Current and Potential Roles of Ferroptosis in Bladder Cancer

Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Ferroptosis is a prevalent and primitive form of cell death.Numerous cellular metabolic processes regulate ferroptosis,including redox homeostasis,iron regulation,mitochondrial activity,amino acid metabolism,lipid metabolism,and various disease-related signaling pathways.Ferroptosis plays a pivotal role in cancer therapy,particularly in the eradication of aggressive malignancies resistant to conventional treatments.Multiple studies have explored the connection between ferroptosis and bladder cancer,focusing on its incidence and treatment outcomes.Several biomolecules and tumor-associated signaling pathways,such as p53,heat shock protein 1,nuclear receptor coactivator 4,RAS-RAF-MEK,phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin,and the Hippo-tafazzin signaling system,exert a moderating influence on ferroptosis in bladder cancer.Ferroptosis inducers,including erastin,artemisinin,conjugated polymer nanoparticles,and quinazolinyl-arylurea derivatives,hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment.Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer.In this review,we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer

Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Total pelvic exenteration and a new model of diversion for giant primitive neuroectodermal tumor of prostate: A case report and review of the literature

The present study reports a rare primitive neuroectodermal tumor (PNET) of prostate.A 27-year-old male was admitted to Harbin Medical University Cancer Hospital (Harbin,China) for dysuria and dyschezia. Magnetic resonance imaging (MRI) revealed a large mass thatmay involve the bladder and rectum next to the prostate. Histopathological analysis of biopsyof prostate indicated mesenchymal origin tumor, and immunohistochemistric stainingconfirmed diagnosis of PNET of prostate. En bloc total pelvic exenteration and double barrelsigmoidostomy were performed. Double stomas in the skin incision were used for fecal andurinary diversion, respectively. Short-term outcome is satisfactory, while long-term efficacyremains to be poor. Clinical features of PNET of prostate should be paid much more attentionand radical surgery and adjuvant chemotherapy should be recommended.

EFFECTS OF ALCOHOL INTAKE ON PENILE STRUCTURE AND FUNCTION IN RATS

Objective To investigate the effects of alcohol intake on penile structure and function in rats. Methods Thirty adult male Wistar rats were randomly divided into two groups: control group and alcohol intake group. They were administered with 2 mL of normal saline and 40% alcohol solution respectively through gastric tubes every day. Three months later, the animal model of alcohol intake was evaluated by modified Nayagida's method, and the effects of alcohol on the rats were studied by sexual behavior, the number of apomorphine-induced penile erection, level of testosterone in the sera, and the content of penile smooth muscle. Results The scores of animal model of alcohol intake evaluated by Nayagida's method were 0.66±2.05 in the control group and 9.26±5.50 in the alcohol intake group(P<0.05), which indicated that an animal model of alcohol intake was successfully established. Sexual behavior, the number of apomorphine-induced penile erection, testosterone level in the sera, and the content of penile smooth muscle of the alcohol intake group were all statistically different as compared with the control group(P<0.05). Conclusion Alcohol intake induces sexual dysfunction in rats, which may be due to the decline of testosterone level in the sera and decline of penile smooth muscle.

Themechanism of resistance to CDK4/6 inhibition and novel combination therapy with RNR inhibition for chemo-resistant bladder cancer

Bladder cancer(BCa)is the most prevalent urological cancer worldwide[1].A significant proportion of BCa(89%)exhibits molecular alterations in the cell cycle pathway,and targeting cyclin-dependent kinases 4 and 6(CDK4/6)is deemed as a promising therapeutic strategy[2].Selective inhibitors of CDK4/6(CDK4/6is)have been approved by the US Food and Drug Administration(FDA)[3].