bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4241: Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines
Authors: Sakai Toshinori , Guo Yi , Ramez Eskander , Mefford Jason , Hopkins Justin , Zi Xiaolin , Bhatia Nitin N. , Hoang Bang H. 
Published: June 2012

Abstract
Synovial sarcoma (SS) is a soft tissue sarcoma with poor prognosis and lack of response to conventional cytotoxic chemotherapy. The regulatory mechanisms for the rapid proliferation of synovial sarcoma poorly understood. Surgical resection with/without adjuvant radiotherapy and chemotherapy are the mainstay of treatment. Although the sarcoma cell lines have moderate chemosensitivity to isofamide and doxorubicin therapy, the overall prognosis is still poor. Therefore, further development of the treatment for SS is required. Kava is an ancient crop of the western Pacific. The root extract of kava has been served as a traditional beverage for Pacific Islanders. Consumption of this traditional beverage has been thought to be correlated with low and uncustomary sex ratios of cancer incidence in 3 kava-drinking countrites: Fiji, Vanuatu and Western Samoa. We have already reported that a kind of fravokawains from kava extracts (FKA: flavokawein A) induced apoptosis against bladder cancer cells, and flavokawein B (FKB) was also significant effective in inhibiting the growth of prostate cancer cells. In this study, we examined the inhibitory proliferation effects of the FKB in synovial sarcoma growth and whether FKB modulates tumor apoptosis cascades in human synovial sarcoma cell lines. We treated 2 cell lines of synovial sarcoma (SYO-I, HS-SY-II) by different concentrations of FKB (0, 2.5, 5.0, 7.5 μg/μl) for 24 hours. From the results of real time PCR, depending on the concentrations of FKB in both cell lines, the expression of Survivin was found to be decreased, while those of DR5, Puma, and Bim were increased. These results indicated that FKB effectively induces apoptosis of the two cell lines depending on the concentration. In conclusion, our findings demonstrate that FKB is effective for growth inhibition of synovial sarcoma cell lines in vitro and suggest that FKB may be a new therapeutic option for patients with synovial sarcoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4241. doi:10.1158/1538-7445.AM2011-4241
Abstract 4246: Enhanced anti-vascular and anti-tumor effects upon combination therapy with aflibercept (VEGF Trap) and other anti-angiogenic drugs
Authors: Adler Alexander P. , Vangala Pranitha , Castanaro Carla , Daly Christopher , Thurston Gavin , Eichten Alexandra 
Published: June 2012

Abstract
Experimental and clinical development of anti-angiogenic drugs to date has mostly focused on the VEGF pathway, although other signaling pathways, including Dll4-Notch and Angiopoietin-Tie, are now also being explored. Targeting one pathway, however, might not result in maximum anti-vascular and anti-tumor effects. In this study, we compared the rapid effects on tumor perfusion of single agent blockade of VEGF, Dll4 or Ang2 to the effects of combined therapy (VEGF blockade plus either Dll4 or Ang2 blockade), and compared long-term tumor growth responses to these early effects on tumor perfusion. Using aflibercept (VEGF Trap) alone and in combination with a blocking Dll4 antibody or a blocking Ang2 antibody, we compared various tumors with a wide range of long-term growth responses to each agent: C6 rat glioma tumors, HT1080 human fibrosarcoma and Colo205 human colon carcinoma tumors, all grown subcutaneously in SCID/CB17 mice. Tumor vascular perfusion was assessed using contrast-enhanced micro-ultrasound at 24 and 72 hr after treatment. We found that aflibercept treatment rapidly decreased vascular perfusion in C6 (59% after 24 hr) and Colo205 (32%) tumors, whereas there was no decrease observed in HT1080 tumors. These changes in perfusion correlated with long-term tumor growth inhibition upon aflibercept treatment. Dll4 blockade resulted in decreased vascular perfusion in C6 (30% after 24 hr), Colo205 (77%), and HT1080 (54%) tumors, which again correlated with long-term growth inhibition of the different tumors. Treatment with an anti-Ang2 antibody produced a slight decrease in perfusion of Colo205 tumors (13% after 24 hr), associated with a decrease in tumor growth. However, combination treatments with aflibercept plus either anti-Dll4 or anti-Ang2 antibodies were more potent in all tumor types compared to single agent treatments at reducing tumor perfusion as well as inhibiting long-term tumor growth. Taken together, these data show that changes in tumor perfusion correlate with long-term tumor responses to combination treatment of aflibercept plus either anti-Dll4 or anti-Ang2 antibody suggesting that decreases in tumor perfusion could be an early biomarker predictive of response to anti-angiogenic therapies. Measuring the increased effectiveness of combination therapy in patients treated with different anti-angiogenic drugs may facilitate the improvement of current treatment regimens.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4246. doi:10.1158/1538-7445.AM2011-4246
Abstract 4247: Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab
Authors: Ohara Toshiaki , Noma Kazuhiro , Watanabe Shinichiro , Ohnishi Teppei , Nishitani Seishi , Tomono Yasuko , Hashimoto Yuuri , Tazawa Hiroshi , Fujiwara Toshiyoshi 
Published: June 2012

Abstract
[Introduction] Lung cancer is one of the most aggressive malignancies with poor prognosis. Many kinds of new medicine for chemotherapy have been developed and introduced in clinical practice, whereas the mortality has not been satisfied. Furthermore, development of new medicine for chemotherapy costs a vast sum of money, which leads expensive treatment. Therefore, It's expected that development of new strategy extremely enhances the efficacy of ordinary therapeutic strategy. Iron metabolism and its relationship with cancer cell have been studied for a long time. Iron overload is known to induce some kinds of cancer, which suggests that prevention of iron overload could be a therapeutic strategy of cancer prevention. In fact, iron deficiency is also known to suppress the tumor growth in vivo study. However the efficacy is not superior to the ordinary chemotherapy, it's not a standard therapeutic strategy of cancer. In this study, we demonstrated that iron deficiency induced the suppression of the tumor growth and unwillingly up-regulation of angiogenesis in vitro and in vivo studies. Moreover using Bevacizumab together strongly suppressed the tumor growth in NSCLC. This result suggests that Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab.
[Materials and Methods] A549, H1299 NSCLC cell lines were used. In vivo study, Normal diet and Iron deficient diet are prepared. Normal diet and Iron deficient diet were fed for 3 weeks before implantation of A549 cells in athymic male nude mice(n=8/group). In Bevacizumab administration study, as shown above, Bevaicuzmab(5 mg/kg) was administrated twice a week in each diet group. In vitro study, Iron chelator deferasirox was used in vitro study. Cell viability was determined by WST-1 assay. Cell cycle analysis was measured by flow cytometry. To determine angiogenesis via hypoxia, western blotting analysis and VEGF ELISA assay were done.
[Results] Tumor growth was suppressed in iron deficient diet group (p=0.0037). Bevacizumab revealed to have an additive effect to inhibit the tumor growth. Deferasirox reduces A549 and H1299 cell proliferation in a concentration manner via cell cycle arrest. Deferasirox induces VEGF in A549 and H1299 supernatant via up-regulation of HIF1a.
[Conclusion] Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4247. doi:10.1158/1538-7445.AM2011-4247
Abstract 4325: Localization and expression of osteopontin in a chitosan-treated ovarian cancer cell line, SKOV-3
Authors: Regisford E. Gloria C. , Stone Julia M. , Carson Laura E. , Kelly-Brown Cordella , Traisawatwong Pasakorn , Hicks Antoine 
Published: June 2012

Abstract
Ovarian cancer is the deadliest gynecological malignancy and despite current treatments, such as chemotherapy and radiotherapy, reoccurrence of this deadly malignancy is high. Although elevated levels of osteopontin (OPN), a phosphorylated glycoprotein, are always present in the ovaries, recent studies have implicated osteopontin (OPN) protein as a novel biomarker for ovarian cancer. Early detection of ovarian cancer is imperative, and furthermore, novel treatments with fewer adverse effects than current treatments of chemotherapy and radiation, are currently being investigated. Chitosan, a natural polysaccharide that is biodegradable and biocompatible, may serve as a potential alternative treatment for ovarian cancer, and may function by regulating OPN expression. Therefore, the objective of this study was to determine the effects of chitosan on the expression and localization of OPN in SKOV-3 cells. It was hypothesized that the expression of OPN protein will be down-regulated in a dose-dependent manner. To test this hypothesis, SKOV-3 cells were treated with 0, 50, 100, 250, and 500, ng/mL of chitosan for 48 hours. An MTT assay was performed to determine cell viability and proliferation rate. Cells were harvested; total protein was isolated and then subjected to SDS-PAGE and Western blot analysis. The localization of OPN was determined using immunocytochemistry, after chitosan treatment of SKOV-3 cells on two-chamber slides for 48 hours. The expression of OPN decreased in SKOV-3 cells in a dose-dependent manner. In addition, cell proliferation tended to decrease with increasing dose of chitosan. These data indicate that chitosan may inhibit SKOV-3 cell proliferation by decreasing OPN production and secretion.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4325. doi:10.1158/1538-7445.AM2011-4325
Abstract 4330: Endometrial hyperplasia resulting from myeloid-specific targeting of the tumor suppressor APC
Authors: Kitchen-Goosen Susan M. , Alberts Art 
Published: June 2012

Abstract
The Adenomatous polyposis coli (APC1) tumor suppressor is a multi-function protein with a central role in Wnt-regulated cell growth and differentiation. Additionally, APC functions to modulate microtubule and microfilament dynamics to establish polarity in epithelia during directed cell migration and asymmetric cell division. APC frequently collaborates with the canonical Diaphanous-related formin, mDia1 (DIAPH1), which also binds microfilaments and microtubules to modulate cytoskeletal dynamics. APC1 and DIAPH1 are genetically linked on chromosome 5q in a region frequently disrupted in myeloproliferative neoplasms (MPNs). mDia1 knockout mice develop an age-dependent outgrowth of myeloid-lineage cells. The physical and functional linkage of APC and mDia1 as 5q tumor suppressors and in cytoskeletal remodeling led us to explore the role of APC in tumor suppression in myeloid-derived cell lineages affected by mDia1 knockout.
To test this hypothesis in a genetic model, we created a mouse in which APC was knocked out in myeloid lineage cells by breeding the Apc-flox mice with mice expressing Cre recombinase under the control of lysozyme M (LyzsM) gene promoter. The resulting phenotype was unexpected and 100% penetrant: Female mice developed cystic endometrial hyperplasia and were unable to sustain pregnancy. Embryo implantation occurred, but embryos were resorbed mid-gestation irrespective of progeny genotype. Two hypothesized mechanisms to explain the initiation of endometrial hyperplasia are being pursued. The first hypothesis is that loss of APC impairs the homeostasis between growth and differentiation of myeloid lineage stem/progenitor cells that transdifferentiate into uterine epithelia. An alternate hypothesis is that loss of APC expression affects the inflammatory response of resident uterine macrophages that lead to defects in epithelial morphology. In either case, these genetic studies imply that APC gene defects in myeloid lineage cells may be an initiating event in endometrial cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4330. doi:10.1158/1538-7445.AM2011-4330
Abstract 4331: Characterization of targeted overexpression of Claudin-1 transgenic mice
Authors: Pope Jillian L. , Bhat Ajaz , Krishnan Moorthy , Beauchamp R. D. , Singh Amar , Dhawan Punita 
Published: June 2012

Abstract
Disruption of cell-cell junctions and changes in the expression of junctional proteins is a critical event in the progression of cancer. We have previously reported a tumor stage specific increase in the expression of a tight junction protein, Claudin-1, in colorectal cancer and its association with tumor-growth and metastasis. Furthermore, our studies have shown that in colon cancer cells, claudin-1 expression is regulated by a complex interaction between APC, Smad4 and β-catenin, three important regulators of colorectal carcinogenesis. We wanted to investigate the consequence of overexpression of claudin -1 in vivo specifically in the colon.
We have generated a transgenic mouse model in which Claudin-1 is expressed under the control of the villin promoter. The villin promoter is expressed in the adult intestinal epithelium and has been frequently used for intestinal-specific overexpression of several genes of interest. Western blot analysis demonstrated a robust expression of claudin-1 in the colon, small intestine and cecum of transgenic mice while low levels of expression were present in wild type mice. These results are confirmed with immunohistochemistry analysis where claudin-1 was largely expressed on the membrane in the same tissues. Colonic permeability was assayed using FITC-dextran, however, there was no significant difference between the flux of FITC-dextran in wild-type and transgenic mice. Real-Time PCR analysis for inflammatory cytokine expression showed a decrease in IL-10 mRNA in transgenic mice compared to that of wild-type mice. Further, treatment with Dextran Sodium Sulfate (DSS) to induce colitis showed a significant decrease in body weight of claudin-1 transgenic mice as compared to wild type mice on DSS. An increase in disease severity was observed in transgenic mice as determined by histology scoring, as well as a significant difference in the ratio of colon weight to colon length. Claudin-1 expression in transgenic mice is localized to the membrane, where it maintains its normal function. Further experiments with this model include combined treatment with DSS and AOM to examine the effect of Claudin -1 overexpression in inflammation-induced-tumorigenesis as well as performing crosses with sporadic models of tumorigenesis involving mutations in the APC gene, to examine the role of claudin-1 upregulation in tumor formation and progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4331. doi:10.1158/1538-7445.AM2011-4331
Abstract 4368: Targeting of head and neck cancer stem cells using salinomycin
Authors: Kuo Selena Z. , Blair Katherine J. , Abhold Eric L. , Kiang Alan , Haas Martin , Wang-Rodriguez Jessica , Ongkeko Weg M. 
Published: June 2012

Abstract
Cancer stem cells are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Gupta and colleagues recently reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells. In our study we sought to determine the effect of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. We observed that salinomycin inhibits self-renewal capacity in HNSCC stem cells, as shown by a dose-dependent decrease in sphere formation. In addition, treatment with salinomycin resulted in a decrease in mRNA expression of the stem cell markers CD44 and BMI-1, both of which are critical for maintaining tumorigenicity in HNSCC. In combination with the chemotherapeutic agents cisplatin and doxorubicin, salinomycin synergistically killed HNSCC cancer stem cells more effectively compared to either drug alone, as demonstrated by cell proliferation and TUNEL assays. High-throughput analysis revealed a set of differentially expressed microRNAs in salinomycin-treated HNSCC stem cells, warranting further investigation into the possibility of microRNA-mediated pathways that are regulated by salinomycin. Taken together, our findings indicate promise for using salinomycin or related derivatives as a novel treatment for HNSCC, although further studies are needed to confirm efficacy in vivo.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4368. doi:10.1158/1538-7445.AM2011-4368
Abstract 4370: Network-based signatures for drug repositioning and combination for the breast tumor initiating cells
Authors: Jin Guangxu , Zhao Hong , Cong Yang , Fu Changhe , Chang Jenny , Lewis Michael , Wong Stephen 
Published: June 2012

Abstract
Understanding the signaling mechanisms of breast tumor initiating cells (TIC) is important to design efficient therapeutic and management strategies of breast cancer. We present a network-based signature and a comprehensive signaling map for identification of candidates of drug repositioning and combinations for breast TIC. The network-based signature is based on an extended concept of network motifs, known as cancer-signaling bridges (CSBs), which can be used to expand the cancer drug-targets of known signaling pathways. We use the profiles of TIC derived from CD44+/CD24-/low breast cancer cells and mammospheres (MS) cells to establish network-based signatures. Facilitated by the signaling pathways that are highly connected with CSBs, e.g., MAPK, NOTCH, ECM-receptor, Jak-STAT, and Wnt, we first identify the high-confidence signaling paths automatically chosen out of CSBs by two scoring systems, namely, Differential Expression Score (DES) and Signaling Pathway Score (SPS). The high-confidence signaling paths are used to build the network-based signature that characterizes the breast TIC. The network-based signature for CD44+/CD24-/low cells is composed by 140 proteins and 132 protein-protein interactions and that for mammospheres contains 153 proteins and 119 protein-protein interactions. The FDA-approved drugs whose targets are included in the network-based signatures are repositioned to breast TIC as the candidates for the repositioning. Furthermore, we curate a comprehensive signaling map for breast TIC by using the available signaling transductions in BioCarta, KEGG, and IPA and include seven signaling pathways, PI3K/AKT, JAK/STAT, Notch, HH, Wnt, P53, and ECM. The signaling map enables us to further refine the repositioning candidates and eventually propose combination candidates by using the cross-talks of signaling pathways in the map. Using this mapping approach, the drugs targeting on TNF, KDR, and IKBKB, such as sunitinib, Arsenic trioxide, and Atorvastatin, are repositioned for treating breast TIC, while the crosstalks between pathways such as Notch+hedgehog and Hedgehog+wnt+PI3K are used to identify drug combination candidates from the target combinations, TNF+KDR, and TNF+IKBKB.
Acknowledgements: This research is partially funded by NIH ICBP U54CA149169. The authors would also appreciate the discussion and advice of Jeff Rosen and David Tweardy from Baylor College of Medicine during the generation of comprehensive signaling map for breast TICs.
Guangxu Jin and Hong Zhao contribute to this work equally.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4370. doi:10.1158/1538-7445.AM2011-4370
Abstract 4375: Cancer protection by pregnancy – a link with microchimeric fetal/maternal stem cells in a stromal niche: Breast cancers are hypochimeric, but the HER2-subtype is hyperchimeric
Authors: Dhimolea Eugen , Denes Viktoria , Aziz-Zaman Sonya , Geck Peter 
Published: June 2012

Abstract
The PURPOSE of our studies was to investigate the origin and cancer relations of embryonic/fetal stem cells in breast cancer.
HYPOTHESIS. During pregnancy the documented exchange of fetal and maternal stem/progenitors establish long-term integration in the recipient organism. We propose that the breast is a potential niche and this new stem cell pool may affect breast cancer.
OBJECTIVES. (i) To work out more sensitive methods to detect Y- and X-chromosomal markers from embedded, formaldehyde-fixed tissue samples; (ii) To find the tissue compartment for the long-term microchimerism niche in the breast; and (iii) to collect quantitative chimerism data to investigate non-chimeric, hypochimeric, microchimeric and hyperchimeric contribution to cancer.
EXPERIMENTS. We developed new systems for Y-signal detection (single-amplicon/multiple-target analysis) and X-haplotype analysis with significantly increased sensitivity from low-integrity samples. We analyzed 55 normal samples representing stromal, ductal and lobular tissues and 102 invasive ductal breast cancer samples. Quantitative amplifications were performed following recent MIQE recommendations. We used fluorescent in-situ hybridizations (FISH) to confirm microchimerism. The data were analyzed by extensive statistical analyses and only data with statistical significance are presented.
RESULTS. We found 19.6% microchimerism in cancer samples, in contrast to 40% in normal tissues. The results confirm that hypochimerism promotes but microchimerism protects from cancer. We show for the first time that the long-term niche for post-pregnancy microchimeric (male) cells is the mammary stroma but they don't integrate into the ducts, the site of most cancers. Based on the findings we propose that breast cancer protection by pregnancy may be a stromal function and involves fetal microchimerism. Unexpectedly, we also found that a cohort of breast cancers show runaway microchimerism with significantly increased male-cell content. This is the first report that hyperchimerism correlates with the HER2-subtype and unfavorable prognosis.
CONCLUSIONS. We developed a new assay and our studies demonstrate previously unrecognized significant stromal integration of fetal/maternal stem cells in protection from breast cancer. We also found, however, that excessive microchimerism promotes cancer and correlates with the HER2-subtype.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4375. doi:10.1158/1538-7445.AM2011-4375