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.
Background:Little is known about the association between venous thromboembolism (VTE) and tumors. In this study, we identified the clinical features of patients with liver cancer who presented with at least 1 VTE episode.Methods:This was a retrospective case-control study of a single-institution database with univariate and multivariate analyses using χ2 and Fisher exact tests. Statistical significance was set at P<0.05. Results:The overall incidence of VTE in the patients with liver cancer was 1.2%. More than half (53.8%) of the 13 patients with liver cancer and venous thrombosis died within 2 months. The thrombus in 12 patients (92.3%) was located within the deep veins, whereas the other patient (7.7%) was diagnosed with a pulmonary embolism. Of the 11 patients, 9 (69.2%) had swelling and/or pain symptoms. All 6 patients with peripherally inserted central catheters (PICCs) had thrombosis, accounting for 46.2% of all patients with liver cancer and venous thrombosis. Compared with the controls, liver cancer patients with PICC tubes, thrombosis-related symptoms such as swelling and pain, traumatic stimulation such as fracture, acute respiratory distress syndrome, and interventional therapy or hemostasis drugs were prone to be diagnosed with VTE ( P<0.05). Conclusions:Liver cancer and thrombosis are rare and have poor prognoses. Liver cancer with thrombosis may be associated with PICC catheterization, traumatic stimulation, or hemostatic drugs. Patients with liver cancer and thrombosis often present with swelling and pain.
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.
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。
Aims The aim of this study was to examine the effects of Xiaoaiping on the stemness of hepatocellular carcinoma (HCC) cells in vivo and to investigate the underlying molecular mechanism. Methods A subcutaneous xenograft nude mouse model was established using Hep3B-derived HCC cells. The mice were randomly assigned to the 100 mg/kg Xiaoaiping or 100 μL/20 g normal saline (control) groups (n =3/sex/group) for daily intragastric administration for 14 days. The tumor size was closely monitored during the dosing phase. After the treatment period, the tumor tissues were weighed and harvested for mRNA and protein isolation. qPCR and Western blotting were used to evaluate the expression of cancer stemness markers (epithelial cell adhesion molecule [EpCAM], cluster of differentiation [CD13], CD90, aldehyde dehydrogenase 1 [ALDH1], CD44, and CD45), totipotency factors (sex determining region Y-box 2 [Sox2], Nanog, and octamer-binding transcription factor 4 [Oct4]), and genes involved in the Notch, Wnt/β-catenin, Hedgehog, and Hippo signaling pathways. Key Findings The tumor size and weight were significantly reduced in the nude mice treated with 100 mg/kg Xiaoaiping when compared with the controls. The Xiaoaiping effects on the stemness markers and totipotency factors included decreased expression of EpCAM, CD24, CD47, Sox2, Oct4, and sal-like protein 4 (SALL4), as well as increased expression of CD13 and ALDH1. In addition, Xiaoaiping inhibited the Hippo, Wnt, and Hedgehog signaling pathways. Conclusion Xiaoaiping significantly inhibited the growth of HCC xenograft in nude mice. These antitumor effects may be mediated by modulating the expression of multiple stemness markers and totipotency factors and inhibition of the Hippo, Wnt, and Hedgehog signaling pathways.