bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4611: Cancer reversal by dual strategy: A new molecular target?
Authors: Gosalvez Mario G. 
Published: August 2012

Abstract
Haste is a bad counselor when one is striving to address important issues. The new technique, which I draw your attention to, was first started in the 1980's and was completed in 2010 (Gosalvez, M. Thioproline and the reversal of cancer. The Lancet, p. 1108, May 14 1983. M Gosalvez. Mitochondrial Filamentation. AACR 101 Meeting. April 2010. Washington, USA). Throughout these 30 years several molecular targets for a cancer cure have been developed. The last hope, despite countless efforts, malignant neoplasia genetic therapy, has not yet consolidated itself. We trust that our colleagues, dedicated to therapeutic experimentation on human beings, will now address this new possibility, either alone, or in combination with other efforts. Better agents than Quelamycin (Cortes-Funes H, Brugarolas A and Gosalvez M. Quelamycin: A summary of Phase I Clinical Trials. Recent Results in Cancer Research, 74, 200-206, 1980. Eds. G Mathe and FM Muggia, Springer-Verlag. Germany) and Thioproline (Brugarolas A and Gosalvez M. Preliminary clinical results with Norgamem (thioproline) and Revercan (2-amino-2- thiazoline): The first inducers of reverse transformation. In: “Adjuvant Therapies of Cancer”. Mathe, Bonnadona and Salmon Eds.Springer-Verlag, Germany.1982, 346) can be gathered, with the precise cronotherapeutic emphasis, by correctly measuring the mobility (Gosalvez M, Blanco M, Bueno M and Balaguer R. Treatment of Leukaemia 1210 intravenous transplants with tumour modifiers, redoubt cytotoxics and minor tranquilizers, Lubec G and Rosenthal GA Eds. In: “Aminoacids. Chemistry, Biology and Medicine”. Escom Sciences Publishers, 704-711, 1990. Gosalvez, M. Reversal of Cancer by Dual Strategy. Madrid. Editorial Gober. 1992) of the patients under study. Now, after sufficient time has elapsed for the consideration of previous propositions, which have only had partial success, perhaps now the right moment has arrived for our proposal. We believe that, after a few years, the light at last will be seen at the end of the tunnel of suffering for patients and their families. If this proves to be the case, we could now, with the collaboration of everyone, tackle the possibility of using cancer as a therapeutic agent. All the sciences around our problem demand a great commitment for all involved.
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 4611. doi:1538-7445.AM2012-4611
Abstract 4612: Overexpression of cholesterol metabolism regulatory gene farnesyl diphosphate farnesyltransferase is associated with poor prognosis of non-small cell lung cancer patient and promotes metastasis through feedback regulation of SPP1-PI3K-AKT signaling pathway
Authors: Yang Yi-Fang , Tsia Hong-Yuan , Lee Chien-Hsin , Lim Christina H , Hsiao Michael 
Published: August 2012

Abstract
Lung cancer is the leading cause of the human cancer-related death in the world and non-small cell lung cancer (NSCLC) accounts for up to 80 % of those patients. Cholesterol metabolism is especially active in cancer cells, whereas cholesterol synthesis inhibition has been show to reduce tumor cell growth. However, the involvement of farnesyl diphosphate farnesyltransferase (FDFT1) in lung cancer development and progression remains unclear. FDFT1 was involved in cholesterol biosynthesis. In this study, we investigated the clinical significance and biological effects of FDFT1 in NSCLC. Immunohistochemical studies performed on 141 primary NSCLC specimens revealed a high prevalence of FDFT overexpression (51%), which was significantly associated with lymph node metastasis (regional, P = 0.022), advanced tumor stage (P = 0.004), and poorer disease-free survival (P = 0.001, log-rank test; P = 0.001, Cox proportional hazard model). FDFT1 down-regulation by two shRNAs significantly reduced cell migration and invasion in highly invasive lung cancer cell lines in vitro, as well as lung metastases in vivo. Conversely, overexpression of FDFT1 in weakly invasive lung cancer cell lines in vitro and orthotopic metastasis assay in vivo shows enhanced cell motility and lung metastases. In addition, inhibition of FDFT1 decreased AKT activation and thereby suppressing the migration of human lung cancer cell in vitro. The results suggested that FDFT1 can positive feedback to regulate AKT. In weakly invasive lung cancer cell lines, FDFT1 overexpression was associated with the upregulation of secreted phosphoprotein 1(SPP1). The shRNA mediated knockdown of SPP1 was found to block FDFT1-enhanced invasion. Taken together, we have identified cholesterol metabolism regulatory gene FDFT1 as a cancer progression biomarker who overexpression leading to poor prognosis and result tumor metastasis feedback regulation of SPP1-PI3K-AKT signaling pathway.
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 4612. doi:1538-7445.AM2012-4612
Abstract 4616: Age dependent increase in Prostaglandin pathway coincides with onset of ovarian cancer in laying hens
Authors: Eilati Erfan , Pan Lurui , Bahr Janice M. , Hales Dale Buchanan 
Published: August 2012

Abstract
The link between chronic inflammation and cancer has been recognized for many years. Cyclooxygenase (COX) (PTGS) is the rate limiting enzyme in catalyzing the conversion of arachidonic acid to prostaglandins. Two isoforms of cyclooxygenase has been identified, COX-1 and COX-2. Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecological malignancy. Ovarian cancer is mainly seen in older women when their ovaries are not reproductively functional. Hens spontaneously develop ovarian adenocarcinomas that are similar in histological appearance to human ovarian carcinomas and share similar symptoms of the disease thus the laying hen is the only accessible animal model that recapitulates human ovarian cancer. Many hypotheses about etiology of ovarian cancer have been proposed but the factors that contribute to correlation of age and ovarian cancer are unknown. The purpose of this study was to examine the expression of inflammatory factors and compare them to age. White Leghorn hens aged 12-45 months were used. The incidence of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 mRNA were extracted from ovarian tissue, preserved in RNAlater and their expression was determined using quantitative real-time PCR (qRT-PCR). Protein of both COX enzymes was isolated from ovarian tissue frozen in liquid nitrogen and were analyzed by Western blot. Ovarian tissue fixed in neutral buffered formalin was used for histology. Prostaglandin E2 amounts was measured in frozen ovarian tissues using ELISA. A significant increase in the incidence of ovarian cancer with age in laying hen was detected. The expression of both COX-1 and COX-2 protein and mRNA was remarkably increased in older hens compared to younger hens. In correlation with increased ovarian cancer incidence, expression of both COX enzymes and PGE2 concentration were elevated significantly with age. Our finding suggests that the up-regulation of COX mRNA and protein levels with age is the main contributing factor in the age associated increase in prostaglandin E2. The present study provides the first insight into the age-related changes in the expression of COX-1, COX-2 and prostaglandin E2. The results of current study demonstrated that PGE2 was elevated in ovaries of hens concomitant with age indicating its possible role in initiation and/or progression of ovarian malignancies. These finding may provide the basis for clinical trials utilizing COX specific inhibitors or dietary intervention targeting prostaglandin biosynthesis for the treatment and prevention of ovarian 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 4616. doi:1538-7445.AM2012-4616
Abstract 4631: Anti-CD70 antibody-drug conjugates containing pyrrolobenzodiazepine dimers demonstrate robust antitumor activity
Authors: Jeffrey Scott , Burke Patrick , Meyer David , Lyon Robert , Miyamoto Jamie , Anderson Martha , Stone Ivan , Law Che-Leung , Senter Peter 
Published: August 2012

Abstract
Antibody-drug conjugates (ADCs) represent an important approach for the selective delivery of highly potent small molecules to malignant cells. Recently, we have adapted the highly cytotoxic class of minor groove DNA crosslinking agents, pyrrolobenzodiazepine dimers (PBDs), in order to conjugate them to monoclonal antibodies. These totally synthetic molecules alkylate guanine bases in a sequence-specific manner to cause cell death at pM concentrations. In this report, we describe for the first time a novel PBD that can be stably conjugated to the anti-CD70 monoclonal antibody (mAb) h1F6 via maleimide conjugation to engineered cysteine residues created by the single amino acid substitution S239C on each heavy chain. This results in a uniform loading of two drugs per antibody. The resulting ADC binds selectively to CD70 on renal cell carcinoma cell lines and releases the free drug upon internalization and cleavage of the dipeptide linker in the lysosome. The ADC retains the robust cytotoxicity of the free drug, displaying immunologically selective antitumor activity in xenograft models at well tolerated doses as low as 0.1 mg/kg. The PBDs represent a promising new class of cancer drugs for targeted delivery.
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 4631. doi:1538-7445.AM2012-4631
Abstract 4657: Differential regulation of autophagy vs. apoptosis as a potentially unique mechanism of cancer cell specific radiosensitization with fluoxetine
Authors: Moran-Guiati Nicci P. 
Published: August 2012

Abstract
Introduction: Prior data demonstrate that selective serotonergic reuptake inhibitors (SSRIs) are cytotoxic to cancer cells and that fluoxetine can sensitize cells to radiotherapy (XRT) potentially through induction of autophagy; however, there is limited information on the effects of serotonergic receptor modulation and mechanisms of other SSRIs on cytotoxicity with radiotherapy. Methods: Human lung cancer lines (A549 and H460) and oropharyngeal cancer cells (FaDu) were treated with dose escalated SSRIs (fluoxetine, sertraline, paroxetine), serotonergic receptor (5-HTR) agonists (CP809101, S14506), or 5-HTR antagonists (agomelatine, spiroxatrine) alone or in combination with dose escalated XRT to evaluate the effects of on cell survival using clonogenic survival assays. 5-HTR expression, apoptosis, and autophagy were evaluated as potential mechanisms of the effects of SSRIs on XRT. Results: Fluoxetine, paroxetine, or sertraline alone had a cytotoxic effect on cancer cells in a concentration dependent manner. Fluoxetine had a sensitizing effect in combination with XRT in a cell specific manor; however, sertraline and paroxetine had an additive cytotoxic effect on XRT. 5-HTR agonists and antagonists did not demonstrate any significant sensitizing effects, but agonists were cytotoxic at 10-50 uM with no apparent cytotoxicity from antagonists. Western blot analysis demonstrated that fluoxetine, paroxetine, or sertraline decreased apoptosis (cleaved caspase-3 and cleaved PARP) and increased autophagy (LC3B-II) in H460 cells associated with the sensitizing effect of fluoxetine on XRT. In contrast, the additive cytotoxicity of sertraline or paroxetine was not associated with a differential regulation of apoptosis vs. autophagy in A549 cells. Conclusions: SSRIs appear to have a cytotoxic effect alone or in combination with XRT potentially through a non 5-HTR based mechanism. The cell specific differential regulation of apoptosis vs. autophagy associated with fluoxetine warrants further examination of a potentially unique mechanism of radiosensitization.
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 4657. doi:1538-7445.AM2012-4657
Abstract 466: Synthetic triterpenoids target cell migration and cell adhesion via GSK3β
Authors: To Ciric , Di Guglielmo Gianni M. 
Published: August 2012

Abstract
Synthetic triterpenoids are a class of anti-tumor compounds that target various cellular functions including apoptosis, growth inhibition, anti-inflammation and cytoprotection. Previously, we have shown that triterpenoids also inhibit cell migration and the objective of our current study is to examine the molecular mechanisms. Since cellular adhesion dynamics play a critical role in cell migration, we investigated the effects of triterpenoids on focal adhesion morphology. Using immunofluorescence microscopic analysis of focal adhesion markers, paxillin and Focal Adhesion Kinase (FAK), we found that cells that were treated with synthetic triterpenoids possessed enlarged focal adhesions. Interestingly, numerous focal adhesion related proteins including IQGAP1, paxillin, FAK and Glycogen Synthase Kinase 3 (GSK3) were identified as drug-binding proteins using pull down and mass spectrometry approaches. Therefore, we investigated if triterpenoids target these proteins and affect cell adhesion turnover to inhibit cell migration. We found that focal adhesion re-establishment was altered by triterpenoids while pre-existing focal adhesions remained largely unaffected. To further explore the underlying mechanism of triterpenoids on GSK3β dependent cell adhesion dynamics, we analyzed GSK3β activity. We found that triterpenoids stimulate the phosphorylation of GSK3β at serine 9, however, both FAK and paxillin phosphorylation was largely unaffected by the triterpenoids. In parallel studies, we observed that focal adhesion staining was enlarged with cells that were treated with the GSK3β inhibitors, lithium chloride and SB216763. In addition, GSK3β inhibition affected the localization of not only GSK3β but also IQGAP1, an important scaffolding protein involved in cell polarity. From our results, we postulate that synthetic triterpenoids may affect cell migration by targeting GSK3β, which in turns, inhibits its activity and displaces its localization from the leading edge. More importantly, GSK3β inhibition by the triterpenoids and by GSK3β inhibitors also lead to the displacement of IQGAP1 from the leading edge, which further suggests that triterpenoids may act via a GSK3β mechanism to affect focal adhesions and cell migration.
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 466. doi:1538-7445.AM2012-466
Abstract 4799: Identification of drug resistance targets in ovarian cancer using a proteomic approach
Authors: Cruz Isa , Angelino Rita , Coley Helen , Schatzlein Andreas , Yang Min 
Published: August 2012

Abstract
Ovarian cancer ranks first in the number of deaths and second in the number of new cases among gynecological cancers. In the majority of the cases, surgery is the intervention of choice, but chemotherapy has progressed considerably over the last years. First-line treatment for advanced-stage disease is a combination of carboplatin and paclitaxel. However, drug resistance has become a major obstacle to the successful chemotherapeutic treatment of human cancers. Currently, there is no clear consensus on treatment options for ovarian cancer patients who acquired drug resistance, due to the lack of knowledge about drug resistance mechanisms. There is an urgent need to explain how drug resistance occurs and to identify proteins related to this phenomenon, so that inhibitors can be designed. The aims of this study are to develop and optimise a two-dimensional gel electrophoresis method to compare protein profile of human ovarian cancer cell lines, which are sensitive or resistant to anticancer chemotherapy, so that proteins related to drug resistance can be identified using mass spectrometry. The parental ovarian cancer cell line models PEO1 and SKOV-3 are used as drug sensitive reference cell lines. Novel drug resistant models, derived from the parental lines, with in vitro acquired resistance to paclitaxel and carboplatin are used alongside their respective drug sensitive parental counterparts. Proteins related to tumorigenesis or drug resistance, either new or previously reported, were identified in at least one of the three cell lines. These proteins belong to different classes and are responsible for distinct functions within the cell, such as cytoskeleton and cell structure, detoxification and stress response, and cellular metabolism. This is the first proteomic study on these specific ovarian cancer cell lines using paclitaxel and carboplatin. The results obtained will be useful for further studies of resistance mechanisms and screening of resistance biomarkers for the development of tailored therapeutic strategies.
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 4799. doi:1538-7445.AM2012-4799
Abstract 4801: p90/CIP2A may play a role in regulating the phosphorylation of CREB1 in cancer
Authors: Peng Bo , Lei Ningjing , Peng Xuanxian , Qian Wei , Tan Eng M. , Zhang Jianying 
Published: August 2012

Abstract
Cancerous inhibitor of PP2A (CIP2A) is a tumor-associated autoantigen migrating in SDS-PAGE as a protein of 90kD (also called p90). This protein was shown to be expressed in the mouse embryonic stage but inactivated in adult tissues. It has been shown to inhibit PP2A function thus stabilizing the oncogene c-myc in human malignancies. In the present study, we used two-dimensional electrophoresis-based approach and identified 47 differentially expressed proteins upon the loss of p90/CIP2A in H1299 lung cancer cell line. Among these 47 proteins, 30 proteins have been well documented to be associated with cancer, of which 12 proteins are up-regulated and 18 proteins are down-regulated after knock-down of p90/CIP2A via shRNA. To investigate whether these proteins are associated with any known cancer-related pathway, differentially expressed proteins were analyzed using Pathway Studio bioinformatics software. The resulting data indicated that four possible transcription factors (c-myc, ESR-1, ETS-1 and CREB) may involve in the regulation of the differentially expressed proteins. Further studies showed that down-regulation of p90/CIP2A may affect CREB phosphorylation: treatment with serum induced less phosphorylation of CREB in cells transduced with p90/CIP2A shRNA than the cells tranduced with control shRNA. However, other treatments like KCl and forskolin did not show significant difference between these two groups. We also found that the phosphorylation of the CREB upstream kinase, AKT, was also down-regulated while other kinases p38 and p90RSK was unaffected. These preliminary data imply that p90/CIP2A may target AKT-CREB pathway to promote cell proliferation in a c-myc independent manner.
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 4801. doi:1538-7445.AM2012-4801
Abstract 4817: Using the Mendelian randomization approach to clarify the role of well-done meat and heterocyclic amine exposure in the etiology of colorectal polyps
Authors: Fu Zhenming , Shrubsole Martha J. , Li Guoliang , Cai Qinyin , Smalley Walter E. , Hein David W. , Chen Zhi , Shyr Yu , Ness Reid , Zheng Wei 
Published: August 2012

Abstract
Background: High red meat intake and meat-derived mutagen heterocyclic amines (HCAs) exposure have been linked to the risk of colorectal polyps and cancer. HCAs are activated and detoxified by a group of carcinogen metabolizing enzymes. Internal exposure dose to these carcinogens is determined by both external exposure and genetic polymorphisms in genes encoding these enzymes, providing a unique opportunity to conduct a Mendelian randomization analysis to reduce bias associated with observational epidemiological studies. Methods: In a colonoscopy-based case-control study, we recruited 5,386 participants, including 2,057 patients with colorectal polyps, and 3,329 polyp-free controls. Twenty single nucleotide polymorphisms (SNPs) were analyzed to construct a HCA metabolizing score. Data on dietary intake of meat by cooking methods and doneness level were obtained through telephone interviews to derive dietary HCA exposure level. Interactions between HCA metabolizing score and dietary exposure variables were evaluated using multivariate unconditional logistic regression models to derive odds ratios (ORs) and 95% confidence intervals (CIs). Results: HCA metabolizing score was unrelated to polyp risk among those with a low intake of total meat or red meat and low dietary HCA exposure. These dietary variables also tended to not be associated with polyp risk among those with a low HCA metabolizing score. Risks of polyps associated with meat intake and HCA exposure, however, were elevated among those with a high risk HCA metabolizing score. The interactions between dietary meat exposures and HCA metabolizing score were statistically significant for most of the analyses (P α0.05). Participants with the highest meat intake and HCA exposure level and a high risk HCA metabolizing score had a 30% to 40% elevated risk of developing any polyps and 60% to 80% elevated risk of developing advanced or multiple adenomas. Conclusions: Dietary meat intake and dietary exposure to HCAs is associated with an elevated risk of colorectal polyps, and this association is modified by genetic polymorphisms in HCA metabolizing enzymes. This study provides strong evidence supporting a causal role of HCA exposure in the etiology of colorectal tumors.
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 4817. doi:1538-7445.AM2012-4817