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)

Patients with Hodgkin's disease have higher a prevalence of thyroid function abnormalities and, perhaps, orbitopathy than the general population, but the pathophysiology of this association and its relationship to Hodgkin's disease treatment remain unclear. We analyzed the frequency of thyroid function abnormalities, autoantibodies against thyroid antigens, and autoimmunity against extraocular muscle cell antigens by Western blot analyses and antibody-dependent cellular cytotoxicity (ADCC) assays in patients with Hodgkin's disease (n = 20) and controls (n = 10). Hodgkin's disease patients were subdivided into those treated with thyroidal external beam radiation therapy (XRT, n = 15) or chemotherapy (MOPP/ABVD, n = 5). The ADCC assay against extraocular muscle cells was increased in patients with Hodgkin's disease (5.5% vs. <1.0%, p = .026) when compared with controls. In addition, Hodgkin's disease patients treated with XRT (with or without chemotherapy) had significantly higher ADCC tests than controls (9.7% vs. <1.0%, p = .010), In contrast, ADCC assays were not different between Hodgkin's disease patients treated with chemotherapy alone and controls (<1.0% vs. <1.0%, p = .53). Hodgkin's patients treated with XRT had higher ADCC assays than those treated with chemotherapy alone (p = .087), although this difference did not achieve statistical significance. Serum measurements of antithyroid peroxidase (TPO) antibodies, antithyroglobulin (Tg) antibodies, thyroid binding inhibitory immunoglobulins (TBII), and thyroid stimulating immunoglobulin (TSI) were similar in all groups. Antibodies against the 64 kDa orbital antigen were detected in 1 patient and 1 control subject. Excluding patients already treated with L-thyroxine for hypothyroidism (n = 5), free T3, but not free T4, was lower in the Hodgkin's disease group than in controls (2.2 pg/mL vs. 2.7 pg/mL, p = .008). Thyrotropin (TSH) concentrations were not statistically different between these groups. In summary, these data show: (1) ADCC against human orbital muscle cells is increased in patients with Hodgkin's disease compared with controls: (2) these differences were noted among Hodgkin's disease patients treated with thyroidal XRT, with or without chemotherapy, and not among those patients treated with chemotherapy alone; and (3) no statistically significant differences in the frequency of thyroid autoantibodies were found. These data suggest that patients with Hodgkin's disease display altered antibody-dependent immune function toward extraocular muscle cells that may possibly be related to by XRT. Larger, prospective studies assessing thyroid and orbital-related immunologic abnormalities in Hodgkin's disease are warranted.
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PMID:Hodgkin's disease treated with neck radiation is associated with increased antibody-dependent cellular cytotoxicity against human extraocular muscle cells. 922 15

Bcl-2 overexpression has been shown to be associated with several malignancies, including B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL), mainly low-grade and follicular in type. It has as yet not been described in hairy cell leukemia (HCL). In 30 patients with CLL and 14 with HCL who were consecutively selected for treatment with purine analogues (Fludarabine in CLL and 2-chloro-deoxy-adenosine in HCL), we evaluated bcl-2 oncoprotein expression in leukemic cells on marrow sections that were taken before treatment and stained immunohistochemically with a monoclonal antibody (Dakopatts 124 clone), by the avidin-biotin-peroxidase method. All samples were found to be bcl-2 positive, with a staining intensity that was moderate to strong in CLL and weak to moderate in HCL. 83% of CLL and 100% of HCL patients were responsive to purine analogues. These findings show that bcl-2 is overexpressed in almost all cases CLL and HCL and that bcl-2 overexpression does not predict a poor response to purine analogues, which are believed to induce apoptosis.
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PMID:BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy-adenosine. 961 87

We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.
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PMID:A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature. 1043 11

The utility of staining Reed-Sternberg (RS) cells with CD30, CD15 and CD45 as a diagnostic aid in Hodgkin's disease (HD) and the value of microwave citrate antigen retrieval (AR) method in improving the results of immunohistochemical (IHC) studies were evaluated. Histological and immunohistological studies were carried out on 21 patients with HD seen from January 1987 to December 1996 in the Pathology Department of the Cumhuriyet University, School of Medicine. Avidin biotin peroxidase complex (ABC) was used in IHC study as a method for detection of RS cells. Monoclonal antibodies CD30, CD15 and CD45 were applied on formalin fixed paraffin embedded tissue sections. In order to enhance the immunoreactivity, microwave citrate AR method and proteolytic pretreatment were used. The reactivity of RS cells and staining patterns were determined. In 14 (70%) of the 20 patients, RS cells stained positively with CD30, in 16 (80%) CD15 staining was positive and only 1 (5%) was positively stained with CD45. A combination of cytoplasmic with cell surface staining was common with CD30, while paranuclear deposit with cell surface and cytoplasmic staining was common with CD15. In conclusion, to facilitate the detection of RS cells in formalin fixed paraffin embedded tissues, the application of a panel of markers appears to be necessary. Also AR method seems to be helpful in obtaining optimal results on formalin fixed paraffin embedded tissue.
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PMID:Utility of CD15, CD30 & CD45 in the immunohistochemical diagnosis of Hodgkin's disease by antigen retrieval method. 1048 40

The purpose of this study was to analyse the proliferative fraction with the monoclonal antibody M1-R-R to M1-subunit ribonucleotide reductase and with MIB-1 to Ki-67 antigen in relation to p53 protein expression in fine needle aspirates from B-cell non-Hodgkin's lymphomas. One hundred and thirty-seven cases, previously diagnosed and sub-typed according to the Kiel classification and characterized by immunophenotyping, were included in the study. The M-1 subunit ribonucleotide reductase (M1-R-R), Ki-67 and p53 antigens were detected using monoclonal antibodies on stored cytospin preparations. There was a good correlation (r = 0.72) between Ki-67 and M1-R-R positive cell fraction in both high and low grade lymphomas. High-grade lymphomas had a median percentage of M1-R-R/MIB-1 positive cells of 53.0/73.0 for lymphoblastic, 61.0/52.0 for immunoblastic and 33.5/41.0 for centroblastic lymphomas, respectively. In low grade lymphomas figures of median percentage of M1-R-R/MIB-1 were 9.0/15.0 for centroblastic/centrocytic, 11.0/9.5 for chronic lymphocytic leukaemia, 16.0/27.0 for centrocytic and 12.0/9.0 for immunocytomas, respectively. The median percentages of M1-R-R/MIB-1 for high and low grade lymphomas were 37.0/50.5 and 11.0/12.0, respectively. In the p53 positive cases the proliferation rate as measured by staining for M1-R-R and MIB-1 was higher than in p53 negative cases, but the difference was not statistically significant. The results show that cytospin material obtained by fine needle aspiration and stored at -70 degrees C for years can be used reliably for both peroxidase-avidin-biotin and three-step alkaline phosphatase immunocytochemical staining. In addition, proliferation fraction determined by M1-R-R monoclonal antibody staining correlates well with that measured by an established marker for cell proliferation, the Ki-67 antibody. However, the proliferation fraction as measured by the two antibodies differs in the various subtypes of non-Hodgkin's lymphoma which indicates that they may contribute different prognostic information.
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PMID:Analysis of proliferating cell fraction determined by monoclonal antibody to M1-subunit ribonucleotide reductase and Ki-67 in relation to p53 protein expression in fine-needle aspirates from non-Hodgkin's lymphomas. 1101 56

Excessive apoptosis has a central role in ineffective hematopoiesis in myelodysplastic syndrome (MDS). The aim of the study was to quantify apoptosis and Bcl-2 expression in patients with MDS and to use these parameters in the evaluation of treatment efficacy with compounds modulating proapoptotic cytokines. Bone marrow (BM) samples from eight MDS patients were studied: four with refractory anemia and four with refractory anemia with ringed sideroblasts. Two patients with Hodgkin disease without BM determination were studied for control. Therapy consisted in administration of pentoxyphylline, dexamethasone and ciprofloxacin. Biochemical assay of apoptosis and Bcl-2 was performed using annexin V-biotin conjugate antibody and anti-human Bcl-2 antibody respectively, followed by streptavidine-peroxidase conjugate, and peroxidase substrate. Ultrastructural investigation of BM samples was performed with standard electron microscopy techniques. Most of BM hematopoietic cells in the MDS patients had ultrastructural features of various stages of apoptosis including chromatin condensation and margination, cytoplasm condensation and budding of nuclear and plasma membranes to produce apoptotic bodies. Bcl-2 expression showed an inverse correlation with the rate of the apoptotic process. Periodic evaluation of these two parameters has shown an increase of Bcl-2 expression and a decrease of apoptotic rate in patients who had responded to the treatment. Response to the treatment was appreciated in accordance with their transfusion needs. Treatment efficiency diminished in time. The rate of apoptosis was inversely correlated with the level of Bcl-2 expression. These results confirm the importance of the apoptotic process evaluation in monitoring MDS treatment.
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PMID:Apoptotic rate in patients with myelodisplastic syndrome treated with modulatory compounds of pro-apoptotic cytokines. 1459 56

Effective antibody-drug conjugates (ADC) combine high drug-linker stability in circulation and efficient intratumoral release of drug. Conjugation of monomethyl auristatin E (MMAE) to the anti-CD30 monoclonal antibody (mAb), cAC10, produced a selective and potent ADC against CD30(+) anaplastic large cell lymphoma and Hodgkin's disease models. This ADC, cAC10-valine-citrulline-MMAE, uses a protease-sensitive dipeptide linker designed to release MMAE by lysosomal cathepsin B in target cells but maintain a stable linkage and attenuate drug potency in circulation. To evaluate ADC stability in vivo, we developed methods for measuring drug/mAb ratios at progressive times in plasma from ADC-treated mice and nonhuman primates. Anti-idiotype mAb permitted the capture and quantitation of mAb cAC10, whereas antidrug mAb and MMAE-conjugated horseradish peroxidase reporter provided quantitative detection of conjugated drug following its in vitro release by cathepsin B. These data were validated by an alternative ELISA using anti-idiotype and anti-MMAE mAbs for capture and detection, respectively. Both methods differentiated ADC with variable levels of drug loading and were subsequently applied to stability studies in severe combined immunodeficient mice and cynomolgus monkeys. Evaluation of ADC from mouse circulation showed the linker half-life to be approximately 144 hours (6.0 days), significantly greater than that reported for disulfide- or hydrazone-linked ADCs in mice or human trials. In cynomolgus monkey, the apparent linker half-life was approximately 230 hours (9.6 days), suggesting that the drug-linker will be highly stable in humans. These data represent the longest reported drug-linker half-life to date and provide the basis for the pronounced specificity and antitumor activity of cAC10-valine-citrulline-MMAE.
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PMID:In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. 1570 75

There is little quantitative information about the amount of fibrosis in lymphomas. The aim of the present study was to investigate the amount of fibrosis in lymphomas and to highlight the relationship between fibrosis and mast cells, the key players of fibrosis. Tissue sections of 60 patients with diagnosis of lymphoma were reevaluated for classification. The mean fibrotic-stained area percentage (F-SAP) was determined in van Gieson-stained digital images using image analysis (Mediscope, Dokuz Eylul University, Clinical Engineering, Turkey). Mast cells were visualized using streptavidin peroxidase immunohistochemistry with anti-tryptase staining. Twenty-seven (44%) cases were Hodgkin's lymphoma (HL). F-SAP was 11.09+/-8.96 and 1.72+/-1.76 for HL and non-HL cases (Mann-Whitney U, p<0.000), and the mean mast cell count (MMCC) was 24.63+/-13.58 and 8.03+/-8.07, respectively (Mann-Whitney U test, p<0.000). There was a significant difference between F-SAP and MMCC concerning different types of lymphomas (Kruskal-Wallis test, p>0.000). F-SAP was highest in nodular sclerosis HL, and MMCC was highest in mixed cellular HL. There was a strong positive correlation between MMCC and F-SAP (Pearson Correlation test, p<0.000, r=0.51). These results suggest that the amount of fibrosis demonstrates differences in subtypes of lymphomas, and mast cells are increased in fibrosing lymphomas. However, it seems likely that more than one cell type is involved.
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PMID:Fibrosis in Hodgkin and non-Hodgkin lymphomas. 1780 76

Nitric oxide ((.)NO) induces apoptosis at high concentrations by S-nitrosating proteins such as glyceraldehyde-3-phosphate dehydrogenase. This literature analysis revealed that failure to sustain high (.)NO concentrations is common to all cancers. In cervical, gastric, colorectal, breast, and lung cancer, the cause of this failure is the inadequate expression of inducible nitric oxide synthase (iNOS), resulting from the inhibition of iNOS expression by TGF-beta1 at the mRNA level. In bladder, renal, and prostate cancer, the reason for the insufficient (.)NO levels is the depletion of arginine, resulting from arginase overexpression. Arginase competes with iNOS for arginine, catalyzing its hydrolysis to ornithine and urea. In gliomas and ovarian sarcomas, low (.)NO levels are caused by inhibition of iNOS by N-chlorotaurine, produced by infiltrating neutrophils. Stimulated neutrophils express myeloperoxidase, catalyzing H2O2 oxidation of Cl- to HOCl, which N-chlorinates taurine at its concentration of 19 mM in neutrophils. In squamous cell carcinomas of the skin, ovarian cancers, lymphomas, Hodgkin's disease, and breast cancers, low (.)NO concentrations arise from the inhibition of iNOS by N-bromotaurine, produced by eosinophil-peroxidase-expressing infiltrating eosinophils. Eosinophil peroxidase catalyzes the H2O2 oxidation of Br- to HOBr, which N-brominates taurine to N-bromotaurine at its concentration of 15 mM in eosinophils. In microvascularized tumors, the (.)NO concentration is further depleted; (.)NO is rapidly consumed by red blood cells (RBCs) through S-nitrosation of RBC glutathione and hemoglobin, and by oxidation to nitrate by RBC oxyhemoglobin. Angiogenesis-inhibiting antibodies are currently used to treat cancers; their mode of action is not, as previously thought, reduction of the tumor O2 or nutrient supply. They actually decrease the loss of (.)NO to RBCs.
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PMID:Apoptosis-inducing high (.)NO concentrations are not sustained either in nascent or in developed cancers. 1875 45

Epigenetic gene silencing due to promoter methylation is observed in human neoplasia, including lymphoma and certain cancer types. One important target for gene methylation analysis in non-Hodgkin lymphoma (NHL) is inhibitor of DNA binding 4 (ID4). The present study aimed to investigate the gene methylation status of ID4, the expression of ID4 protein and the effect of demethylating agent 5-aza-2'-deoxycytosine (CdR) in the Raji human Burkitt's lymphoma cell line in vitro. Following assessment of the inhibition of Raji cell growth by various concentrations of CdR, the effects of CdR on the expression of ID4 protein were assessed using the immunocytochemical streptavidin-peroxidase method and semi-quantitative analysis, while apoptosis and cell cycle were determined by flow cytometry. The ID4 gene methylation status of Raji cells was tested using methylation-specific polymerase chain reaction analysis. ID4 was methylated and its protein expression was low in the control group, while ID4 was partly or completely demethylated and its protein expression was upregulated in Raji cells treated with CdR. In addition, CdR induced apoptosis and cell cycle arrest in Raji cells in a dose- and time-dependent manner. These results demonstrated that ID4 is hypermethylated and its protein expression is low in Burkitt's lymphoma cells, while CdR reversed the abnormal DNA methylation and induced re-expression of ID4 protein. Hypermethylation of ID4 promotes the proliferation of Burkitt's lymphoma cells; ID4 may function as a tumor suppressor and can be targeted with demethylating compounds such as CdR for the treatment of Burkitt's lymphoma.
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PMID:Inhibitor of DNA binding 4 functions as a tumor suppressor and is targetable by 5-aza-2'-deoxycytosine with potential therapeutic significance in Burkitt's lymphoma. 2664 13


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