Biphasic function of GSK3β in gefitinib‑resistant NSCLC with or without EGFR mutations.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, are effective in the treatment of non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, the mechanism underlying acquired resistance to EGFR-TKIs remains largely unknown. Therefore, the present study generated gefitinib-resistant PC-9 (PC-9G) cells, which were revealed to be more resistant to gefitinib-induced reductions in proliferation, migration and invasion, and increases in apoptosis, and had no detectable EGFR mutations compared with the control PC-9 cell line.

Altered Wnt5a expression affects radiosensitivity of non-small cell lung cancer via the Wnt/β-catenin pathway.

It has been reported that upregulation of wingless-type protein 5a (Wnt5a) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Wnt5a expression is often upregulated in radiation-resistant NSCLC cells. However, the biological functions or molecular mechanisms of radiosensitivity in NSCLC remain unknown.

Wnt7a inhibits transformed cell proliferation while promoting migration and invasion in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) is the most important cause of lung cancer death. Wnt7a is a known tumor suppressor gene which is often downregulated in NSCLC, and restoration of Wnt7a leads to decreased NSCLC cell proliferation. However, the biological role of Wnt7a in the migration and invasion in NSCLC remains unclear.

Overexpression of Wnt7a enhances radiosensitivity of non-small-cell lung cancer via the Wnt/JNK pathway.

The Wingless-type protein 7a (Wnt7a) plays an antiproliferative role in non-small-cell lung cancer (NSCLC). Previous studies have indicated that Wnt7a expression was downregulated in radiation-resistant NSCLC cells. However, little is known about its biological functions and molecular mechanisms in radiosensitivity of NSCLC.

Comparison of the effects of nimodipine and deferoxamine on brain injury in rat with subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) may lead to brain atrophy and cognitive dysfunction. This study aimed to compare the efficacy of nimodipine and deferoxamine on these sequelae of SAH. A rat model of SAH was established by the double-hemorrhage method.

Brain structure alterations and cognitive impairment following repetitive mild head impact: An in vivo MRI and behavioral study in rat.

Mild traumatic brain injury (mTBI) or concussion is a common health issue. Several people repeatedly experience head impact milder than that causing concussion. The present study aimed to confirm the effects of such repeated impact on the brain structure and cognitive abilities.

Cerebral vasospasm and corticospinal tract injury induced by a modified rat model of subarachnoid hemorrhage.

Objective: Double-hemorrhage rat models of subarachnoid hemorrhages (SAH) are most effective at simulating delayed cerebral vasospasms (CVS). The present study modified the models to minimize additional trauma and investigated injury of the corticospinal tract (CST) using diffusion tensor imaging (DTI).

Methods: On the first day, 0.

Immunohistochemical demonstration of alteration of β-catenin during tumor metastasis by different mechanisms according to histology in lung cancer.

The protein β-catenin exhibits a dual function in cells, by acting as a major structural component of cell-cell adherens junctions and as a central signaling molecule in the Wnt signaling pathway. However, how the regulation of β-catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC) varies according to histological type remains unclear. To investigate the regulatory mechanism of β-catenin on tumor metastasis, the present study compared the expression of Wnt1, β-catenin and E-cadherin in 41 primary NSCLC tumors and their corresponding metastatic lesions by immunohistochemistry.

Multiple low doses of erythropoietin delay the proliferation of hepatocytes but promote liver function in a rat model of subtotal hepatectomy.

Purpose: The impact of various doses of erythropoietin (EPO) on liver regeneration after partial hepatectomy (PH) in different animal models is still under debate. We investigated the impact of low doses of EPO on liver regeneration in a rat model of subtotal hepatectomy.

Methods: We established a 90 % PH rat model with perioperative injections of low-dose EPO (1,000 IU/kg).

Analysis of protein-protein interaction network and functional modules on primary osteoporosis.

Background: Primary osteoporosis is an age-related disease, and the main cause of this disease is the failure of bone homeostasis. Previous studies have shown that primary osteoporosis is associated with gene mutations.To explore the functional modules of the PPI (protein-protein interaction) network of differentially expressed genes (DEGs), and the related pathways participating in primary osteoporosis.

Aberration of the Wnt signaling pathway in pulmonary fatal adenocarcinoma: a case report.

We report a case of a 58-year-old woman showed a homogeneous well-defined perihilar mass in the right upper lobe and fully surrounded by aerated parenchyma at computed tomography (CT). A right upper lobectomy with mediastinal lymph node sampling was performed. A pathologic diagnosis of well-differentiated fetal adenocarcinoma of the lung was made and staged as T2bN0M0.

Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice.

Aim: To evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment.

Methods: Hepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment.

Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosine Kinase Inhibitor Treatment.

Background: The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (EGFR) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate EGFR mutational status as determined by each method with the clinical response to EGFR tyrosine kinase inhibitors (TKIs).

Methods: Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the EGFR gene (exons 18-21).

Results: Mutations in the EGFR gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing.

Overexpression of epithelial-mesenchymal transition-related markers according to cell dedifferentiation: clinical implications as an independent predictor of poor prognosis in cholangiocarcinoma.

Although increased evidence has suggested that epithelial-mesenchymal transition has been implicated in cancer invasion and is associated with poor prognosis, its significance in cholangiocarcinoma remains unclear. We evaluated the levels of expression of epithelial-mesenchymal transition-related genes and proteins in 2 established human cholangiocarcinoma cell lines with different morphological characteristics and performed transwell cell invasion assays. Furthermore, we investigated the association between altered expression of 6 epithelial-mesenchymal transition-related proteins and clinical outcomes in human cholangiocarcinoma patients (n = 119) by immunohistochemistry using a tissue microarray approach.

Discordance between anaplastic lymphoma kinase status in primary non-small-cell lung cancers and their corresponding metastases.

Aims:   The anaplastic lymphoma kinase gene (ALK) has attracted considerable attention as a potential molecular target in non-small-cell lung cancer (NSCLC). However, it is unclear whether ALK alterations are acquired during the metastatic progression of NSCLC.

Methods And Results:   ALK status and ALK expression were evaluated in a series of 67 primary NSCLCs and their corresponding metastatic lesions using fluorescence in-situ hybridization and immunohistochemistry.

Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer.

The Akt/mammalian target of rapamycin (mTOR) pathway is up-regulated in many human cancers, and agents targeting the mTOR pathway are in various stages of clinical development and application. Expression of pAkt and mTOR was studied by immunohistochemical analysis of 574 surgically resected non-small cell lung cancer (NSCLC) specimens on a tissue microarray. The results were correlated with clinicopathological features.

High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas: correlation with histologic subtypes, EGFR/TTF-1 expressions, and clinical features.

Introduction: Epidermal growth factor receptor (EGFR) mutation has been known to be associated with adenocarcinoma with bronchioloalveolar carcinoma (BAC; lepidic) feature. This study was aimed to characterize the frequency of EGFR mutations and their association with histologic subtypes in Korean nonsmall cell lung cancer (NSCLC) patients.

Methods: Three hundred eighty-two (88 biopsies and 294 resections) NSCLC patients were investigated for EGFR mutations (exons 18-21) by polymerase chain reaction and direct sequencing method.

Detection of ALK gene rearrangement in non-small cell lung cancer: a comparison of fluorescence in situ hybridization and chromogenic in situ hybridization with correlation of ALK protein expression.

Introduction: Accurate determination of ALK rearrangement is important in lung cancer patients, especially in determining their eligibility for crizotinib therapy. Fluorescence in situ hybridization (FISH) has been regarded as the gold standard method for detecting ALK rearrangement. However, FISH requires a fluorescence microscope, and the signals are labile and rapidly fade over time.

Aberrant Wnt1/β-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery.

Introduction: The Wnt signaling pathway plays a major role in cancer development and progression. As a novel anticancer drug can be developed using inhibitors of this pathway, we investigated the clinical significance of the Wnt signaling pathway molecules in non-small cell lung cancer (NSCLC).

Methods: Immunohistochemical analysis of a tissue microarray with 262 resected NSCLC specimens was performed to study the expression and subcellular localization of Wnt1 in relation to downstream molecules, including GSK-3β, β-catenin, c-Myc, cyclin D1, and p53.

Clinical and molecular evidences of epithelial to mesenchymal transition in acquired resistance to EGFR-TKIs.

Background: Epithelial-to-mesenchymal transition (EMT), which was related with an acquired resistance to gefitinib, was found in the A549 lung cancer cell line. However, the clinical feasibility of this finding is still questionable. Here, we investigated whether EMT could be detected in a more clinically suitable situation using patient's tumor and cells with deletion mutation on exon 19 of EGFR gene.

The accuracy of frozen section diagnosis of pulmonary nodules: evaluation of inflation method during intraoperative pathology consultation with cryosection.

Introduction: Intraoperative frozen section diagnosis (FSD) is a very important pathologic examination that can determine the extent of the subsequent surgical procedure. However, FSD is especially difficult in small pulmonary nodules due to severe architectural distortion during cryosection. This study was undertaken to determine the accuracy of FSD of pulmonary nodules and to evaluate the inflation method during cryosection.

Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas: Comparison of four commercially available antibodies by immunohistochemistry and fluorescence in situ hybridization study.

Epidermal growth factor receptor (EGFR) overexpression in nonsmall cell lung carcinomas (NSCLC) is variable ranging from 19% to 89% and its prognostic value remains controversial. We tried to investigate (1) EGFR protein expression using four different antibodies, (2) the correlation between protein overexpression and EGFR gene amplification, and (3) the correlation between EGFR genetic status and clinicopathologic features in NSCLC. We examined EGFR protein expression using four different antibodies including Zymed EGFR kit (Clone 31G7), Dako EGFR pharmDx kit (Clone 2-18C9), Dako (Clone H11) and Novocastra (Clone EGFR 113) by immunohistochemical analysis.