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  • American Association for Cancer Research (AACR)  (9)
  • 1
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 28, No. 2 ( 2019-02-01), p. 248-257
    Abstract: Although alcohol drinking is an established risk factor of head and neck cancer (HNC), less is known about its role in the prognosis of HNC. The current study investigated the association between pretreatment alcohol consumption and the overall survival (OS) of HNC patients. Methods: Cox proportional hazards models were performed to evaluate the association between prediagnosis alcohol drinking and the OS of HNC patients. In addition, the influence of the polymorphisms of two ethanol-metabolizing genes, ADH1B and ALDH2, on this relationship was also evaluated. Results: The results showed a significant positive dose–response relationship between prediagnosis alcohol use and worse OS of HNC patients. This association was more significant for oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer than for oral cancer. The association between alcohol use and the poorer OS of HNC patients was mainly through its association with a higher stage of HNC at diagnosis. The worst OS associated with alcohol use was observed among HNC patients with the fast ADH1B and the slow/nonfunctional ALDH2 genotype combination. Conclusions: Our analysis showed a significant positive dose–response relationship between prediagnosis alcohol use and a worse OS of HNC. This association was mainly due to the higher stage of HNC among alcohol drinkers. In addition, the polymorphisms of the ethanol-metabolizing genes, ADH1B and ALDH2, modified the relationship between prediagnosis alcohol use and the OS of HNC patients. Impact: Prediagnosis alcohol use may be a prognostic indicator of HNC.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2015
    In:  Clinical Cancer Research Vol. 21, No. 16 ( 2015-08-15), p. 3678-3684
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 16 ( 2015-08-15), p. 3678-3684
    Abstract: Background: The TGF-β signaling pathway is crucial in the progression and metastasis of malignancies. We investigated whether the serum TGF-β1 level was related to the outcomes of patients treated with sorafenib for advanced hepatocellular carcinoma (HCC). Experimental Design: We selected patients who had received sorafenib-containing regimens as first-line therapy for advanced HCC between 2007 and 2012. Serum TGF-β1 levels were measured and correlated with the treatment outcomes. The expression TGF-β1 and the sensitivity to sorafenib were examined in HCC cell lines. Results:Ninety-one patients were included; 62 (68%) were hepatitis B virus surface antigen (+), and 11 (12%) were anti-hepatitis C virus (+). High (≥ median) pretreatment serum TGF-β1 levels (median 13.7 ng/mL; range, 3.0–41.8) were associated with high α-fetoprotein levels, but not with age, gender, or disease stage. Patients with high pretreatment serum TGF-β1 levels exhibited significantly shorter progression-free survival (median, 2.5 vs. 4.3 months; P = 0.022) and overall survival (median 5.6 vs. 11.6 months; P = 0.029) than did patients with low serum TGF-β1 levels. Compared with pretreatment levels, the serum TGF-β1 levels were significantly increased at disease progression (n = 29, P = 0.010). In preclinical models of HCC, higher TGF-β1 expression levels were associated with poorer sensitivity to sorafenib. Conclusions: High pretreatment serum TGF-β1 levels were associated with poor prognoses, and increased serum TGF-β1 levels were associated with the disease progression of advanced HCC patients. TGF-β pathway may be explored as a therapeutic target for advanced HCC. Clin Cancer Res; 21(16); 3678–84. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 3
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    Online Resource
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Prevention Research Vol. 1, No. 3 ( 2008-08-01), p. 187-191
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 1, No. 3 ( 2008-08-01), p. 187-191
    Abstract: The nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a critical role in protecting various tissues against inflammation, which is a potential risk factor for colorectal and other cancers. Our previously published mouse model work showed that Nrf2 helps protect against dextran sulfate sodium (DSS)–induced colitis/inflammation, and others have shown that Nrf2 helps protect against inflammation-associated colorectal carcinogenesis (aberrant crypt foci). The present study extended these important earlier findings by exploring the role of Nrf2 in colitis-associated colorectal cancer in a mouse model involving azoxymethane/DSS–induced colorectal carcinogenesis in Nrf2 knockout mice. Azoxymethane/DSS–treated Nrf2 knockout mice had increased incidence, multiplicity, and size of all colorectal tumors, including adenomas, versus treated wild-type (WT) mice, and the proportion of tumors that were adenocarcinoma was much higher in knockout (80%) versus WT (29%) mice. Compared with WT mice, knockout mice also had increased markers of inflammation in tumor tissue (cyclooxygenase-2 and 5-lipoxygenase expressions and prostaglandin E2 and leukotriene B4 levels) and in inflamed colonic mucosa (nitrotyrosine expression), supporting the association of knockout mouse tumor formation with inflammation. The phase II detoxifying/antioxidant enzymes NAD(P)H-quinone reductase 1 and UDP-glucurosyltransferase 1A1 were elevated in the normal mucosa of WT, but not Nrf 2 knockout, mice treated with azoxymethane/DSS. Our findings show that Nrf2 plays a critical role in protecting against inflammation-associated colorectal cancer.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 1309-1309
    Abstract: Purpose: Although imatinib mesylate (IM) has revolutionized the management of gastrointestinal stromal tumors (GISTs), drug resistance remains a challenge. Previous studies have shown that the expression of aurora kinase A (AURKA) predicts recurrence in patients with primary surgically-resected GISTs. The current study aims to evaluate the significance of AURKA as an unfavorable prognostic marker for advanced GISTs, and provides evidence that AURKA could be a potential treatment target of GISTs. Experimental Design: The prognostic significance of AURKA, along with other clinicopathological factors, was analyzed in a cohort of 99 IM-treated patients with advanced GISTs using immunohistochemistry. The potential use of an AURKA inhibitor as therapeutic agent against GISTs was also tested in GIST cell lines. Results: Among 99 enrolled patients, poor performance status, large tumor size, drug response, and AURKA overexpression were independent poor prognostic factors for progression-free survival (PFS). For overall survival (OS), only large tumor size and AURKA overexpression were identified as independent unfavorable factors. In an in vitro study, MLN8237, an AURKA inhibitor, was demonstrated to inhibit growth of both IM-sensitive and IM-resistant GIST cells in a concentration-dependent manner. The inhibitory effect of MLN8237 on GIST cells could be attributed to the induction of G2/M arrest, apoptosis, and senescence, possibly through up-regulation of pro-apoptotic proteins. Conclusions: Our study showed that AURAK is an independent poor prognostic factor for both PFS and OS in patients with advanced GISTs treated with IM. AURKA inhibitor could be used as therapeutic agent for both IM-sensitive and IM-resistant GISTs. Citation Format: Chun-Nan Yeh, Chueh-Chuan Yen, Yeng-Yang Chen, Chi-Tung Cheng, Shih-Chiang Huang, Ting-Wei Chang, Fang-Yi Yao, Yung-Chan Lin, Yao-Shan Wen, Kun-Chun Chiang, Jen-Shi Chen, Ta-Sen Yeh, Cheng-Hwai Tzeng, Ta-Chung Chao, Jonathan A. Fletcher. Identification of aurora kinase a as an unfavorable prognostic factor and potential treatment target for metastatic gastrointestinal stromal tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1309. doi:10.1158/1538-7445.AM2014-1309
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 681-681
    Abstract: The attempts of target therapy in ovarian cancer therapy mostly fail. There is a need of biomarkers for better patient stratification in clinical trials. Epigenetics is a driving force for cancer development and may serve as a molecular marker of disease. The present study was to analyze the clinical relevance of methylation phenotypes and figure out the mechanism in ovarian cancer. We integrated the analysis using public dataset of epigenomics and transcriptomics, and our hospital-based methylomic database and tissue arrays of patients diagnosed with epithelial ovarian cancers (EOC). Bioinformatics results were verified and validated in cell lines and clinical samples. From 25 genes, we identified even genes, ADRA1A, CD248, HS3ST2, NEFH, IGSF21, POU4F2, and TWIST1, of which hypermethylation was significantly related to the poor overall survival (OS). The association of NEFH and HS3ST2 hypermethylation and poor 5-year OS was validated in our independent dataset and TCGA database. The NEFH/HS3ST2 hypermethylated signature was an independent risk factor for 5-year OS (adjusted Hazard ratio = 2.93, 95% confidence interval = 1.25 to 6.85, P = 0.013). In vitro experiment re-expressing HS3ST2 repressed migration and invasion, and suppressed IL-6 signaling pathways. The combination of hypermethylation of HS3ST2 and high expression of IL-6 confers the worse outcome. Our data suggested that methylation of NEFH/HS3ST2 constituted a poor prognostic signature of ovarian cancer. The sulfation status of proteoglycan modified by HS3ST2 implicates an intrinsic sensitivity of ovarian cancer cells to IL-6, which shed a new light on the application of HS3ST2 as a biomarker for personalized medicine of targeting IL-6. Note: This abstract was not presented at the meeting. Citation Format: Rui-Lan Huang, Hsiang-Ju Chan, Lin-Yu Chen, Yaw-Wen Hsu, Tai-Kuang Chao, Po-Hsuan Su, Yu-Chun Weng, Chiou-Chung Yuan, Hung-Cheng Lai. Methylomics profiling reveals epigenetically silenced HS3ST2 sensitize IL6 signaling and confers poor prognosis of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 681. doi:10.1158/1538-7445.AM2017-681
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 85-85
    Abstract: Obese patients have higher levels of free fatty acids (FFAs) in their plasma and a higher risk of cancer than their non-obese counterparts. However, the mechanisms involved in the regulation of cancer metastasis by FFAs remain unclear. In this study, we found that oleic acid (OA) induced angiopoietin-like 4 (ANGPTL4) protein expression and secretion and conferred anoikis resistance to head and neck squamous cell carcinomas (HNSCCs). The autocrine production of OA-induced ANGPTL4 further promoted HNSCC migration and invasion. In addition, the expression of peroxisome proliferator-activated receptor (PPAR) was essential for the OA-induced ANGPTL4 expression and invasion. The levels of OA-induced epithelial-mesenchymal transition markers, such as vimentin, MMP-9, and fibronectin and its downstream effectors Rac1/Cdc42, were significantly reduced in ANGPTL4-depleted cells. Knocking down fibronectin not only inhibited the expression of MMP-9 but also repressed OA- and recombinant ANGPTL4-induced HNSCC invasion. On the other hand, ANGPTL4 siRNA inhibited OA-induced MMP-9 expression, which was reversed in fibronectin-overexpressing cells. Furthermore, the depletion of ANGPTL4 impeded the OA-primed metastatic seeding of tumor cells in the lungs. These results demonstrate that OA enhances HNSCC metastasis through the ANGPTL4/fibronectin/Rac1/Cdc42 and ANGPTL4/fibronectin/MMP-9 signaling axes. The inhibition of ANGPTL4 could be a potential strategy for the treatment of FFA-mediated HNSCC metastasis. Citation Format: Chih-Jie Shen, Shih-Hung Chan, Chung-Ta Lee, Wan-Chen Huang, Jhih-Peng Tsai, Kwang-Yu Chang, Wen-Chang Chang, Ben-Kuen Chen. Oleic acid promotes head and neck squamous cell carcinoma anoikis resistance and metastasis via ANGPTL4/fibronectin pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 85.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 7
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 4763-4763
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 4763-4763
    Abstract: Whilst traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. Treatment resistance and metastasis have been attributed to expansion of cancer stem-like cells (CSCs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximal tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts that induces the expression and secretion of ELR-motif-positive (ELR+) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into CSCs and promote their invasive behaviors, leading to paradoxical tumor aggression following the therapy. By contrast, the same total accumulated dose administered as a low-dose-metronomic chemotherapy regimen largely prevented the therapy-induced stromal ELR+-chemokine paracrine signaling for CSCs, thereby substantially enhancing treatment response and extending survival of mice carrying desmoplastic cancers (Chan et al, J. Exp. Med. 2016). These studies illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy. Note: This abstract was not presented at the meeting. Citation Format: Kelvin K. Tsai, Tze-Sian Chan, Chung-Chi Hsu, Vincent C. Pai, Shenq-Shyang Huang, Valerie M. Weaver. Metronomic chemotherapy prevents therapy-induced stromal activation and induction of cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4763. doi:10.1158/1538-7445.AM2017-4763
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 8
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2865-2865
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2865-2865
    Abstract: Background: TGF-β (Transforming growth factor β) signaling pathway plays a significant role in mediating progression, metastasis, and immune evasion of human malignancies. Previous studies have found that serum TGF-β1 levels were elevated in patients with hepatocellular carcinoma (HCC) compared to patients with chronic hepatitis or cirrhosis. However, the prognostic role of serum TGF-β1 levels in patients with advanced HCC is currently unknown. Patients and Methods: We enrolled patients who had received sorafenib or sorafenib-based combination therapy for advanced HCC, defined as metastatic or locally advanced diseases not amenable to loco-regional therapies, at National Taiwan University Hospital, Taipei, Taiwan, between 2007 and 2012. The baseline blood samples were collected before sorafenib treatment with the consent of the patients. Serum TGF-β1 levels were measured by Human TGF-β1 Instant ELISA (eBioscience, Vienna, Austria), and were correlated with disease control rate (DCR), progression- free survival (PFS), and overall survival (OS) of the patients. Results: The study enrolled 91 patients (M:F=82:9), with a median age of 56.9 years. Sixty-nine patients (75.8 %) had chronic hepatitis B virus (HBV) infection, 18 (19.7%) had chronic hepatitis C infection, 82 (90.1%) had Barcelona Clinic Liver Cancer stage C disease, 81(89.0%) had either extrahepatic metastasis or macrovascular invasion, and 88 (96.7%) had Eastern Cooperative Oncology Group performance status of ≤ 1. All patients had Child-Puch class A liver function reserve. Patients with high baseline serum TGF-β1 levels (higher than the median level of the whole patient cohort), compared to patients with low serum TGF-β1 levels, had significantly shorter PFS (median, 2.54 vs. 4.27 months, p = 0.022) and OS (median, 5.57 vs. 11.6 months, p = 0.029). The DCRs for patients with high and low TGF-β1 were not statistically different (54.3 % vs. 62.2%, p = 0.4463). High baseline TGF-β1 levels tended to associate with high serum alpha-fetal protein (AFP) levels and high Cancer of the Liver Italian Program (CLIP) scores, although not reaching statistical significance. Conclusions: High baseline serum TGF-β1 levels were associated with poor PFS and OS in patients with advanced HCC. (This study was supported by grants NRPB-100CAP1020-2, NSC101-2314-B-002-141 & NSC102-2314-B-002 -120). Citation Format: Tzu-Hsuan Lin, Yu-Yun Shao, Soa-Yu Chan, Chung-Yi Huang, Ann-Lii Cheng, Chih-Hung Hsu. High serum transforming growth factor β1 levels associated with poor survivals in patients with advanced hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2865. doi:10.1158/1538-7445.AM2014-2865
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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  • 9
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 3, No. 1_Supplement ( 2010-01-07), p. B135-B135
    Abstract: Background: There has been emerging knowledge on the serious burden of diseases attributable to Hepatitis C carriers (HCV). However, the extent of the life time risk of HCV, when independently assessed, is as yet fully understood, particularly regarding associated risk factors that are amenable to reductions. Objectives: We assessed the mortality risks and life-shortening effect of HCV, along with its associated risk factors, based on following up a large healthy cohort in Taiwan. Methods: The cohort, consisting of 487,369 subjects, participated in a standardized medical screening program since 1994. Based on the hepatitis carrier status (either HBV or HCV or both), three sub-cohorts were created. As of 2007, 16,920 deaths were identified, including 1,383 liver cancer and 631 cirrhosis, with average follow up of 8.5 years. Hazard ratio (RR) was calculated using Cox proportionate hazard model. National prevalence was arrived at by standardizing age and educational status, a surrogate for socioeconomic status (SES) to those in Taiwan. Glomerular Filtration Rate (GFR) was calculated by MDRD equation. Results: National Prevalence for HCV: 3.6% above age 20, and 6.6% above age 40 (male 6.0% and female 7.3%) increased with age and with lower SES. Rates of diabetes, hypertension, obesity, and HDL among HCV+ participants were significantly higher, but total cholesterol and triglycerides were lower. They had 35% more chronic kidney disease (CKD), with 54% more proteinuria and 13% more reduced GFR (13%). Cohort mortality results: HCV+ male participants had 7.37 years shorter than the total cohort at age 20, compared to 3.36 years for HBV+. In contrast to one out of 7 deaths (13.7%) in the total cohort was liver related, one out of two in the HCV+ sub-cohort. With HR for all-cause being 2.42, 58.7% of the deaths were HCV-related, larger than HBV counterparts (36.7%). The number of HCV related cirrhosis was 1/4 (28%) that of HCC, and HCV related risk, 10.74, was slightly smaller than that for HCC, 14.56. Nearly one out of 10 HCV+ coexisted with HBV (8.9%), and the risk became synergistic, with 2/3 of them dying from liver-related causes. Kidney cancer (5.46), diabetes (2.31), and stroke (1.91) were also significantly increased. In the order of ranking All Cause mortality risks among HCV+ subjects, diabetes (4.5), proteinuria (4.1), smoking (3.5), obesity (3.3), drinking (3.2) and hypertension (2.9) were all significantly increased. Conclusion: The life expectancy of HCV+ carriers was shortened by 7.37–8.45 years. While the main effect was liver cancer and cirrhosis, HCV also involved kidney damage, producing proteinuria and reduced GFR, and led to an increased mortality from diabetes and stroke. The ranking order of reducible HCV risks were diabetes, CKD including proteinuria, smoking, obesity, drinking and hypertension. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B135.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2422346-3
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