bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5714: Screening of some tropical Indian plants for their anticancer activity
Authors: Nawab Akbar , Gupta Sanjay 
Published: February 2011

Abstract
Carcinoma of the breast, colon and prostate are highly prevalent malignancies in the Western nations. Although much innovation in diagnosis and treatment of these cancers has been done but no satisfactory treatment options are currently available. New agents are required which can be developed as anticancer drugs. Despite major scientific and technological progress in combinatorial chemistry, plant derived drugs still make an enormous contribution to drug discovery. Tropical plant species namely Artemisia vulgaris (Compositae), Cichorium intybus (Compositae), Smilax glabra (Liliaceae), Solanum nigrum (Solanaceae) and Swertia chirayata (Gentianaceae) are commonly used for medicinal purposes in traditional forms of Indian medicine. Extracts derived from various parts have shown anti-inflammatory and anti-pyretic properties. However, the anticancer property has not been elucidated. We used human cancer cell lines derived from breast (T47-D), colon (RKO) and prostate (PC-3), to conduct our work. Aqueous freeze dried extracts were prepared from inflorescence (Artemisia vulgaris), seeds (Cichorium intybus), rhizome (Smilax glabra), berries (Solanum nigrum) and whole plant (Swertia chirayata) at the doses ranging from 1-1000μg/mL used to determine EC50 value by performing MTT assay. Exposure of aqueous extract obtained from berries of Solanum nigrum for 24-72h caused 40-87% growth inhibition of PC-3 cells and EC50 value determined to be 220μg/mL after 24 h of treatment. Similarly T47-D cells demonstrated 48-79% inhibition (EC50 550μg/mL) and RKO cells exhibited 40-76% inhibition of cell growth and EC50 value determined to be &gt;1000 μg/mL. Furthermore, aqueous extracts of Artemisia vulgaris, Cichorium intybus, Smilax glabra and Swertia chirayata exhibited cell growth inhibition in all three cell lines but the EC50 values determined were &gt;1000μg/mL. Treatment of cells with 500μg/mL doses of various plant extract for 48h exhibited DNA laddering in all three cell lines with Solanum nigrum. To further verify the apoptotic effect Solanum nigrum we investigated changes in the activity of the apoptotic-related proteins: poly (ADP-ribose) polymerase and caspase 3, which were cleaved in all three cell lines suggesting induction of apoptosis through perturbation of apoptotic signal pathway. A mechanistic understanding of the anti-proliferative and anticancer effects of Solanum nigrum remains to be elucidated.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5714.
Abstract 5739: Lifetime recreational physical activity, hormone therapy use and breast cancer risk in postmenopausal women
Authors: Dieli-Conwright Christina , Sullivan-Halley Jane , Patel Alpa , Press Michael , Malone Kathi , Ursin Giske , Burkman Ronald , Strom Brian , Simon Michael , Bernstein Leslie 
Published: February 2011

Abstract
Studies consistently demonstrate that physical activity is inversely associated with postmenopausal breast cancer. Whether the strength of this association varies with exposure to menopausal hormone therapy (HT) is clearly important given the marked decline in HT use since 2002. The Women's Contraceptive and Reproductive Experiences Study, a multi-center population-based case-control study of invasive breast cancer recruited white women and black women ages 35-64 years, and collected histories of lifetime exercise activity and HT use. Unconditional logistic regression models assessed possible associations between lifetime exercise activity measures (hr/wk/yr and metabolic equivalents of energy expenditure [MET]-hrs/wk/yr) and breast cancer among postmenopausal women (1908 case patients, 2013 control subjects) stratified by duration of HT use (never, ≤5 years of use, or ≥5 years of use), and current HT-use status (current use of estrogen-alone therapy [ET], current use of estrogen plus progestin therapy [EPT], or past HT use). Breast cancer risk decreased as level of physical activity increased among women who had never used HT, among women who used HT for fewer than 5 years, and among current ET users; Ptrend values ranged from 0.004 to 0.019. Despite the lack of association among long-term HT users, current EPT users, and past HT users, no statistical heterogeneity of trends was observed across duration-of-use categories or by current-use status. Although the inverse association between physical activity and breast cancer was limited to women with no HT use, short duration of HT use or current ET use, this study did not demonstrate effect modification by HT use.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5739.
Abstract 5749: Birth weight and sex hormones in adolescent girls: Results from the Dietary Intervention Study in Children (DISC)
Authors: Ruder Elizabeth H. , Hartman Terryl J. , Rovine Michael J. , Dorgan Joanne F. 
Published: February 2011

Abstract
The purpose of the present study is to explore the association of birth weight and concentrations of sex hormones (serum estrogens, progesterone, androgens and sex hormone blinding globulin (SHBG)) among girls participating in the Hormone Ancillary Study (HAS) of the Dietary Intervention Study in Children (DISC), a randomized controlled clinical trial to evaluate the effect of a reduced fat diet intervention on serum hormones. Serum was collected at 5 points during the study and captured the participants’ before, during, and after puberty. Of the 301 girls in DISC, 263 participated in the HAS and had a reported birth weight. Hormones were measured by radioimunnoassay and SHBG was measured by an immunoradiometric assay. Mixed linear regression models were used to calculate hormone concentrations during follow-up after controlling for potential covariates including DISC intervention assignment. Preliminary results for 203 participants suggest an inverse association of birth weight and concentration of DHEAS throughout the 7 years of follow-up after adjusting for years until/ since menarche and other covariates (P ≤ 0.05). An inverse association between birth weight and pre-menarche concentration of androstenedione was observed (P ≤ 0.05), but the relationship did not maintain statistical significance after adjusting for years until menarche (P ≤ 0.24); suggesting that effect of birth weight on pre-menarche androstenedione concentrations may occur in part via the association of birth weight and age at menarche. Post-menarche concentrations of SHBG were positively associated with birth weight, independent of years since menarche (P ≤ 0.05) and other covariates. Luteal phase estradiol, free estradiol and estrone concentrations were positively associated with birth weight, independent of years since menarche and other covariates (P = 0.04, 0.03, 0.05 respectively). No association was found among the other hormones under investigation or the follicular phase estrogens. In conclusion, these data suggest that pre-menarche androstenedione concentration may be inversely associated with birth weight, but this association is likely mediated by the relationship of birth weight and age at menarche. Conversely, the relationships between birth weight and DHEAS, post-menarche SHBG, and certain luteal phase estrogens appear to be independent of the effect of birth weight on age at menarche. Although untested, it is possible that birth weight, as a proxy for in utero hormone exposure, could potentially influence breast cancer risk via long-term effects on pubertal sex hormones on breast tissue development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5749.
Abstract 5778: Fragment-based drug discovery of selective inhibitors of fibroblast growth factor receptor (FGFr)
Authors: Saxty Gordon , Squires M S. , Murray C W. , Berdini V , Ward G A. , Miller D , Rich S J. , Cleasby A , Saalau-Bethell S M. , Coyle J , Madin A , Carr M G. , O'Brien M A. , Jones C Griffiths , Vickerstaff E , Nijjar R K. , Graham B , Pike A , Lewis E J. , Perera T , Angibaud P , Newell H 
Published: February 2011

Abstract
Recent data in a number of tumour types has implicated Fibroblast Growth Factor (FGF) and Fibroblast Growth Factor receptor (FGFr) signalling as being key to the molecular pathology of cancer. This poster will describe fragment based drug discovery using biophysical screening to identify initial fragments. Subsequently, in the fragments-to-leads stage a detailed structural understanding of the binding interactions between the fragment and its target protein utilised X-ray crystallography and NMR. Starting with different fragments allows several lead series to be identified, often by synthesizing only small numbers of compounds.
A fragment screening campaign was conducted against the FGFr-1 to detect very low molecular weight compounds that bound to the hinge region of the kinase. The screening produced several fragment molecules (Molecular Weight &lt;250 Da) which were in the micromolar range and confirmed binding mode in X-ray crystallography. One X-ray hit series that was 120 uM verse FGFr-3 will be described. Several iterations of structure-guided medicinal chemistry led to the identification of a lead compound with 3 nM affinity for FGFr-3, good cell activity and 30-fold selectivity verse VEGFr-2 with good oral activity. The lead was optimised to afford a compound that showed good PK/PD and efficacy.
This poster represents first disclosure of the structure of the lead series and illustrates how a fragment-based drug discovery approach can be efficiently used to discover compounds advanced nanomolar compounds with oral bioavailability.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5778.
Abstract 578: Combination of 4-HPR and EGCG induces apoptosis and inhibits angiogenesis and tumorigenesis of neuroblastoma SH-SY5Y and SK-N-DZ cells
Authors: George Joseph , Banik Naren L. , Ray Swapan K. 
Published: February 2011

Abstract
Neuroblastomas are extracranial, malignant solid tumors in childhood with a dismal prognosis. N-(4-Hydroxyphenyl) retinamide (4-HPR) is a synthetic retinoid that induces apoptosis in tumor cells. (-)-Epigallocatechin-3-gallate (EGCG) is a potent antioxidant abundant in green tea with anticancer properties. In the present investigation, we have studied the combined effect of 4-HPR and EGCG to induce apoptosis and to inhibit angiogenesis and tumor progression of human neuroblastoma malignant SH-SY5Y and SK-N-DZ cells in vivo. The cells were treated with 1 μM 4-HPR, 10 μM EGCG, or combination of both and subjected to MTT assay and TUNEL staining. Western blotting was performed for molecules involved in both receptor and mitochondria mediated apoptotic pathways. Angiogenesis and subcutaneous tumor growth studies were performed in immunocompromised mice. Treatment with combination of 4-HPR and EGCG resulted in more than 70% apoptosis and 80% inhibition in cell proliferation in both cell lines. Apoptosis was associated with induction of both receptor and mitochondria mediated pathways. Our in vivo angiogenesis studies demonstrated significant inhibition of neovascularization after treatment with either agent alone and complete inhibition after treatment with combination of both agents. Studies also demonstrated marked suppression of subcutaneous tumorigenesis and solid tumor formation after treatment with combination of 4-HPR and EGCG. In conclusion, our studies demonstrated that treatment with combination of 4-HPR and EGCG effectively induced apoptosis and inhibited cell proliferation, angiogenesis, and growth of neuroblastomas in vivo. Therefore, the combination of 4-HPR and EGCG could be used as a potential therapeutic regimen for effectively controlling the growth of human malignant neuroblastomas. This investigation was supported in part by the R01 grants (NS-57811 and CA-91460) from the National Institutes of Health (Bethesda, MD).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 578.
Abstract 599: Development of poly(Asp-DET) cationic polymers for nonviral gene delivery
Authors: Mirosevich Janni , Cardoen Gregoire , Sill Kevin , Burke Brian 
Published: February 2011

Abstract
Cationic polymers have received much attention as promising non-viral vectors for gene transfer. However, identification of polymers able to systemically deliver nucleic acids continues to be a significant hurdle to the success of this methodology. The purpose of this study was to develop a new biocompatible and biodegradable cationic polymer system as a non-viral gene delivery agent for plasmid DNA.
Poly-aspartate-diethylene triamine (“P(Asp-DET)”) polymers were synthesized and utilized to complex plasmid DNA. The resulting polymer/DNA complexes, also known as “polyplexes,” were further modified by covalent coupling with polyethylene glycol (PEG), known as “PEGylation,” and characterized. Polyplexes were evaluated for efficiency of encapsulation, particle size, zeta potential and morphology by TEM. Stability of the complexed plasmid DNA was assessed by challenging polyplexes with nucleases. Efficacy of DNA delivery and gene expression was examined by performing transfection experiments using HCT-116 cells. In vivo DNA delivery was also investigated using tumor-bearing nude mice.
Asp-DET polymers were found to bind to plasmid DNA with polymer to DNA (+/-) charge ratios of above 1.5. In addition, these polymers formed polyplex particles of approximately 50-150 nm with zeta potentials between neutral and +40 mV. TEM showed that the polyplexes were uniform and spherical in shape. It was also demonstrated that the polyplexes maintained the structural integrity of DNA following incubation in nucleases. The polyplexes were also capable of transfecting HCT-116 culture cells, with non-PEG complexes having significantly higher GFP and luciferase expression. Tail vein injections of post-PEGylated polyplexes into tumor bearing nude mice did not reveal any observable toxicities. Notably, nucleic acid accumulation was found in tumors with expression detected in lymph nodes.
P(Asp-DET) cationic polymers show enormous potential as non-viral drug delivery agents. Further, the surface modification of described polyplexes with PEG allowed for systemic delivery of nucleic acids to tumors. The characterization of post-PEGylated Asp-DET/DNA polyplexes provides insights that can be used to design vectors for targeted nucleic acid delivery.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 599.
Abstract 624: Synergistic effects of combining the Akt inhibitor triciribine with erlotinib in EGFR TKI-resistant NSCLC
Authors: Gills Joell J. , Morrow Betsy , Kawabata Shigeru , Mercado Jose , Hennessy Bryan , Kunnumakkara Ajaikumar B. , Pao William , Dennis Phillip A. 
Published: February 2011

Abstract
EGFR tyrosine kinase inhibitors (TKIs) are clinically useful agents for the treatment of NSCLC, yet resistance ultimately develops. In an effort to develop strategies to combat resistance and prolong patient benefit, EGFR TKIs were combined with the Akt inhibitor triciribine in a panel of EGFR TKI-resistant NSCLC cell lines. The combination synergistically reduced proliferation in cells that expressed a variety of resistance mechanisms, including intrinsic EGFR T790M mutations, K-Ras mutations, and Met amplification. The combination of erlotinib and triciribine significantly increased apoptosis in H1975 and H1650 cells. It also decreased the phosphorylation of Akt and PRAS40, C-Raf, MEK, and ERK to a greater extent than either drug alone. Unbiased analysis using reverse phase lysate arrays confirmed decreased activation of PI3K/Akt pathway components as well as ERK. The effect of the combination appeared to depend on downregulation of Akt, since a constitutively active form of Akt abrogated the decreased proliferation and increase in cell death caused by the combination. In vivo, the combination inhibited the growth of H1975 xenografts to a greater extent than either drug alone. When tested in an invariably progressive, transgenic model of EGFR-driven lung tumorigenesis (EGFR L858R/T790M), the combination did not cause regression of tumors but stabilized disease in approximately 80% of mice. We conclude the combination of triciribine with EGFR TKIs is promising and should be explored clinically, and that combining inhibitors of the PI3K/Akt pathway with EGFR TKIs may be a useful strategy to overcome EGFR TKI resistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 624.
Abstract 647: Xenograft Models of Breast Cancer: the Link between Characteristics of Biomarker Expression and the Anti-tumor Effect of the Representative Therapies
Authors: Zhang Juan , Guan Ziqiu , Song Xiaoming , Chen Taiping , Wery Jean-Pierre , Chen Yiyou 
Published: February 2011

Abstract
Gene expression analysis has led to the identification of 5 subtypes of breast cancer (basal-like, HER2-like, luminal A and B, and normal-like) that have distinct biological features, clinical outcomes, and responses to conventional chemotherapy and targeted therapy. Animal models possessing genetic and other biomarker abnormalities similar to each subtype of the human counterpart are thus of crucial importance in the development of new therapeutic strategies. Human breast cancer xenograft model is one of the more difficult models with transplantation of either established cell lines or primary tumors. We have successfully established 6 xenograft models derived from established cell lines and 2 xenograft models by transplanting primary human tumor fragments. The immunohistochemical results classified the 9 models into 4 major groups: ER negative and HER2 negative (MX-1, MDA-MB-231, MCF-7-CB1, and SKBR3-CB1), ER negative and HER2 positive (BT-474-CB1), ER positive and HER2 negative (MCF-7), and ER positive and HER2 positive (BT-474), which well resembled basal-like/normal-like, HER2-like, luminal A, and luminal B breast cancer types in human. The mutation status of TP53, BRCA1, BRCA2 and EGFR was investigated, and compared with the in vivo efficacy results by using various test drugs including cytotoxic agents, paclitaxel and doxorubicin; ER antagonist, tamoxifen; anti-HER2 monoclonal antibody, trastuzumab; HER2 inhibitor, HKI-272 and EGFR inhibitor, erlotinib. These data closely mimicked the heterogeneity in clinical outcomes of the human disease. Therefore, these models provide valuable platform for the development of personalized therapy for breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 647.
Abstract 660: Clinical significance of FGFR2 amplification in gastric cancer
Authors: Park Joon Oh , Lee Jeeyun , Jang Hye-Lim , Jang Jiryeon , Park Se Hoon , Park Young Suk , Lim Ho Yeong , Kang Won Ki 
Published: February 2011

Abstract
Background: The fibroblast growth factor receptor (FGFR) tyrosine kinase family, which is comprised of four kinases that differentially respond to 18 FGF ligands, has long been implicated in cancer. Among them, activating somatic mutations in FGFR2 have been recently identified in several types of human cancer and are shown to be sensitive to FGFR2 kinase inhibition in the cell lines bearing such FGFR2 mutations, implicating FGFR2 as a novel therapeutic target. Therefore, we undertook this study to understand the clinical impact of FGFR2 amplification on gastric cancer patients. Patients and Methods: FGFR2 amplification was tested by qPCR using TaqMan probe and dual-color FISH in a panel of 37 gastric cancer cell lines and tumor specimens from 482 gastric cancer patients. Results: Of the 482 patients, 119 (24.8%) of the patients had FGFR2 copy number greater than 3.0 copies. FGFR2 amplification was not associated with clinicopathological parameters such as age, sex, histology, Bormann type, Lauren Classification, tumor location and TNM staging. Patients with FGFR2 amplification showed a trend toward shorter DFS (5-year DFS; 49.6% vs. 59.6%; FGFR2 amplification (+) vs. FGFR2 amplification (-); P=.065) and poorer survival (5-year OS; 47.9% vs. 58.41%; P=.084). We are currently performing preclinical study to investigate FGFR2-correlated sensitivity to several types of molecular-targeted agents. Conclusion: These results suggest that the FGFR2 amplification plays an important role in determining prognosis in gastric cancer patients. However, this study did not cover a predictive role of the FGFR2 amplification for the treatment response to FGFR2 kinase inhibitors, which should be further explored as a novel therapeutic target in upcoming clinical trials.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 660.