scholarly journals Polymorphisms in multidrug resistance 1 (MDR1) gene are associated with refractory Crohn disease and ulcerative colitis

2004 ◽  
Vol 5 (7) ◽  
pp. 530-539 ◽  
Author(s):  
U Potočnik ◽  
I Ferkolj ◽  
D Glavač ◽  
M Dean
Keyword(s):  
Ulcerative Colitis ◽  
Multidrug Resistance ◽  
Crohn Disease ◽  
Mdr1 Gene

Effect of MicroRNA145 on the multidrug resistance gene of ulcerative colitis in rats

Life Sciences ◽  
2021 ◽  
pp. 119603
Author(s):  
Ping Wangs ◽  
Yan Chen ◽  
La-Mei Zhang ◽  
Si-Qi Yuan ◽  
Shen-Ao Lu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Multidrug Resistance Gene

scholarly journals Gene transfer of multidrug resistance into a factor-dependent human hematopoietic progenitor cell line: in vivo model for genetically transferred chemoprotection

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2723-2731 ◽  
Author(s):  
P Schwarzenberger ◽  
S Spence ◽  
N Lohrey ◽  
T Kmiecik ◽  
DL Longo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Gene Transfer ◽  
Hematopoietic Progenitor Cells ◽  
Mdr1 Gene ◽  
In Vivo Model ◽  
Hematopoietic Progenitor ◽  
Human Dna

To develop a rapid preclinical in vivo model to study gene transfer into human hematopoietic progenitor cells, MO-7e cells (CD-34+, c-kit+) were infected with multidrug resistance (MDR1)-containing retroviruses and then transplanted into nonobese diabetic severe combined immunodeficient mice (NOD SCID). MO-7e cells infected with a retrovirus encoding the human MDR1 cDNA showed integration, transcription, and expression of the transfered MDR1 gene. This resulted in a 20-fold increase in the resistance of MO-7e cells to paclitaxel in vitro. The expression of the MDR1 gene product was stable over a 6-month period in vitro without selection in colchicine. MO-7e and MDR1-infected MO-7e cells were transplanted into NOD SCID mice to determine whether MDR1 could confer drug resistance in vivo. A sensitive polymerase chain reaction method specific for human sequences was developed to quantitate the level of human cell engraftment in NOD SCID bone marrow (BM) cells. The percentage of human DNA in BM cells from MO-7e- transplanted mice was 10.9% and decreased to 0.7% in mice treated with paclitaxel. The percentage of human DNA in infected-MO-7e transplanted mice was 7.6% and that level was unchanged in mice treated with paclitaxel. These results show that expression of the MDR1 gene in human hematopoietic progenitor cells can confer functional drug resistance in an in vivo model.

Regulatory polymorphisms of multidrug resistance 1 (MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia

2007 ◽  
Vol 31 (12) ◽  
pp. 1633-1640 ◽  
Author(s):  
Hiroyoshi Hattori ◽  
Aiko Suminoe ◽  
Morimasa Wada ◽  
Yuhki Koga ◽  
Kimitoshi Kohno ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Mdr1 Gene

scholarly journals Tumor Necrosis Factor Inhibition and Parkinson Disease

Neurology ◽  
2021 ◽  
Vol 96 (12) ◽  
pp. e1672-e1679
Author(s):  
Xiaoying Kang ◽  
Alexander Ploner ◽  
Nancy L. Pedersen ◽  
Sara Bandres-Ciga ◽  
Alastair J. Noyce ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Ulcerative Colitis ◽  
Tumor Necrosis Factor ◽  
Crohn Disease ◽  
Tumor Necrosis ◽  
Mendelian Randomization ◽  
Age At Onset ◽  
Multiple Sclerosis Risk ◽  
Necrosis Factor

ObjectiveTo evaluate the effects of long-term tumor necrosis factor (TNF) inhibition on the risk and age at onset of Parkinson disease (PD), we performed a 2-sample Mendelian randomization study using genome-wide association studies (GWAS) summary statistics.MethodsGenetic variants in the vicinity of TNFRSF1A, the gene encoding TNF receptor 1 (TNFR1), were identified as predictive of pharmacologic blockade of TNFR1 signaling by anti-TNF therapy, based on genetic associations with lower circulating C-reactive protein (CRP; GWAS n = 204,402). The effects of TNF-TNFR1 inhibition were estimated for PD risk (ncases/controls = 37,688/981,372) and age at PD onset (n = 28,568) using GWAS data from the International Parkinson's Disease Genomics Consortium and 23andMe, Inc. To validate variants as proxies of long-term anti-TNF treatment, we also assessed whether variant associations reflected anticipated effects of TNFR1 inhibition on Crohn disease, ulcerative colitis, and multiple sclerosis risk (n = 38,589-45,975).ResultsTNF-TNFR1 signaling inhibition was not estimated to affect PD risk (odds ratio [OR] per 10% lower circulating CRP = 0.99; 95% confidence interval [CI] 0.91–1.08) or age at onset (0.13 years later onset; 95% CI −0.66 to 0.92). In contrast, genetically indexed TNF-TNFR1 signaling blockade predicted reduced risk of Crohn disease (OR 0.75; 95% CI 0.65–0.86) and ulcerative colitis (OR 0.84; 95% CI 0.74–0.97) and increased multiple sclerosis risk (OR 1.57; 95% CI 1.36–1.81). Findings were consistent across models using different genetic instruments and Mendelian randomization estimators.ConclusionsOur findings do not imply that TNF-TNFR1 signaling inhibition will prevent or delay PD onset.Classification of EvidenceThis study provides Class II evidence that TNF-TNFR1 signaling inhibition is not associated with the risk or age at onset of PD.

Pathophysiology and Diagnosis of Ulcerative Colitis and Crohn Disease

2017 ◽  
Author(s):  
Julia B. Greer ◽  
Miguel D. Regueiro
Keyword(s):  
Computed Tomography ◽  
Ulcerative Colitis ◽  
Crohn Disease ◽  
Extraintestinal Manifestations ◽  
Infectious Colitis ◽  
Computed Tomographic ◽  
Computed Tomography Images ◽  
Computed Tomographic Scan ◽  
Inflammatory Bowel ◽  
Toxic Colitis

Inflammatory bowel disease (IBD) encompasses both ulcerative colitis and Crohn disease, and is characterized by recurrent bouts of inflammation of the gastrointestinal tract. IBD affects approximately 4 million people worldwide, and rates are gradually increasing. This review covers the etiology, epidemiology, definition and pathophysiology, extraintestinal manifestations, and other disease-related complications of IBD. Figures show the distribution of ulcerative colitis and Crohn disease by location, several colonoscopic photographs of patients with ulcerative colitis as well as those with Crohn disease, computed tomography images of patients with Crohn disease, small bowel follow-through and fluoroscopic spot images of a patient with chronic structuring Crohn disease, and a computed tomographic scan showing extraenteric manifestations of Crohn disease. Tables list the differential diagnosis of ulcerative colitis, types of infectious colitis, complications of IBD, diagnostic criteria of toxic colitis, physical signs of Crohn disease, differences between Crohn disease and ulcerative colitis, and common extraintestinal manifestations of IBD. This review contains 11 highly rendered figures, 7 tables, and 63 references.

Clinical Features and Differential Diagnosis of Ulcerative Colitis and Crohn Disease

2015 ◽  
Author(s):  
Edward L. Barnes ◽  
Jonathan S. Levine
Keyword(s):  
Ulcerative Colitis ◽  
Differential Diagnosis ◽  
Clinical Features ◽  
Crohn Disease ◽  
Clinical Utility ◽  
Fecal Calprotectin ◽  
Position Emission Tomography ◽  
Extraintestinal Manifestations ◽  
Pet Ct ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is composed of two major subtypes, ulcerative colitis (UC) and Crohn disease (CD). These chronic disorders, characterized by inflammation of the gastrointestinal tract, demonstrate a variety of clinical features, including intestinal and extraintestinal manifestations during periods of relapse and remission over many years. This review examines the clinical features of IBD, including the extraintestinal manifestations and diagnosis. Figures include examples of images conducted via computed tomography (CT), magnetic resonance imaging, and position emission tomography (PET)/CT. Tables list the location frequencies of UC and CD at the time of diagnosis, extraintestinal manifestations of IBD, differential diagnosis of UC and CD, and clinical utility of fecal calprotectin in the evaluation and management of IBD. This review contains 4 highly rendered figures, 5 tables, and 48 references. 

scholarly journals Transplantation of bone marrow cells from transgenic mice expressing the human MDR1 gene results in long-term protection against the myelosuppressive effect of chemotherapy in mice

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 1087-1093 ◽  
Author(s):  
GH Mickisch ◽  
I Aksentijevich ◽  
PV Schoenlein ◽  
LJ Goldstein ◽  
H Galski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multidrug Resistance ◽  
Transgenic Mice ◽  
Dose Escalation ◽  
Blot Analysis ◽  
Messenger Rna ◽  
Bone Marrow Cells ◽  
Selective Advantage ◽  
Mdr1 Gene ◽  
Human Mdr1

Abstract Many human cancers that are initially responsive to chemotherapy eventually fail to respond to treatment. For some drugs, dose escalation that may be required for a cure cannot be achieved because sensitive tissues such as bone marrow (BM) limit cytotoxic therapy. Approaches to prevent or circumvent BM toxicity are therefore a high priority of research on dose escalation protocols. In this study, we have transplanted BM cells from transgenic mice that constitutively express physiologic amounts of a functional human multidrug resistance (MDR1) cDNA to lethally irradiated C57BL/6 x SJL F1 mice (n = 36). From 6 weeks to 10 months after the transplant, all animals contained MDR1 DNA in spleen and BM specimens as indicated by Southern blot analysis, and expressed MDR1 messenger RNA in BM samples as detected by slot blot analysis. In addition, these animals were resistant to the myelosuppressive effect of doxorubicin, daunomycin, taxol, vinblastine, vincristine, etoposide, and actinomycin D, whereas control animals that were reconstituted with normal BM were drug sensitive. Finally, the chemoprotection afforded by the MDR1 gene could readily be reversed by adding chemosensitizers such as cyclosporin A and R-verapamil to chemotherapy. Hence, it appears that BM cells expressing the human MDR1 gene maintain this function after transplantation to host animals for a minimum of 10 months, and confer multidrug resistance to these BM recipients. This selective advantage conferred by expression of the MDR1 cDNA suggests a strategy for the use of MDR1 gene therapy in cancer chemotherapy and for the introduction of otherwise nonselectable genes into BM.

Sign in / Sign up

Export Citation Format

Share Document