Screening of Anti-EGFR Components from Aconitum Soongaricum Stapf. in Xinjiang Province Based on Cell Membrane Chromatography / 中国药师

Objective:To screen anti-EGFR components from Aconitum soongaricum Stapf. and investigate their inhibitory effect on HEK293 cells and EGFR/HEK293 high expression cell lines. Methods:A two-dimensional online system (EGFR/CMC-HPLC-MS) was built to screen anti-EGFR active compounds from Aconitum soongaricum Stapf.;molecular docking assay was performed to determine the binding affinity of the components to EGFR;MTT was used to confirm the inhibition effect of the screened compounds on HEK293 cells and EGFR/HEK293 high expression cell lines.Results:The screening results showed that aconitine,12-epi-napellin and songorine were the active components acting on EGFR like gefitinib; molecular docking assay showed the targeting components acting on EGFR in the similar manner with gefitinib used as a positive control drug; MTT assay confirmed the screened components had inhibitory effects on HEK293 cells and EGFR/HEK293 high expression cell lines in a dose-dependent manner within the dose range of 0.4- 50.0 μmol·L-1. Conclusion:The screening results are apparently consistent with the pharmacological effect. The online EGFR/CMC-HPLC-MS method has a good application prospect in the rapid screening of the active compounds in the complex system of traditional Chinese medicines,and fully demonstrates such advantages of cell membrane chromatography as simple and rapid with high efficiency.

Caracteres clínico-patológicos y perfil genético en el carcinoma colorrectal / Clinical-pathological features and gene profile in colorectal cancer

El cáncer colorrectal es el tercer cáncer más frecuente en hombres y el segundo más frecuente en mujeres, con una incidencia mundial aproximada de 1.2 millones de casos nuevos por año. Nuestro objetivo primario fue estudiar la relación existente entre las características clínico-histológicas en individuos con cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS (7 mutaciones validadas), con el fin de hallar un marcador histopatológico para los tumores mutados. El objetivo secundario fue determinar cuántos pacientes tenían mutaciones adicionales en los codones 15 y 61 del gen KRAS y 600 del gen BRAF que podrían modificar el fenotipo tumoral. Fueron seleccionados 60 individuos con cáncer colorrectal (30 wild-type y 30 con mutaciones validadas en los codones 12 y 13 del gen KRAS). Se amplificaron y secuenciaron del gen KRAS los exones 2 y 3, y del gen BRAF el exón 15. La información recolectada se examinó mediante un análisis descriptivo, análisis univariado y/o análisis multivariado, según correspondiese. En conclusión, no se encontró relación entre las características clínico-histológicas de los tumores de individuos con diagnóstico de cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS. No hallamos un marcador histopatológico para los tumores mutados. En pacientes con adenocarcinomas colorrectales avanzados y KRAS wild-type resulta de interés considerar el estudio del codón 600 del gen BRAF.

Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.

Impact of KRAS Mutation Status on Outcomes in Metastatic Colon Cancer Patients without Anti-Epidermal Growth Factor Receptor Therapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Activating mutation of the KRAS oncogene is an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, KRAS mutation as a prognostic factor of survival outcome remains controversial in CRC, independent of anti-EGFR therapies. MATERIALS AND METHODS: We conducted a retrospective analysis of 103 CRC patients who were available for evaluation of KRAS mutation status. None of the patients analyzed had received anti-EGFR therapies. The role of KRAS mutation status was evaluated as a predictive factor for oxaliplatin or irinotecan and as a prognostic factor in CRC patients who did not receive anti-EGFR therapies. RESULTS: Mutations in KRAS were observed in 48.5% of patients. The response for oxaliplatin- (p=0.664) and irinotecan-based (p=0.255) cytotoxic chemotherapy did not differ according to the KRAS mutation status. In addition, no significant difference in progression free survival (PFS; oxaliplatin, p=0.583 and irinotecan, p=0.426) and overall survival (OS; p=0.258) was observed between the wild and mutant type of the KRAS gene. In univariate and multivariate analyses, KRAS mutations did not have a major prognostic value regarding PFS (oxaliplatin: hazard ratio, 0.892; 95% confidence interval [CI], 0.590 to 1.347; p=0.586 and irinotecan: hazard ratio, 0.831; 95% CI, 0.524 to 1.319; p=0.433) or OS (hazard ratio, 0.754; 95% CI, 0.460 to 1.236; p=0.263). In addition, anti-vascular endothelial growth factor therapies did not affect PFS to oxaliplatin or irinotecan and OS. CONCLUSION: KRAS mutation is not a prognostic marker for PFS to oxaliplatin or irinotecan and OS in CRC patients who did not receive anti-EGFR therapies.

Novel therapeutic strategies for advanced pancreatic cancer: targeting the epidermal growth factor and vascular endothelial growth factor pathways / 中国癌症杂志

The introduction of novel agents targeted to specific molecular targets of cancer cells offers more treatment options and improvement in outcome for exocrine pancreatic adenocarcinoma. Due to the limitations in the scope and scale of researches, this review of clinical studies presents the effects of administering the agents targeting the receptors or ligands of epidermal growth factor (EGF) or vascular endothelial growth factor (VEGF) to treat advanced pancreatic carcinoma. In addition, the basic knowledge on the mechanisms of therapy targeting EGFR and VEGFR were described. Among all agents, erlotinib has been approved by the U.S. Food and Drug Administration and incorporated in a number of treatment guidelines. It has been shown, in a randomized phase Ⅲ clinical trial reported by the National Cancer Institute of Canada, to extend survival when used in combination with gemcitabine;however,its use as monotherapy has not produced significant efficacy. Furthermore, results from a muiticenter randomized clinical trial has demonstrated that the combined utilization of erlotinib and bevaeimlmab, in current with gemcitabine significantly improved the progression-free survival, but has no significant effect on overall survival of patients with advanced pancreatic cancer. Other agents including cetuximab, bevaeizumab, sorafenib, sunitinib, etc. used along or in combination with chemotherapy are under active investigation.

THE THERAPEUTIC EFFECT OF MONOCLONAL ANTI EGFR ANTIBODY LEADING CHEMOTHERAPY TO HUMAN TUMOR / 肿瘤研究与临床

Objective:To explore the therapeutic effect of monoclonal anti EGFR antibody leading chemotherapy to human tumors.Methods:To prepare immunoconjugate of chemotherapy drugs with anti EGFR antibody and apply to clinic,and to observe it′s therapeutic effect and side effect. Results: This conjugated method could relief clinic symptoms and reduce side effect of tissues and organs significantly.Conclusion:Conjugates of monoclonal therapy of anti EGFR antibody and drug attached chemotherapy is a new and effective way for treatment of human tumors, and it can reduce side effect of the drugs meanwhile.

Challenges and common sense of PS≥2 patients with non-small cell lung cancer / 肿瘤研究与临床

The performance status(PS)≥2 patients with non-small cell lung cancer(NSCLC) are short of effective management.The phase Ⅱ/Ⅲ clinical trails of target therapy of anti EFGR of VEGFR have already got promise results.This article expatiates the actuality and development of the chemotherapy and novel target therapy for the PS≥2 patients with NSCLC.