bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A18: Association of anthropometric factors with risk of colorectal neoplasia in the Black Women's Health Study
Authors: Dash Chiranjeev , Rosenberg Lynn , Yu Jeffrey , Nomura Sarah , Palmer Julie , Adams-Campbell Lucile L. 
Published: December 2017

Abstract
Evidence for the association of anthropometric factors with colorectal neoplasms is limited for African Americans. Association of 6 anthropometric measures with the risk of both colorectal adenomas and colorectal cancer (CRC) in the ongoing Black Women's Health Study cohort was examined. Using a nested case-control design for the adenoma analyses, 954 cases of colorectal adenoma were compared with 3,816 controls without a colorectal polyp, matched on age and follow-up time. For the CRC analyses, 413 incident CRC cases were identified over a 16-year follow up (802,783 person-years). Cases of adenoma and CRC were verified by medical record review. We used multivariable logistic regression analyses (for adenoma) and Cox proportional hazards analyses (for CRC) that included anthropometric exposures and selected confounders. Among postmenopausal women, risk of adenoma increased by 10% (95% CI: 1.00, 1.22), 11% (95% CI: 1.01, 1.29), and 9% (1.00, 1.19) with 1 standard deviation increase in body mass index, waist circumference, and weight change since age 18 , respectively. Anthropometric factors were not associated with adenoma risk among premenopausal women. None of the anthropometric factors were associated with CRC risk among either pre- or postmenopausal women. Future research should attempt to replicate the modest association of obesity with colon adenoma risk but not CRC risk among postmenopausal African American women.
Citation Format: Chiranjeev Dash, Lynn Rosenberg, Jeffrey Yu, Sarah Nomura, Julie Palmer, Lucile L. Adams-Campbell. Association of anthropometric factors with risk of colorectal neoplasia in the Black Women's Health Study [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A18.
Abstract B01: Association of cholangiocarcinoma and hepatocellular carcinoma: Which one should be treated?
Authors: Mazouzi Khaoula 
Published: December 2017

Abstract
Introduction: The combination of cholangiocarcinoma and hepatocellular carcinoma is a rare entity.
Methods: We will present a clinical case involving a combination of cholangiocarcinoma and hepatocellular carcinoma in a patient with post-viral C cirrhosis.
Results: A 60 Y.O male know with a personal history of hepatitis treated in 1969 by an unknown injectable treatment for two years, was presented at the consultation for evolving abdominal bloating.
CT-scan revealed ascites with a total portal vein thrombosis and a heterogeneous tumor occupying the right liver without “wash-out” sign. The patient was put under anticoagulation with LMWH. After a week, liver MRI found that the ascites has totally dried, the thrombosis disappeared, and revealed that the tumor had a typical aspect of cholangiocarcinoma. Alfa-fetal protein test was to 1156 IU / ml. Liver biopsy was contradictory; on some pieces hepatocellular carcinoma was found and on others cholangiocarcinoma. Because Sorafenib is a multikinase inhibitor with anti-angiogenic and anti-proliferative action it can be effective on many tumors as they use the same ligands and signaling pathways similar to proliferate, it was chosen instead of chemotherapy at 400 mg/day. Sure enough, after two weeks of treatment, alfa fetoprotein decreased to 834 IU/ml and after two months biology and imaging found a satisfactory partial response. Currently, after six months of treatment, the patient is in complete clinical, biological and radiological remission except that the treatment cannot be interrupted for the time. Surgeons are discussing a partial surgery to the residual liver retraction.
Conclusion: This association is rare and needs deep research especially molecular testing for patients who have a spectacular response.
Citation Format: Khaoula Mazouzi. Association of cholangiocarcinoma and hepatocellular carcinoma: Which one should be treated? [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B01.
Abstract B03: The EWS/FLI oncogene exerts pro-migratory and anti-apoptotic effects via dysregulation of focal adhesion kinase (FAK) signaling in Ewing sarcoma
Authors: Steinestel Konrad , Trautmann Marcel , Rehkaemper Jan , Wardelmann Eva , Dirksen Uta , Hartmann Wolfgang 
Published: December 2017

Abstract
Ewing sarcoma (ES), an aggressive bone tumor of childhood and adolescence, is one of the most genetically normal tumors. The oncogenic potential is derived from chimeric fusions of EWS and ETS family transcription factors, with EWS-FLI1 rearrangements in 85% of cases. (Micro-) metastatic dissemination is the major threat for patients, and earlier studies have shown that cytoskeletal rearrangements upon EWS/FLI oncoprotein expression contribute to a migratory phenotype in ES cells.
Using a patient-derived ES cell line with a stable EWS/FLI knockdown (A673-iEF), we show here that key tumorigenic effects of EWS/FLI are mediated via autophosphorylation of FAK on tyrosine 397, resulting in enhanced formation of focal adhesions and actin stress fibers as well as tumor cell migration, but impaired caspase-3-mediated anoikis (detachment-induced cell death) in vitro. This effect was not limited to A673 cells, but could also be observed in TC-32 and CADO-ES1 ES cells. Application of the FAK inhibitor 1, 2, 4, 5-Benzenetetraamine tetrahydrochloride (Y15) impaired cell migration and enhanced caspase-mediated apoptosis. Taken together, our results show that key oncogenic effects of EWS rearrangements are mediated via FAK autophosphorylation in ES and provide a rationale for the use of FAK inhibitors to impair metastatic dissemination of ES.
Citation Format: Konrad Steinestel, Marcel Trautmann, Jan Rehkaemper, Eva Wardelmann, Uta Dirksen, Wolfgang Hartmann. The EWS/FLI oncogene exerts pro-migratory and anti-apoptotic effects via dysregulation of focal adhesion kinase (FAK) signaling in Ewing sarcoma [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B03.
Abstract B12: Investigating the specificity of the small molecule inhibitor INI-43 for Kpnβ1 in cancer cells
Authors: Carden Sarah , Watt Pauline van der , Lavia Patrizia , Leaner Virna 
Published: December 2017

Abstract
Karyopherin β1 (Kpnβ1) is the major nuclear import protein involved in the shuttling of cargo proteins and mRNAs into the cell nucleus. Recent studies have found that Kpnβ1 levels are significantly upregulated in cancer cells, and that targeted inhibition of Kpnβ1 with siRNA results in reduced proliferation and the induction of apoptosis, suggesting that Kpnβ1 is important for cancer cell survival. Inhibitor of Nuclear Import-43 (INI-43) is a small molecule inhibitor identified in our laboratory as having the potential to interfere with the nuclear import function of Kpnβ1. It has been shown to inhibit the nuclear localization of both Kpnβ1 and known Kpnβ1 cargoes such as NFκB and NFAT, as well as inhibit the proliferation of cancer cells of different tissue origins. This study aimed to investigate the specificity of INI-43 for Kpnβ1 by performing experiments to determine whether expression of exogenous Kpnβ1-GFP was able to rescue cells from the effects of INI-43 treatment. Results show that Kpnβ1 overexpression rescues cell viability, as well as the inhibitory effects that INI-43 has on the nuclear import of NFκB/p65 and NFAT. Overexpression of Kpnβ1 also rescues cells from an INI-43 induced G2/M cell cycle block. In addition, treatment of cells with INI-43 enhances degradation of Kpnβ1, but not of other members of the Karyopherin family. These results suggest that the small molecule inhibitor INI-43 is acting, at least in part, by targeting Kpnβ1.
Citation Format: Sarah Carden, Pauline van der Watt, Patrizia Lavia, Virna Leaner. Investigating the specificity of the small molecule inhibitor INI-43 for Kpnβ1 in cancer cells [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B12.
Abstract B13: A growth of human choriocarcinoma cells was selectively inhibited by therapeutic neural stem cells expressing cytosine deaminase and interferon-β in cellular and xenograft models
Authors: Kim Gyu-Sik , Choi Kyung-Chul 
Published: December 2017

Abstract
In this study, human neural stem cells (hNSCs) expressing Escherichia coli cytosine deaminase (CD) and human interferon-β (IFN-β) was used to cancer treatment strategy for human choriocarcinoma cancer. Prodrug 5-fluorocytosine (5-FC) is converted to 5-fluorouacil (5-FU) by CD, which induces an effect of killing the tumor cells through DNA synthesis inhibition. Also, IFN-β suppresses tumor growth through the apoptotic process. To manufacture animal models xenografted with choriocarcinoma, CMFDA pre-labeled JEG-3 cells (2×106) were injected intravenously (i.v.) into the tail vein of athymic nude mice (group A) and injected subcutaneously (s.c.) into the back of the mice (group B). Subcutaneously injected cancer cells were mixed with Matrigel (BD Biosciences, Bedford, MA, USA) at 1:1 volume ratio of Matrigel to PBS in 100 μl. On group A, CM-dil pre-labeled hNSCs (2×106) were injected intravenously after a week. On group B, when the tumor volume reached at 100mm3, CM-Dil pre-labeled hNSCs (2×106) were injected subcutaneously adjacent to the tumor mass. Every mice received i.p. injections of 5-FC (500 mg/kg/day) every day for 21 days. In a modified trans-well migration assay, NSCs selectively migrated to JEG-3 choriocarcinoma cells. It was revealed that the tumor-tropic properties of engineered NSCs were attributed to chemoattractant factors (CXCR4, SCF, SDF-1a, VEGF) secreted by JEG-3 cells. When JEG-3 cells co-cultured with engineered NSCs in the presence of 5-FC, the viability of JEG-3 cells was markedly decreased. The present results suggested that NSCs expressing CD gene and IFN-β gene have a potential therapeutic effect against choriocarcinoma. Consequently, hNSC therapy may be a clinically effective tool for the treatment of human choriocarcinoma cancer. In addition, we are currently studying on an in vivo model to demonstrate that selective anti-tumor effect of NSCs.
Note: This abstract was not presented at the conference.
Citation Format: Gyu-Sik Kim, Kyung-Chul Choi. A growth of human choriocarcinoma cells was selectively inhibited by therapeutic neural stem cells expressing cytosine deaminase and interferon-β in cellular and xenograft models [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B13.
Abstract B14: Injection of therapeutic stem cells expressing cytosine deaminase and interferon-beta resulted in the inhibition of K562 human chronic myeloid leukemia cells in a xenograft model
Authors: Park Geon-Tae , Choi Kyung-Chul 
Published: December 2017

Abstract
Gene-directed enzyme/prodrug therapies have been found to be more advantageous compared to conventional cancer treatment method. One of these, a cytosine deaminase (CD)/5-fluorocytosine (5-FC) system, is known to induce apoptosis of cancer cells by converting 5-FC, a prodrug, to its metabolically active form, 5-fluorouracil. In this study, human neural stem cells (hNSCs) derived enzyme/prodrug therapy was used to treat leukemia. The parental hNSCs, HB1.F3, were engineered to express E. coli CD and/or human interferon-β. To manufacture animal models xenografted with leukemia, K-562 cells (1×106) were mixed with Matrigel (BD Biosciences, Bedford, MA, USA) at 1:1 volume ratio of Matrigel to PBS in 100 μl and injected subcutaneously (s.c.) into the back of athymic nude mice. This animal study was performed for 24 days after hNSCs injections. When tumor volume reached 500 mm3, CM-Dil pre-labeled hNSCs (4 x 106 cells per mouse) were injected subcutaneously adjacent to the tumor mass. Another group, CM-dil pre-labeled hNSCs (4 x 106 cells per mouse) was injected intravenously. hNSCs were injected on the first day of each week. Two days after the injection of hNSCs, all mice received i.p. injections of 5-FC (500 mg/kg/day in 100 μl PBS) every day for 24 days. At 24 h after the last 5-FC treatment, the mice were euthanized and tumor masses were harvested for molecular analysis. In a xenografted mouse model administered with hNSCs intravenously or subcutaneously, hNSC significantly inhibits the growth of tumor mass and extends survival date in the presence of a prodrug. In addition, HB1.F3.CD.IFN-β treatment group showed more antitumor effect compared with HB1.F3.CD treatment group, indicating that IFN- β may have a synergistic effect for directly killing leukemia tumors. The present results represent that engineered hNSCs and prodrug treatment inhibited the proliferation of leukemia. These results suggest that gene therapy employing genetically engineered stem cells expressing CD and IFN-β may be effective for treating leukemia.
Note: This abstract was not presented at the conference.
Citation Format: Geon-Tae Park, Kyung-Chul Choi. Injection of therapeutic stem cells expressing cytosine deaminase and interferon-beta resulted in the inhibition of K562 human chronic myeloid leukemia cells in a xenograft model [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B14.
Abstract B16: Two kills with one shot: A biomarker with therapeutic implications in poor prognosis gastric cancers
Authors: Sato Ko 
Published: December 2017

Abstract
Bioinformatic approaches are useful to predict significance of gene expression in clinical outcome. Utilizing these non-biased approaches, we now identify that upregulation of aldosterone-regulated sodium reabsorption (ARSR) is seen in a subset of gastric cancers with poor prognosis. Our analysis of a clinical cohort of gastric cancers shows a subunit component of ARSR, SCNNIG, is indeed often overexpressed and is linked to poor survival. To understand this mechanism of the poor survival, overexpression of SCNNIG causes rapid growth of tumors in a xenograft model. Inhibition of aldosterone by spironolactone, a traditional diuretic, specifically kills cancer cells with overexpression of SCNNIG in vitro and in vivo, suggesting a clinical and therapeutic benefit for evaluating patients for this biomarker.
Citation Format: Ko Sato. Two kills with one shot: A biomarker with therapeutic implications in poor prognosis gastric cancers [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B16.
Abstract B17: Targeting the oncogenic TBX3 and its co-factors in anti-cancer drug development
Authors: Willmer Tarryn , Smyly Shannon , Smuts Danica , Prince Sharon 
Published: December 2017

Abstract
Sarcomas are heterogeneous neoplasms of mesenchymal origin whose clinical management is compromised due to inadequate diagnostic markers and limited therapeutic options. While the incidence rates for sarcomas in Africa remain uncertain, there is a widely held view that they are common in black African children and adolescents. Indeed, according to a Nigerian study, soft tissue sarcomas make up as much as 11.3% of all childhood cancers. We recently reported that the transcription factor, TBX3, is overexpressed in a diverse range of sarcoma subtypes where it plays a direct oncogenic role and it has been proposed as a novel target for their treatments. Direct targeting of transcription factors for therapies however continues to represent a serious challenge and therefore the molecular mechanisms that mediate its biological activity may be more amenable as anti-cancer drug targets. To address this, affinity purifications coupled with mass spectrometry was performed to identify TBX3 protein co-factors that regulate its oncogenic activity in sarcomas. Here we describe the validation of nucleolin as TBX3 co-factor by co-immunoprecipitation assays and confocal microscopy/co-localization analysis. The effect of nucleolin on TBX3 function was determined using RNAi rescue experiments coupled with growth curve and scratch motility assays to assess cell proliferation and migration respectively. Finally, the effect of the nucleolin targeting aptamer, AS1411, on the cell viability of a range of sarcoma subtypes was tested. Results show that the overexpression of TBX3 and nucleolin are common in a number of sarcoma subtypes. We provide compelling evidence that nucleolin interacts with and co-operates with TBX3 to promote proliferation and migration of chondrosarcoma, liposarcoma and rhabdomyosarcoma cells. Furthermore, AS1411 exhibits potent anti-cancer activity in these sarcomas whilst it has no effect on normal cells. In conclusion, we propose that TBX3 and nucleolin can be used in combination as biomarkers for the diagnosis and targeted therapy of a diverse range of sarcomas which are highly aggressive and treatment resistant cancers.
Citation Format: Tarryn Willmer, Shannon Smyly, Danica Smuts, Sharon Prince. Targeting the oncogenic TBX3 and its co-factors in anti-cancer drug development [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B17.
Abstract B21: Potassium dichromate and sodium arsenite toxicities: Modification by methanol extract of Rauvolfia vomitoria in albino mice
Authors: Akinwumi Kazeem Akinyinka , Osifeso Olabode Olatunbosun , Aboyewa Olajumoke Jumoke , Odunola Oyeronke Aduni 
Published: December 2017

Abstract
Exposure to arsenic and hexavalent chromium is a major public health concern especially in the developing part of the world and there is still no reliable treatment. This study evaluates the effect of combined exposure to potassium heptaoxochromate VI (K2Cr2O7) and sodium arsenite (NaAsO2) in mice as well as the effect of methanol leaf extracts of Rauvolfia vomitoria (MRV) on the toxicity of both toxicants. Test mice were pre-treated with 275mg/kg body weight MRV before being challenged with either NaAsO2 and/ or K2Cr2O7 on the seventh day. The control animals were exposed to distilled water or a single dose of 2.5 mg/kg body weight NaAsO2 or 12mg/kg of K2Cr2O7 a day before the animals were sacrificed. The frequency of micronucleated polychromatic erythrocytes (mPCEs) was monitored in bone marrow cells, while aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were assessed in the plasma. Hepatic glutathione (GSH) and malondialdehyde (MDA) levels as well as catalase (CAT) and glutathione-S-transferase (GST) activities were also monitored. The NaAsO2 and K2Cr2O7 significantly (P&lt;0.05) increased the frequency of mPCE formation, AST, ALT, CAT and GST activities when compared with the control. Simultaneous exposure to NaAsO2 and K2Cr2O7 further increased (p&lt;0.05) the levels of the markers. In addition, GSH and GST were significantly (p&lt;0.05) reduced in mice exposed to NaAsO2 or K2Cr2O7 or their combination. However, MRV reversed the markers towards that of the control. Our study therefore suggests that MRV ameliorates NaAsO2 and K2Cr2O7 induced toxicities via reduction of oxidative stress and fortification of anti-oxidant system
Note: This abstract was not presented at the conference.
Citation Format: Kazeem Akinyinka Akinwumi, Olabode Olatunbosun Osifeso, Olajumoke Jumoke Aboyewa, Oyeronke Aduni Odunola. Potassium dichromate and sodium arsenite toxicities: Modification by methanol extract of Rauvolfia vomitoria in albino mice [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B21.
Abstract B23: The anticancer properties of South African herbal teas utilizing an in vitro pre-exposure anti-inflammatory UVB/keratinocyte model
Authors: Keet Lana , Riedel Sylvia , Swart Amanda C. , Joubert E , Gelderblom WCA 
Published: December 2017

Abstract
The incidence of skin cancer, resulting from exposure to UVB irradiation, has become a global concern as it continues to rise rapidly with the non-melanoma skin cancers, comprised of basal cell carcinoma and squamous cell carcinoma, being the most frequently diagnosed in Caucasian populations. Chronic inflammation is suggested to contribute to cancer development and therefore poses a potential target for chemoprevention. In the skin, keratinocytes and macrophages play an integral part in acute and chronic inflammation, with interleukin 1-α (IL-1α) and tumor necrosis factor α (TNF-α) as key cytokines governing this process. Green tea (Camellia sinensis) and the South African herbal teas, rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) displayed anti-inflammatory effects in mouse and human skin. To further investigate the anti-inflammatory properties of green tea and the herbal teas, rooibos and honeybush (C. subternata and C. maculata) herbal teas, a pre-exposure UVB-irradiated/keratinocytes cell culture model was developed and validated utilizing human keratinocytes (HaCaT) utilizing the intracellular accumulation of IL-1α as endpoint. Aqueous extracts of the green tea and unfermented herbal teas were prepared, their polyphenolic composition determined by high performance liquid chromatography (HPLC) and their antioxidant activity characterized utilizing different antioxidant assays. Green tea and rooibos exhibited similar antioxidant activities while C. maculata displayed the lowest overall antioxidant activity mainly due to a high mangiferin level, the major polyphenol in honeybush. UVB-induced IL-1α was decreased by pre-exposing the keratinocytes to the green tea extract for 16 hrs prior to UVB-irradiation while a far weaker response was obtained with the rooibos extract. Both the honeybush extracts displayed a significant anti-inflammatory effect in the reduction of IL-1α with C. subternata exhibiting a slightly increased protection at a lower extract concentration. Flavonoid diversity of the teas is likely to explain the differential effects regarding their antioxidant and anti-inflammatory activities. Proposed mechanisms for the anti-inflammatory effects include the modulation of UVB-induced oxidative stress via various pathways and the subsequent down regulation of nuclear factor kappa β (NFκB) and activated protein-1 (AP-1) which are key regulators of cytokine production governing the inflammatory response.
Citation Format: Lana Keet, Sylvia Riedel, Amanda C. Swart, E Joubert, WCA Gelderblom. The anticancer properties of South African herbal teas utilizing an in vitro pre-exposure anti-inflammatory UVB/keratinocyte model [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B23.