tbuckley/cabot-search huggingface dataset:
Clinical epidemiology of childhood cancer in Central America and Caribbean countries
Authors: M.G. Valsecchi, G. Tognoni, M. Bonilla, N. Moreno, F. Baez, C. Pacheco, A.P. Hernandez, F. Antillon-Klussmann, S. Machin, R. Cabanas, M. Navarrete, R. Nieves, P. De Lorenzo, G. Masera
Journal: Annals of Oncology (2004)

BackgroundCountries with scarce resources have the right to appropriate essential health care but very few reports discuss how this can be achieved. We assessed the survival of a large cohort of pediatric oncological patients to provide hard data on which to base realistic evaluation and planning schemes.Patients and methodsThis multicenter retrospective survey covered consecutively diagnosed and treated patients admitted to eight national level hospitals in seven countries in Central America and the Caribbean. The research protocol was discussed extensively, so the data to be collected and the criteria for their evaluation were clearly pre-defined. We analysed 2214 patients diagnosed between 1996 and 1999 with various cancers, classified as hemato-oncological disorders (70%) and solid tumors (30%).ResultsThree-year overall survival was 48.4% [standard error (SE) 1.3]. Detailed analysis of acute lymphoblastic leukemia highlighted the wide intercountry variability: 3-year survival was 62.2% (SE 5.3) in Cuba, 74.2% (SE 3.3) in Costa Rica, 61.7% (SE 4.9) in Nicaragua, and lower in the other four countries.ConclusionsThe yield of diagnostic-therapeutic protocols depends largely on the context of care in which they are applied. This paper documents the importance of including epidemiological research in interventions for cooperation in complex health areas such as pediatric oncology.
Tandem Duplication Producing a Novel Oncogenic <i>BRAF</i> Fusion Gene Defines the Majority of Pilocytic Astrocytomas
Authors: David T.W. Jones, Sylvia Kocialkowski, Lu Liu, Danita M. Pearson, L. Magnus Bäcklund, Koichi Ichimura, V. Peter Collins
Journal: Cancer Research (2008)

Abstract Brain tumors are the most common solid tumors of childhood, and pilocytic astrocytomas (PA) are the most common central nervous system tumor in 5 to 19 year olds. Little is known about the genetic alterations underlying their development. Here, we describe a tandem duplication of ∼2 Mb at 7q34 occurring in 66% of PAs. This rearrangement, which was not observed in a series of 244 higher-grade astrocytomas, results in an in-frame fusion gene incorporating the kinase domain of the BRAF oncogene. We further show that the resulting fusion protein has constitutive BRAF kinase activity and is able to transform NIH3T3 cells. This is the first report of BRAF activation through rearrangement as a frequent feature in a sporadic tumor. The frequency and specificity of this change underline its potential both as a therapeutic target and as a diagnostic tool. [Cancer Res 2008;68(21):8673–7]
Alteration of Gene Expression in Macroscopically Normal Colonic Mucosa from Individuals with a Family History of Sporadic Colon Cancer
Authors: Chun-Yi Hao, Dan H. Moore, Patrick Wong, James L. Bennington, Nancy M. Lee, Ling-Chun Chen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We have shown that the expression of several genes associated with human colon cancer is altered in the morphologically normal colonic mucosa (MNCM) of APCmin mice and humans with colon cancers. To determine whether these alterations also occur in the MNCM of individuals who have not developed colon cancer but are at high risk of doing so, we measured gene expression in the MNCM of individuals with a family history of colon cancer. Methods: Expression of 16 genes in the MNCM of 12 individuals with a first-degree relative with sporadic colon cancer and 16 normal controls were measured by quantitative reverse transcription-PCR. All subjects tested had normal colonoscopic examinations. Biopsy samples of MNCM were obtained from the ascending, transverse, descending, and rectosigmoid regions of the colon (2-8 biopsy samples were obtained from each region). Results: Relative to normal controls, the expression of several genes, including PPAR-γ, SAA1, and IL-8 were significantly altered in the macroscopically normal rectosigmoid mucosa from individuals with a family history of colon cancer. Conclusions: Molecular abnormalities that precede the appearance of adenomatous polyp are present in the MNCM of individuals who have a family history of colon cancer. This observation raises the possibility of screening for individuals who are at an increased risk of developing colon cancer by analysis of gene expression in rectosigmoid biopsy samples. To assess this possibility, prospective studies will be needed to determine whether or not altered gene expression is associated with the subsequent development of adenomatous polyps and/ or colonic carcinomas.
Functional Aspects of a Second Mechanism of Candidacidal Activity by Human Neutrophils
Authors: Robert I. Lehrer
Journal: Journal of Clinical Investigation (1972)

We tested the ability of human neutrophils to kill five Candida species and the yeast Torulopsis glabrata. C. parapsilosis and C. pseudotropicalis were found to be killed readily by normal and myeloperoxidase-deficient neutrophils and were selected to probe the myeloperoxidase-independent fungicidal mechanisms of the neutrophil. These organisms were killed with relatively normal (C. parapsilosis) or moderately reduced (C. pseudotropicalis) effectiveness by neutrophils from two boys with X-linked chronic granulomatous disease. Azide (2 mm) and sulfadiazine (4 mm) exerted a relatively small inhibitory effect on the ability of normal neutrophils to kill C. parapsilosis. These compounds did not, however, inhibit the killing of C. parapsilosis by myeloperoxidase-deficient neutrophils, although they blocked their iodination of ingested Candida cells. Anaerobic incubation conditions inhibited the ability of normal neutrophils to kill C. parapsilosis slightly but did not impair this function in myeloperoxidase-deficient cells. All of the Candida species tested had catalase activity, yet their sensitivity to H(2)O(2) in cell-free systems varied considerably. Our C. parapsilosis strain was extraordinarily resistant to H(2)O(2) (LD(75): 0.14 m), as compared with C. pseudotropicalis or with our reference strain of C. albicans (LD(75): 2.3 x 10(-3)m and 3.4 x 10(-3)m, respectively). These data establish the existence in human neutrophils of a second mechanism that exerts microbicidal activity against certain Candida species; the mechanism is unrelated to myeloperoxidase, iodination, or to the direct effects of H(2)O(2) generated by the endogenous metabolic processes of the neutrophil. As yet unidentified, this mechanism appears to remain operative in the neutrophils of subjects with hereditary myeloperoxidase deficiency or chronic granulomatous disease.
Prednisone versus tamoxifen in patients with idiopathic retroperitoneal fibrosis: an open-label randomised controlled trial
Authors: Augusto Vaglio, Alessandra Palmisano, Federico Alberici, Umberto Maggiore, Stefania Ferretti, Rocco Cobelli, Francesco Ferrozzi, Domenico Corradi, Carlo Salvarani, Carlo Buzio
Journal: The Lancet (2011)
Tamoxifen and Anastrozole As a Sequencing Strategy: A Randomized Controlled Trial in Postmenopausal Patients With Endocrine-Responsive Early Breast Cancer From the Austrian Breast and Colorectal Cancer Study Group
Authors: Peter C. Dubsky, Raimund Jakesz, Brigitte Mlineritsch, Sabine Pöstlberger, Hellmut Samonigg, Werner Kwasny, Christoph Tausch, Herbert Stöger, Karin Haider, Florian Fitzal, Christian F. Singer, Michael Stierer, Paul Sevelda, Gero Luschin-Ebengreuth, Susanne Taucher, Margaretha Rudas, Rupert Bartsch, Günther G. Steger, Richard Greil, Lidija Filipcic, Michael Gnant
Journal: Journal of Clinical Oncology (2012)

Purpose Anastrozole (ANA) alone delivers significant disease-free survival benefits over tamoxifen (TAM) monotherapy in postmenopausal women with early estrogen receptor–positive breast cancer. The ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients. Patients and Methods Endocrine receptor–positive patients with G1 or G2 tumors were eligible. After surgery, patients were randomly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA. Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria. Intention-to-treat and censored analyses of on-treatment recurrence-free survival (RFS) were performed, and exploratory survival end points and toxicity were investigated. Results Information from 3,714 patients, including 17,563 woman-years, with a median of 60 months of follow-up was available for this analysis. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS (hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.01; P = .06). Exploratory analyses of distant relapse-free survival indicated a 22% improvement (HR, 0.78; 95% CI, 0.60 to 1.00). On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment. Conclusion Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse, the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits.
Patterns of Polymorphism and Divergence from Noncoding Sequences of Drosophila melanogaster and D. simulans: Evidence for Nonequilibrium Processes
Authors: Andrew D. Kern, David J. Begun
Journal: Molecular Biology and Evolution (2004)

Despite the fact that D. melanogaster and D. simulans have been the central model system for molecular population genetics, few data are available for noncoding regions. Here, we present an analysis of population genetic data from intergenic regions and comparisons of these data to previously collected data from introns and exons. Polymorphisms and fixations were categorized as A/T to G/C or G/C to A/T changes and were polarized by inferring the ancestral state using both parsimony and maximum likelihood. Noncoding fixations in both D. melanogaster and D. simulans were consistent with equilibrium base-composition evolution. However, polarized noncoding polymorphisms, revealed a different pattern. Although A/T to G/C and G/C to A/T polymorphisms in D. simulans were consistent with equilibrium, we observed a highly significant dearth of A/T to G/C polymorphisms in D. melanogaster introns but not in intergenic sequences. Such data could be explained by recent evolution of mutational biases associated with transcription or by lineage-specific selection on base composition. These data reveal the complexity of evolutionary processes acting even on noncoding DNA in Drosophila.
Spectrum of statin hepatotoxicity: Experience of the drug-induced liver injury network
Authors: Mark W. Russo, Jay H. Hoofnagle, Jiezhun Gu, Robert J. Fontana, Huiman Barnhart, David E. Kleiner, Naga Chalasani, Herbert L. Bonkovsky
Journal: Hepatology (2014)

The HMG-CoA reductase inhibitors (statins) are widely prescribed for patients with hyperlipidemia and are generally well tolerated. Mild elevations in serum aminotransferases arise in up to 3% of treated patients, but clinically apparent drug-induced liver injury is rare. The aim of this study is to report the presenting features and outcomes of 22 patients with clinically apparent liver injury due to statins. Among 1,188 cases of drug-induced liver injury enrolled between 2004 and 2012 in a prospective registry by the U.S. Drug Induced Liver Injury Network, 22 were attributed to a statin. All patients were evaluated in a standard fashion and followed for at least 6 months after onset. The median age was 60 years (range 41-80), and 15 (68%) were female. The latency to onset of liver injury ranged from 34 days to 10 years (median = 155 days). Median peak levels were alanine aminotransferase 892 U/L, alkaline phosphatase 358 U/L, and total bilirubin 6.1 mg/dL. Nine patients presented with cholestatic hepatitis and 12 patients presented with hepatocellular injury, of which six had an autoimmune phenotype. Nine patients were hospitalized, four developed evidence of hepatic failure, and one died. All commonly used statins were implicated. Four patients developed chronic liver injury, of which three had an autoimmune phenotype of liver injury. Conclusion : Drug-induced liver injury from statins is rare and characterized by variable patterns of injury, a range of latencies to onset, autoimmune features in some cases, and persistent or chronic injury in 18% of patients, most of whom have an autoimmune phenotype. (Hepatology 2014;60:679–686)
Psychosocial sequelae of stoma surgery for inflammatory bowel disease in childhood.
Authors: B Lask, J Jenkins, L Nabarro, I Booth
Journal: Gut (1987)

Three matched groups of children with inflammatory bowel disease: (a) stroma group, (b) ileorectal anastomosis group and (c) no-surgery group were compared for psychosocial adjustment. No differences were found between the groups for psychological adjustment, selfesteem, or quality of life. It is concluded that providing children are well prepared and followed up carefully and sensitively, then stroma surgery should not be deferred for fear of adverse psychological consequences.
Differential Regulation of Mitogen-Activated Protein Kinases in the Failing Human Heart in Response to Mechanical Unloading
Authors: Markus Flesch, Kenneth B. Margulies, Hans-Christian Mochmann, David Engel, Natarajan Sivasubramanian, Douglas L. Mann
Journal: Circulation (2001)

Background Mechanical unloading of the heart with a left ventricular assist device (LVAD) leads to favorable changes in the biology of the failing cardiac myocyte. To determine a potential mechanism for these improvements, we examined the regulation of mitogen-activated protein kinases (MAPKs) in the failing heart in the presence and absence of LVAD support. Methods and Results We examined the degree of activation (ie, phosphorylation) of p44/42 extracellularly regulated kinase, p38 kinase, and c-Jun N-terminal kinase (JNK1/2), and the corresponding activity levels of these MAPKs in myocardial samples obtained from 11 patients with LVAD support and in 11 patients without LVAD support. MAPK activity was also examined in an additional 6 patients from whom paired samples were obtained before and after LVAD support. The activity of p44/42 and JNK1/2 were reduced significantly, whereas p38 activity levels were significantly increased after LVAD support. We examined functional parameters that are linked to MAPK activation, namely cardiac myocyte hypertrophy and apoptosis. Both cardiac myocyte cell size and the incidence of cardiac myocyte apoptosis were significantly reduced after LVAD support. Conclusions Mechanical unloading of the failing heart leads to differential regulation of MAPKs. These changes in MAPK activity are associated with changes in myocyte hypertrophy and viability, suggesting a potential mechanistic basis for some of the observed salutary changes after LVAD support.
Molecular and immunological characterization of hr44, a human ocular component immunologically cross-reactive with antigen Ov39 of Onchocerca volvulus.
Authors: G Braun, N M McKechnie, W Gürr
Journal: The Journal of Experimental Medicine (1995)

Structural similarities between host self-antigens and infectious organisms may be involved in the expression of autoimmune reactivity and development of autoimmune disease. The unique eye pathology associated with Onchocerca volvulus infection, particularly the development of posterior segment lesions, may be promoted by such autoreactive responses. Ov39 is a parasite-derived antigen that has been shown previously to be antigenically cross-reactive with a 44,000-M(r) host ocular component. A clone, designated hr44, was isolated from a cDNA library of human retina by immunoscreen using serum to Ov39. A monoclonal antibody raised to Ov39 also reacted with hr44 and gave evidence for a shared conformational epitope. The primary structure analysis showed that identities between the antigens are limited and confined to small peptides. The cross-reactivity between the antigens appears to involve T cells, since Ov39-specific T cells can be stimulated by hr44, a neural-specific antigen. Based on secondary structure prediction, hr44 has the typical features of a membrane-associated type I antigen with an amino-terminal extracellular domain. mAbs and antisera localized the antigen in the optic nerve, neural retina, retinal pigment epithelium, as well as the epithelial layers of ciliary body and iris.
Disease progression according to IPF phenotype
Authors: David McAllister, Pauline Macfarlane, Gareth Stewart, Andrew Robson, William Wallace, John Murchison, John Simpson, Nik Hirani
Journal: European Respiratory Journal (2012)

Introduction 

Our understanding of disease progression in IPF is based on cohorts of patients with 'definite' IPF. Such studies have reported a prognostic index for IPF (Du Bois 2011 AJRCCM 184; 459). In practice a diagnosis of definite IPF is not always attained; in some cases where the HRCT pattern is not incontrovertibly UIP, corroboratory invasive investigations are not performed. We define this condition 'probable IPF'.

Aims 

To determine 1) disease progression and 2) the prognostic value of an IPF index in definite or probable IPF.

Methods 

Consecutively presenting patients with IPF were prospectively recruited to a database. All IPF diagnoses required an HRCT appearance of UIP with ≥ 70% probability. Patients with HRCT scans with ≥ 95% probability of UIP, or a UIP biopsy were defined as definite IPF. BAL was not included in the diagnostic criteria.

Results 

Of 193 patients, 89 had definite IPF. Median survival for definite v probable IPF was 3.2 v 6.0 years respectively (HR 1.45; 95%CI 0.94 to 2.25, p=0.09 adjusting for age, sex, height, VC and smoking). A relative decline in VC of 5-10% in the first 6 months was associated with increased risk of death (HR 3.12; 95% CI 1.55 to 6.30). Similar results were obtained in patients with definite and probable IPF. An IPF index was calculated in our cohort. Scores of 0-8 (n=97), 10-29 (n=76) and 30-61 (n=20) predicted median survival of 74, 48 (HR 2.02; 95%CI 1.26 to 3.23) and 12 months (HR 15.3; 95%CI 8.22 to 28.4) respectively (p < 0.001). The index had similar predictive value in definite and probable IPF.

Conclusions 

Patients with both definite and probable IPF have poor prognoses but survival was worse in definite IPF. The IPF index may be of clinical value in definite and probable IPF.
Stimulation of Erythropoietic Differentiation in BALB/c Mice Infected With Rauscher Leukemia Virus23
Authors: A. Weitz-Hamburger, T. N. Fredrickson, J. LoBue, W. D. Hardy, J. F. Camiscoli, P. Ferdinand, V. Gallicchio, A. S. Gordon
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Stimulation of Erythropoietic Differentiation in BALB/c Mice Infected With Rauscher Leukemia Virus Get access A. Weitz-Hamburger, A. Weitz-Hamburger Search for other works by this author on: Oxford Academic PubMed Google Scholar T. N. Fredrickson, T. N. Fredrickson Search for other works by this author on: Oxford Academic PubMed Google Scholar J. LoBue, J. LoBue Search for other works by this author on: Oxford Academic PubMed Google Scholar W. D. Hardy, Jr., W. D. Hardy, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. F. Camiscoli, J. F. Camiscoli Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Ferdinand, P. Ferdinand Search for other works by this author on: Oxford Academic PubMed Google Scholar V. Gallicchio, V. Gallicchio Search for other works by this author on: Oxford Academic PubMed Google Scholar A. S. Gordon A. S. Gordon Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 5, November 1975, Pages 1171–1175, https://doi.org/10.1093/jnci/55.5.1171 Published: 01 November 1975 Article history Received: 17 March 1975 Accepted: 08 July 1975 Published: 01 November 1975
Sequential and simultaneous "in series" hemodialysis and hemoperfusion in the management of theophylline intoxication.
Authors: R Hootkins, M J Lerman, J R Thompson
Journal: Journal of the American Society of Nephrology (1990)

Hemodialysis and hemoperfusion have been evaluated, and both are effective in removing theophylline. We report two consecutive cases of theophylline intoxication in which the sequential treatment of charcoal hemoperfusion and hemodialysis is contrasted to the simultaneous "in series" treatment of hemodialysis and charcoal hemoperfusion. Analysis of the two methodologies shows that the combined in series technique offers several advantages, including increased extraction efficiency, decreased time of hemoperfusion cartridge saturation, and rapid correction of electrolyte and acid-base abnormalities, and that it is well tolerated clinically. Simultaneous hemodialysis and charcoal hemoperfusion should be considered in cases of extreme theophylline intoxication.
Tumor Suppressor BRCA1 Is Expressed in Prostate Cancer and Controls Insulin-like Growth Factor I Receptor (<i>IGF-IR</i>) Gene Transcription in an Androgen Receptor–Dependent Manner
Authors: Hagit Schayek, Kathy Haugk, Shihua Sun, Lawrence D. True, Stephen R. Plymate, Haim Werner
Journal: Clinical Cancer Research (2009)

The insulin-like growth factor (IGF) system plays an important role in prostate cancer. The BRCA1 gene encodes a transcription factor with tumor suppressor activity. The involvement of BRCA1 in prostate cancer, however, has not yet been elucidated. The purpose of the present study was to examine the functional correlations between BRCA1 and the IGF system in prostate cancer.An immunohistochemical analysis of BRCA1 was done on tissue microarrays comprising 203 primary prostate cancer specimens. In addition, BRCA1 levels were measured in prostate cancer xenografts and in cell lines representing early stages (P69 cells) and advanced stages (M12 cells) of the disease. The ability of BRCA1 to regulate IGF-I receptor (IGF-IR) expression was studied by coexpression experiments using a BRCA1 expression vector along with an IGF-IR promoter-luciferase reporter.We found significantly elevated BRCA1 levels in prostate cancer in comparison with histologically normal prostate tissue (P<0.001). In addition, an inverse correlation between BRCA1 and IGF-IR levels was observed in the androgen receptor (AR)-negative prostate cancer-derived P69 and M12 cell lines. Coexpression experiments in M12 cells revealed that BRCA1 was able to suppress IGF-IR promoter activity and endogenous IGF-IR levels. On the other hand, BRCA1 enhanced IGF-IR levels in LNCaP C4-2 cells expressing an endogenous AR.We provide evidence that BRCA1 differentially regulates IGF-IR expression in AR-positive and AR-negative prostate cancer cells. The mechanism of action of BRCA1 involves modulation of IGF-IR gene transcription. In addition, immunohistochemical data are consistent with a potential survival role of BRCA1 in prostate cancer.