Wound healing is a complex process and has been the subject of intense research for a long time. The recent emergence of nanotechnology has provided a new therapeutic modality in silver nanoparticles ...for use in burn wounds. Nonetheless, the beneficial effects of silver nanoparticles on wound healing remain unknown. We investigated the wound‐healing properties of silver nanoparticles in an animal model and found that rapid healing and improved cosmetic appearance occur in a dose‐dependent manner. Furthermore, through quantitative PCR, immunohistochemistry, and proteomic studies, we showed that silver nanoparticles exert positive effects through their antimicrobial properties, reduction in wound inflammation, and modulation of fibrogenic cytokines. These results have given insight into the actions of silver and have provided a novel therapeutic direction for wound treatment in clinical practice.
A healing touch: The ability to produce silver nanoparticles has enabled us to elucidate the effects of silver on wound healing. We demonstrate that silver nanoparticles significantly decrease the time of burn wound healing in an animal model. The results provide a novel therapeutic direction for wound treatment in clinical practice.
Due to an increased understanding of molecular biology and the genomics of cancer, new and potent agents have been approved by the Food and Drug Administration (FDA) to fight this disease. However, ...all of these drugs cause severe side effects and resistance inevitably develops, re-activating tumor growth and dissemination. For this reason, patients turn to natural compounds as alternative or complementary treatment options, since it has been found that natural plant products may block, inhibit, or reverse cancer development. The present review focusses on the role of the natural compound sulforaphane (SFN) as an anti-tumor agent in urologic cancer. SFN is a natural compound found in cruciferous vegetables from the Brassicaceae family such as broccoli, cauliflower and cabbage. Several epidemiologic and clinical studies have documented chemopreventive properties of SFN, making it an interesting candidate for additive cancer treatment. SFN shows remarkable anti-tumor effects in vitro and in vivo without exerting toxicity. The review summarizes the current understanding of SFN and provides insights into its molecular mode of action with particular emphasis on epigenetic tumor control.
•Sulforaphane is found in cruciferous vegetables such as broccoli, cauliflower and cabbage.•Sulforaphane exerts potential chemopreventive properties.•Sulforaphane attenuates tumor growth, metastasis and angiogenesis in vitro and in vivo.•Sulforaphane alters acetylation of histones and modifies intracellular signaling.•Sulforaphane might be a valuable additive for future anti-tumor protocols.
Abstract Background Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and ...comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease. Objective To examine the risk of 10-yr cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathologic characteristics of patients treated with radical prostatectomy (RP) for high-risk PCa. Design, setting, and participants Within a multi-institutional cohort, 3828 men treated with RP for high-risk PCa (defined as the presence of at least one of these risk factors: prostate-specific antigen >20 ng/ml, biopsy Gleason score 8–10, clinical stage ≥T3) were identified. Intervention All patients underwent RP and pelvic lymph node dissection. Outcome measurements and statistical analysis Competing-risk Poisson regression analyses were performed to simultaneously assess the 10-yr CSM and OCM rates after RP. The same analyses were also conducted after stratification of patients according to age at surgery, comorbidity status assessed by the Charlson Comorbidity Index (CCI), and number of risk factors (one vs two or more). Results and limitations Overall, 229 patients (5.9%) died from PCa; 549 (14.3%) died from other causes. The 10-yr CSM and OCM rates ranged from 5.1% to 12.8% and from 4.3% to 37.4%, respectively. Age and CCI were the major determinants of OCM; their impact on CSM was minimal. OCM was the leading cause of death in all patient groups except in young men (≤59 yr) with no comorbidities, regardless of the number of risk factors (10-yr CSM and OCM 6.9–12.8% and 5.5–6.3%, respectively). The main limitation was the lack of patients managed conservatively. Conclusions Even in the context of high-risk PCa, long-term CSM after RP is modest and represents the leading cause of death only in young, healthy patients. Conversely, older and sicker patients with multiple risk factors are at the highest risk of dying from OCM while sharing very low CSM rates.
Background Nonadherence to antihypertensive medications is the leading cause of poor blood pressure control and thereby cardiovascular diseases and mortality worldwide. Methods and Results We ...investigated the global epidemiology, regional differences, and trend of antihypertensive medication nonadherence via a systematic review and meta‐analyses of data from 2010 to 2020. Multiple medical databases and clinicaltrials.gov were searched for articles. Observational studies reporting the proportion of patients with anti‐hypertensive medication nonadherence were included. The proportion of nonadherence, publication year, year of first recruitment, country, and health outcomes attributable to antihypertensive medication nonadherence were extracted. Two reviewers screened abstracts and full texts, classified countries according to levels of income and locations, and extracted data. The Joanna Briggs Institute prevalence critical appraisal tool was used to rate the included studies. Prevalence meta‐analyses were conducted using a fixed‐effects model, and trends in prevalence were analyzed using meta‐regression. The certainty of evidence concerning the effect of health consequences of nonadherence was rated according to Grading of Recommendations, Assessment, Development and Evaluations. A total of 161 studies were included. Subject to different detection methods, the global prevalence of anti‐hypertensive medication nonadherence was 27% to 40%. Nonadherence was more prevalent in low‐ to middle‐income countries than in high‐income countries, and in non‐Western countries than in Western countries. No significant trend in prevalence was detected between 2010 and 2020. Patients with antihypertensive medication nonadherence had suboptimal blood pressure control, complications from hypertension, all‐cause hospitalization, and all‐cause mortality. Conclusions While high prevalence of anti‐hypertensive medication nonadherence was detected worldwide, higher prevalence was detected in low‐ to middle‐income and non‐Western countries. Interventions are urgently required, especially in these regions. Current evidence is limited by high heterogeneity. Registration URL: www.crd.york.ac.uk/prospero/ ; Unique identifier: CRD42021259860.
Background
In contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation ...is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint.
Methods
Within the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used.
Results
In 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation,
p
< 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio HR 1.8,
p
< 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (
p
< 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (
p
< 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (
p
< 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM.
Conclusions
In contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM.
Purpose
The currently used scheme for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC) consists of 4–6 cycles of 6.0–7.4 GBq
177
LuLu-PSMA-617 each. ...This standard treatment scheme has proved safe and effective resulting in objective response in most patients with no significant toxicity. Many patients, however, show high-volume residual tumor burden after the sixth cycle and may benefit from treatment continuation. Extended treatment with additional cycles has been withheld due to concerns on potential increased toxicity.
Methods
Twenty-six patients with high-volume residual tumor burden (according to CHAARTED) after standard RLT with
177
LuLu-PSMA-617 and no alternative treatment option received additional RLT cycles reaching a median of 10 (range 7–16) cycles with a mean activity of 7.4 ± 0.9 GBq per cycle. Response assessment with
68
GaGa-PSMA-11 PET/CT was done every 2–3 cycles or if disease progression was clinically suspected or based on change in PSA value (according to the PCWG3 criteria). Toxicity was measured using routine blood work up including blood counts, liver and renal function, and was graded according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan-Meier method.
Results
Further PSA decline of 33 ± 28% during the extended treatment was observed in 21/26 (81%) patients, whereas 5/26 (19%) patients showed a PSA increase; correspondingly in 11/21 patients with an initial response (PR or SD) to extended cycles, treatment was discontinued due to progressive disease, whereas six (23%) patients achieved low-volume residual disease. Two (8%) patients died without showing progression, and two (8%) patients are still under therapy. The median progression-free survival was 19 (95% CI: 15–23) months, and the overall survival was 29 (95% CI: 18–40) months. Grade ≥ 3 hematological toxicities occurred in 4/26 (15%) patients during treatment extension, and nephrotoxicity (grade ≥ 3) was observed in 1/26 (4%) patient during the follow-up.
Conclusion
Extended radioligand therapy is a feasible treatment option in patients with high-volume residual tumor after the completion of standard treatment with six cycles of
177
LuLu-PSMA-617. Improved survival and the acceptable safety profile warrant further investigation of the concept of additional cycles in selected patients.
The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) ...treatment alternatives.
We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes.
Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6-10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order.
The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.
The anti-cancer properties of curcumin in vitro have been documented. However, its clinical use is limited due to rapid metabolization. Since irradiation of curcumin has been found to increase its ...anti-cancer effect on several tumor types, this investigation was designed to determine whether irradiation with visible light may enhance the anti-tumor effects of low-dosed curcumin on renal cell carcinoma (RCC) cell growth and proliferation. A498, Caki1, and KTCTL-26 cells were incubated with curcumin (0.1⁻0.4 µg/mL) and irradiated with 1.65 J/cm² visible light for 5 min. Controls were exposed to curcumin or light alone or remained untreated. Curcumin plus light, but not curcumin or light exposure alone altered growth, proliferation, and apoptosis of all three RCC tumor cell lines. Cells were arrested in the G0/G1 phase of the cell cycle. Phosphorylated (p) CDK1 and pCDK2, along with their counter-receptors Cyclin B and A decreased, whereas p27 increased. Akt-mTOR-signaling was suppressed, the pro-apoptotic protein Bcl-2 became elevated, and the anti-apoptotic protein Bax diminished. H3 acetylation was elevated when cells were treated with curcumin plus light, pointing to an epigenetic mechanism. The present findings substantiate the potential of combining low curcumin concentrations and light as a new therapeutic concept to increase the efficacy of curcumin in RCC.
Purpose To our knowledge the impact of body mass index on oncologic outcomes in nonmuscle invasive bladder cancer has not been evaluated. We hypothesized that higher body mass index is associated ...with worse outcomes in patients with clinical primary T1 high grade urothelial carcinoma of the bladder. Materials and Methods We retrospectively analyzed data from 892 patients with primary nonmuscle invasive bladder cancer from 7 centers. Patients were treated with transurethral resection of the bladder with or without intravesical therapy. Body mass index was analyzed as a continuous and a categorical variable (nonobese—body mass index less than 30 kg/m2 vs obese—body mass index 30 kg/m2 or greater). Disease progression was defined as the development of T2 or higher tumor stage. Results Median followup was 42.8 months (IQR 56). Of the patients 44.3% were obese and median body mass index was 29.2 kg/m2 (IQR 8). On univariable analyses higher body mass index and age were associated with an increased risk of disease recurrence, progression, cancer specific mortality and any cause mortality (all p ≤0.001). On multivariable analyses that adjusted for the effects of gender, concomitant carcinoma in situ, tumor size, number of tumors and intravesical therapy, higher body mass index and age remained independent predictors of disease recurrence, progression, cancer specific mortality and any cause mortality (all p <0.05). This study was limited by its design (ie lack of data on repeat transurethral resection of the bladder and intravesical therapy protocol). Conclusions Patients diagnosed with clinical T1 high grade urothelial carcinoma of the bladder who are obese have worse cancer specific outcomes compared to their nonobese counterparts. Further work is needed to improve our understanding of clinical T1 high grade outcomes in the growing population of obese patients.
Although the therapeutic armamentarium for bladder cancer has considerably widened in the last few years, severe side effects and the development of resistance hamper long-term treatment success. ...Thus, patients turn to natural plant products as alternative or complementary therapeutic options. One of these is curcumin, the principal component of
that has shown chemopreventive effects in experimental cancer models. Clinical and preclinical studies point to its role as a chemosensitizer, and it has been shown to protect organs from toxicity induced by chemotherapy. These properties indicate that curcumin could hold promise as a candidate for additive cancer treatment. This review evaluates the relevance of curcumin as an integral part of therapy for bladder cancer.
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