bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2520: CHC promotes tumor growth and angiogenesis through regulation of HIF-1α and VEGF signaling
Authors: Tung Kuo-Hua , Wu Han-Chung 
Published: August 2012

Abstract
Pancreatic adenocarcinoma is an aggressive disease with a high mortality rate. Currently, treatment options are limited. In an effort to improve the efficacy of treatments for pancreatic adenocarcinoma, we have newly generated a monoclonal antibody (mAb), Pa65-2, which specifically binds to various cancer cells and tumor blood vessels but not to normal cells. According to immunoaffinity chromatography, LC-MS/MS analysis, co-immunoprecipitation and RNA interference studies, the target protein of Pa65-2 is human clathrin heavy chain (CHC). Knocking down CHC with shRNA reduced tumor cell growth, colony formation and invasion in vitro, and inhibited tumor angiogenesis and growth. One of the key functions of CHC was to bind with the transcription factor subunit HIF-1α, increasing the stability of this protein and facilitating its nuclear translocation, thereby regulating the expression of VEGF. In animal studies using NOD/SCID mice bearing pancreatic cancer xenografts, Pa65-2 and CHC shRNA could each inhibit tumor growth and angiogenesis by regulating HIF-1α and VEGF. Furthermore, the expression of CHC, HIF-1α and VEGF was significantly correlated with tumor stage, suggesting that CHC might be a useful prognostic indicator for cancer. Considered together, our results indicate that CHC interacts with and stabilizes HIF-1α, and plays a role in HIF-1α nuclear localization and HRE promoter binding, leading to an increased production of VEGF. These results suggest that the CHC mAb, Pa65-2, can potentially be used to inhibit tumor angiogenesis and growth.
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 2520. doi:1538-7445.AM2012-2520
Abstract 2523: The in vitro effects of immobilized epratuzumab, a non-blocking anti-CD22 humanized monoclonal antibody, on malignant B cells
Authors: Gupta Pankaj , Michel Rosana B. , Goldenberg David M. , Chang Chien-Hsing 
Published: August 2012

Abstract
Epratuzumab (hLL2), a humanized anti-CD22 monoclonal antibody, is currently in advanced trials in non-Hodgkin lymphoma (NHL) and systemic lupus erythematosus (SLE) patients. As a single agent, hLL2 is well tolerated and depletes 30 to 50% of circulating B cells in patients with NHL and SLE. The mechanisms by which hLL2 depletes B cells in vivo is still largely unknown and continues to be a subject of current research interest. In vitro, hLL2 shows moderate antibody-dependent cell-mediated cytotoxicity, but no detectable complement-dependent toxicity, and displays cytotoxicity to CD22-expressing cells, for example, Ramos and Daudi human Burkitt lymphomas, only when immobilized onto plastic plates or in combination with a suboptimal amount (1 μg/mL) of anti-IgM plus a crosslinking secondary antibody. We have previously reported that hLL2, despite a lack of direct cytotoxicity, is effective in inducing the phosphorylation of CD22, translocation of CD22 to lipid rafts, and internalization of CD22. In this study, we evaluated the various effects of immobilized hLL2 on D(1-1), a subclone of Daudi selected for a higher expression of membrane IgM (mIgM). Our findings demonstrate for the first time that many of the intracellular events induced by binding CD22 to immobilized hLL2 were similar to those induced by binding mIgM with a sufficient high concentration (10 μg/mL) of anti-IgM; for example, both were found to induce phosphorylation of CD22, CD79a and CD79b, and the translocation of all three into the lipid rafts, which is critical for the observed cytotoxicity. Immunofluorescence analysis revealed CD22 colocalized with BCR and formed caps before being internalized. Like anti-IgM, immobilized hLL2 induced substantial apoptosis (25 to 40%) in D(1-1), which was caspase-dependent, accompanied by a pronounced increase in both pERKs and pJNKs with a concurrent decrease in the constitutively-activated p38, and preventable by inhibitors to JNKs or caspases. The involvement of mitochondria in the apoptotic pathway was evidenced by changes in mitochondrial membrane potential and generation of reactive oxygen species, as well as upregulation of Bax (pro-apoptotic) and downregulation of Bcl-xl, Mcl-1 and Bcl-2 (anti-apoptotic). Further studies are underway to elucidate how hLL2 interferes with B-cell survival in vivo.
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 2523. doi:1538-7445.AM2012-2523
Abstract 2534: Anti-LOXL2 conjugated gold nanoparticles: therapeutic probes for pancreatic cancer
Authors: Guo Yang , Zhang Zhuoli , Li Weiguo , Nicolai Jodi , Omary Reed , Larson Andrew 
Published: August 2012

Abstract
PURPOSE: Multi-functional gold nanoparticles may play an important role in the treatment of pancreatic cancer. The purpose of this study was to demonstrate the feasibility of using these anti-LOXL2 conjugated gold nanoparticles (anti-LOXL2@GoldMag) as therapeutic probes for the treatment of human pancreatic cancer cells. MATERIALS & METHODS: Human pancreatic cancer cell lines (PANC-1, BxPC-3 and Capan-1 cells) was used in this study. Western blot of LOXL2 expression in three cell lines were analyzed and compared to EGFR proteins. GoldMag, the hybrid gold shell and iron oxide core nanoparticles were purchases and their imaging characteristics (R2 and R2* relativity) was measured. Anti-LOXL2@GoldMag probes were constructed according to the instruction and the coupling efficacy of anti-LOXL2 antibodies with GoldMag were tested using a mass spectrophotometer. The specific targeting efficacy of anti-LOXL2@GoldMag was tested using immunofluorescence staining and electronic microscope. Pancreatic cancer cells were treated with anti-LOXL2@GoldMag at the concentrations of 0, 35, 70, 140 and 280 μg/ml and compared to anti-LOXL2 treatment alone at the same dosing concentration. After allowing for 48 hours incubation, the remaining number of viable cells was counted using trypan blue staining; cell proliferation percentage was calculated based on the total number of viable cells after treatment compared to the controls. RESULTS: The therapeutic efficacy of anti-LOXL2@GoldMag demonstrated similar therapeutic efficacy at both lower dose (18-51% reduced total viable cells) and enhanced therapeutic efficacy at the higher dose (86-99% reduced total viable cells) when compared to LOXL2 antibody alone. This suggests that binding of the LOXL2 antibodies to the GoldMag nanoparticles doesn't inhibit immunotherapeutic efficacy. MRI studies demonstrated that R2 and R2* measurements were well correlated to GoldMag probe concentrations. CONCLUSION: Our findings demonstrated significant anti-neoplastic efficacy in three different human pancreatic cancer cell lines. MRI could serve as a non-invasive imaging method to monitor the biodistribution of gold nanoparticles. Further pre-clinical investigations are now warranted in animal models of pancreatic cancer.
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 2534. doi:1538-7445.AM2012-2534
Abstract 2597: Identification of new genes for hereditary breast cancer
Authors: Kuligina Ekaterina Sh. , Sokolenko Anna P. , Suspitsin Evgeny N. , Iyevleva Aglaya G. , Chekmariova Elena V. , Abysheva Svetlana N. , Imyanitov Evgeny N. 
Published: August 2012

Abstract
Major hereditary breast cancer (BC) genes, BRCA1 and BRCA2, contribute to no more than 20-25% of familial BC clustering; therefore the majority of BC-predisposing mutations remain to be identified. We have selected for the study 95 BC cases, which showed accumulation of clinical signs of the genetic disease (e.g., occurrence of BC among multiple relatives and/or bilaterality and/or young age at onset), but could not be explained either by BRCA1/2 sequence alterations or by Russian founder mutations in CHEK2 (c.1100delC, c.444+1G&gt;A, del5395) or NBN (657del5) genes. The entire coding regions of DNA repair genes were examined using high resolution melting (HRM) analysis and DNA sequencing. Three of 16 genes selected for the study (CHEK2, NBN, PALB2, BRIP1, BARD1, RAD51C, BLM, FANCG, CHEK1, PARP1, PARP2, ERCC1, XPE, BRD7, RNF8, RAD51A) contained potentially deleterious mutations. Two patients carried inactivating lesion in the PALB2 gene (p.R414X and p.Q921X); both these carriers had the bilateral form of BC disease. 1 woman harbored mutation in the FANCG gene (c.520_524delTCTAinsC), which resulted in the loss of serine at position 174 and lysine to glutamine substitution at position 175. The analysis of the BLM gene revealed two heterozygous carriers of the c.1642 C&gt;T (Q548X) allele. This mutation was subjected to the extended study, which confirmed its recurrent character and strong association with BC risk: BLM c.1642 C&gt;T (Q548X) heterozygotes were detected in 17/1,498 (1.1%) BC patients as compared to 2/1,093 (0.2%) healthy females (p = 0.004). As expected for BC-predisposing gene, the BLM 1670 C&gt;T allele tended to be associated with first-degree family history of BC, early onset and bilateral appearance of the disease. This is the first demonstration of the role of the BLM heterozygosity in the determination of BC risk. The impact of constitutional BLM mutations in hereditary cancer predisposition deserves to be tested in other ethnic groups as well as in other tumor types.
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 2597. doi:1538-7445.AM2012-2597
Abstract 2602: CHEK2 contribution to hereditary breast cancer in non-BRCA famillies
Authors: Desrichard Alexis , Uhrhammer Nancy , Bidet Yannick , Bignon Yves-Jean 
Published: August 2012

Abstract
Mutations in the BRCA1 and BRCA2 genes are responsible for only a part of hereditary breast cancer (HBC). The origins of “non BRCA” HBC families may be attributed in part to mutations in genes giving moderate risk, such as CHEK2. We investigated the contribution of CHEK2mutations to non-BRCA HBC by direct sequencing of its entire coding sequence. Fifteen mutations were discovered among 507 non-BRCAHBC cases and four among 513 controls. The frequency of CHEK2variants was significantly higher among cases (p= 0.0076), and gave an OR for breast cancer of 4.72 for deleterious mutation carriers. We then used both in silico tools and in vitro kinase activity to evaluate recombinant mutant proteins. Tumor characteristics and tumor grade of paraffin-embedded tissue blocks from 8 CHEK2 mutated patients were evaluated by histology. To further characterize those tumors, breast cancer immunohistochemical markers such as hormone receptors, HER2 and P53 were assessed. Because the mechanisms of tumorigenesis in association with CHEK2 variants are still unclear, we performed genetic and epigenetic analysis of those tumors. Three relevant SNPs spanning the CHEK2 gene locus were used to determine loss of heterozygosity (LOH). Also, the proximal CpG islands of the CHEK2 gene were investigated for hypermethylation. Our results suggest a contribution of CHEK2 mutations to non-BRCA HBC, though the usefulness of moderate penetrance genes for genetic counseling remains controversial.
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 2602. doi:1538-7445.AM2012-2602
Abstract 2610: Association of polymorphisms and haplotypes in the insulin-like growth factor 1 receptor (IGF1R) gene with breast cancer in Korean women
Authors: Kim Mi Kyung , Kang Han-Sung , Ahn Sei Hyun , Hong Kyeong-Man , Mishra Siddhartha Kumar , Shin Kyung Hwan , Ro Jungsil , Lee Keun Seok , Kim Seok Won 
Published: August 2012

Abstract
Abstract The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase growth factor receptor that plays important roles in numerous cellular functions and signal transduction pathways. IGF1R may also play a role in the initiation and progression of breast cancer. However, studies of common variation in the IGF1R gene, involved in steroid hormone and IGF-1 metabolism, have yet to provide convincing evidence that such variants predict breast cancer risk. We genotyped 384 tagging single nucleotide polymorphisms (SNPs) in 1026 cases of breast cancer and 392 age-matched control in a population of Korean women. Of the 384 SNPs, fifty one SNPs in the IGF1R gene were examined for association with breast cancer in the study. All the SNPs investigated were in Hardy-Weinberg equilibrium. These SNPs tested were significantly associated with breast cancer risk, after correction for multiple comparisons stratified by adjusting for age at diagnosis, BMI, age at menarche, and age at first parturition. Among 51 IGF1R SNPs, three intron located SNPs (rs8032477, rs11635251, and rs12916884) with homozygous genotype (variant genotype) had increased risk of breast cancer (OR(CI 95%): 0.66(0.44-0.99), 0.54(0.37-0.80), and 0.59(0.37-0.94)). Seven of the 51 IGF1R SNPs were in LD and in one haplotype block, and were likely to be associated with breast cancer risk. Overall, this comprehensive case-control study found statistically significant associations between breast cancer risk and polymorphisms in IGF1R gene. Taking the status of the IGF1R polymorphism into consideration, our results may help in improving the ability to develop effective treatment modalities for those conditions in which IGF1R is involved. To the best of our knowledge, this study is the first to demonstrate the association between IGF1R polymorphisms with the risk of breast cancer.
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 2610. doi:1538-7445.AM2012-2610
Abstract 2616: Association of UGT2B17 gene copy number variation with breast cancer risk: The Nashville Breast Health Study
Authors: Li Guoliang , Deming Sandra L. , Cai Qiuyin , Fair Alecia M. , Shrubsole Martha J. , Shu Xiao Ou , Kelley Mark , Zheng Wei 
Published: August 2012

Abstract
UDP-glucuronosyltransferase 2B17 (UGT2B17) catalyzes the transfer of glucuronic acid from uridine diphosphoglucuronic acid to a variety of substrates, including estrogen, a hormone that plays an important role in the etiology of breast cancer. Glucuronidated estrogens are more polar and water soluble; thus, they are more easily excreted in the bile and urine. The UGT2B17 gene displays variations in copy number (0 copies, 1 copy, and 2 copies), and the null genotype (0 copies) is associated with lower glucuronidating activity in human liver microsomes. In this study, we evaluated the association of UGT2B17 gene copy number variation with breast cancer risk. Included in the study were 1,536 breast cancer cases and 1,205 matched controls recruited into the Nashville Breast Health Study, a population-based, case-control study based in Nashville, Tennessee. Copy number of the UGT2B17 gene was evaluated by real-time PCR by using ABI's TaqMan Copy Number Assays reagents. UGT2B17 gene copy number variation was associated with breast cancer risk with odds ratios of 1.17 (95% CI: 1.00-1.38) and 1.33 (95% CI: 1.02-1.74), respectively, for 1 and 0 copies of the UGT2B17 gene, compared with 2 copies of the gene. The association varied little by menopausal status. The association was consistent in both whites and African Americans. Our study suggests that UGT2B17 gene copy number variation may play a role in the etiology of breast cancer.
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 2616. doi:1538-7445.AM2012-2616
Abstract 2620: Contribution of risk variant in miR-125b binding site of BMPR1B in women of African ancestry with breast cancer
Authors: Yoshimatsu Toshio F. , Zheng Yonglan , Zhang Jing , Huo Dezheng , Olopade Olufunmilayo I. 
Published: August 2012

Abstract
MicroRNAs play a fundamental role in gene regulation by selective binding to the 3′ UTR of specific mRNAs. Dysregulation of this post-transcriptional regulatory mechanism, in turn, has emerged to be an important process in cancer etiology. Recently a particular single nucleotide polymorphism (SNP) at mir-125b binding locus of BMPR1B, rs1434536, was reported as significant risk factor for breast cancer pathogenesis in Caucasians. The BMPR1B gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The C/T allelic variation within the target site disrupts the regulation of miR-125b, whereby increased BMPR1B expression ultimately elevates disease risk. To validate whether rs1434536 also contributes to breast cancer risk in women of African ancestry, we performed a case-control study of 805 breast cancer cases (422 African Americans (AA) and 383 Nigerians (NG)) and 786 controls (402 AA and 384 NG). The average age (±SD) was 46.9 ± 11.9 years for cases and 45.1 ± 12.4 years for controls. Genotyping was conducted using polymerace chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Test for Hardy-Weinberg equilibrium (HWE) suggested that there was no deviation from HWE (P &gt; 0.05) in AA, or NG. Pearson's chi-squared tests showed that this SNP was significantly associated with breast cancer in AA (p=0.03) but not in NG (p=0.96). After adjusting for age in the logistic regression, we found the heterozygous genotype CT was associated with nearly 30% lower odds of breast cancer compared to CC genotype (OR=0.74, 95% CI 0.55-0.99; p=0.04) in AA. In the pooled analysis adjusting for both age and sites, the CT genotype was not statistically significant (OR=0.85, 95% CI 0.68-1.06; p=0.15). The common allele T (allele frequency = 0.60) was the risk allele in the previous study conducted in Caucasians, whereas the T allele was the minor allele in subjects of African descent (allele frequency = 0.129 in NG and = 0.232 in AA). In conclusion, our preliminary study found the T allele to have a trend for a protective effect in AA, which is disagreement with the observation made in the original study. Thus, this study indicates the need for replication studies in diverse populations to validate whether rs1434536 is a risk variant for specific subtypes of breast cancer.
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 2620. doi:1538-7445.AM2012-2620
Abstract 2635: association between CASP7 and CASP14 genetic polymorphisms and the risk of childhood leukemia
Authors: Park Chulbum , Song Nan , Han Sohee , Choi Ji-Yeob , Park Sue K , Jeon Sujee , Kang Daehee , Ahn Hyo Seop , Shin Hee Young , Kang Hyoung Jin , Koo Hong Hoe , Seo Jong Jin , Choi Ji Eun 
Published: August 2012

Abstract
Current evidence suggests that apoptosis and the cell cycle system play an important role in cancer development. To identify susceptible genetic markers in these mechanisms, we did an association study in 63 patients and 148 controls. A total of 304 SNPs in 31 gene regions were selected. We evaluated an association at a gene region level by computing the minimum p-value (minP) and doing the false discovery rate (FDR) test. Both SNP and gene-based analyses presented associations with the risk of childhood leukemia for 5 genes: CASP7, CASP14, CASP8AP2, MYC, and RIPK1 (Ptrend &lt; 0.05). There were statistically significant associations for CASP7 (rs12416109 and rs3814231, Ptrend = 0.002 and 0.009, respectively, minP = 0.013, FDR = 0.042) and CASP14 (rs8110862, Ptrend &lt; 0.001, minP = 0.002, FDR = 0.027). This study suggests that genetic polymorphisms in apoptosis and cell cycle related genes might play a role in childhood leukemia development.
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 2635. doi:1538-7445.AM2012-2635
Abstract 2639: A community-based study of nucleotide excision repair polymorphisms in relation to risk of non-melanoma skin cancer
Authors: Wheless Lee E. , Kistner-Griffin Emily , Jorgensen Timothy J. , Ruczinski Ingo , Berthier-Schaad Yvette , Kessing Bailey , Hoffman-Bolton Judith , Woodward Lesley , Yao Yin , Strickland Paul T. , Kao W.H Linda , Alani Rhoda M. , Smith Michael W. , Alberg Anthony J. 
Published: August 2012

Abstract
Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against ultraviolet radiation-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically-confirmed cases of NMSC (n=900) were matched to controls (n=900) on age, gender, and skin type. Associations were measured between NMSC and 221 SNPs in 26 NER genes. Using the additive model, two tightly linked functional SNPs in ERCC6 were significantly associated with increased risk of NMSC: rs2228527 (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.20 - 2.05), and rs2228529 (OR 1.57, 95% CI 1.20 - 2.05). These associations were confined to basal cell carcinoma of the skin (BCC) (rs2228529, OR 1.78, 95% CI 1.30 - 2.44; rs2228527 OR 1.78, 95% CI 1.31 - 2.43). These novel, hypothesis-generating findings suggest functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC.
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 2639. doi:1538-7445.AM2012-2639