tbuckley/cabot-search huggingface dataset:
Extended Lymph Node Dissection for Gastric Cancer: Who May Benefit? Final Results of the Randomized Dutch Gastric Cancer Group Trial
Authors: H.H. Hartgrink, C.J.H. van de Velde, H. Putter, J.J. Bonenkamp, E. Klein Kranenbarg, I. Songun, K. Welvaart, J.H.J.M. van Krieken, S. Meijer, J.T.M. Plukker, P.J. van Elk, H. Obertop, D.J. Gouma, J.J.B. van Lanschot, C.W. Taat, P.W. de Graaf, M.F. von Meyenfeldt, H. Tilanus, M. Sasako
Journal: Journal of Clinical Oncology (2004)

The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years.Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years.A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years.Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.
THE EFFECTS OF BLOOD LOSS AND BLOOD DESTRUCTION UPON THE ERYTHROID CELLS IN THE BONE MARROW OF RABBITS
Authors: Brandt F. Steele
Journal: The Journal of Experimental Medicine (1933)

The relative proportion of the various sorts of erythroid cells of the bone marrow has been determined after acute and chronic hemorrhage and after damage to the marrow with acetyl phenylhydrazine. The normal erythroid pattern shows megaloblasts and erythroblasts in the lowest percentage, then normoblasts, reticulocytes, and mature erythrocytes respectively, in increasing proportions. All three states studied show an increasing "shift to the left" up to a condition after acetyl phenylhydrazine, in which the erythroblasts and megaloblasts exceed the mature erythrocytes. The marrow pattern finds direct expression in terms of the cells of the blood.
4-Aminobiphenyl-Induced Liver and Urinary Bladder DNA Adduct Formation in Cyp1a2(-/-) and Cyp1a2(+/+) Mice
Authors: Y. Tsuneoka, T. P. Dalton, M. L. Miller, C. D. Clay, H. G. Shertzer, G. Talaska, M. Medvedovic, D. W. Nebert
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Metabolites of the potent human carcinogen 4-aminobiphenyl (ABP) induce oxidative stress and form DNA adducts that are associated with hepatic and urinary bladder toxicity and bladder tumorigenesis. Results of in vitro and cell culture studies have suggested that cytochrome P450 1A2 (CYP1A2) is the major metabolic activator of ABP. We used Cyp1a2(–/–) knockout mice to examine the role of CYP1A2 in ABP–DNA adduct formation in the liver and the bladder. Methods: Cyp1a2(+/+) wild-type and Cyp1a2(–/–) mice (total of four mice per group) were treated topically with 10 mg/kg ABP for various times, with or without pretreatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an inducer of CYP1A2 activity. We evaluated ABP-induced toxicity by carrying out quantitative histology (of the liver, skin, and bladder), oxidative stress by measuring hepatic thiol levels, and liver and bladder DNA adduct formation by using 32P-postlabeling. Data were analyzed by general linear models and analysis of variance. All statistical tests were two-sided. Results: At the experimental times selected, we observed no histologic evidence of toxicity in the liver, skin, or bladder. Overall, Cyp1a2(+/+) mice had fewer DNA adducts 24 hours after ABP treatment than similarly treated Cyp1a2(–/–) mice. Compared with male mice, female mice had more DNA adducts in the liver but fewer adducts in the bladder, regardless of Cyp1a2 genotype. TCDD pretreatment was associated with a decrease in ABP–DNA adduct levels overall. After 2 hours of ABP treatment, hepatic thiol levels underwent statistically significant declines of severalfold in Cyp1a2(+/+) and Cyp1a2(–/–) males and in Cyp1a2(–/–) females. Conclusions: Contrary to our expectations, CYP1A2 expression was not associated with ABP-induced hepatic oxidative stress or with ABP–DNA adduct formation. Either CYP1A2 is not the major metabolic activator of ABP or other enzymes metabolically activate ABP in mice in the absence of CYP1A2.
Plasminogen Is a Joint‐Specific Positive or Negative Determinant of Arthritis Pathogenesis in Mice
Authors: Harini Raghu, Alice Jone, Carolina Cruz, Cheryl L. Rewerts, Malinda D. Frederick, Sherry Thornton, Jay L. Degen, Matthew J. Flick
Journal: Arthritis & Rheumatology (2014)

A fundamental metric in the diagnosis of arthropathies is the pattern of joint involvement, including differences in proximal versus distal joints and patterns of symmetric or asymmetric disease. The basis for joint selectivity among arthritides and/or within a defined disease such as rheumatoid arthritis remains enigmatic. Coagulation and fibrinolytic activity are observed in both experimental animals with inflammatory joint disease and patients with inflammatory arthritis. However, the contribution of specific hemostatic factors to joint disease is not fully defined. We sought to determine the contribution of the fibrinolytic protease, plasminogen, to tumor necrosis factor α (TNFα)-driven arthritis in distinct joints in mice.The impact of plasminogen and/or fibrinogen genetic deficiencies on arthritis progression was evaluated in Tg197 mice genetically predisposed to spontaneous, nonabating, and erosive polyarthritis due to exuberant human TNFα expression.Elimination of plasminogen in Tg197 mice significantly exacerbated the incidence and severity of arthritis within the paw joints, but simultaneously and dramatically diminished the entire spectrum of pathologies within the knee joints of the same animals. These opposing outcomes were both mechanistically linked to fibrin(ogen), in that superimposing fibrinogen deficiency reversed both the proarthritic phenotype in the paws and arthritis resistance in the knees of plasminogen-deficient mice. Intriguingly, the change in disease severity in the knees, but not the paws, was associated with a plasminogen-dependent reduction in matrix metalloproteinase 9 activity.Plasminogen is a key molecular determinant of inflammatory joint disease capable of simultaneously driving or ameliorating arthritis pathogenesis in distinct anatomic locations in the same subject.
A defect in hematopoietic stem cell migration explains the nonrandom X-chromosome inactivation in carriers of Wiskott-Aldrich syndrome
Authors: Catherine Lacout, Elie Haddad, Siham Sabri, Fedor Svinarchouk, Loic Garçon, Claude Capron, Adlen Foudi, Rym Mzali, Scott B. Snapper, Fawzia Louache, William Vainchenker, Dominique Duménil
Journal: Blood (2003)
Comparison of Kinome Profiles of Barrett's Esophagus with Normal Squamous Esophagus and Normal Gastric Cardia
Authors: Jantine W.P.M. van Baal, Sander H. Diks, Ronald J.A. Wanders, Agnieskza M. Rygiel, Francesca Milano, Jos Joore, Jacques J.G.H.M. Bergman, Maikel P. Peppelenbosch, Kausilia K. Krishnadath
Journal: Cancer Research (2006)

Abstract The precursor metaplastic mucosal lesion that predisposes for esophageal adenocarcinoma is Barrett's esophagus. Because the signal transduction events that occur in Barrett's esophagus are poorly understood, this study aimed at generating a comprehensive description of cellular kinase activity in Barrett's esophagus, normal squamous esophagus, and gastric cardia to gain more insight into the pathogenesis of Barrett's esophagus. Peptide arrays, exhibiting 1,176 specific consensus sequences for protein kinases, were used to produce a global analysis of cellular kinase activity in biopsies of Barrett's esophagus, and results were compared with the neighboring cardia and squamous epithelia. Several differences in kinase activity using immunoblot analysis and enzyme activity assays were validated in biopsies of 27 Barrett's esophagus patients. Three unique kinome profiles are described and compared. We identified cascades of activated kinases showing that mitogen-activated protein kinase and epidermal growth factor receptor activity are both significantly altered in Barrett's esophagus compared with squamous and gastric cardia epithelia. Another novel finding is that the glycolysis pathway is significantly up-regulated in Barrett's esophagus, which is illustrated by an up-regulated pyruvate kinase activity. Here, the unique kinome profile of Barrett's esophagus is made available as a comprehensive database. Several signaling pathways are revealed as specifically expressed in Barrett's esophagus when compared with the adjacent normal epithelia. These unique findings provide novel insight in the pathogenesis of Barrett's esophagus that will ultimately help to resolve the increasing problem of Barrett's esophagus and prevention of esophageal adenocarcinoma. (Cancer Res 2006; 66(24): 11605-12)
Evaluation of prostate segmentation algorithms for MRI: The PROMISE12 challenge
Authors: Geert Litjens, Robert Toth, Wendy van de Ven, Caroline Hoeks, Sjoerd Kerkstra, Bram van Ginneken, Graham Vincent, Gwenael Guillard, Neil Birbeck, Jindang Zhang, Robin Strand, Filip Malmberg, Yangming Ou, Christos Davatzikos, Matthias Kirschner, Florian Jung, Jing Yuan, Wu Qiu, Qinquan Gao, Philip “Eddie” Edwards, Bianca Maan, Ferdinand van der Heijden, Soumya Ghose, Jhimli Mitra, Jason Dowling, Dean Barratt, Henkjan Huisman, Anant Madabhushi
Journal: Medical Image Analysis (2013)
Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response
Authors: Andreas Rosenwald, Eric Y. Chuang, R. Eric Davis, Adrian Wiestner, Ash A. Alizadeh, Diane C. Arthur, James B. Mitchell, Gerald E. Marti, Daniel H. Fowler, Wyndham H. Wilson, Louis M. Staudt
Journal: Blood (2004)
Murine models of asthma
Authors: J.C. Kips, G.P. Anderson, J.J. Fredberg, U. Herz, M.D. Inman, M. Jordana, D.M. Kemeny, J. Lötvall, R.A. Pauwels, C.G. Plopper, D. Schmidt, P.J. Sterk, A.J.M. Van Oosterhout, B.B. Vargaftig, K.F. Chung
Journal: European Respiratory Journal (2003)

In vivo animal models can offer valuable information on several aspects of asthma pathogenesis and treatment. The mouse is increasingly used in these models, mainly because this species allows for the application in vivo of a broad range of immunological tools, including gene deletion technology. Mice, therefore, seem particularly useful to further elucidate factors influencing the response to inhaled allergens. Examples include: the role of immunoregulatory mechanisms that protect against T-helper cell type 2 cell development; the trafficking of T-cells; and the contribution of the innate immunity. However, as for other animal species, murine models also have limitations. Mice do not spontaneously develop asthma and no model mimics the entire asthma phenotype. Instead, mice should be used to model specific traits of the human disease. The present task force report draws attention to specific aspects of lung structure and function that need to be borne in mind when developing such models and interpreting the results. In particular, efforts should be made to develop models that mimic the lung function changes characteristic of asthma as closely as possible. A large section of this report is therefore devoted to an overview of airway function and its measurement in mice.
BLOOD PRESSURE AND ERYTHROPOIETIN
Authors: C.R.V. Tomson, M.C. Venning, M.K. Ward, G. Mayer, Th. Stefenelli, E.M. Cada, J. Thum, H.K. Stummvoll, H. Graf, M.E. Edmunds, J. Walls
Journal: The Lancet (1988)
Prevention of adhesions in gynaecological endoscopy
Authors: C. Nappi, A. Di Spiezio Sardo, E. Greco, M. Guida, S. Bettocchi, G. Bifulco
Journal: Human Reproduction Update (2007)

Adhesions resulting from gynaecological endoscopic procedures are a major clinical, social and economic concern, as they may result in pelvic pain, infertility, bowel obstruction and additional surgery to resolve such adhesion-related complications. Although the minimally invasive endoscopic approach has been shown to be less adhesiogenic than traditional surgery, at least with regard to selected procedures, it does not totally eliminate the problem. Consequently, many attempts have been made to further reduce adhesion formation and reformation following endoscopic procedures, and a wide variety of strategies, including surgical techniques, pharmacological agents and mechanical barriers have been advocated to address this issue. The present review clearly indicates that there is no single modality proven to be unequivocally effective in preventing post-operative adhesion formation either for laparoscopic or for hysteroscopic surgery. Furthermore, the available adhesion-reducing substances are rather expensive. Since excellent surgical technique alone seems insufficient, further research is needed on an adjunctive therapy for the prevention and/or reduction of adhesion formation following gynaecological endoscopic procedures.
Immunologic Purging of Autologous Peripheral Blood Stem Cell Products Based on CD34 and CD133 Expression Can Be Effectively and Safely Applied in Half of the Acute Myeloid Leukemia Patients
Authors: Nicole Feller, Marjolein A. van der Pol, Taco Waaijman, Geert W.D. Weijers, Guus Westra, Gert J. Ossenkoppele, Gerrit J. Schuurhuis
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Several studies have shown survival benefit by autologous stem cell transplantation in acute myeloid leukemia (AML) after purging of grafts. This has, however, not been confirmed in randomized studies due to high toxicity of purging modalities for normal progenitor/stem cells. In this study, we investigated whether positive selection for CD34+ and/or CD133+ cells, which results in high recovery of normal progenitor/stem cells, is applicable for purging AML grafts. Experimental Design: Positive selections of normal stem cells using CD34 and/or CD133 can be done if one or both markers are absent or have dim expression and remain so during the course of the disease. Marker expressions in newly diagnosed AML were measured with flow cytometry using a cutoff value for positivity of 1%. Stability of marker expression was studied by pairwise comparison of material at diagnosis and relapse. Leukemia associated phenotype expression was used to measure the efficacy of tumor cell reduction. Results: In newly diagnosed AML (n = 165), we found no CD34 and/or CD133 expression in 32% of the cases and dim expression in 20% of the cases. No increase in the percentage of CD34+ cells (n = 44) and CD133+ cells (n = 29) was found in corresponding relapses. Positive selection using grafts contaminated with AML blasts, showing either no or dim expression of CD34 or CD133, resulted in a 3 to 4 log tumor cell reduction (n = 11) with median 50% recovery of normal stem cells. Conclusions: Purging by positive selection of CD34+ and/or CD133+ cells can safely, effectively, and reproducibly be applied in about 50% of AML cases.
Reply to V. Paleri et al and J.A. de Souza et al
Authors: Max Lonneux, Marc Hamoir
Journal: Journal of Clinical Oncology (2010)

We read with great interest the comments of Paleri and Zammit-Maempel 1 and de Souza and Cohen. 2 First, we would like to emphasize that the study design was made to evaluate the additional value of fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging over conventional staging (based on a panel of procedures including the conventional imaging modalities [CIMs] of computed tomography [CT] or magnetic resonance imaging [MRI]) and not to perform a head-to-head sensitivity/specificity comparison of one imaging modality versus another modality, as has been done in many previous studies.The key issue is not whether PET-FDG should replace conventional staging but whether PET-FDG should be added to CIMs.Head-to-head comparisons have consistently shown comparable nodal staging accuracies for CT, MRI, and PET.In a clinical setting, the purpose of multiple imaging techniques is to increase the accuracy of the work-up, and in this study, only the discordant cases were worth analyzing.The diagnostic accuracy of conventional imaging cannot be stated as poor; indeed, PET and CIM were concordant in 57% of the patients (133 of 233 patients), and in discordant patients, PET was more frequently correct than CIM.Reporting the sensitivity/specificity figures in the concordant group was beyond the scope of this study.As a matter of fact, there is a lack of gold standard in the group of patients in whom PET and conventional methods were concordant because no histopathology was available in 115 of 134 patients.Indeed, referred physicians went on to treatment concordant patients, whereas discordant patients were more frequently further explored because it was required in the study design.Therefore, although an analysis of the diagnostic accuracies on the whole patient population was not possible, we think that this analysis has been performed specifically in previous studies.The impact on patient management was also related to the detection (or exclusion) of metastatic disease (thus, beyond N stage diagnostic accuracy).Again, this study was not designed to make head-to-head comparisons with CIM, and our conclusion is not to substitute CIM with PET but, instead, to use PET as an additional imaging method to increase the pretherapeutic staging of head and neck squamous cell carcinomas.de Souza and Cohen regret that the clinical and pathologic characteristics of the 100 discordant patients were not reported.We acknowledge that this information would have been interesting within
Auditing Access to Specialty Care for Children with Public Insurance
Authors: Joanna Bisgaier, Karin V. Rhodes
Journal: New England Journal of Medicine (2011)

Health care reform has expanded eligibility to public insurance without fully addressing concerns about access. We measured children's access to outpatient specialty care to identify disparities in providers' acceptance of Medicaid and the Children's Health Insurance Program (CHIP) versus private insurance.Between January and May 2010, research assistants called a stratified, random sample of clinics representing eight specialties in Cook County, Illinois, which has a high proportion of specialists. Callers posed as mothers of pediatric patients with common health conditions requiring outpatient specialty care. Two calls, separated by 1 month, were placed to each clinic by the same person with the use of a standardized clinical script that differed by insurance status.We completed 546 paired calls to 273 specialty clinics and found significant disparities in provider acceptance of Medicaid-CHIP versus private insurance across all tested specialties. Overall, 66% of Medicaid-CHIP callers (179 of 273) were denied an appointment as compared with 11% of privately insured callers (29 of 273) (relative risk, 6.2; 95% confidence interval [CI], 4.3 to 8.8; P<0.001). Among 89 clinics that accepted both insurance types, the average wait time for Medicaid-CHIP enrollees was 22 days longer than that for privately insured children (95% CI, 6.8 to 37.5; P=0.005).We found a disparity in access to outpatient specialty care between children with public insurance and those with private insurance. Policy interventions that encourage providers to accept patients with public insurance are needed to improve access to care.
An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer
Authors: Katherine Stemke-Hale, Ana Maria Gonzalez-Angulo, Ana Lluch, Richard M. Neve, Wen-Lin Kuo, Michael Davies, Mark Carey, Zhi Hu, Yinghui Guan, Aysegul Sahin, W. Fraser Symmans, Lajos Pusztai, Laura K. Nolden, Hugo Horlings, Katrien Berns, Mien-Chie Hung, Marc J. van de Vijver, Vicente Valero, Joe W. Gray, René Bernards, Gordon B. Mills, Bryan T. Hennessy
Journal: Cancer Research (2008)

Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy-based sequencing and reverse-phase protein arrays to 547 human breast cancers and 41 cell lines, we determined the subtype specificity and signaling effects of PIK3CA, AKT, and PTEN mutations and the effects of PIK3CA mutations on responsiveness to PI3K inhibition in vitro and on outcome after adjuvant tamoxifen. PIK3CA mutations were more common in hormone receptor-positive (34.5%) and HER2-positive (22.7%) than in basal-like tumors (8.3%). AKT1 (1.4%) and PTEN (2.3%) mutations were restricted to hormone receptor-positive cancers. Unlike AKT1 mutations that were absent from cell lines, PIK3CA (39%) and PTEN (20%) mutations were more common in cell lines than tumors, suggesting a selection for these but not AKT1 mutations during adaptation to culture. PIK3CA mutations did not have a significant effect on outcome after adjuvant tamoxifen therapy in 157 hormone receptor-positive breast cancer patients. PIK3CA mutations, in comparison with PTEN loss and AKT1 mutations, were associated with significantly less and inconsistent activation of AKT and of downstream PI3K/AKT signaling in tumors and cell lines. PTEN loss and PIK3CA mutation were frequently concordant, suggesting different contributions to pathophysiology. PTEN loss rendered cells significantly more sensitive to growth inhibition by the PI3K inhibitor LY294002 than did PIK3CA mutations. Thus, PI3K pathway aberrations likely play a distinct role in the pathogenesis of different breast cancer subtypes. The specific aberration present may have implications for the selection of PI3K-targeted therapies in hormone receptor-positive breast cancer.