tbuckley/cabot-search huggingface dataset:
Abstract 1612: Overexpression or inducible expression of Snail, Zeb1 or TGFβ recapitulates epithelial-mesenchymal transition (EMT) in colorectal cancer cell lines in vitro
Authors: Shripad V. Bhagwat, Nicole E. Hamm, Yu-Chih Hsu, Yuewei Qian, Robert Wild, Jonathan A. Lee, Sheng-Bin Peng
Journal: Cancer Research (2016)

Abstract Epithelial-mesenchymal transition (EMT) is one of the hallmarks of cancer and a critical process providing tumor cells with the ability to metastasize to distant sites. Several previous studies have revealed that EMT plays a crucial role in the progression and aggressiveness of colorectal cancer (CRC). Snail, Zeb1 and TGFβ are considered as master EMT genes and their overexpression has been linked to metastatic disease. Our study was conducted to establish an EMT platform in-house to determine the role of Snail, Zeb1 and TGF-β1 in mediating EMT in CRC cell lines in vitro and using them for studying drug sensitivity and target validation. Screening of six CRC cell lines for expression of epithelial (E) and mesenchymal (M) markers by western blot analysis suggested that DLD-1 and HT-29 cells are epithelial in nature and were used to generate stable overexpression and tet-inducible models. Overexpression of Snail or Zeb1 or TGF-β1 induced EMT in both DLD-1 and HT-29 colorectal cancer cells as indicated by downregulation of E-cadherin and upregulation of vimentin by western blot analysis and immunofluorescence staining. These cells which have undergone EMT also showed significant growth advantage in 3D growth on matrigel or soft agar. Stable ‘E’ and ‘M’ cells were also used to test the sensitivity of various inhibitors including erlotinib, salinomycin and chemotherapeutic agents such as paclitaxel, gemcitabine, cisplatin, oxaloplatin and 5-FU. Consistent with previous findings, erlotinib showed sensitivity only in ‘E’ cells and not ‘M’ cells. Chemotherapy agents have also shown higher sensitivity in ‘E’ cells than ‘M’ cells. In contrast, Salinomycin showed equipotent sensitivity in ‘E’ and ‘M’ cells. We have also generated tet-inducible models of Snail, Zeb1 and TGF-β1 and they behaved very similar to overexpression models. These inducible models were useful to determine whether any inhibitor treatment or knock down of specific gene (target) can block EMT. In our studies, testing of a Focal Adhesion Kinase (FAK) inhibitor or Dasatinib (SFK inhibitor) as examples showed blockade of EMT in these models. Overall, establishing several EMT models in-house enabled us to validate new targets involved in EMT, test new inhibitors whether it can block EMT or study drug sensitivity in ‘E’ vs. ‘M’ cells. Citation Format: Shripad V. Bhagwat, Nicole E. Hamm, Yu-Chih Hsu, Yuewei Qian, Robert Wild, Jonathan A. Lee, Sheng-Bin Peng. Overexpression or inducible expression of Snail, Zeb1 or TGFβ recapitulates epithelial-mesenchymal transition (EMT) in colorectal cancer cell lines in vitro. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1612.
Abstract 1562: miRNAs in exosomes from prostate cancer cells modify normal fibroblasts and osteoblasts favoring tumor spread and metastasis
Authors: Eliana Andahur, Enrique A. Castellon, Chistian Ramos, Juan A. Fulla, Catherine A. Sanchez
Journal: Cancer Research (2016)

Abstract Introduction: Exosomes from bulk and cancer stem cells (CSCs) from prostate cancer primary cultures present a differential pattern of miRNAs. The most abundant miRNA in all exosomes is miR-100, while miR-21 and miR-139 were the most abundant differentially expressed miRNAs in bulk and CSCs exosomes, respectively. Bioinformatics analysis suggested that these miRNAs were related with tumor progression. The functional effect of these miRNAs on targets related with changes at primary and pre-metastatic microenvironment was evaluated in prostatic stromal cells and osteoblasts. Methods: Normal human undifferentiated osteoblasts (hFOB1.19) and prostate fibroblasts (WPMY-1) cell lines were transfected, by separated, with 25 nM of the following miRNas: miR-100-5p, miR-21-5p, miR-139-5p. let7c was included as transfection control. After 48 hours, changes in the expression of metalloproteinases (MMP)-2, -9 and-13, RANKL, OPG and IL-8 at mRNAs and protein levels were evaluated by qPCR and western blot, respectively. As transfection control, expression of specific targets previously described for each miRNA was evaluated. Besides, the effect of miRNAs in fibroblast migration was evaluated by transwell assay. Results: In fibroblasts, transfection with miR-21, -100 and -139 increased significantly expression of RANKL, IL8 and all MMPs, with a higher effect in MMP-9. Besides, miR-21 increased fibroblast migration. In osteoblasts, transfection with miRNAs changed the balance that triggers vicious circle at the bone, increasing RANKL and diminishing OPG expression. miRNAs also increased MMPs expression. The greater effect was observed with miR-21 transfection. Conclusions: Through exosomes, prostate cancer cells recruit normal cells to favor their growth and spread. miRNAs in exosomes increase expression of proteins (in particular, MMPs and RANKL) and cell migration of fibroblasts that create a favorable microenvironment for tumor progression at the primary niche. Besides, through bloodstream, tumoral exosomes can reach the bone, preparing the premetastatic niche. miRNAs from these exosomes change the balance RANKL/OPG that triggers osteoclast recruitment facilitating metastases by activation of the bone vicious circle. miR-21, overexpressed in bulk cells, the main cellular component of tumor, has the higher effect in modify microenvironment, being a potential therapeutic target. (FONDECYT 11121525 and 1140417). Citation Format: Eliana Andahur, Enrique A. Castellon, Chistian Ramos, Juan A. Fulla, Catherine A. Sanchez. miRNAs in exosomes from prostate cancer cells modify normal fibroblasts and osteoblasts favoring tumor spread and metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1562.
Intravenous vinorelbine (NVBiv) on D1 and oral vinorelbine(NVBo) on D8 in combination with carboplatin (CBDCA) as firstline treatment in advanced non-small lung cancer (NSCLC)patients: preliminary results of a prospective study
Authors: Jana Skřičková, Jana Keilová, Tereza Janásková, Vítězslav Kolek, Jiří Chalupa, Jaromír Roubec, Tomáš Třasoň, Marcela Tomíšková, Bohdan Kadlec, Jiřina Švecová, Ivona Grygárková, Milan Kohoutek
Journal: Journal of Thoracic Oncology (2009)
Abstract 18013: Which Measure of Renal Function is the Best Predictor of Outcome in Heart Failure? A Comparison of Cockcroft Gault, Modification of Diet in Renal Disease Study Group and Chronic Kidney Disease Epidemiology Collaboration Formulae
Authors: Andrea Pozzi, Pardeep Jhund, Ana Cristina Perez-Moreno, Dirk J. van Veldhuisen, Michael Böhm, John Wikstrand, John Cleland, John Kjekshus, Mark Petrie, John McMurray
Journal: Circulation (2013)

Introduction: Renal function is an important predictor of prognosis in heart failure (HF). Several formulae can be used to estimate glomerular filtration (eGFR) but which of these is best at predicting outcome in HF is uncertain. We compared the performance of the Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study Group (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in predicting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Methods: We studied the 5011 patients aged ≥60 years with symptomatic (NYHA class II-IV) HF of ischemic etiology and a LVEF ≤40% (≤35% in NYHA class II) enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA). Mortality rates were calculated for patients in the eGFR categories &lt;45, 45-59 and ≥60 ml/min/1.73m 2 (reference). The performance of the equations was compared using receiver operating characteristic curve (ROC) analysis. Results: The rate and risk of death was highest in those with the lowest eGFR for each formula (Table). The area under the ROC for CG was 0.64, MDRD 0.59 (P&lt;0.001 versus CG) and CKD-EPI 0.61 (P&lt;0.0001 versus CG). Conclusion: Risk prediction with CG was better than with MDRD or CKD-EPI in patients with HfrEF in CORONA. †Rate per 100 patient years *Reference group
Case 61-1962
Authors: Arthur S. Pier, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of CaseA sixty-one-year-old man was admitted to the hospital because of hemoptysis.Nineteen years previously hemoptysis first occurred, and x-ray films of the chest were said to show apical scarring as well as bronchiectasis and atelectasis involving the right lower lobe. In the interim the patient had a persistent cough that was most severe at night and on arising. The cough was productive of copious amounts of green or yellow-white sputum, and there were brief episodes of hemoptysis at least once a year. He continued to smoke a package of cigarettes daily. Five months before entry the productive . . .
Abstract 5240: Lacking hepatic retinoid storage in mice suppresses NASH-related hepatocarcinogenesis
Authors: Takayasu Ideta, Yohei Shirakami, Tsuneyuki Miyazaki, Hiroyasu Sakai, Takuji Tanaka, William S. Blaner, Masahito Shimizu
Journal: Cancer Research (2016)

Abstract Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, has become one of the most common causes of chronic liver disease in developed countries. Some patients with NAFLD develop a more serious form of the disease, non-alcoholic steatohepatitis (NASH), and NASH can develop cirrhosis or even hepatocellular carcinoma (HCC). Although hepatic retinoid (vitamin A) stores are progressively lost during the development of liver diseases, how this affects NAFLD/NASH and NASH-related hepatocarcinogenesis is unknown. In order to investigate this, we used streptozotocin (STZ) and high-fat diet (HFD) to induce NASH and related hepatic tumorigenesis in matched wild-type and lecithin:retinol acyltransferase (LRAT) knockout (KO) mice, which lack stored retinoid in the liver. LRAT is the sole enzyme responsible for hepatic retinyl ester synthesis since LRAT KO mice completely lack lipid droplets in hepatic stellate cells. Mice were injected with STZ within 48 hours after birth and then fed HFD from 4 to 16 weeks of age. At the termination of the experiment, liver tumors were observed macroscopically and microscopically in both groups. In LRAT KO mice, the development of hepatic adenoma and HCC was significantly suppressed compared to control group. LRAT KO mice showed decreased expression levels of cyclin D1 and TGF-beta mRNA in the liver. The serum levels of d-ROMs and BAP were measured and the d-ROM/BAP ratio, which indicates oxidative stress, markedly decreased in LRAT KO mice. The fibrosis in the liver of the LRAT KO mice was decreased. In addition, liver fibrosis in LRAT KO mice was suppressed. These findings indicate that LRAT KO mice are less susceptible to STZ and HFD-induced liver tumorigenesis due to regulation of cell cycle and attenuation of oxidative stress. The amount of hepatic retinoid may affect the progression of NASH and the development of NASH-related HCC. Citation Format: Takayasu Ideta, Yohei Shirakami, Tsuneyuki Miyazaki, Hiroyasu Sakai, Takuji Tanaka, William S. Blaner, Masahito Shimizu. Lacking hepatic retinoid storage in mice suppresses NASH-related hepatocarcinogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5240.
Abstract 3812: FAK inhibition resensitizes platinum-resistant serous ovarian cancer
Authors: Lisa M. Bean, Florian J. Sulzmaier, Isabelle Tancioni, Sean Uryu, Christine Jean, Christine Lawson, Xiao Lei Chen, Elizabeth G. Kleinschmidt, Kristen M. Anderson, Edward A. Cordasco, Joshua Axelrod, Vihren N. Kolev, Jonathan A. Pachter, Dwayne G. Stupack, David D. Schlaepfer
Journal: Cancer Research (2016)

Abstract Platinum and taxol administration is standard of care chemotherapy for serous ovarian cancer. Tumor recurrence occurs in a high percentage of patients, and this is directly related to poor overall survival. Ovarian cancer stem cell (CSC) resistance to chemotherapy treatment can give rise to tumor recurrence. Focal adhesion kinase (FAK), an intracellular tyrosine kinase, has been linked to mesothelioma and breast CSC survival. Here, we find that FAK activation is elevated in platinum (CP)-resistant ovarian cancer cells and that FAK tyrosine phosphorylation is increased after CP treatment of CP-sensitive ovarian cancer cells. Nanomolar levels of FAK inhibitor (VS-4718) selectively blocked CP-resistant ovarian carcinoma methylcellulose colony growth via cell cycle inhibition but not apoptosis. Oral VS-4718 administration to mice reduces CP-resistant orthotopic tumor burden with a concomitant decrease in tumor-associated aldehyde dehydrogenase (ALDH) activity, a marker of ovarian CSCs. Residual ovarian tumor cells from VS-4718-treated mice exhibit reduced ALDH activity and secondary tumor initiating capacity. CRISPR-mediated FAK knockout or VS-4718 treated ovarian carcinoma cells exhibit diminished Oct-4 transcription factor and ALDH-1A1 CSC-associated protein marker expression. Co-administration of VS-4718 with CP-taxol chemotherapy reduced CP-resistant tumor burden and exhibited additive inhibitory effects on ovarian carcinoma spheroid growth. As we find that CP activates FAK and that FAK activity sustains ovarian carcinoma CSC phenotypes, our results support the testing of FAK inhibitors in combination with CP to prevent recurrent and chemo-resistant ovarian cancer. Citation Format: Lisa M. Bean, Florian J. Sulzmaier, Isabelle Tancioni, Sean Uryu, Christine Jean, Christine Lawson, Xiao Lei Chen, Elizabeth G. Kleinschmidt, Kristen M. Anderson, Edward A. Cordasco, Joshua Axelrod, Vihren N. Kolev, Jonathan A. Pachter, Dwayne G. Stupack, David D. Schlaepfer. FAK inhibition resensitizes platinum-resistant serous ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3812.
Venous thromboembolism in patients with hematologic malignancy and thrombocytopenia
Authors: Nabin Khanal, R. Gregory Bociek, Baojiang Chen, Julie M. Vose, James O. Armitage, Philip J. Bierman, Lori J. Maness, Matthew A. Lunning, Krishna Gundabolu, Vijaya R. Bhatt
Journal: American Journal of Hematology (2016)

The optimal management of hematologic malignancy-associated venous thromboembolism (VTE) in patients with moderate-to-severe thrombocytopenia is unclear. This is a retrospective study of 128 adult patients with hematologic malignancies who were diagnosed with VTE. The outcome of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Forty-seven patients (36.7%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation. The median nadir platelet count in those with significant thrombocytopenia was 10,000/µL (range 2,000-45,000/µL) versus 165,000/µL (50,000-429,000/µL) in those without (P < 0.001). The median duration of significant thrombocytopenia in the first group was 10 days (1-35 days). Therapy during the period of significant thrombocytopenia included prophylactic-dose low-molecular-weight heparin (LMWH) (47%), therapeutic-dose LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%), and observation (17%). Patients without thrombocytopenia were managed with the standard of care therapy. At a median follow-up of more than 2 years, the risk of clinically significant bleeding (11% vs 6%, P = 0.22) including major bleeding (6% vs 2%) and clot progression or recurrence (21% vs 22%, P = 1.00) were similar in patients with or without significant thrombocytopenia. In a multivariate analysis, the risk of recurrence/progression (hazard ratio, HR 0.59, 95% CI 0.21-1.66, P = 0.31) and hemorrhage rate (HR 0.29, 95% CI 0.05-1.56, P = 0.15) did not differ based on the presence of significant thrombocytopenia. Within the limits of this retrospective study, cautious use of prophylactic-dose LMWH may be safe in thrombocytopenic patients with hematologic malignancy-associated VTE. Am. J. Hematol. 91:E468-E472, 2016. © 2016 Wiley Periodicals, Inc.
Imaging and pathological characters in pig liver after MR-guided microwave ablation.
Authors: Jun Dong, Xiuyu Cai, Liang-Ping Xia, Peihong Wu
Journal: Journal of Clinical Oncology (2016)

e15608 Background: Recent clinical guidelines recommend ablation therapy as a curative treatment for primary liver cancer. Ultrasound and computerized tomography (CT) are commonly used to guide these ablation procedures; however, ultrasound has poor quality images and CT exposes the operator to radiation. Magnetic resonance (MR)-guided microwave ablation is a potential-developed technique, which overcomes these limitations. However, there are no detailed illustrations on continuous changes of both the MR images and histology after the ablation. Methods: We performed MR-guided microwave ablation in 10 Wuzhishan pigs, and obtained an MR scan immediately after ablation (0 weeks), and at 1, 2, 3, and 4 weeks after ablation. We compared the ablation assessed on MR images to tissue specimens obtained during follow-up. Results: We found no significant difference in the ablation size between MR images and tissue specimens (t-test, P > 0.05). Instantly after ablation, we found that carbonization and cavities in the ablation centre. MRI showed oval in shape, black in colour, with low signal intensity around the antenna tract on T1WI, T2WI, and enhanced T1WI. However, hyperintensity changed and lasted overtime after ablation on T2WI images. In the peripheral ablation zone, we observed coagulation necrosis, causing necrotic cells to keep their shape. Hypointense remained on T2WI while hyoerintense remained on T1WI and enhanced T1WI. In the inflammatory zone around the ablation area, the T2WI image showed hyperintensity and the T1W1 image showed hypointensity. It finally disappeared two weeks after ablation, and became fibrotic capsule. Therefore, it became hypointense on the T2WI, while hypointense remained on the T1WI over time. The MR images could accurately mapped the histological changes in tissue samples after the ablation. Conclusions: The dynamic imaging and pathological features outlined in this study may provide a reference for understanding how ablated zone changes in follow-up after MR-guided microwave ablation in the future.
Sequential Therapy with Crizotinib and Alectinib in ALK -Rearranged Non–Small Cell Lung Cancer—A Multicenter Retrospective Study
Authors: Kentaro Ito, Osamu Hataji, Hiroyasu Kobayashi, Atsushi Fujiwara, Masamichi Yoshida, Corina N D’Alessandro-Gabazza, Hidetoshi Itani, Motoaki Tanigawa, Takuya Ikeda, Kentaro Fujiwara, Hajime Fujimoto, Tetsu Kobayashi, Esteban C. Gabazza, Osamu Taguchi, Nobuyuki Yamamoto
Journal: Journal of Thoracic Oncology (2016)
Abstract 3399: CTGF promotes tumor angiogenesis process in osteosarcoma through induction of angiopoietin-2
Authors: Yu-che Cheng, Hsiao-Chi Tsai, Tzu-Wei Tan, Chih-Hsin Tang
Journal: Cancer Research (2016)

Abstract Osteosarcoma is the most common primary malignant bone tumor. Angiogenesis is essential for the tumor growth. Angiopoietin-2 (Angpt2) plays a critical role in angiogenesis and tumor progression. Connective tissue growth factor (CTGF), a secreted protein that binds to integrins, modulates the angiogenesis of certain human cancer cells. However, the effect of CTGF on Angpt2 expression in human osteosarcoma cells is mostly unknown. In this study, we found that overexpression of CTGF in osteosarcoma promoted angiogenesis in vitro and in vivo by tube formation assay, and Matrigel plug assay. Knockdown of CTGF obviously reduced expression of Angpt2 and angiogenesis. Recently, microRNAs (miRNAs) have been demonstrated that functions as oncogenes or angiogenesis regulators in human cancer. Here, we also found that overexpression of CTGF significantly decreased miR-543 in osteosarcoma cells. Transfection of miR-543 mimic reduced Angpt2 expression and angiogenesis. Taken together, CTGF promotes angiogenesis via up-regulation of Angpt2 by decreasing miR-543 in human osteosarcoma. These findings certify that CTGF functions as a tumor enhancer gene, suggesting that CTGF may be a potential therapeutic target for osteosarcoma patients. Citation Format: Yu-che Cheng, Hsiao-Chi Tsai, Tzu-Wei Tan, Chih-Hsin Tang. CTGF promotes tumor angiogenesis process in osteosarcoma through induction of angiopoietin-2. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3399.
Transplantation of tissue engineering neural network and formation of neuronal relay into the transected rat spinal cord
Authors: Bi-Qin Lai, Ming-Tian Che, Bao-Ling Du, Xiang Zeng, Yuan-Huan Ma, Bo Feng, Xue-Chen Qiu, Ke Zhang, Shu Liu, Hui-Yong Shen, Jin-Lang Wu, Eng-Ang Ling, Yuan-Shan Zeng
Journal: Biomaterials (2016)
Deep mural injury and perforation after colonic endoscopic mucosal resection: a new classification and analysis of risk factors
Authors: Nicholas G Burgess, Milan S Bassan, Duncan McLeod, Stephen J Williams, Karen Byth, Michael J Bourke
Journal: Gut (2016)

Perforation is the most serious complication associated with endoscopic mucosal resection (EMR). We propose a new classification for the appearance and integrity of the muscularis propria (MP) after EMR including various extents of deep mural injury (DMI). Risk factors for these injuries were analysed.Endoscopic images and histological specimens of consecutive patients undergoing EMR of colonic laterally spreading lesions ≥20 mm at a large Australian tertiary referral endoscopy unit were retrospectively analysed using our new DMI classification system. DMI was graded according to MP injury (I/II intact MP without/with fibrosis, III target sign, IV/V obvious transmural perforation without/with contamination). Histological specimens were examined for included MP and patient outcomes were recorded. All type III-V DMI signs were clipped if possible, types I and II DMI were clipped at the endoscopists' discretion.EMR was performed in 911 lesions (mean size 37 mm) in 802 patients (male sex 51.4%, mean age 67 years). DMI signs were identified in 83 patients (10.3%). Type III-V DMI was identified in 24 patients (3.0%); clipping was successfully performed in all patients. A clinically significant perforation occurred in two patients (0.2%). Only one of the 59 type I/II cases experienced a delayed perforation. 85.5% of patients with DMI were discharged on the same day, all without sequelae. On multivariable analysis, type III-V DMI was associated with transverse colon location (OR 3.55, p=0.028), en bloc resection (OR 3.84, p=0.005) and high-grade dysplasia or submucosal invasive cancer (OR 2.97, p 0.014).In this retrospective analysis, use of the new classification and management with clips appeared to be a safe approach. Advanced DMI types (III-V) occurred in 3.0% of patients and were associated with identifiable risk factors. Further prospective clinical studies should use this new classification.NCT01368289; results.