tbuckley/cabot-search huggingface dataset:
Infant milk formulas differ regarding their allergenic activity and induction of T-cell and cytokine responses
Authors: H. Hochwallner, U. Schulmeister, I. Swoboda, M. Focke-Tejkl, R. Reininger, V. Civaj, R. Campana, J. Thalhamer, S. Scheiblhofer, N. Balic, F. Horak, M. Ollert, N. G. Papadopoulos, S. Quirce, Z. Szepfalusi, U. Herz, E. A. F. van Tol, S. Spitzauer, R. Valenta
Journal: Allergy (2016)

Several hydrolyzed cow's milk (CM) formulas are available for avoidance of allergic reactions in CM-allergic children and for prevention of allergy development in high-risk infants. Our aim was to compare CM formulas regarding the presence of immunoreactive CM components, IgE reactivity, allergenic activity, ability to induce T-cell proliferation, and cytokine secretion.A blinded analysis of eight CM formulas, one nonhydrolyzed, two partially hydrolyzed (PH), four extensively hydrolyzed (EH), and one amino acid formula, using biochemical techniques and specific antibody probes was conducted. IgE reactivity and allergenic activity of the formulas were tested with sera from CM-allergic patients (n = 26) in RAST-based assays and with rat basophils transfected with the human FcεRI, respectively. The induction of T-cell proliferation and the secretion of cytokines in Peripheral blood mononuclear cell (PBMC) culture from CM allergic patients and nonallergic individuals were assessed.Immune-reactive α-lactalbumin and β-lactoglobulin were found in the two PH formulas and casein components in one of the EH formulas. One PH formula and the EH formula containing casein components showed remaining IgE reactivity, whereas the other hydrolyzed formulas lacked IgE reactivity. Only two EH formulas and the amino acid formula did not induce T-cell proliferation and proinflammatory cytokine release. The remaining formulas varied regarding the induction of Th2, Th1, and proinflammatory cytokines.Our results show that certain CM formulas without allergenic and low proinflammatory properties can be identified and they may also explain different outcomes obtained in clinical studies using CM formulas.
Abstract 1640: SORBS1-related multiprotein complex regulates metastasis of cancer
Authors: Woo-Cheol Cho, Ja-Lok Ku
Journal: Cancer Research (2016)

Abstract Purpose: CAP (Cbl-associated protein), also known as Sorbin and SH3 domain-containing protein 1 is encoded by the SORBS1 gene. These proteins contain a conserved sorbin homology (SOHO) domain and three SH3 domains. CAP is an adaptor protein that has been associated with the actin cytoskeleton, signaling through receptor tyrosine kinases and cell adhesion. Although, CAP is proven to have many known functions, this protein is only reported in specific field of signaling pathway. Cell adhesion and actin dynamics which have been supposed to participate in CAP are crucial factors of cancer metastasis. The role of CAP has been described in the literature, although their specific roles remain to be clarified in cancer. Methods and materials: Colorectal cancer cell lines were transduced by lentivirus containing shRNA plasmid (shSORBS1 plasmid). To elucidate function of SORBS1 as regulator of cancer metastasis, western blotting, cell migration assay and immunoprecipitation assays were performed. Conclusion: According to the several reports of SORBS1 function, phosphorylation of ERK and mTOR was identified. Although ERK phosphorylation were not changed in normal condition, there were different aspects between control group and SORBS1 knockdown group with insulin treatment. Moreover, mTOR phosphorylation of SORBS1 knockdown group was less in the control group than in the normal condition. Immunoprecipitation of SORBS1 was performed to search for the binding compounds. We chose the AHNAK protein as the convincing candidate protein related with SORBS1. Several studies reported that AHNAK protein is related to proliferation and EMT by binding of specific signaling molecules. Indeed, there were remarkable differences of invasiveness ability between control group and knockdown group. Citation Format: Woo-Cheol Cho, Ja-Lok Ku. SORBS1-related multiprotein complex regulates metastasis of 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 1640.
Delta-Neutrophil Index Is a Useful Indicator for Initiation of Peripheral Blood Stem Cell Collection in Chemo-Mobilized Patients
Authors: June-Won Cheong, Soo-Jeong Kim, Yundeok Kim, Ji-Eun Jang, Hyun-Sung Park, Jung-Yeon Lee, Jin Seok Kim, Yoo Hong Min, Yu Ri Kim
Journal: Blood (2014)
Abstract 2203: Targeting monoclonal antibodies to the tumor microenvironment for cancer immunotherapy
Authors: Frederick L. Hall, Sant P. Chawla, Neal S. Chawla, Erlinda M. Gordon
Journal: Cancer Research (2016)

Abstract Therapeutic antibodies and immune checkpoint inhibitors can be delivered more efficiently to the tumor microenvironment (TME) by targeting the exposed collagenous (XC) proteins at the site/s of tumor invasion, stroma formation, and neoangiogenesis.Purpose: To assess the ability of bifunctional fusion polypepetides (mAb-Tropins) to selectively deliver monoclonal antibodies (mAbs) to the TME in tumor-bearing nude mice.Materials and Methods: Synthetic peptide probes and polypeptide aptamers (25-45 aa), fluorescein-labeled IgGs, and an anti-VEGF human mAb were tested in vitro in exposed collagen (XC)-agarose binding assays, in HUVEC cultures, and in vivo in a human xenograft model of pancreatic cancer in nude mice.Results: The XC-targeted mAb-Tropins, bound non-covalently to FITC-labeled IgGs [but not to truncated F(Ab’)2 fragments], exhibited selectivity for XC-agarose over control agarose matrices. Importantly, the biological activity of the XC/mAb-Tropin-bound anti-VEGF mAbs was fully preserved, as demonstrated by inhibition of endothelial cell proliferation in HUVEC cultures. In vivo, intense fluorescence was observed in tumors of mice injected with mAb-Tropin targeted IgGs at 15 and 60 minutes after intravenous injection, but not in non-targeted IgG-treated mice (see Figure below).Conclusions: Tumor XC-targeted mAb-Tropins are an effective method of delivering therapeutic mAbs precisely to the tumor compartments, with meaningful implications for cancer immunotherapy. Figure Figure Legend: The performance of mAb-Tropin 277 is evaluated in vitro in XC-binding assays and in vivo in a murine xenograft model of metastatic cancer. XC-agarose chromatography using mAb-Tropin 277 and FITC-IgGs, followed by stringent washing and analysis of column eluates and retentates (A,B), demonstrates aptamer-dependent binding of IgGs to XC-proteins (retentates), as well as depletion of the fluorescent IgGs from solution (column pass-through). The mAb-Tropin 277 dependent targeting of fluorescent IgGs (via the systemic circulation) to tumors is demonstrated in a murine metastatic cancer model (C). Taken together with the in vitro binding data—which showed that the bifunctional mAb-targeting onco-aptamers efficiently sequester IgGs (A) and concentrate the bound IgGs on collagen matrices (B)—this in vivo data indicates that mAb-Tropins concentrate and compartmentalize IgGs/mAbs within the TME (C). Citation Format: Frederick L. Hall, Sant P. Chawla, Neal S. Chawla, Erlinda M. Gordon. Targeting monoclonal antibodies to the tumor microenvironment for cancer immunotherapy. [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 2203.
Abstract 5076: Ras association (RalGDS/AF-6) domain family member integrates with notch signaling to regulate tumor cell migration
Authors: Lakshmi R. Perumalsamy, Mahalingam S.
Journal: Cancer Research (2016)

Abstract Tumor metastasis, the spread of tumor cells to distant tissues from its site of initiation is a multi-step and multi-factorial process. Hyperactivation of RAS pathway is reported in &amp;gt;50% of different cancers and is associated with metastasis and poor prognosis. Since Ras signaling pathway is essential for normal development, its been difficult to develop drugs against it in tumors. This led to the identification of several Ras effectors. Ras association (RalGDS/AF-6) domain family (RASSF) proteins are non-enzymatic effectors of Ras. RASSF7 is a member of the less characterized N-terminal RASSFs. Similar to other RASSFs, RASSF7 also associates with Ras. Several mutations within RASSF7 open reading frame as well as differential expression pattern were observed in various tumors. The role of RASSF7 and its downstream signaling is not yet clearly understood. Microarray analysis for RASSF7 identified several differentially regulated genes with enrichment for pathways including cell adhesion, inflammation, actin cytoskeleton and cell-cell communication suggesting that RASSF7 might regulate cell migration. Ectopic expression of RASSF7 inhibited cell migration of multiple cancer cell lines in vitro. RT-qPCR and western blotting analysis suggest that RASSF7 can transcriptionally upregulate Notch1 expression. Knockdown of Notch1 abrogated RASSF7 mediated inhibition of cell migration. Our experiments suggest that RASSF7 alters the localization of Notch1. Cross-talk Notch signaling is a key signaling pathway regulating tumor progression across several different cancers. Collectively, our data suggests that RASSF7 impinges on Notch1 to regulate cell migration. Citation Format: Lakshmi R. Perumalsamy, Mahalingam S. Ras association (RalGDS/AF-6) domain family member integrates with notch signaling to regulate tumor cell migration. [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 5076.
Association of AR-V7 and Prostate-Specific Antigen RNA Levels in Blood with Efficacy of Abiraterone Acetate and Enzalutamide Treatment in Men with Prostate Cancer
Authors: Fangfang Qu, Wanling Xie, Mari Nakabayashi, Haitao Zhang, Seong Ho Jeong, Xiaodong Wang, Kazumasa Komura, Christopher J. Sweeney, Oliver Sartor, Gwo-Shu Mary Lee, Philip W. Kantoff
Journal: Clinical Cancer Research (2016)

Abstract Purpose: We evaluated the association of PSA and androgen receptor splice variant-7 (AR-V7) transcript levels in patients' blood with time to treatment failure (TTF) and overall survival (OS) with abiraterone acetate and/or enzalutamide treatment in castration-resistant prostate cancer (CRPC) patients. Experimental Design: RNA levels of AR-V7 and PSA in peripheral blood collected before treatment were quantified using droplet digital-PCR in retrospective cohorts treated with abiraterone acetate (N = 81) or enzalutamide (N = 51) for CRPC. Multivariable Cox regression adjusted for known prognostic factors was used for analyses. Results: PSA transcripts were detected in 57% of abiraterone acetate–treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients [adjusted HR = 2.27 (95% confidence interval (CI) 1.26–4.10) and 2.60 (95% CI, 1.19–5.69); P = 0.006 and 0.017 in abiraterone acetate and enzalutamide cohorts, respectively]. Patients with a higher-AR-V7 transcript level had a shorter TTF with abiraterone acetate and enzalutamide in univariate analysis (median 8.0 months vs. 15.6 months, P = 0.046 in abiraterone acetate-cohort and 3.6 months vs. 5.6 months; P = 0.050 in enzalutamide cohort). In multivariable models, the association with TTF remained significant in the enzalutamide cohort (adjusted HR = 2.02; 95% CI, 1.01–4.05; P = 0.048), but statistically insignificant in the abiraterone acetate cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS. Conclusions: PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with abiraterone acetate or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells. Clin Cancer Res; 23(3); 726–34. ©2016 AACR.
Abstract 4937: Atm expression predicts ABT-888 and CPT-11 sensitivity in gastric cancer cells by mediating p53 independent regulation of cell cycle and apoptosis
Authors: Vinod Vijayasubhash, Shihui Tan, Fui Leng Yan, Natalia Liem, Wei Peng Yong
Journal: Cancer Research (2016)

Abstract Background: Identification of synthetically lethal cellular targets and synergistic drug combinations are important in cancer chemo therapy as they help to overcome treatment resistance and increase efficacy. The Ataxia Telangiectasia Mutated (ATM) kinase is a nuclear protein that plays a major role in the initiation of DNA repair signalling and cell cycle check points during DNA damage. Although ATM was shown to be associated with poor prognosis in gastric cancer, its potential implication as a predictive biomarker for cancer chemotherapy remains unexplored. The present study evaluated ATM induced synthetic lethality and its role in sensitization of gastric cancer cells to PARP and TOP1 inhibitors, ABT-888 and CPT-11 respectively. Methods: ATM expression in a panel of 10 gastric cancer cells were detected by immunohistochemistry and the IC50 against ABT-888 and CPT-11 was determined by MTS cell proliferation assay. The synergistic effect of ABT-888 and CPT-11 in gastric cancer cells was determined by cell cycle and DNA damage assays. ATM expression was knocked down using siRNA and its effect in P53 induced cell cycle regulation and apoptosis was determined by immunoblot analysis. Results and Conclusion: ATM deficiency was found to be associated with enhanced sensitivity to ABT-888 and CPT-11 monotherapy, hence suggesting a mechanism of synthetic lethality. Cells with high ATM expression showed reduced sensitivity to monotherapy, however showed a higher synergistic effect towards ABT-888 and CPT-11 combinational therapy that predisposed cells to enhanced drug sensitivity. Furthermore, ATM expression was shown to play a major role in cellular homeostasis by regulating cell cycle progression and apoptosis in a P53 independent manner. The present study highlights the clinical utility of ATM expression as a predictive marker for sensitivity of gastric cancer cell to PARP and TOP1 inhibition and provides a deeper mechanistic insight into ATM dependent regulation of cellular processes. Citation Format: Vinod Vijayasubhash, Shihui Tan, Fui Leng Yan, Natalia Liem, Wei Peng Yong. Atm expression predicts ABT-888 and CPT-11 sensitivity in gastric cancer cells by mediating p53 independent regulation of cell cycle and apoptosis. [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 4937.
European Society of Gastrointestinal Endoscopy – Establishing the key unanswered research questions within gastrointestinal endoscopy
Authors: Colin Rees, Wee Ngu, Jaroslaw Regula, Raf Bisschops, Adrian Saftoiu, Evelien Dekker, Ian Gralnek, Mihai Ciocirlan, Mario Dinis-Ribeiro, Rodrigo Jover, Søren Meisner, Cristiano Spada, Cesare Hassan, Roland Valori, Tomas Hucl, Olivier Le Moine, Dirk Domagk, Michal Kaminski, Michael Bretthauer, Matthew Rutter, Lars Aabakken, Thierry Ponchon, Paul Fockens, Peter Siersema
Journal: Endoscopy (2016)

<b>Background and study aim:</b> Gastrointestinal endoscopy is a rapidly evolving research field. The European Society of Gastrointestinal Endoscopy (ESGE) plays a key role in shaping opinion and endoscopy activity throughout Europe and further afield. Establishing key unanswered questions within the field of endoscopy and prioritizing those that are important enables researchers and funders to appropriately allocate resources. <b>Methods:</b> Over 2 years, the ESGE Research Committee gathered information on research priorities and refined them through a modified Delphi approach. Consultations were held with the ESGE Governing Board and Quality Improvement Committee to identify important unanswered questions. Research workshops were held at the 21st United European Gastroenterology Week. Research questions were refined by the ESGE Research Committee and Governing Board, compiled into an online survey, and distributed to all ESGE members, who were invited to rank each question by priority. <b>Results:</b> The final questionnaire yielded 291 responses from over 60 countries. The three countries with the highest response rates were Spain, Italy, and United Kingdom. Most responders were from teaching hospitals (62 %) and were specialist endoscopists (51 %). Responses were analyzed with weighted rankings, resulting in prioritization of 26 key unanswered questions. The top ranked generic questions were: 1) How do we define the correct surveillance interval following endoscopic diagnosis? 2) How do we correctly utilize advanced endoscopic imaging? 3) What are the best markers of endoscopy quality? <b>Conclusion:</b> Following this comprehensive process, the ESGE has identified and ranked the key unanswered questions within the field of gastrointestinal endoscopy. Researchers, funders, and journals should prioritize studies that seek to answer these important questions.
Abstract 842: The NALP3 inflammasome and IL-1â signaling link asbestos-induced inflammation with the development of malignant mesothelioma
Authors: Yuwaraj Kadariya, Craig W. Menges, Jacqueline Talarchek, Qi Cai, Andres J. Klein-Szanto, Ralph A. Pietrofesa, Melpo Christofidou-Solomidou, Brooke T. Mossman, Arti Shukla, Joseph R. Testa
Journal: Cancer Research (2016)

Abstract Exposure to asbestos is causally associated with the development of malignant mesothelioma (MM), a cancer of cells lining the internal body cavity. MM is an aggressive cancer that is resistant to all current therapies. Once inhaled or ingested, asbestos causes inflammation in and around tissues that come in contact with these carcinogenic fibers. Recent studies suggest that inflammation is a major contributing factor in the development of many types of cancer, including MM. The NALP3 inflammasome, including the component ASC, is an important mediator of inflammation that senses extracellular insults, such as infection or asbestos, and activates a signaling cascade resulting in release of mature IL-1â and recruitment of inflammatory cells. To determine if inflammasome-mediated inflammation contributes to asbestos-induced MM, we chronically exposed Asc-deficient mice to asbestos and evaluated tumor incidence, latency and overall survival. Asc-deficient mice showed a significant delay in tumor onset compared to wild-type animals, suggesting that the NALP3 inflammasome plays a role in MM carcinogenesis. We also tested whether inflammation-related release of IL-1â promotes tumor development in an accelerated mouse model of asbestos-induced MM. Nf2+/-;Cdkn2a+/- mice exposed to asbestos in the presence of the IL-1â antagonist, anakinra, showed a 50% longer disease-free survival than in similarly exposed mice given vehicle control, consistent with IL-1â signaling contributing significantly to MM development. Collectively, these studies provide evidence for a link between asbestos-associated inflammation/IL-1â signaling and the development of MM; furthermore, these findings provide rationale for chemoprevention strategies targeting inflammation-related IL-1â signaling in high risk, asbestos-exposed populations. Citation Format: Yuwaraj Kadariya, Craig W. Menges, Jacqueline Talarchek, Qi Cai, Andres J. Klein-Szanto, Ralph A. Pietrofesa, Melpo Christofidou-Solomidou, Brooke T. Mossman, Arti Shukla, Joseph R. Testa. The NALP3 inflammasome and IL-1â signaling link asbestos-induced inflammation with the development of malignant mesothelioma. [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 842.
Abstract 4104: Characterization and validation of an implantable chronic lung imaging window
Authors: David Entenberg, Allison Harney, Sonia E. Voiculescu, Yarong Wang, Maja Oktay, John Condeelis
Journal: Cancer Research (2016)

Abstract Metastatic disease is the major cause of cancer mortality and is responsible for over 1/2 million deaths each year in the U.S. alone. Of the three most common sites of metastasis observed clinically (bone, lung and liver), the most difficult to study using intravital microscopy is the lung; a delicate organ in perpetual motion. Recent advances in intravital microscopy have enabled visualization of the live intact lung, but are limited in the duration over which they can be utilized (hours) and require major invasive surgeries. Both of these limitations reduce their usefulness in the study of single cell events in the lung and are susceptible to introducing artefacts. We report the development of a novel, minimally invasive surgical protocol for the implantation of a long-lasting lung imaging window. Once implanted, this window allows for the repeated, non-invasive visualization of living, breathing lung tissue over a period of two weeks without the need for ventilation, vacuum plates, or gated imaging equipment. Here we characterize and validate the use of this window in living mice. The window is well tolerated, does not cause infection or inflammation, and offers a 4mm view of the left lung. We utilize it to visualize, with single cell resolution, the progression of experimental metastasis from the arrival of a single cell to the formation of micro-metastases. The development of this novel optical window will allow visualization of, with single cell resolution, tumor microenvironments and metastatic progression within the lung over extended periods of time. This approach to imaging live lung tissue has the potential to reveal the mechanisms underlying many diseases affecting the lung as well as the means to directly evaluate responses to therapeutics in in real time and within a single animal. Citation Format: David Entenberg, Allison Harney, Sonia E. Voiculescu, Yarong Wang, Maja Oktay, John Condeelis. Characterization and validation of an implantable chronic lung imaging window. [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 4104.