ABSTRACT
Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.
ABSTRACT
ObjectiveTo compare the clinical efficacy of sorafenib combined with capecitabine in Hui versus Han residents with advanced hepatocellular carcinoma (HCC) in Sanya, Hainan, China. MethodsA total of 96 Hui and Han residents with advanced HCC took oral capecitabine 1500 mg/m2 twice daily for 14 days followed by a 7-day withdrawal, which was repeated at least twice; besides, sorafenib was given orally at a dose of 400 mg twice daily until tumor progression occurred. Comparison of continuous data between the two groups was made by t test, while comparison of categorical data was made by chi-square test. ResultsIn the two groups of Hui and Han patients, the rates of alpha-fetoprotein reduction were 60.9% and 40.0%, respectively (χ2=4.173, P=0.041); the rates of serum ferritin reduction were 50.0% and 30.0%, respectively (χ2=4.007, P=0.027); the rates of tumor regression were 54.3% and 34.0% as shown by CT (χ2=4.030, P=0.045); the response rates were 32.6% and 14.0%, respectively (χ2=4.697, P=0.030). Survival analysis suggested the combination of sorafenib and capecitabine had provided a significantly higher overall survival rate in Hui patients than in Han patients (P＜0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P＞0.05). ConclusionIn Sanya, a combination of sorafenib and capecitabine has better efficacy in Hui patients with advanced HCC than in Han patients, and the former have a higher overall survival rate.
ABSTRACT
0.05).Compared with non-SRHCC matched selective operation group(group),second stage hepatectomy(group C)had similar rate of complications and mortality,but the long-term survival was worse(P