tbuckley/cabot-search huggingface dataset:
Abstract 4220: Tumor-targeting Salmonella typhimurium A1-R efficacy on colon cancer liver metastasis alone and in combination with fluorescence-guided surgery
Authors: Takashi Murakami, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, MIchael Bouvet, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2016)

Abstract Liver metastasis is the most frequent cause of death from colon and other cancers. Surgical treatment of liver metastasis has had limited success. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R alone and in combination with fluorescence-guided surgery on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) developed liver metastasis after orthotopic implantation. In the orthotopic nude-mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth (p &amp;lt; 0.01) after i.v. administration. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase overall survival (p = 0.01) and disease-free survival (p &amp;lt; 0.01) after bright-light surgery (BLS) of liver metastasis. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R treatment of liver metastasis. Citation Format: Takashi Murakami, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, MIchael Bouvet, Itaru Endo, Robert M. Hoffman. Tumor-targeting Salmonella typhimurium A1-R efficacy on colon cancer liver metastasis alone and in combination with fluorescence-guided surgery. [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 4220.
An Open-Label, Multicenter, Randomized, Phase II Study of Cisplatin and Pemetrexed With or Without Cixutumumab (IMC-A12) as a First-Line Therapy in Patients With Advanced Nonsquamous Non–Small Cell Lung Cancer
Authors: Silvia Novello, Giorgio Scagliotti, Gilberto de Castro, Murat Kiyik, Rubén Kowalyszyn, Karl-Matthias Deppermann, Edurne Arriola, Lionel Bosquee, Ruslan D. Novosiadly, Tuan S. Nguyen, Amelie Forest, Shande Tang, Siva Rama Prasad Kambhampati, Jan Cosaert, Martin Reck
Journal: Journal of Thoracic Oncology (2016)

IntroductionType 1 insulin-like growth factor receptor is deregulated in solid tumors. Cixutumumab, a monoclonal antibody that inhibits the activity of type 1 insulin-like growth factor receptor, was investigated in combination with pemetrexed/cisplatin in the frontline setting.MethodsIn this open-label, phase II study, patients with stage IV nonsquamous NSCLC and a performance status of 0 to 1 were randomized (1:1) to receive 20 mg/kg cixutumumab, 500 mg/m2 pemetrexed, and 75 mg/m2 cisplatin (cixutumumab [n = 87]) or pemetrexed and cisplatin (control [n = 85]). Eligible patients received pemetrexed-based maintenance therapy with cixutumumab (cixutumumab arm) or without it (control arm). The primary end point was progression-free survival. Secondary end points assessed overall survival, objective response rate, and safety. Survival was analyzed by the Kaplan-Meier method and Cox proportional hazard model. Exploratory correlative analyses were also performed.ResultsThe mean age of the intent-to-treat population (n = 172) was 59 years (range 32–83). Median progression-free survival was 5.45 months with cixutumumab versus 5.22 months in the control (hazard ratio = 1.15, 95% confidence interval: 0.81–1.61; p = 0.44). Median overall survival was 11.33 months with cixutumumab versus 10.38 months in the control (hazard ratio = 0.93, 95% confidence interval: 0.64–1.36). Objective response rate did not differ between treatments (p = 0.338). Grade 3 or 4 hyperglycemia occurred at a higher rate with cixutumumab than in the control (9.4% versus 1.2%). One death possibly related to cixutumumab occurred.ConclusionsEfficacy was not improved in patients with nonsquamous NSCLC when cixutumumab was added to pemetrexed/cisplatin. Combination therapy was well tolerated and no new safety concerns were reported.
Epidémie d'infections à calicivirus associée à la consommation de framboises congelées
Authors: A Pönka, L Maunula, C. H. von Bonsdorff, O Lyytikaïnen
Journal: Eurosurveillance (1999)

Les petits virus ronds (SRSV, small round structured viruses) auxquels appartiennent les calici-, astro- et enterovirus, sont la cause la plus courante des epidemies de gastro-enterites non bacteriennes dans le monde (1,2). La transmission de ces virus par l’eau et divers aliments dont les salades, les pâtisseries, les fruits frais, le poulet, les huitres et les moules est connue. A l’exception des epidemies liees a l’eau et aux coquillages, la contamination d’aliments par des virus est generalement attribuee a leur manipulation par des employes infectes du secteur alimentaire. Le developpement recent des techniques de biologie moleculaire pour la detection et la differenciation des SRSV a permis d’augmenter la sensibilite et la specificite du diagnostic des gastro-enterites virales (3,4).
Papers Relating to the Pituitary Body, Hypothalamus and Parasympathetic Nervous System.
Journal: Annals of Internal Medicine (1933)

Musser 's book, like Cecil-s, is exclusively of United States' authorship.Perhaps the ideal text is yet to be compiled which shall be a composite of international medicine though the difficulties besetting its editorship might well be discouraging.In this text a novelty has been introduced in the matter of classification.Internal diseases are grouped in four parts: (1) infectious diseases; (2) systemic diseases, including circulatory,.respiratory, alimentary, urinary, endocrine, blood, spleen and reticulo-endothelial, and locomotor; (3) diseases of nutrition, allergy, metabolism, physical and chemical agents; (4) diseases of the nervous system, including mental disorders and organic diseases of the nervous system.While it is doubtful if this arrangement
Survival of Multiple Myeloma Patients in the Era of Novel Agents and Autologous Stem Cell Transplantation: A Multicenter Retrospective Collaborative Study of the Japanese Society of Myeloma
Authors: Shuji Ozaki, Hiroshi Handa, Takayuki Saitoh, Hirokazu Murakami, Mitsuhiro Itagaki, Hideki Asaoku, Kenshi Suzuki, Atsushi Isoda, Morio Sawamura, Jun Konishi, Kazutaka Sunami, Naoki Takezako, Shotaro Hagiwara, Yoshiaki Kuroda, Takaaki Chou, Eiko Shibata, Kazuyuki Shimizu, Eiichi Nagura
Journal: Blood (2014)
Abstract 1850: Transcription factor E2F3 up-regulates the expression of Gadd45b gene in the mouse liver
Authors: Jung-Hwan Kim, Frank J. Gonzalez
Journal: Cancer Research (2016)

Abstract Growth arrest and DNA damage-inducible beta (GADD45b) plays an important role in many intracellular events, such as cell survival- and cell death-related signaling. In normal condition, Gadd45b is suppressed by the negative regulator, such as STAT3, however, when it induced by the PPARa agonist, Wy-14,643. Thus, we investigated the positive regulator of Gadd45b. Based on the Gadd45b-reporter assay, we assumed that E2Fs could regulate the Gadd45b. As results, E2F3 mRNA was induced only in the liver of Wy-14,643-treated mice. In addition, deletion of E2Fs consensus sequence in the Gadd45b reporter gene showed significant decrease of luciferase activity. Furthermore, overexpression of E2F3 significantly increased the Gadd45b-luciferase activity and this was inhibited by the siE2F3 in the Hepa1c1c7 cells. Taken together, E2F3 may play a pivotal role in the Gadd45b induction as a positive regulator. Citation Format: Jung-Hwan Kim, Frank J. Gonzalez. Transcription factor E2F3 up-regulates the expression of Gadd45b gene in the mouse liver. [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 1850.
Abstract 1214: Development of anti-5T4 antibody-drug conjugates, ZV05-ADCs for targeted cancer therapy in different type of cancers
Authors: Zhaohui Li, Zhangming Xie, Qian Zhang, Jie Fang, Liqin Wu, Hedi Fang, Hong Zhang, Tong Zhu, Gang Chen, David Miao, Sheldon Cao
Journal: Cancer Research (2016)

Abstract 5T4 is an N-glycosylated transmembrane 72 kDa glycoprotein expressed in a number of carcinomas, and has been explored as a target for cancer therapy in different type of cancers, including NSCLC, RCC, colorectal, ovarian, pancreatic and gastric cancers. The expression of 5T4 in normal tissue is very limited, but widespread in malignant tumors throughout their development, making it an attractive target for antibody-drug conjugate (ADC). In this aspect, a 5T4-MMAF ADC from Pfizer is under clinical investigation in phase I/II trials. We have developed novel anti-5T4 ADCs, using our proprietary conjugation technologies. A highly potent anti-5T4 antibody ZV05 was conjugated to a variety of internally developed linkers and toxins and purified to populations containing defined DAR (Drug-Antibody Ratio) numbers. The ADCs were studied both in vitro and in vivo for their activity against a variety of tumors. The results showed that the lead ZV05 ADCs were potent towards a bunch of cancer cell lines that express 5T4, and also dramatically inhibited tumor growth in several models in vivo. In the xenograft studies, a single dose of the lead ZV05 ADCs completely wiped out the tumors and kept the tumor volume down for the whole period of studies. ZV05 ADCs are currently under further evaluation to select a candidate for clinical treatment of 5T4-positive cancers. Citation Format: Zhaohui Li, Zhangming Xie, Qian Zhang, Jie Fang, Liqin Wu, Hedi Fang, Hong Zhang, Tong Zhu, Gang Chen, David Miao, Sheldon Cao. Development of anti-5T4 antibody-drug conjugates, ZV05-ADCs for targeted cancer therapy in different type of cancers. [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 1214.
Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation ( PVT1 ) as a novel regulator of the asthmatic phenotype in human airway smooth muscle
Authors: Philip J. Austin, Eleni Tsitsiou, Charlotte Boardman, Simon W. Jones, Mark A. Lindsay, Ian M. Adcock, Kian Fan Chung, Mark M. Perry
Journal: Journal of Allergy and Clinical Immunology (2016)

The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma.
Case 60-1963
Authors: Arnold N. Weinberg, Robert E. Scully
Journal: New England Journal of Medicine (1963)

Presentation of CaseA thirteen-year-old girl entered the hospital because of fever and somnolence.The patient had been well until two days before admission, when headache and fatigue developed. The fatigue increased, accompanied by nausea. During the evening before entry she vomited, appeared febrile and complained of pain in the back, abdomen and shoulders, as well as of a painful lump in the back of the neck. On the following day she was found in a deep sleep by an aunt, who also observed a "prickly-heat rash" over the body.There was no history of neurologic disease or exposure to . . .
Abstract 1497: Development of a novel TCR-like bi-specific T-cell engager targeting endogenous PR1/HLA-A2 leukemia antigen
Authors: Amanda Cernosek Herrmann, Jin S. Im, Sijie Lu, Anna Sergueeva, Jeffrey Molldrem
Journal: Cancer Research (2016)

Abstract PR1 (VLQELNVTV) is a HLA-A2 restricted peptide derived from endogenous tumor associated antigens proteinase-3 and neutrophil elastase that are aberrantly expressed in myeloid leukemia blasts. Previously, we have developed a high affinity T-cell receptor-like monoclonal antibody (h8F4) specific for PR1/HLA-A2, and demonstrated the effective killing of myeloid leukemia blasts via antibody dependent cellular cytotoxicity (ADCC). To improve the therapeutic efficacy of h8F4, we adopted a novel antibody engineering strategy, bi-specific T-cell engaging (BiTE) antibody that can bring T cells in close proximity to leukemia blasts through the binding of both PR1/HLA-A2 and CD3, resulting in T-cell mediated cytolysis of leukemia blasts. Here we successfully generated h8F4-BiTE proteins using a eukaryotic expression system and investigated binding characteristics, target specificities, and subsequent T-cell activation with the h8F4-BiTE. The h8F4 BiTE showed binding affinities in the nM range for PR1/HLA-A2 and CD3 moiety of T cells. Within 18 hours of h8F4-BiTE engagement with PR1 pulsed T2 cells, polyclonal T cells from healthy donors up-regulated surface expression of CD69 and down-regulated CD3 in a PR1/HLA-A2 specific and concentration dependent manner, suggesting successful T-cell activation. In conclusion, we developed a novel h8F4 BiTE antibody that recognizes both the CD3 on T cells and endogenous PR1/HLA-A2 complexes on myeloid leukemia, and demonstrated high affinity bindings and subsequent T cell activation. We envision our novel TCR-like BiTE antibody will provide a safer and more potent treatment option for patients with aggressive myeloid leukemias that will improve upon currently available highly toxic standard therapies. Citation Format: Amanda Cernosek Herrmann, Jin S. Im, Sijie Lu, Anna Sergueeva, Jeffrey Molldrem. Development of a novel TCR-like bi-specific T-cell engager targeting endogenous PR1/HLA-A2 leukemia antigen. [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 1497.
Abstract 4047: Salmonella protein AvrA activates the STAT3 signaling pathway in colon cancer
Authors: Rong Lu, Shaoping Wu, Yong-Guo Zhang, Yinglin Xia, Zhongren Zhou, Ikuko Tako, Hui Dong, Marc Bissonnette, Jun Sun
Journal: Cancer Research (2016)

Abstract Salmonella infection in humans can become chronic which leads to low grade persistent inflammation. These chronic infections increase the risk of several gastrointestinal diseases, including cancer. A recent study has shown that antibody against Salmonella flagellin was higher in colorectal cancer and pre-cancer cases than controls in two distinct populations in US and the Netherlands and that dietary intake is the one of the mediating factors, suggesting a potential link of Salmonella to colorectal cancer. Salmonella AvrA is a multifunctional protein that influences eukaryotic cell pathways by regulating ubiquitination and acetylation. In an animal model, we have demonstrated that infection with AvrA expressing Salmonella induces beta-catenin signals and enhances colonic tumorigenesis. Beta-catenin signaling is a key player in intestinal proliferation and tumorigenesis. The relative contributions of AvrA-induced proliferation and inflammation on tumorigenesis, however, are unknown. STAT3 is activated in chronically inflamed intestines in human inflammatory bowel diseases and in colitis-associated colon cancer. In the current study, mice were colonized with Salmonella AvrA-sufficient or AvrA-deficient bacterial strains. Then, inflammation-associated colon cancer was induced through the use of azoxymethane/dextran sulfate sodium. We determined that AvrA expressing bacteria activated the STAT3 pathway, which is predicted to increase inflammation, enhance proliferation, and promote tumorigenesis. Transcriptional activity of STAT3 and its target genes were up-regulated by Salmonella expressing AvrA, thus promoting proliferation and intestinal tumorigenesis. Our current findings provide new insights regarding a STAT3-dependent mechanism by which the specific bacterial product AvrA enhances the development of infection-associated colon cancer. Our observations also raise a note of caution regarding the use of mutant Salmonella organisms as vectors for ant-cancer therapy. Finally, these studies could suggest biomarkers (such as AvrA level in gut) to assess cancer risk in susceptible individuals and infection-related dysregulation of STAT/β-catenin signaling in colon cancer. Citation Format: Rong Lu, Shaoping Wu, Yong-Guo Zhang, Yinglin Xia, Zhongren Zhou, Ikuko Tako, Hui Dong, Marc Bissonnette, Jun Sun. Salmonella protein AvrA activates the STAT3 signaling pathway in colon 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 4047.
Public Health and Human Ecology
Journal: JAMA (1988)

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Abstract 1734: Body mass index, physical activity and risk of colorectal cancer in the Korean Multi-center Cancer Cohort (KMCC)
Authors: Sooyoung Cho, Aesun Shin, Sue K. Park, Hai-Rim Shin, Soung-Hoon Chang, Keun-Young Yoo
Journal: Cancer Research (2016)

Abstract Objectives: To examine the association between body mass index (BMI), physical activity and colorectal cancer risk among Korean adults. Methods: Data from the Korean Multi-center Cancer Cohort (KMCC) between 1993 and 2005 were analyzed. The study population comprised 12,379 subjects aged above 20 years old. The subjects were followed until December 31, 2011 (median follow-up of 10.1 years). Measured weight and height values was used to calculate BMI and self-reported total time spent for physical activity were used. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of BMI and physical activity for colorectal cancer risk. Results: Men who did moderate physical activity showed a lower risk for colorectal cancer (HR 0.35, 95% CI: 0.19-0.65 for 30-419 minutes compared to who spend less than 30 minutes a week doing moderate activities). We did not find any association between the total time of vigorous activities and muscle-strengthening activities and colorectal cancer risk in both men and women. Men with BMI of 25 or higher showed an increased risk for colorectal cancer compared to men with BMI of 18.5 to 22.9 (HR 1.64, 95% CI 0.94-2.88 for 25.0-29.9 kg/m2; HR 1.64, 95% CI 0.94-2.88 for greater than 30.0 kg/m2). Conclusions: Moderate physical activities were associated with lower colorectal cancer risk among Korean men. Citation Format: Sooyoung Cho, Aesun Shin, Sue K. Park, Hai-Rim Shin, Soung-Hoon Chang, Keun-Young Yoo. Body mass index, physical activity and risk of colorectal cancer in the Korean Multi-center Cancer Cohort (KMCC). [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 1734.
Abstract 550: Evaluating changes in T cell activation by measuring expression of IL-2, CTLA-4, NFAT, and NF-kB in Jurkat cells
Authors: Jacquelyn M. Bement, Yuko J. Miyamoto
Journal: Cancer Research (2016)

Abstract Insufficient stimulation of T cells due to activated checkpoint pathways can lead to ineffective clearance of tumor cells and thus, tumor growth and cancer. Developing methods to measure changes in the activation of such pathways are needed to evaluate the efficacy of immunotherapy approaches to treating cancer by altering T cell activation. Current methods that use measurments of IL-2 expression are limited by the fact that IL-2 is not specific to T cell activation and that it provides little insight into the mechanisms by which activation is affected. This project aims to address such limitations by determining whether changes in T cell activation can be effectively evaluated by measuring expression of CTLA-4, NFAT, and NF-kB, in addition to IL-2. Jurkat cells were cultured and activated with PMA (100 ng/mL) and ionomycin (500 ng/mL) for five hours. Staining for IL-2 and CTLA-4 with antibodies and transfection of the cells with genetic constructs that link NFAT and NF-kB to fluorescent proteins provided the means to link expression of fluorescence to expression of the molecules of interest. FACS analysis was then used to measure changes in the expression of the four signaling molecules in response to the induced changes in activation. Activation of the cells resulted in increased expression of all four molecules. Following activation, fluorescence due to CTLA-4, NFAT, and NF-kB expression changed by average fold increases of 2.58, 1.10 and 1.13, respectively. By measuring these key elements of T cell signaling pathways in addition to IL-2, these methods provide a potentially more effective alternative to current methods for evaluating the efficacy of immunotherapeutic treatments for cancer. Citation Format: Jacquelyn M. Bement, Yuko J. Miyamoto. Evaluating changes in T cell activation by measuring expression of IL-2, CTLA-4, NFAT, and NF-kB in Jurkat cells. [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 550.