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  • American Association for Cancer Research (AACR)  (33)
  • 11
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 22, No. 10 ( 2013-10-01), p. 1868-1876
    Abstract: Background: Statins are a class of cholesterol-lowering drugs that affect many intracellular pathways that may have implications for chemoprevention against cancer. Epidemiologic data on statins and breast cancer are conflicting. We analyzed updated data from the Women's Health Initiative (WHI) to assess the relationship between statins and breast cancer risk. Methods: The population included 154,587 postmenopausal women ages 50 to 79 years, with 7,430 pathologically confirmed cases of breast cancer identified over an average of 10.8 (SD, 3.3) years. Information on statins was collected at baseline and years one, three, six, and nine. Self- and interviewer-administered questionnaires were used to collect information on risk factors. Cox proportional hazards regression was used to calculate HRs with 95% confidence intervals (CI) to evaluate the relationship between statin use and cancer risk. Statistical tests were two-sided. Results: Statins were used by 11,584 (7.5%) women at baseline. The annualized rate of breast cancer was 0.42% among statin users and 0.42% among nonusers. The multivariable adjusted HR of breast cancer for users versus nonusers was 0.94 (95% CI, 0.83–1.06). In the multivariable-adjusted, time-dependent model, the HR for simvastatin was 0.87 (95% CI, 0.71–1.07). There was no significant trend by overall duration of use (P value for trend 0.68). There was no effect of tumor stage, grade, or hormone receptor status. Conclusion: Overall, statins were not associated with breast cancer risk. Impact: Our study is one of the largest prospective observational studies on this topic, and substantially adds to the literature suggesting no relationship between statins and breast cancer risk. Cancer Epidemiol Biomarkers Prev; 22(10); 1868–76. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 12
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2847-2847
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2847-2847
    Abstract: Previous gene mapping efforts, including a recent admixture mapping study, concluded that there is likely at least one prostate cancer susceptibility locus on 7q32. Podocalyxin (PODXL) is the strongest candidate gene in this region, particularly for risk of aggressive disease (Casey et al. Human Molecular Genetics, 5: 735-741, 2006). Therefore, we examined 34 tagSNPs in the PODXL gene in relation to prostate cancer risk and aggressiveness in a sample of unrelated cases (n=626) and controls (n=239) from metropolitan Detroit, MI. Men were recruited from Henry Ford Health System; cases were diagnosed with prostate cancer between 2001 and 2004, and controls were frequency matched to cases on 5 year age groups and race. Logistic regression models were adjusted for family history of prostate cancer, race, age, and ancestry where appropriate. Carrying at least one copy of the variant A allele in SNP rs3212299 was associated with a decrease in prostate cancer risk (OR=0.60, 95% CI: 0.41, 0.90). Having at least on copy of the C allele in SNP rs11773254 was associated with a 70% increased risk of prostate cancer (OR = 1.70, 95% CI: 1.13, 2.58). The G allele of rs1733874 was marginally protective in the entire sample (OR=0.74, 95% CI: 0.49, 1.02). These risk estimates did not appreciably vary after stratifying by race [African American (AA), European American (EA)], age ( & lt; age 62, & gt; age 62), or prostate cancer aggressiveness (Gleason sum 3+4 or lower, Gleason sum 4+3 or higher). In addition, a protective effect of the C allele in SNP rs3800684 was observed in AA men (OR=0.56, 95% CI: 0.35, 0.90) but not in EA men (OR=1.38, 95% CI: 0.92, 2.09), and there was a statistically significant interaction between race and genotype at this marker (p=0.005). After stratifying by median age, the A allele of SNP rs10224884 was marginally associated with increased prostate cancer risk in the older age group (OR=1.44, 95% CI : 0.92, 2.27), but not the younger age group (OR=0.69, 95% CI: 0.42, 1.13), and the interaction between age group and genotype was statistically significant (0.03). Overall, we conclude that SNPs in the PODXL gene are associated with prostate cancer risk, but not prostate cancer aggressiveness, and that some of these variants may have race- and age-specific effects. 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 2847.
    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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  • 13
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 26, No. 2 ( 2017-02-01), p. 285-285
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 26, No. 2 ( 2017-02-01), p. 285-285
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 14
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 8 ( 2021-04-15), p. 1988-2001
    Abstract: Hepatic fat accumulation is associated with diabetes and hepatocellular carcinoma (HCC). Here, we characterize the metabolic response that high-fat availability elicits in livers before disease development. After a short term on a high-fat diet (HFD), otherwise healthy mice showed elevated hepatic glucose uptake and increased glucose contribution to serine and pyruvate carboxylase activity compared with control diet (CD) mice. This glucose phenotype occurred independently from transcriptional or proteomic programming, which identifies increased peroxisomal and lipid metabolism pathways. HFD-fed mice exhibited increased lactate production when challenged with glucose. Consistently, administration of an oral glucose bolus to healthy individuals revealed a correlation between waist circumference and lactate secretion in a human cohort. In vitro, palmitate exposure stimulated production of reactive oxygen species and subsequent glucose uptake and lactate secretion in hepatocytes and liver cancer cells. Furthermore, HFD enhanced the formation of HCC compared with CD in mice exposed to a hepatic carcinogen. Regardless of the dietary background, all murine tumors showed similar alterations in glucose metabolism to those identified in fat exposed nontransformed mouse livers, however, particular lipid species were elevated in HFD tumor and nontumor-bearing HFD liver tissue. These findings suggest that fat can induce glucose-mediated metabolic changes in nontransformed liver cells similar to those found in HCC. Significance: With obesity-induced hepatocellular carcinoma on a rising trend, this study shows in normal, nontransformed livers that fat induces glucose metabolism similar to an oncogenic transformation.
    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: 2021
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  • 15
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2004
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 13, No. 1 ( 2004-01-01), p. 87-93
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 13, No. 1 ( 2004-01-01), p. 87-93
    Abstract: Risk estimation in breast cancer families is often estimated by use of the Claus tables. We analyzed the family histories of 196 counselees; compared the Claus tables with the Claus, the BRCA1/2, the BRCA1/2/ models; and performed linear regression analysis to extend the Claus tables with characteristics of hereditary breast cancer. Finally, we compared the Claus extended method with the Claus, the BRCA1/2, and the BRCA1/2/u models. We found 47% agreement for Claus table versus Claus model; 39% agreement for Claus table versus BRCA1/2 model; 48% agreement for Claus table versus BRCA1/2/u model; 37% agreement for Claus extended method versus Claus model; 44% agreement for Claus extended model versus BRCA1/2 model; and 66% agreement for Claus extended method versus BRCA1/2/u model. The regression formula (Claus extended method) for the lifetime risk for breast cancer was 0.08 + 0.40 ∗ Claus Table + 0.07 ∗ ovarian cancer + 0.08 ∗ bilateral breast cancer + 0.07 ∗ multiple cases. This new method for risk estimation, which is an extension of the Claus tables, incorporates information on the presence of ovarian cancer, bilateral breast cancer, and whether there are more than two affected relatives with breast cancer. This extension might offer a good alternative for breast cancer risk estimation in clinical practice.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2004
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  • 16
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 15 ( 2006-08-01), p. 7429-7437
    Abstract: High-grade gliomas are devastating brain tumors associated with a mean survival of & lt;50 weeks. Two of the most common genetic changes observed in these tumors are overexpression/mutation of the epidermal growth factor receptor (EGFR) vIII and loss of PTEN/MMAC1 expression. To determine whether somatically acquired EGFRvIII expression or Pten loss accelerates high-grade glioma development, we used a previously characterized RasB8 glioma-prone mouse strain, in which these specific genetic changes were focally introduced at 4 weeks of age. We show that both postnatal EGFRvIII expression and Pten inactivation in RasB8 mice potentiate high-grade glioma development. Moreover, we observe a concordant loss of Pten and EGFR overexpression in nearly all high-grade gliomas induced by either EGFRvIII introduction or Pten inactivation. This novel preclinical model of high-grade glioma will be useful in evaluating brain tumor therapies targeted to the pathways specifically dysregulated by EGFR expression or Pten loss. (Cancer Res 2006; 66(15): 7429-37)
    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: 2006
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  • 17
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5621-5621
    Abstract: Uveal melanoma is the most common cancer of the eye and metastasizes in approximately 50% of patients. None of the current therapies prevents the development of metastases or extends the survival time of these patients. Bi-specific T cell engager (BiTE) are based on recombinant single-chain antibody constructs. These molecules can transiently connect T cells to tumor cells, leading to concomitant T cell activation and serial lysis of tumor cells. Recently, a BiTE antibody bi-specific for CD19 and CD3 (blinatumomab) has shown very high response rates in patients with refractory non-Hodgkin's B cell lymphoma (100%) and B-precursor acute lymphocytic leukemia (80%). These findings suggest that the mode of BiTE antibody action may also be useful for treatment of solid tumors. Human melanoma-associated chondroitin sulfate proteoglycan (MCSP, also known as HMW-MAA, gp240, or CSPG4), is expressed on the surface of & gt;90% of human cutaneous melanoma lesions and cell lines, with restricted distribution in normal tissues. MCSP expression has also been detected in uveal melanoma tumor-tissue sections and could serve as a target antigen for immunotherapeutic approaches. Here we report that primary and metastatic uveal melanoma cell lines express MCSP and that CD4+ and CD8+ T cells are activated to lyse MCSP-expressing uveal melanoma cells by a novel BiTE antibody, which is bispecific for MCSP and CD3 (MCSP-BiTE). The surface of uveal melanoma cells was stained by anti-MCSP monoclonal antibodies when analyzed by flow cytometry. Seven out of 9 primary and 1 out of 3 metastatic uveal melanoma cell lines expressed MCSP at various expression levels. For functional analysis, CD4+ and CD8+ T cells were isolated from peripheral blood mononuclear cells (PBMC) of healthy donors using magnetic bead sorting. Both PBMC and unstimulated CD8+ T cells specifically lysed MCSP+ uveal melanoma cells in the presence of MCSP-BiTE as determined by 51Cr-release assays. As detected by ELISA, unstimulated CD4+ T cells produced IFNγ in response to MCSP-expressing uveal melanoma cells in the presence of MCSP-BiTE, and redirected lysis was evident by microscopy. In contrast, co-culture of T cells with MCSP-expressing uveal melanoma cells alone, or in the presence of a control BiTE, did not result in cytolytic activity or IFNγ release. Furthermore, naïve CD4+ and CD8+ T cells upregulated expression of T cell activation markers CD25 and CD137 solely in response to MCSP-expressing uveal melanoma cells decorated with MCSP-BiTE. BiTE-induced T cell activation required the expression of MCSP, as co-culture of T cells with MCSP-negative uveal melanoma cells in combination with MCSP-BiTE did not result in T cell activation. In conclusion, MCSP-BiTE can induce CD4+ and CD8+ T cells against MCSP-expressing uveal melanoma cells and should therefore be tested as a novel immunotherapy for uveal melanoma patients. 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 5621.
    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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  • 18
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 2 ( 2018-01-15), p. 501-515
    Abstract: Radiotherapy is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo, resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage, and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome in radiotherapy-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant breast cancer xenografts highly amenable to sensitization by cotreatment with a miR-139-5p mimetic. Significance: The microRNA described in this study offers a potentially useful predictive biomarker of radiosensitivity in solid tumors and a generally applicable druggable target for tumor radiosensitization. Cancer Res; 78(2); 501–15. ©2017 AACR.
    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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  • 19
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2007
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 16, No. 4 ( 2007-04-01), p. 803-808
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 16, No. 4 ( 2007-04-01), p. 803-808
    Abstract: 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the major heterocyclic amine generated from cooking meats at high temperatures, and dietary exposures have been shown to induce prostate cancer in rats. PhIP derives its carcinogenic potential through the formation of PhIP-DNA adducts. The purpose of this study was to examine whether self-reported consumption and preparation doneness of grilled meats were associated with PhIP-DNA adduct levels in prostate epithelial cells. The study population consisted of 268 African-American and Caucasian men who underwent radical prostatectomy for prostate cancer. PhIP-DNA adducts in tumor and adjacent nontumor cells were measured using immunohistochemical methods, and dietary meat intake information was based on food frequency questionnaires. Data were analyzed using multivariate linear regression models. After adjusting for age at prostatectomy and race, grilled meat consumption (P = 0.002) was significantly associated with higher adduct levels in tumor cells, but this association seemed to be primarily due to consumption of grilled red meats (P = 0.001) as opposed to grilled white meat consumption (P = 0.15). Among the specific food items, grilled hamburger consumption had the most significant association with adduct level in tumor cells (P = 0.002). Similar trends in positive associations with grilled meat consumption and adduct levels were observed in nontumor cells, but none of these associations reached statistical significance. Our results suggest that dietary interventions targeted at lower consumption of grilled red meats may reduce prostate cancer risk via the PhIP prostate carcinogenic pathway. (Cancer Epidemiol Biomarkers Prev 2007;16(4):803–8)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 20
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 16, No. 6 ( 2007-06-01), p. 1236-1245
    Abstract: Polycyclic aromatic hydrocarbon (PAH)-DNA adducts may induce mutations that contribute to carcinogenesis. We evaluated potential associations between smoking and polymorphisms in PAH metabolism [CYP1A1 Ile462Val, CYP1B1 Ala119Ser and Leu432Val, microsomal epoxide hydrolase (mEH) Tyr113His and His139Arg, CYP3A4 A(−392)G] and conjugation [glutathione S-transferase (GST) M1 null deletion, GSTP1 Ile105Val] genes and PAH-DNA adduct levels (measured by immunohistochemistry) in tumor and nontumor prostate cells in 400 prostate cancer cases. Although no statistically significant associations were observed in the total sample, stratification by ethnicity revealed that Caucasian ever smokers compared with nonsmokers had higher adduct levels in tumor cells (mean staining intensity in absorbance units ± SE, 0.1748 ± 0.0052 versus 0.1507 ± 0.0070; P = 0.006), and Caucasians carrying two mEH 139Arg compared with two 139His alleles had lower adducts in tumor (0.1320 ± 0.0129 versus 0.1714 ± 0.0059; P = 0.006) and nontumor (0.1856 ± 0.0184 versus 0.2291 ± 0.0085; P = 0.03) cells. African Americans with two CYP1B1 432Val compared with two 432Ile alleles had lower adducts in tumor cells (0.1600 ± 0.0060 versus 0.1970 ± 0.0153; P = 0.03). After adjusting for smoking status, carrying the putative “high-risk” genotype combination, the faster metabolism of PAH-epoxides to PAH-diol-epoxides (CYP1B1 432Val/Val and mEH 139Arg/Arg) with lower PAH-diol-epoxide conjugation (GSTP1 105Ile/Ile), was associated with increased adducts only in Caucasian nontumor cells (0.2363 ± 0.0132 versus 0.1920 ± 0.0157; P= 0.05). We present evidence, for the first time in human prostate that the association between smoking and PAH-DNA adducts differs by race and is modified by common genetic variants. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1236–45)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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    detail.hit.zdb_id: 1153420-5
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