analysis Information regarding the known major baseline prognostic factors was required: time from prior chemotherapy, hemoglobin, performance status, albumin, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival (OS). Results and limitations Data were available from eight trials including 370 patients; two trials ( n = 109) evaluated single-agent chemotherapy with docetaxel ( n = 72) and cremophor-free paclitaxel ( n = 37), and six trials ( n = 261) evaluated combination chemotherapy with gemcitabine–paclitaxel (two trials, with n = 99 and n = 24), paclitaxel–cyclophosphamide ( n = 32), paclitaxel–ifosfamide–nedaplatin ( n = 45), docetaxel–ifosfamide–cisplatin ( n = 26), and paclitaxel–epirubicin ( n = 35). On multivariable analysis after adjustment for baseline prognostic factors, combination chemotherapy was independently and significantly associated with improved OS (hazard ratio: 0.60; 95% confidence interval, 0.45–0.82; p = 0.001). The retrospective design of this analysis and the trial-eligible population were inherent limitations. Conclusions Patients enrolled in trials of combination chemotherapy exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC. Prospective randomized trials are required to validate a potential role for rational and tolerable combination chemotherapeutic regimens for the salvage therapy of advanced UC. Patient summary This retrospective study suggests that a combination of chemotherapy agents may extend survival compared with single-agent chemotherapy in selected patients with metastatic urothelial cancer progressing after prior chemotherapy.
Abstract Objective To investigate the expression of the kynurenine (KYN) pathway components and the prognostic role of the KYN-to-tryptophan ratio (KTR) in a cohort of patients with clear cell renal ...cell carcinoma (ccRCC). Materials and methods The expression of KYN pathway components was investigated by tissue microarray-based immunohistochemistry, indirect immunofluorescence, and confocal microscopy analysis in 100 ccRCC cases and 30 normal renal samples. The role of this pathway in sustaining cancer cell proliferation, migration, and chemoresistance was evaluated. In addition, tryptophan and KYN concentrations and their ratio were measured in serum of 195 patients with ccRCC using a sandwich enzyme-linked immunosorbent assay. The role of KTR as a prognostic factor for ccRCC cancer-specific survival (CSS) and progression-free survival (PFS) was assessed. Results Tissue microarray-based immunohistochemistry and indirect immunofluorescence staining showed an increased signal for KYN pathway components in ccRCC. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high vs. low KTR. In particular, patients with high KTR values had a 5-year survival rate of 76.9% as compared with 92.3% for subjects with low levels ( P < 0.0001). Similar findings were observed for PFS (72.8% vs. 96.8% at 5 y). At multivariate analysis, KTR was an independent adverse prognostic factor for CSS (hazard ratio = 1.24, P = 0.001), and PFS (hazard ratio = 1.14, P = 0.001). Conclusions The involvement of the KYN pathway enzymes and catabolites in ccRCC occurs via both immune and nonimmune mechanisms. Our data suggest that KTR could serve as a marker of ccRCC aggressiveness and as a prognostic factor for CSS and PFS.
The evaluation of environmental exposure risk requires a global analysis of pollution phenomena, including biological effects and potentially correlated clinical outcomes in susceptible populations. ...Although human biomonitoring plays a fundamental role in assessing the degree of contamination, it is not effective alone in identifying a direct link between exposure, biomolecular effects and outcomes on target organisms. While toxicogenomics and epidemiology are mainly focused on the investigation of molecular reactions and clinical outcomes, the monitoring of environmental matrices works independently to characterize the territorial distribution of toxic compounds, without proving any correlated health risk for residents.
We propose a new biomonitoring model based on a whole systemic analytical evaluation of environmental context. The paradigm of the method consists of identifying the sources of pollution, the migration pathways of those pollutants and their effects on target organisms. By means of this innovative, holistic epidemiological approach, we included healthy human subjects in a cohort to identify potential risks of exposure and predict possible correlated clinical outcomes. 4205 residents of the Campania region were enrolled in the “SPES” biomonitoring study, which especially focused on the areas dubbed “Land of Fires” in the recent decades.
The analysis of environmental exposure risk suffers the lack of data integration from various science fields, and this comes down to a limited point of view and a limited knowledge of phenomena.
In implementing our model, we first constructed an analytical picture of the Real-world situation. We next conducted a comparative risk assessment, in order to identify possible correlations between pollution and health within a holistic view.
This type of research activities aims to support the implementation of public health interventions and to become a reference model in the evaluation of the risk of exposure to environmental pollutants.
In the last decades, the prognosis of metastatic renal cell carcinoma (mRCC) has remarkably improved following the advent of the "targeted therapy" era. The expanding knowledge on the prominent role ...played by angiogenesis in RCC pathogenesis has led to approval of multiple anti-angiogenic agents such as sunitinib, pazopanib, axitinib, cabozantinib, sorafenib, and bevacizumab. These agents can induce radiological responses and delay cancer progression for months or years before onset of resistance, with a clinically meaningful activity. The need for markers of prognosis and efficacy of anti-angiogenic agents has become more compelling as novel systemic immunotherapy agents have also been approved in RCC and can be administered as an alternative to angiogenesis inhibitors. Anti PD-1 monoclonal antibody nivolumab has been approved in the second-line setting after tyrosine kinase inhibitors failure, while combination of nivolumab plus anti CTLA-4 monoclonal antibody ipilimumab has been approved as first-line therapy of RCC patients at intermediate or poor prognosis. In this review article, biomarkers of prognosis and efficacy of antiangiogenic therapies are summarized with a focus on those that have the potential to affect treatment decision-making in RCC. Biomarkers predictive of toxicity of anti-angiogenic agents have also been discussed.
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