tbuckley/cabot-search huggingface dataset:
Should the Results of the New EPOC Trial Change Practice in the Management of Patients With Resectable Metastatic Colorectal Cancer Confined to the Liver?
Authors: Bernard Nordlinger, Graeme J. Poston, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2014)

2][3] Patients with resectable CRC metastases limited to the liver represent an intermediate group in terms of their burden of disease and prognosis.5][6] In patients with resectable liver-limited CRC randomly assigned to treatment with surgery alone or perioperative chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX), the risk of cancer relapse after surgery in the cohort randomly assigned to perioperative FOLFOX was reduced by one quarter. 4A logical next step is to raise the question, Can outcomes be improved further by combining treatment with biologic and cytotoxic agents in the perioperative setting in this increasingly common patient population?The New EPOC (Eloxatin Peri-Operative Chemotherapy) trial was organized in the United Kingdom to address this question, and the results were published and recently updated. 7,8The trial compared two groups of patients who were determined to have resectable liver metastases, all of whom received perioperative chemotherapy with FOLFOX, oxaliplatin and capecitabine (XELOX), or fluorouracil, leucovorin, and irinotecan (FOLFIRI) with a random assignment to treatment with or without the addition of the epidermal growth factor receptor-blocking antibody cetuximab.The trial initially enrolled patients regardless of KRAS mutation status in the tumor but was later restricted to patients whose tumors were found to be KRAS (exon 2) wild type.On the basis of their study's outcome, the investigators concluded that combinations of cetuximab with chemotherapy in the perioperative setting for treatment of patients with potentially resectable colorectal liver metastases conferred no survival benefit and were actually detrimental.
Avulsion fracture of peroneus longus at the first metatarsal insertion: a case report
Authors: T Murakami, K Okamura, S Harada, M Setojima, Y Ikushiba, Y Miyamoto, S Li, M Yamada
Journal: British Journal of Sports Medicine (2004)

Reports of isolated avulsion fracture at the planter lateral base of the first metatarsal without injury of the tarsometatarsal joint are very rare. A 24 year old man sustained an avulsion fracture at the plantar lateral base of the first metatarsal. Normal alignment of metatarsal bones and tarsometatarsal joint was maintained. In this paper, we describe internal fixation of the displaced fragment using x ray and minimally invasive surgery with good results.
A Synergistic Therapeutic Scheme for Hyperglycemia and Nephrotic Disorders in Diabetes
Authors: Qingyi He, Xing Zhang, Baosan Han, Jianzhong Xu, Kanglai Tang, Zhiren Fu, Hao Yin
Journal: Theranostics (2014)

We previously demonstrated that the utilization of an electrospun scaffold could boost functional outputs of transplanted islets.In this study, we aim to develop a drug-eluting scaffold with a payload of pioglitazone to simultaneously rein in hyperglycemia and recoup lost renal functions in diabetic mice that underwent islet transplantation.The in vivo proliferation of islets was measured by a non-invasive bio-imaging technology whereas the blood insulin, blood glucose and renal proteins were assayed.The local stimulation of transplanted islets by pioglitazone saw an accelerated in vivo proliferation without apoptosis caused by the drug-eluting scaffold.In addition, pioglitazone contributed to an increased secretion of insulin and C-peptide 2, giving rise to an accelerated rein-in of hyperglycemia and enhanced tolerance of sudden oral glucose challenge.Moreover, the accelerated decrease of blood creatinine, urine creatinine and blood urea nitrogen suggested that pioglitazone contributed to the recovery of renal functions compromised by diabetes.Our bioengineering strategy effectively ameliorated hyperglycemia and associated nephrotic disorders, and shed a new light on an engineering approach to combat diabetes.
Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer
Authors: J. Beyer, P. Albers, R. Altena, J. Aparicio, C. Bokemeyer, J. Busch, R. Cathomas, E. Cavallin-Stahl, N.W. Clarke, J. Claßen, G. Cohn-Cedermark, A.A. Dahl, G. Daugaard, U. De Giorgi, M. De Santis, M. De Wit, R. De Wit, K.P. Dieckmann, M. Fenner, K. Fizazi, A. Flechon, S.D. Fossa, J.R. Germá Lluch, J.A. Gietema, S. Gillessen, A. Giwercman, J.T. Hartmann, A. Heidenreich, M. Hentrich, F. Honecker, A. Horwich, R.A. Huddart, S. Kliesch, C. Kollmannsberger, S. Krege, M.P. Laguna, L.H.J. Looijenga, A. Lorch, J.P. Lotz, F. Mayer, A. Necchi, N. Nicolai, J. Nuver, K. Oechsle, J. Oldenburg, J.W. Oosterhuis, T. Powles, E. Rajpert-De Meyts, O. Rick, G. Rosti, R. Salvioni, M. Schrader, S. Schweyer, F. Sedlmayer, A. Sohaib, R. Souchon, T. Tandstad, C. Winter, C. Wittekind
Journal: Annals of Oncology (2012)

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo
Authors: Toshiaki Ohteki, Hiroyuki Tada, Kazuto Ishida, Taku Sato, Chikako Maki, Taketo Yamada, Junji Hamuro, Shigeo Koyasu
Journal: The Journal of Experimental Medicine (2006)

Interleukin (IL)-15 is expressed in a variety of inflammatory diseases. However, the contribution of dendritic cell (DC)–derived IL-15 to the development of diseases is uncertain. Using established models of Propionibacterium acnes (P. acnes)– and zymosan-induced liver inflammation, we observed granuloma formation in the livers of wild-type (WT) and RAG-2−/− mice but not in those of IL-15−/− mice. We demonstrate that this is likely caused by an impaired sequential induction of IL-12, IFN-γ, and chemokines necessary for monocyte migration. Likewise, lethal endotoxin shock was not induced in P. acnes– and zymosan-primed IL-15−/− mice or in WT mice treated with a new IL-15–neutralizing antibody. In both systems, proinflammatory cytokine production was impaired. Surprisingly, neither granuloma formation, lethal endotoxin shock, nor IL-15 production was induced in mice deficient for DCs, and adoptive transfer of WT but not IL-15−/− DCs restored the disease development in IL-15−/− mice. Collectively, these data indicate the importance of DC-derived IL-15 as a mediator of inflammatory responses in vivo.
Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial
Authors: Hans Erik Bøtker, Rajesh Kharbanda, Michael R Schmidt, Morten Bøttcher, Anne K Kaltoft, Christian J Terkelsen, Kim Munk, Niels H Andersen, Troels M Hansen, Sven Trautner, Jens Flensted Lassen, Evald Høj Christiansen, Lars R Krusell, Steen D Kristensen, Leif Thuesen, Søren S Nielsen, Michael Rehling, Henrik Toft Sørensen, Andrew N Redington, Torsten T Nielsen
Journal: The Lancet (2010)
Advances in Nanoparticle Imaging Technology for Vascular Pathologies
Authors: Ananth Annapragada
Journal: Annual Review of Medicine (2015)

Nanoparticle imaging agents for vascular pathologies are in development, and some agents are already in clinical trials. Untargeted agents, with long circulation, are excellent blood-pool agents, but molecularly targeted agents have significant advantages due to the signal enhancement possible with nanoparticle presentation of the contrast agent molecules. Molecular targets that are accessible directly from the vasculature are optimal for such agents. Targets that are removed from the vasculature, such as those on tumor cell surfaces, have limited accessibility owing to the enhanced permeation and retention effect. Yet, efforts at molecular targeting have tested small molecules, peptides, antibodies, and most recently aptamers as possible targeting ligands. The future is bright for nanoparticle-based imaging of vascular pathologies.
Chest radiography and pneumonia in primary care: diagnostic yield and consequences for patient management
Authors: A. M. Speets, A. W. Hoes, Y. van der Graaf, S. Kalmijn, A. P. E. Sachs, W. P. Th. M. Mali
Journal: European Respiratory Journal (2006)

The current prospective cohort study assessed the diagnostic yield of chest radiography (CXR) in primary-care patients suspected of pneumonia. In total, 192 patients with a clinical suspicion of pneumonia aged ≥18 yrs were referred by their general practitioner (GP) for CXR to one of the three participating hospitals in the Netherlands. All GPs were asked to complete a standardised form before and after CXR. Pneumonia was diagnosed by GPs in 35 (18%) patients, of whom 27 (14%) patients had a positive CXR, and eight (4%) patients a negative CXR, but with an assumed high probability of pneumonia by the GP. CXR clearly influenced the diagnosis of pneumonia by the GP in 53% of the patients. CXR ruled out pneumonia in 47% and the probability of pneumonia substantially increased in 6% of the patients. Patient management changed after CXR in 69% of the patients, mainly caused by a reduction in medication prescription (from 43 to 17%) and more frequent reassurance of the patient (from 8 to 35%). In conclusion, pneumonia was frequently over diagnosed clinically by general practitioners. Chest radiography is a valuable diagnostic tool to substantially reduce the number of patients misdiagnosed and is particularly important for the exclusion of pneumonia in general practice.
Thrombocytopenia in association with a wandering spleen
Authors: Stephan Moll, J. Dirk Igelhart, Thomas L. Ortel
Journal: American Journal of Hematology (1996)

An ectopic, so-called wandering spleen is an uncommon occurrence. We present the case of a young woman who presented with abdominal pain and was found to have an enlarged spleen, located in the lower abdomen and pelvis. The possibility of lymphoma was entertained because of concomitant findings of thrombocytopenia and a possible mesenteric mass. The mass was subsequently found at laparotomy to be the tail of the malpositioned pancreas, and the thrombocytopenia resolved with splenectomy. Review of the literature indicates that lymphoma is an uncommon finding in wandering spleens, that wandering spleens are enlarged in most cases, and that thrombocytopenia, while uncommon, can be seen, in particular when associated with torsion of an elongated splenic pedicle. © 1996 Wiley-Liss, Inc.
Trading spaces: Computation, representation, and the limits of uninformed learning
Authors: Andy Clark, Chris Thornton
Journal: Behavioral and Brain Sciences (1997)

Some regularities enjoy only an attenuated existence in a body of training data. These are regularities whose statistical visibility depends on some systematic recoding of the data. The space of possible recodings is, however, infinitely large – it is the space of applicable Turing machines. As a result, mappings that pivot on such attenuated regularities cannot, in general, be found by brute-force search. The class of problems that present such mappings we call the class of “type-2 problems.” Type-1 problems, by contrast, present tractable problems of search insofar as the relevant regularities can be found by sampling the input data as originally coded. Type-2 problems, we suggest, present neither rare nor pathological cases. They are rife in biologically realistic settings and in domains ranging from simple animat (simulated animal or autonomous robot) behaviors to language acquisition. Not only are such problems rife – they are standardly solved! This presents a puzzle. How, given the statistical intractability of these type-2 cases, does nature turn the trick? One answer, which we do not pursue, is to suppose that evolution gifts us with exactly the right set of recoding biases so as to reduce specific type-2 problems to (tractable) type-1 mappings. Such a heavy-duty nativism is no doubt sometimes plausible. But we believe there are other, more general mechanisms also at work. Such mechanisms provide general (not task-specific) strategies for managing problems of type-2 complexity. Several such mechanisms are investigated. At the heart of each is a fundamental ploy – namely, the maximal exploitation of states of representation already achieved by prior, simpler (type-1) learning so as to reduce the amount of subsequent computational search. Such exploitation both characterizes and helps make unitary sense of a diverse range of mechanisms. These include simple incremental learning (Elman 1993), modular connectionism (Jacobs et al. 1991), and the developmental hypothesis of “representational redescription” (Karmiloff-Smith 1979; 1992). In addition, the most distinctive features of human cognition – language and culture – may themselves be viewed as adaptations enabling this representation/computation trade-off to be pursued on an even grander scale.
In Breast Carcinoma Tissue, Immature Dendritic Cells Reside within the Tumor, Whereas Mature Dendritic Cells Are Located in Peritumoral Areas
Authors: Diana Bell, Pascale Chomarat, Denise Broyles, George Netto, Ghada Moumneh Harb, Serge Lebecque, Jenny Valladeau, Jean Davoust, Karolina A. Palucka, Jacques Banchereau
Journal: The Journal of Experimental Medicine (1999)

We have analyzed the presence of immature and mature dendritic cells (DCs) within adenocarcinoma of the breast using immunohistochemistry. Immature DCs were defined by expression of CD1a-, Langerin-, and intracellular major histocompatibility complex class II-rich vesicles. Mature DCs were defined by expression of CD83 and DC-Lamp. Breast carcinoma cells were defined by morphology and/or cytokeratin expression. We demonstrate two levels of heterogeneity of DCs infiltrating breast carcinoma tissue: (a) immature CD1a(+) DCs, mostly of the Langerhans cell type (Langerin(+)), were retained within the tumor bed in 32/32 samples and (b) mature DCs, CD83(+)DC-Lamp(+), present in 20/32 samples, are confined to peritumoral areas. The high numbers of immature DCs found in the tumor may be best explained by high levels of macrophage inflammatory protein 3alpha expression by virtually all tumor cells. Confirming the immature/mature DC compartmentalization pattern, in vitro-generated immature DCs adhere to the tumor cells, whereas mature DCs adhere selectively to peritumoral areas. In some cases, T cells are clustering around the mature DCs in peritumoral areas, thus resembling the DC-T cell clusters of secondary lymphoid organs, which are characteristic of ongoing immune reactions.
Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/– mast cells
Authors: Yang Feng-Chun, David A. Ingram, Shi Chen, Cynthia M. Hingtgen, Nancy Ratner, Kelly R. Monk, Travis Clegg, Hilary White, Laura Mead, Mary Jo Wenning, David A. Williams, Reuben Kapur, Simon J. Atkinson, D. Wade Clapp
Journal: Journal of Clinical Investigation (2003)

The NF1 tumor suppressor gene encodes a GTPase-activating protein called neurofibromin that negatively regulates Ras signaling. Mutations in NF1 cause neurofibromatosis type 1 (NF1). The development of neurofibromas, which are complex tumors composed of multiple cell types, is a hallmark of NF1. Somatic inactivation of murine Nf1 in Schwann cells is necessary, but not sufficient, to initiate neurofibroma formation. Neurofibromas occur with high penetrance in mice in which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant (Nf1+/–) microenvironment. Mast cells infiltrate neurofibromas, where they secrete proteins that can remodel the ECM and initiate angiogenesis. Thus, identification of mechanisms responsible for mast cell migration to tumor microenvironments is important for understanding tumorigenesis and for designing potential therapies. Here, we show that homozygous Nf1 mutant (Nf1–/–) Schwann cells secrete Kit ligand (KitL), which stimulates mast cell migration, and that Nf1+/– mast cells are hypermotile in response to KitL. Furthermore, we link hyperactivation of the Ras-class IA-PI3K-Rac2 pathway to increased Nf1+/– mast cell migration. Thus, these studies identify a novel interaction between Nf1–/– Schwann cells and Nf1+/– mast cells that is likely to be important in neurofibroma formation.
Morphologic Responses to a Murine Erythroblastosis Virus&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: W H Kirsten, L A Mayer
Journal: JNCI Journal of the National Cancer Institute (1967)

A recently described mouse erythroblastosis virus (MEV) was passed to newborn W/Fu rats. The rats developed generalized malignant lymphomas after 6-7 months. Two separate serial cell-free passage series were initiated. Rat lymphomas induced erythroblastosis in less than 20% of the rats that died within 4 weeks after inoculation. The surviving rats remained apparently healthy for months until they died from lymphomas. Inoculation of newborn C3Hf/Gs mice with the same Filtrates caused only lymphomas in 35-50% of the mice after 3-8 months. The lymphomas were morphologically indistinguishable from thymic lymphomas induced in mice and rats by Gross' leukemia virus. A different morphologic response was observed by serial passages of spleen filtrates or plasma from rats with erythroblastosis. All rats died within 4 weeks with erythroblastosis. In addition, multiple sarcomas and polyostotic osteolytic lesions were found in most rats of such erythroblastosis passages. The same rat erythroblastosis filtrates induced erythroblastosis and sarcomas but no osteolytic lesions in C3Hf/Gs mice. Erythroblastosis in rats was similar to the disease previously described in mice, except for a marked normoblastosis and cerebral hemorrhages which did not occur in erythroblastotic mice. The sarcomas arose in multiple sites and were histologically undifferentiated. The osteolytic lesions were likewise multicentric in origin, affecting particularly the vertebrae and long bones. Their exact nature could not be determined.
Epidermal Growth Factor Receptor Activity Determines Response of Colorectal Cancer Cells to Gefitinib Alone and in Combination with Chemotherapy
Authors: Sandra Van Schaeybroeck, Anthi Karaiskou-McCaul, Donal Kelly, Daniel Longley, Leeona Galligan, Eric Van Cutsem, Patrick Johnston
Journal: Clinical Cancer Research (2005)

Up to now, there have been no established predictive markers for response to epidermal growth factor receptor (EGFR/HER1/erbB1) inhibitors alone and in combination with chemotherapy in colorectal cancer. To identify markers that predict response to EGFR-based chemotherapy regimens, we analyzed the response of human colorectal cancer cell lines to the EGFR-tyrosine kinase inhibitor, gefitinib (Iressa, AstraZeneca, Wilmington, DE), as a single agent and in combination with oxaliplatin and 5-fluorouracil (5-FU).Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet cell viability assays and analyzed by ANOVA. Apoptosis was measured by flow cytometry, poly(ADP-ribose) polymerase, and caspase 3 cleavage. EGFR protein phosphorylation was detected by Western blotting.Cell lines displaying high constitutive EGFR phosphorylation (a surrogate marker for EGFR activity) were more sensitive to gefitinib. Furthermore, in cell lines exhibiting low constitutive EGFR phosphorylation, an antagonistic interaction between gefitinib and oxaliplatin was observed, whereas in cell lines with high basal EGFR phosphorylation, the interaction was synergistic. In addition, oxaliplatin treatment increased EGFR phosphorylation in those cell lines in which oxaliplatin and gefitinib were synergistic but down-regulated EGFR phosphorylation in those lines in which oxaliplatin and gefitinib were antagonistic. In contrast to oxaliplatin, 5-FU treatment increased EGFR phosphorylation in all cell lines and this correlated with synergistic decreases in cell viability when 5-FU was combined with gefitinib.These results suggest that phospho-EGFR levels determine the sensitivity of colorectal cancer cells to gefitinib alone and that chemotherapy-mediated changes in phospho-EGFR levels determine the nature of interaction between gefitinib and chemotherapy.