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cDNA Microarray Analysis (cdna + microarray_analysis)
Selected AbstractsCDNA microarray analysis of gene expression in fibroblasts of patients with x-linked Emery,Dreifuss muscular dystrophyMUSCLE AND NERVE, Issue 6 2002Toshifumi Tsukahara PhD Abstract To clarify the molecular nature of the pathogenesis in X-linked Emery,Dreifuss muscular dystrophy (EDMD), we monitored the expression of 2400 genes in control and EDMD fibroblasts by using complementary DNA (cDNA) microarray techniques. A total of 60 genes whose expression was altered in EDMD fibroblasts when compared with control fibroblasts were identified. Twenty-eight genes whose expression was altered with the emerin deficiency were rescued by infection with a recombinant adenovirus expressing emerin. The altered expression in five genes, including the lamin A/C gene, was confirmed by reverse transcription,polymerase chain reaction. Our preliminary results suggest a correlation between disease similarity and gene expression. We conclude that the cDNA microarray is a very efficient tool to clarify genetic and pathological features of diseases. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 898,901, 2002 [source] Ginkgo biloba extracts and cancer: a research area in its infancyFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2003Francis V. DeFeudis Abstract Recent studies conducted with various molecular, cellular and whole animal models have revealed that leaf extracts of Ginkgo biloba may have anticancer (chemopreventive) properties that are related to their antioxidant, anti-angiogenic and gene-regulatory actions. The antioxidant and associated anti-lipoperoxidative effects of Ginkgo extracts appear to involve both their flavonoid and terpenoid constituents. The anti-angiogenic activity of the extracts may involve their antioxidant activity and their ability to inhibit both inducible and endothelial forms of nitric oxide synthase. With regard to gene expression, a Ginkgo extract and one of its terpenoid constituents, ginkgolide B, inhibited the proliferation of a highly aggressive human breast cancer cell line and xenografts of this cell line in nude mice. cDNA microarray analyses have shown that exposure of human breast cancer cells to a Ginkgo extract altered the expression of genes that are involved in the regulation of cell proliferation, cell differentiation or apoptosis, and that exposure of human bladder cancer cells to a Ginkgo extract produced an adaptive transcriptional response that augments antioxidant status and inhibits DNA damage. In humans, Ginkgo extracts inhibit the formation of radiation-induced (chromosome-damaging) clastogenic factors and ultraviolet light-induced oxidative stress , effects that may also be associated with anticancer activity. Flavonoid and terpenoid constituents of Ginkgo extracts may act in a complementary manner to inhibit several carcinogenesis-related processes, and therefore the total extracts may be required for producing optimal effects. [source] Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomasINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008Suely K.N. Marie Abstract We have performed cDNA microarray analyses to identify gene expression differences between highly invasive glioblastoma multiforme (GBM) and typically benign pilocytic astrocytomas (PA). Despite the significant clinical and pathological differences between the 2 tumor types, only 63 genes were found to exhibit 2-fold or greater overexpression in GBM as compared to PA. Forty percent of these genes are related to the regulation of the cell cycle and mitosis. QT-PCR validation of 6 overexpressed genes: MELK, AUKB, ASPM, PRC1, IL13RA2 and KIAA0101 confirmed at least a 5-fold increase in the average expression levels in GBM. Maternal embryonic leucine zipper kinase (MELK) exhibited the most statistically significant difference. A more detailed investigation of MELK expression was undertaken to study its oncogenic relevance. In the examination of more than 100 tumors of the central nervous system, we found progressively higher expression of MELK with astrocytoma grade and a noteworthy uniformity of high level expression in GBM. Similar level of overexpression was also observed in medulloblastoma. We found neither gene promoter hypomethylation nor amplification to be a factor in MELK expression, but were able to demonstrate that MELK knockdown in malignant astrocytoma cell lines caused a reduction in proliferation and anchorage-independent growth in in vitro assays. Our results indicate that GBM and PA differ by the expression of surprisingly few genes. Among them, MELK correlated with malignancy grade in astrocytomas and represents a therapeutic target for the management of the most frequent brain tumors in adult and children. © 2007 Wiley-Liss, Inc. [source] Global analysis of gene expression profiles in ileum in a rat bladder augmentation model using cDNA microarraysINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004HIDEAKI MIYAKE Abstract Background: The objective of the present study was to globally characterize the changes in the gene expression profile in the ileum after long-term urine exposure in a rat ileal augmented bladder model using cDNA microarrays. Methods: Bladder augmentation using the ileum was performed in female 8-week-old rats. The ileal epithelia used for bladder augmentation were harvested 1 and 3 months postoperatively and changes in the gene expression in these tissues were compared with that of intact ileal epithelia from sham-operated rats using cDNA microarrays consisting of 1176 rat genes. Results: Marked changes in gene expression in the ileum used for bladder augmentation were observed for 30 genes (16 up-regulated and 14 down-regulated genes). The differentially expressed genes include those associated with signal transduction, cell adhesion and stress response. Subsequent evaluation of changes in two randomly selected genes from the 30 differentially expressed genes by semiquantitative reverse transcription-polymerase chain reaction demonstrated the reliability of the present cDNA microarray analyses. Conclusion: The present experiments identified an extensive list of genes differentially expressed in the ileum after bladder augmentation, providing valuable information for the pathophysiological assessment of patients who undergo urinary reconstruction and representing a source of novel targets for treating complications after urinary diversion. [source] Reduced Activity of CD13/Aminopeptidase N (APN) in Aggressive Meningiomas Is Associated with Increased Levels of SPARCBRAIN PATHOLOGY, Issue 1 2010Christian Mawrin Abstract Meningiomas are the second most common brain tumors in adults, and meningiomas exhibit a tendency to invade adjacent structures. Compared with high-grade gliomas, little is known about the molecular changes that potentially underlie the invasive behavior of meningiomas. In this study, we examined the expression and function of the membrane alanyl-aminopeptidase [mAAP, aminopeptidase N (APN), CD13, EC3.4.11.2] zinc-dependent ectopeptidase in meningiomas and meningioma cell lines, based on its prior association with tumor invasion in colorectal and renal carcinomas. We found a significant reduction of APNmRNA and protein expression, as well as enzymatic activity, in high-grade meningiomas. While meningioma tumor cell proliferation was not affected by either pharmacologic APN inhibition or siRNA-mediated APN silencing, APN pharmacologic and siRNA knockdown significantly reduced meningioma cell invasion in vitro. Next, we employed pathway-specific cDNA microarray analyses to identify extracellular matrix and adhesion molecules regulated by APN, and found that APN-siRNA knockdown substantially increased the expression of secreted protein, acidic and rich in cysteine (SPARC)/osteonectin. Finally, we demonstrated that SPARC, which has been previously associated with meningioma invasiveness, was increased in aggressive meningiomas. Collectively, these results suggest that APN expression and enzymatic function is reduced in aggressive meningiomas, and that alterations in the balance between APN and SPARC might favor meningioma invasion. [source] Differentially expressed genes associated with CIS -diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and CDNA microarrayHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2003Eisaku Higuchi MD Abstract Background. The mechanism by which cancer cells become resistant to cis -Diamminedichloroplatinum (II) (cDDP) is not completely understood. To investigate the molecular markers involved in the cDDP resistance, we compared the gene expression profiles between a head and neck squamous cell carcinoma (HNSCC) line sensitive to cDDP and its cDDP-resistant variant. Methods. Both a fluorescent differential display and a cDNA microarray analysis were applied to distinguish the gene profiles between KB, a human HNSCC line, and its cDDP-resistant variant (KB/cDDP). These results were confirmed by Northern blot analysis. Results. One up-regulated gene, glycoprotein hormone ,-subunit, and two down-regulated genes coding membrane proteins, human folate receptor and tumor-associated antigen L6, were identified in KB/cDDP cells. Conclusions. Our findings suggest that development of the cDDP-resistant phenotype is accompanied by alternations of gene expression including a glycoprotein hormone and membrane proteins. These gene products could be new molecular markers for resistance to cDDP. © 2003 Wiley Periodicals, Inc. Head Neck 25: 187,193, 2003 [source] Identification of SPARC as a candidate target antigen for immunotherapy of various cancersINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Mitsuhiro Inoue Abstract To establish efficient anticancer immunotherary, it is important to identify tumor-associated antigens (TAAs) directing the immune system to attack cancer. A genome-wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine (SPARC) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. This study attempted to identify HLA-A24 (A*2402)-restricted and SPARC-derived CTL epitopes. We previously identified H-2Kd -restricted and SPARC-derived CTL epitope peptides in BALB/c mice, of which H-2Kd -binding peptide motif is comparable with that of HLA-A24 binding peptides. By using these peptides, we tried to induce HLA-A24 (A*2402)-restricted and SPARC-reactive human CTLs and demonstrated an antitumor immune response. The SPARC-A24-1143,151 (DYIGPCKYI) and SPARC-A24-4225,234 (MYIFPVHWQF) peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A24 (A*2402) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA-A24 (A*2402). Furthermore, the adoptive transfer of the SPARC-specific CTLs could inhibit the tumor growth in nonobese diabetic/severe combined immunodeficient mice bearing human cancer cells expressing both HLA-A24 (A*2402) and SPARC. These findings suggest that SPARC is a potentially useful target candidate for cancer immunotherapy. [source] Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stromaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Takafumi Sangai Abstract Cancer-stromal interaction is well known to play important roles during cancer progression. Recently we have demonstrated that bone marrow-derived vascular endothelial cells (BMD-VE) and myofibroblasts (BMD-MF) are recruited into the human pancreatic cancer cell line Capan-1 induced stroma. To assess the effect of the difference in cancer cell types on the recruitment of BMD-VE and BMD-MF, 10 kinds of human cancer cell line were implanted into the subctaneous tissue of the immunodeficient mice transplanted with bone marrow of double-mutant mice (RAG-1,/, ,-gal Tg or RAG-1,/, GFP Tg). The recruitment frequency of BMD-VE (%BMD-VE) and BMD-MF (%BMD-MF), and tumor-associated parameters [tumor volume (TV), microvessel density (MVD) and stromal proportion (%St)] were measured. The correlation among them was analyzed. Although %BMD-VE and %BMD-MF varied (from 0 to 21.6%, 0 to 29.6%, respectively), depending on the cancer cell line, both parameters were significantly correlated with %St (p < 0.005). Furthermore %BMD-VE and %BMD-MF also significantly correlated (p < 0.005). In order to assess the effect of tumor growth sites on the recruitment of the cells of interest, a human pancreatic cancer cell line, Capan-1, was transplanted into 5 different sites: subcutaneous tissue, peritoneum, liver, spleen and lung. Tumors in the subcutaneous tissue and peritoneum induced desmoplastic stroma (%St = 22.7%, 19.5%, respectively) and contained BMD-VE (%BMD-VE = 21.6%, 16.5% respectively) and BMD-MF (%BMD-MF = 29.6%, 24.5%, respectively), but weak stromal induction without recruitment of BMD-VE or -MF was observed in the tumors at of the liver, spleen and lung (%St = 9.7%, 9.1%, 5.4%, respectively). cDNA microarray analysis identified the 29 genes that expression was especially up- or down-regulated in the cell line that induced an abundant stromal reaction. However they did not encoded the molecules that were directly involved in stromal cell recruitment (chemokines), differentiation (cytokines) or proliferation (growth factors). These results indicate that the recruitment of BMD-VE and -MF is required for stromal formation during cancer progression and that the cancer microenvironment is important in stromal reaction and the recruitment of BMD-VE and -MF. © 2005 Wiley-Liss, Inc. [source] 20-O-,-D-Glucopyranosyl-20 (S)-protopanaxadiol (compound K) induces expression of hyaluronan synthase 2 gene in transformed human keratinocytes and fibroblasts and increases hyaluronan in hairless mouse skinINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2004S. Kim Ginsenosides, the major active ingredient of ginseng, show a variety of biomedical efficacies such as anti-aging, anti-oxidation and anti-inflammatory activities. To understand the effects of 20-O-,-D-glucopyranosyl-20 (S)-protopanaxadiol (compound K), one of the major metabolites of ginsenosides on the skin, we assessed the expression level of approximately 100 transcripts in compound K-treated HaCaT cells using cDNA microarray analysis. Compound K treatment induced differential expression of 40 genes, which have been reported to be involved in the organization of the structure of the extracellular matrix as well as defense responses in human skin cells. One of the most interesting findings is a two-fold increase in hyaluronan synthase2 (HAS2) gene expression by compound K. We found that change in expression of HAS2 gene represents a specific response of HaCaT cells to compound K because hyaluronan synthase 1,3 was not changed by treatment with compound K. We also demonstrated that the compound K effectively induced hyaluronan synthesis in human skin cells and hairless mouse skin. A human clinical study indicated that topical application of compound K containing oil-in-water emulsion showed improvement of xerosis, wrinkle and fine lines in the aged skin. We concluded that compound K has anti-aging effects by the induction of HAS2 gene expression and following hyaluronan synthase. [source] Identification of Novel Target Genes of the Bone-Specific Transcription Factor Runx2,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2004Michael Stock Abstract Fifteen putative transcriptional target genes regulated by the osteogenic transcription factor Runx2 were identified by cDNA microarray and differential hybridization techniques. Expression pattern and regulation of one gene, Pttg1ip, was analyzed in detail. Introduction: The transcription factor Runx2 is a key regulator of osteoblast development and plays a role in chondrocyte maturation. The identification of transcriptional target genes of Runx2 may yield insight into how osteoblastic differentiation is achieved on a molecular level. Materials and Methods: Using a differential hybridization technique (selective amplification through biotin and restriction-mediated enrichment [SABRE]) and cDNA microarray analysis, 15 differentially expressed genes were identified using mRNA from C3H 10T1/2 cells with constitutive and inducible overexpression of Runx2. Results and Conclusions: Among the 15 genes identified, 4 encode the extracellular matrix proteins Ecm1, Mgp, Fbn5, and Osf-2, three represent the transcription factors Esx1, Osr1, and Sox9, whereas others were Ptn, Npdc-1, Hig1, and Tem1. The gene for Pttg1ip was upregulated in Runx2-expressing cells. Pttg1ip is widely expressed during development, but at highest levels in limbs and gonads. The Pttg1ip promoter binds Runx2 in a sequence specific manner, and Runx2 is able to transactivate the Pttg1ip promoter in MC3T3-E1 cells. Therefore, Pttg1ip is likely to be a novel direct transcriptional target gene of Runx2. In conclusion, the genes identified in this study are important candidates for mediating Runx2 induced cellular differentiation. [source] Abnormal expression of Smurf2 during the process of rat liver fibrosisJOURNAL OF DIGESTIVE DISEASES, Issue 4 2006Yu CAI OBJECTIVE: Liver fibrosis is a prelude of liver cirrhosis. Currently the molecular mechanism of liver fibrosis is not clear. The purpose of this study is to screen the abnormally expressed genes of liver fibrosis and to illustrate the changes of Smurf2 expression in the process of liver fibrosis. METHODS: A liver fibrosis model was established in rats by injection of tetrachlormethane (CCl4). A cDNA microarray analysis was performed on the liver at mid-stage of fibrosis. Thereafter, a semi-quantitative RT-PCR, Western blot analysis and immunohistochemistry test were performed for determining Smurf2, Smad2 and SnoN at week 1, 2, 4 and 8 of establishing the liver fibrosis model. RESULTS: Smurf2, FGG, PTAFR, CYP2D6, among others, increased in the fibrosis liver and a semi-quantitative RT-PCR confirmed the reliability of the cDNA microarray analysis. Smurf2 in the liver fibrosis model group was at the same level as that of control group at week 1, but decreased at week 2 and 8 and increased at the week 4. Smad2 increased at week 2 and 8 but increased at week 4. However, Smad2 mRNA increased to the same level at week 4 as that at week 2 and 8. The decrease of Smad2 at week 4 may be due to the enhancement of ubiquitination and proteolytic degradation of Smad2 by the increase of Smurf2. SnoN decreased at week 4 and 8 because of the ubiquitination and degradation caused by Smurf2. The decrease of SnoN may explain the progress of liver fibrosis in spite of the decrease of Smad2 at week 4. CONCLUSION: This study screened the abnormally expressed genes of liver fibrosis and illustrated the changes of Smurf2, Smad2 and SnoN during the process of liver fibrosis. [source] Increases in expression of 14-3-3 eta and 14-3-3 zeta transcripts during neuroprotection induced by ,9 -tetrahydrocannabinol in AF5 cells,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2007Jia Chen Abstract The molecular mechanisms involved in N-methyl-D-aspartate (NMDA)-induced cell death and ,9-tetrahydrocannabinol (THC)-induced neuroprotection were investigated in vitro with an AF5 neural progenitor cell line model. By microarray analysis, Ywhah, CK1, Hsp60, Pdcd 4, and Pdcd 7 were identified as being strongly regulated by both NMDA toxicity and THC neuroprotection. The 14-3-3 eta (14-3-3,; gene symbol Ywhah) and 14-3-3 zeta (14-3-3,; gene symbol Ywhaz) transcripts were deceased by NMDA treatment and increased by THC treatment prior to NMDA, as measured by cDNA microarray analysis and quantitative real-time RT-PCR. Other 14-3-3 isoforms were unchanged. Whereas up-regulation of 14-3-3, expression was observed 30 min after treatment with THC plus NMDA, down-regulation by NMDA alone was not seen until 16 hr after treatment. By Western blotting, THC increased 14-3-3 protein only in cells that were also treated with NMDA. Overexpression of 14-3-3, or 14-3-3, by transient plasmid transfection increased 14-3-3 protein levels and decreased NMDA-induced cell death. These data suggest that increases in 14-3-3 proteins mediate THC-induced neuroprotection under conditions of NMDA-induced cellular stress. © 2007 Wiley-Liss, Inc. [source] Microarray analysis of transcription factor gene expression in melatonin-treated human peripheral blood mononuclear cellsJOURNAL OF PINEAL RESEARCH, Issue 4 2006Eunyoung Ha Abstract:, The existence of specific melatonin-binding sites in lymphoid cells led to the discovery of signal transduction pathway for melatonin in human lymphocytes and immunomodulatory role of melatonin in immune cells. In recent years, transcriptional regulation of melatonin on various transcription factors has been demonstrated. Therefore, this study was designed to assess by cDNA microarray analysis the regulatory effects of melatonin on transcription factors in human peripheral blood mononuclear cells (PBMCs). Forty-six genes were upregulated and 23 were downregulated more than twofold in melatonin-treated PBMCs. Of the more than twofold upregulated transcription factor genes, homeo box A4 (HOXA4), forkhead box O1A (FOXO1A), transcription elongation factor B (SIII), polypeptide 3 (TCEB3), and peroxisome proliferative activated receptor delta (PPARD) were identified. Of the more than twofold downregulated genes, PHD finger protein 15 (PHF15) and zinc finger protein 33a (ZNF33A) were identified. In summary, identification of these genes by cDNA microarray analysis in response to melatonin administration may provide a foundation for further studies on the function of melatonin in human PBMCs. [source] Estrogen-induced uterine abnormalities in TIMP-1 deficient mice are associated with elevated plasmin activity and reduced expression of the novel uterine plasmin protease inhibitor serpinb7MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2009Xuan Zhang Abstract Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional protein capable of regulating a variety of biological processes in a wide array of tissue and cell types. We have previously demonstrated that TIMP-1 deficient mice exhibit alterations in normal uterine morphology and physiology. Most notably, absence of TIMP-1 is associated with an altered uterine phenotype characterized by profound branching of the uterine lumen and altered adenogenesis. To begin to assess the mechanism by which TIMP-1 may control these uterine events, we utilized steroid-treated ovariectomized wild-type and TIMP-1 null mice exposed to estrogen for 72 hr. Administration of estrogen to TIMP-1 deficient mice resulted in development of an abnormal uterine histo-architecture characterized by increased endometrial gland density, luminal epithelial cell height, and abnormal lumen structure. To determine the mediators which may contribute to the abnormal uterine morphology in the TIMP-1 deficient mice, cDNA microarray analysis was performed. Analysis revealed that expression of two plasmin inhibitors (serpbinb2 and serbinb7) was significantly reduced in the TIMP-1 null mice. Associated with the reduction in expression of these inhibitors was a significant increase in plasmin activity. Localization of the novel uterine serpinb7 revealed that expression was confined to the luminal and glandular epithelial cells. Further, expression of uterine serpinb7 was decreased by estrogen and showed an inverse relationship with plasmin activity. We conclude from these studies that in addition to controlling MMP activity, TIMP-1 may also control activity of serine proteases through modulation of serine protease inhibitors such as serpinb7. Mol. Reprod. Dev. 76: 160,172, 2009. © 2008 Wiley-Liss, Inc. [source] Gene expression profiling of Dunaliella sp. acclimated to different salinitiesPHYCOLOGICAL RESEARCH, Issue 1 2010Minjung Kim SUMMARY To investigate which genes may be important for growth under extreme conditions such as very low or high salinities, a survey of the Dunaliella sp. transcriptome was performed with a cDNA microarray which had been generated previously representing 778 expressed sequence tags. The comparative microarray analysis indicated that 142 genes differed in expression levels by more than twofold in cells grown at extreme salinities (0.08 M and 4.5 M NaCl) when compared with cells grown at intermediate salinity (1.5 M NaCl). Of these genes, 28 had increased expression and 57 were suppressed in cells grown at low salinity. In cells grown at high salinity, 43 genes showed increased expression and 69 genes showed suppressed expression. However, we did observe a large overlap in the expression of extreme salinity-responsive genes based on Venn diagram analysis, which found 55 genes that responded to both of the two extreme salinity conditions. Further, we found that several genes had similar expression levels under low and high salinities, including some general stress response genes that were upregulated in both extreme salinity conditions. For confirmation of the validity of the cDNA microarray analysis, expression of several genes was independently confirmed by the use of gene-specific primers and real-time polymerase chain reaction. The present study is the first large-scale comparative survey of the transcriptome from the microalga Dunaliella sp. acclimated to extreme salinities, thus providing a platform for further functional investigation of differentially expressed genes in Dunaliella. [source] Novel tumor marker REG4 detected in serum of patients with resectable pancreatic cancer and feasibility for antibody therapy targeting REG4CANCER SCIENCE, Issue 11 2006Akio Takehara Pancreatic ductal adenocarcinoma (PDAC) shows the worst mortality rate among common malignancies, with a 5-year survival rate of only 4%, and the majority of PDAC patients are diagnosed at an advanced stage in which no effective therapy is available at present. Although the proportion of curable cases is still not so high, surgical resection of early stage PDAC is the only way to cure the disease. Hence, establishment of a screening strategy to detect early stage PDAC by novel serological markers is required urgently, and development of novel molecular therapies for PDAC treatment is also eagerly expected. We here report overexpression of REG4, a new member of the regenerating islet-derived (REG) family, in PDAC cells on the basis of genome-wide cDNA microarray analysis as well as reverse transcription,polymerase chain reaction and immunohistochemical analysis. We also detected significant elevation of REG4 in the serum of some patients with early-stage PDAC using our enzyme-linked immunosorbent assay system, indicating the possibility of REG4 as a new serological marker of PDAC. Furthermore, we found that knockdown of endogenous REG4 expression in PDAC cell lines with small interfering RNA caused a decrease in cell viability. Concordantly, addition of recombinant REG4 to the culture medium enhanced growth of a PDAC cell line in a dose-dependent manner. A monoclonal antibody against REG4 neutralized its growth-promoting effects and attenuated significantly the growth of PDAC cells. These findings indicate that REG4 is a promising tumor marker to screen early-stage PDAC, and also that neutralization of REG4 by the antibody may offer novel potential tools for the treatment of PDAC. (Cancer Sci 2006; 97: 1191,1197) [source] Distinct pattern of gene expression in pyothorax-associated lymphoma (PAL), a lymphoma developing in long-standing inflammationCANCER SCIENCE, Issue 10 2004Mieko Nishiu Pyothorax-associated lymphoma (PAL) is a unique lymphoma developing in the pleural cavity after long-standing pyothorax. They are diffuse large B-cell lymphomas (DLBCLs), frequently with immunoblastic morphology, and show a strong association with Epstein-Barr virus (EBV) infection. In this study, cDNA microarray analysis was performed in six cases with PAL and 12 with nodal DLBCL. Among 5516 informative genes, 348 displayed more than 2-fold difference (higher or lower) of expression level between PAL and nodal DLBCL (P>0.001). These genes are known to be involved in apoptosis, interferon response, and signal transduction. One of the most differentially expressed genes, IFI27 (interferon-,-inducible protein 27) was subjected to quantitative RT-PCR analysis, and increased expression of IFI27 was confirmed. Over-expression of IFI27 was also found in cell lines derived from PAL, but not in other lymphoid cell lines. This study shows that PAL is a distinctive subtype of DLBCL not only in its clinical presentation, but also in its molecular profile. [source] Isolation of p53-target genes and their functional analysisCANCER SCIENCE, Issue 1 2004Yusuke Nakamura Mutations of the p53 gene are the most common genetic alterations found in human cancers, and are known to play crucial roles in tumor development and progression. The p53 gene encodes a protein functioning as a transcription factor, and the biological functions of p53 are manifested through the activities of its downstream genes. Identification of these downstream genes involved in the p53-signaling pathway should provide more detailed insight into the molecular mechanisms that mediate tumor-suppressor activities, as well as various responses to cellular stress. We have been attempting to isolate p53-target genes by means of various approaches, including differential display, cDNA microarray analysis, and direct cloning of the p53-binding sequences from human genomic DNA. Here I review our recent work on isolation of p53-target genes and their functional analysis. The physiological functions of p53-target genes include apoptosis (GML, p53AIP1, and STAG1), DNA repair (p53R2), inhibition of angiogenesis (BAI1), re-entry into the cell cycle (p53RFP), oxidative stress (CSR), and determination of cell fate (p53RDL1). (Cancer Sci 2004; 95: 7,11) [source] Aberrant methylation of the vascular endothelial growth factor receptor-1 gene in prostate cancerCANCER SCIENCE, Issue 6 2003Yasushi Yamada Transcriptional silencing of cancer-related genes by DNA methylation is observed in various cancers. To identify genes controlled by methylation in prostate cancer, we used cDNA microarray analysis to investigate gene expression in prostate cancer cell lines LNCaP and DU145 treated with a methyltransferase inhibitor alone or together with a histone deacetylase inhibitor. We detected significant changes (3.4,5.7%) in gene expression in prostate cancer cell lines with the drug treatments. Among the affected genes, that for the vascular endothelial growth factor receptor 1 (VEGFR-1) was re-expressed in LNCaP and DU145 after the drug treatments. Bisulfite sequencing revealed the promoter and exon 1 of the VEGFR-1 to be hypermethylated in the cell lines. These results support the idea that methylation is associated with loss of VEGFR-1 mRNA expression in prostate cancer cell lines. Combined bisulfite restriction analysis (COBRA) showed the gene to be methylated in 24 (38.1%) of 63 primary local prostate cancer samples, while in all 13 benign prostate samples it was not. These findings indicate that methylation of VEGFR-1 is related with prostatic carcinogenesis. [source] Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical TrialsARCHIV DER PHARMAZIE, Issue 9 2010Adeeb Shehzad Abstract Curcumin (diferuloylmethane), a derivative of turmeric is one of the most commonly used and highly researched phytochemicals. Abundant sources provide interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer. The pleiotropic role of this dietary compound includes the inhibition of several cell signaling pathways at multiple levels, such as transcription factors (NF-,B and AP-1), enzymes (COX-2, MMPs), cell cycle arrest (cyclin D1), proliferation (EGFR and Akt), survival pathways (,-catenin and adhesion molecules), and TNF. Curcumin up-regulates caspase family proteins and down-regulates anti-apoptotic genes (Bcl-2 and Bcl-XL). In addition, cDNA microarrays analysis adds a new dimension for molecular responses of cancer cells to curcumin at the genomic level. Although, curcumin's poor absorption and low systemic bioavailability limits the access of adequate concentrations for pharmacological effects in certain tissues, active levels in the gastrointestinal tract have been found in animal and human pharmacokinetic studies. Currently, sufficient data has been shown to advocate phase II and phase III clinical trials of curcumin for a variety of cancer conditions including multiple myeloma, pancreatic, and colon cancer. [source] | |||||||||||||