Label-free and high-sensitive detection of Kirsten rat sarcoma viral oncogene homolog and epidermal growth factor receptor mutation using Kelvin probe force microscopy

2017 ◽  
Vol 87 ◽  
pp. 222-228 ◽  
Author(s):  
Kuewhan Jang ◽  
Jaeyeong Choi ◽  
Chanho Park ◽  
Sungsoo Na
2013 ◽  
Vol 59 (10) ◽  
pp. 1447-1456 ◽  
Author(s):  
Michael J Duffy ◽  
John Crown

BACKGROUND Companion biomarkers are biomarkers that are used in combination with specific therapies and that prospectively help predict likely response or severe toxicity. In this article we review the role of companion biomarkers in guiding treatment in patients with cancer. CONTENT In addition to the established companion biomarkers such as estrogen receptors and HER2 (human epidermal growth factor receptor 2) in breast cancer, several new companion biomarkers have become available in recent years. These include v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations for the selection of patients with advanced colorectal cancer who are unlikely to benefit from anti–epidermal growth factor receptor antibodies (cetuximab or panitumumab), epidermal growth factor receptor (EGFR) mutations for selecting patients with advanced non–small cell lung cancer (NSCLC) for treatment with tyrosine kinase inhibitors (gefitinib or erlotinib), v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations for selecting patients with advanced melanoma for treatment with anti-BRAF agents (vemurafenib and dabrafenib), and anaplastic lymphoma receptor tyrosine kinase (ALK) translocations for identifying patients with NSCLC likely to benefit from crizotinib. SUMMARY The availability of companion biomarkers should improve drug efficacy, decrease toxicity, and lead to a more individualized approach to cancer treatment.


2015 ◽  
Vol 139 (1) ◽  
pp. 14-23 ◽  
Author(s):  
Zongming Eric Chen ◽  
Fan Lin

Context Diagnosis of primary gastrointestinal and liver neoplasms is usually straightforward. Immunohistochemistry is most helpful to differentiate metastatic carcinomas with morphologic similarity and to resolve tumors of unknown origin. Recently, several new markers highly sensitive and specific for primary liver and gastrointestinal tumors have been discovered. Their potential diagnostic application has not been widely appreciated by general practicing pathologists. In addition, a new trend in immunohistochemistry application has started, focusing on assessing predictive markers (such as human epidermal growth factor receptor 2) and mutation-specific markers (v-raf murine sarcoma viral oncogene homolog B V600E) to directly guide clinical management. Practicing pathologists need to be aware of and prepared for this evolving trend. Objectives To summarize the usefulness of several recently discovered immunohistochemical markers in the study of gastrointestinal and liver tumors; to suggest the most current and effective immunohistochemical panels addressing common diagnostic challenges for these tumors; to share practical experience and useful tips for human epidermal growth factor receptor 2 testing in gastric and gastroesophageal junction adenocarcinoma and v-raf murine sarcoma viral oncogene homolog B V600E immunohistochemistry in colorectal carcinoma. Data Sources Sources include literature review, and authors' research data and practice experience. The cases illustrated are selected from the pathology archives of the Geisinger Medical Center (Danville, Pennsylvania). Conclusions Application of immunohistochemistry in gastrointestinal and liver tumors continues to evolve. New tumor-specific markers constantly emerge and help pathologists to further improve diagnostic accuracy. Assessment of predictive and prognostic markers by immunohistochemistry in routine pathologic diagnosis is a new trend and will greatly facilitate the advancement of personalized cancer therapy.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Meng Li ◽  
Li Zhang ◽  
Wei Tang ◽  
Jian-Chun Duan ◽  
Yu-Jing Jin ◽  
...  

Abstract Background Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) are the two most frequent and well-known oncogene of lung adenocarcinoma. The purpose of this study is to compare the characteristics measured with dual-energy spectral computed tomography (DESCT) in lung adenocarcinoma patients who have KRAS and EGFR gene mutations. Methods Patients with surgically resected lung adenocarcinoma (n = 72) were enrolled, including 12 patients with KRAS mutations and 60 patients with EGFR mutations. DESCT quantitative parameters, including the CT number at 70 keV, the slopes of the spectral attenuation curves (slope λ HU), normalized iodine concentration (NIC), normalized water concentration (NWC), and effective atomic number (effective Z), were analyzed. A multiple logistic regression model was applied to discriminate clinical and DESCT characteristics between the types of mutations. Results The KRAS mutation was more common in people who smoked than the EGFR mutation. Nodule type differed significantly between the KRAS and EGFR groups (P = 0.035), and all KRAS mutation adenocarcinomas were solid nodules. Most DESCT quantitative parameters differed significantly between solid nodules and subsolid nodules. CT number at 70 keV, slope λ HU, NIC, and effective Z differed significantly between the KRAS and EGFR groups (P = 0.006, 0.017, 0.013 and 0.010) with solid lung adenocarcinoma. Multivariate logistic analysis of DESCT and clinical features indicated that besides smoking history, the CT value at 70 keV (OR = 0.938, P = 0.009) was significant independent factor that could be used to differentiate KRAS and EGFR mutations in solid lung adenocarcinoma. Conclusions DESCT would be a potential tool to differentiate lung adenocarcinoma patients with a KRAS mutation from those with an EGFR mutation.


Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5893-5904 ◽  
Author(s):  
Masatomo Kusaka ◽  
Yuko Katoh-Fukui ◽  
Hidesato Ogawa ◽  
Kanako Miyabayashi ◽  
Takashi Baba ◽  
...  

The gonadal primordium first emerges as a thickening of the embryonic coelomic epithelium, which has been thought to migrate mediodorsally to form the primitive gonad. However, the early gonadal development remains poorly understood. Mice lacking the paired-like homeobox gene Emx2 display gonadal dysgenesis. Interestingly, the knockout (KO) embryonic gonads develop an unusual surface accompanied by aberrant tight junction assembly. Morphological and in vitro cell fate mapping studies showed an apparent decrease in the number of the gonadal epithelial cells migrated to mesenchymal compartment in the KO, suggesting that polarized cell division and subsequent cell migration are affected. Microarray analyses of the epithelial cells revealed significant up-regulation of Egfr in the KO, indicating that Emx2 suppresses Egfr gene expression. This genetic correlation between the two genes was reproduced with cultured M15 cells derived from mesonephric epithelial cells. Epidermal growth factor receptor signaling was recently shown to regulate tight junction assembly through sarcoma viral oncogene homolog tyrosine phosphorylation. We show through Emx2 KO analyses that sarcoma viral oncogene homolog tyrosine phosphorylation, epidermal growth factor receptor tyrosine phosphorylation, and Egfr expression are up-regulated in the embryonic gonad. Our results strongly suggest that Emx2 is required for regulation of tight junction assembly and allowing migration of the gonadal epithelia to the mesenchyme, which are possibly mediated by suppression of Egfr expression.


Sign in / Sign up

Export Citation Format

Share Document