Search

Introduction: Urothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC), which are characterized by frequent recurrences and progression rate, respectively. The diagnosis and monitoring are obtained through invasive methods as cystoscopy and post-surgery biopsies. Thus, a panel of biomarkers able to discriminate BC based on grading or staging represents a significant step forward in the patients' workup. In this perspective, long non-coding RNAs (lncRNAs) are emerged as reliable candidates as potential biomarker given their specific and regulated expression. In the present work we propose two lncRNAs, the Small Ubiquitin Modifier 1 pseudogene 3 (SUMO1P3), a poorly characterized pseudogene, and the Urothelial Carcinoma Associated 1 (UCA1) as candidates to monitor the BC progression. Methods: This study was a retrospective trial enrolling NMIBC and MIBC patients undergoing surgical intervention: the expression of the lncRNA SUMO1P3 and UCA1 was evaluated in urine from 113 subjects (cases and controls). The receiver operating characteristic curve analysis was used to evaluate the performance of single or combined biomarkers in discriminating cases from controls. Results: SUMO1P3 and UCA1 expression in urine was able to significantly discriminate low grade NMIBC, healthy control and benign prostatic hyperplasia subjects versus high grade NMIBC and MIBC patients. We also demonstrated that miR-320a, which binds SUMO1P3, was reduced in high grade NMIBC and MIBC patients and the SUMO1P3/miR-320a ratio was used to differentiate cases versus controls, showing a statistically significant power. Finally, we provided an automated method of RNA extraction coupled to ddPCR analysis in a perspective of clinical application. Discussion: We have shown that the lncRNA SUMO1P3 is increased in urine from patients with high grade NMIBC and MIBC and that it is likely to be good candidate to predict bladder cancer progression if used alone or in combination with UCA1 or with miRNA320a. [ABSTRACT FROM AUTHOR]

Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for patients with limited-stage muscle-invasive bladder cancer. RC is associated with a complication rate of approximately 50–88%. Immunonutrition (IMN) refers to the administration of substrates, such as omega-3 fatty acids, arginine, glutamine, and nucleotides, that modulate the immune response. IMN has been associated with improved outcomes following surgery for esophagogastric, colorectal and pancreatic cancer. In this paper, we describe a study protocol for a multicentre, randomised, open-label clinical trial to evaluate the effect of IMN in patients undergoing RC for bladder cancer. A 7-day preoperative course of IMN is compared with a standard high-calorie high-protein oral nutritional supplement. The primary outcome of this study is the rate of complications (infectious, wound-related, gastrointestinal, and urinary complications) in the first 30 days after RC. Secondary outcomes include time to recovery of bowel function and postoperative mobilisation, changes in muscle strength and body weight, biochemical modifications, need for blood transfusion, length of stay, readmission rate, and mortality. The results of this study may provide new insights into the impact of IMN on postoperative outcomes after RC and may help improve IMN prescribing based on patient nutritional status parameters. [ABSTRACT FROM AUTHOR]

Simple Summary: Preoperative nutritional status is a pivotal aspect to consider in cancer patients undergoing radical cystectomy, as malnourished individuals are more prone to post-surgical complications. The loss of muscle mass is a significant consequence of cancer-related malnutrition and is associated with increased risks of readmission, longer hospital stays, and higher mortality rates. This narrative review explores the concept of "immunonutrition", which consists of the use of specific nutrients to boost the immune system and improve postoperative outcomes. By reviewing existing scientific literature, promising evidence was found that supports immunonutrition in reducing complications, including infections, after bladder surgery. These findings highlight the need for further research to determine the optimal approach, regardless of nutritional status, for improving patient outcomes after bladder surgery. The development of uniformly designed randomized controlled trials is necessary to establish the most effective dosage, timing, and duration of perioperative immunonutrition and to confirm the available preliminary evidence. Preoperative nutritional status is a pivotal aspect to consider in patients with cancer undergoing radical cystectomy (RC), as those at risk of malnutrition or already malnourished are more prone to post-surgical complications. The loss of muscle mass is a major consequence of cancer-related malnutrition. It is associated with increased risk of hospital readmission, longer hospitalization, and higher mortality. Nowadays, the close relationship between nutritional and immunological aspects under stressful conditions, such as surgery, represents an emerging scientific and clinical issue. Indeed, the synergistic action of reduced food intake and systemic inflammation generates metabolic derangements with tissue catabolism, including skeletal muscle breakdown, which is, in turn, associated with immune system dysfunction. In order to offer an additional immune-nutritional boost to the post-surgical phase, particularly in malnourished patients, nutritional support may include oral nutritional supplements and/or enteral formulas enriched with specific nutrients such as omega-3 fatty acids, arginine, glutamine, and nucleotides, with acknowledged immune-modulating effects. In the present narrative review, we addressed the state of the art of the available scientific literature on the benefit of immunonutrition in patients undergoing RC for cancer and suggest possible future perspectives to be explored. Although the role of immunonutrition was found to be little explored in the context of urologic oncology, the preliminary available data on radical cystectomy, summarized in the present paper, are promising and suggest that it may improve postoperative outcomes through immunomodulation, regardless of nutritional status before surgery. [ABSTRACT FROM AUTHOR]

The use of pembrolizumab has been largely accepted in several advanced types of cancers. PURE 01 study (NCT02736266) enrolled consecutively 143 patients with muscle‐invasive bladder cancer who received 3 cycles of pembrolizumab 200 mg every 3 weeks before planned radical cystectomy (RC). Clinical, pathological and laboratory data were collected to investigate the relationship between renal function, immunotherapy and cancer‐related outcomes. Serum creatinine and estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) creatinine‐equation 2009 were reported at baseline and after every cycle of pembrolizumab; the T stage from clinical classification TNM (cTNM) was stated before the treatment. Our analysis did not demonstrate a significant impairment of eGFR after any cycle of pembrolizumab, neither in the overall cohort nor in subgroups considering the T stages or the CKD G‐categories according to K‐DIGO 2012 classification. In conclusion, in neoadjuvant setting before RC our results suggest that pembrolizumab administration is safe for renal function preservation. What's new? Immune checkpoint inhibitors have been tested in the neoadjuvant setting of muscle‐invasive bladder cancer with promising pathological complete response rates, but to date there is no consensus on whether perioperative immunotherapy is appropriate. This study shows that pembrolizumab can safely be used as neo‐adjuvant immunotherapy in patients with muscle‐invasive bladder cancer affected by advanced chronic kidney disease, with no significant side effects in term of renal decay (acute kidney injury development or chronic kidney disease worsening) before surgery. The findings support that patients with severe renal dysfunction could be treated with immunotherapy before surgery without risks for renal function preservation. [ABSTRACT FROM AUTHOR]

Crocus Sativus L. (saffron) has been used for centuries as a medicinal plant in traditional medicine. Its main bioactive secondary metabolites, which include crocins, crocetin, picrocrocin and safranal, are known to possess significant antioxidant as well as anti-proliferative activities. With the aim to test the activity of saffron on kidney and bladder cancer cell lines, we tested the effect of extracts obtained from dried stigmas derived from different Italian regions (Lombardy and Tuscany) in two different years, on the cell viability. The treatment with saffron extracts showed a significant reduction of cell viability in most of our tumoral cellular systems, while the standards crocin and safranal alone at the same concentrations did not exerted any cytotoxicity. When the extracts and standards were mixed together, they exerted a milder inhibition of cell viability, indicating that the antitumor activity is likely a result of the synergy of the various compounds. In addition, in a circular economy vision, we recovered Crocus Sativus flowers and tested them on cancer cells, demonstrating a consistent reduction of cell viability, while kaempferol (main compound present in flower extracts) did not show compatible results. Our results extend the interests around saffron-derived bioactive molecules for their potential in therapeutics. [Display omitted] • Crocin and safranal are the main secondary metabolites of saffron stigmas extracts. • Saffron extracts reduce cell viability in kidney and bladder cancr cell lines • Pure crocin and safranal standards alone do not exert any cytotoxicity. • Extracts efficacy suggests phytocomplex synergy of numerous phenolic compounds. [ABSTRACT FROM AUTHOR]

The endocannabinoid system is a signaling system involved in a wide range of biological effects. Literature strongly suggests the endocannabinoid system role in the pathogenesis of cancer and that its pharmacological activation produces therapeutic benefits. Last research promotes the endocannabinoid system modulation by inhibition of endocannabinoids hydrolytic enzymes instead of direct activation of endocannabinoid receptors to avoid detrimental effects on cognition and motor control. Here we report the identification of N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitors able to reduce cell proliferation and migration and cause cell death on different bladder cancer cell lines. These molecules were designed, synthesized and characterized and active compounds were selected by a fluorescence high-throughput screening method set-up on human recombinant NAAA that also allows to characterize the mechanism of inhibition. Together our results suggest an important role for NAAA in cell migration and in inducing tumor cell death promoting this enzyme as pharmacological target against bladder cancer. [ABSTRACT FROM AUTHOR]