Dynamic genomic changes in methotrexate-resistant human cancer cell lines beyond DHFR amplification suggest potential new targets for preventing drug resistance.

Background: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood.

Methods: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance.

Results: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)).

Differential expression of serum proteins in rats subchronically exposed to arsenic identified by iTRAQ-based proteomic technology-14-3-3 ζ protein to serve as a potential biomarker.

Arsenic is a multi-system toxicant. However, the mechanism of arsenic toxicity is not fully clarified and few effective protein biomarkers could be used for arsenic poisoning. This study was to investigate the differentially expressed proteins in the serum of rats subchronically exposed to arsenic.

Astrocyte elevated gene-1 mediates glycolysis and tumorigenesis in colorectal carcinoma cells via AMPK signaling.

To investigate the role of AEG-1 in glycolysis and tumorigenesis, we construct myc-AEG-1 expression vector and demonstrate a novel mechanism that AEG-1 may increase the activity of AMPK by Thr172 phosphorylation. The higher expression levels of AEG-1 in colorectal carcinoma cells were found but showed significant difference in different cell lines. To study the role of AEG-1 in colorectal cells, myc-AEG-1 vector was constructed and transfected into NCM460 colonic epithelial cells.

[Overexpression of p-Stat3 and Mcl-1, and their correlation with differentiation and apoptotic resistance in esophageal squamous cell carcinoma].

Objective: To detect the expression of phosphorylated-signal transducer and activator of transcription 3 (p-Stat3) and myeloid leukemia-1 (Mcl-1) as well as their correlation, and to investigate the functional role of Stat3 and Mcl-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC).

Methods: Stat3 activity in ESCC cells was inhibited with JAK/Stat3 inhibitors (AG490 or JSI-124). Specific siRNA was used to inhibit the Stat3 expression.

Role of the calcium-sensing receptor in cardiomyocyte apoptosis via the sarcoplasmic reticulum and mitochondrial death pathway in cardiac hypertrophy and heart failure.

Aims: Alterations in calcium homeostasis in the intracellular endo/sarcoplasmic reticulum (ER/SR) and mitochondria of cardiomyocytes cause cell death via the SR and mitochondrial apoptotic pathway, contributing to ventricular dysfunction. However, the role of the calcium-sensing receptor (CaR) in cardiac hypertrophy and heart failure has not been studied. This study examined the possible involvement of CaR in the SR and mitochondrial apoptotic pathway in an experimental model of heart failure.

Overexpression of focal adhesion kinase correlates with increased lymph node metastasis and poor prognosis in non-small-cell lung cancer.

Background: The aim of this study was to investigate whether focal adhesion kinase (FAK) overexpression correlates with lymph node metastases and prognosis.

Methods: The protein expression of FAK was investigated in 153 paraffin-embedded tissues by immunohistochemical analysis and then correlated with various clinicopathologic parameters. FAK mRNA level was detected with quantitative RT-PCR in 57 NSCLC frozen tissues and 20 normal matched tissues.

Characterization of gene rearrangements resulted from genomic structural aberrations in human esophageal squamous cell carcinoma KYSE150 cells.

Chromosomal rearrangements and involved genes have been reported to play important roles in the development and progression of human malignancies. But the gene rearrangements in esophageal squamous cell carcinoma (ESCC) remain to be identified. In the present study, array-based comparative genomic hybridization (array-CGH) was performed on the ESCC cell line KYSE150.

The Raf-1 inhibitor GW5074 and the ERK1/2 pathway inhibitor U0126 ameliorate PC12 cells apoptosis induced by 6-hydroxydopamine.

6-Hydroxydopamine (6-OHDA) is a widely used dopaminergic neurotoxin that leads to cell apoptosis in vivo and in vitro, and is a widely accepted experimental model of neurodegeneration in Parkinson's disease. However, the molecular mechanisms responsible for 6-OHDA-induced cell apoptosis are unclear. We found that the treatment of PC12 cells with 6-OHDA resulted in a significant decrease in cell viability and elevated apoptosis as detected by MTT assay, Hoechst 33258 staining, and flow cytometry.

Characterization of genetic rearrangements in esophageal squamous carcinoma cell lines by a combination of M-FISH and array-CGH: further confirmation of some split genomic regions in primary tumors.

Background: Chromosomal and genomic aberrations are common features of human cancers. However, chromosomal numerical and structural aberrations, breakpoints and disrupted genes have yet to be identified in esophageal squamous cell carcinoma (ESCC).

Methods: Using multiplex-fluorescence in situ hybridization (M-FISH) and oligo array-based comparative hybridization (array-CGH), we identified aberrations and breakpoints in six ESCC cell lines.

Ten SNPs of PAX6, Lumican, and MYOC genes are not associated with high myopia in Han Chinese.

Purpose: To investigate whether the PAX6, Lumican, and MYOC genes are related to high myopia in Han Chinese since the association between these genes and high myopia is unclear in this patient population.

Methods: Peripheral venous blood samples were collected for DNA extraction from 220 subjects with high myopia (refractive error ≤-10.00 D) vs.

Genetic polymorphisms in DNA repair genes OGG1, APE1, XRCC1, and XPD and the risk of age-related cataract.

Purpose: To analyze the association of the polymorphisms in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP endonuclease-1 (APE1) genes in the base excision repair pathway and xeroderma pigmentosum complementation group D (XPD) in the nucleotide excision repair pathway with the risk of cataract in a Chinese population.

Design: Case-control study.

Participants: Subjects with cataract (n = 415) or no cataract (n = 386) in the Age Related Eye Disease Ancillary Study.

Calcium overload induces C6 rat glioma cell apoptosis in sonodynamic therapy.

Purpose: Our aim was to study calcium overload-induced apoptosis and its relation to reactive oxygen species (ROS) in rat C6 glioma cells after sonodynamic treatment (SDT).

Materials And Methods: Hematoporphyrin monomethyl ether (HMME) was used as the sonosensitizer. The concentration of intracellular Ca(2+) ([Ca(2+)](i)) was measured by fluorometry.

Comparison of the antiangiogenic activity of modified RGDRGD-endostatin to endostatin delivered by gene transfer in vivo rabbit neovascularization model.

Purpose: Endostatin plays an important role in inhibiting corneal neovascularization (CNV). The aim of this study was to evaluate the antiangiogenic activities of lipid-mediated subconjunctival injection of the modified RGDRGD (arginine- glycin- aspartic- arginine- glycin- aspartic- endostatin gene in a rabbit model of neovascularization in vivo.

Methods: A modified human endostatin gene containing an RGDRGD motif was obtained by rapid site-directed mutagenesis.

Downregulated expression of inhibitor of growth 4 (ING4) in advanced colorectal cancers: a non-randomized experimental study.

Colorectal cancer has a high cure rate if it can be detected early. Identifying and understanding the genes involved may enable early diagnosis and reduce mortality. The aim of our study was to investigate the correlation between the expression of ING4 and the pathological features in patients with colorectal cancer.

Cdk5 mediates vimentin Ser56 phosphorylation during GTP-induced secretion by neutrophils.

Secretion by neutrophils contributes to acute inflammation following injury or infection. Vimentin has been shown to be important for secretion by neutrophils but little is known about its dynamics during secretion, which is regulated by cyclin-dependent kinase 5 (Cdk5). In this study, we sought to examine the vimentin dynamics and its potential regulation by Cdk5 during neutrophil secretion.

Inhibitory effect of biopolymer materials on scar formation following trabeculectomy.

Aim: To investigate the inhibitory effects of amniotic membrane, polylactic acid membrane and chitosan membrane on scar formation following trabeculectomy.

Methods: A total of 24 New Zealand white rabbits (48 eyes) were randomly divided into 4 groups: amniotic membrane group, polylactic acid membrane group, chitosan membrane group, and control group, with 6 rabbits (12 eyes) in each group. The left eyes underwent routine trabeculectomy, and the right eyes were considered as controls.

[Inhibitory effect of transforming growth factor-β(1) on oral squamous cell carcinoma brain metastasis Tb cell line].

Objective: To investigate the inhibitory effect of transforming growth factor (TGF)-β₁ on oral squamous cell carcinoma (OSCC) Tb cell line.

Methods: Cell counting method was used to examine the inhibitory effect of TGF-β₁ on Tb cell and flow cytometry (FCM) assay performed to measure the changes of cell cycle. Superarray was used to screen the changing expression of genes in TGF-β₁/Smads signaling pathway.

Down-regulation of ING4 is associated with initiation and progression of lung cancer.

Aims: Tumour suppressor ING4 is one of ING family genes, which are involved in cell cycle arrest, gene transcription regulation, DNA repair and apoptosis. ING4 inhibition has been reported in various tumours, including gliomas, breast tumours, and stomach adenocarcinoma. The aim was to evaluate ING4 expression in lung cancers.

Anti-apoptotic effects of a calpain inhibitor on cardiomyocytes in a canine rapid atrial fibrillation model.

Purpose: This study was designed to evaluate the effects of a calpain inhibitor on cardiac muscle apoptosis in rapid pacing canine atrial fibrillation (AF) models.

Methods: Twenty one dogs were divided into three groups: a sham operation group, a control AF group and a calpain inhibitor group. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute.

[Gene mapping and mutation detection in a family with congenital nuclear cataract].

Objective: To map and detect the gene responsible for congenital nuclear cataract in a Chinese family.

Methods: Genomic DNA was extracted from the peripheral blood samples of members of the pedigree. Gene scan was performed using approximately 400 microsatellite markers spaced at about 10 cM intervals (ABI).

RUNX3 inhibits cell proliferation and induces apoptosis by TGF-beta-dependent and -independent mechanisms in human colon carcinoma cells.

Background: Genes involved in the TGF-beta signaling pathway are often altered in several types of cancers. The TGF-beta-resistant human colon cancer cell line HT-29 has inactivated TbetaRII and deficient expression of RUNX3 and Smad4, which are involved in the TGF-beta signaling pathway.

Methods: Western blot and immunocytochemistry were performed to confirm gene expression, the MTT assay to detect cell growth, flow cytometry to investigate the cell cycle and the TUNEL to detect cell apoptosis.

[Functional significance of TGF-beta1 signal transduction pathway in oral squamous cell carcinoma].

Objective: The aim of this study was to investigate the expression of transforming growth factor-beta1 (TGF-beta1) and its signaling pathway molecules in oral squamous cell carcinoma (OSCC) and analyze the association between these factors and genesis and metastasis of OSCC.

Methods: The express of TGF-beta1, TbetaRI, TbetaRII and Smad4, a pivotal downstream molecule of its signaling, in 10 normal oral mucosa tissues and 108 OSCC was detected by SP immunohistochemistry, and thier correlation with genesis and metastasis of OSCC were assessed.

Results: The expressions of TbetaRII and Smad4 were lower in the tumors (34.