tbuckley/cabot-search huggingface dataset:
Impact of Complete Response to Chemotherapy on Overall Survival in Advanced Colorectal Cancer: Results From Intergroup N9741
Authors: Grace K. Dy, James E. Krook, Erin M. Green, Daniel J. Sargent, Thierry Delaunoit, Roscoe F. Morton, Charles S. Fuchs, Ramesh K. Ramanathan, Stephen K. Williamson, Brian P. Findlay, Barbara A. Pockaj, Robert P. Sticca, Steven R. Alberts, Henry C. Pitot, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2007)

To evaluate clinical characteristics and survival outcomes among patients with locally advanced or metastatic colorectal cancer who achieve a complete response (CR) to systemic treatment either alone or with multimodality approach.Data were collected retrospectively from CRC patients enrolled onto the phase III trial N9741, a National Cancer Institute-funded and Gastrointestinal Cancer Intergroup-sponsored study coordinated by the North Central Cancer Treatment Group. Patients were randomly assigned to combinations of oxaliplatin, fluorouracil (FU)/leucovorin (LV) and irinotecan. The three treatment arms consist of IFL (irinotecan + FU/LV), FOLFOX4 (oxaliplatin + FU/LV), and IROX (irinotecan + oxaliplatin). Median follow-up was 42.6 months.Sixty-two (4%) of 1,508 patients had a CR to chemotherapy alone, and an additional 32 (2%) had a CR after multimodality treatment. Factors associated with achieving CR with systemic chemotherapy alone included FOLFOX4 treatment, patients with assessable disease, or a single site of metastasis. Continuing protocol treatment beyond two cycles after documentation of CR was not associated with improved survival. The rate of curative intent resection was significantly higher for patients treated with oxaliplatin-containing regimens (P = .02). Median survival was similar between patients with CR after chemotherapy alone (44.3 months) or after multimodality approach (47.4 months; P = .81).FOLFOX4 was more likely to produce a CR than were IFL or IROX. Oxaliplatin regimens were more likely to result in successful surgical resections. Patients who have CR to systemic chemotherapy alone can achieve impressive survival outcomes similar to those seen among patients who attained a CR status after multimodality treatment.
“Genetics” and DNA polymorphisms
Authors: Robert Plomin
Journal: Behavioral and Brain Sciences (1995)

Abstract Four questions are raised about Mealey's genetic argument: (1) Where is the evidence that secondary sociopathy is less heritable than primary sociopathy? (2) What is the genetic correlation between the two types of sociopathy? (3) How does genotype-environment interaction relate? (4) How strong are the links between our evolutionary past and current heritability?
THE INFLUENCE OF THE ANTERIOR LOBE OF THE PITUITARY BODY UPON THE GROWTH OF CARCINOMATA
Authors: T. Brailsford Robertson, Theodore C. Burnett
Journal: The Journal of Experimental Medicine (1915)

1. The administration of emulsions of the anterior lobe of the ox pituitary increases very markedly the rate of growth of the primary tumor in rats inoculated with carcinoma. The growth of small tumors is accelerated relatively more than that of large tumors. 2. This acceleration is only evidenced, however, at a certain stage in the growth of the tumor, subsequent to the twentieth day succeeding inoculation. The administrations do not enhance the tendency of the tumors to metastasize. 3. Liver emulsion does not cause an acceleration of the growth of carcinomata in rats.
A Phase I Pharmacologic and Pharmacogenetic Trial of Sequential 24-Hour Infusion of Irinotecan Followed by Leucovorin and a 48-Hour Infusion of Fluorouracil in Adult Patients with Solid Tumors
Authors: Maurice A. Wright, Geraldine Morrison, Pengxin Lin, Gregory D. Leonard, Dat Nguyen, Xaiodu Guo, Eva Szabo, Jon L. Hopkins, Jorge P. Leguizamo, Nancy Harold, Suzanne Fioravanti, Barbara Schuler, Brian P. Monahan, M. Wasif Saif, Mary G. Quinn, Janet Pang, Jean L. Grem
Journal: Clinical Cancer Research (2005)

Abstract Purpose: In preclinical studies, sequential exposure to irinotecan (CPT-11) then fluorouracil (5-FU) is superior to concurrent exposure or the reverse sequence; a 24-hour infusion of CPT-11 may be better tolerated than shorter infusions. Experimental Design: CPT-11 was first given at four levels (70-140 mg/m2/24 hours), followed by leucovorin 500 mg/m2/0.5 hours and 5-FU 2,000 mg/m2/48 hours on days 1 and 15 of a 4-week cycle. 5-FU was then increased in three cohorts up to 3,900 mg/m2/48 hours. Results: Two patients had dose-limiting toxicity during cycle 1 at 140/3,900 of CPT-11/5-FU (2-week delay for neutrophil recovery; grade 3 nausea despite antiemetics); one of six patients at 140/3,120 had dose-limiting toxicity (grade 3 diarrhea, grade 4 neutropenia). Four of 22 patients with colorectal cancer had partial responses, two of which had prior bolus CPT-11/5-FU. The mean 5-FU plasma concentration was 5.1 μmol/L at 3,900 mg/m2/48 hours. The end of infusion CPT-11 plasma concentration averaged 519 nmol/L at 140 mg/m2/24 hours. Patients with UDP-glucuronosyltransferase (UGT1A1; TA)6/6 promoter genotype had a lower ratio of free to glucuronide form of SN-38 than in patients with ≥1 (TA)7 allele. Thymidylate synthase genotypes for the 28-base promoter repeat were 2/2 (13%), 2/3 (74%), 3/3 (13%); all four responders had a 2/3 genotype. Conclusions: Doses (mg/m2) of CPT-11 140/24 hours, leucovorin 500/0.5 hours and 5-FU 3,120/48 hours were well tolerated.
Upregulation of microRNA-122 by farnesoid X receptor suppresses the growth of hepatocellular carcinoma cells
Authors: Jialin He, Kai Zhao, Lu Zheng, Zhizhen Xu, Wei Gong, Shan Chen, Xiaodong Shen, Gang Huang, Min Gao, Yijun Zeng, Yan Zhang, Fengtian He
Journal: Molecular Cancer (2015)

microRNA-122 (miR-122) is the most abundant and specific miRNA in the liver. It acts as an important tumor suppressor in hepatocellular carcinoma (HCC) through regulating its target genes, but details of its own regulation are largely unknown. Farnesoid X receptor (FXR), a transcription factor with multiple functions, plays an important role in protecting against liver carcinogenesis, but it is unclear whether the anti-HCC effect of FXR is involved in the regulation of miR-122. The levels of miR-122 and FXR in HCC tissues and cell lines were examined by quantitative real-time PCR (qRT-PCR). qRT-PCR was also used to detect the expression of miR-122 target genes at mRNA level, while Western blotting was used to analyze that of their protein products. The effect of FXR on the transcriptional activity of miR-122 promoter was evaluated by a luciferase reporter assay. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were performed to identify the FXR binding site within miR-122 promoter region. The cell proliferation was analyzed by a CCK-8 assay. The influence of FXR on tumor growth and miR-122 expression in vivo was monitored using HCC xenografts in nude mice. The expression of FXR was positively correlated with that of miR-122 in HCC tissues and cell lines. Activation of FXR in HCC cells upregulated miR-122 expression and in turn downregulated the expression of miR-122 target genes including insulin-like growth factor-1 receptor and cyclin G1. FXR bound directly to the DR2 element (−338 to −325) in miR-122 promoter region, and enhanced the promoter's transcriptional activity. Functional experiments showed that the FXR-mediated upregulation of miR-122 suppressed the proliferation of HCC cells in vitro and the growth of HCC xenografts in vivo. miR-122 is a novel target gene of FXR, and the upregulation of miR-122 by FXR represses the growth of HCC cells, suggesting that FXR may serve as a key transcriptional regulator for manipulating miR-122 expression, and the FXR/miR-122 pathway may therefore be a novel target for the treatment of HCC.
Cyclooxygenase-1 and -2 Knockout Mice Demonstrate Increased Cardiac Ischemia/Reperfusion Injury but Are Protected by Acute Preconditioning
Authors: Michael G.W. Camitta, Scott A. Gabel, Patricia Chulada, J. Alyce Bradbury, Robert Langenbach, Darryl C. Zeldin, Elizabeth Murphy
Journal: Circulation (2001)

The purpose of this study was to examine the effects of cyclooxygenase (COX) deficiency on baseline functional characteristics and on recovery of left ventricular developed pressure (LVDP) after 20 minutes of global ischemia and 40 minutes of reperfusion in untreated and preconditioned hearts.Compared with hearts from wild-type (WT) and COX-2(-/-) mice, baseline cardiac prostaglandin (PG) E(2) and 6-keto-PGF(1alpha) levels were significantly decreased in hearts from COX-1(-/-) mice. After ischemia, cardiac PGE(2) levels increased in WT, COX-1(-/-), and COX-2(-/-) mice (P<0.05). Recovery of function (LVDP) after global ischemia in hearts from COX-1(-/-) and COX-2(-/-) mice was significantly less than in WT hearts. Pretreatment of WT mice with indomethacin for 2 days before ischemia significantly decreased LVDP recovery; however, perfusion of WT hearts with indomethacin for 40 minutes before ischemia did not significantly alter LVDP recovery. Postischemic recovery of LVDP in COX-1(-/-) and COX-2(-/-) was unchanged by perfusion with 5 micromol/L PGE(2), PGD(2), PGF(2alpha), or carboprostacyclin. Hearts from COX-2(-/-) mice showed an increase in ischemic contracture compared with hearts from WT and COX-1(-/-) mice; however, hearts did not differ in intracellular pH, ATP, or inorganic phosphate during ischemia. Ischemic preconditioning significantly improved postischemic LVDP recovery in COX-1(-/-), COX-2(-/-), and WT mice.Genetic disruption or 2-day chemical inhibition of COX-1 and COX-2 decreases recovery of LVDP after ischemia; however, acute perfusion with indomethacin is not detrimental. These data are consistent with protection due to the altered expression of some protein that is modulated by COX or its metabolites.
Soluble transferrin receptor level: a new marker of iron deficiency anemia, a common manifestation of gastric autoimmunity in type 1 diabetes.
Authors: C E De Block, C M Van Campenhout, I H De Leeuw, B M Keenoy, M Martin, V Van Hoof, L F Van Gaal
Journal: Diabetes Care (2000)

A total of 15-20% of type 1 diabetic patients have parietal cell antibodies (PCAs). PCA+ subjects are at increased risk for iron deficiency anemia and atrophic gastritis. Recently, soluble transferrin receptor (sTfR) levels have proven to be a sensitive indicator for iron deficiency They are, in contrast with ferritin levels, independent of inflammation, liver and hormonal status, and sex. We are the first to evaluate sTfR levels in type 1 diabetes and tested the hypothesis of higher sTfR levels in patients with PCAs and/or autoimmune gastritis.We examined 148 type 1 diabetic patients (85 men and 63 women; 50 were PCA+) and 59 sex- and age-matched control subjects (30 men and 29 women). The main outcome measures were sTfR levels, iron deficiency anemia, and atrophic gastritis. Logistical regression analysis tested risk factors for iron deficiencyIron deficiency was present in 38 subjects. Iron (P<0.0001) and ferritin (P<0.0001) levels but not sTfR levels were lower in women. sTfR levels were similar in diabetic and control subjects but were higher in PCA+ subjects (P = 0.015). In diabetic subjects, iron deficiency anemia was more prevalent in PCA+ than in PCA- patients (odds ratio 3.07, P = 0.013) and was associated with sex (P = 0.0001), age (P = 0.046), and sTfR (P = 0.0008) levels. Atrophic gastritis was present in 15 of 28 PCA+ and in 1 of 11 PCA diabetic subjects (P = 0.014). sTfR levels tended to be higher in patients with atrophic gastritis (P = 0.062).In type 1 diabetes, sTfR levels can be used to diagnose iron deficiency anemia, which is more prevalent in PCA+ subjects. sTfR levels are higher in PCA+ individuals who are at risk for developing atrophic gastritis.
Detectable Inhibition of Heparin-Binding Growth Factor Activity in Sera From Patients Treated With Pentosan Polysulfate
Authors: B. W. Parker, S. M. Swain, G. Zugmaier, R. L. DeLap, M. E. Lippman, A. Wellstein
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Detectable Inhibition of Heparin-Binding Growth Factor Activity in Sera From Patients Treated With Pentosan Polysulfate Get access Bernard W. Parker, Bernard W. Parker Cancer Research Center and Department of Pharmacology, Georgetown University Medical CenterWashington, D.C. Correspondence to: Anton Wellstein, M.D., Ph.D., Georgetown University, Lombardi Cancer Center, 3800 Reservoir Rd., Washington, D.C. 20007. Search for other works by this author on: Oxford Academic PubMed Google Scholar Sandra M. Swain, Sandra M. Swain Cancer Research Center and Department of Pharmacology, Georgetown University Medical CenterWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerhard Zugmaier, Gerhard Zugmaier Cancer Research Center and Department of Pharmacology, Georgetown University Medical CenterWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert L. DeLap, Robert L. DeLap Cancer Research Center and Department of Pharmacology, Georgetown University Medical CenterWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marc E. Lippman, Marc E. Lippman Cancer Research Center and Department of Pharmacology, Georgetown University Medical CenterWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Anton Wellstein Anton Wellstein Cancer Research Center and Department of Pharmacology, Georgetown University Medical CenterWashington, D.C. * See “Notes” section following “References.” Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 13, 7 July 1993, Pages 1068–1073, https://doi.org/10.1093/jnci/85.13.1068 Published: 07 July 1993 Article history Received: 14 October 1992 Revision received: 11 February 1993 Accepted: 07 April 1993 Published: 07 July 1993
Guinea pigs with inherited deficiencies of complement components C2 or C4 have characteristics of immune complex disease.
Authors: E C Böttger, T Hoffmann, U Hadding, D Bitter-Suermann
Journal: Journal of Clinical Investigation (1986)

Guinea pigs genetically deficient in the second (C2) or fourth component of complement (C4) generally appear healthy in contrast to humans with a C2 or C4 deficiency. However, upon investigation of these genetic deficiencies in guinea pigs for signs of dysregulation in the humoral immune system and especially autoantibodies, many complement-deficient guinea pigs (greater than 50%) had elevated levels of serum IgM and higher concentrations of anti-hapten (dinitrophenyl) antibodies as signs of polyclonally stimulated antibody synthesis. In addition, a significant number of the complement-deficient animals, on average 30%, had IgM rheumatoid factors in their sera compared with less than 1% of the normal animals. These observations, therefore, indicate that guinea pigs, genetically deficient in C2 or C4, show characteristics of immune complex disease in general.
Age-related changes in the concentration of plasma cholesterol and triglycerides in two groups of rats with inherited widely different levels of spontaneous physical activity.
Authors: E W Rasmussen, A T Hłstmark
Journal: Circulation Research (1978)

The plasma concentration of cholesterol and triglycerides was determined in two groups of rats with inherited widely different levels of spontaneous physical activity. Active as well as passive rats of each sex were divided into two subgroups, one with free access to wheel running activity (exercising group), and another for which admittance to the drum was closed (nonexercising group). Plasma concentrations of cholesterol and triglycerides were followed from the age of 3-8 months in females and 3 months to 1 year in males. A pronounced increase with age in the plasma concentration of these lipids was observed in the active male rats. In the passive male rats and in all females, there were no major changes in plasma levels of cholesterol and triglycerides. Corresponding groups of exercising and nonexercising rats had similar plasma levels of these components. The data for male rats show a positive association between the inherited tendency to perform spontaneously a high level of physical activity and an age-related increase in plasma lipids. However, running activity per se does not seem to have any influence on the level of plasma cholesterol and triglycerides in these rats.
Prevalence of radiographic lumbar spondylosis and its association with low back pain in elderly subjects of population-based cohorts: the ROAD study
Authors: S Muraki, H Oka, T Akune, A Mabuchi, Y En-yo, M Yoshida, A Saika, T Suzuki, H Yoshida, H Ishibashi, S Yamamoto, K Nakamura, H Kawaguchi, N Yoshimura
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: Although lumbar spondylosis is a major cause of low back pain and disability in elderly people, few epidemiological studies have been performed. The prevalence of radiographic lumbar spondylosis was investigated in a large-scale population study and the association with low back pain was examined. Methods: From a nationwide cohort study (Research on Osteoarthritis Against Disability; ROAD), 2288 participants aged ⩾60 years (818 men and 1470 women) living in urban, mountainous and coastal communities were analysed. The radiographic severity at lumbar intervertebral levels from L1/2 to L5/S was determined by Kellgren/Lawrence (KL) grading. Results: In the overall population the prevalence of radiographic spondylosis with KL⩾2 and ⩾3 at the severest intervertebral level was 75.8% and 50.4%, respectively, and that of low back pain was 28.8%. Although KL⩾2 spondylosis was more prevalent in men, KL⩾3 spondylosis and low back pain were more prevalent in women. Age and body mass index were risk factors for both KL ⩾2 and KL⩾3 spondylosis. Although KL = 2 spondylosis was not significantly associated with low back pain compared with KL = 0 or 1, KL⩾3 spondylosis was related to the pain only in women. Conclusions: This cross-sectional study in a large population revealed a high prevalence of radiographic lumbar spondylosis in elderly subjects. Gender seems to be distinctly associated with KL⩾2 and KL⩾3 lumbar spondylosis, and disc space narrowing with or without osteophytosis in women may be a risk factor for low back pain.
Enhanced Sensitivity of the <i>RET</i> Proto-Oncogene to Ionizing Radiation <i>In vitro</i>
Authors: Claudia Béu Volpato, Minerva Martínez-Alfaro, Raffaella Corvi, Coralie Gabus, Sylvie Sauvaigo, Pietro Ferrari, Elena Bonora, Alessandro De Grandi, Giovanni Romeo
Journal: Cancer Research (2008)

Abstract Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia and thyroid cancer. It has been known for a long time that exposure of cells to radiation results in extensive DNA damage; however, a small number of studies have tried to explain the mechanisms of radiation-induced carcinogenesis. The high prevalence of RET/PTC rearrangements in patients who have received external radiation, and the evidence of in vitro induction of RET rearrangements in human cells, suggest an enhanced sensitivity of the RET genomic region to damage by ionizing radiation. To assess whether RET is indeed more sensitive to radiations than other genomic regions, we used a COMET assay coupled with fluorescence in situ hybridization, which allows the measurement of DNA fragmentation in defined genomic regions of single cells. We compared the initial DNA damage of the genomic regions of RET, CXCL12/SDF1, ABL, MYC, PLA2G2A, p53, and JAK2 induced by ionizing radiation in both a lymphoblastoid and a fetal thyroid cell line. In both cell lines, RET fragmentation was significantly higher than in other genomic regions. Moreover, a differential distribution of signals within the COMET was associated with a higher percentage of RET fragments in the tail. RET was more susceptible to fragmentation in the thyroid-derived cells than in lymphoblasts. This enhanced susceptibility of RET to ionizing radiation suggests the possibility of using it as a radiation exposure marker. [Cancer Res 2008;68(21):8986–92]
877 SERUM LEVELS OF OMENTIN, CHEMERIN AND ADIPSIN IN PATIENTS WITH BIOPSY-PROVEN NONALCOHOLIC FATTY LIVER DISEASE
Authors: Y. Yilmaz, O. Yonal, R. Kurt, Y.O. Alahdab, F. Eren, N. Imeryuz, C. Kalayci, E. Avsar
Journal: Journal of Hepatology (2011)
PTU-049 How Rewarding Is Gastroscopy In Diagnosis Of Cancer In Isolated Iron Deficiency Anaemia?
Authors: SK Butt, K Besherdas
Journal: Gut (2014)

<h3>Introduction</h3> The ultimate goal of the UK Cancer plan is to ‘offer patients a maximum one month wait from an urgent referral for suspected cancer to the beginning of treatment’. The North London Cancer Network has devised and implemented a suspected cancer referral form for Primary Care Practitioners for patients to be seen within two weeks of referral to secondary care. One group referred on the suspected upper GI cancer referral form is patients unexplained iron deficiency anaemia (IDA) without other symptoms. Whilst IDA is a recognised finding in upper GI cancer we hypothesise that it is a rare presentation of upper GI cancer in the absence of other symptoms. <h3>Methods</h3> The aim of this study is to assess the presenting symptoms in patients diagnosed with upper GI cancer when endoscopy is performed for anaemia as the primary indication. A single centre, retrospective analysis of all patients undergoing endoscopy for IDA from August 2008 for 5 years at a District General Hospital in North London was performed. Data was collected using electronic patient records and unisoft endoscopy database. Those diagnosed with upper GI cancer were scrutinised for presence of symptoms in addition to anaemia at presentation. <h3>Results</h3> Over the study period, 1529 patients were gastroscoped for IDA, and 1228 colonoscopied for IDA. 20 upper GI cancers (16 stomach, 4 oesophageal) were detected during the study. No patients with upper GI cancer had IDA alone with addition symptoms including weight loss (9 patients), malaena (3), dysphagia (3), abdominal pain (2), anorexia (2), abnormal CT scan (2), altered bowel habit (2). Other benign diagnosis at gastroscopy in anaemic patients included: Barrett’s oesophagus (52), oesophagitis (159), oesophageal varices (11), gastric erosions (27), gastritis (438), pyloric stenosis (2), angiodysplasia (20), duodenal ulcer (35), duodenitis (139). In the group colonoscopied for anaemia findings included: Normal in 550, 66 had colorectal cancer, polyps in 173, angiodysplasia in 33, and IBD in 16. <h3>Conclusion</h3> From this study we conclude that upper GI cancer is diagnosed on gastroscopy in only 1.3% of patients presenting with IDA. When Upper GI cancer is diagnosis in IDA it is always associated with an additional symptom such as weight loss, anorexia, dysphagia, malaena or an abnormal CT scan. Patients should not be referred with IDA on a suspected upper GI cancer referral form unless accompanied by additional alarm features. If a patient has isolated IDA and cancer is suspected a diagnostic colonoscopy is more rewarding than a gastroscopy and it is more appropriate to refer these patients to the colorectal cancer pathway. If similar findings are replicated than National guidelines should be informed and altered accordingly. <h3>Disclosure of Interest</h3> None Declared.