Isolated Superior Oblique Muscle Swelling Causing Acute Vertical Strabismus in Graves' Disease.

Purpose: To report a case of isolated superior oblique muscle swelling causing acute vertical strabismus in Graves' disease.

Case: A 26-year-old woman with a 1-month history of misalignment of the right eye and diplopia was referred to us. Her visual acuity and intraocular pressures were normal in both eyes, but eye movement tests showed clear misalignment of her right eye.

Corneal Perforation during Combination Chemotherapy including Cetuximab in a Patient with a History of Herpetic Keratitis.

Purpose: To report a case of corneal perforation, in a patient with a history of herpetic keratitis, during combination chemotherapy including cetuximab.

Case: We report the case of a 71-year-old man who was diagnosed with a hypopharyngeal carcinoma and received radiation therapy combined with cetuximab, the epidermal growth factor receptor (EGFR) inhibitor monoclonal antibody. He was referred to us because of ocular hyperemia and corneal perforation in his left eye.

Quantification of Eccentric Fixation Using Spectral-Domain Optical Coherence Tomography.

Purpose: This study aimed to evaluate the utility of optical coherence tomography (OCT) in the quantification of eccentric fixation in amblyopic patients.

Material And Methods: In this study, 14 amblyopic patients and 10 healthy volunteers were enrolled. Under non-mydriatic conditions, fixation tests were performed directly using a fixation ophthalmoscope and indirectly using spectral-domain OCT.

Neurotrophic Keratopathy after Trigeminal Nerve Block for Treatment of Postherpetic Neuralgia.

Purpose: To report a case of persistent corneal epithelial defect that had occurred after a trigeminal nerve block.

Case Presentation: A 75-year-old female had suffered from postherpetic neuralgia for 8 years. She underwent Gasserian ganglion block surgery and noticed declining visual acuity in the right eye on the following day.

Extracellular Collagen Promotes Interleukin-1β-Induced Urokinase-Type Plasminogen Activator Production by Human Corneal Fibroblasts.

Purpose: Keratocytes maintain homeostasis of the corneal stroma through synthesis, secretion, and degradation of collagen fibrils of the extracellular matrix. Given that these cells are essentially embedded in a collagen matrix, keratocyte-collagen interactions may play a key role in regulation of the expression or activation of enzymes responsible for matrix degradation including urokinase-type plasminogen activator (uPA), plasmin, and matrix metalloproteinases (MMPs). We examined the effect of extracellular collagen on the production of uPA by corneal fibroblasts (activated keratocytes) stimulated with the proinflammatory cytokine interleukin-1β (IL-1β).

Impact of Tight Junction Protein ZO-1 and TWIST Expression on Postoperative Survival of Patients with Hepatocellular Carcinoma.

Background: Epithelial-mesenchymal transition (EMT) is considered to play a critical role in cancer progression and metastasis. However, the impact of EMT on the prognosis of hepatocellular carcinoma (HCC) is still elusive. In this study, we examined the relationship between the expression of EMT markers and recurrence-free survival (RFS) and overall survival (OS) in HCC patients after hepatic resection.

The roles of urokinase-type plasminogen activator in leukocyte infiltration and inflammatory responses in mice corneas treated with lipopolysaccharide.

Purpose: Urokinase-type plasminogen activator (u-PA) plays an important role in corneal wound healing, yet its role in corneal inflammation remains poorly understood. We investigated the role of u-PA in a murine model of lipopolysaccharide (LPS)-induced corneal inflammation.

Methods: The corneal epithelium was scraped and LPS was applied to u-PA wild-type (u-PA(+/+)) and u-PA-deficient (u-PA(-/-)) mice.

Slug increases sensitivity to tubulin-binding agents via the downregulation of βIII and βIVa-tubulin in lung cancer cells.

Transcription factor Slug/SNAI2 (snail homolog 2) plays a key role in the induction of the epithelial mesenchymal transition in cancer cells; however, whether the overexpression of Slug mediates the malignant phenotype and alters drug sensitivity in lung cancer cells remains largely unclear. We investigated Slug focusing on its biological function and involvement in drug sensitivity in lung cancer cells. Stable Slug transfectants showed typical morphological changes compared with control cells.

Slug is upregulated during wound healing and regulates cellular phenotypes in corneal epithelial cells.

Purpose: The involvement of the epithelial mesenchymal transition (EMT) in the process of corneal wound healing remains largely unclear. The purpose of the present study was to gain insight into Slug expression and corneal wound healing.

Methods: Slug expression during wound healing in the murine cornea was evaluated using fluorescence staining in vivo.

SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer.

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly posttranslational modification.

Integrated analysis of whole genome exon array and array-comparative genomic hybridization in gastric and colorectal cancer cells.

Whole genome-scale integrated analyses of exon array and array-comparative genomic hybridization are expected to enable the identification of unknown genetic features of cancer cells. Here, we evaluated this approach in 22 gastric and colorectal cancer cell lines, focusing on protein kinase genes and genes belonging to the cadherin-catenin family. Regarding alternative splicing patterns, several cancer cell lines predominantly expressed isoform 1 of protein kinase A catalytic subunit beta (PRKACB).

Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors.

Resveratrol (3, 4', 5-trihydroxy-trans-stilbene), a natural phytoalexin found in grapes and wine, has anti-proliferative activity on human-derived cancer cells. In our study, we used a conventional condensation reaction between aldehydes and amines to provide a number of aza-resveratrol (3, 4', 5-trihydroxy-trans- aza-stilbene) derivatives in an attempt to screen for compounds with resveratrol's action but with increased potency. Aza-resveratrol and its hydroxylated derivative (3, 4, 4', 5-tetrahydroxy-trans- aza-stilbene) showed a more enhanced anti-proliferative effect than resveratrol in an MCF-7 breast carcinoma cell line.

Acquired drug resistance to vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor in human vascular endothelial cells.

Acquired resistance to antiangiogenic drugs has emerged as a potentially important issue in clinical settings; however, the underlying molecular and cellular mechanism of resistance to vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) remains largely unclear. We evaluated the cellular characteristics of human umbilical vein endothelial cell (HUVEC) clones, which are resistant to VEGFR2-TKI (Ki8751) to elucidate this mechanism of resistance to antiangiogenic drugs. Resistant HUVEC clones were 10-fold more resistant to VEGFR2-TKI than the parental cells and they exhibited an almost complete absence of VEGF-mediated cellular proliferation.

Sorafenib inhibits the hepatocyte growth factor-mediated epithelial mesenchymal transition in hepatocellular carcinoma.

The epithelial mesenchymal transition (EMT) has emerged as a pivotal event in the development of the invasive and metastatic potentials of cancer progression. Sorafenib, a VEGFR inhibitor with activity against RAF kinase, is active against hepatocellular carcinoma (HCC); however, the possible involvement of sorafenib in the EMT remains unclear. Here, we examined the effect of sorafenib on the EMT.

TGF-β induces sustained upregulation of SNAI1 and SNAI2 through Smad and non-Smad pathways in a human corneal epithelial cell line.

Purpose: The aim of this study was to investigate the expression changes of epithelial mesenchymal transition (EMT)-related molecules induced by TGF-β signaling in a human corneal epithelial cell line (HCECs).

Methods: The cellular response to TGF-β was evaluated by immunoblotting, quantitative real-time RT-PCR, and immunofluorescence microscopy in HCECs.

Results: TGF-β significantly increased mRNA expression of SNAI1, SNAI2, VIM, and FN1, but not TWIST1 through Smad and non-Smad pathways in HCECs.

Antitumor activity of BIBF 1120, a triple angiokinase inhibitor, and use of VEGFR2+pTyr+ peripheral blood leukocytes as a pharmacodynamic biomarker in vivo.

Purpose: BIBF 1120 is a potent, orally available triple angiokinase inhibitor that inhibits VEGF receptors (VEGFR) 1, 2, and 3, fibroblast growth factor receptors, and platelet-derived growth factor receptors. This study examined the antitumor effects of BIBF 1120 on hepatocellular carcinoma (HCC) and attempted to identify a pharmacodynamic biomarker for use in early clinical trials.

Experimental Design: We evaluated the antitumor and antiangiogenic effects of BIBF 1120 against HCC cell line both in vitro and in vivo.

Bortezomib potentially inhibits cellular growth of vascular endothelial cells through suppression of G2/M transition.

Bortezomib, a selective 26S proteasome inhibitor, has shown clinical benefits against refractory multiple myeloma. The indirect anti-angiogenic activity of bortezomib has been widely recognized; however, the growth-inhibitory mechanism of bortezomib on vascular endothelial cells remains unclear, especially on the cell cycle. Here, we showed that bortezomib (2 nM of the IC(50) value) potently inhibited the cellular growth of human umbilical vascular endothelial cells (HUVECs) via a vascular endothelial growth factor receptor (VEGFR)-independent mechanism resulting in the induction of apoptosis.

FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth.

Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family, and it has recently been proposed to participate in gastric acid secretion and mucin gene expression in mice. However, the role of FOXQ1 in humans and especially in cancer cells remains unknown. We found that FOXQ1 mRNA is overexpressed in clinical specimens of colorectal cancer (CRC; 28-fold/colonic mucosa).

mTOR signal and hypoxia-inducible factor-1 alpha regulate CD133 expression in cancer cells.

The underlying mechanism regulating the expression of the cancer stem cell/tumor-initiating cell marker CD133/prominin-1 in cancer cells remains largely unclear, although knowledge of this mechanism would likely provide important biological information regarding cancer stem cells. Here, we found that the inhibition of mTOR signaling up-regulated CD133 expression at both the mRNA and protein levels in a CD133-overexpressing cancer cell line. This effect was canceled by a rapamycin-competitor, tacrolimus, and was not modified by conventional cytotoxic drugs.