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  • American Association for Cancer Research (AACR)  (22)
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  • American Association for Cancer Research (AACR)  (22)
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  • Medicine  (22)
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  • 1
    Online Resource
    Online Resource
    BRCA1 Insufficiency Induces a Hypersialylated Acidic Tumor Microenvironment That Promotes Metastasis and Immunotherapy Resistance
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 15 ( 2023-08-01), p. 2614-2633
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 15 ( 2023-08-01), p. 2614-2633
    Abstract: Cancer metastasis is an extremely complex process affected by many factors. An acidic microenvironment can drive cancer cell migration toward blood vessels while also hampering immune cell activity. Here, we identified a mechanism mediated by sialyltransferases that induces an acidic tumor-permissive microenvironment (ATPME) in BRCA1-mutant and most BRCA1-low breast cancers. Hypersialylation mediated by ST8SIA4 perturbed the mammary epithelial bilayer structure and generated an ATPME and immunosuppressive microenvironment with increased PD-L1 and PD1 expressions. Mechanistically, BRCA1 deficiency increased expression of VEGFA and IL6 to activate TGFβ–ST8SIA4 signaling. High levels of ST8SIA4 led to accumulation of polysialic acid (PSA) on mammary epithelial membranes that facilitated escape of cancer cells from immunosurveillance, promoting metastasis and resistance to αPD1 treatment. The sialyltransferase inhibitor 3Fax-Peracetyl Neu5Ac neutralized the ATPME, sensitized cancers to immune checkpoint blockade by activating CD8 T cells, and inhibited tumor growth and metastasis. Together, these findings identify a potential therapeutic option for cancers with a high level of PSA. Significance: BRCA1 deficiency generates an acidic microenvironment to promote cancer metastasis and immunotherapy resistance that can be reversed using a sialyltransferase inhibitor.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-22-3398
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    Online Resource
    Online Resource
    SIRT6 Promotes COX-2 Expression and Acts as an Oncogene in Skin Cancer
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 20 ( 2014-10-15), p. 5925-5933
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 20 ( 2014-10-15), p. 5925-5933
    Abstract: SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability, and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer. Here, we challenge this concept by presenting evidence that skin-specific deletion of SIRT6 in the mouse inhibits skin tumorigenesis. SIRT6 promoted expression of COX-2 by repressing AMPK signaling, thereby increasing cell proliferation and survival in the skin epidermis. SIRT6 expression in skin keratinocytes was increased by exposure to UVB light through activation of the AKT pathway. Clinically, we found that SIRT6 was upregulated in human skin squamous cell carcinoma. Taken together, our results provide evidence that SIRT6 functions as an oncogene in the epidermis and suggest greater complexity to its role in epithelial carcinogenesis. Cancer Res; 74(20); 5925–33. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-14-1308
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    Identification of an Integrated SV40 T/t-Antigen Cancer Signature in Aggressive Human Breast, Prostate, and Lung Carcinomas with Poor Prognosis
    American Association for Cancer Research (AACR) ; 2007
    In:  Cancer Research Vol. 67, No. 17 ( 2007-09-01), p. 8065-8080
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 67, No. 17 ( 2007-09-01), p. 8065-8080
    Abstract: Understanding the genetic architecture of cancer pathways that distinguishes subsets of human cancer is critical to developing new therapies that better target tumors based on their molecular expression profiles. In this study, we identify an integrated gene signature from multiple transgenic models of epithelial cancers intrinsic to the functions of the Simian virus 40 T/t-antigens that is associated with the biological behavior and prognosis for several human epithelial tumors. This genetic signature, composed primarily of genes regulating cell replication, proliferation, DNA repair, and apoptosis, is not a general cancer signature. Rather, it is uniquely activated primarily in tumors with aberrant p53, Rb, or BRCA1 expression but not in tumors initiated through the overexpression of myc, ras, her2/neu, or polyoma middle T oncogenes. Importantly, human breast, lung, and prostate tumors expressing this set of genes represent subsets of tumors with the most aggressive phenotype and with poor prognosis. The T/t-antigen signature is highly predictive of human breast cancer prognosis. Because this class of epithelial tumors is generally intractable to currently existing standard therapies, this genetic signature identifies potential targets for novel therapies directed against these lethal forms of cancer. Because these genetic targets have been discovered using mammary, prostate, and lung T/t-antigen mouse cancer models, these models are rationale candidates for use in preclinical testing of therapies focused on these biologically important targets. [Cancer Res 2007;67(17):8065–80]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-07-1515
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    Online Resource
    Online Resource
    Abstract 2695: Olfactomedin 4 gene is associated with progression of prostate cancer: Evidence from an OLFM4 knockout mouse model
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2695-2695
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2695-2695
    Abstract: The olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein whose physiological and pathological functions are largely unknown. We have previously reported that expression of OLFM4 is down regulated during the progression of human prostate cancer, and that reduced expression is due to gene deletions of OLFM4 (36.7%) and/or hyper-methlytion of CpG sites in the promoter region. We also demonstrated that ectopic expression of OLFM4 in several human prostate cancer cell lines inhibits proliferation, invasion and metastatic potential. In this study, we further investigated the potential role of OLFM4 in the carcinogenesis of prostate cancer utilizing an OLFM4 knock out mouse model. Histopathological analysis revealed that homozygous OLFM4 mutant mice develop prostatic epithelial lesions in an age-dependent manner. The prostatic epithelial hyperplasia was seen at 6 months of age, prostatic intraepithelial neoplasia (PIN) was found at 10-12 months of age, and prostate adenoma was observed from 18-24 months of ages in the both anterior prostate (AP) and dorsal-lateral prostate (DLP) of OLFM4-null mice. The frequency of PIN lesions at the AP and DLP was 0 % (0/20) at 3-6 months, 38% (5/13) at 10-12 months and 44% (11/25) at 18-24 months. The frequency of prostatic adenoma was 28% (7/25), and 8% (2/25) of OLFM4-null mice developed lung metastases at 18-24 months of age. To determine whether OLFM4 affects proliferation or apoptosis of prostatic epithelial cells in the OLFM4-null mice, we carried out Ki-67 immunohistochemical staining and TUNEL assays. The ratio of Ki-67 positive cells was significantly higher at 3-6 months (p=0.04180), 10-12 months (P=0.002) and 18-20 months (p=0.0038) compared to age-matched controls, OLFM4 wild type mice, or heterozygous mice, thus indicating an increase in proliferation in OLFM4-null prostate tissues. There was no difference in the number of apoptotic cells in the control versus null mice. Since we have previously found that OLFM4 blocks CXCL12 induced AKT activity in the human prostate cancer cell PC-3, and inhibits cell invasion, we studied the phosphorylation of AKT and downstream signaling pathway components by Western blot analysis of prostate samples from 3-4 month old mice. Compared with OLFM4 wild type mice, pAKT, pGSK3β, β-catenin, cyclin D1 and c-Myc were increased in the OLFM4-null mice tissue even in the absence of morphological abnormalities. Elevated β-catenin protein in OLFM4-null mice prostate epithelial cells was also observed in PIN and tumor cells at 18 months of age, and positive staining with Cyclin D1 in OLFM4-null tumor was also detected. Taken together, the data show OLFM4-null prostatic epithelial cells exhibit higher levels of AKT and β-catenin, suggesting this is the mechanism leading to their enhanced cellular proliferation and carcinogenetic potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2695. doi:1538-7445.AM2012-2695
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-2695
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    Online Resource
    Online Resource
    Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma
    American Association for Cancer Research (AACR) ; 2023
    In:  Clinical Cancer Research Vol. 29, No. 19 ( 2023-10-02), p. 3986-4001
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 29, No. 19 ( 2023-10-02), p. 3986-4001
    Abstract: Sarcoma is the second most common solid tumor type in children and adolescents. The high level of tumor heterogeneity as well as aggressive behavior of sarcomas brings serious difficulties to developing effective therapeutic strategies for clinical application. Therefore, it is of great importance to identify accurate biomarkers for early detection and prognostic prediction of sarcomas. Experimental Design: In this study, we characterized three subtypes of sarcomas based on tumor immune infiltration levels (TIIL), and constructed a prognosis-related competing endogenous RNA (ceRNA) network to investigate molecular regulations in the sarcoma tumor microenvironment (TME). We further built a subnetwork consisting of mRNAs and lncRNAs that are targets of key miRNAs and strongly correlated with each other in the ceRNA network. After validation using public data and experiments in vivo and in vitro, we deeply dug the biological role of the miRNAs and lncRNAs in a subnetwork and their impact on TME. Results: Altogether, 5 miRNAs (hsa-mir-125b-2, hsa-mir-135a-1, hsa-mir92a-2, hsa-mir-181a-2, and hsa-mir-214), 3 lncRNAs (LINC00641, LINC01146, and LINC00892), and 10 mRNAs (AGO2, CXCL10, CD86, CASP1, IKZF1, CD27, CD247, CD69, CCR2, and CSF2RB) in the subnetwork were identified as vital regulators to shape the TME. On the basis of the systematic network, we identified that trichostatin A, a pan-HDAC inhibitor, could potentially regulate the TME of sarcoma, thereby inhibiting the tumor growth. Conclusions: Our study identifies a ceRNA network as a promising biomarker for sarcoma. This system provides a more comprehensive understanding and a novel perspective of how ceRNAs are involved in shaping sarcoma TME.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-22-3396
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 6
    Online Resource
    Online Resource
    SIRT3 Is a Mitochondrial Tumor Suppressor: A Scientific Tale That Connects Aberrant Cellular ROS, the Warburg Effect, and Carcinogenesis
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 10 ( 2012-05-15), p. 2468-2472
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 10 ( 2012-05-15), p. 2468-2472
    Abstract: Tumors exhibit metabolic reprogramming characterized by increased cellular reactive oxygen species (ROS) and the preferential use of glucose, which is known as the Warburg effect. However, the mechanisms by which these processes are linked remain largely elusive. Murine tumors lacking Sirt3 exhibit abnormally high levels of ROS that directly induce genomic instability and increase hypoxia-inducible factor 1α (HIF-1α) protein levels. The subsequent transcription of HIFα-dependent target genes results in cellular metabolic reprogramming and increased cellular glucose consumption. In addition, agents that scavenge ROS or reverse the Warburg effect prevent the transformation and malignant phenotype observed in cells lacking Sirt3. Thus, mice lacking Sirt3 provide a model that mechanistically connects aberrant ROS, the Warburg effect, and carcinogenesis. Cancer Res; 72(10); 2468–72. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-11-3633
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    Online Resource
    Online Resource
    Oxidative Stress Activates SIRT2 to Deacetylate and Stimulate Phosphoglycerate Mutase
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 13 ( 2014-07-01), p. 3630-3642
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 13 ( 2014-07-01), p. 3630-3642
    Abstract: Glycolytic enzyme phosphoglycerate mutase (PGAM) plays an important role in coordinating energy production with generation of reducing power and the biosynthesis of nucleotide precursors and amino acids. Inhibition of PGAM by small RNAi or small molecule attenuates cell proliferation and tumor growth. PGAM activity is commonly upregulated in tumor cells, but how PGAM activity is regulated in vivo remains poorly understood. Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. Increased levels of reactive oxygen species stimulate PGAM2 deacetylation and activity by promoting its interaction with SIRT2. Substitution of endogenous PGAM2 with an acetylation mimetic mutant K100Q reduces cellular NADPH production and inhibits cell proliferation and tumor growth. These results reveal a mechanism of PGAM2 regulation and NADPH homeostasis in response to oxidative stress that impacts cell proliferation and tumor growth. Cancer Res; 74(13); 3630–42. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-13-3615
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    Online Resource
    Online Resource
    Abstract 699: The prognostic value of DNA polymerase ≤ for breast cancers
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 699-699
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 699-699
    Abstract: DNA polymerase eta (Pol β, POLH) is a eukaryotic DNA polymerase involved in DNA repair by translesion synthesis. To address whether Pol ≤ impacts breast cancer survival, we conducted a retrospective outcome study on 145assessable cases of breast cancers collected from affiliated hospital of Zhejiang University (ZJU set). The results were validated on six published microarray data sets (1,154 cases) with pathoclinical and follow-up information. In the ZJU set, the protein levels of Pol ≤ were determined by IHC. The specificity of antibody against Pol ≤ was validated by using peptide blocking assay. It was shown that protein expression level of Pol ≤ positively correlates with cell proliferative marker Ki-67 (trends P=0.019). The Kaplan-Meier analysis revealed that Pol ≤ was significantly related that better overall survival in breast cancer patients who received chemotherapy or radiotherapy (Log rank p=0.003). Multivariate COX analysis further confirmed that the hazard ratio (HR) of Pol ≤ for overall and progress-free survival were 0.23(95% CI 0.05-0.95) and 0.32(0.11-0.96). Further stratification analysis demonstrated that Pol ≤ prognoses better survival in Luminal A and B molecular subtypes (HR=0.155 95% CI 0.04-0.62), but not HER 2 Positive or Triple negative breast cancer. Above findings were further validated in public microarray database. In Ivshina's dataset, the increase of POLH mRNA was significantly and negatively related with lymphnode involvement in a dose-dependent manner (trend p=0.044). The Kaplan-Meier analysis also revealed that the mRNA levels of POLH was significantly related to progress-free survival of breast cancer. In Chin's data, multivariate COX analysis also revealed that the HR increased significantly as with increase of POLH mRNA levels (HR= 0.22 95% CI 0.03-0.86, highest quartile vs. lowest quartile). Above findings suggested that the protein and mRNA expression levels of Pol ≤ prognoses better survival in breast cancer, especially in Luminal A or B breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 699. doi:1538-7445.AM2012-699
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-699
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
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    Online Resource
    Abstract 706: Ribonucleotide reductase small subunit M2 is a potential prognostic biomarker in human epidermal growth factor receptor 2- positive and triple negative breast cancers
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 706-706
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 706-706
    Abstract: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer and triple negative breast cancer (TNBC) are two subtypes with poor outcome of all breast carcinomas. However, among all the patients in these two subtypes some still yielded relatively better prognosis. Ribonucleotide reductase (RR) small subunits M2 was associated with cancer cell invasiveness and metastasis, which prognoses poor survival in many cancers. Here we investigated whether RRM2 could serve as a prognostic biomarker for breast cancers, especially HER2- positive and TNBC subgroups. One hundred seventy five assessable breast cancers (40 cases were HER2-positive or TNBC) were collected from affiliated hospital of Zhejiang University (ZJU set); and six published microarray data sets (total 1154 cases, 63 cases were identified as HER2- positive or TNBC) with pathoclinical and follow- up information were employed for validation. In the ZJU set, the protein level of RRM2 was determined by IHC. It was indicated that RRM2 was positively correlated with cell proliferative marker Ki-67 (trends P=0.018) and stem/progenitor cell marker CD44+/CD24-/low (P=0.044). Multivariate COX model revealed that RRM2 was an independent prognostic biomarker for both OS (Hazard Ratio, HR=2.79, 95%Cl 1.21-6.75) and PFS (Hazard Ratio, HR=1.82, 95%Cl 1.02-3.26) for all the breast cancers. Moreover, in HER2-positive or TNBC breast cancers, RRM2-high was significantly associated with poor survival (P=0.025). Consequently, none of the patients with RRM2-low died of breast cancer in HER2-positive or TNBC subgroups. Furthermore, above findings were validated in the published data sets. The mRNA level of RRM2 evaluated significantly in highly-invasive subtypes including Luminal B, HER2-positive and TNBC in comparison with Luminal A and unclassified subgroups (P & lt;0.05). Overexpression of RRM2 was positively associated with poor differentiation (P & lt;0.05), advanced AJCC stage (P & lt;0.05) as well as poor survival (P & lt;0.05) in a dose-dependent manner. It was also revealed that high expression of RRM2 prognosed poor survival (HR=5.56, 95% CI 1.14-99.9) in HER2-positive breast cancers or TNBC. Moreover, the RRM2-high (protein or mRNA levels) was associated with better response to chemotherapy comparing to RRM2-low. Taken together, the above findings suggested that RRM2 was a potential biomarker for poor survival in breast cancer, especially in HER2- positive breast cancer and TNBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 706. doi:1538-7445.AM2012-706
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-706
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 10
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    Online Resource
    Up-regulation of Inflammatory Signalings by Areca Nut Extract and Role of Cyclooxygenase-2 −1195G〉A Polymorphism Reveal Risk of Oral Cancer
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Research Vol. 68, No. 20 ( 2008-10-15), p. 8489-8498
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 68, No. 20 ( 2008-10-15), p. 8489-8498
    Abstract: Because the mRNA expression of cyclooxygenase-2 (COX-2) is up-regulated by arecoline in human gingival fibroblasts, as shown in our previous study, we further investigated the mRNA expression level of COX-2 and its upstream effectors in three oral epithelial carcinoma cell lines (KB, SAS, and Ca9-22) by using areca nut extract (ANE) and saliva-reacted ANE (sANE). A case-control study of 377 oral squamous cell carcinoma (OSCC) patients and 442 controls was conducted to evaluate the gene-environment interaction between COX-2 promoter polymorphisms and substance use of alcohol, betel quid, and cigarettes (ABC) in risk of OSCC. The heterogeneous characteristics of the oral site and the COX-2 −1195G & gt;A polymorphism in these cell lines showed diverse inflammatory response (KB≫Ca9-22 & gt;SAS) after 24-hour ANE/sANE treatments, and the COX-2 up-regulation might be mostly elicited from alternative nuclear factor-κB activation. In the case-control study, betel chewing [adjusted odds ratios (aOR), 42.2] posed a much higher risk of OSCC than alcohol drinking and cigarette smoking (aORs, 2.4 and 1.8, respectively), whereas the COX-2 −1195A/A homozygote presented a potential genetic risk (OR, 1.55). The strongest joint effect for OSCC was seen in betel chewers with −1195A/A homozygote (aOR, 79 .44). In the non–betel chewing group, the −1195A/G and A/A genotypes together with the combined use of alcohol and cigarettes increased risk to 15.1-fold and 32.1-fold, respectively, compared with the G/G genotype without substance use. Taken together, these findings illustrate a valuable insight into the potential role of the COX-2 promoter region in contributing to the development of betel-related OSCC, including ANE/sANE–induced transcriptional effects and enhanced joint effects of COX-2 −1195A allele with substance use of ABC. [Cancer Res 2008;68(20):8489–98]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-08-0823
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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