bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3751: Expression analysis of the IL28A, IL28B, IL29 and IL28L genes in primary human peripheral blood mononuclear cells and hepatocytes: Effects of activation mode, time-course and genotypes
Authors: Muchmore Brian , Park Heiyoung , Dickensheets Harold , O'Brien Thomas , Rehermann Barbara , Donnelly Raymond , Prokunina-Olsson Ludmila 
Published: June 2012

Abstract
Expression analysis of the IL28A, IL28B, IL29 and IL28L genes in primary human peripheral blood mononuclear cells and hepatocytes: Effects of activation mode, time-course and genotypes.
Chronic hepatitis C virus (HCV) infection is the leading cause of liver cancer and liver transplantation in the United States. Recently, several genome-wide association studies (GWAS) identified genetic variants within the IL28A/B locus on chromosome 19q13.2 as the strongest predictors of outcome of HCV infection and response to treatment (e.g. rs12980275, p=2.84×10-27, OR=17.7; 95% CI=10.0-31.3, Tanaka, Nat. Gen. 2009). This region harbors the highly homologous IL29, IL28A, IL28B genes and a pseudogene IL28-like (IL28L), also known as interferon-lambda-1, interferon-lambda-2, interferon-lambda-3 and interferon-lambda-4-pseudo, respectively. We hypothesized that the associated genetic variants might affect mRNA expression of one or more of these genes.
We performed mRNA expression analysis of IL28A, IL28B, IL29 and IL28L in human peripheral blood mononuclear cells (PBMCs) and primary hepatocytes using highly specific custom-designed assays to overcome the up to 97% sequence homology between these genes. In PBMCs and hepatocytes, mRNA transcripts were not expressed under baseline conditions, but activation of these cells with IFN-alpha or IFN-lambda did moderately induce expression of some transcripts after 24 hours of activation. However, when IL28A, IL28B, IL29 and IL28L were activated with the immunostimulant poly I:C, a Toll-like receptor-3 agonist that mimics infection by RNA viruses, expression of all transcripts was strongly increased. Gene expression was measured at 0, 1, 2, 4, 8 and 24 hours and was compared to the 2-hour point, at which expression was first stably seen. We observed a suggestive association between time-specific activation of all transcripts and genetic variants correlated with HCV infection and treatment outcome. In hepatocytes, mRNA levels of all transcripts were increased in carriers of risk alleles associated with poor treatment outcome at 24 hours compared to 2 hours (60-fold for IL28A, 85-fold for IL28B, 222-fold for IL29 and 5-fold for IL28L) suggesting that under certain circumstances increased baseline interferon production in carriers of risk variants could be deleterious. The clinical relevance of our in vitro findings should be validated by similar studies in primary liver and blood samples derived from HCV-infected individuals.
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 3751. doi:10.1158/1538-7445.AM2011-3751
Abstract 3758: The relationship of calcium and magnesium intakes, VDR polymorphisms and the risk of colorectal adenoma: results from the Tennessee Colorectal Polyp Study
Authors: Xiangzhu Zhu , Shrubsole Martha J. , Ness Reid M. , Cai Qiuyin , Edwards Todd L. , Long Jirong , Chen Zhi , Deng Xinqing , Sun Pin , Luo Jianfeng , Smalley WalterSmalley E. , Zheng Wei , Dai Qi 
Published: June 2012

Abstract
Background: Epidemiological studies suggest that high calcium intake and adequate vitamin D levels may reduce risk of colorectal cancer or adenoma although findings have not been entirely consistent. Some previous studies found that the association between calcium intake and colorectal cancer or adenoma was modified by polymorphisms in vitamin D receptor (VDR) gene. In addition to regulating calcium level, vitamin D is also involved in magnesium homeostasis. However, no study has investigated possible interaction between magnesium intake and VDR polymorphisms. Objectives: To investigate whether intakes of calcium, particularly magnesium, interact with VDR genetic variants in relation to colorectal adenoma risk. Methods: Included in the study are 958 adenoma cases and 909 healthy controls from the Tennessee Colorectal Polyp Study (TCPS), an ongoing colonoscopy-based case control study conducted in Nashville, TN. Genotyping was performed using the Affymetrix Human Mapping 500K array set. Dietary nutrients intakes were obtained from food frequency questionnaire (FFQ) and dietary supplements and adjusted for total energy intake using the residual method. Multivariate unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Multiplicative interactions for gene-nutrients interactions were evaluated in logistic regression models by using likelihood ratio tests. Results: Eighteen tagging SNPs in the VDR gene were analyzed. Two SNPs (rs12717991, rs2189480) were significantly associated with a reduced risk of colorectal adenoma. Furthermore, intakes of calcium (p for interaction, 0.01) and magnesium (p for interaction, 0.03) significantly interacted with rs2189480 in relation to adenoma risk. The inverse association with rs2189480 was of borderline significance among participants with a low calcium intake (P for trend=0.06) with ORs (95% CI) of 0.80 (0.58, 1.10) and 0.67 (0.41, 1.10), respectively, for GT and TT. Among participants with high intake of magnesium, the inverse association was significant (P for trend=0.007) with ORs (95%CI) of 0.52 (0.38, 0.72) and 0.72 (0.44, 1.18), respectively for GT and TT. Conclusions: These findings suggest that some genetic variations in the VDR gene may interact with dietary intakes of calcium and magnesium intake in the risk of colorectal adenoma.
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 3758. doi:10.1158/1538-7445.AM2011-3758
Abstract 3767: Familial colorectal cancer registry in Hispanics: A feasibility study
Authors: Diaz-Algorri Yaritza , Joy Leilani , Balbuena-Merle Raisa , Acosta Delma , Nunez Cristina , Torres-Cintron Mariela , Figueroa-Valles Nayda , Cardona Alberto , Lacourt-Ventura Mercedes , Bernabe-Dones Raul , Lopez-Enriquez Reynold , Haile Robert , Mosquera-Fernandez Rafael , Members APG , Cruz-Correa Marcia 
Published: June 2012

Abstract
BACKGROUND: In Puerto Rico (PR), colorectal cancer (CRC) represents the second most common cause of cancer in men and women. Incidence and mortality of CRC are increasing in Puerto Rican Hispanics, especially among young individuals. Screening rates for CRC are lower in Hispanic-American individuals compared to non-Hispanic patients. However, there is limited data on genetic epidemiological CRC disparities in Hispanic patients.
OBJECTIVES: (1) To prospectively identify and recruit 30 probands with a family history of CRC and 15 family-history negative (2) To prospectively identify and recruit selected relatives from the 45 probands.
METHODS: Eligible cases are Hispanic patients with incident diagnosis of CRC, ≥ 21 years old. We identified the probands and their selected family members using the Puerto Rico Central Cancer Registry from July 1, 2007 to the present.
PRELIMINARY DATA AND RECRUITMENT: Seven hundred and fifty-one communications were sent to the physicians, three hundred and seventy-four communications were responded (374/751=49.8%).Three hundred and forty-one communications were sent to the patients, one hundred and forty-seven letters were responded (147/341=43.1%) and 16 refused.
One hundred and fifty-nine participants (probands and relatives) were enrolled. One hundred and two probands (mean age 56.9 ±13.3 yrs., 54.9% male); 30 with and 72 without family history of CRC. At present, we collected 153 (96.2%) risk factors questionnaires, 135 (84.9%) blood samples and 60 (52.6%) blocks of tissue.
CONCLUSIONS: Successful implementation of logistics for identification of incident CRC through the PR Central Cancer Registry during a three-year period. We established the first Familial CRC island-wide registry in Puerto Rico through the implementation of a network of community physicians, laboratories and professional societies. We are developing a tissue and blood bank with epidemiological, nutritional, and demographic data that will assist us to understand the genetic epidemiology of CRC in Puerto Ricans.
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 3767. doi:10.1158/1538-7445.AM2011-3767
Abstract 3829: Inducible silencing of PKD3 reveals a critical role for PKD3 in prostate cancer growth and metastasis
Authors: LaValle Courtney R. , Zhang Liyong , Eiseman Julie , Wang Q. Jane 
Published: June 2012

Abstract
Protein kinase D is a family of novel serine/threonine kinases that act as major mediators of several signaling pathways related to cancer development. Increasing evidence has demonstrated that specific PKD isoforms are deregulated in human cancers and that PKD plays an active role in cancer cell proliferation, migration, and invasion. Here, we present evidence on the development of a PC3 tetracycline-inducible PKD3 knockdown prostate cancer cell line and its application in both the study of PKD3 function in cells and the validation of PKD3 as a therapeutic target in vivo. We show that tetracycline treatment results in &gt;50% knockdown of endogenous PKD3 expression in two distinct clones expressing PKD3 shRNA (shPKD3-C7 and shPKD3-C26), but has no effect on cells expressing scrambled shRNA (shSCR). Furthermore, endogenous PKD1 or PKD2 expression levels are not altered in PKD3 knockdown cells treated with tetracycline, supporting the specific targeting of the shRNA to the PKD3 isoform. Phenotypic analysis revealed that, similar to studies utilizing PKD siRNAs or novel PKD inhibitors, tetracycline-induced silencing of PKD3 causes potent arrest in cell growth and motility. Additionally, we found that conditioned media collected from tetracycline-treated shPKD3-C7 cells causes a reduction in PC3 cell migration, and we observed increased secretion of the tissue inhibitor of metalloproteinases-2 (TIMP-2) protein, which has important anti-angiogenic functions, from tetracycline-treated shPKD3-C7 cells. Western blotting revealed that both siRNA-mediated transient knockdown of PKD2 or PKD3 or treatment with novel PKD inhibitors led to decreased levels of the matrix metalloproteinases MMP-9, MMP-11, and MMP-14 in PC3 cells. Finally, we found that reduction of PKD3 expression by tetracycline-inducible shRNA significantly retarded both tumor growth in a subcutaneous xenograft model as well as tumor growth and metastasis in an orthotopic prostate cancer xenograft model. Taken together, these data suggest that PKD is a critical signaling protein that modulates prostate cancer cell growth and motility through a pathway involving multiple secreted factors, and that PKD3 is a potential therapeutic target in the treatment of prostate cancer.
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 3829. doi:10.1158/1538-7445.AM2011-3829
Abstract 3862: Functional characterization of sFRP1 expression loss in human papillary bladder cancer
Authors: Rogler Anja , Hartmann Arndt , Goebell Peter , Wullich Bernd , Stoehr Robert 
Published: June 2012

Abstract
Introduction: Secreted frizzled-related protein 1 (sFRP1) is an inhibitor of the Wnt-signaling pathway and expression loss is associated with e.g. colon and breast cancer. Our previous studies revealed an involvement of sFRP1 loss in progression of papillary bladder cancer.
We therefore performed functional studies to characterise the role of sFRP1 in papillary bladder cancer cell lines.
Material and methods: Human papillary bladder cancer cell lines RT112 and BFTC 905 were used for the analyses. mRNA-expression status of sfrp1 and Wnt-target genes c-myc and cyclin D1 was determined using qRT-PCR. Methylation status of sfrp1 promoter was analysed with MS-PCR. sFRP1 knockdown was performed using sFRP1-specific siRNAs. 5’ Aza-2’deoxycytidine (5’Aza) treatment was used for promoter demethylation and restoration of sFRP1 expression. To determine Wnt pathway activity a luminescence-based TOP flash/FOP flash assay was used. Proliferation level was investigated with ELISA-based BrdU Cell Proliferation assay.
Results: RT112 is strongly expressing sfrp1 on mRNA level, whereas BFTC905 showed no sfrp1 expression. MS-PCR revealed sfrp1-promoter methylation in BFTC905. This methylation could be reversed after 5’-Aza-treatment and led to re-expression of sfrp1 on mRNA level. sfrp1 siRNA transfection in RT112 led to ∼80% gene silencing. sfrp1 knockdown resulted in an upregulation of c-myc (515%) and cyclin D1 (51,5%) on mRNA level, however TCF/LEF-presence could not be detected, neither in untreated nor in siRNA transfected RT112 cells. Untreated BFTC905 cells showed a very weak Wnt signalling activitiy, compared to positive control cell line SW480, but 7-fold higher than in untreated and siRNA treated RT112. sfrp1 knowdown in RT112 had no influence on cell proliferation.
Conclusion: sfrp1 knockdown in RT112 cells is associated with an up-regulation of proliferation-associated genes c-myc and cyclin D1, whereas this increased expression showed no effects on proliferation behaviour of the cells. Knockdown of sFRP1 did not result in significant Wnt-signaling activity in RT112 cells. Reduced sFRP1 expression might increase the proliferative potential of the cells; however additional genetic events might have to occur to induce increased proliferation of the cells. Ongoing analyses of BFTC905 with transient restoration of sFRP1 expression will give further insights into the role of sFRP1 in papillary bladder cancer.
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 3862. doi:10.1158/1538-7445.AM2011-3862
Abstract 4346: Differential response of a novel protein kinase C-iota inhibitor (ICA-1) on neuroblastoma cells
Authors: Pillai Prajit P. , Acevedo-Duncan Mildred 
Published: June 2012

Abstract
Neuroblastoma is the most common extra cranial tumor diagnosed in children and in infants. The focus of this research was to establish the efficacy of ICA-1 as a novel chemotherapeutic agent for neuroblastoma. ICA-1 was designed to target Protein kinase C-iota (PKC-ι) which has been shown to promote resistance to drug-induced apoptosis in cancer cells, a major obstacle to good prognosis in neuroblastoma. Our preliminary results from in-vitro kinase activity assay demonstrated that ICA-1 selectively downregulated the activity of PKC-ι but had no effect on the activity of PKC-zeta, the closely related family member of the atypical PKC family. Phenotypically, neuroblastoma cells can be divided into 3 distinct groups- sympathoadrenal neuroblasts or N-type that form slow growing tumors, non-neuronal precursor cells or S-type which are non-malignant and I-type which are morphologically and biochemically intermediate to that of N and S cells. ICA-1 inhibited the cell proliferation of LA1-55n (N-type) and BE(2)-C (I-type) neuroblastoma cells. The IC50 was 0.1 µM for both cell lines. Interestingly, ICA-1 had no significant effect on the proliferation of LA1-5s (S-type) non-malignant cells. Furthermore, ICA-1 treatment also induced apoptosis in neuroblastoma cells as shown by TUNNEL assay, Caspase activation and PARP cleavage. Thus, our results provide evidence suggesting that ICA-1 is a promising chemotherapeutic for neuroblastoma with negligible toxicity to normal 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 4346. doi:10.1158/1538-7445.AM2011-4346
Abstract 4397: Bioavailability of substituted quinoline, a gap junction enhancer
Authors: Ding Ying , Prasain Keshar , Hua Duy H. , Nguyen Thu Annelise 
Published: June 2012

Abstract
Breast cancer is one of the most malignant diseases that threaten the health of women all over the world, especially in western countries. It ranks the second leading cause of cancer deaths among women in the United States. Several drugs have been discovered to target different pathways of breast cancer cells; however, drug resistance and side effects have increasingly become a major concern. One of the effective methods is combinational treatment of different drugs. Loss of gap junctional intercellular communication (GJIC) is thought as one of the important hallmarks of cancer. It is believed that restoration of GJIC in cancer cells is related to reduction of tumorigenesis and increase of drug sensitivity. Gap junctions are intercellular channels connecting adjacent cells, allowing cells to transport small molecules (&lt; 1.2kDa) from one cell to the next. This ordination of communication keeps cells at homeostasis. Previous report showed that combinational treatment of substituted quinoline (PQ1, a gap junction enhancer) and tamoxifen (a common used chemotherapeutic agent for breast cancers) can lower the concentration of tamoxifen in T47D breast cancer cells. It was also reported that PQ1 could increase 70% GJIC in T47D cells, whereas had no effect on GJIC in normal human mammary epithelial cells (HMECs) in vitro. However, the toxicity of PQ1 in vivo is still unknown. In this study, bioavailability of PQ1 was studied in mice. Twenty-five micrograms/kg body weight of PQ1 was administered orally to 5 week old mice. After 1, 12, or 24 hours of treatment, mice were sacrificed, and amounts of PQ1 in different organs were tested by HPLC and mass spectrometry. Expressions of connexin 43 and different protein markers (survivin, caspase-8, cleaved caspase-3, and aryl hydrocarbon receptor (AhR)) in organs were tested by western blot analysis. Hematoxylin and eosin staining was performed. Our results showed that compared to control, the expression of Cx43 in normal organs of the mice treated with PQ1 decreased, which is contrary to the effect of PQ1 on cancer cells. We also found that PQ1 can increase the expression of survivin and decrease the expression of caspase-8 and cleaved caspase-3 in nearly all the tested organs. Expression of AhR in liver was directly related with PQ1 amount, which means PQ1 is mediated through AhR and can be metabolized by liver. Histological results of the liver implied that PQ1 is not toxic to the tissue structure. Our studies demonstrate that PQ1 is a promising anti-cancer drug as well as in combinational treatment with other antineoplastic drugs with high specificity to cancer cells and low toxicity to normal organs.
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 4397. doi:10.1158/1538-7445.AM2011-4397
Abstract 4509: BAY 87-2243 targets hypoxia-induced activation and stabilization of HIF-1α: A novel approach to overcome resistance mechanisms in cancer therapy
Authors: Berhoerster Kerstin , Haerter Michael , Ellinghaus Peter , Heisler Iring , Beck Hartmut , Greschat Susanne , Thierauch Karl-Heinz , Wilhelm Scott , von Ahsen Oliver , Hess-Stumpp Holger , Ziegelbauer Karl 
Published: June 2012

Abstract
The development of resistance against radio- or chemotherapy is one of the main causes for relapse after treatment and ultimately cancer progression. Local hypoxia within tumors is associated with radio- and chemoresistance as well as aggressive tumor growth and invasion (Vaupel et al., 2004). The transcription factor HIF-1α (hypoxia-inducible factor) is stabilized under low oxygen tension and heterodimerizes with HIF-1ß to regulate the expression of a plethora of genes involved in cellular energy metabolism, neoangiogenesis, anti-apoptotic and pro-proliferative mechanisms promoting tumor progression and metastasis (Calzada et al. 2007). Because hypoxia-induced upregulation of HIF-1α appears to be of pivotal importance in tumor resistance mechanisms during cancer treatment, we screened for inhibitors of hypoxia-induced HIF-1 activation.
A HCT116 cell line containing 4X-hypoxia response element-luciferase reporter was used in high-throughput screening of small molecule inhibitors under hypoxic condition (1% O2). Lead optimization resulted in the identification of BAY 87-2243, a highly selective and potent inhibitor of hypoxia-induced HIF-1α stabilization and activation. In vitro characterization showed that BAY 87-2243 specifically suppressed HIF-1 regulated target genes as assayed by qPCR. Analyses addressing the mode of action revealed that BAY 87-2243 acts upstream of VHL and PHD because the compound did not suppress HIF-1α protein stabilization and HIF target gene expression either in the presence of a PHD inhibitor in H460 cells or in VHL-null RCC4 cells. In preclinical animal models, BAY 87-2243 dosed orally was well tolerated at therapeutic doses up to 15 mg/kg and showed moderate to high anti-tumor growth inhibitory activity as monotherapy in various subcutaneous and orthotopic xenograft models. Analysis of tumor samples demonstrated a decrease of nuclear HIF-1α protein level by immunohistochemistry as well as a specific suppression of HIF-1 target genes. These data indicate that specific inhibition of hypoxia-induced HIF-1 activation is achievable with small molecule inhibitors and is a novel approach to cancer therapy.
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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 4509. doi:10.1158/1538-7445.AM2011-4509