bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2701: Antitumor effects of peptide Rb4 derived from proteolipid protein 2 (PLP2) in a syngeneic murine melanoma model
Authors: Maia Vera S C , Berzaghi Rodrigo , Arruda Denise C. , Melo Pollyana M S , Travassos Luiz R. 
Published: May 2015

Abstract
Peptides have increasingly being investigated as drug candidates for treatment of pathologies ranging from Alzheimer`s disease to cancer. Literature shows that over expression of proteolipid protein 2 (PLP2) was associated with metastasis of B16F10 melanoma. Authors showed later that knock-down of PLP2 inhibited growth and metastasis of melanoma cells. The present work aimed at studying the antitumor activity of peptide Rb4 derived from protein PLP2. Peptide Rb4, tested as synthetic peptide on B16F10-Nex2 cells showed antitumor effects in vitro and in vivo. Rb4 induces a remarkable F-actin depolymerization, and also antagonizes thapsigargin blockade of calcium channels on the endoplasmic reticulum (ER). Such effects on actin dynamics and calcium flow cause apoptosis in murine melanoma B16F10-Nex2, and reduce the viability of several human cancer cell lines. Chromatin condensation, DNA fragmentation, caspase 9 and caspase 3 activation are compatible with tumor cell apoptosis. Early effects of the peptide were cell rounding and aggregation, followed by substrate detachment. In vivo, peptide Rb4 reduced metastatic activity of B16F10-Nex2 cells and delayed the subcutaneous growth of murine melanoma in the syngeneic model. The protective effect of Rb4 observed in the metastatic melanoma model was not, however, observed in immunodeficient mice. Peptide Rb4 induces the expression of two DAMPs (damage-associated molecular patterns), HMGB1 and calreticulin in B16F10-Nex2. Apart from a direct adjuvant effect of Rb4 on dendritic cells (DCs), the expression of DAMPs by tumor cells may also contribute to DCs activation thus explaining the protective effect of the peptide in vivo against B16F10-Nex2 melanoma. In conclusion, we suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug. Supported by FAPESP grant 2010/51423-0 and the Brazilian National Research Council (CNPq).
Citation Format: Vera S C Maia, Rodrigo Berzaghi, Denise C. Arruda, Pollyana M S Melo, Luiz R. Travassos. Antitumor effects of peptide Rb4 derived from proteolipid protein 2 (PLP2) in a syngeneic murine melanoma model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2701. doi:10.1158/1538-7445.AM2014-2701
Abstract 2703: Effect of route and dosing regimen on efficacy of SH7139 in mouse Burkitt's lymphoma xenografts
Authors: Balhorn Rodney , Mirick Gary , DeNardo Gerald L. , Beckett Laurel , Li Judy , Hok Saphon , Balhorn Monique 
Published: May 2015

Abstract
SH7139, our most advanced small molecule therapeutic for non-Hodgkin's lymphoma, was designed to bind to a unique site on HLA-DR10, a cell surface receptor found on B-cell lymphocytes and over-expressed on B-cell derived malignancies. Studies conducted with lymphoma and other cell lines have shown that SH7139 binds selectively and is highly cytotoxic only to tumor cells expressing HLA-DR10. A previous study also showed SH7139 to be highly effective in treating human Burkitt's lymphoma (Raji) in a mouse xenograft model. We have used this same mouse model to compare the efficacy of SH7139 delivered by different routes and using different treatment regimens. The results show that the greatest survival times were achieved with mice given SH7139 by i.p. injection on days 0, 7 and 14. Doses delivered i.p. on days 0, 2 and 4 and orally on days 0,7,14,21,28 and 35 were slightly less effective, and a single dose delivered i.p. on day 0 and three doses delivered orally on days 0, 7, and 14 were the least effective. The concentration of SH7139 that achieved these effects in vivo, which was determined by measuring xenograft uptake of 111-In-labeled SH7139, was found to be in the sub-nanomolar range. In addition to identifying the best route and dosing regimen for future studies and confirming the drug works in vivo at concentrations similar to those found to be effective in cells cultured in vitro, these studies also show the drug can be effective when administered orally.
Citation Format: Rodney Balhorn, Gary Mirick, Gerald L. DeNardo, Laurel Beckett, Judy Li, Saphon Hok, Monique Balhorn. Effect of route and dosing regimen on efficacy of SH7139 in mouse Burkitt's lymphoma xenografts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2703. doi:10.1158/1538-7445.AM2014-2703
Abstract 2707: In vitro and in vivo evaluation of SNG1153, a synthetic modulator of ER-α36
Authors: Zhang Bo , Meng Kun , Shang Xiao , Wang Zhaoyi , Zhang Yanzhong , Fang Fang , Wang Jing , Wang Zonghui , Wang Jun , Guo Yuming , Liu Shiyang , Chen Feng , Ding Hongxia , Zhang Jiancun , Bao Jun 
Published: May 2015

Abstract
Background: ER-α36, a novel truncated variant of estrogen receptor α, was recently discovered and extensively studied as a potential therapeutic target. ER-α36 was found to be overexpressed in many cancers including estrogen-positive and negative breast cancer, lung cancer, prostate cancer, endometrial cancer, liver cancer and other cancers. This suggests that ER-α36 is potentially a promising target for the development of novel anticancer agents with broader clinical applications. This study aims to evaluate the in vitro and in vivo performance of SNG1153, an orally available, synthetic modulator of ER-α36. Methods: the viabilities of ER-α36 overexpressed cancer cells were evaluated using a CCK-8 assay after exposure to SNG1153. Pharmacokinetic study was conducted in rat and SNG1153 was administered orally in escalated doses. In-vivo efficacies of SNG1153 were evaluated in Bcap-37 xenograft model, Ishikawa xenograft model and SPC-A-1 xenograft model. Results: SNG1153 showed significant inhibition at low micromolar concentrations in ER-α36 overexpressed cell lines including the one resistant to tamoxifen. SNG1153 exhibited a linear PK profile with a bioavailability of more than 55% in the rat PK study. In the in-vivo efficacy studies, 3 doses were investigated and SNG1153 showed dose-dependent inhibition. The tumor growth inhibition at high dose was 57% in the breast cancer Bcap-37 xenograft model, 65% in the endometrial cancer Ishikawa xenograft model and 52% in lung adenocarcinoma SPC-A-1 xenograft model. No signs of toxicity were observed in these models. Conclusion: SNG1153, as a synthetic ER-α36 modulator, showed promising activities in many in vitro and in vivo models. It is currently in preclinical development stage.
Citation Format: Bo Zhang, Kun Meng, Xiao Shang, Zhaoyi Wang, Yanzhong Zhang, Fang Fang, Jing Wang, Zonghui Wang, Jun Wang, Yuming Guo, Shiyang Liu, Feng Chen, Hongxia Ding, Jiancun Zhang, Jun Bao. In vitro and in vivo evaluation of SNG1153, a synthetic modulator of ER-α36. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2707. doi:10.1158/1538-7445.AM2014-2707
Abstract 271: Rising rates of acute lymphocytic leukemia in Hispanic children: A review of trends in childhood leukemia incidence from 1973-2010
Authors: Barrington-Trimis Jessica , Cockburn Myles , Metayer Catherine , Gauderman W. James , Wiemels Joseph , McKean-Cowdin Roberta 
Published: May 2015

Abstract
Background: Childhood leukemia is the most common cancer in children under 20 years of age in the United States, and incidence rates have increased over the last few decades. The incidence rate for all childhood leukemia is higher among Hispanic children [2006-2010 age-adjusted incidence rate (AAIR)= 5.71; 95%CI: 5.47, 5.97] than among non-Hispanic White children (2006-2010 AAIR=3.95; 95%CI: 3.81, 4.09). This analysis aims to describe secular trends from 1992-2010 in the incidence of childhood leukemia, independently for Hispanic and non-Hispanic children.
Methods: Surveillance, Epidemiology and End Results (SEER) data were used to evaluate trends in the incidence of childhood leukemia diagnosed in children less than 20 years of age between 1992-2010 by ethnicity. Trends among Hispanic and non-Hispanic children were examined overall and by age, gender, and histologic subtype. AAIRs, annual percent change (APC) estimates, and 95% confidence intervals (95%CIs) were calculated using SEER*stat v.8.0.4.
Results: Hispanic children were more likely than non-Hispanic children to be diagnosed with leukemia (all subtypes combined), and with acute lymphocytic leukemia when examined by gender and by age (0-4, 5-9, 10-14, 15-19 years at diagnosis). A greater increase in AAIRs was observed for Hispanic children as compared to non-Hispanic children for all types of leukemia from 1992-2010 (APCHispanic=1.16; 95%CI: 0.55, 1.76; APCnon-Hispanic=0.52; 95%CI: 0.01, 1.03). When restricting to acute lymphocytic leukemias (ALL), statistically significant increases were observed for Hispanic children (APC=1.31; 95%CI:0.68, 1.94), but not for non-Hispanic children (APC=0.50; 95%CI: -0.19, 1.19). Among Hispanic children, the strongest increase was found among children diagnosed from 10-19 years of age. Incidence rates were higher for Hispanic males (AAIR=5.26; 95%CI: 4.93, 5.60;) than for Hispanic females (AAIR=4.07; 95%CI: 3.78, 4.39).
Conclusion: Incidence rates of childhood leukemia rose from 1992-2010, with the greatest increase for ALL among older Hispanic children (aged 10-19 years). In future studies aimed at evaluating exposures responsible for increasing incidence rates of childhood ALL, researchers should consider risk factors that may explain the rising rates among Hispanic children.
Citation Format: Jessica Barrington-Trimis, Myles Cockburn, Catherine Metayer, W. James Gauderman, Joseph Wiemels, Roberta McKean-Cowdin. Rising rates of acute lymphocytic leukemia in Hispanic children: A review of trends in childhood leukemia incidence from 1973-2010. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 271. doi:10.1158/1538-7445.AM2014-271
Abstract 2711: CARP-1 functional mimetics are a novel class of small molecule inhibitors of malignant pleural mesothelioma cells
Authors: Jamal Shazia , Cheriyan Vino T. , Muthu Magesh , Munie Sara , Levi Edi , Ashour Abdelkader E. , Pass Harvey I. , Wali Anil , Singh Mandip , Rishi Arun K. 
Published: May 2015

Abstract
Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of pro-apoptotic stress-activated kinases (SAPKs) p38 and JNK, elevated CARP-1 expression, cleavage of PARP1, and loss of the oncogene c-myc as well as mitotic cyclin B1. Treatments of MPM cells with CFM-4 resulted in depletion of NF-κB signaling inhibitor ABIN1 and Inhibitory κB (IκB)α and β, while increasing expression of pro-apoptotic death receptor (DR) 4 protein. CFM-4 enhanced expression of serine-phosphorylated podoplanin and cleavage of vimetin. CFMs also attenuated biological properties of the MPM cells by blocking their abilities to migrate, form colonies in suspension, and invade through the matrix-coated membranes. Both podoplanin and vimentin regulate processes of cell motility and invasion, and their expression often correlates with metastatic disease, and poor prognosis. The fact that phosphorylation of serines in the cytoplasmic domain of podoplanin interferes with processes of cellular motility, CFM-4-dependent elevated phosphorylated podoplanin and cleavage of vimentin underscore a metastasis inhibitory property of these compounds, and suggest that CFMs and/or their future analogs have potential as anti-MPM agents.
Citation Format: Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi. CARP-1 functional mimetics are a novel class of small molecule inhibitors of malignant pleural mesothelioma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2711. doi:10.1158/1538-7445.AM2014-2711
Abstract 2712: ISC-4, a novel inhibitor of hedgehog-Gli signaling, inhibits growth of CSC and CTC of melanoma patients
Authors: Sharma Arun K. , Jani Jitesh , Sharma Cristian , Cleary Patrick , Sharma Michael , Satish Shruthi , Gomez Esteban , Prez Michael , Amezcua Natalee , Navel Mariam , Karelia Deepkamal N. , Desai Dhimant , Amin Shantu , Sharma Jay 
Published: May 2015

Abstract
Melanoma is one of the most aggressive cancers, and its incidence and mortality rate are on rise since no treatment options are available for metastatic disease. Recent evidences from in vitro and in vivo studies have demonstrated that aberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway regulates genes that promote cellular proliferation in various human cancer stem cells (CSC) 36118-45. In melanoma cells, RAS-MEK and AKT signaling has also been shown to regulate the nuclear localization and transcriptional activity of Gli-1. Therefore, the agents that inhibit activation of Gli transcription factors have emerged as promising novel therapeutic drugs for pancreatic cancer. Through extensive structure-activity studies in our laboratory, based on naturally occurring isothiocyanates (ITCs) and their isosteric selenium analogs, we have recently identified phenylbutyl isoselecynate (ISC-4) as a promising agent that significantly retarded melanoma tumor growth without any systemic toxicity. We demonstrate here the effect of ISC-4 on the proliferation of CSC and 36118-45CTC (circulating tumor cell) cells isolated from a melanoma patient. ISC-4 treatments resulted in a dose-dependent inhibition of SHH signaling (SMO, PTCH-1, Gli1, Gli2, and Gli3) and induced significant growth inhibition of CSC and CTC cells. The data demonstrate that Hh signaling regulates proliferation of CSC and CTC of human melanoma and treatment with agents like ISC-4 might be a novel approach to prevent growth and metastasis of human melanoma.
Citation Format: Arun K. Sharma, Jitesh Jani, Cristian Sharma, Patrick Cleary, Michael Sharma, Shruthi Satish, Esteban Gomez, Michael Prez, Natalee Amezcua, Mariam Navel, Deepkamal N. Karelia, Dhimant Desai, Shantu Amin, Jay Sharma. ISC-4, a novel inhibitor of hedgehog-Gli signaling, inhibits growth of CSC and CTC of melanoma patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2712. doi:10.1158/1538-7445.AM2014-2712
Abstract 2716: Discovery of novel TAM family kinase inhibitors
Authors: Zhang Zaihui , Li Rick , Lee Erica , Hu Yuxiang , Yan Jun , Sanghera Jasbinder 
Published: May 2015

Abstract
TAM family (Tyro3, Axl, and Mer) of receptor tyrosine kinases mediated signaling is involved in cell survival, proliferation, migration and adhesion, vascular smooth muscle homeostasis, platelet function and erythropoiesis, and regulation of inflammatory cytokine release. These RTKs are frequently co-expressed in vascular, reproductive, nervous, and immune system in adults. TAM family kinases can be activated by vitamin K-dependent ligands GAS6 and Protein S. Tyro3, Axl, and Mer also display ectopic or overexpression in numerous cancers, including myeloid and lymphoblastic leukemias, melanoma, breast, lung, colon, liver, gastric, kidney, ovarian, uterine, and brain cancers. Therefore, they represent another class of kinase targets for development of cancer therapy. In this study, we report the discovery of a new class of potent and selective inhibitors of TAM family. These new compounds have demonstrated in vitro potency in nM range against these kinases and selectivity against other kinases in a selected panel. Many of these new compounds can dramatically reduce the pAkt levels in several cancer cell lines in a dose dependent manner. In thymidine incorporation assay, some compounds showed inhibition of cell proliferation at sub-micromolar concentrations. Furthermore, some compounds have demonstrated efficacy in colony formation assays. The most promising compounds are now being selected for in vivo proof-of-concept studies. The pharmaceutical properties of these compounds together with ADME profile were also evaluated. Taken together, the data generated so far indicates that these new inhibitors of TAM family kinases represent a new approach for cancer therapy.
Citation Format: Zaihui Zhang, Rick Li, Erica Lee, Yuxiang Hu, Jun Yan, Jasbinder Sanghera. Discovery of novel TAM family kinase inhibitors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2716. doi:10.1158/1538-7445.AM2014-2716
Abstract 2718: Targeting ribosome biogenesis with CX5461 as a potential treatment for melanoma and ovarian cancer
Authors: Sheppard Karen E. , Brajanovski Natalie , Hannan Katherine M. , Ahearn Jessica , Ellul Jason , Drygin Denis , O'Brien Sean , McArthur Grant , Hannan Ross D. , Pearson Richard B. 
Published: May 2015

Abstract
Ribosome biogenesis provides the molecular machinery required for protein synthesis, thus it dictates the ability of a cell to grow and proliferate. We have recently demonstrated that inhibiting ribosome biogenesis with a small molecule that inhibits RNA Polymerase (POL) I driven transcription (CX5461) selectively killed B-lymphoma cells in vivo while maintaining a viable wild-type B cell population (Bywater et al., Cancer Cell 22: p51, 2012). The therapeutic effect was mediated via nucleolar disruption and activation of p53-dependent apoptotic signalling. Although this response was dependent on p53, cell lines from solid tumors with mutant p53 also respond to CX5461 (Drygin et al., Cancer Res 71: p1418, 2011).
Dysregulation of both the PI3K and RAS/ERK pathways are common in ovarian cancer and BRAF is mutated and activated in over 50% of melanomas; a cancer that also commonly expresses wild type-p53. Given that both these pathways are critical regulators of ribosome biogenesis, we hypothesized that targeting ribosome biogenesis may be a new and potent approach to treating these cancers.
To determine the efficacy of CX5461 a panel of ovarian cancer and melanoma cell lines were treated with CX5461 and cell proliferation assessed. The majority of cell lines were sensitive to CX5461 and differential gene expression between resistant and sensitive ovarian cancer cell lines revealed sensitivity was associated with signatures of increased MYC signalling and BRCA1 and 2 mutation. Gene expression and assessment of rDNA transcription suggested that resistance in both ovarian cancer and melanoma cell lines was associated with an inability of CX5461 to inhibit POL1 driven transcription. These studies indicate that targeting ribosome biogenesis and function may provide a new therapeutic option for treating ovarian cancer and melanoma.
Citation Format: Karen E. Sheppard, Natalie Brajanovski, Katherine M. Hannan, Jessica Ahearn, Jason Ellul, Denis Drygin, Sean O'Brien, Grant McArthur, Ross D. Hannan, Richard B. Pearson. Targeting ribosome biogenesis with CX5461 as a potential treatment for melanoma and ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2718. doi:10.1158/1538-7445.AM2014-2718
Abstract 2721: Novel biisoquinoimidazolium-derivatives for breast cancer therapy
Authors: Narayan Satya , Jaiswal Aruna S. , Hong Sukwon 
Published: May 2015

Abstract
Breast cancer is the most frequently diagnosed cancer in women. This cancer is classified according to its expression of hormone/growth factor receptors. It is divided into three groups: (i) Estrogen receptor (ER) and progesterone receptor (PR)-positive; (ii) Human epidermal growth factor receptor 2 (HER2)-positive; and (iii) ER, PR, and HER2-negative (triple-negative). Most chemotherapeutic anti-cancer drugs used in the clinical practice include an anti-estrogenic agent that interferes with ER and prevents tumor progression; however, it is still a big challenge to manage the triple-negative breast tumors. Mitosis and other distinct pathways of apoptosis are considered as a potential target for the development of novel anti-mitotic drugs. In the present investigation, we designed the biisoquinoimidazoliums class of drugs which is structurally similar to anti-mitotic drugs. We synthesized various derivatives of biisoquinoimidazoliums, tested their potency, and suitability as therapeutic agents in preclinical biological system using clonogenic assay. Results showed a strong growth inhibitory effect of these compounds on both triple-positive and triple-negative breast cancer cell lines in the following order: DHO2-93-1 ≥ DHO2-85-3 ≥ DHO2-75-3 ≥ DHO2-85-1. DH02-75-1 also showed some activity, while DHO2-75-2 and DHO2-107-1 did not show any growth inhibitory effect on these cells. From these results, we concluded that DHO2-93-1 may have therapeutic implication as a novel anti-tumor drug for the intervention of both triple-positive and triple-negative breast cancers.
Citation Format: Satya Narayan, Aruna S. Jaiswal, Sukwon Hong. Novel biisoquinoimidazolium-derivatives for breast cancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2721. doi:10.1158/1538-7445.AM2014-2721