bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 259: Antitumor activities of yuanhuadine, a daphnane diterpene from Daphne genkwa, via epidermal growth factor receptor signaling in non-small cell lung cancer cells
Authors: Hong Ji-Young , Park Hyen Joo , Chung Hwa-Jin , Kim Gi Dae , Song Jayoung , Lee Min Ai , Bae Song Yi , Pyee Yuna , Shin Yoonho , Lee Sang Kook 
Published: August 2012

Abstract
The growth inhibition and antitumor activities of yuanhuadine (1), a daphnane diterpenoid from the flowers of Daphne genkwa, were investigated in human lung cancer cells. Compound 1 exhibited a relatively selective growth inhibition against human lung cancer cells compared to other solid human cancer cell lines. The potent antiproliferative activity by 1 was associated with cell-cycle arrest and modulation of cell signaling pathways. Cell-cycle arrest in the G0/G1 and G2/M phase was induced by 1 in A549 human non-small cell lung cancer cells, and these events were correlated with the expression of checkpoint proteins including the up-regulation of p21, and down-regulation of cyclins, cyclin-dependent kinases 2 (CDK2) and 4 (CDK4), and c-Myc. Compound 1 also suppressed the expression of the Akt/mammalian target of rapamycin (mTOR) and its downstream effector molecules including p70 S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1). The ligand-induced epidermal growth factor receptor (EGFR) and c-Met signalings were also inhibited by 1. The oral administration of 1 (0.5 mg/kg body weight, daily) for 14 days inhibited tumor growth in athymic xenograft nude mouse model bearing human lung A549 cells significantly, without any overt toxicity. Synergistic antiproliferative effects of compound 1 were also found in combination with the EGFR inhibitor gefitinib. Cell-cycle arrest and suppression of Akt/mTOR and EGFR signaling pathways might be plausible mechanisms of actions for the antiproliferative and antitumor activity of 1 in human non-small cell lung cancer cells
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 259. doi:1538-7445.AM2012-259
Abstract 2652: Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib +/− megestrol acetate for patients with cancer-related anorexia/cachexia syndrome
Authors: Madeddu Clelia , Dessi Mariele , Panzone Filomena , Serpe Roberto , Antoni Giorgia , Recchia Francesco , Mantovani Giovanni 
Published: August 2012

Abstract
Aims: A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib +/− megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and six minute walk test. Methods: Sixty eligible patients were randomly assigned to: arm 1, L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. Results: The results did not show a significant difference between treatment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. Conclusions: The results of the present study showed a non-inferiority of arm 1 (two drug-combination) vs arm 2 (two drug-combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favourable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS 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 2652. doi:1538-7445.AM2012-2652
Abstract 2653: Racial and ethnic differences in survival after cancer diagnosis
Authors: Lovy Andrew J. , Gorlick Richard G. , Geller David S. 
Published: August 2012

Abstract
Introduction: Racial differences in cancer survival have been well established based on national and independent cancer registries. Multiple extrinsic factors including stage, socioeconomic status (SES) and treatment have been postulated as causative, questioning whether race is a significant independent predictor of cancer survival. The purpose of this study was to evaluate racial differences in overall cancer survival rates in a diverse NY population. Methods: Study population included 18,556 patients (28% White, 31% African American (AA), 27% Hispanic) diagnosed and/or treated for primary cancer from 1/1/2000 through 1/1/2007 at Montefiore Medical Center (MMC), identified through MMC's Cancer Registry. Demographics, clinical information and survival were obtained through the Cancer Registry. SES was determined using census tract data. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare overall survival by race. Results: White patients were older (67.6 vs. 60.9 & 58.7) and of higher SES than AA and Hispanic patients, with similar rates of stage III/IV cancer and surgical treatment. Unadjusted analysis revealed that Whites had a significantly higher risk of death compared to all other patients (HR 1.29, 95%CI 1.23-1.35). Adjusting for age, sex, stage at diagnosis, surgical treatment and SES in all cancer types combined, revealed a significantly higher risk of death compared to all other patients (HR 1.14, 95%CI 1.06-1.21). However, race was no longer a significant predictor of cancer survival in multivariate models stratified by cancer type. Conclusion: Contrary to published literature, White patients had significantly lower survival rates than AA and Hispanic patients in unadjusted models. Racial differences in cancer survival diminished in adjusted models, and were absent when stratifying by cancer type. These results suggest that racial disparities in cancer survival may be better explained by variables such as age, stage at presentation, SES, 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 2653. doi:1538-7445.AM2012-2653
Abstract 2663: Phase I study of azacitidine and cisplatin in patients with advanced head and neck or non-small cell lung cancer
Authors: Liao Yu-Min , Mirshahidi Hamid , Zhang Kangling , Mirshahidi Saied , Williamson Stephen , Hsueh Chung-Tsen 
Published: August 2012

Abstract
Background: DNA hypomethylation agents such as azacitidine may be used for epigenetic sensitization of cisplatin treatment, and therefore leading to improvement of treatment outcome. We conducted a phase I study of azacitidine and cisplatin to determine safety, toxicity, and effect of global DNA methylation in peripheral blood mononuclear cells. Methods: Azacitidine was given as subcutaneous injection daily from day 1 to day 5, and cisplatin was given at 75 mg/m2 IV on day 8. The treatment was repeated every 28 days. Four patients received azacitidine 37 mg/m2 daily from day 1 to day 5 on dose level 1. Two patients were treated on dose level 2, and received azacitidine 60 mg/m2 daily from day 1 to day 5. Peripheral blood samples were collected before and after azacitidine treatment. DNA was extracted from peripheral blood mononuclear cells, and subjected to gas chromatography/mass spectrometry to measure the level of global DNA methylation, as reflected by the ratio of 5-methylcytosine to the sum of 5-methylcytosine and cytosine. Results: No patient had dose-limiting toxicities. Four patients completed at least 2 cycles of treatment, and were evaluated for clinical response by CT scan and DNA methylation effect. One partial response was noted in patient with metastatic tongue cancer after 2 cycles of treatment on dose level 1 of azacitidine. This patient received total 3 cycles of treatment and achieved free of progression for about 15 months on chemotherapy holiday. One patient with recurrent salivary gland cancer achieved stable disease after 2 cycles of treatment on dose level 2, and maintained in free of progression for more than 6 months after 4 cycles of treatment. There was inhibition of global DNA methylation after azacitidine treatment ranging from 12 to 36% in all 4 patients. Furthermore, the inhibition of global DNA methylation was associated with the increase of fetal hemoglobin in patients’ peripheral blood. Conclusion: Sequential administration of azacitidine followed by cisplatin is well tolerated, and demonstrates encouraging activity in patients with advanced head and neck cancer. This combination deserves further clinical investigation to study the correlation between clinical response and biological effects.
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 2663. doi:1538-7445.AM2012-2663
Abstract 2666: Receptor protein tyrosine phosphatase type kappa is a prognostic marker, essential for regulating malignant behavior of glioma cells
Authors: Agarwal Supreet , Sibenaller Zita , Ryken Timothy C. , Assem Mahfoud 
Published: August 2012

Abstract
Malignant gliomas have a poor survival resulting from rapid growth of the tumor and extensive dispersion throughout the brain parenchyma. Discovery of tumor-specific biomarkers hold great promise in improving survival and thus call for better understanding of regulatory signals driving glioma cell migration and dispersal. Using genome-wide exploration, we have identified frequent genetic alterations at the Receptor protein tyrosine phosphatase type kappa (PTPRK) locus. These PTPRK alterations were among the top significant and very relevant to glioma biology since PTPRK is a dephosphorylation regulator of tyrosine phosphorylation (TP) signaling, a frequently altered signaling cascade in glioma as reported previously. Understanding PTPRK function will provide relevant novel insights into the molecular mechanisms underlying glioma cell growth and migration. PTPRK expression was analyzed by quantitative-RT-PCR and western blot. Mutations of PTPRK were identified by sequencing full length PTPRK transcripts from a subset of patients’ samples showing PTPRK loss of heterozygosity. Two major PTPRK variants were cloned and expressed in cells harboring altered PTPRK (U87MG cell line) to study their effect on PTPRK phosphatase activity and functionality. PTPRK locus undergoes allelic loss in glioma and contributes to cancer phenotype. It is an independent prognostic marker in glioma. Patients with altered PTPRK (23%) have shorter survival compared to those with normal PTPRK molecular status (p=0.001, Log-rank test, 14 vs. 30 months). PTPRK mRNA as well as protein levels were lower in tumor biopsies compared to non-tumor specimens. Mutational analysis revealed missense mutations in the phosphatase domain, resulting in altered PTPRK phosphatase activity, possibly due to changes in active site conformation. Further, PTPRK alterations changed expression profiles of the PTPRK protein as a result of altered post-translational processing. Reconstitution of PTPRK expression in glioma cells (U87MG cell line) harboring PTPRK deletions suppressed cell growth and migration which was alleviated by the PTPRK variants to differing extent. PTPRK knockdown via shRNA down-regulated its onco-suppressive function compared to PTPRK expressing cells. Our findings provide the first evidence of the key role of PTPRK expression in glioma and shed light on the biological consequences of mutations in the PTPRK gene which significantly alter PTPRK functionality. Biological relevance of PTPRK variants will be determined and validated on a large scale.
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 2666. doi:1538-7445.AM2012-2666
Abstract 2676: A secreted tissue engineered extracellular matrix (shECM) prevents recurrence in post-resection pancreatic cancer models
Authors: Pinney Emmett , Menen Rhiana , Hassanein Mohamed , Montes-Camacho Mayra , Naughton Gail , Bouvet Michael , Hoffman Robert M. 
Published: August 2012

Abstract
Pancreatic cancer is a highly treatment-resistant cancer. Gemcitabine, which is first-line therapy, results in toxicity without meaningful survival benefit. We report here that a extracellular matrix (ECM) secreted by human embryone fibroblasts in culture inhibit human pancreatic cancer growth and post-surgical recurrence in an orthotopic nude mouse models. Post-resection, all untreated control mice had recurrent disease. In contrast, only 2 of 8 mice (p=0.004) in the treatment group had palpable masses after 6 weekly intravenous treatments. In a second study, targeting the one surgical site with ECM treatment followed by 8 weekly i.p. treatments of ECM, 7 of 8 treated mice survived beyond 10 weeks while none of the untreated control mice survival 8 weeks. No measurable toxicity was observed in the treatment group. These results demonstrate the potential of ECM treatment 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 2676. doi:1538-7445.AM2012-2676
Abstract 2678: Traditional Chinese Medicine (TCM) in combination with S. typhimurium A1-R for cancer treatment
Authors: Zhang Yong , Zhang Nan , Su Shibing , Hoffman Robert M. , Zhao Ming 
Published: August 2012

Abstract
Traditional Chinese Medicine (TCM) has long shown promise for the treatment of cancer. We have previously developed a bacterial cancer therapy strategy using the genetically-engineered strain, Salmonella typhimurium A1-R, which is auxotrophic for arg and leu, which attenuates growth in normal tissue but allows high tumor virulence. S. typhimurium A1-R is effective against metastatic human prostate, breast, and pancreatic cancer cell lines as well as osteosarcoma, fibrosarcoma, and glioma cell lines in clinically-relevant nude-mouse and syngeneic-mouse models. The current study evaluated TCM as combination treatment during bacterial therapy in metastatic mouse models of human cancer. TCM prevented hemorrhagic spots on the skin, liver, and spleen after bacterial infection. Fur discoloration and reduced activity was also observed in mice treated with S. typhimurium A1-R. These symptoms were ameliorated when bacterial treatment was combined with TCM. In a syngeneic lung cancer metastatic model in immunocompetent mice, the combination of TCM and S. typhimurium A1-R enabled S. typhimurium to be safely administered at a dose of 2×105 CFU twice a week i.v. in immunocompotent mice with increased treatment efficacy compared to monotherapy with S. typhimurium A1-R. The results of the present study suggest that combination of S. typhimurium A1-R and TCM has important potential for cancer therapy.
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 2678. doi:1538-7445.AM2012-2678
Abstract 2679: Color-coded selective chemotherapy of methioninase-synchronized S-phase cancer cells expressing cell-cycle-specific fluorescent reporters: A general approach to the treatment of cancer
Authors: Yano Shuya , Li Shukuan , Han Qinghong , Tan Yuying , Fujiwara Toshiyoshi , Hoffman Robert M. 
Published: August 2012

Abstract
Cancer cells of all types have a generally elevated requirement for methionine compared to normal cells. This phenomenon is termed methionine-dependence and may be due to excessive methylation reactions in cancer cells, since methionine is the global source of cellular methyl groups. Deprivation of methionine α,β lyase (methioninase or METase) selectively arrests cancer cells during late S-phase, where they are highly sensitive to chemotherapy drugs which damage DNA. Cancer cells, transformed to express different color fluorescent reporters during specific phases of the cell cycle (fluorescent ubiquitination-based cell cycle indicator [FUCCI]), were used to monitor the onset of the S-phase block due to methionine deprivation effected by METase. The S-phase-blocked cancer cells fluoresced yellow or green, in contrast to cancer cells in G1 which fluoresced red. Cancer cells, synchronously blocked in S-phase by METase and identified by their yellow-green fluorescence, were administered chemotherapy drugs which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin or 5-fluorouracil. We have termed this strategy color-coded chemotherapy. The procedure was highly effective against the cancer cells. In contrast, treatment of cancer cells with drugs only, and without methioninase-effected S-phase synchrony, led to the majority of the cancer cell population being blocked in G phase (red fluorescent) where they were resistant to the drugs. The selective anticancer strategy and technology described in this report, whereby cancer cells are selectively and synchronously blocked in S-phase in the most drug-sensitive phase of the cell cycle where they are identified by fluorescent reporters and then treated with S-phase-specific-drugs, should be a general approach to the treatment of 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 2679. doi:1538-7445.AM2012-2679
Abstract 2685: Imaging the various mechanisms of cancer-cell killing by Salmonella typhimurium A1-R
Authors: Zhao Ming , Zhang Yong , Uchugonova Aisada , Salz Renee , Liu Fang , Suetsugu Atsushi , Zhang Lei , Hoffman Robert M. 
Published: August 2012

Abstract
We have developed a genetically-modified bacterial strain of Salmonella typhimurium, auxotrophic for leucine and arginine, which also expresses green fluorescent protein (GFP), termed S. typhimurium A1-R. S. typhimurium A1-R was found to be effective against metastatic human prostate, breast, and pancreatic cancer cell lines as well as osteosarcoma, fibrosarcoma and glioma cell lines in clinically-relevant nude mouse models. To understand the tumor-killing mechanism of S. typhimurium A1-R-GFP, we have studied their interaction with fluorescence-labeled cancer cells in vitro and in vivo. S. typhimurium-GFP invasion, proliferation, and virulence in the cancer cells were visualized by confocal fluorescence microscopy with the Olympus FV1000. We found that A1-R-induced cancer cell death had different mechanisms in different cancer cell lines. Some S. typhimurium A1-R-treated cancer cell lines became apoptotic and necrotic, and other cell lines burst after extensive intracellular bacterial growth. The time for S. typhimurium A1-R-GFP to kill the majority of the cancer cells varied from line to line, ranging from 2 hours to 72 hours. The understanding of the various mechanisms of cell killing by S. typhimurium A1-R will be important for its use as a general therapeutic for 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 2685. doi:1538-7445.AM2012-2685
Abstract 2689: Inhibition of metastasis of circulating tumor cells by extracellular matrix secreted by human embryonic cells
Authors: Menen Rhiana , Pinney Emmett , Hassanein Mohamed K. , Bouvet Michael , Hoffman Robert M. 
Published: August 2012

Abstract
We have previously demonstrated the increased metastatic potential of human prostate cancer PC-3 CTCs compared to their parental counterparts in both chick embryo and mouse models. In the present study, we tested the effects of human embryonic extracellular matrix (ECM), secreted by human embryonic cells including conditioned medium (CM) and a semi-solid form (hECM), on metastasis of PC-3 CTC in the chick embryo model. The chorioallentoic membrane (CAM) of 18 chicken embryos were inoculated with either 106 PC-3 human prostate cancer cells or PC-3 CTCs, both stably expressing GFP. Twelve hours later, embryos were divided into 6 groups each containing three embryos: PC-3 parental control; PC-3 + CM; PC-3 + hECM; CTC control; CTC + CM; and CTC+ hECM. Twelve hours following inoculation of the cells, a single dose of 100 μL of either treatment was given to the appropriate group. Embryo brains were removed on day 8 post-inoculations, and processed for cryo-sectioning, generating 3 slides of brain tissue per embryo taken at various depths. Imaging was performed using the IV-100 scanning laser microscope (Olympus Corp, Tokyo, Japan) in order to count metastatic foci. PC-3 controls had an average of 11.1 metastatic foci compared to 2.55 in the PC-3 + hECM group (p&lt; 0.0001) and 2.76 in the PC-3 + CM group (p&lt; 0.0001) The treatment showed even greater response on the CTC cells which an average of 30.9 metastatic foci in the CTC controls compared to 4.38 in the CTC + hECM group (p&lt; 0.0001) and 4.18 in the CTC + CM group (p&lt; 0.0001). Thus, human embryonic secreted ECM compound drastically decreased the metastatic potential of human prostate cancer CTCs in the chick embryo model.
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 2689. doi:1538-7445.AM2012-2689