Challenges and future of HER2-positive gastric cancer therapy.

Gastric cancer is the fifth most common cancer worldwide, and the treatment of advanced gastric cancer has relatively little progress. With the continuous development of molecularly targeted therapy for tumors, it has been discovered that human epidermal growth factor receptor 2 (HER2) contributes to the poor prognosis and pathogenesis of various cancers. In order to treat HER2-positive advanced gastric cancer, Trastuzumab has emerged as the first first-line targeted medication used in conjunction with chemotherapy. The consequent trastuzumab resistance has become an important issue, and various new HER2-targeted gastric cancer drugs are emerging to address this challenge. This review's primary concern is the drug mechanism of various HER2-positive gastric cancer targeted therapy and fresh techniques of detection.

Hepatocellular Carcinoma Complicated by Echinococcal Cyst: A Case Report.

Hepatocellular carcinoma (HCC), combined with hepatic hydatid disease, is a rare clinical case, having certain specificity in clinical diagnosis and treatment. We report a case of HCC combined with hepatic hydatid disease treated in our clinic to arouse the attention of clinicians to the disease. A 54-year-old female patient was admitted to the clinic on October 31, 2016 because of "Intermittent upper abdominal pain and discomfort for 1 month." Abdominal CT in the previous hospital showed liver space-occupying lesions, and hepatic hydatid disease should be considered. The patient had a history of hepatitis B virus (HBV) infection since childhood but has not received antiviral treatment. She did have a history of life in pastoral areas. Laboratory examination results were as follows: alpha-fetoprotein (AFP) 1,210 ng/ml, HBV DNA: 5.32E + 3 IU/ml. Casoni test was positive. Enhanced CT of abdomen suggestion was: malignant liver tumor, hepatic hydatid disease. Gastroscopy and colonoscopy showed no abnormalities. She underwent an operation on November 10, 2016. Segment 5, 8 of hepatic, echinococcus internal capsule, and cholecyst were all removed. She took albendazole (0.4 g/day) for 6 months and oral entecavir (0.5 mg/day) antiviral treatment for a long time after surgery. From May 2017 to October 2019, a total of 5 cycles of transarterial chemotherapy embolization (TACE) were performed. The patient underwent surgical treatment, followed by TACE, antiviral therapy, and sequential albendazole treatment. The AFP level increased significantly, but there was no obvious recurrence of HCC in imaging.

Random-forest algorithm based biomarkers in predicting prognosis in the patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) one of the most common digestive system tumors, threatens the tens of thousands of people with high morbidity and mortality world widely. The purpose of our study was to investigate the related genes of HCC and discover their potential abilities to predict the prognosis of the patients. METHODS: We obtained RNA sequencing data of HCC from The Cancer Genome Atlas (TCGA) database and performed analysis on protein coding genes. Differentially expressed genes (DEGs) were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted to discover biological functions of DEGs. Protein and protein interaction (PPI) was performed to investigate hub genes. In addition, a method of supervised machine learning, recursive feature elimination (RFE) based on random forest (RF) classifier, was used to screen for significant biomarkers. And the basic experiment was conducted by lab, we constructe a clinical patients' database, and obtained the data and results of immunohistochemistry. RESULTS: We identified five biomarkers with significantly high expression to predict survival risk of the HCC patients. These prognostic biomarkers included SPC25, NUF2, MCM2, BLM and AURKA. We also defined a risk score model with these biomarkers to identify the patients who is in high risk. In our single-center experiment, 95 pairs of clinical samples were used to explore the expression levels of NUF2 and BLM in HCC. Immunohistochemical staining results showed that NUF2 and BLM were significantly up-regulated in immunohistochemical staining. High expression levels of NUF2 and BLM indicated poor prognosis. CONCLUSION: Our investigation provided novel prognostic biomarkers and model in HCC and aimed to improve the understanding of HCC. In the results obtained, we also conducted a part of experiments to verify the theory described earlier, The experimental results did verify our theory.

Knockdown of Nedd8­conjugating enzyme UBE2M suppresses the proliferation and induces the apoptosis of intrahepatic cholangiocarcinoma cells.

As an important regulator of neddylation, neural precursor cell expressed developmentally downregulated 8 (Nedd8)­conjugating enzyme E2M (UBE2M) mediates cullin neddylation. Upregulation of the neddylation pathway is associated with tumor progression in intrahepatic cholangiocarcinoma (ICC). The present study was designed to assess the effects of Nedd8­conjugating enzyme UBE2M knockdown on intrahepatic cholangiocarcinoma cells, and to determine the potential underlying mechanisms. UBE2M and associated protein expression levels were determined via immunohistochemistry and western blotting. ICC cells were transfected with short hairpin RNA to knockdown UBE2M expression. Cell Counting Kit­8 and colony formation assays, and xenograft experiments were used to examine cell viability and colony survival in vitro, and tumor formation in vivo. Survival was evaluated using Kaplan­Meier analysis and log­rank tests. Patients with ICC presenting high expression of UBE2M exhibited worse accumulative recurrence and overall survival compared with patients with low expression. Knockdown of UBE2M expression led to a decrease in the viability and clonogenic survival of QBC939 and HUCCT1 cells, and suppressed tumor formation in vivo. UBE2M silencing caused accumulation of cullin­RING ligase substrates (chromatin­licensing and DNA replication factor 1 and origin recognition complex subunit 1), inducing DNA damage responses and apoptosis. The present findings suggested that UBE2M serves an important role in ICC progression and may present as a novel target for the treatment of ICC.

Interactional role of microRNAs and bHLH-PAS proteins in cancer (Review).

MicroRNAs (miRNAs) are recognized as an emerging class of master regulators that regulate human gene expression at the post-transcriptional level and are involved in many normal and pathological cellular processes. Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcriptional regulators that sense and respond to environmental signals (such as chemical pollutants) or to physiological signals (for instance hypoxia). In the normal state, bHLH-PAS proteins are responsible for multiple critical aspects of physiology to ensure the cell accurate homeostasis, but dysregulation of these proteins has been shown to contribute to carcinogenic events such as tumor initiation, promotion, and progression. Increasing epidemiological and experimental studies have shown that bHLH-PAS proteins regulate a panel of miRNAs, whereas some miRNAs also target bHLH-PAS proteins. The interaction between miRNAs and certain bHLH-PAS proteins [hypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AHR)] is relevant to many vital events associated with tumorigenesis. This review will summarize recent findings on the interesting and complicated underlying mechanisms that miRNAs interact with HIFs or AHR in tumors, hopefully to benefit the discovery of novel drug-interfering targets for cancer therapy.

Cholelithiasis, cholecystectomy and risk of hepatocellular carcinoma: a meta-analysis.

Available evidence of the relationship between cholelithiasis, cholecystectomy, and risk of liver cancer and hence we conducted a meta-analysis to investigate the relationships. PubMed, EMBASE, and ISI Web of Knowledge were searched to identify all published cohort studies and case-control studies that evaluated the relationships of cholelithiasis, cholecystectomy and risk of liver cancer and single-cohort studies which evaluated the incidence of liver cancer among patients who understood cholecystectomy (up to February 2013). Comprehensive meta-analysis software was used for meta-analysis. A total of 11 observational studies (six cohort studies and five case-control studies) were included in this meta-analysis. The result from meta-analysis showed that cholecystectomy (risk ratio [RR]: 1.59, 95% confidence interval [CI]: 1.01-2.51, I2=72%) and cholecystolithiasis (RR: 5.40, 95% CI: 3.69-7.89, I2=93%) was associated with more liver cancer, especially for intrahepatic cholangiocarcinoma (ICC) (cholecystectomy: RR: 3.51, 95% CI: 1.84-6.71, I2=26%; cholecystolithiasis: RR: 11.06, 95% CI: 6.99-17.52, I2=0%). The pooled standardized incidence rates (SIR) of liver cancer in patients who understood cholecystectomy showed cholecystectomy might increase the incidence of liver cancer (SIR: 1.57, 95% CI: 1.13-2.20, I2=15%). Based on the results of the meta-analysis, cholecystectomy and cholecystolithiasis seemed to be involved in the development of liver cancer, especially for ICC. However, most available studies were case-control studies and short-term cohort studies, so the future studies should more long-term cohort studies should be well-conducted to evaluate the long-term relationship.

Epidemiology, quality and reporting characteristics of systematic reviews of traditional Chinese medicine interventions published in Chinese journals.

BACKGROUND: Systematic reviews (SRs) of TCM have become increasingly popular in China and have been published in large numbers. This review provides the first examination of epidemiological characteristics of these SRs as well as compliance with the PRISMA and AMSTAR guidelines. OBJECTIVES: To examine epidemiological and reporting characteristics as well as methodological quality of SRs of TCM published in Chinese journals. METHODS: Four Chinese databases were searched (CBM, CSJD, CJFD and Wanfang Database) for SRs of TCM, from inception through Dec 2009. Data were extracted into Excel spreadsheets. The PRISMA and AMSTAR checklists were used to assess reporting characteristics and methodological quality, respectively. RESULTS: A total of 369 SRs were identified, most (97.6%) of which used the terms systematic review or meta-analysis in the title. None of the reviews had been updated. Half (49.8%) were written by clinicians and nearly half (47.7%) were reported in specialty journals. The impact factors of 45.8% of the journals published in were zero. The most commonly treated conditions were diseases of the circulatory and digestive disease. Funding sources were not reported for any reviews. Most (68.8%) reported information about quality assessment, while less than half (43.6%) reported assessing for publication bias. Statistical mistakes appeared in one-third (29.3%) of reviews and most (91.9%) did not report on conflict of interest. CONCLUSIONS: While many SRs of TCM interventions have been published in Chinese journals, the quality of these reviews is troubling. As a potential key source of information for clinicians and researchers, not only were many of these reviews incomplete, some contained mistakes or were misleading. Focusing on improving the quality of SRs of TCM, rather than continuing to publish them in great quantity, is urgently needed in order to increase the value of these studies.

[Gefitinib for non-small cell lung cancer: a meta analysis].

BACKGROUND AND OBJECTIVE: Malignant grade and death rate are very high for non-small cell lung cancer, and gefitinib is a new molecule target anticancer drug. The aim of this meta analysis is to evaluate the clinical efficacy and safety of gefitinib for non-small cell lung cancer. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 8, 2010), PubMed (1966-2010.8), EMBASE (1974-2010.8), CNKI (1994-2010.8), VIP (1989-2010.8), and CMD Digital Periodicals (1998-2010.8). Two reviewers independently evaluated the quality of the included studies and extracted the data. Meta-analyses were performed by RevMan 5.0 software. RESULTS: Thirteen randomized controlled trials (RCTs) involving 6,207 patients were included. The results of meta-analyses showed that: gefitinib showed no remarkable advantage in media survival time, 1 year survival rate, complete response rate (CRR), partial response rate (PRR), stable disease (SD) when compared to Placebo, Docetaxel, Cisplatin+Docetaxel, Pemetrexed. Gifitinib could increase overall survival rate compared to Docetaxel, Cisplatin+Docetaxel (RR=1.41, 95%CI: 1.10-1.80; RR=1.93, 95%: 1.26-2.94). When compared to Placebo, Docetaxel, gifitinib could improve life quality of Total-FACT-L improve rate (RR=1.42, 95%CI: 1.16-1.74; RR=1.66, 95%CI: 1.39-1.97). The major adverse event for gifitinib were rash/acne, dry skin, diarrhea. While gifitinib showed lower hematology toxicity. CONCLUSIONS: Gifitinib shows more superiority for non-small cell lung cancer, and its clinical application is worthy to be advocated.