Bladder cancer (BC) is a representative of urological cancer with a high recurrence and metastasis potential. Currently, cisplatin-based chemotherapy and immune checkpoint inhibitors are used as standard therapy in patients with advanced/metastatic BC. However, these therapies often show severe adverse events, and prolongation of survival is unsatisfactory. Therefore, a treatment strategy using natural compounds is of great interest. In this review, we focused on the anti-cancer effects of isothiocyanates (ITCs) derived from cruciferous vegetables, which are widely cultivated and consumed in many regions worldwide. Specifically, we discuss the anti-cancer effects of four ITC compounds—allyl isothiocyanate, benzyl isothiocyanate, sulforaphane, and phenethyl isothiocyanate—in BC; the molecular mechanisms underlying their anti-cancer effects; current trends and future direction of ITC-based treatment strategies; and the carcinogenic potential of ITCs. We also discuss the advantages and limitations of each ITC in BC treatment, furthering the consideration of ITCs in treatment strategies and for improving the prognosis of patients with BC.

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.

Molecular targeted therapies are commonly used in patients with metastatic renal cell carcinoma (RCC). However, the efficacy and safety of these therapeutic interventions require enhancement to improve prognosis in these patients. Royal jelly (RJ) has anti-cancer effects and adverse events across a variety of types of malignancy. The present study investigated the detailed mechanism underlying the effects of oral administration of RJ in patients with advanced RCC that were treated with molecular targeted agents in a randomized clinical trial. The study cohort comprised 16 patients treated with RJ and 17 patients treated with a placebo. Serum levels of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β were measured using enzyme-linked immunosorbent assays. The results of the present study demonstrated a larger decrease in tumor size upon supplementing patients with RJ following molecular targeted therapy compared with that in patients administered with the placebo. Patients exhibited reduced anorexia and fatigue in the RJ group compared with the placebo group. The relative dose intensity for patients in the RJ group was higher than that in patients in the placebo group. Post-and pre-treatment ratios of the serum levels of TNF-α and TGF-β in patients in the RJ group were lower than those in patients in the placebo group, and these ratios correlated with decreasing tumor size and frequency of anorexia or fatigue in patients. In conclusion, the results of the present study indicated that oral intake of RJ improved the efficacy and safety of molecular targeted therapy in patients with RCC and changed the levels of TNF-α and TGF-β in the serum of patients, which is speculated to serve an important role in RJ-induced biological activities.

ObjectiveTo evaluate the effects of tadalafil monotherapy on lower urinary tract symptoms, urodynamic parameters, and oxidative stress levels in male patients.MethodsThis prospective study included 53 male patients with urinary symptoms, who met the criteria for overactive bladder (OAB) (≥ 2 points for Q3 [urgency] in the OAB symptom score [OABSS] assessment and ≥ 3 points for the total score). The patients received 5 mg tadalafil orally once daily, and their symptoms were assessed before and after the 12‐week treatment. The OABSS and international prostate symptom score (IPSS) were used to evaluate the subjective symptoms. The objective findings were assessed using uroflowmetry. Oxidative stress was assessed by determining urinary levels of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) levels with an adjustment for urinary creatinine (CR) concentration.ResultsAfter tadalafil administration, total and individual indices of the OABSS assessment showed significant improvement. In addition, total storage and voiding symptoms that contributed to the IPSS were also significantly improved. The voided volume was increased, and the maximum flow rate was improved after tadalafil treatment (P = .002 and < 0.001, respectively). Urinary 8‐OHdG/CR decreased from 12.4 ± 9.7 ng/mg CR to 7.6 ± 11.6 ng/mg CR (P < .001). In patients who showed OAB improvement and did not meet the criteria for OAB after the treatment (44 patients, 83.0%), the urinary 8‐OHdG/CR level was significantly decreased from 11.6 ± 8.4 ng/mg CR to 6.4 ± 10.3 ng/mg CR (P < .001).ConclusionsTadalafil treatment improves OAB symptoms and urodynamic parameters by decreasing oxidative stress level.

Background/Aim: Stage-specific embryonic antigen-4 (SSEA-4) expression is associated with malignant aggressiveness and is useful as a marker for identifying cancer stem cells. Our aim was to assess the relationship between hormonal therapy and SSEA-4 expression in prostate cancer (PC). Materials and Methods: SSEA-4 expression in paired specimens from PC patients who underwent neoadjuvant hormonal therapy (NHT) and radical prostatectomy (60 pre-NHT specimens and 60 post-NHT specimens) was evaluated using immunohistochemistry. Proliferation index (PI) and apoptotic index (AI) were also evaluated. Results: Post-NHT tissues had significantly elevated SSEA-4 expression whereas anti-tumor effects of NHT were inversely correlated with SSEA-4 expression level. SSEA-4 expression in post-NHT tissues was significantly associated with biochemical recurrence-free survival. SSEA-4 expression in the post-NHT tissues was positively associated with PI and negatively done with AI. Conclusion: SSEA-4 is a potential therapeutic target for limiting the malignant potential in hormone-naïve PC when considering the use of NHT.Prostate cancer (PC) is the most commonly diagnosed cancer among men and the second leading cause of cancer-related deaths among men in the United States (1). Although many patients with early PC have elevated serum concentrations of prostate-specific antigen (PSA), approximately one-third of patients already have metastasis at the time of diagnosis (2). In general, hormonal therapy involves androgendeprivation therapy (ADT), which is a standard and effective treatment for patients with metastatic PC. Unfortunately, the majority of androgen-dependent PC cells gradually become androgen-independent cells during ADT, which leads to metastatic PC becoming resistant to hormonal therapy and progressing to castration-resistant prostate cancer (CRPC) (3). There are various treatments for CRPC, which involve chemotherapeutic agents, androgen receptor-axis-targeted agents, and immunotherapeutic agents (4-6). While these treatments can improve survival outcomes in CRPC cases, the increase in progression-free survival (PFS) and overall survival (OS) remains suboptimal.The suboptimal outcomes in CRPC cases are partly related to our poor understanding of the molecular mechanisms that lead to hormonal therapy resistance. In this context, it is important to understand that cancer stem cells (CSCs) play important roles in PC tumor growth and treatment resistance, as their pluripotency and self-renewal capability allow these cells to differentiate into diverse new cancer cells (7). Sex determining region Y-box-2 (Sox-2) is a major CSC marker, and its expression in PC cells is increased after androgen deprivation. The latter has been positively associated with cell growth and resistance to anti-androgen agents in both androgen-dependent and androgen-independent PC cells (8). Therefore, it is important to understand the interactions between hormonal therapy and CSCs, which may provide insight regarding PC tumor development and resista...

Objectives: Pelvic organ prolapse (POP) is a cause of overactive bladder (OAB), and transvaginal mesh (TVM) surgery can improve the symptoms. Bladder wall thickness (BWT) is a useful and safe marker to evaluate bladder function in urinary disorders. The main purpose of this study is to clarify the relationship between BWT and changes in the OAB symptom score (OABSS) after TVM operation in patients with POP.Methods: BWT was measured by ultrasonography before and 6 months after surgery at three sites in the bladder: the anterior wall, trigone, and dome. Similarly, the OABSS was evaluated at the time of BWT measurement. Changes induced in BWT at each site and the mean BWT at all sites after TVM surgery were analyzed. Similarly, the relationship between presurgical BWT and the decrease in OABSS was investigated.Results: TVM surgery improved OABSS in 30 patients (responders; 73.2%), while 11 patients were judged as nonresponders (26.8%). BWT at the anterior bladder wall and dome as well as the mean BWT at all three sites were significantly decreased by TVM surgery (P < .001). Similar trends were identified in OABSS responders; however, all markers showed no significant changes in OABSS nonresponders. All the BWT-related markers before surgery were significantly lower in OABSS responders than in OABSS nonresponders.Conclusions: BWT at the bladder anterior wall and dome, but not the trigone, were decreased by TVM surgery. We conclude that presurgical BWT may be a useful marker to predict the improvement in OAB symptoms by TVM surgery in patients with POP-related OAB.

Bladder cancer (BC) is a common urological cancer, with poor prognosis for advanced/metastatic stages. Various intensive treatments, including radical cystectomy, chemotherapy, immune therapy, and radiotherapy are commonly used for these patients. However, these treatments often cause complications and adverse events. Therefore, researchers are exploring the efficacy of natural product-based treatment strategies in BC patients. Fucoidan, derived from marine brown algae, is recognized as a multi-functional and safe substrate, and has been reported to have anti-cancer effects in various types of malignancies. Additionally, in vivo and in vitro studies have reported the protective effects of fucoidan against cancer-related cachexia and chemotherapeutic agent-induced adverse events. In this review, we have introduced the anti-cancer effects of fucoidan extracts in BC and highlighted its molecular mechanisms. We have also shown the anti-cancer effects of fucoidan therapy with conventional chemotherapeutic agents and new treatment strategies using fucoidan-based nanoparticles in various malignancies. Moreover, apart from the improvement of anti-cancer effects by fucoidan, its protective effects against cancer-related disorders and cisplatin-induced toxicities have been introduced. However, the available information is insufficient to conclude the clinical usefulness of fucoidan-based treatments in BC patients. Therefore, we have indicated the aspects that need to be considered regarding fucoidan-based treatments and future directions for the treatment of BC.

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