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  • American Association for Cancer Research (AACR)  (36)
  • 1
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 13, No. 5 ( 2007-03-01), p. 1412-1420
    Abstract: Purpose: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. In a previous study, we showed that GNMT acts as a susceptibility gene for hepatocellular carcinoma. Here, we report on our efforts to characterize the haplotypes, loss of heterozygosity (LOH), and expression levels of the GNMT in prostate cancer. Experimental Design: Peripheral blood mononuclear cell DNA collected from 326 prostate cancer patients and 327 age-matched controls was used to determine GNMT haplotypes. Luciferase reporter constructs were used to compare the promoter activity of different GNMT haplotypes. GNMT LOH rates in tumorous specimens were investigated via a comparison with peripheral blood mononuclear cell genotypes. Immunohistochemical staining was used to analyze GNMT expression in tissue specimens collected from 5 normal individuals, 33 benign prostatic hyperplasia patients, and 45 prostate cancer patients. Results: Three major GNMT haplotypes were identified in 92% of the participants: A, 16GAs/DEL/C (58%); B, 10GAs/INS/C (19.9%); and C, 10GAs/INS/T (14.5%). Haplotype C carriers had significantly lower risk for prostate cancer compared with individuals with haplotype A (odds ratio, 0.68; 95% confidence interval, 0.48-0.95). Results from a phenotypic analysis showed that haplotype C exhibited the highest promoter activity (P & lt; 0.05, ANOVA test). In addition, 36.4% (8 of 22) of the prostatic tumor tissues had LOH of the GNMT gene. Immunohistochemical staining results showed abundant GNMT expression in normal prostatic and benign prostatic hyperplasia tissues, whereas it was diminished in 82.2% (37 of 45) of the prostate cancer tissues. Conclusions: Our findings suggest that GNMT is a tumor susceptibility gene for prostate cancer.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3880-3880
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3880-3880
    Abstract: The purpose of this abstract was to assess the efficacy of peptide targeted chemotherapy for pancreatic carcinoma. Previously we have constructed four peptides that bind specifically to cancer cell lines, which were derived from three different carcinoma cell lines and their vascular endothelia: L-peptide: (L-P, anti-cancer cell membrane), RLLDTNRPLLPY; SP-94-P (anti-hepato-pancreatic cancer cell membrane), SFSHHTPILP; PC5-52-peptide (anti-tumor endothelia), SVSVGMKPSPRP; and control peptide, RLLDTNRGGGGG. These peptides were linked to pegylated liposomal iron oxide nanoparticles to identify the targeted tumor cells and vascular endothelia using MRI analysis, and were also linked to dextran coated liposomal doxorubicin (L-D) for treatment of non-obese diabetic, severe combined immunodeficiency (NOD-SCID) mice bearing pancreatic cancer cell (PANC-1) xenografts. Our results demonstrated that the tumor intensity of MRI is clearly decreased after SP-94-P-iron oxide was applied, and that in combination of application of L-P linked L-D (L-P-L-D) plus SP-94-P linked L-D (SP-94-P-L-D) and PC5-52-P linked L-D (PC5-52-P-L-D), they could inhibit pancreatic tumor growth with very mild adverse events. The use of the control peptide linked L-D also led to a decrease of the xenograft size, but also induced marked apoptotic change of their visceral organs. It is concluded that the combination of L-P-L-D, SP-94-P-L-D and PC5-52-P-L-D to treat pancreatic cancer xenograft in NOD SCID mice can clearly inhibit pancreatic cancer growth with minimal adverse events. Citation Format: Chin-Tarng Lin, Chen-Der Wu, Jen-Chieh Lee, Han-Chung Wu, Chung-Wei Lee, Chin-Feng Lin, Ming-Chieh Hsu. Peptide-targeted chemotherapy for pancreatic cancer [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 3880.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 3
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    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3423-3423
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3423-3423
    Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers with high mortality worldwide. Hypoxia is considered as a driving force to trigger the progression of malignancy, such as epithelial-mesenchymal transition (EMT) process, tumor metastasis, and recurrence. Because of the high recurrence rate caused by frequent metastasis and the lack of effective systemic treatment, development of new biomarkers and therapeutic targets for HCC treatment is urgently needed. Loss of E-cadherin is an early and critical step in EMT process and tumor metastasis. Consequently, modulation of the expression of E-cadherin may be a potential way to prevent tumor metastasis. Recently, we have demonstrated that overexpression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) not only down-regulated the cyclin D1 expression and inhibited growth of hepatoma HepG2 cells, but also up-regulated the E-cadherin expression and concomitantly down-regulated the mesenchymal marker, and decreased the vimentin expression as well as the migration of HepG2 cells. In this study, we observed a significant increase in the expression level of Kruppel-like factor 4 (KLF4) in HepG2 cells when PGC-1α was overexpressed by adenovirus mediated gene transfer. Using wound healing assay and Western blotting, we further observed increased cell migration and decreased expression of KLF4 in HepG2, Hep3B, and HA22T/VGH hepatoma cell lines under hypoxia condition. Moreover, the KLF4 expression level in HepG2 cells under hypoxia and combined with drug treatment was also examined. We found that treatment of sodium nitroprusside, a nitric oxide donor, can protect HepG2 cells from hypoxia- and glucose depletion-induced cytotoxicity through repressing the KLF4 and Bip/Grp78 expression. After treatment with a cytotoxic dose (1 μM) of doxorubicin, the KLF4 expression of HepG2 cells was decreased under normoxia while it was increased under hypoxia. These results together suggest that PGC-1α may regulate the expression of E-cadherin via KLF4, and the KLF4 expression correlated with the response of HepG2 cells to doxorubicin under hypoxia. PGC-1α and KLF4 may serve as potential targets to inhibit the growth and metastasis of hepatoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3423. doi:10.1158/1538-7445.AM2011-3423
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 23 ( 2011-12-01), p. 7270-7279
    Abstract: Extracellular glycosylation is a critical determinant of malignant character. Here, we report that N-acetylgalactosaminyltransferase 2 (GALNT2), the enzyme that mediates the initial step of mucin type-O glycosylation, is a critical mediator of malignant character in hepatocellular carcinoma (HCC) that acts by modifying the activity of the epidermal growth factor receptor (EGFR). GALNT2 mRNA and protein were downregulated frequently in HCC tumors where these events were associated with vascular invasion and recurrence. Restoring GALNT2 expression in HCC cells suppressed EGF-induced cell growth, migration, and invasion in vitro and in vivo. Mechanistic investigations revealed that the status of the O-glycans attached to the EGFR was altered by GALNT2, changing EGFR responses after EGF binding. Inhibiting EGFR activity with erlotinib decreased the malignant characters caused by siRNA-mediated knockdown of GALNT2 in HCC cells, establishing the critical role of EGFR in mediating the effects of GALNT2 expression. Taken together, our results suggest that GALNT2 dysregulation contributes to the malignant behavior of HCC cells, and they provide novel insights into the significance of O-glycosylation in EGFR activity and HCC pathogenesis. Cancer Res; 71(23); 7270–9. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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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
    American Association for Cancer Research (AACR) ; 2013
    In:  Molecular Cancer Research Vol. 11, No. 3 ( 2013-03-01), p. 261-271
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 11, No. 3 ( 2013-03-01), p. 261-271
    Abstract: Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme responsible for the elimination of superoxide radical. The role of MnSOD in tumor progression in different human cancers is still controversial. In the present study, MnSOD expression in lung cancer cells was explored by knockdown or overexpression using transfection of a short hairpin RNA (shRNA) or an expression vector, respectively, to determine whether MnSOD expression mediates lung cancer cell migration, invasion, and oncogenic potential by increasing FoxM1 and MMP2 expression. Western blotting showed that FoxM1 and MMP2 expression was dependent on MnSOD expression, suggesting that FoxM1 could be upregulated by MnSOD. Three FoxM1 promoters were constructed to verify this activation of FoxM1 by MnSOD and to determine the transcription factors responsible. Luciferase reporter and chromatin immunoprecipitation assays indicated that MnSOD overexpression in lung cancer cells promoted binding of E2F1 and Sp1 to their putative FoxM1 promoter-binding sites and activated FoxM1 reporter activity. MnSOD also enhanced the potential for cell migration, invasion, and anchorage-independent colony growth on soft-agar plates, again via upregulation of FoxM1 and MMP2 expression. In patients with lung cancer, evaluation of MnSOD expression in lung tumors by immunohistochemistry indicated a positive correlation between FoxM1 and MMP2 mRNA expressions. Kaplan–Meier and Cox regression analysis revealed a poorer overall survival (OS) and relapse-free survival (RFS) in patients with MnSOD-positive tumors than with MnSOD-negative tumors. We conclude that MnSOD may promote tumor aggressiveness via upregulation of the FoxM1–MMP2 axis, and that MnSOD expression can independently predict survival and relapse in patients with resected lung adenocarcinoma. Mol Cancer Res; 11(3); 261–71. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5051-5051
    Abstract: Oral squamous cell carcinoma (OSCC) is a highly invasive disease displaying frequent tumor recurrence and lymph node metastasis. Genes involved in cytoskeleton remodeling, cell attachment, and cell mobility are suspicious candidates that promote invasiveness. A genomewide study based on Sty1 250K SNP array platform revealed the involvement of TLN1 gene in the 9p13.3 amplicon. Although large scale screening on 123 tumor tissues by dual color-fluorescence in situ hybridization (FISH) indicated low frequency (around 7.3%) of TLN1 amplification in OSCC, the overall gene expression levels were significantly higher in tumor tissues as compared to the adjacent normal oral epithelium (P & lt; 0.01). As compared to other cytoskeleton crossing linkers that can trigger integrin activation, TLN1 stood out to be the most highly expressed one in OSCC. A mouse study revealed that TLN1 overexpression could be detected in invasive tumors but not in the lesions at early stages. Immunohistochemistry (IHC) data revealed stronger TLN1 immunereactivity in OSCC than in normal tissues. More intense staining pattern was detected at the leading edge of cancer cells under going angiogenesis or lymphogenesis. Patients with TLN1 overexpression had a significantly shorter overall survival and higher recurrence rate than those without. Collectively, our study suggested an important role of TLN1 in oral cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5051.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 7
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 5 ( 2020-03-01), p. 1185-1197
    Abstract: Hepatitis promotes the development and recurrence of hepatocellular carcinoma (HCC). Receptor tyrosine kinases (RTK) play critical roles in the development of many cancers. We explored the potential roles of RTKs in hepatitis-related liver cancers. Experimental Design: We conducted loss-of-function screening to elucidate the roles of RTKs in the development of HCC in vitro and in vivo. Results: Many RTKs were coexpressed in HCC and were involved in tumor development and growth. Of these, TYRO3 promoted tumor growth and was clinically associated with hepatitis activity and poor prognosis. In mice, chemical-induced hepatitis transcriptionally activated Tyro3 expression via IL-6/IL6R–STAT3 signaling. Moreover, hepatitis-associated apoptotic cells facilitated the presentation of GAS6, a TYRO3 ligand, to further activate TYRO3-mediated signaling. Furthermore, TYRO3 activation elicited intracellular SRC- and STAT3 signaling. In mice, hepatitis and Tyro3 synergistically promoted HCC development. Silencing TYRO3 expression or inhibiting its kinase activity suppressed xenograft HCC growth in nude mice. Conclusions: Many RTKs are simultaneously involved in HCC development. Hepatitis exerts dual effects on the activation of TYRO3-mediated signaling in HCC cells, which further elicits the “TYRO3–STAT3–TYRO3” signaling loop to facilitate tumor growth. Our findings unveil a previously unrecognized link between RTKs and hepatitis-associated HCC and suggest TYRO3 as a marker and therapeutic target for the HCCs with higher hepatitis activity.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2184-2184
    Abstract: The efficacy of systemic cytotoxic chemotherapy has been widely assessed in patients with advanced hepatocellular carcinoma (HCC). For example, doxorubicin is the most commonly studied chemotherapeutic agent for HCC. However, it has been shown to have a response rate of only 10-20% in clinical trial. In addition, its potential benefit has been reduced by the related adverse effect. So far, the multikinase inhibitor, sorafenib, is considered to provide survival benefit over supportive care. However, the long term prognosis of those cancer patients still remain poor. Therefore, in the present experiment, we proposed to use the so-called peptide targeting chemotherapy to overcome the adverse event in the conventional targeted chemotherapy. In order to perform this experiment, we have construct some specific peptides which can bind specifically to the cancer cells and cancer vascular endothelia by using a phage displayed 12-mer random peptide library. We have obtained 3 different peptides and one control peptide. Each contains 12 amino acids: a. L-peptide: RLLDTNRPLLPY (anti-different cancer cell membrane); b. control peptide: RLLDTNRGGGGG; c. SP-94-peptide: SFSHHTPILP (anti-NPC tumor cell and hepatoma cell membranes) and d. PC5-52-peptide: SVSVGMKPSPRP (anti-tumor endothelia). Those L-peptide (L-P), SP-peptide (SP-P), PC5-52-peptide and a control peptide (C-P) were linked to liposomal iron oxide nanoparticles; and also used those peptides to link liposomal doxorubicin (L-D). Using peptide linked liposomal iron oxide, we can localize the peptide targeted tumor cells and tumor endothelia, and then we used those peptides linked liposomal doxorubicin to treat SCID mice bearing different cancer xenografts. Our results showed that when L-P-L-D containing 2mg/kg of SCID mouse body weight was used to treat xenografts bearing SCID mice, the tumor could be well controlled, and no specific adverse event was seen. However, when the control peptide was used to replace the specific peptide, the xenograft size was also shown decrease, but the visceral organs revealed marked apoptotic change. In conclusion, the specific peptides linked liposomal doxorubicin nanoparticles can be used for treatment of SCID mice bearing cancer xenografts with minimal adverse event, especially in the SCID miceγspecies (NGS), which show a remarkable tumor suppression. Note: This abstract was not presented at the meeting. Citation Format: Chin-Tarng Lin, Cheng-Der Wu, Jen-Chien Lee, Han-Chung Wu, Chung-Wei Lee, Ming-Chieh Hsu. Preclinical verification of the efficacy of targeting peptides linked liposomal nanoparticles for therapy of hepatocellular and nasopharyngeal carcinomas and breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2184.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 9
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    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Prevention Research Vol. 10, No. 6 ( 2017-06-01), p. 355-362
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 10, No. 6 ( 2017-06-01), p. 355-362
    Abstract: We integrated genetic risk scores (GRS) and environmental factors for identifying high-risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case–control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between GRS and betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1, and HSPA13 genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores = 4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ, and cigarette: adjusted OR = 4.42 [95% confidence interval (95% CI), 1.34–14.55]. The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR = 70.77; 95% CI, 8.70–575.73). The synergy index was 16.58 (95% CI, 2.27–70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high-risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence. Cancer Prev Res; 10(6); 355–62. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2422346-3
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 18 ( 2012-09-15), p. 4652-4661
    Abstract: Tumor microenvironment plays a critical role in regulating tumor progression by secreting factors that mediate cancer cell growth. Stromal fibroblasts can promote tumor growth through paracrine factors; however, restraint of malignant carcinoma progression by the microenvironment also has been observed. The mechanisms that underlie this paradox remain unknown. Here, we report that the tumorigenic potential of breast cancer cells is determined by an interaction between the Robo1 receptor and its ligand Slit2, which is secreted by stromal fibroblasts. The presence of an active Slit2/Robo1 signal blocks the translocation of β-catenin into nucleus, leading to downregulation of c-myc and cyclin D1 via the phosphoinositide 3-kinase (PI3K)/Akt pathway. Clinically, high Robo1 expression in the breast cancer cells correlates with increased survival in patients with breast cancer, and low Slit2 expression in the stromal fibroblasts is associated with lymph node metastasis. Together, our findings explain how a specific tumor microenvironment can restrain a given type of cancer cell from progression and show that both stromal fibroblasts and tumor cell heterogeneity affect breast cancer outcomes. Cancer Res; 72(18); 4652–61. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    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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