Humans are exposed to various chemical mixtures daily. The toxic response to a mixture of chemicals could be potentiated or suppressed. This study demonstrates that non-toxic doses of pesticides can induce cellular changes that increase cell sensitivity to other toxins or stress. Pesticide exposure is an environmental risk factor for ...

Exposure to high levels of manganese (Mn) results in a neurological condition termed manganism, which is characterized by oxidative stress, abnormal dopamine (DA) signaling, and cell death. Epidemiological evidence suggests correlations with occupational exposure to Mn and the development of the movement disorder Parkinson's disease (PD), yet the molecular determinants ...

Luteoprotective mechanisms of luteinizing hormone (LH) involved in the maintenance of bovine corpus luteum (CL) function have not been completely clarified. Since antioxidant enzymes are well documented as antiapoptotic factors in the CL of many mammals, we hypothesized that the luteoprotective action of LH is mediated by stimulating the local ...

One of the main pathological symptoms of early diabetic retinal neuropathy is retina neuronal apoptosis. In the present work we investigated the effects of indoleamine hormone melatonin, a powerful free radical scavenger, on streptozotocin-induced retina neuronal cell apoptosis in high blood glucose rat. After melatonin treatment (10 mg/kg/day), tunel detection was ...

In human, mutation of the transcription factor SATB2 causes severe defects to the palate and jaw. The expression and sequence of SATB2 is highly conserved across vertebrate species, including zebrafish. We sought to understand the regulation of satb2 using the zebrafish model system. Due to the normal expression domains of ...

ABSTRACT: BACKGROUND: Ten generations of domestication selection has caused farmed Atlantic salmon Salmo salar L. to deviate from wild salmon in a range of traits. Each year hundreds of thousands of farmed salmon escape into the wild. Thus, interbreeding between farmed escapees and wild conspecifics represents a significant threat to ...

Tubulointerstitial fibrosis (TIF) is one of the major problems in nephrology because satisfactory therapeutic strategies have not been established. Here, we demonstrate that maxacalcitol (22-oxacalcitriol (OCT)), an analog of active vitamin D, protects the kidney from TIF by suppressing the autoinduction of transforming growth factor-β1 (TGF-β1). OCT suppressed the tubular ...

Collapsin response mediator protein 4 (CRMP4) is a molecular marker for immature neurons but only limited information is available on the spatiotemporal gene expression changes of Crmp4 in the developing rodent. In the present study, the variation of CRMP4 mRNA expression in the mouse brain was investigated from postnatal day ...

Small leucine rich proteoglycans (SLRPs) are important constituents of extracellular matrix (ECM) and contribute to the production, organization and remodelling of collagen and elastin through complex biological systems. The relative expression and distribution of SLRPs in a variety of different mammalian tissues is poorly characterized. The aim of this study ...

Myxomatous degenerative mitral valve disease (MMVD) is a common heart disease in dogs. Although several morphological similarities occur between human and canine MMVD differences exist. However, in advanced stages the accumulation of proteoglycans is the main finding in both species. The extracellular matrix (ECM) in normal canine and human mitral ...

Intact p53 function is essential for responsiveness to cancer therapy. However, p53 activity is attenuated by the proto-oncoprotein Mdm2, the adenovirus protein E1B 55kD, and the p53 C-terminal domain. To confer resistance to Mdm2, E1B 55kD, and C-terminal negative regulation, we generated a p53 variant (p53VPΔ30) by deleting the N-terminal ...

Cyclooxygenase isoenzyme-2 (COX-2) and vascular endothelial growth factor (VEGF) contribute to angiogenesis and are overexpressed in various malignancies. The aim of the study was to evaluate expression, prognostic value and correlation between COX-2 and VEGF expression in esophageal adenocarcinoma (EAC). Surgical specimens of 154 patients with EAC were used to ...

Mitochondrial transcription factor A (mtTFA) is necessary for both the transcription and maintenance of mitochondrial DNA (mtDNA). The present study investigated the relationship between clinicopathological factors, prognosis and the immunohistochemical expression of mtTFA in the tumors of patients diagnosed with primary colorectal cancer (CRC). Surgical specimens from 105 colorectal patients were ...

Kaempferol has been reported to reduce the risk of ovarian cancer, but the mechanism is not completely understood. In this study, we tend to expand our understanding on how kaempferol regulates VEGF expression and angiogenesis in ovarian cancer cells. We timed VEGF secretion, and studied in-vitro angiogenesis by kaempferol treatment. ...

Epithelial-mesenchymal transition (EMT) is a process implicated in tumor invasion, metastasis, embryonic development, and wound healing. ZEB2 is a transcription factor involved in EMT that represses E-cadherin transcription. Although E-cadherin downregulation is a major event during EMT and tumor progression, E-cadherin reduction is probably not sufficient for full invasiveness. The ...

Messenger RNA decay is a critical mechanism to control the expression of many inflammation- and cancer-associated genes. These transcripts are targeted for rapid degradation through AU-rich element (ARE) motifs present in the mRNA 3' untranslated region (3'UTR). Tristetraprolin (TTP) is an RNA-binding protein that plays a significant role in regulating ...

MicroRNAs (miRNAs) are small (∼18-25 nucleotides), endogenous, noncoding RNAs that regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or the inhibition of protein translation. miRNAs are predicted to target up to one-third of all human mRNAs. Each miRNA can target hundreds of transcripts and proteins ...

The versatile-peroxidase (VP) encoded by mnp4 is one of the nine members of the manganese-peroxidase (MnP) gene family that constitutes part of the ligninolytic system of the white-rot basidiomycete Pleurotus ostreatus (oyster mushroom). VP enzymes exhibit dual activity on a wide range of substrates. As Mn(2+) supplement to P. ostreatus ...

Up-regulation of the most abundant H family human endogenous retrovirus (HERV-H), especially env-related transcripts, correlates with colon cancer. However, expression pattern of spliced non-coding transcripts of HERV-H is not clear. In this study, expression of HERV-H spliced transcripts in colon cancer was investigated by a RT-PCR strategy using primers targeting ...

The expression of EphA2 and three epithelial-mesenchymal transition-related proteins (E-cadherin, β-catenin and vimentin) was detected by immunohistochemistry in human gastric cancer and normal gastric mucosa. The expression of EphA2 and vimentin was significantly higher in gastric cancer tissues than in normal gastric mucosa tissues, and similar results were found for ...

The tumor suppressor gene hypermethylated in cancer 1 (HIC1), which encodes a transcriptional repressor, is epigenetically silenced in many human tumors. Here, we show that ectopic expression of HIC1 in the highly malignant MDA-MB-231 breast cancer cell line severely impairs cell proliferation, migration, and invasion in vitro. In parallel, infection ...

Dysregulation of microRNA metabolism has been observed in a variety of human cancers. In this study, we evaluated the expression of the enzymes of the machinery Dicer, Drosha and DGCR8, in transitional cell carcinomas (TCCs) of the urinary bladder. The expression of Dicer, Drosha and DGCR8 was analyzed using semi-quantitative ...

Particularly interesting new cysteine-histidine-rich protein (PINCH) was found to be up-regulated in the stroma of colorectal carcinomas (CRCs) in our previous studies and was involved in angiogenesis through activation of fibroblasts in extracellular matrix (ECM) in response to tumors. Here, we examined PINCH mRNA expression in colorectal cancer and investigated ...

MicroRNA (miRNA) alterations are likely to contribute to the development of pancreatic cancer and may serve as markers for the early detection of pancreatic neoplasia. To identify the miRNA alterations that arise during the development of pancreatic cancer, we determined the levels of 735 miRNAs in 34 pancreatic intraepithelial neoplasias ...

Upregulation of the proto-oncogene plasminogen activator inhibitor-1 (PAI-1) is a common hallmark of various solid tumours, but the mechanisms controlling its expression are not fully understood. We investigate microRNAs (miRNAs) regulating PAI-1 in a panel of normal bladder urothelial biopsies, superficial Ta bladder tumours and invasive T1-T4 tumours using expression ...

MUC1 is transmembrane mucin aberrantly overexpressed in various cancers. However, little is known about how MUC1 expression is associated with hypoxia, glucose metabolism, and epidermal growth factor receptor (EGFR) pathway, which are related to cancer progression. The aim of this study is to evaluate the relationship between MUC1 expression and ...

The multiple enzymatic activities and functions of transglutaminase type 2 (TG2) may be attributed to alternative TG2 molecules produced by differential splicing of TG2 mRNA. Different RNA transcripts of the human TG2 gene (TGM2) have been identified, but the expression of TG2 multiple transcripts has never been systematically addressed. We ...

PURPOSE: Pleiotrophin (PTN) is an important developmental secretory cytokine expressed in many types of cancer and involved in angiogenesis and tumor growth; however, the significance of PTN expression in colorectal cancer (CRC) has not been established. METHODS: Immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect PTN expression ...

Oncogenic mutations of ras and B-raf frequently occur in many cancer types and are critical for cell transformation and tumorigenesis. Death receptor 5 (DR5) is a cell surface pro-apoptotic death receptor for tumor necrosis factor-related apoptosis-inducing ligand and has been targeted in cancer therapy. The current study has demonstrated induction ...

Xu H-T, Li Q-C, Dai S-D, Xie X-M, Liu D, Wang E-H. The expression patterns and correlations of chibby, β-catenin, and DNA methyltransferase-1 and their clinicopathological significance in lung cancers. APMIS 2011; 119: 750-8. Chibby is an inhibitor of the Wnt pathway. The expression and correlation of chibby in lung ...

As deregulation of miRNAs and chemokine CCL20 was shown to play a role in colorectal cancer (CRC) pathogenesis, we analyzed the functional interactions of candidate miRNAs with CCL20 mRNA. After target prediction software programs indicated a role for miR-21 in CCL20 regulation, we applied the luciferase reporter assay system to ...

DNA copy number aberrations (CNA) and subsequent altered gene expression profiles (mRNA levels) are characteristic features of cancerous cells. Integrative genomic analysis aims to identify recurrent CNA that may have a potential role in cancer development, assuming that gene amplification is accompanied by overexpression, while deletions give rise to downregulation ...

Manganese superoxide dismutase (MnSOD) plays a critical role in the survival of aerobic life, and its aberrant expression has been implicated in carcinogenesis and tumor resistance to therapy. However, despite extensive studies in MnSOD regulation and its role in cancer, when and how the alteration of MnSOD expression occurs during ...

Transcription factors are proteins that regulate gene expression by modulating the synthesis of messenger RNA. Since this process is often one dominant control point in the production of many proteins, transcription factors represent the key regulators of numerous cellular functions, including proliferation, differentiation and apoptosis. Pancreatic cancer progression is characterised ...

Lamina-associated polypeptide 2 alpha (LAP2α) plays a role in maintaining nuclear structure, in nuclear assembly/disassembly, and in transcriptional regulation. Elevated LAP2α mRNA expression has been previously reported to associate with certain cancer types. The aim of this study was to investigate LAP2α expression in cervical cancer and transformed cells and ...

Recently, we have identified GSK-3 as a new therapeutic target in renal cell cancer (RCC). miR-199a could potentially downregulate GSK-3β expression. Here, we found a decreased miR-199a expression in 59% (32 of 54) of RCCs and it was correlated with higher tumor stage (p<0.05) and nuclear overexpression of GSK-3β (p<0.05). ...

BACKGROUND: Thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) RNA expression in peripheral blood was examined as a noninvasive molecular predictor of response to neoadjuvant radiochemotherapy in patients with locally advanced cancer of the esophagus. METHODS: Blood samples were drawn from 29 patients with esophageal cancer (10 squamous cell carcinomas and ...

Melatonin exerts anti-proliferative and pro-apoptotic effects in various cancer cell lines. Furthermore, there is evidence for impaired melatonin secretion in human breast and colorectal cancer. Additionally, several studies revealed a modulated expression of the melatonin receptor 1 (MT1), in human breast cancer specimens. Since melatonin binding sites were already identified ...

The aim of this study was to evaluate the diagnostic utility of lung-specific X protein (LUNX) mRNA expression in bronchial brushing specimens from patients with lung cancer. LUNX mRNA levels were assessed by performing RT-PCR on liquid-based cytology bronchial brushing specimens from patients with lung cancer (n=104) or benign lung ...

The potential benefits of drugs directly targeting the ErbB receptors for cancer therapy have led to an extensive development within this field. However, the clinical effects of ErbB receptor-targeting drugs in cancer treatment are limited due to a high frequency of resistance. It has been reported that, when inhibiting the ...

Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the transcription of protein-coding mRNAs is dependent on RNA polymerase II (Pol II). The multi-subunit transcription cofactor Mediator complex is proposed to regulate most, if not all, of the Pol II-dependent transcription. Here ...

Choroideremia (CHM) is essential for the posttranslational activation of retina-specific Rab protein. Transcript variants (a and b) of the CHM gene were detected in human cancer cells and tissues. Sequence analysis of the both variants found that isoform b is caused by an LTR12C element offering an alternative splicing site ...

The phosphatidylinositol 3-kinase/AKT (PI3K/AKT) pathway plays a critical role in human cancer. We determined the expression patterns of class I PI3K catalytic subunits and evaluated their importance in the development or progression of colorectal cancer (CRC). For this purpose, expression of class I PI3K isoforms was evaluated in 82 primary ...

An essential component of the chromatin remodeling machinery is NURF (Nucleosome Remodeling Factor), the founding member of the ISWI family of chromatin remodeling complexes. In vertebrates and invertebrates alike, NURF has many important functions in chromatin biology including regulating transcription, establishing boundary elements, and promoting higher order chromatin structure. Since ...

Syndecans are reported to have variable expression in several solid tumors and blood cancers. The cause provoking altered expression of syndecans is not known to date. We studied copy number status of syndecan-1 (SDC1) and significance of SDC1 gene product (syndecan-1, SDC1) expression in cervical cancers. Using 121 cases of ...

SUMMARY: MicroRNAs are small non-protein-coding RNAs which repress gene expression, through base pair matching with messenger RNA (mRNA). A single microRNA is capable of regulating hundreds of mRNA sequences. Only a small fraction of the over 1000 discovered microRNAs have currently known functions; many are crucial in the regulation of ...

Vascular endothelial growth factor (VEGF) has a central role in breast cancer development and progression, but the mechanisms that control its expression are poorly understood. Breast cancer tissue microarrays revealed an inverse correlation between the Forkhead transcription factor Forkhead box class O (FOXO)3a and VEGF expression. Using the lapatinib-sensitive breast ...

Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. The majority of CRCs, which develop from adenoma precursor lesions, show gain of chromosome arm 20q, where BCL2L1 is located. BCL2L1 is an important apoptosis regulating gene that codes for both an anti-apoptotic (Bcl-x(L) ) ...

Dysregulation of Maspin expression and constitutive activation of NF-κB subunits are important events in tumorigenesis of prostate cancer. Recent finding points that RelB, which contributes to the alternative NF-κB activity, interferes with carcinogenesis in the prostate. We report here, that both the classical and the alternative NF-κB activities are constitutively ...

microRNAs (miRNA) are small noncoding transcripts that play an important role in carcinogenesis. miRNA expression profiles have been shown to discriminate between different types of cancers. The aim of this study was to analyze global miRNA signatures in various groups of colorectal cancers (CRC) based on the presence of microsatellite ...