Pan-cancer molecular analysis of EGFR large fragment deletion in the Asian population.

BACKGROUND: Large fragment deletion (LFD) of EGFR was associated with carcinogenesis in many types of cancers. However, the molecular features of EGFR-LFD have not been studied in the Asian cancer population. METHOD: Here we retrospectively analyzed the targeted sequencing data from a large cancer database. RESULTS: EGFR-LFD was detected at a frequency of 0.03% with EGFRvIII being the most frequently observed LFD. TERTp variants were identified in 60% of the cases. TP53 alterations (33%) were mutually exclusive with TERTp variants and coexisted with EGFR-LFD in lung cancer and colorectal cancer. EGFR amplification (67%) and chromosome 10p deletion (53%) were the most focal-level and arm-level CNV in this cohort. EGFR exon2-17 skipping was found in the tumor tissue of one patient after progressing on osimertinib. CONCLUSION: Our study provided valuable insights into the distribution and molecular characteristics of EGFR-LFD, hoping to shed light on the treatment management for EGFR-LFD carriers.

Transcutaneous Neuromodulation improved inflammation and sympathovagal ratio in patients with primary biliary ssscholangitis and inadequate response to Ursodeoxycholic acid: a pilot study.

BACKGROUND: At present, ursodeoxycholic acid (UDCA) is internationally recognized as a therapeutic drug in clinic. However, about 40% Primary Biliary Cholangitis (PBC) patients are poor responders to UDCA. It has been demonstrated that Transcutaneous Neuromodulation (TN) can be involved in gut motility, metabolism of bile acids, immune inflammation, and autonomic nerve. Therefore, this study aimed to explore the effect of TN combined with UDCA on PBC and related mechanisms. METHODS: According to inclusion and exclusion criteria, 10 healthy volunteers and 15 PBC patients were recruited to control group and TN group, respectively. PBC patients were alternately but blindly assigned to group A (TN combined with UDCA) and group B (sham-TN combined with UDCA), and a crossover design was used. The TN treatment was performed via the posterior tibial nerve and acupoint ST36 (Zusanli) 1 h twice/day for 2 weeks. T test and nonparametric test were used to analyze the data. RESULTS: 1. TN combined with UDCA improved the liver function of PBC patients shown by a significant decrease of alkaline phosphatase and gamma-glutamyltransferase (γ-GT) (P < 0.05). 2. The treatment also decreased serum IL-6 levels (P < 0.05), but not the level of Tumor Necrosis Factor-α, IL-1ß or IL-10. 3. TN combined with UDCA regulated autonomic function, enhanced vagal activity, and decreased the sympathovagal ratio assessed by the spectral analysis of heart rate variability (P < 0.05). 4. There was no change in 13 bile acids in serum or stool after TN or sham-TN. CONCLUSIONS: TN cssombined with UDCA can significantly improve the liver function of PBC patients. It is possibly via the cholinergic anti-inflammatory pathway. TN might be a new non-drug therapy for PBC. Further studies are required. TRIAL REGISTRATION: The study protocol was registered in Chinese Clinical Trial Registry (number ChiCTR1800014633 ) on 25 January 2018.

A case series study of hypopituitarism in older patients with and without gastrointestinal symptoms.

OBJECTIVES: Some older individuals who present with gastrointestinal symptoms as their chief complaint were ultimately diagnosed with hypopituitarism instead of gastrointestinal diseases. The aim of this study was to find the characteristics of biochemical indicators in these patients so as to reduce early misdiagnosis. METHODS: We conducted a retrospective review of 45 patients with hypopituitarism who were at least 60 years of age. Two groups were included: group of hypopituitarism patients with gastrointestinal symptoms (Group G) included 23 patients with gastrointestinal symptoms and group of hypopituitarism patients without gastrointestinal symptoms (Group N) included 22 patients without these symptoms. In Group G, we investigated the prevalence of different gastrointestinal symptoms, the response of these symptoms to treatment, the occurrence of electrolyte disorders, and target gland dysfunction. Then, we compared the electrolyte and target gland function indices between the two groups. RESULTS: Nausea and vomiting were the most common complaints, accounting for 69.57% of the gastrointestinal symptoms in Group G. Hyponatremia was the most common electrolyte disorder, occurring in 72.86% (n = 18) of patients in Group G. Hypoadrenalism and hypothyroidism were reported by 69.57% and 60.78% of patients, respectively, in Group G. None of the gastrointestinal symptoms were relieved by 4 weeks of treatment with antacid and motility drugs. As mentioned, 18 patients also experienced refractory hyponatremia during early treatment including regular sodium supplements; however, their gastrointestinal symptoms and hyponatremia improved after only a week of treatment for hypopituitarism. Regarding the biochemical indicators, only serum sodium and cortisol in Group G were statistically lower compared with those in Group N (P < .05). CONCLUSION: Nausea and vomiting were the most common gastrointestinal symptoms in older patients with hypopituitarism, which were associated with lower serum sodium and cortisol. In addition, we hope to share the research to our gastroenterologists that serum sodium and cortisol should be tested when meeting elder patients with unexplained gastrointestinal symptoms.

Sinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression.

Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance.