The Effect of Gefitinib on B-RAF Mutant Non-small Cell Lung Cancer and Transfectants

Abstract:We previously reported one patient with squamous cell carcinoma of the lung that showed the long-term effect to gefitinib with complete response. In the present report, we examine the epidermal growth factor receptor (EGFR) and K-RAS, HER2, and B-RAF mutations in this patient to find a B-RAF exon11 mutation, resulting in a substitution of valine by phenylalanine at codon 470 (V470F) as a novel type of B-RAF mutation in human cancers. In addition, the fluorescence in situ hybridization analysis for EGFR showed the high polysomy status. B-RAF is a nonreceptor serine/threonine kinase whose kinase domain has a structure similar to other protein kinases, including EGFR members. Of interest, the B-RAF V470F mutation corresponds to a position similar to the EGFR G719X mutation located on the phosphate binding (P)-loop of EGFR that clamps ATP into the catalytic cleft. This observation suggests that gefitinib may have an anti-cancer effect on B-RAF mutant tumors. Indeed, previous reports demonstrated that H1666 cells harboring B-RAF G465V mutations showed sensitivity to gefitinib, inhibiting phosphorylation of ERK1/2. We examined the effect of gefitinib on transient transfectants of the B-RAF mutant, but no drastic inhibition of ERK1/2 phosphorylation that was one of the downstream molecules of B-RAF was induced by gefitinib.In summary, we found a novel B-RAF V470F mutation in lung squamous cell carcinoma that showed response to gefitinib. However, our in vitro investigation did not explain the response observed in this particular patient. Further investigation is necessary to elucidate the mechanism of tumor sensitivity to EGFR tyrosine kinase inhibitors

Intraluminal migration of a spacer with small bowel obstruction: a case report of rare complication

The spacer placement is a prevalent procedure to separate the surrounding normal tissues from locally recurrent rectal tumor before the application of radiotherapy. However, complications could occur due to the foreign nature of the spacer. This report describes a case of 60-year-old man who had undergone radiotherapy two years earlier for a recurrent rectal tumor and presented with small bowel obstruction. A spacer was used before radiotherapy. Radiological assessment and laparotomy revealed the presence of the spacer inside the small bowel lumen. It is possible that the spacer established contact with the intestine, elicited local inflammatory reaction that facilitated the complete penetration of the intestinal wall without causing any clinical symptoms

Existence of a Neuropathic Pain Component in Patients with Osteoarthritis of the Knee

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Data from: Worldwide core collections of tea (Camellia sinensis) based on SSR markers

Tea (Camellia sinensis (L.) O. Kuntze) is the world’s most popular beverage crop. However, to date, no core collection has been selected from worldwide germplasm resources on the basis of genotype data. In this study, we analyzed 788 tea germplasm accessions using 23 simple sequence repeat (SSR) markers. Our population structure analysis divided the germplasms into a Japanese group and an exotic group. The latter could be divided into var. sinensis and var. assamica. The genetic diversity was higher in germplasms from China, Taiwan, India, and Sri Lanka than in those from other countries, and low in germplasms from Japan. Using the number of SSR alleles as a measure of genetic diversity, we developed a core collection consisting of 192 accessions and three subcore collections with 96, 48, and 24 accessions. Although the results might be affected by marker-selection bias, the core 192 collection adequately covered the range of variation of the 788 accessions in floral morphology, and the chemical composition of first-flush leaves. These collections will be powerful tools for breeding and genetic research in tea

Cerebral infarct with idiopathic cervical internal carotid artery vasospasm: A case report and literature review

Intracranial vasospasm that results from subarachnoid hemorrhage mostly leads to cerebral infarct. On the other hand, cervical internal carotid artery (CICA) vasospasm is caused by various factors such as cervical surgery, taking ergotamine, or is of unknown origin. We report here a rare case of cerebral infarct due to repeated idiopathic bilateral CICA vasospasm, and present a review of the literature. A 38-year-old man, who had a medical history of cerebral infarcts at the ages of 27 and 35, was admitted complaining of disturbance of consciousness and aphasia. MRI and MRA revealed cerebral infarct of the left middle cerebral artery (MCA) area due to occlusion of the left cervical internal carotid artery. Cerebral angiography at 9 days after onset, we demonstrated that the right CICA was occluded, whereas the left CICA was recanalized. On the 32nd day after onset, MRA showed the bilateral CICA to be recanalized. Idiopathic CICA vasospasm should be considered as a cause of juvenile-onset cerebral infarct. Regular follow-up is therefore needed because idiopathic CICA vasospasm is prone to recurrence. Keywords: Cervical internal carotid artery vasospasm, Juvenile-onset cerebral infarct, Internal carotid artery dissection, Fibromuscular dysplasia, Rho kinase inhibito

genotype

This file contains the genotype data of 788 tea accessions used in this study