bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B39: Human FANCA binds to nucleic acids and prefers single-stranded forms
Authors: Yuan Fenghua , Qian Liangyue , Liu Jesse Y. , Zhao Xinliang , Song Limin , D'Urso Gennaro , Jain Chaitanya , Zhang Yanbin 
Published: June 2012

Abstract
Fanconi anemia (FA) is an autosomal recessive or X-linked disorder characterized by bone marrow failure, developmental defects, predisposition to cancer, and hypersensitivity of crosslinking agents. Fanconi anemia complementation group A (FANCA) gene is one of the 15 disease-causing genes and has been found to be mutated in ∼60% of all FA patients. Using the purified human WT-FANCA protein, we report that FANCA possesses intrinsic affinity to nucleic acids. FANCA binds to single-stranded DNA with affinity significantly higher than double-stranded DNA. FANCA also binds to single-stranded RNA with similar affinity to single-stranded DNA. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determine the minimum numbers of nucleotides required for FANCA recognition are −30 and −40 for DNA and RNA respectively. A patient-derived FANCA truncation mutation, Q772X, has diminished affinity to both DNA and RNA. On the contrary, the complementing C-terminal fragment of Q772X, 772–1455, retains the differentiated DNA binding activity (ssDNA&gt;dsDNA), indicating that the nucleic acids binding domain of FANCA is located at its C-terminus where most disease-causing mutations are found.
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 B39.
Abstract B68: Chemomodulatory potential of aloe vera gel on DMBA-induced skin papillomagenesis, drug metabolizing and antioxidant enzymes
Authors: Singh M. , Singh S. , Kale R. K. 
Published: June 2012

Abstract
Aloe vera has traditionally been used as a folk medicine around the world. Therefore, we evaluated the chemopreventive potential of A. Vera on cell proliferation and apoptosis in DMBA induced skin papillomagenesis in mice, using three different concentrations as well as its influence on phase-I, phase-II and antioxidant enzymes, glutathione content, lactate dehydrogenase and peroxidative damage in the liver of the mice. DMBA and croton oil was used to induce and promote skin papillomagenesis respectively. Skin papillomagenesis study was done by giving three different doses of A. vera [low dose 1:3 dilution, mid dose 1:1 dilution and high dose 1:0 dilution] to mice till termination of the experiment. Using relatively effective dose [1:1 dilution] of A. vera, its chemopreventive potential was examined at pre-initiational, peri-initiational, post-initiational and promotional stage in terms of tumor incidences and tumor multiplicity. In addition, the expression of cell proliferation, glutathione-S-transferase, and apoptosis were analyzed in the skin tumors by immunohistochemical study. For biochemical studies, mice were given with the same doses of A. Vera gel in drinking water for two weeks. Results showed a significant reduction in the skin tumors (upto 42%) in A. vera gel treated animals, as compared to the control group of animals. A. vera was found to be more effective in inhibiting the tumor multiplicity (upto 72 %) compared to the tumor incidence (30 %). Relative to control (100 %), the tumor incidence were 77 %, 80 %, 92 % and 54% in case of pre-initiational, peri-initiational, post-initiational and promotional treatment of A. Vera gel respectively. Since A. Vera inhibited phase-I enzyme system and enhanced phase-II enzyme system, it could be considered as dual acting chemopreventive agent. Increased antioxidant enzyme system and decreased peroxidation damage suggestive of its potential to enhance the antioxidant status of animals which might contribute to chemopreventive property.
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 B68.
Abstract C11: Investigation of a novel molecular descriptor for the lead optimization of 4-aminoquinazolines as vascular endothelial growth factor receptor-2 inhibitors
Authors: Kawakami Joel K. , Martinez Yannica , Sasaki Brandi , Harris Melissa , Kurata Wendy E. , Lau Alan F. 
Published: June 2012

Abstract
We investigated the use of infrared vibrational frequency of ligands as a potential novel molecular descriptor in three different molecular target and chemical series. The vibrational energy of a ligand was approximated from the sum of infrared (IR) absorptions of each functional group within a molecule and normalized by its molecular weight (MDIR). Calculations were performed on a set of 4-aminoquinazolines with similar docking scores for the VEGFR2/KDR receptor. 4-Aminoquinazolines with MDIR values ranging 192–196 provided compounds with KDR inhibitory activity. The correlation of KDR inhibitory activity was similarly observed in a separate chemical series, the pyrazolo[1,5-a]pyrimidines. Initial exploration of this molecular descriptor supports a tool for rapid lead optimization in the 4-aminoquinazoline chemical series and a potential method for scaffold hopping in pursuit of new inhibitors.
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 C11.
Abstract C16: miR-148a regulates the expression of PTEN in hepatitis B associated hepatocellular carcinoma
Authors: Yuan Ke , Lian Zhaorui , Sun Bill , Clayton Marcia M. , Ng Irene O. L. , Feitelson Mark A. 
Published: June 2012

Abstract
Previous work has shown that hepatitis B virus encoded X antigen (HBx) is a trans-regulatory protein that alters the activity of selected transcription factors and cytoplasmic signal transduction pathways. The resulting changes in host gene expression are thought to contribute importantly to the development and progression of hepatocellular carcinoma (HCC). In this context, HBx up-regulates the expression of a unique gene, URG11, which in turn up-regulates β-catenin, thereby contributing importantly to hepatocarcinogenesis. Changes in the expression levels of microRNAs (miRNAs) are also characteristic of many tumors, including HCC. To determine whether altered miRNA expression contributes to the mechanism whereby HBx and URG11 contribute to HCC, recombinant retroviruses encoding HBx, URG11, or the bacterial chloramphenicol acetyltransferase (CAT) gene (the latter used as a negative control) were used to infect separate cultures of HepG2 and Hep3B cells. When these cells were compared by miRNA array analysis, both HBx and URG11 were shown to promote the expression of miR-148a. This was confirmed by quantitative (q)RT/PCR analysis. Elevated levels of miR-148a strongly correlated with HBx positive staining in liver samples from infected patients by qRT/PCR (P&lt; 0.001). To study the function of miR-148a, anti-miR-148a was introduced into HepG2 and Hep3B cells stably expressing HBx or stably over-expressing URG11. Anti-miR-148a suppressed cell proliferation (P &lt; 0.01), cell cycle progression (P &lt; 0.01), cell migration (P &lt; 0.01), anchorage independent growth in soft agar (P &lt; 0.01) and subcutaneous tumor formation in SCID mice (P &lt; 0.05). Introduction of anti-miR-148a also increased PTEN mRNA and protein expression, suggesting that PTEN was targeted by miR-148a. This was verified in experiments where anti-miR-148a failed to suppress PTEN expression when co-transfected with reporter gene mutants of the 3′UTR of PTEN mRNA. When HBx positive HepG2 and Hep3B cells were transiently transfected with URG11 specific siRNA, both URG11 and miR-148a levels were suppressed, suggesting that up-regulated expression of miR-148a in HBx positive cells was URG11 dependent. Finally, anti-miR-148a blocked the stimulation of Akt signaling by HBx and URG11, resulting in decreased expression of β-catenin (P &lt; 0.05). Thus, miR-148a appears to contribute a central role to HBx/URG11 mediated HCC, and may be an early diagnostic marker and/or therapeutic target associated with this tumor type.
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 C16.
Abstract C30: p53-independent 8-amino-adenosine mediated breast cancer cell death
Authors: Polotskaia Alla , Bargonetti Jill 
Published: June 2012

Abstract
Nucleoside analogues are routinely used as breast cancer chemotherapeutics however which death pathways they trigger in the various subtypes of breast cancer, based on the p53 biomarker status, has not been adequately assessed. Here we compare the effectiveness of the novel compound 8-amino-adenosine to gemcitabine (a commonly used nucleoside analogue for the treatment of breast cancer). Gemcitabine requires functional wild-type p53 to work as a cytotoxic drug and we asked if 8-amino-adenosine could act as a cytotoxic agent independently of p53. We found that regardless of the p53-status, 8-amino-adenosine was highly cytotoxic in a panel of breast cancer cell lines. 8-amino-adenosine was a more effective cytotoxic agent than either gemcitabine or etoposide in the breast cancer cell line MCF-7 (having wild-type p53) or MDA-MB-468 and T47-D, (having oncogenic mutant p53) as well as with the cell line MDA-MB-231 (highly metastatic containing mutant p53). Importantly, in the presence of wild-type p53, in contrast to the outcomes with gemcitabine and etoposide, 8-amino-adenosine did not increase transcription of the p53 target gene p21 or protein levels of either p53 or p21. The death pathway mediated by 8-amino-adenosine in MCF-7 cells was apoptotic as the pan-caspase inhibitor ZVAD blocked cell death and PARP cleavage. Additionally, knockdown of functional p53 by inducible shRNA did not inhibit 8-amino-adenosine mediated cell death, further supporting a p53-independent death pathway. Interestingly, the death pathway mediated by 8-amino-adenosine in the metastatic cell line MDA-MB-231 (containing mutant p53) correlated with an increase in LC3-II and no PARP cleavage, suggesting an increase in autophagy. In conclusion, 8-amino-adenosine is cytotoxic to breast cancer cells with non-functional p53 and may be an effective treatment of breast cancer regardless of the status of the p53 biomarker.
Acknowledgement: We thank Steven T. Rosen, Mala Shanmugam and Nancy Krett for the 8-amino-adenosine compound and valuable discussions. The Breast Cancer Research Foundation supported this work.
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 C30.
Abstract C57: Role of aneuploidy in cellular adaptation, drug resistance, and cancer
Authors: Rancati Giulia , Pavelka Norman , Zhu Jin , Li Rong 
Published: June 2012

Abstract
Cancer is a multistep Darwinian process whereby mutant cells able to escape internal, environmental, or drug-mediated proliferative roadblocks expand and outcompete less-fit cells. Mutations characterizing this somatic evolution range from single-point mutations to whole-chromosome aneuploidy. Although sequence mutations clearly play a role in cancer evolution, the role of aneuploidy in cancer is far less clear. Previously, we investigated how yeast cells can adapt in response to a proliferative roadblock and the role of aneuploidy during this process. We showed that aneuploidy could provide a source of heritable variation driving the emergence of large phenotypic changes that can be adaptive under strong selective conditions. Recently, we provided evidence that aneuploidy is sufficient to generate global changes at the proteome level and to provide phenotypic variation. Taken together, our data suggest that aneuploidy might thus be beneficial to cancer cells that are trying to escape growth inhibitory signals and chemotherapy treatment.
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 C57.
Abstract C68: Transforming growth factor-beta and vascular endothelial growth factor are enhanced in plasma of breast cancer patients resistent to hormone therapy
Authors: Zavadova Eva , Konopásek Bohuslav , Vocka Michal , Petruzelka Lubos 
Published: June 2012

Abstract
Even with high therapeutic efficacy of first-line hormonal treatment, most patients with metastatic breast cancer will develop resistance. It appears that a factor contributing to the resistance may be a transforming growth factor-beta (TGF-beta). It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors and stimulates production of vascular endotelial growth factor (VEGF). Defects in the immune response correlated with poor prognosis and therefore in recent years, research focused on a precise description of the status and function of the immune system and its possible effect in cancer patients.
The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer resistant to hormone therapy, particularly the examination of cellular (CD4, CD8, HLA-DR) as well as humoral immunity. TGF-beta and VEGF production was monitored and we analyzed the changes during hormonal treatment.
Methods: Patients included in the research project were implemented routine cancer treatment with hormonal therapy. Basic parameters (histological type and grade, the degree of expression of ER and PR, HER2, and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF-beta and VEGF were mesured by ELISA and antitumor cellular immunity (CD4, CD8, antigen presenting cells) will be measured by flow cytometry.
Results: In patients with resistance to hormone therapy mainly depression in cellular immunity was found. Immunglobulin plasma level was decreased as well (mainly IgG4 subtype). Most patients have shown clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections) TGF-beta as well as VEGF plasma level were increased. Significant increase of autoantibodies production was found, particulary in those, involved into blood coagulacion process/antiphospholipide and anticardiolipin autoantibodies.
Conclusion: Correlation of these factors with resistance to hormonal therapy, and the state of anticancer immunity could help in the future with the the prediction of resistance to hormonal therapy and contribute to the selection of targeted immune therapy in cancer patients.
Acknowledgement: This project was supported by grant IGA NT11168-3/2010.
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 C68.
Abstract IA21: Role of Tet1-catalyzed 5mC hydroxylation in transcriptional regulation and ES cell maintenance
Authors: Zhang Yi , Chase Chevy 
Published: June 2012

Abstract
Epigenetic modifications play important roles in diverse biological processes that range from regulation of gene expression, embryonic development, stem cell reprogramming, and human diseases such as cancers. One of the epigenetic modifications is DNA methylation. Although enzymes responsible for DNA methylation have been well characterized, enzymes responsible for active DNA demethylation in mammalian cells have remained elusive. Recent studies have demonstrated that a novel family of proteins— Tet1–3—have the capacity to convert 5mC to 5hmC, raising the possibility that Tet proteins may catalyze the initial step leading to DNA demethylation. Interestingly, Tet1 plays an important role in stem cell self-renewal and maintenance. To understand how Tet1 contributes to these processes, we profiled the genome-wide location of Tet1 and 5hmC in ES cells. This study revealed that Tet1 has a dual function in activating pluripotency stem cell genes and silencing lineage-specific differentiation genes. Further studies revealed that Tet1 contributes to gene silencing by facilitating recruitment of PRC2. Thus, our studies establish a link between Tet1 and PRC2 and revealed a dual function for Tet1 and 5hmC in transcriptional regulation.
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 IA21.
Abstract PR7: An oncolytic vaccinia virus encoding the human sodium iodide symporter facilitates long-term deep-tissue image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer
Authors: Haddad Dana , Szalay Aladar A. , Fong Yuman , Zanzonico Pat B. , Carlin Sean , Chen Chun-Hao , Chen Nanhai G. , Zhang Qian , Yu Yong A. , Longo Valerie , Mojica Kelly 
Published: June 2012

Abstract
To assess therapeutic response and potential toxicity of oncolytic virotherapy, a noninvasive, deep-tissue imaging modality is needed. This study aimed to assess the feasibility, parameters, determining factors of serial imaging and long-term monitoring of systemic virotherapy together with radiotherapeutic response of pancreatic cancer xenografts treated with a vaccinia virus encoding the human sodium iodide symporter (hNIS), GLV-1 hi 53.
hNIS, an intrinsic plasma membrane protein, mediates the active transport, and trapping of iodine mainly in the thyroid and some extrathyroidal tissues such as the stomach. Pancreatic cancer xenografts (PANC-1) in nude mice were treated systemically or intratumorally with GLV-1h153 and serially imaged using 124I-PET at 1, 2, 3, and 5 weeks post virus injection and 4 hours post radiotracer injection. At week 1 and 2 post virus injection, mice were also imaged at 1, 8, 24, 48, and 72 hours post radiotracer injection in order to obtain time-activity curves for dosimetry calculations of radioiodine uptake. The PET signal intensity was compared with tumor therapeutic response and optical imaging. Tumors were histologically analyzed for morphology and presence of virus particles. Autoradiography was performed utilizing technecium-pertechtenate and gamma-scintigraphy to assess determining factors for radiouptake in tumors. Combination therapy with GLV-1h153 and systemic radioiodine was also explored. GLV-1h153 successfully facilitated serial long-term imaging of virotherapy with PET signal intensity correlating to antitumor response. Colonization of tumors with GLV-1h153 mediated radioiodine uptake at potentially therapeutic doses. Successful radiouptake required presence of virus, adequate blood flow, and viable tissue, while loss of signal intensity was linked to tumor death and necrosis. Finally, combining systemically administered GLV-1h153 and 131I led to enhanced tumor kill when compared to virus or 131I treatment alone (P&lt;0.001). GLV-1h153 is thus a promising oncolytic agent for the treatment, long-term imaging, and monitoring of the therapeutic response of cancer. GLV-1h153 provided insights into tumor biological activity and facilitated enhanced tumor kill when combined with systemic targeted radiotherapy. Further investigation into parameters and potential synergistic effects of combination therapy is warranted.
This abstract is also presented as Poster C7.
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 PR7.
Abstract A89: Concentrations of IGF-I and IGFBP3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Rohrmann Sabine , Grote Verena A. , Susen Becker , Rinaldi Sabine , Bueno-de-Mesquita Bas , Kaaks Rudolf 
Published: June 2012

Abstract
Background: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation and proliferation and have been found to be associated with risk of cancer of various sites. The results of the prospective studies with respect to pancreatic cancer are rather inconsistent, with most studies showing no clear association of circulating IGF-I or IGFBP-3 levels with pancreatic cancer risk (Douglas et al, 2010; Lin et al, 2004; Stolzenberg-Solomon et al, 2004; Wolpin et al, 2007). Because of the inconsistencies of previous studies, we examined the association between IGF-I, IGFBP-3 and pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Methods: Following recruitment of the study participants between 1992 and 2000, 638 pancreatic cancer cases were observed until December 2006; 578 of them were primary exocrine pancreatic tumors. Blood specimens were available for 422 of these cases. Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in these 422 cases and 422 controls matched on age, sex, study center, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for smoking, history of diabetes, and body mass index.
Results: Neither circulating levels of IGF-I (OR=1.13, 95% CI 0.63–1.81 for top vs. bottom quartile, p-trend 0.57) nor IGFBP-3 (OR=0.94, 95% CI 0.60–1.47, p-trend 0.65) were statistically significantly associated with the risk of pancreatic cancer. There was also no association of the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level, with pancreatic cancer risk (OR=1.35, 95% CI 0.79–2.31, p-trend 0.31). No associations were observed when using only microscopically confirmed cases (n=307) or when we stratified the analyses by sex, follow-up time, waist circumference, history of type-2 diabetes, or circulating C-peptide concentrations.
Conclusion: Based on these results, circulating levels of components of the insulin-like growth factor axis do not appear to be a risk factor for pancreatic cancer, which is consistent with most results of previously published prospective studies.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A89.