bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3334: Antiangiogenic activity of honokiol through inhibition of vascular vessel formation in the mouse embryonic stem cell-derived endothelial cells
Authors: Kim Gi Dae , Bae Song Yi , Pyee Yuna , Shin Yoonho , Lee Min Ai , Song Jayoung , Chung Hwa Jin , Park Hyen Joo , Lee Sang Kook 
Published: August 2012

Abstract
Embryonic stem (ES) cells, which are characterized by pluripotency and self-renewal, have recently been highlighted in several aspects of drug discovery. In particular, the potential of ES cells to differentiate into specific-cell types make them an extremely useful tool in the evaluation of the biological activity of test compounds. In the present study, we employed mouse embryonic stem (mES) cell-derived embryoid bodies (EBs) to evaluate the antiangiogenic activity of natural compounds. Honokiol, a major neolignan derived from the bark of Magnolia obovata Thunberg (Magnoliaceae), was capable of inhibiting differentiation and vascular vessel formation in mES cell models. EBs were formed using hanging drop cultures. The induction of vascular formation was carried out on gelatin-coated plates in EGM-2 medium. Cell proliferation was measured by MTT assay. RT-PCR, immunocytochemistry, and Western blotting were used to measure differentiation of EBs into endothelial cells and vessel formation. The growth inhibition of honokiol in EB-derived endothelial cells was found that honokiol is more sensitive in the differentiated cells (on day 8) compared to the undifferentiated EB-derived endothelial cells (on day 1) with the IC50 values of 6.0 and 17.8 μM, respectively. Honokiol also dramatically decreased the expressions of an endothelial biomarker PECAM in the differentiated EB-derived endothelial cells (on day 11). Honokiol also suppressed the activation of p38 MAPK, Akt, ERK1/2 and SAPK/JNK in EB-derived endothelial cells. The antiangiogenic activity of honokiol is associated with the suppression of PECAM and the MAPK pathway in EB-derived endothelial 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 3334. doi:1538-7445.AM2012-3334
Abstract 3337: TGF-β from niche fibroblasts increases the stemness cancer stem cell-like side population cells in gastric cancer
Authors: Hasegawa Tsuyoshi , Yashiro Masakazu , Morisaki Tamami , Aomatsu Naoki , Hirakawa Toshiki , Fukuoka Tatsunari , Matsuoka Junko , Sakurai Katsunobu , Kimura Kenjiro , Nagahara Hisashi , Amano Ryosuke , Noda Eiji , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Yamada Nobuya , Maeda Kiyoshi , Ohira Masaichi , Ishikawa Tetsuro , Hirakawa Kosei 
Published: August 2012

Abstract
Introduction: Cancer Stem Cells (CSCs) are thought to possess tumor initiation and self-renewal and are associated with tumor progression. The niche cells of microenvironment, such as fibroblast might play an important role for the progression of cancer cells. The aim of this study is to examine the effect of cancer-associated fibroblasts on the stemness of CSCs. Material and Methods: A gastric cancer cell line, OCUM-12, and cancer-associated gastric fibroblast, CaF-37, were used. SP cells, known as CSCs rich population, were isolated from OCUM-12 cells by flowcytometry using Hoechest33342, and were named as OCUM-12/SP. The percentage of SP cells was evaluated by flowcytometry, after it was cultured with condition medium from CaF-37 for three days. SP fraction was evaluated by flowcytometry, in the presence or absence of TGF-β receptor inhibitor, FGF receptor inhibitor, and c-Met Receptor inhibitor. In vivo, tumorigenicity of OCUM-12/SP cells were evaluated by subcutaneous inoculation in the presence or abcence of CaF-37. Results: The inoculation of 1.5x105, 5x104, and 1.5x104 OCUM-12/SP cells with 5x105 CaF-37 fibroblasts resulted in tumor formation in all of mice, respectively. However, the inoculation of 1.5x105, 5x104, and 1.5x104 OCUM-12/SP cells alone results in poor tumor formation at 3(60%) of 5 mice, 0(0%) of 5 mice and 0(0%) of 5 mice, respectively. The percentage of SP fraction of OCUM-12/SP was significantly increased in the presence of condition medium from CaF-37. The increase of SP fraction of OCUM-12/SP cells by condition medium from CaF-37 was inhibited by TGF-β receptor inhibitor, but not FGF receptor inhibitor and c-Met inhibitor. Conclusion: TGF-β from the niche, fibroblasts, might sustain the stemness of CSCs and might be associated with the progression of 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 3337. doi:1538-7445.AM2012-3337
Abstract 3341: Chronic TNFα treatment enhances cancer stem cell-like phenotype via Notch1 activation in oral squamous cell carcinoma cells
Authors: Lee Sung Hee , Kim Reuben , Kang Mo , Park No-Hee , Shin Ki-Hyuk 
Published: August 2012

Abstract
Although there is an increasing evidence of chronic inflammation-associated tumorigenesis, the molecular and cellular mechanisms linking chronic inflammation to tumorigenesis have not yet been fully understood. Recent studies have uncovered and validated the pathophysiological role of self-renewing cells, named cancer stem cells (CSC; also called tumor-initiating cells), in long-term sustenance of cancers. In this study, we investigated the effect of chronic inflammation on CSC phenotype of oral squamous cell carcinoma cells (OSCC). We treated OSCC cell lines with tumor necrosis factor alpha (TNFα), a major proinflammatory cytokine, for extended periods and examined the effect of chronic TNFα on CSC characteristics, i.e., undifferentiated tumor sphere forming ability, stem cell-associated genes expression and chemo-radioresistance. Chronic treatment of OSCC with TNFα enhanced CSC phenotype, which is shown by increased tumor sphere forming ability, greatly increased tumorigenicity and chemo-radioresistance, and increased expression of stemness-related genes. Moreover, activation of Notch1 signaling was detected in the TNFα treated cell, and suppression of Notch1 signaling inhibited CSC phenotype. Furthermore, we demonstrated that inhibition of Hes-1, the downstream target of Notch1, led to suppression of CSC phenotype. Taken together, the data suggest that proinflammatory cytokine exposure can generate or/and enrich OSCC CSC population, in part, by activation of the Notch1 signaling pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3341. doi:1538-7445.AM2012-3341
Abstract 3347: A proneural signature profile predicts response to Notch inhibition in glioma stem cells
Authors: Saito Norihiko , Fu Jun , Yao Jun , Verhaak Roel GW , Koul Dimpy , Yung W.K. Alfred 
Published: August 2012

Abstract
The Cancer Genome Atlas Network described genomic abnormalities and gene expression-based molecular subtypes of GBM that showed a strong relationship between subtypes, genomic alterations and different neural lineages. Future studies are required to elucidate the intricate relationship between tumor subtypes and treatment response. We have thus embarked on a comprehensive effort to detecting expression signatures that are associated with response to the therapy and these signatures may allow prospective selection of patients with high likelihood of responding to therapy. Notch signaling pathway is an evolutionarily conserved pathway that plays an important role in multiple cellular and developmental processes including cell fate decision, differentiation, proliferation, survival, angiogenesis and migration. Recent studies indicate that the Notch signaling pathway regulates normal stem cells in the brain, and glioma stem Cells (GSCs) with high Notch activity. We investigated the effects of Notch pathway inhibition on GSCs growth using commercially available inhibitors. Drug cytotoxicity test on 16 GSCs show differential growth response to Notch inhibitors stratifying GSCs into two groups: responders (6 cell lines) vs non-responders (10 cell lines). Gene expression clustering identified a responder gene signature enriched in 1: proneural genes such as Olig2, Sox-9, NKX2-2, and 2: Notch signaling component such as Notch-1, Notch-3, Hes-3 and Hes-5. These signature were validated by western blot analysis. Treatment with Notch inhibitors reduced neurosphere formation in vitro accompanied with attenuated Notch intracellular domain (NICD), Hes-1, Hes-3, and Hes-5. In addition, the expression of nestin-the stem cell marker was reduced and an increased expression of lineage differentiation markers TuJ1 and GFAP was observed following Notch inhibition. In conclusion, we have identified a responder signature for a group of glioma stem cells that can be targeted by Notch inhibitors and this may allow the selection of patients with high likelihood of responding to this 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 3347. doi:1538-7445.AM2012-3347
Abstract 3359: Salinomycin reduces stem cell properties and induces apoptosis in mammary epithelial cell
Authors: sook An Hyun , Kang Han-Na , Kang Myoung-Hee , Kim Jung-Lim , Kim Jun-Suk , Seo Jea-Hong 
Published: August 2012

Abstract
Tumor initiating cells or cancer stem cells (CSCs) were characterized as a unique subpopulation with stem cell features in many types of cancer. Although there has been a number of studies on breast cancer stem cells, inhibitory mechanisms of tumor initiation, progression, and resistance to therapy are unknown. Salinomycin is a chemical isolated from Streptomyces albus and a potassium ionophore. It has been used for many years to control coccidiosis. Recently, salinomycin has been reported to act as selective breast cancer stem cell inhibitor because of its property of reducing the cancer stem cell and inducing the apoptosis in cancer cell. Thus, we investigated the anti-cancer property of salinomycin in mouse mammary epithelial cell. With CDμgeo (mouse mammary epithelial cell), MTT assay was used to confirm cell viability after salinomycin treatment (0, 0.5, 1, 2, 5, 10 μm/ml) upon anchorage-dependent state. We observed that salinomycin reduced the cell proliferation dose-dependently. Also, mammosphere formation assay was performed to observe stem cell-like property after salinomycin treatment in anchorage-independent state. We confirmed salinomycin reduced the number and the size of mammosphere in 72, 144, and 216 hours. We performed salinomycin pre-treatment (0, 0.5, 1, 2, 5 μm/ml) for 12-48 hours upon anchorage-dependent state. Results by western blotting revealed that salinomycin promoted apoptosis of mouse mammary epithelial cells by activating both caspase-3 and -9 and inducing PARP cleavage. To confirm the reduction of the side population level, we performed FACS analysis using CD49+, CD29+, and CD24+ markers. Based on our findings, we concluded that anti-cancer effect of salinomycin reduced stemness and induced apoptosis in mouse mammary epithelial cell.
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 3359. doi:1538-7445.AM2012-3359
Abstract 3360: The hedgehog pathway inhibitor GDC-0449 alters intracellular Ca2+-homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells
Authors: Tian Fei , Huber Rudolf Maria , Schrödl Kathrin , Tufman Amanda , Kiefl Rosemarie , Bergner Albrecht 
Published: August 2012

Abstract
Cisplatin-resistance is an important issue in lung cancer. The hedgehog signaling pathway (Hh) has been shown to be activated in cancer. GDC-0449 is a low-molecular Hh pathway inhibitor that binds to and inhibits Hh pathway receptor SMO. It is the first systemic SMO-inhibitor that has entered clinical trials. Recently, we could show that GDC-0449 is effective in lung cancer cell lines and that combination with cisplatin gives an additional effect. However, no data on the effect of GDC-0449 on cisplatin-resistant lung cancer cells are available. We aimed at investigating if the hedgehog pathway inhibitor GDC-0449 is effective in cisplatin-resistant cells and if it alters the intracellular Ca2+-homeostasis. The cytoplasmatic ([Ca2+]cyto) and endoplasmatic ([Ca2+]ER) Ca2+-concentration of HCC (adeno carcinoma of the lung) and H1339 (small cell lung carcinoma) cells was measured with the calcium indicator dye Fura-2 AM. The expression of the inositol-1,4,5-trisphosphate receptor (IP3R) and Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were analyzed using Western Blot analysis. GDC-0449 inhibited cell growth in cisplatin-naïve and -resistant cells. In both cell types, GDC-0449 increased [Ca2+]cyto and reduced endoplasmatic [Ca2+]ER. Cisplatin failed to considerably alter the Ca2+-homeostasis in resistant cells. The effects of GDC-0449 on the intracellular Ca2+-homeostasis were not mediated by an altered expression of IP3R or SERCA. We demonstrate that GDC-0449 alters the intracellular Ca2+-homeostasis and inhibits cell growth in cisplatin-resistant 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 3360. doi:1538-7445.AM2012-3360
Abstract 3372: Mouse keratinocyte side-population plays an important role during malignant progression to skin squamous cell carcinomas
Authors: Kim Sun Hye , Lee Sung Hyun , Rodriguez-Puebla Marcelo 
Published: August 2012

Abstract
A subset of cells, termed side-population (SP), with characteristics of adult stem cells (SC) has been identified in several tissues, cell lines, as well as human and experimental tumors. The main feature of these putative stem cells is the high efflux capability for antimitotic drugs. The role of this SP in tumorigenesis is controversial; though, a role as cancer stem cells has been reported. Here, we have investigated whether a functionally equivalent SP exists in cell lines derived from mouse epidermis and skin tumors in order to define the extent of which the presence of SP is associated with tumor progression. We observed increased percentage of the SP in cell lines derived from skin squamous cell carcinomas (SCCs; cell lines CH72 and JWF2) compared with those arose from skin papillomas (308 and MT1/2) and mouse epidermis (C50). Side populations were isolated by the high capability to efflux Hoechst upon FACS analysis. Interestingly, qRT-PCR analysis of SP and non-SP shows elevated expression of the ABCG2/BCRP1 transporter -which participates in the dye efflux- in SP; while the expression of the hair follicle stem cell markers keratin 15 (K15), CD34 and Lgr6 were similar between SP and non-SP. These results suggest that the SP is not related to the well characterized stem cells from the bulge region of the hair follicle (BuSC). Importantly, the relevant correlation among the SP size and tumor progression suggests that these cells are positively selected during tumor progression. In order to localize the SP in mouse epidermis and tumors, we performed immunofluorescence analysis of skin papillomas and SCCs generated through the two-stage carcinogenesis protocol. We identified the ABCG2 transporter in a region near and above the BuSC area. Notably, this region was also positive for the thymic epithelial progenitor marker MTS24 which defines a keratinocyte population with characteristic of stem cells. Importantly, the ABCG2 transporter and MTS24 were localized in patches of cells on the proliferative basal cell layer of skin papillomas. Furthermore, we observed an elevated number of putative stem cells expressing ABCG2 and MTS24 in tumors from our previously published K5CDK4 mouse which showed increased malignant progression to SCC. Collectivelly, our results suggest that a putative stem cell population –different from the BuSCs–, play an important role during the malignant progression SCC. Supported by NIH grant CA116328.
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 3372. doi:1538-7445.AM2012-3372
Abstract 3840: Evaluation of the synergetic effect of a combination of dehydroxymethylepoxyquinomicin and gemcitabine on liver metastasis of pancreatic cancer
Authors: Suzuki Keiichi , Takeuchi Osamu , Takizawa Asako , Umezawa Kazuo , Kitagawa Yuko 
Published: August 2012

Abstract
Activation of the nuclear transcription factor-kappaB (NF-κB) has been implicated in the progression and metastasis of pancreatic cancer. This study was designed to evaluate the effects of a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) in inhibition of liver metastasis of pancreatic cancer in a clinical liver metastasis-mimicking mouse model in which cancer cells were intra-portal injected under small laparotomy. Moreover, the synergistic effect of combination therapy with DHMEQ and gemcitabine (GEM) was investigated. Cytotoxicity of DHMEQ and GEM was evaluated by cell growth inhibition assay. Both DHMEQ and GEM monotherapies inhibited cell growth of the human pancreas cell line AsPC-1. However, there was no synergistic effect in the combination therapy. For the in vivo study, male BALB/c nude mice were xenografted with intra-portal vein injection of AsPC-1. Mice were divided into four groups: 1) control (without any treatment), 2) GEM-treated group, 3) DHMEQ-treated group, and 4) combined treatment group (GEM+DHMEQ). Mice were fed for four weeks, and the number of liver metastases, induction of apoptosis in metastasis focuses and angiogenesis were investigated after sacrifice. The number of liver metastasis was decreased significantly in GEM group, DHMEQ group and GEM+DHMEQ group compared with control group. Significant inductions of apoptosis were revealed in GEM group and DHMEQ group compared with control group, in which apoptosis bodies in metastasis sections were counted by using the TUNEL method. Moreover, combination therapy of DHMEQ+GEM resulted in the strongest inductions of apoptosis. Tumor vessels were identified by immunohistochemical staining of tumor metastasis sections with an antibody against CD31. There was a large reduction in the number of CD31-positive vessels in the tumor of DHMEQ or/and GEM-treated mice as compared with control group. However, there was an inconsistency in the results of cell growth inhibition assay (in vitro) and mice metastasis model (in vivo). Thus we evaluated effect of combination therapy in the invasive potential of tumor cells by using chemoinvasion assay. The invasion ability was significantly inhibited in the GEM group, DHMEQ group and GEM+DHMEQ group. Furthermore, real-time PCR was performed to evaluate expression of mRNA of MMP-9. The expression levels of MMP-9 were inhibited in respective groups in the same order. In conclusion, the anti-tumor effects of combination therapy were significant, as evidenced by angiogenesis inhibition, apoptosis induction and invasiveness inhibition rather than cell growth inhibition.
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 3840. doi:1538-7445.AM2012-3840
Abstract 3844: A novel sorafenib-derivative SC-1 induces apoptosis in breast cancer cells through STAT3 inhibition
Authors: Liu Chun-Yu , Tseng Ling-Ming , Chang Kung-Chi , Shiau Chung-Wai , Su Jung-Chen , Chen Kuen-Feng 
Published: August 2012

Abstract
Background: STAT3 has emerged as a novel potential anti-cancer target and its signaling is constitutively activated in various cancers including breast cancer. Our previous study has shown that STAT3 is a major kinase-independent target of sorafenib in HCC. (J Hepatol. 2011). We have designed and synthesized a series of sorafenib analogues devoid of sorafenib's kinase inhibition activity, some of which showed stronger p-STAT3 inhibition and apoptosis-inducing effects than sorafenib in HCC cells (Eur J Med Chem. 2011). Here, we tested the efficacy of our previously published sorafenib derivative, SC-1, in breast cancer cells and examined the drug mechanism. Methods: breast cancer cell lines were used for in vitro studies. Apoptosis was examined by both flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western Blot. Tyrosine Phosphatase Assay Kit was used for SHP-1 activity assay. Gene silencing was done by small interference RNA (siRNA). In vivo efficacy of Sorafenib, and SC-1 were tested in xenografted nude mice. Results: Sorafenib, and SC-1 induced apoptosis in association with down-regulation of P-STAT3 and its downstream proteins Cyclin D1 and survivin in a dose-dependent manner in breast cancer cell lines (HCC-1937, MDA MB-468, MDA MB-231, MDA MB-453, SKBR-3, MCF-7) and the apoptotic effects induced by SC-1 were more potent than Sorafenib. Over-expression of STAT3 in MDA MB-468 cells protected cells from apoptosis induced by sorafenib and SC-1. Moreover, SC-1 up-regulated higher SHP-1 activity than sorafenib by in vitro phosphatase assays. Knockdown of SHP-1, but not SHP-2 or PTP-1B, by siRNA reduced apoptosis induced by SC-1. Importantly, SC-1 showed in vivo efficacy in MDA-468 xenografted tumor. These data indicated that inhibiton of P-STAT3 by up-regulating SHP-1 activity mediated apoptotic effects of sorafenib and SC-1 in breast cancer cells. Conclusions: novel sorafenib-derivative SC-1 induces apoptosis in breast cancer cells through SHP-1 dependent p-STAT3 inhibition. (Supported by NSC100-2325-B-002-036, NSC98-2320-B-010-005-My3 and NSC-100-2325-B-010-007, VGHTPE V100D-005-4, 101DHA0100318, and 101DHA0100230.) Keyword: Sorafenib, breast cancer, STAT3, SHP-1, apoptosis
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 3844. doi:1538-7445.AM2012-3844