HER2+ mCRC patients with exon 20 R784G substitution mutation do not respond to the cetuximab therapy

The human epidermal growth factor 2 (HER2) gene undergoes various mutations that could alter its activity or respond to the antibody therapies. Cetuximab, a known anti-EGFR monoclonal antibody (mAB), is widely administered in metastatic colorectal cancer (mCRC) cases. Here we identified mCRC patients who did not respond to cetuximab (500 mg/m², q2w) after fluoropyrimidine/oxaliplatin regimen failure. Tumor samples were examined with immunohistochemistry for protein distribution, polymerase chain reaction (PCR) sequencing for mutation detection and real-time PCR for mRNA expression pattern analysis between cetuximab sensitive and resistance patients. The conformational differences of normal and mutated protein structures were predicted by bioinformatics analysis. The 5-year survival rates of target groups were estimated using the Kaplan–Meier method. Immunohistochemistry showed that all cases had high level of HER2 protein. No K-Ras or B-Raf mutation was observed among the study population; however, cetuximab resistance patients harbored a somatic mutation R784G at the exon 20 region of HER2 coding sequence. According to bioinformatics analysis, this mutation caused a notable misfold in protein conformation. Meanwhile, survival analysis showed R784G mutated mCRC patients had shortened survival rate compared with the mCRC cases with wild-type HER2. Collectively, these data report a new mechanism of resistance to cetuximab and might be applicable in modifying new therapeutic strategies for HER2 involved cancers.     

MiRNAs and inflammatory bowel disease: An interesting new story

Inflammatory bowel disease (IBD), as a chronic and recurrent inflammatory disorder, is caused by a dysregulated and aberrant immune response to exposed environmental factors in genetically susceptible individuals. Despite huge efforts in determining the molecular pathogenesis of IBD, an increasing worldwide incidence of IBD has been reported. MicroRNAs (miRNAs) are a set of noncoding RNA molecules that are about 22 nucleotides long, and these molecules are involved in the regulation of the gene expression. By clarifying the important role of miRNAs in a number of diseases, their role was also considered in IBD; numerous studies have been performed on this topic. In this review, we attempt to summarize a number of studies and discuss some of the recent developments in the roles of miRNAs in the pathophysiology, diagnosis, and treatment of IBD.     

Small interfering RNA–mediated gene suppression as a therapeutic intervention in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the lethal and difficult-to-cure cancers worldwide. Owing to the late diagnosis and drug resistance of malignant hepatocytes, treatment of this cancer by conventional chemotherapy agents is challenging, and researchers are seeking new alternative treatment options to overcome therapy resistance in this neoplasm. RNA interference (RNAi) is a potent and specific approach in targeting gene expression and has emerged as a novel therapeutic tool for many diseases, including cancers. Small interfering RNA (siRNA) is a type of RNAi that is produced intracellularly from exogenous synthetic oligonucleotides and can selectively knock down target gene expression in a sequence-specific manner. Various factors play roles in the initiation and progression of HCC and provide multiple candidate targets for siRNA intervention. In addition, due to the liver's unique architecture and availability of some hepatic siRNA delivery methods, this organ has received much more attention as a target tissue for such oligonucleotide action. Recent advances in designing nanoparticle systems for the in vivo delivery of siRNAs have markedly enhanced the potency of siRNA-mediated gene silencing under clinical development for HCC therapy. The utility of siRNAs as anti-HCC agents is the subject of the current review. siRNA-based gene therapies could be one of the main feasible approaches for HCC therapy in the future.     

A volatile producing endophytic Bacillus siamensis YC7012 promotes root development independent on auxin or ethylene/jasmonic acid pathway

Plant and Soil - In many mixed grass-shrub ecosystems, increased shrub biomass tends to promote overall carbon storage, but the distribution of carbon pools may be complicated by disturbances such...     

The Implication of Early Chromatin Changes in X Chromosome Inactivation

1. Download high-res image (238KB)
2. Download full-size image

     

Synergistic effect of coronatine and sorbitol on artemisinin production in cell suspension culture of Artemisia annua L. cv. Anamed

Plant Cell, Tissue and Organ Culture (PCTOC) - Artemisinin is an efficient anti-malarial drug and it possesses biological activity against a wide range of cancers. The combined application of two...     

Radioprotective effect of olanzapine as an anti-psychotic drug against genotoxicity and apoptosis induced by ionizing radiation on human lymphocytes

Molecular Biology Reports - Olanzapine (OLA), is prescribed as an anti-psychotic medicine in schizophrenia patients. In this study, the protective effect of OLA against genotoxicity and...     

Resolving the pathogenicity factors of a novel opportunistic fungus Schizophyllum commune at molecular level

Molecular Biology Reports - Schizophyllum commune is a well-known mushroom forming fungi which is an edible one due to its nutritive value. It exhibits a special wood degrading mechanism to grow in...     

Insecticidal effect of plant extracts on common pistachio psylla,Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Aphalaridae)

The common pistachio psylla, Agonoscena pistaciae (Hemiptera: Aphalaridae) is one of the most detrimental pests to pistachio trees. Nowadays various pesticides are used to control the common pistachio psylla, but extensive pesticide spraying against this pest over a period of several years has overpowered its natural enemies. The plant’s byproducts come as an alternative ecologically more compatible in substitution to the synthetic insecticides. This work aims to evaluate the insecticidal potential of herbal extracts of fruit peels of Citrus sinensis and Citrus reticulata, seeds of C. sinensis and Rubia tinctorum, and leaves of Lawsonia inermis against common pistachio psylla. Five concentration 40, 47, 56, 67 and 80 µl/ml, of these plant extracts were sprayed on the fifth instar nymphs of common pistachio psylla by Potter Spray Tower under laboratory conditions (26?±?2?°C, 60–70% RH and a photoperiod of 16L: 8D h). Results showed significant differences among the treatments of the plant extracts and between the concentrations. The LC₅₀ values of C. sinensis peels, C. reticulata peels, C. sinensis seeds, R. tinctorum seeds and L. inermis leaves were 62.04, 38.84, 43.60, 59.01 and 33.99 µl/ml, respectively. Also, all extracts showed the greatest mortality effect in 80 µl/ml concentration. According to these results, these plant extracts may use as herbal pesticides chemical control programme of common pistachio psylla.