bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3689: Association of thymidylate synthase gene polymorphisms with efficacy and toxicity of oral fluoropyrimidine based chemotherapy in advanced gastric cancer
Authors: Kim Gun Min , Jeung Hei-Cheul , Kwon Woo Sun , Rha Sun Young , Kim Hyo Song , Jung Inkyung , Nam Byung-Ho , Lee Kyung Hee , Chung Hyun Cheol 
Published: August 2012

Abstract
Purpose: Oral fluoropyrimidines (S-1 or capecitabine) are metabolized by different enzymes. We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6), carboxylesterase 2(CES 2), thymidylate synthase (TS), and excision repair cross complementation group 1 (ERCC1) and toxicity of advanced gastric cancer patients treated with oral fluoropyrimidine based chemotherapy. Methods: A total of 123 patients received S-1 80mg/m2 or capecitabine 2000 mg/m2 plus oxaliplatin 130 mg/m2 for advanced gastric cancer. We analyzed polymorphisms of CYP2A6, CES 2, TS and ERCC1 by using genomic DNA extracted from prospectively collected peripheral blood sample. Associations between polymorphisms and toxicity of these patients treated with oral fluoropyrimidines based chemotherapy were evaluated individually. Results: Patients who were 2R/3R for the double repeat in the TS promoter region had more toxicity of oral fluoropyrimidines. Patients with a 2R/3R and 2R/2R or 3R/3R genotype had a grade 2 or more gastrointestinal toxicity rate of 50 and 22%, respectively (P = .049). Response rate was higher in patients with a 2R/3R than those with a 2R/2R or 3R/3R (50% vs. 32%, P = .082). Polymorphisms of CYP2A6, CES 2, and ERCC1 were not associated with efficacy and toxicity of oral fluoropyrimidine based chemotherapy for advanced gastric cancer. Conclusion. This study demonstrated that TS genotyping could be of help in predicting toxicity to oral fluoropyrimidine based chemotherapy in advanced gastric cancer patients.
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 3689. doi:1538-7445.AM2012-3689
Abstract 3691: The correlation analysis of postoperative anxiety scale of colorectal cancer patient and the postoperative complication
Authors: Wang Xiaodong , Fang Chao , Hu Zongli , Yang Jiqiao , Shu Bingyan , Li Li 
Published: August 2012

Abstract
Objectives Aim at evaluating the influence of postoperative anxiety scales on postoperative complications of colorectal cancer by clinically using the Hamilton anxiety. Methods Prospectively enrolling 126 patients definitely diagnosed with colorectal cancer from February to May in 2010at the Center of Gastrointestinal Surgery, West China Hospital, Sichuan University. By dividing them into three groups according to the anxiety scales, postoperative complication rates were compared between groups, relating postoperative anxiety factors were evaluated and clinical rating value between postoperative anxiety scale and postoperative complication incidence rate of patients was explored. Results There was a significant different of post complication rates among the three groups(x2=17.904, P&lt;0.001), and the potential anxiety group(anxiety score=7-13)'s postoperative complication rate is lower than non-anxiety group(anxiety score&lt;7) (x2=11.027, p=0.002)and anxiety group(anxiety score&gt;14)(x2=20.677, P&lt;0.001).The difference between the anxiety group and the non-anxiety group had no statistical significance(x2=1.636, p=0.274). The risk factors for postoperative anxiety were type of expense(p=0.053), resides(p=0.018), medical complication(p=0.014), neoadjuvant chemotherapy(p=0.053), the DUKE'S stage(p=0.009), the ordinary diet day after operation(p=0.001).After analyzing, the critical value was 17 point for anxiety score and the postoperative complication morbidity of patients was higher when the post anxiety scale was over 17(X2=12.538, P=0.004). Conclusions the postoperative anxiety scale of the colorectal patients has some corelations with the postoperative complication morbidity, and the ones whose score are high in anxiety scale are more likely to suffer from postoperative complications. However, the postoperative complication morbidity is relatively low in moderate anxiety patients.
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 3691. doi:1538-7445.AM2012-3691
Abstract 3692: Single center phase II study of yttrium-90 radioactive resin microspheres in the treatment of liver predominant metastatic colorectal adenocarcinoma after failure of 1st-line combination chemotherapy
Authors: Roeland Eric J. , Dad Shakeela , Shimabukuro Kelly , Fanta Paul , Rose Steven , Reid Tony 
Published: August 2012

Abstract
Background: Colorectal cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer death. Liver metastases develop in half of all the colorectal cancer (CRC) cases and cause death in ∼90% of patients. We are evaluating the treatment of liver metastases through the incorporation of selective internal radiation therapy (SIRT) using Yttrium-90 radioactive microspheres for subjects with liver progressive disease following failure of first-line FOLFOX (± bevacizumab). We are presenting our preliminary data for the phase II study evaluating the tumor response rates, PFS, and long-term safety and toxicity to SIRT following FOLFOX (± bevacizumab) prior to FOLFIRI. Methods: Subjects with predominantly hepatic metastatic CRC whose disease progressed on first-line FOLFOX (± bevacizumab) based therapy are eligible. Interventional radiology and nuclear medicine assess the liver lesions and the subject receives their SIRT treatment(s) followed by second-line FOLFIRI based therapy 4-6 weeks after the final SIRT treatment. Optimal timing for microsphere treatment relative to chemotherapy is not clearly established. Results: To date, 9 metastatic CRC subjects have been treated and 11 subjects enrolled (goal 30 subjects). One subject was withdrawn due to progressive lung metastases. Four of 8 subjects (50%) achieved PFS at 6 months and average TTP is 6.7 months (0.7-17.3 months). Overall treatment has been well tolerated, but one possible study related SAE of liver failure occurred (Subject 8). The OS endpoint has not been achieved. Conclusions: Historically, second-line FOLFIRI has achieved a 2.5 months median PFS. In 8 subjects with predominant liver metastatic CRC, we have observed 50% PFS at 6 months. These encouraging results demonstrate the utility of an innovative direct approach to metastatic CRC after failure of first-line combination chemotherapy.

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 3692. doi:1538-7445.AM2012-3692
Abstract 3695: Efficacy of gemcitabine combined with hyperthermia therapy in the treatment of unresectable pancreatic cancer: Phase II study
Authors: Tsuchiya Reiko , Ishikawa Takeshi , Okajima Manabu , Matsuyama Tatsuzo , Yoshida Naohisa , Katada Kazuhiro , Kamada Kazuhiro , Sakamoto Naoyuki , Uchiyama Kazuhiko , Handa Osamu , Takagi Tomohisa , Ysuda Hiroaki , Sakagami Jyunichi , Konishi Hideyuki , Yagi Nobuaki , Kokura Satoshi , Naito Yuji 
Published: August 2012

Abstract
[Background] Pancreatic cancer is an aggressive malignant tumor. Gemcitabine is the standard first line therapy for pancreatic cancer. Several gemcitabine based chemotherapy combinations were studied for the treatment of pancreatic cancer, but these combination therapies showed no major success over single agent gemcitabine in the treatment of pancreatic cancer. Hyperthermia has been shown to increase the cytotoxic effects of some anticancer agents by facilitating drug penetration into tissue, and Gemcitabine has recently been shown to be a potent hyperthermic sensitizer in preclinical studies. We conducted a phase II study to determine the availability of combination therapy with gemcitabine and hyperthermia in the treatment of unresectable pancreatic cancer. [Methods] Patients who participated in the study had advanced pancreatic cancer and their performance status score ware 0-2. The primary end point was one-year survival rate. And the secondary end points were safety and response rate. We set the expectation one-year survival rate to 30% Gemcitabine (1000mg/m2) was given weekly for 3 weeks (day 1,8,15) in four-week cycles, and hyperthermia (40min/once) weekly. This schedule was repeated until disease progression. [Result] From November 2008 to November 2009,18 patients were enrolled in this study. Median patient age was 64 years old(range 47-78), male/female:10/8 All patient died until September 2011, and the one year survival rate is 33.3%, exceeded the expected rate. Disease control rates (CR+PR+SD) were 61.1% (PR/SD/PD=2/9/7) Median survival times were 6 months. Adverse events (Grade3/4) were neutropenia (16.7%), anemia (16.7%), anorexia (5.6%), gastrointestinal bleeding (5.6%). [Conclusion] Combination therapy with gemcitabine and hyperthermia is both a safe and effective treatment in patients with advanced unresectable pancreatic cancer. To clarify the effects of sequential combination of hyperthermia and Gemcitabine as compared with Gemcitabine monotherapy, further studies should be performed, particularly prospective randomized trials.
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 3695. doi:1538-7445.AM2012-3695
Abstract 3700: Anticancer effects and mechanisms of action of novel flavonoid didymin in neuroblastomas
Authors: Nagaprashantha Lokesh , Singhal Jyotsana , Awasthi Sanjay , Singhal Sharad S. 
Published: August 2012

Abstract
Neuroblastomas arise from the neural crest cells and represent the most common solid tumors outside the nervous system in children. The amplification of N-Myc plays a primary role in the pathogenesis of neuroblastomas whereas acquired mutations of p53 lead to refractory and relapsed cases of neuroblastomas. In this regard, dietary compounds which can target N-Myc and exert anti-cancer effects independent of p53 status acquire significance in the management of neuroblastomas. Hence, we investigated the anti-cancer properties of the flavonoid didymin in neuroblastomas. Didymin effectively inhibited proliferation and induced apoptosis irrespective of p53 status in neuroblastomas. Didymin down regulated PI3K, pAkt, Akt, vimentin and up regulated RKIP levels. Didymin induced G2/M arrest along with decreasing the levels of cyclin D1, CDK4 and cyclin B1. Importantly, didymin inhibited N-Myc as confirmed at protein, mRNA and transcriptional level by promoter-reporter assays. HPLC analysis of didymin (2 mg/kg b.w.) treated mice serum revealed effective oral absorption with free didymin concentration of 2.1 µM. Further in vivo mice xenografts studies revealed that didymin (2 mg/kg b.w.) treated animals had significant reductions in tumors size compared to controls. Didymin strongly inhibited the proliferation (Ki67) and angiogenesis (CD31) markers as well as N-Myc expression as revealed by the histopathological examination of paraffin embedded section of resected tumors. Collectively, our in vitro and in vivo studies elucidated the anti-cancer properties and mechanisms of action of a novel, orally active and palatable flavonoid didymin which makes it a potential new approach for neuroblastoma therapy (NANT) to target pediatric neuroblastomas. (Supported in part by NIH grant CA 77495)
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 3700. doi:1538-7445.AM2012-3700
Abstract 3712: Gap junction enhancer potentiates cytotoxic effect of cisplatin
Authors: Ding Ying , Nguyen Thu A. 
Published: August 2012

Abstract
Cisplatin is one of the most widely used anti-cancer drugs due to its highly effective apoptosis induction and DNA damage function. However, increasing reports of side effects and drug resistances indicate the limitation of cisplatin in cancer therapeutics. Recent studies showed that inhibition of gap junctions is one of the reasons that diminishes the cytotoxic efficiency and contributes to drug resistance. Therefore, identification of molecules that counteracts gap junctional inhibition without decreasing the anticancer effect of cisplatin in combinational treatment is essential to reverse resistance and potentiate drug efficacy. This study investigates the effects of combinational treatment of cisplatin and substituted quinoline PQ1, a gap junction enhancer, in T47D breast cancer cells. Cell viability was studied by both trypan blue method and morphology change. Ki67 was used as a marker to examine cell proliferation. Gap junction activity was examined by scrap load/dye transfer (SL/DT) and the expressions of connexins, the components of gap junction. Expressions of apoptotic factors, caspase-8, caspase-9, caspase-3, Bax, and Bcl-2, were measured by western blot analysis. Our results showed that compared with single cisplatin treatment, combinational treatment of PQ1 and cisplatin increased gap junctional intercellular communication (GJIC) as well as expressions of connexins (Cx26, Cx32 and Cx43), and subsequently decreased cell viability. Ki67 was greatly decreased by combinational treatment indicating the inhibition of proliferation. Expressions of pro-apoptotic factors, caspase-3, caspases-8, caspase-9, and bax, were activated or increased by pretreating T47D cells with PQ1; whereas, the pro-survival factor, bcl-2, was decreased by the pretreatment. Our studies imply that PQ1 has the potential to be used in the combinational treatment to counteract the drug resistance and potentiate the efficacy of cisplatin in breast cancer treatment.
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 3712. doi:1538-7445.AM2012-3712
Abstract 3714: Characterization of a selective focal adhesion kinase (FAK) inhibitor in a panel of glioblastoma cell lines identify rational drug-drug combination strategies
Authors: Chen Shujuan , Johnson Natalie , Auger Kurt R. , Xiao Yonghong , Ying Haoqiang , Marszalek Joseph , Middleton Richard , Andersen Jannik N. , McGrath John P. , Chin Lynda 
Published: August 2012

Abstract
Focal Adhesion Kinase (FAK) is a key regulator of cancer cell migration and invasion and overexpression of FAK and Src has been associated with resistance to current anticancer therapies. Thus, inhibition of FAK may represent a promising therapeutic approach to anti-cancer treatment. We investigated the anti-cancer activity of the FAK inhibitor (GSK2256098) in a panel of 26 human glioblastoma (GBM) cell lines. GBM is one of the most aggressive and lethal forms of cancer, characterized by exponential growth and diffuse invasiveness. Herein, we report that 8/26 GBM cell lines displayed sensitivity to FAK inhibition in both migration and Matrigel invasion assays. GSK2256098 had minimal effect on 2D cell proliferation. Integrated genomic and proteomic analyses revealed up-regulation of the PI3K and MAPK pathways in the FAK inhibitor-resistant GBM cell lines, suggesting possible drug combination strategies. To test this hypothesis, we assessed the effects of combining GSK2256098 with a PI3K inhibitor and a MEK inhibitor in the FAK inhibitor-resistant GBM cell lines. Our results suggest that multi-agent inhibition of FAK and MEK or PI3K may provide an attractive therapeutic strategy for GBM.
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 3714. doi:1538-7445.AM2012-3714
Abstract 3717: Pigment epithelium-derived factor prolongs survival and enhances the in vivo antitumor activities of low-dose chemotherapy in castration-refractory prostate cancer
Authors: Filleur Stephanie , Pardue Natalie , Rinard Katherine , Gillen Jessica , Nelius Thomas 
Published: August 2012

Abstract
Background: The development of metronomic/low-dose administration of conventional chemotherapeutic drugs has recently shown great promise in the treatment of castration-refractory prostate cancer (CRPC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which has been shown to be down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF could enhance the cytotoxic effects of low-dose docetaxel (Doc) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: Human CRPC PC3 and CL1 cell lines were genetically modified to stably co-express the fluorescent DsRed Express protein with PEDF. Resulting cell lines were characterized in vitro for PEDF expression by Western blot and for proliferation by growth curves and clone formation in Matrigel. PEDF anti-tumor effects were assessed on established subcutaneous xenografts in mice treated with Doc (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg ip every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1 cells, pre-mixed with 50nM hr-PEDF or carrier control, into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF inhibits the proliferation and induces the differentiation of all CRPC cells tested in vitro. Similarly, PEDF expression decreases the development of subcutaneous PC3 and CL1 tumors in immune-compromised mice by 85% and 70%, respectively. In the survival study, we found that all control animals die within 61 days after surgery while 50% of PEDF-pretreated animals were still alive. Most importantly, we demonstrated that PEDF enhances the cytotoxic effects of low-dose chemotherapy on established tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for both PC3 and CL1). Conclusions: This data reinforces the significance of PEDF as a potential new target for the treatment of advanced prostate cancer. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low-dose Doc and CTX chemotherapies.
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 3717. doi:1538-7445.AM2012-3717
Abstract 3718: Oncolytic reovirus synergizes with bortezomib and dexamethasone in overcoming therapy resistance of multiple myeloma
Authors: Thirukkumaran Chandini M. , Shi Zhong-Qiao , Luider Joanne , Bahlis Nizar , Neri Paola , Morris Don 
Published: August 2012

Abstract
Introduction: Multiple myeloma (MM) is an incurable hematologic malignancy that accounts for 10% of hematopoietic neoplasms. Recently we have demonstrated the potential of reovirus as novel therapeutic agent for a majority of MM cell lines and ex vivo patient tumor. However, therapy resistant disease still remains a problem. In the present study we demonstrate that reovirus acts synergistically with bortezomib and/or dexamethasone in oncolysis of therapy resistant MM cell lines. Methods: The MM cell lines RPMI 8226, U266, NCIH929, U266, INA-6, KMS11 and OPM2 were incubated with live (LV) or UV-inactivated (DV) reovirus at a multiplicity of infection (MOI) of 40 for 24, 48, and 72 hours respectively and cell death was assessed via the WST assay. Reovirus resistant OPM2 and moderately sensitive KMS-11 that are also resistant to bortezomib and dexamethasone were selected for combination therapy and treated with reovirus and drugs at various concentrations to evaluate Effective Dose 50% (ED50) values. ED50 values for each drug and reovirus was combined in various concentrations but with consistent ratios and percent toxicity was determined. Using Calcusyn software, combination index (CI) values were generated and synergism determined as per Chou-Talalay method. Results: Highly synergistic cytotoxicity was observed with reovirus and bortezomib in both reovirus and drug resistant cell lines OPM2 and KMS-11 at all drug combination ratios. Dexamethasone and reovirus treatment induced synergy in OPM2 cells. Conclusion: Not all MM cell lines are amenable to reovirus mediated cell death. This has important implications for the future use of reovirus as a therapeutic agent for cancer as phase II clinical trials for MM are underway. This study highlights the importance of preclinical studies in evaluating effective reovirus drug combinations for future use that could be extrapolated to a clinical setting. Currently we are evaluating the effects of these drug combinations under in vivo conditions in a mouse model that represents the clinical course of MM. The underlying mechanism of reovirus and drug induced cytotoxicity is also being investigated at present. Understanding the signalling pathways of resistant tumor will help develop a more personalized approach of reovirus therapy for cancer patients in the future.
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 3718. doi:1538-7445.AM2012-3718