Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

The incidence of pancreatic cancer has been obviously increasing in China over the last decade, however, those patients with advanced pancreatic cancer are suffering from limited treatment strategies and poor clinical prognosis. Chemotherapy improved the overall survival of cases with advanced pancreatic cancer to 8-11 months, and erlotinib brought an additional survival of only 10 days. In this article, the recent progresses on advanced pancreatic cancer were reviewed at the genetic and molecular sub-typing levels, and corresponding clinical transformation studies summarized, some of which have showed encouraging clinical prospects but others have failed due to the complexity of pancreatic cancer. By learning from experiences in the successful therapeutic strategies and lessons from the failed cases, we hope to optimize future clinical research from bedside to bench.

【Objective】 To investigate the central sedative and hypnotic effects and mechanisms of Shumian Capsule. 【Methods】 The blank control group, the positive drug diazepam group, and the low-, medium-, and high-dose groups of Shumian Capsule were designed in the experiments. Male Kunming mice were administered orally by gavage. We conducted the experiment of mouse autonomous activity, and assessed supra- and sub-threshold dose sleep with pentobarbital sodium, respectively. The levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in the brain tissue of the mice were measured by enzyme-linked immunosorbent assay (ELISA) or colorimetric method. Male SD rats were injected intraperitoneally with p-chlorophenyl alanine [PCPA, 350 mg/(kg·d)] to establish an insomnia rat model, after which rats were continuously administered intragastrically for 7 days. The general status and body weight of the rats were observed. Total distance and standing times of rats were measured by open field test. Western blotting and immunohistochemistry assays were used to evaluate the protein expression of 5-HT1A receptor (5-HT1AR) in the rat hippocampus. 【Results】 Compared with the blank control group, the three dose groups of Shumian Capsule [1.6, 3.2, 6.4 mg/(kg·d)] for 14 consecutive days had significantly reduced the number of spontaneous activities and standing times in the mice (P<0.01). The high dose significantly prolonged the sleep duration of the mice induced by the supra-threshold dose of pentobarbital sodium (P<0.01). Compared with the blank control group, each dose group of Shumian Capsule had an increased GABA level in the mouse brain tissue in a dose-dependent manner (P<0.05); the medium- and high-dose groups had significantly reduced Glu levels in the hippocampus (P<0.05), while the high-dose group had significantly reduced Glu level in the cortex (P<0.05). In insomnia model rats, their activity was sluggish; their circadian activity rhythm disappeared; the hair became hard, rough and dull, with severe hair loss; and their weight reduced. After 7 consecutive days of the drug administration, the rats’ mental state in each Shumian Capsule dose group was improved. Compared with the blank control group, the rats’ body weight gains were significantly reduced after intraperitoneal injection of PCPA (P<0.01). Compared with the model group, each rat group of Shumian capsule treatment had significantly increased body weight gains (P<0.01). Compared with the blank control group, the distance of the rats in the model group increased in the open field test, and the expression level of 5-HT1AR protein in the hippocampus decreased. However, the distance of rats in diazepam group and each dose group of Shumian Capsule was significantly reduced (P<0.01), and the expression level of 5-HT1AR protein in the hippocampus of the high- and medium-dose groups of Shumian Capsule and diazepam group increased significantly (P<0.01). 【Conclusion】 Shumian Capsule has obvious effects of sedation, hypnosis and insomnia improvement, and its underlying mechanisms may be related to the increased GABA and decreased Glu contents in brain tissues, as well as up-regulated 5-HT1AR protein expression in the hippocampus.