bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5566: CARP-1 functional mimetics (CFMs): a novel class of small molecule inhibitors (SMIs) of medulloblastoma cell growth.
Authors: Ashour Abdelkader E. , Jamal Shazia , Cheryan Vino , Alafeefy Ahmed M. , Levi Edi , Tarca Adi L. , Polin Lisa A. , Rishi Arun K. 
Published: August 2014

Abstract
Medulloblastomas (MBs) are an aggressive class of intracranial pediatric tumors. Current multimodality treatments for MBs include surgery, ionizing radiation, and chemotherapy. Toxic side effects of therapies coupled with high incidence of recurrence and the metastatic spread warrants development of more effective, less toxic therapies for this disease. CARP-1/CCAR1 is a peri-nuclear phospho-protein that is a co-activator of the cell cycle regulatory anaphase promoting complex/cyclosome (APC/C) E3 ligase. CARP-1 functional mimetics (CFMs) are a novel class of small molecule compounds that interfere with CARP-1 binding with APC/C subunit APC-2, and suppress growth of a variety of cancer cells in part by promoting apoptosis. Here we investigated MB growth inhibitory potential of the CFM-1, 4, and 5, and found that CFMs inhibit growth of MB cells. CFM suppression of MB cell growth involved elevated CARP-1 expression, activation of pro-apoptotic stress-activated protein kinase (SAPK) p38, and apoptosis. Gene-array-based analysis of the CFM-4-treated Daoy MB cells indicated down-regulation of a number of key cell growth and metastasis-promoting genes including cell motility regulating small GTP binding protein p21Rac1, and extracellular matrix metallopeptidase (MMP)-10. Moreover, CFM-4 treatment stimulated expression of a number of growth inhibitory and apoptosis-inducing molecules such as neurotropin (NTF)3, while knock-down of NTF3 interfered with MB growth inhibitory effects of CFM-4. CFMs also attenuated biological properties of the MB cells by blocking their abilities to migrate, form colonies in suspension, and invade through the matrix-coated membranes. Together our data support anti-MB properties of CFM-4, and provide a proof-of-concept basis for further development of CFMs as potential anti-cancer agents for MBs.
Citation Format: Abdelkader E. Ashour, Shazia Jamal, Vino Cheryan, Ahmed M. Alafeefy, Edi Levi, Adi L. Tarca, Lisa A. Polin, Arun K. Rishi. CARP-1 functional mimetics (CFMs): a novel class of small molecule inhibitors (SMIs) of medulloblastoma cell growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5566. doi:10.1158/1538-7445.AM2013-5566
Abstract 5568: Thermochemotherapy with controlled drug delivery using a novel magnetic anti-cancer drug .
Authors: Sato Itaru , Mitsudo Kenji , Umemura Masanari , Feng Xianfeng , Fukumura Hidenobu , Eguchi Haruki , Nakashima Hideyuki , Kioi Mitomu , Tohnai Iwai , Ishikawa Yoshihiro 
Published: August 2014

Abstract
Background:
Radical surgery for patients with oral cancer may cause dysfunction, such as dysphagia, dysarthria, or mastication disorders, leading to decreased quality of life in cancer patients. Here, we report the development of a novel magnetic anti-cancer drug, EI236, which may enable us to reduce such problems. EI236 possesses three features; anti-cancer effect alike cisplatin, controlled drug delivery using a magnet, and hyperthermic effect upon exposure to an alternating current magnetic field (ACMF). We thus examined the efficacy of EI236 in treating oral cancer in a rabbit cancer model.
Methods:
Cell proliferation was measured by MTT assays. We established the rabbit tongue cancer model using VX2 cells, which are readily transplantable in vivo. Electromagnet was used to attract EI236 to the site of tongue cancer by controlled drug delivery (CDR), and ACMF to generate heat from EI236 (HT). Rabbits were divided into 4 groups: control group, intravenous EI236 injection group (5mg/kg×7days) (i.v.), intravenous EI236 injection + electromagnet group (i.v. + CDR), intravenous EI236 injection + electromagnet + ACMF group (i.v. + CDR + HT). The size of tumors was measured daily for 7 days, followed by histopathological evaluation. Of note, EI236 was injected at the same dose in the three groups.
Results:
EI236 showed anti-cancer effects in a dose-dependent manner in VX2 cells. The IC50 value of EI236 was 7.5μM in cultured cells. The resultant tumor volume after EI236 i.v. injection treatment in rabbits was as follows; 319.3±40.0% for control, 228.5±94.3% for i.v., 91.5±27.4X% for i.v. + CDR, 24±8.2% for i.v. + CDR + HT, indicating that the i.v. + CDR + HT group showed the greatest decrease. It also showed the largest necrotic area in H-E staining analysis. The tumor cell nucleus, as determined by Ki67 staining, were mostly disappeared.
Conclusion:
Anti-cancer effect of EI236 was synergistically increased in the presence of CDR and/or HT. EI236 may serve as a novel anti-cancer therapy that enables CDR and HT at the same time.
Citation Format: Itaru Sato, Kenji Mitsudo, Masanari Umemura, Xianfeng Feng, Hidenobu Fukumura, Haruki Eguchi, Hideyuki Nakashima, Mitomu Kioi, Iwai Tohnai, Yoshihiro Ishikawa. Thermochemotherapy with controlled drug delivery using a novel magnetic anti-cancer drug . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5568. doi:10.1158/1538-7445.AM2013-5568
Abstract 5575: Strigolactones: a novel class of plant hormones inhibit cancer cell and cancer stem-like cell growth and survival.
Authors: Yarden Ronit I. , Pollock Claire B. 
Published: August 2014

Abstract
Strigolactones (SLs) are a novel class of plant hormones produced in roots and regulate new above ground shoot branching, by inhibiting self-renewal of undifferentiated meristem cells. Here we show that Strigolactone analogues are able to inhibit proliferation and induce apoptosis of several different types of cancer cells including breast, prostate, lung, colon and osteosarcoma cells but not ‘non-cancer’ lines. Given the therapeutic problem of cancer recurrence which is hypothesized to be due to drug resistant cancer stem cells, we also tested the ability of Strigolactone analogues to inhibit cancer stem cell growth. We show that Strigolactones are potent inhibitors of self-renewal and survival of breast cancer cell lines grown as cancer stem cell enriched mammospheres and even a short exposure leads to irreversible effects on mammosphere dissociation and cell death. Cell cycle analysis showed that all five strigolactone analogues induced G2/M arrest, coupled with increased percentages of cells in the sub-G1 fraction. AnnexinV staining confirmed that Strigolactone treatment induced apoptosis. Strigolactone treatment was hallmarked by increased expression of genes involved in stress signaling, as well as apoptosis, metabolic function and cellular adhesion. Immunoblot analysis of strigolactone treated cells also revealed increased phosphorylation of the stress activated MAPKs: p38 and JNK1/2 and decreased phospho-ERK1/2 and phospho-AKT. In summary, Strigolactones are promising candidates for anticancer therapy by their ability to induce cell cycle arrest and apoptosis in cell lines derived from a wide array of different cancers.
Citation Format: Ronit I. Yarden, Claire B. Pollock. Strigolactones: a novel class of plant hormones inhibit cancer cell and cancer stem-like cell growth and survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5575. doi:10.1158/1538-7445.AM2013-5575
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 5584: Finding predictive markers for tumor response to classical cytotoxic drugs.
Authors: Borst Piet , Rottenberg Sven 
Published: August 2014

Abstract
As attempts to find predictive markers for cytotoxic drugs have been relatively unsuccessful using patient tumor samples (1), we are using a mouse model for BRCA1-deficient mammary tumors to search for such markers. Although these tumors originate in inbred mice from an inactivating deletion of the Brca1 and p53 genes, their response to doxorubicin (2), docetaxel (2), topotecan (3) and PARP inhibitors (4) varies. We have shown that in this tumor model 5 of the 22 tumors respond poorly to docetaxel, because of upregulated drug-transporting P-glycoproteins (5). These 5 were not found by standard gene expression analytical tools, such as significance analysis of microarrays (SAM), and we have shown that SAM only detects resistance markers if present in more than half the tumor samples (5). Better algorithms for the detection of resistance determinants in a subfraction of tumors are being developed by De Ronde and Wessels (5). We are still searching for the cause of the poor docetaxel response in 17 of the 22 tumors.
1. Borst,P. and Wessels,L. (2010). Do predictive signatures really predict response to cancer chemotherapy? Cell Cycle 9, 4836-4840.
2. Rottenberg,S., et al (2007). Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer. Proc. Natl. Acad. Sci. U. S. A. 104, 12117-12122.
3. Zander,S., et al (2010). Sensitivity and acquired resistance of BRCA1; -53-deficient mouse mammary tumors to the topoisomerase I inhibitor topotecan. Cancer Res. 70, 1700-1710.
4. Rottenberg,S., et al (2008). High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc. Natl Acad. Sci. U. S. A 105, 17079-17084.
5. Rottenberg,S., et al (2012). Impact of intertumoral heterogeneity on predicting chemotherapy response of BRCA1-deficient mammary tumors. Cancer Res 72, 2350-2361.
Citation Format: Piet Borst, Sven Rottenberg. Finding predictive markers for tumor response to classical cytotoxic drugs. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5584. doi:10.1158/1538-7445.AM2013-5584
Abstract 559: The molecular kinetics of p21 and Cdk4 dictates irreversible G0/G1 phase cell cycle arrest in CRPC cells.
Authors: Gulappa Thippeswamy , Reddy Rama S. , Suman Suman , Damodaran Chendil 
Published: August 2014

Abstract
Deregulation of cell cycle progression is the hallmark of cancer; to this effect, several small molecules (AG-024322, AT7519, E7070, P1446A-05 and Flavopiridol) against cell cycle kinases are being developed to regulate cell cycle machinery that resulted in inhibition of tumor growth. The present study examined the effect of 3, 9-dihydroxy-2-prenylcoumestan-a furanocoumarin (Pso) on castration resistant prostate cancer cells (CRPC) cells. Treatment of CRPC (PC-3 and C4-2B) cells with Pso significantly caused irreversible G0-G1 cell cycle arrest that resulted in inhibition of cell proliferation. Protein analysis suggested that the expression of cdk inhibitors (CDKI) p21cip1 and p27kip1 were upregulated in both CRPC cell lines by Pso treatment. Studies using real-time reverse transcription-polymerase chain reaction analysis suggest that Pso transcriptionally regulates p21cip1 and p27kip1 in CRPC cells. Our immunofluorescence analysis pointed out that both p21cip1 and p27kip1 accumulated in the nucleus upon the treatment as compared to untreated CRPC cells. In addition, the cell cycle arrest was associated with decreased levels of both cyclins and cyclin-dependent kinases. However, cdk-4 appears to be more significantly downregulated when compared with either cyclins (D1, D2, D3 and Cyclin E) or other Cdk's (cdk2/6). Also, we noted an increased hypophosphorylated level of retinoblastoma (Rb) with a decreased in Rb phosphorylation resulted in inhibition of E2F1 function. Further, transient over expression of Cdk4 overcomes the Pso-induced G0-G1 arrest in CRPC cells. Also, knockdown of p21cip1 and p27kip1 expression with small interfering RNA significantly abrogated the Pso-induced G0-G1 cell cycle arrest suggested that induction of p21cip1 and p27kip1 is required for G0-G1 cell cycle arrest by Pso. Altogether our results strongly suggest that Pso could be a potential candidate for prevention and therapy against CRPC. Our ongoing studies using xenograft models of CRPC in nude mice may reveal the in vivo efficacy of Pso.
Citation Format: Thippeswamy Gulappa, Rama S. Reddy, Suman Suman, Chendil Damodaran. The molecular kinetics of p21 and Cdk4 dictates irreversible G0/G1 phase cell cycle arrest in CRPC cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 559. doi:10.1158/1538-7445.AM2013-559
Abstract 5592: FGFR4-mediated anti-apoptotic signaling classifies subtypes of alveolar rhabdomyosarcoma cells.
Authors: Wachtel Marco , Rakic Jelena , Okoniewski Michal , Bode Peter , Schäfer Beat 
Published: August 2014

Abstract
Both conventional and targeted treatments of cancer are effective only in subsets of patients. A major obstacle for any treatment directed against a certain tumor type is the biological heterogeneity of tumors. Therefore, characterization of treatment-relevant tumor heterogeneity is necessary to develop more specific, tumor-tailored treatments in the future. Here, we evaluated heterogeneity among alveolar rhabdomyosarcoma (aRMS) by assessing differences in anti-apoptotic signaling mediated by FGFR4, a receptor commonly activated in this tumor type. We found that FGFR4 signaling rescues subgroups of aRMS cell lines from apoptosis induced by compounds targeting the IGF1R-PI3K-mTor pathway or by different chemotherapeutics. As a result of differences of involved apoptotic signaling mechanisms composition of the subgroups is compound-dependent. IGF1R-PI3K-mTor targeted treatment induced apoptosis via Bim/Bad in the rescue and via Bmf in the non-rescue group of cells. Gene expression analysis detected signatures specific for these two cell types also in biopsy samples. Expression levels of AP2β discriminate the two cell types and reveal that both cell types are present in different ratios in most aRMS tumors. Behaviour of Rh30 cells suggests that the two cell types reflect different activation states of PAX/FKHR, the fusion transcription factors present in most aRMS and that environmental stimuli can induce a phenotype switch. Combination of targeted or untargeted drugs with FGFR inhibitors therefore represents an opportunity to improve therapeutic efficacy against aRMS cells with active anti-apoptotic FGFR4 signaling.
Citation Format: Marco Wachtel, Jelena Rakic, Michal Okoniewski, Peter Bode, Beat Schäfer. FGFR4-mediated anti-apoptotic signaling classifies subtypes of alveolar rhabdomyosarcoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5592. doi:10.1158/1538-7445.AM2013-5592
Abstract 5605: Pharmacologic inhibition of EphA2 in NRAS and BRAF mutant melanomas.
Authors: Miao Benchun , Zhang Jianming , Ji Zhenyu , Njauw Ching Ni , Taylor Michael , Kumar Raj , Gray Nathanael , Tsao Hensin 
Published: August 2014

Abstract
The Eph receptors are the largest known family of receptor tyrosine kinases (RTKs). Research studies have shown that Eph receptors and ligands may be involved in many diseases including cancer. EphA2 is a member of the Eph family of receptor tyrosine kinases and is highly expressed in many aggressive cancer types, including melanoma. Our previous studies showed that EphA2 levels are elevated in melanoma cells and EphA2 plays critical roles in melanoma cell survival, proliferation, colony formation and migration in vitro and melanoma tumor growth in vivo. Together, these data suggest that EphA2 is a critical oncogene in melanoma and a potential pharmacologic target in the treatment of metastatic disease. Herein we present early evidence that EphA2 inhibitors (ALW-II-41-27 and HG-6-64-1) are effective in inhibiting proliferation of both NRAS and BRAF mutant melanoma cell lines in vitro through suppressing a series of EphA2 downstream signaling pathways. At the same time, EphA2 inhibitors are also effective at suppressing migration and invasion of melanoma cells with a reduction in actin cytoskeleton reorganization and lamellipodia formation. Animal studies are underway to determine the effectiveness of these agents in suppressing melanoma tumor growth in vivo. These results point to EphA2 inhibition as a promising therapeutic strategy for both NRAS and BRAF mutant melanomas either singly or in combination with BRAF or MEK inhibitors currently in trial.
Citation Format: Benchun Miao, Jianming Zhang, Zhenyu Ji, Ching Ni Njauw, Michael Taylor, Raj Kumar, Nathanael Gray, Hensin Tsao. Pharmacologic inhibition of EphA2 in NRAS and BRAF mutant melanomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5605. doi:10.1158/1538-7445.AM2013-5605
Abstract 5606: Gallium maltolate inhibits brain tumor volume and blood volume in xenograft model.
Authors: Pechman Kimberly R. , Lozen Andrew , Al-Gizawiy Mona , Schmainda Kathleen , Chitambar Christopher R. 
Published: August 2014

Abstract
Purpose: There are limited treatment options for glioblastomas (GBM). Tumor cells have a high requirement for iron; the latter is taken up by cells through transferrin receptor-mediated endocytosis of transferrin-iron. These receptors are highly expressed on GBM cells, which makes them an attractive target for transferrin receptor-directed therapies. Gallium is a group IIIa metal that can function as an iron mimetic by avidly binding to transferrin and incorporating into cells through the transferrin receptor. No studies have been performed to determine the efficacy of gallium-based therapies in brain tumors. Consequently, the goal of this study was to evaluate gallium maltolate in the treatment of a U87 xenograft brain tumor model. Methods: Athymc rats bearing U87 human grade IV astrocytoma cells were studied. Gallium maltolate (50 mg/kg/day, n=5) or saline (n=3) was given intravenously. via an alzet mini pump in the jugular vein. Magnetic resonance imaging (MRI) was performed on days 8 and 18 on a Bruker 9.4 T scanner. Enhancing tumor volumes were determined from the post-contrast T1w images, in all slices showing enhancing tumor. The spin and gradient echo relaxation rate changes were then determined giving estimates of microvascular and total blood volume. ((CBVmicro≈R2=R2MION-R*pre-MION CBVTotal≈ R2* = R2*MION-R2*pre-MION). Results: Gallium maltolate inhibited tumor growth (377132%), as measured by enhancing tumor volume, compared to saline controls (863481%). Treatment shows decrease of CBV micro and CBVTotal compared to the controls. The ratio of R2* /R2, which is a measure of mean vessel diameter, increased in saline treated controls but remained unchanged for the gallium maltolate treated rats. To our knowledge this is the first study performed that uses physiologic MRI measurements to investigate the effects of gallium maltolate on brain tumor xenografts. The differences shown are not statistically significant a result likely due to the small sample sizes, which is being remedied by ongoing additional studies. For the imaging studies included here tissue markers of proliferation (Ki67), hypoxia (HIF1) transferrin receptors, and vascular density (vWF) are being analyzed to provide additional information regarding mechanism of action. In general these results demonstrate, for the first time, that the novel gallium maltolate treatment holds promise for the treatment of malignant brain tumors.
Citation Format: Kimberly R. Pechman, Andrew Lozen, Mona Al-Gizawiy, Kathleen Schmainda, Christopher R. Chitambar. Gallium maltolate inhibits brain tumor volume and blood volume in xenograft model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5606. doi:10.1158/1538-7445.AM2013-5606
Abstract 5608: Iron depletion by deferasirox have a synergistic effect on sorafenib in hepatocellular carcinoma.
Authors: Urano Shinichi , Ohara Toshiaki , Watanabe Shinichiro , Noma Kazuhiro , Tomono Yasuko , Tazawa Hiroshi , Kataoka Masafumi , Kazuhiro Nouso , Shirakawa Yasuhiro , Fujiwara Toshiyoshi 
Published: August 2014

Abstract
Purpose. Sorafenib is a multiple kinase inhibitor approved for advanced hepatocellular carcinoma(HCC). However, we couldn't get sufficient effect in clinical use compared to other cancers. Iron metabolism and relationship with cancer cells have been studied for a long time. Iron overload is known to associate with an increased risk of HCC, and the recent study suggests that iron depletion can induce anti-cancer effect against HCC. We hypothesized that iron depletion enhance the effect of sorafenib and investigated it.
Experimental Design. HepG2 (Human hepatocellular liver carcinoma cell line) was used in this study. We used sorafenib and an oral iron chilator, deferasirox (EXJADE TM). The effects of each agent and combination of both were examined by using cell viability assay. We examined anti-proliferative mechanism in vitro using Flow Cytometry and Western blot analysis.
Results. We examined the cell viability of HepG2. Each treatment by sorafenib and deferasirox suppressed the cancer cell proliferation on dose dependent manner. The IC50 values of 48hours of sorafenib was 1.45μM/L,and that of deferasirox was 1.37μM/L. We examined the possibility of combination therapy. The each cell viability of sorafenib 1μM and deferasirox 10μM was 59.4% and 28.1%, the combination one was 21.8%. The combination index was 0.616 in that status, which suggested synergistic effect. To evaluate anti-proliferation mechanism, we performed Flow Cytometry and Western blot analysis. In Flow Cytometry, S and G2/M phase was significantly decreased, which suggested to arrest cell cycle. In Western blot analysis, cyclin D1 was down-regulated.
Conclusion. Iron depletion by deferasirox have anticancer effect by alone and a synergistic effect in combination with Sorafenib. This result suggested that iron depletion therapy can be a novel combination chemotherapy for HCC.
Citation Format: Shinichi Urano, Toshiaki Ohara, Shinichiro Watanabe, Kazuhiro Noma, Yasuko Tomono, Hiroshi Tazawa, Masafumi Kataoka, Nouso Kazuhiro, Yasuhiro Shirakawa, Toshiyoshi Fujiwara. Iron depletion by deferasirox have a synergistic effect on sorafenib in hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5608. doi:10.1158/1538-7445.AM2013-5608