bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2614: Macrophage erythroblast attacher (MAEA) polymorphisms are associated with clinical outcome in TRIBE study mCRC patients treated with 5-fluorouracil/bevacizumab-based therapy
Authors: Soni Shivani , Miyamoto Yuji , Zhang Wu , Berger Martin D. , Cao Shu , Melendez Elizabeth , Puccini Alberto , Naseem Madiha , Tokunaga Ryuma , Battaglin Francesca , Mcskane Michelle , Cremolini Chiara , Falcone Alfredo , Loupakis Fotios , Lenz Heinz-Josef 
Published: August 2018

Abstract
Background: Macrophage erythroblast attacher (MAEA) also known as Emp (Erythroblast macrophage protein) plays indispensable role in erythroblast and macrophage development and targeted disruption of Emp is embryonically lethal (Soni et al., JBC 2006). Recently, down-regulation of Emp was implicated in abnormal cell motility and higher expression of mitogen-activated protein kinase 1 (MAPK 1) and thymoma viral proto-oncogene 1 (Akt 1) (Gulnaz et. al., BCMD 2016). Our preliminary studies, shows that higher expression of MAEA is associated with longer colorectal cancer (CRC) patient survival. We tested two MAEA polymorphisms (rs13149952 and rs1128427), whether these are correlated with clinical outcome in mCRC treated with 5-Fluorouracil / Bevacizumab based therapy. Methods: Genomic DNA was isolated from blood samples of two cohorts of mCRC patients. Cohort 1 included 227 patients treated with FOLFIRI/BEV (TRIBE trial Arm A, RAS wildtype/mutant=55/116, median age=60 years old, median follow-up period=49.3 months). Cohort 2 had 229 patients treated with FOLFOXIRI/BEV (TRIBE trial Arm B, RAS wildtype/mutant=60/115, median age=60 years old, median follow-up period=46.6 months). PCR-based direct Sanger sequencing was used to determine polymorphism. Results: Our results showed that MAEA rs1128427 in TRIBE arm A patients with RAS mutant tumors having any C genotype was significantly associated with longer overall survival as compared to TT genotype in univariate analysis {25.9 vs 18.8 months, HR(95% CI)=0.61(0.38,0.98), p=0.036}. In TRIBE arm B cohort, MAEA rs1128427 in patients with RAS mutant tumors carrying CC genotype showed significantly longer overall survival than patients with any T allele in both univariate and multivariable analyses {33.4 vs 25 months, uni: HR(95% CI)=0.57(0.34,0.95), p=0.028; multi: HR(95% CI)=0.56(0.32,0.96), p=0.034}. Conclusion: Our findings suggest for the first time, that polymorphisms in MAEA may predict the clinical outcome in Bevacizumab based therapies. Further prospective studies are warranted.
Citation Format: Shivani Soni, Yuji Miyamoto, Wu Zhang, Martin D. Berger, Shu Cao, Elizabeth Melendez, Alberto Puccini, Madiha Naseem, Ryuma Tokunaga, Francesca Battaglin, Michelle Mcskane, Chiara Cremolini, Alfredo Falcone, Fotios Loupakis, Heinz-Josef Lenz. Macrophage erythroblast attacher (MAEA) polymorphisms are associated with clinical outcome in TRIBE study mCRC patients treated with 5-fluorouracil/bevacizumab-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2614.
Abstract 2618: The thymidine kinase 1 (TK1) protein concentration in sera from Hodgkin lymphoma patients: A marker for cell death and disruption of malignant cells
Authors: Kumar Jagarlamudi Kiran , Eriksson Staffan , Ulfstedt Johan Mattsson , Venge Per , Molin Daniel 
Published: August 2018

Abstract
TK activity measurements have been used for many years to monitor cancer disease activity. However, what the blood concentrations of TK1 protein reflect is still uncertain. A TK1 immunoassay, the AroCell TK 210 ELISA, has been developed based on specific monoclonal antibodies against the C-terminal region of TK1. We utilized this assay to monitor the blood concentrations of TK1 in a cohort of patients with Hodgkin lymphoma (HL) before and after conventional treatment. TK1 concentrations in serum or plasma were measured using the AroCell TK 210 ELISA. For comparison, a large number of other biomarkers and cells were measured in blood such as C-reactive protein (CRP), Lactate dehydrogenase (LDH), hemoglobin, WBC, platelet counts, erythrocyte sedimentation rates (ESR), albumin, liver enzymes, creatinine. Fifty-eight patients with HL were included before start of treatment. Seventy three percent had the nodular sclerosis subtype and 52% stages I-II and 48% stages III-IV disease. Blood was sampled before treatment, during treatment and twice after completion of treatment. The upper normal TK1 concentration of healthy subjects (n=250) was 0.45 μg/L with a median of 0.25 μg/L (range 0.15-0.66 μg/L) as compared to HL, which was 0.26 μg/L (range 0.03-17 μg/L). The differences in ranges were significant (p&lt;0.0001, F-statistics). Nodular sclerosis patients had higher TK1 levels as compared to the other subtypes (p=0.03). TK1 increased after treatment (p=0.001) in patients with normal concentrations from start i.e. &lt;0.45 μg/L, whereas the concentrations decreased in 5/6 patients with TK1 &gt;0.45 μg/L. TK1 concentrations before start of treatment was correlated to high CRP (p=0.01), low Hemoglobin (p=0.03), high WBC (p&lt;0.001) and high platelet counts (p&lt;0.01), but not to albumin or ESR or any other of the measured biomarkers. In a multivariate regression analysis, TK1 was correlated to LDH as the only independent variable (p&lt;0.0001). In Hodgkin lymphoma patients, serum or plasma concentrations of TK1 may reflect malignant cell death and cell disruption rather than cell proliferation during treatment. Our results and hypothesis may help to interpret TK1 protein measurements as clinical tools in cancer management.
Citation Format: Jagarlamudi Kiran Kumar, Staffan Eriksson, Johan Mattsson Ulfstedt, Per Venge, Daniel Molin. The thymidine kinase 1 (TK1) protein concentration in sera from Hodgkin lymphoma patients: A marker for cell death and disruption of malignant cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2618.
Abstract 2626: Combination of chemotherapy and cytokine facilitates adoptive transferred effector T cells homing to the core of metastatic tumors
Authors: Hu Jiemiao , Zhao Qingnan , Xia Xueqing , Gorlick Richard , Li Shulin 
Published: August 2018

Abstract
Metastatic disease accounts for most cases of cancer mortality, due to its systemic nature and resistance to existing therapeutics for primary tumors. Immune therapy has become a viable alternative for treating drug-resistant tumors. In fact, increased immune density in metastasis lesions is associated with beneficial clinical outcomes. Notably, tumor infiltrating lymphocyte (TIL) infusions extended the overall survival of refractory melanoma patients. However, whether or not T cell therapy could be used to successfully limit the metastatic progression largely depends on the complexity of T cell penetration and tumor-immune cell interaction in distant sites. During the past years, our group has identified a simple combination of an immune stimulatory signal (interleukin-12) and chemotherapy (doxorubicin) that persistently induces NKG2D ligand on tumor cells in vivo across tumor types and developed a novel CD28 stimulation based approach for fast induction of NKG2D receptor on CD8+ T cells. We found in breast carcinoma model (4T-1) and pediatric osteosarcoma models (K7M3 and LM8), adoptive transfer of NKG2D+CD8+ T cells after the combination of IL-12 plus doxorubicin treatment dramatically reduced the numbers and sizes of metastatic nodules, leading to significantly prolonged survival time. Mechanically, the treatment of IL-12 plus doxorubicin widely upregulated the expression of NKG2D ligands exclusively on tumor cells in metastatic lesions, and allowed high density of NKG2D+CD8+ T cell accumulation at both the core and invasive margin areas of metastatic tumors. Furthermore, this combination therapeutic led to reduced regulatory T cell infiltration, resulting in increased CD8+ T cell to regulatory T cell ratios in metastatic tumors. Collectively, here we reported that a simple combination treatment of IL-12 plus doxorubicin with subsequent NKG2D+ CD8+T cell adoptive transfer may transform the metastatic tumor microenvironment to enable the influx of NKG2D+CD8+ T cells which effectively kill tumor cells via NKG2D-NKG2D ligand interaction. This promising therapeutic approach greatly improved the effectiveness and potential of adoptive T cell therapy in treating cancer patients with metastatic diseases.
Citation Format: Jiemiao Hu, Qingnan Zhao, Xueqing Xia, Richard Gorlick, Shulin Li. Combination of chemotherapy and cytokine facilitates adoptive transferred effector T cells homing to the core of metastatic tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2626.
Abstract 2650: Clinical implication of microsatellite instability in early gastric cancer
Authors: Choi Yoon Young , Kim Dong Gyu , Son Taeil , Kim Hyoung-Il , Cheong Jae-Ho , Hyung Woo Jin , Noh Sung Hoon 
Published: August 2018

Abstract
Purpose: The role of microsatellite instability is well established in advanced gastric cancer. However, its clinical implication has not been well addressed in early gastric cancer. The purpose of this study is to evaluate the clinical characteristics of microsatellite instability in early gastric cancer.
Methods:
Patients who underwent gastrectomy with curative intent in Severance hospital from January, 2005 to December, 2010 and diagnosed as early gastric cancer (pT1a/b) were enrolled in this study. Remnant gastric cancer and patients who received chemotherapy before operation were excluded. Microsatellite instability status was evaluated by two mononucleotide repeat markers (BAT25 and BAT26) and three dinucleotide repeat markers (D5S346, D2S123, and D17S250) and instability in two or more markers was defined as miscrosatellite instability high (MSI-H), otherwise classified as microsatellite stable (MSS).
Results: Of 1156 tumors that included the final analysis, 85 (7.4%) were MSI-H. MSI-H cancer was related to frequent female gender (54.1% vs. 32.8%, p&lt;0.001), older age (63.4 ± 10.65 vs. 56.7 ± 11.50, p&lt;0.001), lower body (81.2% vs. 59.7%, p=0.002), intestinal histology (63.5% vs. 48.2%, p=0.005), lympho-vascular invasion (25.9% vs. 13.3%, p=0.001), submucosal invasion (63.5% vs. 48.3%, p=0.007), and trend of lymph node metastasis (17.6% vs. 10.8%, p=0.056) compared to MSS type. Lymph node metastasis and lymph-vascular invasion was not differed by MSI status in mucosal gastric cancer (3.2% vs.
2.3%, p=0.755 and 3.2% vs. 2.3%, p=0.755, respectively). In sumbucosal gastric cancer, however, lympho-vascular invasion was frequently observed in MSI-H tumor (38.9% vs. 25.0%, p=0.027) but there was no difference in lymph node metastasis (25.9% vs. 19.9%, p=0.298). When we compared the disease free survival by MSI status, the prognosis of MSI-H tumor was similar compared to that of MSS tumor (log-rank test p=0.797, adjusted Hazard ratio of MSI-H by age, sex, pTstage and number of metastatic LNs: 0.932 [95% confidence interval: 0.423-2.054, p=0.861]).
Conclusions: MSI status could not be a useful biomarker in early gastric cancer to predict prognosis of it. However, frequent lympho-vascular invasion of MSI-H early gastric cancer would be a warning that careful patient's selection for endoscopic treatment or limited lymph node dissection for surgery is necessary.
Citation Format: Yoon Young Choi, Dong Gyu Kim, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh. Clinical implication of microsatellite instability in early gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2650.
Abstract 2663: CR42-24, a novel colchicine derivative, a therapeutic for bladder cancer
Authors: Bell Clayton , Potts Kyle , Pink Desmond , Lewis John , Tuszynski Jack 
Published: August 2018

Abstract
Colchicine is an anti-mitotic drug that targets unpolymerized tubulin, and inhibits microtubule polymerization. It is primarily used to treat gout but has been investigated in numerous clinical trials to treat conditions such as leukemia (ALL), prostate cancer, Behcet's disease, etc.. However, due to its narrow therapeutic window colchicine has had limited clinical translation. A possible approach to reduce general is to produce a derivative with an increased cancer specificity and selectivity by a narrower molecular target selection. Previously, our lab has designed and synthesized a novel colchicine derivative (CR42-24) with a more favorable pharmacological profile compared to colchicine. This was accomplished by designing a structure with an increased affinity for βIII tubulin. βIII tubulin is a β-tubulin isotype that is incorporated into tubulin dimers that make up microtubules. βIII is an excellent target for novel therapies as it has low expression in healthy tissue, is overexpressed in metastatic cancers, and is a clinical marker of poor prognosis. Using cell line screening we demonstrate that CR42-24 is highly toxic to a variety of cancer types with IC50 values at low nanomolar concentrations. More specifically CR42-24 is shown to be highly effective against bladder cancer. Current chemotherapy for bladder cancer is a combination of gemcitabine and cisplatin (Gem/Cis). Although marginally successful, many patients develop resistance to Gem/Cis leaving them with limited options for a second line therapy, thus development of alternative therapies is highly desired. Using in vitro assays we demonstrate that CR42-24 kills aggressive bladder cancer cell types, and is more effective than gemcitabine and cisplatin. Additionally, CR42-24 doubles survival rates of mice with bladder cancer xenografts. We also show that CR42-24 is highly synergistic with other chemotherapies, thereby increasing its therapeutic potential. Through our studies we have shown that CR42-24 is effective in treating aggressive bladder cancer and thus may serve as an alternative or second line therapy.
Citation Format: Clayton Bell, Kyle Potts, Desmond Pink, John Lewis, Jack Tuszynski. CR42-24, a novel colchicine derivative, a therapeutic for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2663.
Abstract 2676: Radiotherapy-assisted tumor selective metronomic oral chemotherapy
Authors: Cho Youngseok , Chung Seung Woo , Byun Youngro 
Published: August 2018

Abstract
Chemotherapy have commonly been used in maximum tolerated dose (MTD) to completely eradicate the cancer. However, such treatments often failed due to the complex and dynamic nature of cancer. Therefore, it has been suggested that cancer should be treated as a chronic disease, controlling its growth by providing continuous therapeutic pressure for long-term. Such an approach, however, requires a therapy that is non-toxic and orally available with sufficient potency. Herein, we propose a radiotherapy-assisted orally available metronomic apoptosis-targeted chemotherapy, which delivers doxorubicin continuously to the irradiated tumor with high selectivity while causing minimal toxicities to the normal tissues. DEVD-S- DOX/DCK complex is the anticancer prodrug for our strategy that could selectively release doxorubicin in the irradiated tumor tissue with sufficient oral bioavailability. The prodrug was completely inactive by itself, but displayed potent anticancer activity when coupled with radiotherapy. Consequently, the daily oral administration of DEVD-S-DOX/DCK in combination with the low-dose radiotherapy effectively suppressed the growth of tumor in vivo with no significant systemic toxicities despite that the accumulated dose of doxorubicin exceeded 150 mg/kg. Therefore, our novel therapy using DEVD-S-DOX/DCK complex is considered as an outstanding treatment option for treating cancer for long-term attributed to its oral availability and low-toxicity profile as well as the potent anticancer effect.
Citation Format: Youngseok Cho, Seung Woo Chung, Youngro Byun. Radiotherapy-assisted tumor selective metronomic oral chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2676.
Abstract 2679: Cyanobacterial trypsin-3 inhibitor inhibits prostate cancer cell invasion
Authors: Koistinen Hannu , Wahlsten Matti , Ahmed Muhammad N. , Sivonen Kaarina , Nees Matthias , Stenman Ulf-Håkan , Fewer David P. 
Published: August 2018

Abstract
Trypsin-3 is a highly active protease that has recently been identified as a potential therapeutic target for the reduction of tumor growth and metastasis in prostate, breast and pancreatic cancers. Current trypsin inhibitors typically inhibit a broad range of different trypsin-like enzymes. Thus, novel approaches to identify trypsin-3 selective inhibitors are needed. Cyanobacteria produce a vast diversity of natural products with complex chemical structures many of which are potent protease inhibitors.
We screened extracts of 140 cyanobacteria strains and discovered numerous strains showing selectivity towards trypsin-2 and -3 inhibition. We isolated a complex glycopeptide from one of these strains, which selectively inhibited human trypsin-2 and -3 with IC50 values of about 100 nM, while trypsin-1 was not inhibited. Importantly, we also found that this peptide inhibited invasion of aggressive and metastatic PC-3M prostate cancer cells though ECM preparation, while it did not affect the proliferation of the cells.
Our results suggest that microbial natural products may offer a viable alternative source of potent and selective trypsin-3 inhibitors. Such inhibitors may be suitable, after further development, for targeting the mechanisms associated with the invasion and metastatic dissemination of cancer cells, i.e., for treatment of aggressive cancers.
Citation Format: Hannu Koistinen, Matti Wahlsten, Muhammad N. Ahmed, Kaarina Sivonen, Matthias Nees, Ulf-Håkan Stenman, David P. Fewer. Cyanobacterial trypsin-3 inhibitor inhibits prostate cancer cell invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2679.
Abstract 2681: Antiproliferative effects of the naturally occurring solamargine and related glycoalkaloids against liver cancer cells
Authors: Fekry Mostafa I. , Ezzat Shahira M. , Salama Maha M. , Al-Abd Ahmed M. 
Published: August 2018

Abstract
Hepatocellular carcinoma (HCC) is progressively increasing tumor with lack of accurate prognosis and inadequate systemic treatment approaches. Solanum sp. (such as Solanum melongena) is a folk herb which is reported to possess anticancer properties. In a continuity for our interest in pursuing the anticancer activity of compounds isolated from the fruit peels of Solanum melongena, the HPLC profiling and ESI-MS assessment for the methanolic extract evidenced the presence of bioactive glycoalkaloids (solasonine, solasodine and solamargine). These glycoalkaloids were isolated, purified and proved to possess in vitro cytotoxicity against human liver cancer cell lines (Huh7 and HepG2). Herein, we investigated the potential mechanism of action of these compounds using DNA content flow-cytometry and apoptosis/necrosis differential anaylsis using annexin-V/FITC staining. Solasonine, solasodine and solamargine inducd significant antiproliferative effect against liver cancer cells (Huh7 and HepG2) which was attributed to cell cycle arrest at S-phase. Solamargine, solasodine and solasonine induced significant apoptosis in Huh7 cells. Only solamargine-induced cell cycle arrest, was reflected as apoptotic cell killing effect against HepG2 cells. In conclusion, glycoalkaloids derived from Solanum melongena and particularly, solamargine are promising antiproliferative agents with potential anticancer effects.
Citation Format: Mostafa I. Fekry, Shahira M. Ezzat, Maha M. Salama, Ahmed M. Al-Abd. Antiproliferative effects of the naturally occurring solamargine and related glycoalkaloids against liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2681.
Abstract 2687: Cypripedin inhibits non-small cell lung cancer migration through suppression of epithelial-to-mesenchymal transition
Authors: Treesuwan Surassawadee , Pongrakhananon Varisa 
Published: August 2018

Abstract
Lung cancer is one of the most common cause of cancer-related death worldwide because of high metastasis rate. Cancer migration is a prerequisite event among multi-complex processes of metastasis, being one of the interested target for cancer therapy. Accumulative evidence emphasizes that epithelial-to-mesenchymal transition (EMT) plays an important behavior exerting cell motility and survival, and relevant to cancer metastasize. Even the therapeutic approaches have been developed, lung cancer metastasize remains challenge for drug discovery and development. Recent studies highlight the potent anticancer properties of the compounds derived from Orchid. However, the underlying mechanism was unrevealed. This study demonstrated that cypripedin, a phenanthrenequinone extracted from Dendrobium densiflorum, possess an ability to inhibit in vitro cell migration in non-small cell lung cancer H460 and H23 cells. The number of motile cells, examined by transwell migration and wound healing assay, were gradually reduced in a dose-dependent concentration of cypripedin, along with the reduction of colony number and size formed under an anchorage-independent growth. Mechanistic investigation shows that the mesenchymal markers including N-Cadherin, Vimentin and Slug were significantly down-regulated following cypripedin treatment. Our finding suggests that cypripedin potentiates anti-migrative activity in non-small cell lung cancer through the attenuation of EMT process, which support further extensive studies against lung cancer.
Citation Format: Surassawadee Treesuwan, Varisa Pongrakhananon. Cypripedin inhibits non-small cell lung cancer migration through suppression of epithelial-to-mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2687.