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Results for “Drug Resistance, Multiple”

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PubMed2004

[Nitric oxide synthase expression and multiple drug resistance in patients with acute leukemia].

OBJECTIVE: To determine the relationship between nitric oxide synthase (NOS) expression and Pgp/mdr-1. METHODS: The expressions of iNOS, eNOS, and Pgp were detected by immunohistochemistry, and the expressions of iNOS gene and mdr-1 gene were detected by RT-PCR. RESULTS: NOS expression increased in patients with acute leukemia compared with that of the controls. There was some correlation between iNOS and Pgp/mdr-1 gene expression. CONCLUSION: NO may influcence multiple drug resistance in patients with acute leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Biomarkers and multiple drug resistance in breast cancer.

Breast cancer, the most common form of cancer among women in North America and almost all of Europe, is a significant health problem in terms of both morbidity and mortality. It is estimated that each year this disease is diagnosed in over one million people worldwide and is the cause of more than 400,000 deaths. Although chemotherapy forms part of a successful treatment regime in many cases, as few as 50% patients may benefit from this, as a result of intrinsic or acquired multiple drug resistance (MDR). Through the use of in vitro cell culture models, a number of mechanisms of MDR have been identified; many, if not all, of which may contribute to breast cancer resistance in the clinical setting. This phenomenon is complicated by the likely multi-factorial nature of clinical resistance combined with the fact that, although apparently studied extensively in breast cancer, reported analyses have been performed using a range of analytical techniques; many on small sub-groups of patients, with different clinicopathological characteristics and receiving a range of therapeutic approaches. Larger defined studies, using standardised genomic and proteomics profiling approaches followed by functional genomics studies, are necessary in order to definitively establish the degree of complexity contributing to drug resistance and to identify novel therapeutic approaches - possibly involving chemotherapy, drug resistance modulators, and novel targeted therapies - to combat this disease.

Antineoplastic Agents↗
PubMed1992

Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli.

OBJECTIVE: To determine the clinical manifestations of patients with human immunodeficiency virus (HIV) infection and tuberculosis caused by multiple-drug-resistant bacilli compared with those with single-drug-resistant or susceptible bacilli. DESIGN: Descriptive, case-control, and cohort studies. SETTING: A large urban teaching hospital. PATIENTS: Sixty-two patients with tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients with tuberculosis caused by single-drug-resistant or susceptible bacilli (controls). MEASUREMENTS: Characteristics of clinical presentation, radiographs, pathologic abnormalities, antituberculosis treatment, and clinical course. RESULTS: Twenty cases (32%) had concomitant pulmonary and extrapulmonary disease at presentation compared with 9 controls (16%; odds ratio, 2.4; 95% CI, 1.0 to 5.9). More cases had alveolar infiltrates (76%; odds ratio, 3.6; CI, 1.2 to 11.4), interstitial infiltrates with a reticular pattern (67%; odds ratio, 7.8; CI, 1.0 to 83.5), and cavitations (18%; odds ratio, 6.6; CI, 0.8 to 315.3) on initial chest radiographs compared with controls (49%, 19%, and 3%, respectively). Pathologic specimens from cases showed extensive necrosis, poor granuloma formation, marked inflammatory changes with a predominance of neutrophils, and abundant acid-fast bacilli. Twenty-five cases received two or more effective antituberculosis drugs for more than 2 months. Only 2 cases had three consecutive negative cultures for Mycobacterium tuberculosis; one patient died within 1 day of the last negative culture, and the other had positive cultures 496 days later. The remaining 23 cases had persistently or intermittently positive cultures despite therapy. The clinical course of these cases suggested overwhelming miliary tuberculosis with involvement of the lungs (77%), pleura (15%), stool (34%), meninges (13%), bone marrow (16%), blood (10%), lymph nodes (10%), and skin (8%). The median survival time was 2.1 months for cases compared with 14.6 months for controls (P = 0.001, log-rank test). CONCLUSIONS: Tuberculosis caused by multiple-drug-resistant bacilli in patients with HIV infection is associated with widely disseminated disease, poor treatment response with an inability to eradicate the organism, and substantial mortality.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Multiple drug resistant typhoid fever outbreak in Kashmir Valley.

We report the first ever report of multiple drug resistant salmonella typhi epidemic from Asia. The outbreak started in April 1988 and virtually ended by June 1988. The outbreak occurred in Baramullah town of Kashmir valley. In an epidemiological survey 230 cases were diagnosed as enteric fever. 46 cases (20%) were culture positive. A very rare multiple drug resistant strain of S. typhi was identified as phage type biotype II untypeable (UVS2). The strain was sensitive to Norfloxacin. This outbreak of S. typhi has many similarities with Mexico epidemic. Ingestion of contaminated water seems to be the possible cause for the outbreak.

Adolescent↗
PubMed1994

Transfer and expression of the human multiple drug resistance gene in human CD34+ cells.

The human multiple-drug resistance (MDR1) gene has been transferred into human hematopoietic progenitors using retroviral gene transfer. Human bone marrow cells and isolated CD34+ cells isolated from marrow were exposed to growth factors interleukin-3 (IL-3), IL-6, and stem cell factor for 48 hours and then to two changes of MDR retroviral supernatants over the next 24 hours. Progenitor assays in methylcellulose at this time showed that 18% to 70% of BFU-E and 30% to 60% of CFU-GM contain the transferred MDR gene by polymerase chain reaction analysis. Up to 11.2% of the progeny of these cells express increased amounts of MDR glycoprotein on their surface by fluorescence-activated cell sorter (FACS) analysis. In addition, transduced cells are enriched in high MDR-expressing cells after exposure to taxol as assessed by FACS analysis, and by resistance of BFU-E to taxol (Bristol-Myers Squibb, Princeton, NJ). These studies indicate the feasibility of using MDR gene transfer as a means of enriching marrow for MDR-transduced cells. They also provide the basis of a phase 1 clinical protocol in patients with advanced cancers not involving the bone marrow for the use of MDR gene transfer as a means of protecting marrow cells, which normally express low levels of MDR, from the myelosuppressive effects of drugs like taxol.

Antigens, CD↗
PubMed1996

Retroviral transfer and expression of the human multiple drug resistance (MDR) gene in peripheral blood progenitor cells.

The multiple drug resistance (MDR) gene P-glycoprotein product is a transmembrane efflux pump that prevents toxicity of a variety of chemotherapeutic agents, including the anthracyclines, Vinca alkaloids, podophyllins, and taxol. The bone marrow toxicity of these drugs is due to the low or absent expression of MDR in marrow cells. Transfer and expression of the human MDR gene into bone marrow progenitors should prevent this toxicity. We report here the efficient transfer and expression of the MDR gene by retroviral-mediated gene transfer into CD34(+) cells isolated from peripheral blood progenitor cells (PBPCs), comparable to that obtained using bone marrow-derived progenitors. Optimal MDR transduction of these PBPC-derived cells requires exposure to growth factors and a period of preincubation. In addition, we demonstrate that we can transduce up to 100% of progenitor cells derived from PBPCs and can protect up to 25% of these progenitors from a dose of taxol toxic to untransduced controls.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1984

Co-amplification of double minute chromosomes, multiple drug resistance, and cell surface P-glycoprotein in DNA-mediated transformants of mouse cells.

A genetic system comprised of mammalian cell mutants which demonstrate concomitant resistance to a number of unrelated drugs has been described previously. The resistance is due to reduced cell membrane permeability and is correlated with the presence of large amounts of a plasma membrane glycoprotein termed P-glycoprotein. This system could represent a model for multiple drug resistance which develops in cancer patients treated with chemotherapeutic drugs. We demonstrate here that the multiple drug resistance phenotype can be transferred to mouse cells with DNA from a drug-resistant mutant and then amplified quantitatively by culture in media containing increasing concentrations of drug. The amount of P-glycoprotein was correlated directly with the degree of drug resistance in the transformants and amplified transformants. In addition, the drug resistance and expression of P-glycoprotein of the transformants were unstable and associated quantitatively with the number of double minute chromosomes. We suggest that the gene for multiple drug resistance and P-glycoprotein is contained in these extrachromosomal particles and is amplified by increases in double minute chromosome number. The potential use of this system for manipulation of mammalian genes in general is discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

[A bacteriological study of multiple-drug-resistant Pseudomonas aeruginosa isolates derived from 2 patients].

We investigated the isolation circumstances of multiple-drug-resistant Pseudomonas aeruginosa (MDRP) in the UOEH hospital and the bacterial analysis of isolated MDRP. From January to October 2003, MDRP was isolated from 2 patients. During this period, the isolation frequency of MDRP was 0.57% (2/350). Case 1 had 2 MDRP isolates from catheter urine, and case 2 had 5 MDRP isolates from pus. Regarding serotype, 2 isolates from case 1 were B type and the other 16 isolates from case 2 were E type. Pyomelanin was produced by 9 isolates of 16 E type isolates. The same PFGE patterns were observed in 2 isolates from case 1; that is, 9 pyomelanin producers from case 2 and the other 7 isolates from case 2, respectively. Metallo-beta-lactamase was produced by 2 isolates from case 1. bla(IMP) was detected from the 2 isolates by PCR, and the clones from case 1 were quite different from the clones from case 2. Regarding the pyomelanin producing isolates from case 2, although the clones were the same genetically, the MICs of imipenem and meropenem increased from 8 to > 32 microg/ml with the progress of time. In the UOEH hospital, 6 patients with MDRP isolates have been isolated so far, but these 6 patients are not correlated with each other. It is important that we detect and report MDRP as early as possible to prevent nosocomial infection.

Aged↗
PubMed1987

Atypical multiple drug resistance in a human leukemic cell line selected for resistance to teniposide (VM-26).

Resistance to the cytotoxic effects of many natural product drugs after exposure to a single agent is a common observation. The classes of drugs included in the "classic" multiple drug resistance phenotype are Vinca alkaloids, anthracyclines, epipodophyllotoxins, and antibiotics. We report here the characterization of a human leukemic cell line (CEM/VM-1) with "atypical" multiple drug resistance: despite resistance and cross-resistance to etoposide, anthracyclines, mitoxantrone, and 4'-[(9-acridinyl)amino]methanesulphon-m-anisidide (mAMSA), these cells retain sensitivity to the Vinca alkaloids. Further, even though this cell line is approximately equal to 40-fold cross-resistant to the cytotoxic effect of etoposide (VP-16), it is similar to drug-sensitive CEM cells in the cellular pharmacology of [3H]VP-16 as determined by zero time binding, initial influx rate, steady state drug concentration, and unidirectional efflux. Our studies suggest that the resistance of CEM/VM-1 cells to epipodophyllotoxins is due to an altered interaction between drug and its cellular target(s) by a mechanism unrelated to the decreased cellular concentration of drug associated with the "classic" multiple drug resistance phenotype.

Cell Line↗
PubMed1984

[Role of multiple drug resistance in the biology of pathogenic and opportunistic bacteria].

The significance of cloning of pathogenic and opportunistic multiple drug-resistant bacteria is analysed from the present viewpoints of medicine and veterinary. Distribution of drug-resistant strains in men, animals and environment and occurrence of new type hospital and nosocomial infections are described. The controversial points of the antibiotics role in the formation of multiple drug resistance plasmids, occurrence of hospital resistant strains and the part of R plasmids in changing the biological characteristics of pathogenic and opportunistic bacteria are analysed. It is shown in relation to Salmonella that formation of definite clones of multiple drug resistant bacteria results in significant changing of epidemiology of the diseases caused by these organisms. The data on the identity of the biological and genetic characteristics of the Salmonella strains of some phage vars isolated in hospitals and outside the hospitals, as well as the data on the effect of R plasmids on the Salmonella virulence are presented. The thesis of a higher infective capacity of the strains with multiple drug resistance associated with their increased survival levels and a higher colonization ability is accentuated. The danger of occurrence of new type causative agents on formation of complex plasmids with additional determinants connected with the bacteria pathogenicity is discussed. The tasks of the further investigation of these aspects are formulated and the possible means for the control of this phenomenon are presented.

Animals↗
PubMed2002

Molecular cloning and characterization of the Salmonella enterica Serovar Paratyphi B rma Gene, which confers multiple drug resistance in Escherichia coli.

A genomic library from a strain of Salmonella enterica serovar Paratyphi B that exhibits multiple drug resistance (MDR) was constructed in Escherichia coli. Two of the recombinant plasmids, pNOR5 and pNOR5, conferred resistance only to fluoroquinolones in E. coli, whereas the third, pNCTR4, conferred the MDR phenotype. Sequence and subcloning analysis showed that it is the presence of RecA on the first two plasmids which confers resistance to fluoroquinolones in E. coli. A similar analysis established that the MDR phenotype conferred by pNCTR4 is due to a gene, rma (resistance to multiple antibiotics), which encodes a 13.5-kDa polypeptide. The derived sequence for Rma exhibits a high degree of similarity to those of a group of MarA-like activators that confer MDR in E. coli. A MalE-Rma fusion protein was purified to near homogeneity and was shown to interact with a DNA fragment carrying a MarA operator sequence. Furthermore, overexpression of rma in E. coli caused changes in the outer membrane protein profile that were similar to those reported for MarA. These results suggest that Rma might act as a transcriptional activator of the marA regulon.

ATP-Binding Cassette Transporters↗
PubMed1994

Mutations in the yeast PDR3, PDR4, PDR7 and PDR9 pleiotropic (multiple) drug resistance loci affect the transcript level of an ATP binding cassette transporter encoding gene, PDR5.

The yeast pleiotropic (multiple drug) resistance gene PDR5 encodes a product with homology to a large number of membrane transport proteins including the mammalian multiple drug resistance family. In this study, we identified four genes on chromosome II that affect the steady-state level of PDR5 transcript in addition to a previously identified positive regulator, PDR1. The genes in question are PDR3, PDR4, PDR7 and PDR9. We also analyzed the interaction between PDR5 and YAP1. YAP1 encodes a positive regulator with a leucine zipper motif that causes pleiotropic drug resistance when overproduced. YAP1-mediated pleiotropic drug resistance is not dependent on the presence of PDR5 and must act through other genes.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

Antimalarial efficacy of arteether against multiple drug resistant strain of Plasmodium yoelii nigeriensis.

New quick-acting blood schizontocides are needed to contain the spread of multiple drug resistant strains of P. falciparum and for the treatment of the cerebral malaria cases. A multiple drug resistant strain of P. yoelii nigeriensis resistant to mefloquine (128 mg/kg x 6 days), quinine (300 mg/kg x 7 days) and chloroquine (64 mg/kg x 8 days) was found to be completely susceptible to arteether (a 30:70 mixture of alpha and beta enantiomers) and a dose of 5 mg/kg x 3 days by i.m. route was curative in Swiss mice. Artemisinin at 50 mg/kg x 7 days had only suppressive action against this strain.

Animals↗
PubMed2006

Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant pulmonary tuberculosis.

BACKGROUND: The emergence and spread of multiple-drug-resistant tuberculosis (MDR-TB), caused by strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin, is a potential threat to global tuberculosis control. Treatment is prolonged, expensive, more toxic than treatment of susceptible tuberculosis, and often unsuccessful. Experts are still undecided on the management of people exposed to MDR-TB. OBJECTIVES: To evaluate antituberculous drugs given to people exposed to MDR-TB in preventing active tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (January 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to January 2006); EMBASE (1974 to January 2006), LILACS (1982 to January 2006), conference proceedings, and reference lists. We also contacted researchers and organizations. SELECTION CRITERIA: Randomized controlled trials comparing antituberculous drug regimens with an alternative antituberculous drug regimen, placebo, or no intervention given to people exposed to MDR-TB for preventing active tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently inspected titles and abstracts identified by the search in order to identify potentially relevant publications for inclusion and analysis. MAIN RESULTS: No randomized controlled trials met the inclusion criteria. AUTHORS' CONCLUSIONS: The balance of benefits and harms associated with treatment for latent tuberculosis infection in people exposed to MDR-TB is far from clear. Antituberculous drugs should only be offered within the context of a well-designed randomized controlled trial, or when people are given the details of the current evidence on benefits and harms, along with the uncertainties.

Antitubercular Agents↗
PubMed1994

Multiple drug resistance in the pathogenic protozoa.

Evidence for the phenomenon of multiple drug resistance (MDR) in the well studied pathogenic protozoa has been examined. This has been placed in the more familiar context of the MDR efflux transporters and the cloned mdr genes of mammalian cells. Homologues of the mdr gene family in protozoa and their possible role in drug efflux have been compared with their mammalian counterparts. Possible mechanisms and models for drug efflux have been considered. The unusual and extensive range of substrates transported by the ATP-binding cassette (ABC) family of transporters which includes the MDRs has been raised. The impact of kinetics, structure and bioenergetics of the MDR family members on mechanisms of transport has been accentuated to argue that MDR efflux considered in isolation appears bizarre but may be better understood in a broader context.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Synthesis and activity of N-acyl azacyclic urea HIV-1 protease inhibitors with high potency against multiple drug resistant viral strains.

As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P(1)' ligands. The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains.

Aza Compounds↗