As a novel tyrosine kinase inhibitor (TKI), pyrotinib can irreversibly block dual pan-ErbB receptors and has been used in the treatment of advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, there are limited data on the use of pyrotinib in early breast cancer. Therefore, the present meta-analysis was conducted to evaluate the safety and efficacy of pyrotinib in the neoadjuvant setting for patients with early-stage or locally advanced HER2-positive breast cancer. Online databases (Pubmed, Web of Science, Embase and Cochrane Library) were comprehensively searched for eligible prospective clinical trials on August 17, 2023. The primary endpoint was the treatment-related adverse events (TRAEs), and the secondary endpoint was pathological complete response (pCR) rate. In total, seven trials with a total enrolment of 407 patients were included. A total of seven studies evaluated pyrotinib in combination with trastuzumab and chemotherapy in the neoadjuvant setting. The median age ranged from 47-50 years. The most common TRAEs were diarrhea [98% of patients; 95% confidence interval (CI): 92-100%], followed by anemia (71%; 95% CI: 55-89%), vomiting (69%; 95% CI: 55-82%), and leucopenia (66%; 95% CI: 35-91%). No treatment-related deaths occurred. The pooled pCR rate was 57% (95% CI: 47-68%). It was concluded that pyrotinib-containing neoadjuvant therapy could be an effective treatment strategy in patients with early-stage or locally advanced HER2-positive breast cancer; however, the management of adverse events should be a key consideration. The management of adverse events should be paid great attention to, during pyrotinib therapy, although pyrotinib-contained neoadjuvant therapy could be an effective treatment for patients with early-stage or locally advanced HER2-positive breast cancer. Head-to-head randomized clinical trials are warranted to further confirm the benefits and risks associated with pyrotinib therapy in patients with breast cancer.

As the most aggressive tumor, TNM staging does not accurately identify patients with pancreatic cancer who are sensitive to therapy. This study aimed to identify associated risk factors and develop a nomogram to predict survival in pancreatic cancer surgery patients and to select the most appropriate comprehensive treatment regimen. First, the survival difference between radiotherapy and no radiotherapy was calculated based on propensity score matching (PSM). Cox regression was conducted to select the predictors of overall survival (OS). The model was constructed using seven variables: histologic type, grade, T stage, N stage, stage, chemotherapy and radiotherapy. All patients were classified into high- or low-risk groups based on the nomogram. The nomogram model for OS was established and showed good calibration and acceptable discrimination (C-index 0.721). Receiver operating characteristic curve (ROC) and DCA curves showed that nomograms had better predictive performance than TNM stage. Patients were divided into low-risk and high-risk groups according to nomogram scores. Radiotherapy is recommended for high-risk patients but not for low-risk patients. We have established a well-performing nomogram to effectively predict the prognosis of pancreatic cancer patients underlying surgery. The web version of the nomogram https://rockeric.shinyapps.io/DynNomapp/ may contribute to treatment optimization in clinical practice.

Objective Xiaoaiping(XAP)is a traditional Chinese medicine that is a commonly used as an anticancer drug in clinical practice owing to its high efficiency and low toxicity.Specifically,XAP can effectively inhibit the growth of hepatocellular carcinoma(HCC).Alpha-fetoprotein(AFP)is a key HCC diagnostic marker and is closely related to certain malignant cytological behaviors of HCC.However,whether AFP expression and XAP treatment are related to the invasion and metastasis of HCC remains unclear.In the present study,we aimed to evaluate the effects and underlying mechanism of XAP on the invasion and metastasis of HCC..Methods Using a cell scratch assay,Transwell technology,and western blotting we detected the different invasion and metastatic abilities of Hep3B cells in XAP treatment and blank control groups.This allowed comparison of the invasion and metastatic abilities of Hep3B cells with differing levels of AFP expression.AFP mRNA sequencing technology was used to analyze the mechanism of tumor invasion and metastasis associated with AFP and XAP treatment.Results Cell invasion and metastasis abilities in the XAP group were significantly lower than those in the control group(P<0.05).Additionally,compared to the control group,the expression of AFP significantly decreased after XAP treatment(P<0.05).The ability of Hep3B cells to invade and metastasize was promoted when AFP expression was up-regulated,whereas it was inhibited when AFP was silenced.XAP injection and AFP regulate the invasion and metastatic ability of HCC by affecting matrix metalloproteinases(MMPs).Conclusion XAP injection inhibits the invasion and metastatic ability of HCC by influencing the expression of AFP;additionally,this inhibition of AFP is achieved by affecting MMPs.

Objective The objective of this study was to investigate the inhibitory effects of sorafenib and regorafenib on the growth of hepatocellular carcinoma (HCC) using a subcutaneous transplantation tumor model in nude mice and exploring the effects of sorafenib and regorafenib on the expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, and HIF-1β in HCC tissues collected from HCC-transplanted nude mice. Methods HepG2 cells were inoculated intradermally into nude mice. The mice were randomly assigned to either sorafenib treatment (100 mg/kg), regorafenib treatment (20 mg/kg), or solvent control group (dimethylsulfoxide) (n = 8 per group) and received once-daily treatment for 14 days. The tumor volumes were recorded every 3 days after the initiation of treatment. The expression levels of HIF-1α, HIF-1β, HIF-2α, and SART1 in the HCC tissues were examined via quantitative real-time PCR (qRT-PCR) analysis and Western blotting. Results The tumors in the sorafenib and regorafenib treatment groups grew slower and smaller than did the tumors in the solvent control group. qPCR analysis and western blotting demonstrated that the mRNA and protein expressions of HIF-1α and HIF-1β were down-regulated. The expression of HIF-2α and SART1 was up-regulated in the sorafenib treatment group (P < 0.05); meanwhile, the expression of HIF-1α and HIF-1β was up-regulated, and that of HIF-2α and SART1 was down-regulated in the regorafenib treatment group (P < 0.05). Conclusion The expression of hypoxia-associated factor is up-regulated by sorafenib and down-regulated by regorafenib, which may induce the different effects of sorafenib on the expression of HIFs.

Objective This study aims to gain further the potential mechanisms of HIF-2α in tumor progression and tumorigenesis. Methods Mined The Cancer Genome Atlas（TCGA） dataset. In total, 421 participants were enrolled in the TCGAHepatocellular Carcinoma（HCC） study, comprising 371 patients with cancer and 50 healthy controls. From the 371 tumor samples, three samples containing the missense mutation of the HIF-2α gene were compared with 368 wild-type samples to identify differentially expressed genes（DEGs）. Results After filtering, univariate Cox regression and multivariate Cox regression analyses showed that the differentially expressed genes（DEGs） progestagen-associated endometrial protein（PAEP） PNLIPRP2, MIR147B, and pregnancy zone protein（PZP） were significantly correlated with the survival times of patients with HCC. Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery（DAVID） v6.8 database to detect the functional annotation of these four DEGs as well as hub genes obtained from protein-protein interaction（PPI） network analysis using the STRING v10 database. Our analysis focused on the PAEP and PZP genes, whose protein expressions were downregulated in samples with HIF-2α missense mutation. The hub genes of PAEP and PZP were identified using PPI network analysis. Subsequent Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway analysis revealed that PAEP and its hub genes were highly enriched in the TGF-β pathway, which is consistent with the analysis of PZP. Conclusion Our study proved that the missense mutation of HIF-2α induces the upregulation of PAEP, which is positively related to the poor prognosis of patients with HCC, as it may upregulate the TGF-β pathway. In contrast, PZP downregulation showed the opposite phenomenon, as it may downregulate the TGF-β pathway.

Objective Antibodies targeting programmed cell death protein 1 （PD-1） have become the mainstay of treatment for chemotherapy-refractory gastric cancer,characterized by high levels of programmed cell death ligand-1 （PDL-1） expression.However,the routine clinical implementation of PDL-1 testing is currently limited by the lack of robust detection methods.In this regard,the role of plasma γ-glutamyl transpeptidase （GGT）,an N-terminal nucleophilic hydrolase,as an independent predictor of the efficacy of anti-PD-1 therapy remains unknown.In this study,we aimed to assessed the prognostic role of changes in plasma GGT levels （6 weeks vs.baseline） in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy.Methods We retrospectively analyzed data from 57 patients with gastric cancer treated with anti-PD-1 antibodies （camrelizumab,sintilimab,nivolumab,tislelizumab,and toripalimab） at the Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,from July 2018 to February 2021.Results We found that after 6 weeks of treatment,there were significant differences between responders and non-responders with respect to plasma GGT levels （P ＜ 0.001）.Multivariate logistic regression analysis revealed that the continuous value of the 6-week difference in GGT levels （OR=1.437,95% CI=1.116–1.849,P=0.005） and 6-week difference in GGT ≥ 0 or ＜ 0 （OR=53.675,95% CI=6.379–451.669,P ＜ 0.001） were independent predictors of disease control.Survival analysis indicated that a reduction in plasma GGT6 levels during treatment was significantly associated with a favorable progression-free survival （PFS） and overall survival （P ＜ 0.001）.Consistently,univariate and multivariate Cox regression analyses revealed that a reduction in plasma GGT6 levels during treatment was an independent predictor of PFS （HR=1.033,95% CI=1.013–1.053,P=0.001）.Conclusion Alterations in plasma GGT levels during treatment can be used as a predictor of disease progression and survival in patients with advanced gastric cancer undergoing treatment with anti-PD-1 antibodies.

ARNTL2（aryl hydrocarbon receptor nuclear translocator-like）基因属于bHLH-PAS（basic helix-loophelix-PER-ARNT-SIM）结构域转录因子家族，是控制昼夜节律的时钟基因之一。ARNTL2在多种肿瘤中高表达，并与肿瘤的进展、侵袭转移等恶性生物学行为密切相关。同时，ARNTL2的表达与肿瘤的发生和预后临床病理特征有关，有望成为肿瘤的预后指标和特异性肿瘤治疗标志物。本文分析了ARNTL2在不同肿瘤发生发展过程中的作用及潜在的机制，为临床早期发现、有效治疗肿瘤和改善病人预后提供新的理论依据。