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.
Background/Aim: Α previous report showed that immune complex-ceruloplasmin (CP) in urine is associated with carcinogenesis and malignant behavior in bladder cancer (BC). We investigated the pathological significance and prognostic roles of urine and tissue levels of CP protein in BC patients. Materials and Methods: Urine CP levels were measured using an enzyme-linked immunosorbent assay in 97 patients. CP expression in BC tissues was evaluated by immunohistochemical analysis in 176 patient samples. Results: Urine CP levels were positively associated with tumor grade and pT stage in non-muscle invasive BC (NMIBC). CP expression in BC tissues was positively associated with tumor growth and progression. Multivariate analysis demonstrated that high urine CP levels was an independent predictor of recurrence in the urinary tract in NMIBC (hazard ratio=2.87, p=0.016). Conclusion: CPrelated markers, especially urine CP levels, are useful biomarkers of malignant potential and prognosis in NMIBC.
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...
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