bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A56: Tumor alarm gene FHIT activates tumor suppressive system by self-scarifying
Authors: Oh Ah-Young , Lee Sun-Hye , Chung Ji-Yun , Jung Youn-Sang , Park Bum-Joon 
Published: June 2012

Abstract
Human fragile histidine triad (FHIT) is known to be a putative tumor suppressor gene because of frequent deletion and mutation in various kinds of human cancers, in particular, human lung cancer. However, its biological function as tumor suppressor gene, has not been demonstrated. In fact, there are conflict results on the role of FHIT. Oncogenic property of FHIT has been proposed such as overeactivation of ATR/CHK1 pathway in FHIT deficient cells, and low tumor incidence in FHIT-deficient mice. In contrast, tumor suppressive functions such as cell cycle inhibition and induction of apoptosis also proposed. Here we provide the evidences about unexpected working mechanism of FHIT as a tumor alarm gene. FHIT can awake the intracellular tumor suppressive system through reduction or deletion itself. FHIT reduction or deleted cells significantly increase the p21/WAF1 expression as well as p14/ARF-p53. It is achieved at posttranslation level and p53-dependent manner. So loss of FHIT can sequester the cell cycle in G1 phase. FHIT reduction can be achieved by oncogene activation and DNA damage. Thus, FHIT-deficient cells did not response to additional tumor risk and accumulation of additional genetic mutation is easily fixed in genome, which may contribute to tumor progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A56.
Abstract A59: Life and death decision by E2F1 depends on Jab1-mediated expression of E2F apoptotic target genes and is counteracted by PI3K activation.
Authors: Lu Huarui , Hallstrom Timothy C. 
Published: June 2012

Abstract
Rb regulation of cell cycle progression and tumorigenesis is dependent on its control of E2F transcription factor function, a family of proteins that initiate both cell proliferation and cell death. Several classes of E2F target genes have been categorized based on their roles in DNA replication, G2/M & mitosis, apoptosis, DNA repair, etc. However, the mechanisms controlling appropriate expression of genes responsible for these cell fates is poorly understood. We previously showed that Jab1 promotes E2F1-induced apoptosis but not DNA replication as an E2F1-specific binding partner. In this study, we performed gene expression analysis to better understand the control of E2F1 function by Jab1/CSN5. Microarray assay revealed a significant number of apoptotic E2F target genes such as Cyp26b1 and AMPKα2 are profoundly impaired by Jab1 shRNA knockdown, whereas DNA replication genes are generally still highly expressed. The findings of microarray were further confirmed using quantitative real-time PCR. Subsequent chromatin immunoprecipitation indicates that Jab1/E2F1 complex resides on the promoters of E2F1 apoptotic and G2/M, but not DNA replication targets genes. Meanwhile, we found that PI3K activation blocks expression of E2F1/Jab1 co-induced apoptotic target genes and apoptosis induction at least in part by interfering with formation of the pro-apoptotic Jab1/E2F1 complex as determined by co-immunoprecipitation. More importantly, we detected a highly significant correlation between elevated Jab1 levels and PI3K activity in breast, ovarian, lung and prostate cancers. These findings suggest the possibility that Jab1, when elevated in these tumors, may evade triggering tumor-suppressive E2F1 apoptosis and instead induce proliferation through the frequent, simultaneous co-activation of PI3K activity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A59.
Abstract B60: From plasma peptide to phenotype: An emerging role of quiescin-sulfhydryl oxidase 1 in tumor cell invasion
Authors: Katchman Benjamin A. , Antwi Kwasi , Hostetter Galen , Demeure Michael , Wantanabe Aprill , Decker G. Anton , Miller Lawrence J. , Von Hoff Daniel D. , Lake Douglas F. 
Published: June 2012

Abstract
Quiescin-sulfhydryl oxidase (QSOX1) oxidizes sulfhydryl groups to form disulfide bonds in proteins. We previously mapped a peptide in plasma from pancreatic ductal adenocarcinoma patients back to an overexpressed QSOX1 parent protein in tumor cells. It is not known why, or in what capacity, pancreatic tumors overexpress QSOX1. To begin to address this question, we first showed through immunohistochemistry that QSOX1 is overexpressed in patients diagnosed with pancreatic cancer, while it is not expressed in adjacent normal tissue or infiltrating lymphocytes. To determine the potential advantages QSOX1 might provide to tumor cells we knocked down QSOX1 using shRNA that suppressed both short and long isoforms of the protein. Loss of QSOX1 expression suppressed cell growth over time, while changes in cell cycle and apoptotic markers were minimal. However, QSOX1 shRNA dramatically inhibited the abilities of BxPC3 and Panc-1 pancreatic tumor cells to invade through Matrigel in a modified Boyden chamber assay. Mechanistically, gelatin zymography indicated that QSOX1 may play an important role in intracellular processing and extracellular activation of MMP-2 and MMP-9. Taken together, our results suggest that pancreatic tumors that express QSOX1 demonstrate an invasive phenotype through MMP activation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B60.
Abstract B62: Role of classical protein kinase C (PKC) in intestinal cancer
Authors: Kunz Sandra , Leitges Michael 
Published: June 2012

Abstract
PKCs represent a family of serine/threonine kinases consisting of a least 10 isoforms, divided into three subclasses based on their Ca2+ and DAG dependency. The classical PKC (cPKC) isoforms alpha, beta-I, beta-II, and gamma are calcium and diacylglycerol (DAG) dependent whereas novel PKCs (delta, epsilon, eta, and theta) are calcium independent. In contrast the atypical PKC zeta and lambda/iota do neither need calcium ions nor DAG for their activation. All PKCs are thought to be involved in cell growth and differentiation. In particular, studies focusing on expression profiles of PKCs during tumor formation and progression imply a functional link. For example, have we been able to show that PKC-alpha and -beta are differently regulated in the APCMin mouse model, which represents a well-established model for intestinal cancer. Based on these data, we further have identified PKC-alpha as to act like a tumor suppressor in this context. Given the fact that PKCs are activated by PMA/TPA and therefore defined as tumor promotors, this was a very surprising observation.
Material and Methods: This project makes use of mouse intestinal epithelial cell lines that we established from various genetic backgrounds. Using standard Western blot protocols, we first analyzed the abundance and activation status of different signal cascades upon epidermal growth factor (EGF) stimulation.
Results: Earlier studies by us (Oster and Leitges, 2006) have indentified an alteration of the EGF receptor signaling in the APCMin model due to PKC-alpha deficiency. To understand the underlying mechanism, we analyzed EGF receptor signaling in mouse intestinal epithelial cell lines. Thus far it became obvious that PKC-alpha deficiency causes a prolonged Erk1/2 and Akt activity whereas JNK activation was only detectable in the alpha deficiency.
Conclusion: In sum, we have shown that EGF receptor signaling capacity is functionally linked to PKC-alpha activity.
Literature: Oster H, Leitges M. Protein kinase C alpha but not PKC zeta suppresses intestinal tumor formation in APCmin mice. Cancer Res. 2006;66:6955–6963.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B62.
Abstract B64: Outcome of multimodality treatment of pediatric Ewing's sarcoma/PNET
Authors: Pathy Sushmita , Mohanti Bidhukalyan , Bakshi Sameer 
Published: June 2012

Abstract
Aim: To study the clinical symptoms and treatment outcome of multimodality treatment of ES/PNET in Dr BRAIRCH, AIIMS from June 2006 to May 2009.
Material and Methods: The study included 63 patients, 46 male and 17 female, all less than 18 years of age, and registered in our pediatric oncology clinic. All patients had histopathological diagnosis. Majority of patients had involvement of extremity (25/63), followed by thorax (14/63) and head and neck (10/63). Forty-eight patients presented with localized disease and 15 presented with distant metastasis. Chemotherapy consisted of VAC+IE regimen. Mean number of chemotherapy cycles was 13.5. Patients received chemotherapy and local treatment in the form of surgery and radiotherapy. Forty-one patients received CT+RT, 22 patients underwent surgery followed by RT.
In 50 patients, RT was administrated with a curative intent. A dose of 45 Gy in 25 fractions over 5 weeks followed by boost 15Gy in eight fractions over 1.5 wk was delivered. Mean RT dose was 47.9 Gy. Ten patients received palliative RT.
Results: Mean disease-free survival was 23.22 months (std error 1.92 and 95% CI 19.48-26.96). Median DFS was 21.3 months (std error 1.94 and 95%CI 17.50–25.10).
Conclusion: The above regime was well tolerated and detailed clinical profile, treatment outcome will be presented.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B64.
Abstract C15: Telomere length assessment in human archival tumor tissues by quantitative PCR method
Authors: Wang Hui , Go Ning , Pirot Zhu , Bassett Katia 
Published: June 2012

Abstract
Telomeres are essential for maintenance of genomic stability. Short telomeres have been associated with genomic instability, and initiation and progression of human cancers. To protect their telomeres, up to 90% of human cancers activate telomerase. Inhibition of telomerase by imetelstat, a specific and potent inhibitor, has resulted in telomere shortening, as well as tumor response in animal models. We propose that tumors with short telomeres may be more responsive to imetelstat than tumors with long telomeres. This hypothesis will be tested by measuring baseline telomere lengths in archival tumors of patients in imetelstat Phase II clinical trials, and correlating tumor telomere length with clinical outcome. In order to accomplish this, a fast, high-throughput qPCR-based method for telomere length measurement in genomic DNA extracted from FFPE tissue sections was developed. Using this assay, telomere repetitive DNA sequences and single-copy gene control were successfully amplified. The assay required very little genomic DNA (1–10ng per PCR reaction). Thus, small tissue sections (20 mm2) could be easily accommodated. Using this technique, we were able to perform the first comparison of relative telomere lengths in 22 human breast cancer samples and 8 human tumor cell lines in matched fresh-frozen and FFPE samples. Telomere lengths measured in FFPE samples by the qPCR method strongly correlated with the telomere lengths measured by TRF in matched fresh-frozen samples. Therefore, our method provides a useful tool for assessment of telomere length as a potential predictive biomarker of responsiveness to telomerase inhibition in clinical archival tumor tissue.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C15.
Abstract C2: Aspartic acid residues drive the membrane translocation of pHLIP, a therapeutic and imaging agent for solid tumors
Authors: Barrera Francisco N. , An Ming , Wijesinghe Dayanjali D. , Weerakkody Dhammika A. , Anderson Michael , Andreev Oleg A. , Reshetnyak Yana K. , Engelman Donald M. 
Published: June 2012

Abstract
The pHLIP peptide is a new therapeutic and imaging agent for cancer treatment. The pHLIP (pH-Low-Insertion Peptide) is soluble in solution but interestingly, it is able to interact with the plasma membrane and insert as a monomeric transmembrane helix (pKa=6.0). The insertion requires an acidic extracellular environment, such as that found in most solid tumors and inflammation sites. The pHLIP, which is nontoxic in mice, is specifically distributed to tumors (with minor labeling of kidney), as imaged by PET and near-infrared fluorescence.
The insertion of pHLIP is unidirectional, as the C-terminus is translocated across the membrane, while the N-terminus remains exposed to the extracellular medium. The insertion energy can be employed to translocate into the cytoplasm membrane-impermeable molecules. As a proof of principle, we showed that the polar toxin phalloidin (which binds to F-actin, inhibiting its depolymerization) is translocated in a pH-dependent fashion into HeLa, JC, and M4A4 cancer cells, inhibiting cell growth and causing cytoeskeletal immobilization and multinucleation.
Here we study the molecular determinants of pHLIP membrane insertion. The pH-mediated translocation is thought to be triggered by the protonation (loss of negative charge) of carboxyl groups present in pHLIP. Accordingly, the four aspartic acid (Asp) residues of pHLIP were sequentially mutated, and the efficacy of the membrane insertion and exit was studied in a liposome system. We found a correlation between the number and location of Asp with the peptides ability in insert into and exit from the membrane in a pH-dependent manner. We also observed that the number of Asp in the peptide determines the insertion properties (pKa and the cooperativity), suggesting that the tumor labeling properties of pHLIP can be specifically tuned to better match the physiological acidity of solid tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C2.
Abstract C20: The epigenomic fingerprint of hepatocellular carcinoma
Authors: Parpart Sonya , Roessler Stephanie , Dong Fei , Rao Vinay , Loffredo Chris , Wang Xin Wei 
Published: June 2012

Abstract
Globally, hepatocellular carcinoma (HCC) accounts for 70% to 85% of primary liver cancers. HCC remains in the top 10 among the most common cancers and ranks second in the leading cause of male cancer death worldwide. Patients are typically diagnosed with late-stage disease leading to poor survival rates in the United States and developing countries. Serum alpha-fetoprotein (AFP) is a key HCC biomarker associated with patient prognosis. However, serum AFP levels are heterogeneous among HCC patients, suggesting that the biology of AFP+ and AFP- tumors may be different. Identifying the molecular mechanisms underlying these differences may improve our understanding of HCC development and guide future approaches to increase survival. Recently, microRNAs (miRNAs) have been shown to be deregulated in many cancers and are useful biomarkers for early detection, prognosis, and treatment. In this vein, we performed global miRNA profiling analyses of HCCs that differ in AFP expression. We found that miR-29 family members, including miR-29a, miR-29b, and miR-29c, are top-ranked downregulated miRNAs in AFP+ tumors whose expression is inversely correlated with AFP in 242 HCC specimens, suggesting that miR-29 may act as a tumor suppressor in AFP+ HCC. In fact, we have found an association between decreased miR-29 and poor survival. In addition, there is a significant association between AFP and DNA methyltransferases DNMT3A and DNMT3B, which were recently shown to be direct targets of miR-29. Furthermore, we have found an overall trend toward increased methylation in HCC patients with high levels of AFP. These findings led us to hypothesize that AFP may inhibit miR-29, which in turn increases DNA methyltransferase activity and modulates epigenetic changes that contribute to poor outcome in HCC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) reveals that AFP and DNMT3B are both inversely correlated with miR-29 expression in HCC cell lines. We are testing currently whether AFP regulates miR-29 expression and alters DNA methylation patterns in HCC cells. We are also examining how miR-29 expression is regulated to determine whether AFP directly targets mir-29 to effect epigenetic changes or whether this occurs through other signaling pathways. Taken together, these studies will elucidate the molecular mechanisms that link AFP and miR-29 expression to epigenetic alterations and may aid in the development of novel therapeutic agents that may improve survival of HCC patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C20.
Abstract C26: Chromatin remodeling system and visualization of the “archaic” cancer attractors
Authors: Zhang Yue , Calderwood Stuart K. , Moriguchi Hisashi , Li Yinghua 
Published: June 2012

Abstract
The cancer cell attractors theory provides a novel understanding of carcinogenesis. The mechanisms that the ectopic expression of some germline genes result in somatic tumors such as melanoma and brain tumors are emerging but not well understood. From mammals to model organisms like Caenorhabditis elegans and Drosophila melanogaster, the versatile Mi-2/Nucleosome remodeling and histone deacetylation (NuRD) complexes alongside their functionally related chromatin remodeling complexes (CRCs), i.e. the dREAM/Myb-MuvB(MMB)complex and polycomb group (PcG) complex are typical bottle-necked regulators of cell attractors. The trajectory that benign cells switch to cancerous could be the reverse (or close) of navigation of embryonic cells converging from a series of intermediate transcriptional states to a final adult state, which is supported by Gene Expression Dynamics Inspector (GEDI) assays and some cross-species genetic evidences. Hence Cancer could be triggered by cells undergoing abnormal cell attractor transitions, and may be reversible with “cyto-education”. In additon, we identified multidrug resistence genes and extracellular matrix (ECM) genes as conserved hub molecule fro Mi-2/NuRD. A complementary study will go to tumorigenicity and immunogenicity of induced pluripotent stem celles and the strategies of supppression.
The understanding of involvement of CRCs in locking cancer attractors may forecast cancer “weather” and help find the recipes of perturbing genes to achieve successful reprogramming such that the reprogrammed cancer cell function in the same way as the normal cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C26.
Abstract C28: Binding to BCOR defines a subfamily of Psc ortholog mediated polycomb group complexes
Authors: Junco Sarah E. , Bardwell Vivian J. , Kim Chongwoo A. , Wang Renjing , Robinson Angela , Ilangovan Udayar , Taylor Alex , Gearhart Micah D. , Hart P. John , Hinck Andrew P. , Borries Demeler 
Published: June 2012

Abstract
NSPC1 is a Polycomb group (PcG) protein that functions within a multiprotein complex containing BCOR (BCL6 Co-Repressor), a protein which has been shown to drive formation of diffuse large B cell leukemia. NSPC1 is one of six human homologs (BMI1, MEL18, NSPC1, MBLR, PCGF3 and PCGF5) of the Drosophila Polycomb group (PcG) protein Psc. While BMI1 and MEL18 can bind directly to another PcG protein called Polyhomeotic (PH), multi-protein complexes involving MBLR and NSPC1 are absent of PH and no function has yet to be assigned to PCGF3 or PCGF5. We show that the ubiquitin (Ub) fold of NSPC1 and PCGF3 does not bind PH, but instead directly interacts with a previously unrecognized 115 residue region within BCOR while the Ub folds of BMI1 and MEL18 bind only PH. Preliminary structural studies using nuclear magnetic resonance and analytical ultracentrifugation indicate that this region of BCOR can independently fold and possesses a novel structure thereby identifying this domain as a unique PcG recruiting module. Thus, we propose the presence of at least two distinct functional classes of Psc orthologs: Class I, (BMI1 and MEL18) that binds PH and Class II (PCGF3, NSPC1 and likely PCGF5) which bind BCOR. The existence of different classes of Psc homologs demonstrates the evolution of the PcG in order to diversify its silencing function.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C28.