Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over-expression of the MDR-1 gene, which codes for P-glycoprotein, is thought to be an important mechanism in the drug resistance exhibited by many tumours. A number of chemotherapeutic agents which induce MDR-1 expression are also components of combination chemotherapies that are used in the treatment of high grade non-Hodgkin's lymphomas (NHL). We have therefore examined expression of MDR-1 in a series of NHL by Northern blot analysis as well as investigated the localization of P-glycoprotein by immunohistochemistry. The series included 11 hyperplastic reactive nodes and tonsils, 17 low grade NHL and 15 high grade NHL. The levels of MDR-1 mRNA were quantified by scanning densitometry and comparison with levels of glucose-6-phosphate dehydrogenase (G6PD). The MDR-1 mRNA was observed in both non-malignant and NHL tissues. Immunohistochemical staining revealed that expression of MDR-1 mRNA in reactive nodes was related to the presence of P-glycoprotein in lymphocytes, however, P-glycoprotein was apparent in both the reactive lymphocytes and tumour cells in the NHL samples. Elevated mRNA levels (2-3 fold increase) were observed in some low grade and high grade NHL relative to those observed in reactive lymphoid tissue. There appeared to be little correlation, however, between expression of the MDR-1 gene and either treatment intensity or response to therapy. The drug resistance that is often encountered in NHL patients is therefore likely to involve mechanisms other than over-expression of P-glycoprotein.
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PMID:MDR-1 expression in non-Hodgkin's lymphomas is unrelated to treatment intensity or response to therapy. 853 96

We conducted a controlled trial of dexverapamil, an inhibitor of Pgp, in 45 Hodgkin's (HD) and 154 Non-Hodgkin's (NHL) lymphomas refractory to EPOCH chemotherapy. A total of 154 patients initially received EPOCH alone and (4.2%) with stable disease over two cycles or progressive disease "crossed over" to receive dexverapamil with EPOCH. Dexverapamil was escalated 8 dose levels, from 240 to 1200 mg/m2 per day. When possible, serial biopsies were obtained to measure MDR-1 expression by quantitative polymerase chain reaction. Median age was 44 years, 67% had stage IV disease, and median (range) prior regimens were 2 (1-12) in NHL and 1 (1-4) in HD. The maximum tolerated dose of dexverapamil was 900 mg/m2/day, and median plasma average concentrations of dexverapamil and nor-dexverapamil were 1.2 and 1.4 microM, respectively. There were 3 complete and 2 partial responses (12%) and 5 minor responses in NHL, and 2 of 10 HD patients achieved partial responses. MDR-1 was measured in 44 biopsies from 19 patients. Pre-therapy, MDR-1 was low (median 2.5 U) but increased (median 12.2 U) at cross-over. Among 6 patients with MDR-1 > 15, 3 responded to dexverapamil whereas only 1/8 patients with MDR-1 < 15 responded. EPOCH and dexverapamil were well tolerated. This study suggests that MDR-1 plays a role in clinical drug resistance of lymphomas, but also suggests that non-MDR-1 mechanisms are present in such patients. Earlier intervention with dexverapamil may be more effective and warrants further study.
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PMID:Modulation of multidrug resistance by dexverapamil in EPOCH-refractory lymphomas. 869 39

Non-Hodgkin's lymphomas (NHL) are B-cell malignancies which generally present molecular abnormalities, such as bcl-2 translocation t(14; 18) predominantly in the follicular subgroup. Other molecular events have been described in NHL, including p53 gene mutation and overexpression of one chemoresistance mechanism, the multidrug resistance system, P-glycoprotein (MDR 1/P-gp). In this study, we analysed samples from 44 NHL patients with the presence of the bcl-2 major breakpoint region (MBR) rearrangement in 29 and without in 15. Immunochemical analysis revealed that 39 samples were positive for bcl-2 protein expression in tumoral cells (88.6%). Seventeen (38.6%) patients expressed P-gp and 9 (20.5%) expressed p53 proteins. Eleven patients expressed both bcl-2 and P-gp proteins, four expressed bcl-2 and p53 proteins whereas four expressed bcl-2, p53 and P-gp proteins. Our results confirm the importance of p53 expression as a key prognostic factor, and no objective response (OR) was found in patients with p53 positivity. MBR rearrangement was not associated with poor response to chemotherapy (62.1% OR in MBR positive patients v. 60% OR in MBR negative patients). The clinical impact of P-gp cannot be identified because no relationship was observed between P-gp expression and prognosis (58.8% OR in P-gp positive patients v. 63% OR in P-gp negative patients).
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PMID:MBR rearrangement and P-glycoprotein expression are not independent prognostic factors like p53 protein in malignant lymphoma. 968 Dec 18

Tc-99m sestamibi (MIBI) has been used as a tumor-seeking agent. However, its role in detecting lymphomas has not been widely investigated. The aim of the present study was to determine the uptake and clearance characteristics of Tc-99m MIBI in vincristine-resistant lymphoma cell lines. In addition, thallium-201 (Tl-201) and gallium-67 (Ga-67) uptake and clearance characteristics were evaluated for comparison with Tc-99m MIBI. Drug-resistant lymphoma cell lines (monocyte-like, histiocytic lymphoma, human; B-lymphoma cell line, American Burkitt lymphoma, lymphoblastoid, human; Hodgkin's disease, lymphoid, human) were selected by multistep vincristine treatment up to 50 nM. After incubation of the radiotracers, Tc-99m MIBI, Tl-201 and Ga-67, in medium for 0, 10, 20, 30, 60 or 120 min, the uptake and clearance of each radiotracer were measured in the drug-resistant lymphoma cell lines. In addition, P-glycoprotein expression was determined by immunohistochemical study. In a comparison of the three radiotracers, the uptake of Tc-99m MIBI was the greatest in the studied wild-type lymphoma cell lines. Tc-99m MIBI uptake was much lower in drug-resistant tumor cell lines than in non-resistant cell lines. On the other hand, the uptake characteristics of Tl-201 did not differ between drug-resistant and non-resistant cells. Immunohistochemistry analyses of Ab-1 or JSB indicated that tumor cells expressed MDR-1 protein in all three cell lines. Tc-99m MIBI is a good radiotracer for detecting drug resistance in lymphoma cell lines.
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PMID:Comparison of the uptake and clearance of Tc-99m MIBI, Tl-201 and Ga-67 in drug-resistant lymphoma cell lines. 1152 May 98

Vinblastine, vincristine and doxorubicyn are currently used in chemotherapeutic treatments of several malignancies including HIV-1 associated tumours Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL). Hence, AIDS patients also affected by KS and NHL may be simultaneously subjected to highly active antiretroviral therapy (HAART) and cytotoxic drugs to combat HIV-1 infection and cancer aggressiveness. In order to assess if the combination of these therapies may affect cell growth and survival of P-glycoprotein expressing MDR variants of the human CD4+ T-lymphoblastoid CEM cell line, the protease inhibitors (PI's) ritonavir, saquinavir and indinavir were tested in an in vitro assay for their ability to potentiate the vinblastine, vincristine and doxorubicyn cytotoxicity. The results we obtained demonstrated that at the concentration of 10 micrograms/ml, ritonavir and in a lesser extent saquinavir act as MDR reversing agents. By contrast, the PI indinavir at least in the CEM cell system, does not affect the patterns of drug resistance. The level of chemosensitization exerted by ritonavir and saquinavir suggests that these PI's may render P-glycoprotein expressing MDR cells de novo susceptible to the antineoplastic drugs vinblastine, vincristine and doxorubicyn.
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PMID:Modulation of the multidrug resistance (MDR) phenotype in CEM MDR cells simultaneously exposed to anti HIV-1 protease inhibitors (PI's) and cytotoxic drugs. 1276 Mar 35

The effect of CMC-544, a calicheamicin-conjugated anti-CD22 monoclonal antibody, was analysed in relation to CD22 and P-glycoprotein (P-gp) in B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) in vitro. The cell lines used were CD22-positive parental Daudi and Raji, and their P-gp positive sublines, Daudi/MDR and Raji/MDR. Cells obtained from 19 patients with B-cell CLL or NHL were also used. The effect of CMC-544 was analysed by viable cell count, morphology, annexin-V staining, and cell cycle distribution. A dose-dependent, selective cytotoxic effect of CMC-544 was observed in cell lines that expressed CD22. CMC-544 was not effective on Daudi/MDR and Raji/MDR cells compared with their parental cells. The MDR modifiers, PSC833 and MS209, restored the cytotoxic effect of CMC-544 in P-gp-expressing sublines. In clinical samples, the cytotoxic effect of CMC-544 was inversely related to the amount of P-gp (P = 0.003), and to intracellular rhodamine-123 accumulation (P < 0.001). On the other hand, the effect positively correlated with the amount of CD22 (P = 0.010). The effect of CMC-544 depends on the levels of CD22 and P-gp. Our findings will help to predict the clinical effectiveness of this drug on these B-cell malignancies, suggesting a beneficial effect with combined use of CMC-544 and MDR modifiers.
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PMID:CMC-544 (inotuzumab ozogamicin) shows less effect on multidrug resistant cells: analyses in cell lines and cells from patients with B-cell chronic lymphocytic leukaemia and lymphoma. 1938 33

Tissue P-glycoprotein immunostaining was performed in seventy one patients with follicular large, mixed, or small cell non-Hodgkin's lymphomas. Only six patients (8.5%) demonstrated positive immunostaining for P-glycoprotein. All patients had complete and durable responses to initial therapy. P-glycoprotein (MDR) fails to predict for primary drug resistance in follicular lymphomas and is constitutionally expressed in only a few follicular lymphomas at present.
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PMID:P-glycoprotein - low constitutional expression does not correlate with treatment failure in follicular lymphomas. 2157 73

Richter's syndrome is defined as the transformation of low-grade lymphoma to a more aggressive high-grade malignant form, usually diffuse large B-cell lymphoma. Hodgkin's lymphoma variant of Richter transformation is relatively rare, and only approximately 100 cases have been reported in the literature. This study examined a case of a 53-year-old woman who developed Hodgkin's lymphoma almost 5 years after the diagnosis of chronic lymphocytic leukemia (CLL). The major points of interest regarding CLL with Hodgkin's transformation were also considered, such as the potential role of MDR-1 gene polymorphisms. The patient was evaluated for two MDR-1 gene polymorphisms, G2677T polymorphism in exon 21 and silent C3435T polymorphism in exon 26, to ascertain whether polymorphisms affect the risk of Hodgkin's lymphoma variant of Richter transformation and whether genomic polymorphisms provide prognostic information on the clinical progression of the disease. According to the data obtained, the analysis of polymorphisms in the MDR1 gene exons 21 and 26 revealed that the T2677T and T3435T alleles are not a predisposing factor to Richter transformation, while the presence of the wild-type genotype may be associated with a more favorable response to therapy.
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PMID:MDR-1 gene polymorphisms G2677T and C3435T in a case of Hodgkin's variant of Richter's syndrome. 2286 91

The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.
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PMID:Infectious complications in children treated for hodgkin and non-hodgkin lymphomas in polish pediatric leukemia/lymphoma study group: incidence, epidemiology and etiology. 3039 26