The Combination of Trametinib, a MEK Inhibitor, and Temsirolimus, an mTOR Inhibitor, Radiosensitizes Lung Cancer Cells.

Background/aim: We evaluated the radiosensitizing effect of the combination treatment of trametinib, a MEK inhibitor, and temsirolimus, an mTOR inhibitor, on non-small-cell lung carcinoma (NSCLC) cells.

Materials And Methods: The effects of combining trametinib and temsirolimus with radiation in NSCLC cell lines were evaluated using clonogenic survival and apoptosis assays. DNA double-strand breaks and cell cycle distribution were analyzed using flow cytometry.

Anti-tumor effect of CDK inhibitors on CDKN2A-defective squamous cell lung cancer cells.

Background: Squamous cell lung cancer (SqCLC) is a distinct histologic subtype of non-small cell lung cancer (NSCLC). Although the discovery of driver mutations and their targeted drugs has remarkably improved the treatment outcomes for lung adenocarcinoma, currently no such molecular target is clinically available for SqCLC. The CDKN2A locus at 9p21 encodes two alternatively spliced proteins, p16 (p16) and p14 (p14), which function as cell cycle inhibitors.

Cytologic features of primary monophasic synovial sarcoma of the thyroid gland.

Synovial sarcoma (SS) is a rare soft tissue tumor, commonly arising in para-articular areas of extremities, but can also present in the head and neck area. However, primary SS of the thyroid gland is an extremely rare tumor which has been reported only five times in previous English literatures. This report presents fine needle aspiration (FNA) cytology of primary monophasic SS of the thyroid gland.

Altered expression of cellular proliferation, apoptosis and the cell cycle-related genes in lung cancer cells with acquired resistance to EGFR tyrosine kinase inhibitors.

Non-small cell lung cancers harboring somatic gain-of-function mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain respond well to treatment with EGFR tyrosine kinase inhibitors (TKIs) including gefitinib and erlotinib. However, all patients who experience a marked improvement with these drugs eventually develop disease progression due to the acquisition of drug resistance. Approximately half of the cases with acquired resistance to EGFR TKIs can be accounted for by a second-site mutation in exon 20 of the EGFR kinase domain (T790M).

Fhit, a tumor suppressor protein, induces autophagy via 14-3-3τ in non-small cell lung cancer cells.

Inactivation of the fragile histidine triad (Fhit) gene has been reported in the majority of human cancers, particularly in lung cancer. The role of Fhit as a tumor suppressor gene has been well documented, and restoration of Fhit expression suppresses tumorigenicity in tumor cell lines and in mouse models by inducing apoptosis and inhibiting proliferation of tumor cells. Autophagy is a catabolic pathway, whereby cytoplasmic proteins and organelles are sequestered in vacuoles and delivered to lysosomes for degradation and recycling.

The combination of irreversible EGFR TKIs and SAHA induces apoptosis and autophagy-mediated cell death to overcome acquired resistance in EGFR T790M-mutated lung cancer.

To overcome T790M-mediated acquired resistance of lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), second generation TKIs such as BIBW2992 (afatinib) and third generation TKIs including WZ4002 have been developed. However, clinical data on their efficacy in treating T790M mutant tumors are lacking. Histone deacetylase (HDAC) inhibitors have been reported to arrest cell growth and to lead to differentiation and apoptosis of various cancer cells, both in vitro and in vivo.

Gefitinib induces cytoplasmic translocation of the CDK inhibitor p27 and its binding to a cleaved intermediate of caspase 8 in non-small cell lung cancer cells.

Background: The epidermal growth factor receptor (EGFR) represents one of the first rationally selected molecules for targeted therapy in non-small cell lung cancer (NSCLC). Gefitinib is a reversible and highly selective tyrosine kinase inhibitor that competitively blocks the binding of adenosine triphosphate to its binding site in the tyrosine kinase domain of the EGFR. It has been found that treatment with gefitinib induces cell cycle arrest and apoptosis in NSCLC cells harboring activating EGFR mutations.

Autophagy Inhibition with Monensin Enhances Cell Cycle Arrest and Apoptosis Induced by mTOR or Epidermal Growth Factor Receptor Inhibitors in Lung Cancer Cells.

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome.

Performance status during and after radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma multiforme.

For elderly patients with glioblastoma multiforme (GBM), radiotherapy plus concomitant and adjuvant temozolomide has resulted in longer survival. We investigated patient performance status, treatment-related toxicity and overall survival (OS) following treatment. Twenty patients aged 70years or older with a newly diagnosed GBM were treated with radiotherapy (60Gy in 16 patients and 40Gy in four patients) plus concomitant and adjuvant temozolomide.

Dual Inhibition of PI3K/Akt/mTOR Pathway and Role of Autophagy in Non-Small Cell Lung Cancer Cells.

Background: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects.

Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer.

Background: Epithelial-mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer.

The prognosis of anaplastic astrocytoma with radiologic necrosis mimicking glioblastoma.

Anaplastic astrocytoma (AA) sometimes shows a rapid poor course like glioblastoma. In this study, we investigated the prognosis of AA with radiologic necrosis which is the representative radiologic finding of glioblastoma. From 1995 to 2010, we operated on 26 patients who were confirmed to have AA.

Unusual radiologic findings and pathologic growth patterns on choroid plexus papillomas.

Objective: Choroid plexus papillomas (CPPs) are generally regarded as benign tumors with typical radiologic and pathologic findings. However, they sometimes have unusual findings. We have analyzed radiologic findings and pathologic growth patterns on CPPs.

Carcinosarcoma of the gallbladder: report of two cases.

Adenocarcinoma is the predominant histological type of carcinoma of the gallbladder, accounting for more than 80% of all gallbladder carcinomas. In contrast, carcinosarcoma of the gallbladder is an extremely atypical subset of gallbladder malignancies. It is characterized by the presence of both epithelial and mesenchymal components.

Immunohistochemical analysis of developmental neural antigen expression in the balloon cells of focal cortical dysplasia.

Balloon cells (BC) are the histological hallmarks of focal cortical dysplasia (FCD). Expression of the neural stem cell surface marker CD133 and other developmental markers was studied in the BC of FCD using formalin-fixed paraffin-embedded tissue from nine patients with FCD. Labeling indexes were calculated for all antibodies.

Homocysteine as a risk factor for development of microalbuminuria in type 2 diabetes.

Background: Kidney function is critical in homocysteine clearance, and plasma homocysteine level is frequently increased in patients with renal failure. On the other hand, recent studies in animals have shown that hyperhomocysteinemia induces renal injury. In this study, we determined whether hyperhomocysteinemia can be a risk factor for the development of microalbuminuria in patients with type 2 diabetes.