RESUMEN
BACKGROUND: The proteome is an important resource for exploring potential diagnostic and therapeutic targets for cancer. This study aimed to investigate the causal associations between plasma proteins and prostate cancer (PCa), and to explore the downstream phenotypes that plasma proteins may influence and potential upstream intervening factors. METHODS: Proteome-wide Mendelian randomization was used to investigate the causal effects of plasma proteins on PCa. Colocalization analysis examined the common causal variants between plasma proteins and PCa. Summary-statistics-based Mendelian Randomization (SMR) analyses identified associations between the expression of protein-coding genes and PCa. Phenome-wide association study was performed to explore the effect of target proteins on downstream phenotypes. Finally, a systematic Mendelian randomization analysis between lifestyle factors and plasma proteins was performed to assess upstream intervening factors for plasma proteins. RESULTS: The findings revealed a positive genetic association between the predicted plasma levels of nine proteins and an elevated risk of PCa, while four proteins exhibited an inverse association with PCa risk. SMR analyses revealed ZG16B, PEX14 in blood and ZG16B, NAPG in prostate tissue were potential drug targets for PCa. The genetic association of PEX14 with PCa was further supported by colocalization analysis. Further Phenome-wide association study showed possible side effects of ZG16B, PEX14 and NAPG as drug targets. 10 plasma proteins (RBP7, TPST1, NFASC, LAYN, HDGF, SERPIMA5, DLL4, EFNA3, LIMA1, and CCL27) could be modulated by lifestyle-related factors. CONCLUSION: This study explores the genetic associations between plasma proteins and PCa, provides evidence that plasma proteins serve as potential drug targets and enhances the understanding of the molecular etiology, prevention and treatment of PCa.
RESUMEN
Prostate cancer is one of the most common malignant tumors in men, which seriously threatens the survival and quality of life of patients. At present, there are serious limitations in the treatment of prostate cancer, such as drug tolerance, drug resistance and easy recurrence. Sonodynamic therapy and chemodynamic therapy are two emerging tumor treatment methods, which activate specific drugs or sonosensitizers through sound waves or chemicals to produce reactive oxygen species and kill tumor cells. Nanomaterials are a kind of nano-scale materials with many excellent physical properties such as high targeting, drug release regulation and therapeutic monitoring. Sonodynamic therapy and chemodynamic therapy combined with the application of nanomaterials can improve the therapeutic effect of prostate cancer, reduce side effects and enhance tumor immune response. This article reviews the application progress of nanomaterials in the treatment of prostate cancer, especially the mechanism, advantages and challenges of nanomaterials in sonodynamic therapy and chemodynamic therapy, which provides new ideas and prospects for research in this field.
RESUMEN
Sonodynamic therapy (SDT) has emerged as a potential alternative to traditional cancer treatments as it offers deep cellular penetration and reduced invasivity. Sonosensitizers generate reactive oxygen species (ROS) under ultrasound activation, focusing the ultrasound energy on malignant sites located deep in tissues and causing cell apoptosis and necrosis. However, due to tumor hypoxia and the limited levels of intracellular endogenous hydrogen peroxide (H2O2 is a fundamental species for supplying oxygen via catalase activity), SDT efficacy is still insufficient. In this study, a bimetallic and multifunctional system (Fe3O4-TAPP@PVP-CaO2) was prepared by using ferrosoferric oxide (Fe3O4) as a carrier loaded with 5,10,15,20-tetrakis(4-aminophenyl), porphyrin (TAPP), that was then coated with polyvinyl pyrrolidone (PVP) and calcium peroxide (CaO2). The CaO2 layer elevated the levels of H2O2 and Ca2+ in the tumor microenvironment when exposed to intracellular acidity, providing essential elements for oxygen generation. Intracellular hypoxia was alleviated via the catalase-like activity of Fe3O4 inducing calcium overload. Under ultrasonic irradiation, SDT generated toxic reactive oxygen species (ROS, singlet oxygen) and activated calcium influx through acoustic cavitation. Meanwhile, calcium overload therapy efficiently induced cell apoptosis at the moment of uncontrollable cellular accumulation of Ca2+. In addition, we modified the PVP on the surface to make it more stable. This study presents a bimetallic nanoplatform that can efficiently induce cancer cell death by synergistic sonodynamic-calcium overload therapy via modulation of O2/ROS/Ca2+ species, indicating its potential for multi-modality cancer therapy.
Asunto(s)
Calcio , Neoplasias , Humanos , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno , Catalasa , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Hipoxia , Oxígeno , Línea Celular Tumoral , Microambiente TumoralRESUMEN
This paper presents an extremely rare case of testicular metastasis arising from renal pelvis carcinoma. The testicle is a rare site of clinically detectable tumor metastasis, originating rarely from upper tract urothelial carcinoma (UTUC). There are only two cases concerning UTUC metastasis to the testis available in the literature. In this report, we presented a patient who developed serial testicle, lung, liver and retroperitoneal lymph node metastasis from primary urothelial carcinoma of the renal pelvis within one year after surgery and chemotherapy. In conclusion, for patients with a history of UTUC who present with testicular symptoms, clinicians should be highly alert for the possibility of malignant involvement at this site.