tbuckley/cabot-search huggingface dataset:
Predictive Value of Symptoms for Early Detection of Ovarian Cancer
Authors: M. A. Rossing, K. G. Wicklund, K. L. Cushing-Haugen, N. S. Weiss
Journal: JNCI Journal of the National Cancer Institute (2010)

A recent consensus statement encouraged use of certain symptoms to diagnose ovarian cancer earlier. We assessed the sensitivity, specificity, and positive predictive value of a proposed symptom index and of symptoms included in the consensus recommendation.In-person interviews were conducted with 812 case patients, aged 35-74 years, who had epithelial ovarian cancer that was diagnosed from January 1, 2002, through December 31, 2005, and with 1313 population-based control subjects. The symptom index was considered positive when pelvic or abdominal pain or bloating or feeling full was reported at least daily for at least 1 week, with an onset of less than 12 months before diagnosis or a reference date (for control subjects). The consensus criteria were considered fulfilled when any symptom above or urinary urgency or frequency was reported for at least 1 month, with an onset of less than 12 months before diagnosis or a reference date. Positive predictive value was calculated by use of external estimates of cancer prevalence.Most case patients who had a positive index or met consensus criteria did so only within 5 months before diagnosis. Symptoms (except nausea) were somewhat less likely to have occurred among women diagnosed with early-stage than late-stage ovarian cancer. The estimated positive predictive value of the symptom index or symptoms meeting the consensus criteria was 0.6%-1.1% overall and less than 0.5% for early-stage disease.Use of symptoms to trigger medical evaluation for ovarian cancer is likely to result in diagnosis of the disease in only one of 100 women in the general population with such symptoms.
Prospects for TIM3-Targeted Antitumor Immunotherapy
Authors: Shin Foong Ngiow, Michele W.L. Teng, Mark J. Smyth
Journal: Cancer Research (2011)

New insights into the control of T-cell activation and proliferation have led to the identification of checkpoint proteins that either up- or downmodulate T-cell reactivity. Monoclonal antibody immunotherapies that are reactive with cytotoxic T lymphocyte antigen 4 or programmed death receptor 1 have shown promising therapeutic outcomes in mice and humans with established cancer, highlighting the fact that cancer immunotherapy using T-cell checkpoint inhibitors is one of the most promising new therapeutic approaches. T-cell immunoglobulin and mucin domain 3 (TIM3) is one of many similar inhibitory molecules that are gaining attention as targets, but it remains relatively poorly studied in oncology. This review discusses our recent probing of the mechanism of action of anti-TIM3 antibody against established spontaneous and experimental tumors in mice, in the context of the exciting possibility of rationally combining agents that promote tumor-specific T-cell activation, proliferation, effector function, and survival.
CATALASE ACTIVITY OF LIVER AND KIDNEY IN FROGS WITH SPONTANEOUS RENAL CARCINOMA
Authors: Balduin Lucké, Mary Berwick
Journal: The Journal of Experimental Medicine (1954)

The kidney carcinoma of the leopard frog has served for various studies on catalase activity, as a first step in gaining information on enzymatic properties of neoplasms in cold blooded animals. It was found that the activity level of this tumor is reduced to approximately 13 per cent of that of the normal frog's kidney. Systemic effects of the tumor on catalase activity of liver and kidney are evident. Liver catalase in tumor-bearing frogs is diminished to about 50 per cent of the normal, and kidney catalase to an even greater degree; i.e., to about 34 per cent. A positive correlation exists between levels of catalase in tumor and in liver. Frogs kept at 3 different temperatures, 8, 18, and 26.5 degrees C., for upward of 29 days exhibited no significant change in activity levels either of tumor or of livers from normal or from tumor-bearing animals. It is suggested that a seasonal variation may occur in catalase activity of the frog. During the winter months catalase activity of the tumors was found to be higher than during the summer, whereas liver catalase was below the level of normal frogs examined during the summer. Intracoelomic injections of homogenates of tumors promptly lead to diminution of liver catalase lasting for several days. Injection of normal kidney has no such effect. These results with a spontaneous tumor of a cold blooded animal are in essential agreement with the many observations made with transplanted tumors of warm blooded animals. They lend support to the view that neoplasia is a ubiquitous biological process with similar characteristics in all species or classes of vertebrates.
A reproducible grading scale for histological assessment of inflammation in ulcerative colitis
Authors: Karel Geboes, R Riddell, A Ost, B Jensfelt, T Persson, R Löfberg
Journal: Gut (2000)

<h3>BACKGROUND</h3> Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials. <h3>AIM</h3> To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study. <h3>METHODS</h3> A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics. <h3>RESULTS</h3> Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration. <h3>CONCLUSION</h3> A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.
Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy
Authors: Hiroyuki Kashiwagi, Jonathan E McDunn, Peter O Simon, Peter S Goedegebuure, Jinbin Xu, Lynne Jones, Katherine Chang, Fabian Johnston, Kathryn Trinkaus, Richard S Hotchkiss, Robert H Mach, William G Hawkins
Journal: Molecular Cancer (2007)

Resistance to modern adjuvant treatment is in part due to the failure of programmed cell death. Therefore the molecules that execute the apoptotic program are potential targets for the development of anti-cancer therapeutics. The sigma-2 receptor has been found to be over-expressed in some types of malignant tumors, and, recently, small molecule ligands to the sigma-2 receptor were found to induce cancer cell apoptosis.The sigma-2 receptor was expressed at high levels in both human and murine pancreas cancer cell lines, with minimal or limited expression in normal tissues, including: brain, kidney, liver, lung, pancreas and spleen. Micro-PET imaging was used to demonstrate that the sigma-2 receptor was preferentially expressed in tumor as opposed to normal tissues in pancreas tumor allograft-bearing mice. Two structurally distinct sigma-2 receptor ligands, SV119 and WC26, were found to induce apoptosis to mice and human pancreatic cancer cells in vitro and in vivo. Sigma-2 receptor ligands induced apoptosis in a dose dependent fashion in all pancreatic cell lines tested. At the highest dose tested (10 muM), all sigma-2 receptor ligands induced 10-20% apoptosis in all pancreatic cancer cell lines tested (p < 0.05). In pancreas tumor allograft-bearing mice, a single bolus dose of WC26 caused approximately 50% apoptosis in the tumor compared to no appreciable apoptosis in tumor-bearing, vehicle-injected control animals (p < 0.0001). WC26 significantly slowed tumor growth after a 5 day treatment compared to vehicle-injected control animals (p < 0.0001) and blood chemistry panels suggested that there is minimal peripheral toxicity.We demonstrate a novel therapeutic strategy that induces a significant increase in pancreas cancer cell death. This strategy highlights a new potential target for the treatment of pancreas cancer, which has little in the way of effective treatments.
Phase II Trial of mFOLFOX6/CapeOX Plus Bevacizumab with Oxaliplatin in a Stop and Go Fashion in Advanced mCRC
Authors: M. Gamoh, H. Shimodaira, Y. Murakawa, S. Kato, K. Amagai, H. Isoge, T. Niitani, J. Itoh, T. Yoshioka, C. Ishioka
Journal: Annals of Oncology (2013)
Incidence of Urothelial Tumors on Rats Deficient on Essential Fatty Acids&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: B Monis, A R Eynard
Journal: JNCI Journal of the National Cancer Institute (1980)

Wistar rats were fed a diet deficient in essential fatty acids (EFA). Control animals received the same diet to which was added 5% corn oil, a source of EFA. The experimental group showed clinical and chromatographic evidences of EFA deficiency. Groups of deficient and control animals were killed at various periods up to 100 weeks of age. Of 43 EFA-deficient rats, 8 (18.6%) had papillary transitional cell tumors of the urinary tract. None of the 36 controls had tumors (P less than 0.01). In 7 animals, tumors were found in the renal pelvis and upper portion of the ureter; in one, the tumor was in the bladder. The tumors were more frequent at the end of the first year of life and after the first year of life, with no significant sex differences. Tumors showed various degrees of differentiation and a trend toward bilateral involvement. Subepithelial and muscle invasion of tumor was noted in 5 rats. Most tumors were polycentric, and carcinomas in situ were seen. Atypical hyperplasias were found in 35% of the EFA-deficient rats and in 3% of the controls. Typical hyperplasias were seen in 63% of the EFA-deficient rats and in 72% of the controls, Renal calcifications, congestion, inflammation, and hydronephrosis were also seen. No significant differences other than congestion were found in both groups. Our results suggest that the mechanisms regulating proliferation of urothelial cells are upset in EFA-deficient rats; this favors the appearance of atypical hyperplasias and tumors. Therefore, EFA deficiency in the rat may be a useful model for the study of the causes and pathogenesis of human urothelial cancer.
WATER AND BIOTERRORISM: Preparing for the Potential Threat to U.S. Water Supplies and Public Health
Authors: Patricia L. Meinhardt
Journal: Annual Review of Public Health (2004)

Water supplies and water distribution systems represent potential targets for terrorist activity in the United States because of the critical need for water in every sector of our industrialized society. Even short-term disruption of water service can significantly impact a community, and intentional contamination of a municipal water system as part of a terrorist attack could lead to serious medical, public health, and economic consequences. Most practicing physicians and public health professionals in the United States have received limited training in the recognition and evaluation of waterborne disease from either natural or intentional contamination of water. Therefore, they are poorly prepared to detect water-related disease resulting from intentional contamination and may not be adequately trained to respond appropriately to a terrorist assault on water. The purpose of this review is to address this critical information gap and present relevant epidemiologic and clinical information for public health and medical practitioners who may be faced with addressing the recognition, management, and prevention of water terrorism in their communities.
Front-Line and Salvage Therapies With Tyrosine Kinase Inhibitors and Other Treatments in Chronic Myeloid Leukemia
Authors: Jorge Cortes, Andreas Hochhaus, Timothy Hughes, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2011)

Chronic myeloid leukemia (CML) has been a model disease in the development of targeted therapies. After nearly 40 years of the recognition of the chromosomal abnormality that defines CML, specific therapy was developed, initially with imatinib mesylate, which has transformed our treatment algorithms and has changed the natural history of the disease. Today, most patients have the expectation of a favorable outcome when treated with standard-dose imatinib. However, a significant proportion of patients do not achieve the optimal desirable outcome. Effective salvage therapy followed the recognition of some of the most common mechanisms of resistance. More recently, the focus has turned to new areas of research and medical need, such as improving the front-line therapy to minimize the risk of resistance, to fight the most resistant mutant forms of BCR-ABL, and to eliminate minimal residual disease with the goal of achieving total elimination of the disease and treatment discontinuation. In this review, we analyze the current status of therapy of CML, and we discuss some of the most relevant clinical questions that we face today.
Aberrant T cell differentiation in the absence of Dicer
Authors: Stefan A. Muljo, K. Mark Ansel, Chryssa Kanellopoulou, David M. Livingston, Anjana Rao, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (2005)

Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and vertebrates. To test the requirement for Dicer in cell-lineage decisions in a mammalian organism, we have generated a conditional allele of dicer-1 (dcr-1) in the mouse. Specific deletion of dcr-1 in the T cell lineage resulted in impaired T cell development and aberrant T helper cell differentiation and cytokine production. A severe block in peripheral CD8+ T cell development was observed upon dcr-1 deletion in the thymus. However, Dicer-deficient CD4+ T cells, although reduced in numbers, were viable and could be analyzed further. These cells were defective in microRNA processing, and upon stimulation they proliferated poorly and underwent increased apoptosis. Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-γ, the hallmark effector cytokine of the Th1 lineage.
Effect of ethanol upon gastric emptying.
Authors: S E Kaufman, M D Kaye
Journal: Gut (1979)

The effect of ethanol upon gastric emptying in healthy human subjects was studied by measuring the gastric emptying rates of three 750 ml meals, the osmolalities, energy densities, and pH of which were similar. Meal A, which contained 80 ml alcohol, emptied more rapidly than meal B, which contained 40 ml ethanol and 63.3 g dextrose; and meal B emptied more rapidly than meal C, which contained 126.6 g dextrose but no ethanol. The slower rate of emptying of the dextrose meal (C) was not due to an increased gastric secretory rate, as serial measurements of gastric pH were substantially and significantly higher with this than with the other two meals; nor was it due to a greater degree of duodenogastric reflux, as serial measurements of gastric bile acid concentrations were similar for the three meals. We conclude that the duodenal osmoreceptor mechanism is relatively insensitive to ethanol; that the relationship between energy density and gastric emptying rate does not hold in the case of ethanol; and that the gastro-oesophageal reflux which occurs in response to ethanol is not due to impairment of gastric emptying.
Comparative Effectiveness Research in Oncology: An Overview
Authors: Gary H. Lyman, Mark Levine
Journal: Journal of Clinical Oncology (2012)

This Special Issue of Journal of Clinical Oncology provides a broad, in-depth look at the methodologic field that has become known as comparative effectiveness research (CER). The focus is on CER and its past, current, and future impact on cancer research, clinical oncology practice, and national health care policy. An extraordinary assemblage of authorities on a broad range of related topics has been gathered. The authors address issues ranging from those very familiar to oncologists and cancer researchers, such as randomized controlled trials and meta-analyses of such trials, to somewhat less familiar methodologies such as observational studies, decision modeling, and economic analyses of health care policy issues. The importance of our rapidly evolving understanding of the human genome and the molecular and genetic basis of new diagnostic and therapeutic tools will be discussed, along with the multiple challenges that they bring to CER. Important methodologic issues will be addressed, such as capturing patient-reported outcomes, conducting health technology assessments, and developing clinical guidelines to improve the quality of care. Finally, the manner in which CER has affected health care delivery and its cost, both in the United States and other developed nations such as Canada and the United Kingdom, will be discussed. The issue will end on a cautionary but positive note, reconciling the many varied approaches and expectations of CER as we strive to provide the most sophisticated and efficacious cancer care to all patients affected by this disease.
Characterization and Localization of Ventricular Arrhythmias Resulting from Myocardial Ischemia and Infarction
Authors: BENJAMIN J. SCHERLAG, NABIL EL-SHERIF, RONALD HOPE, RALPH LAZZARA
Journal: Circulation Research (1974)

Electrocardiograms and electrograms were recorded in 18 dogs anesthetized with sodium pentobarbital. Using endocardial and epicardial plunge wire electrodes in normal and ischemic or infarcted areas, activation of Purkinje and regular muscle tissue was studied within the first 20-30 minutes and 24 hours after anterior descending coronary artery ligation. The ventricular arrhythmias in the first 20 minutes were abolished during vagally induced atrial arrest, but ventricular automaticity was unchanged from that during the control period. These rate-related arrhythmias were uniformly associated with marked diminution and delay of epicardial activation in the ischemic zone. Slowing of the heart rate caused recovery of the timing, form, and duration of these epicardial potentials with the coincident disappearance of ventricular arrhythmias. The ventricular arrhythmias of the early phase spontaneously subsided with time 20-30 minutes after ligation; concurrently, epicardial activation in the ischemic zone improved. The ventricular arrhythmias noted 24 hours after coronary artery ligation were revealed by vagally induced atrial slowing and suppressed by rapid atrial pacing, indicating the existence of enhanced ventricular automaticity. There was a loss of endocardial muscle activation; Purkinje tissue was depressed but viable in the infarcted zone. The sequence of firing during many of the multifocal ventricular ectopic beats showed that the earliest activation arose from Purkinje tissue in the infarcted zone. However, other ectopic beats appeared to arise from infarcted epicardial muscle.
Densitometry for assessment of effect of lung volume reduction surgery for emphysema
Authors: J. Stolk, M. I. M. Versteegh, L. J. Montenij, M. E. Bakker, E. Grebski, M. Tutic, S. Wildermuth, W. Weder, M. el Bardiji, J. H. C. Reiber, K. F. Rabe, E. W. Russi, B. C. Stoel
Journal: European Respiratory Journal (2007)

To explore if change in the extent of emphysema correlated with change in lung function, the effect of resection of emphysematous tissue was studied by computed tomography (CT) densitometry. In addition, the current authors studied how surgery-induced change in emphysema related to lung density in control subjects. In total, 30 patients (14 females; mean± sd age 59±10 yrs) with severe emphysema before and 3 months after lung volume reduction surgery (LVRS), 48 patients with moderate emphysema and 76 control subjects were investigated. Lung density (15th percentile point) of both lungs and heterogeneity of lung density between 12 isovolumetric partitions in each lung were calculated from chest CT images. The 15th percentile point and its heterogeneity could distinguish controls from subjects with moderate emphysema with a sensitivity and specificity of &gt;95%. LVRS significantly increased lung density by 5.0±10.9 g·L −1 (n = 30). Improvement in the diffusing capacity of the lung for carbon monoxide and in residual volume significantly correlated with an increase in lung density (n = 20 and 28, respectively). Change in forced expiratory volume in one second did not correlate with change in lung density. In conclusion, lung density 15th percentile point is a valuable surrogate marker for detection of both the extent of and reduction in emphysema.
Isolation and Confirmation of a Calcium Excretion Quantitative Trait Locus on Chromosome 1 in Genetic Hypercalciuric Stone-Forming Congenic Rats
Authors: Richard R. Hoopes, Frank A. Middleton, Saunak Sen, Paul A. Hueber, Robert Reid, David A. Bushinsky, Steven J. Scheinman
Journal: Journal of the American Society of Nephrology (2006)

Hypercalciuria is the most common risk factor for kidney stones and has a substantial genetic component. The genetic hypercalciuric stone-forming (GHS) rat model displays complex changes in physiology involving intestine, bone, and kidney and overexpression of the vitamin D receptor, thereby reproducing the human phenotype of idiopathic hypercalciuria. Through quantitative trait locus (QTL) mapping of rats that were bred from GHS female rats and normocalciuric Wistar Kyoto (WKY) male rats, loci that are linked to hypercalciuria and account for a 6 to eight-fold phenotypic difference between the GHS and WKY progenitors were mapped. GHS × WKY rats were backcrossed to breed for congenic rats with the chromosome 1 QTL HC1 on a normocalciuric WKY background. Ten generations of backcrosses produced N10F1 rats, which were intercrossed to produce rats that were homozygous for GHS loci in the HC1 region between markers D1Mit2 and D1Mit32. On a high-calcium diet (1.2% calcium), significantly different levels of calcium excretion were found between male congenic (1.67 ± 0.71 mg/24 h) and male WKY control rats (0.78 ± 0.19 mg/24 h) and between female congenic (3.11 ± 0.90 mg/24 h) and female WKY controls (2.11 ± 0.50 mg/24 h); the congenics preserve the calcium excretion phenotype of the GHS parent strain. Microarray expression analyses of the congenic rats, compared with WKY rats, showed that of the top 100 most changed genes, twice as many as were statistically expected mapped to chromosome 1. Of these, there is a clear bias in gene expression change for genes in the region of the HC1 . Of >1100 gene groups analyzed, one third of the 50 most differentially expressed gene groups have direct or secondary action on calcium metabolism or transport. This is the first QTL for hypercalciuria to be isolated in a congenic animal.