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)

In man, Hodgkin's disease (HD) represents the most frequent lymphoma entity whose pathogenesis is still unknown. In order to contribute to the characterization of the molecular mechanisms of this disease, cDNAs coding for the HD characteristic antigen CD30 were cloned from expression libraries of the human HUT-102 cell line using the monoclonal antibodies Ki-1 and Ber-H2. The open reading frame of the cDNA that can be translated from two mRNA species of 2.6 kb, and 3.8 kb, respectively, predicts a 595 amino acid protein with leader, extracellular, single transmembrane, and intracellular domains. When expressed in COS-1 cells, the cDNA presented properties comparable to native CD30 antigen. The CD30 extracellular domain proved to be homologous to members of the nerve growth factor receptor superfamily. Six cysteine-rich motifs could be recognized within the putative ligand-binding domain.
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PMID:Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. 131 Aug 94

The histopathologic pattern of tissues involved by Hodgkin's disease (HD) suggests excessive activation of environmental cells by cytokines released by Hodgkin-Reed-Sternberg (HRS) cells, which are considered as the neoplastic component of HD lesions. This hypothesis has been supported by many studies performed in vitro using HD cell lines. In this study, we have tried to demonstrate the cytokine-producing cells in an environment as close as possible to the in vivo conditions, using in situ hybridization onto frozen sections of HD samples. [35S]-labelled single-stranded RNA probes were prepared by transcribing human cDNA fragments of the TNF-alpha and IL-1 alpha genes subcloned into appropriate vectors. A total of 19 specimens of HD lesions, including 7 cases of nodular sclerosing (NS) type and 12 cases of mixed cellularity (MC), were tested with both types of probes. Clinical stages included stage I (6 cases), stage II (4 cases), stage III (6 cases) and stage IV (3 cases). TNF-alpha and/or IL-1 alpha expression was observed in 12 among 19 HD cases. However, neither the histological type nor the clinical status of the patients was correlated with the profile of cytokine secretion. Most of the cytokine-producing cells could be identified as HRS cells due to their morphological appearance. In 3 cases, simultaneous analysis by immunohistochemistry and in situ hybridization showed that IL-1 alpha/TNF-alpha mRNA-producing cells simultaneously expressed the CD30 antigen, thereby confirming the HRS nature of these cells.
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PMID:In situ expression of the IL-1-alpha and TNF-alpha genes by Reed-Sternberg cells in Hodgkin's disease. 131 61

Murine monoclonal antibody HRS-4 (Ab1), which defines the cell-bound and soluble CD30 antigen associated with Hodgkin's lymphoma, was used to generate monoclonal anti-idiotypic antibodies (Ab2) in syngeneic BALB/c mice. Murine monoclonal Ab2 14G9 and Ab2 9G10 directed against HRS-4 were shown to be anti-idiotypic Ab2 beta carrying the internal image of the CD30 antigen. These antibodies bound specifically to HRS-4 and effectively inhibited binding of HRS-4 to a CD30 antigen preparation at concentrations as low as 50 ng/ml. KLH-coupled Ab2 beta 14G9 and 9G10 induced in BALB/c mice and New Zealand white rabbits a specific polyclonal humoral response against the 120 kDa band of the CD30 antigen. Moreover, BALB/c mice immunized i.p. with KLH-coupled 14G9 and 9G10 exhibited a statistically significant (p less than 0.01) delayed-type hypersensitivity reaction against CD30 expressing Hodgkin-derived L540-cells. We conclude from these data that Ab2 beta 14G9 and 9G10, mimicking structures of the nominal CD30 antigen, are capable of inducing a CD30-specific T-cell- and B-cell-mediated immune response in mice and even across species barriers in rabbits. These CD30 anti-id antibodies may hold promise for use as vaccines against CD30-antigen-expressing lymphomas.
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PMID:Anti-idiotype vaccine against Hodgkin's lymphoma: induction of B- and T-cell immunity across species barriers against CD30 antigen by murine monoclonal internal image antibodies. 131

The ability of the Ber-H2 (CD30) monoclonal antibody (mAb) to target in vivo Hodgkin (H) and Reed-Sternberg (R-S) cells was investigated in six patients with advanced Hodgkin's disease (HD). The patients were injected with scaled-up quantities of 'cold' Ber-H2 mixed-up to a small dose of 131I-labelled Ber-H2, and in vivo binding of the antibody to H and R-S cells was assessed by immunohistological analysis of tumour biopsies and immunoscintigraphy. Only 50% of tumour sites were imaged at scintigraphy by the 131I-labelled Ber-H2. In contrast, immunohistological studies on tissue biopsies, taken 24-72 h following the mAb injection, showed that H and R-S cells in all tumour sites, including those that were not imaged by immunoscintigraphy, were specifically and strongly labelled in vivo by the injected Ber-H2, at a dose as low as 30-50 mg of antibody. In vivo binding of a single dose of Ber-H2 mAb to H and R-S cells did not result in any anti-tumour effect. The excellent in vivo targeting of H and R-S cells with the Ber-H2 mAb may have been the result of multiple favourable factors, including: (a) the restricted expression of the CD30 antigen in normal human tissues; (b) the low level of soluble CD30 in the serum of our patients; and (c) the high affinity of the Ber-H2 mAb for the CD30 molecule. The immunohistological results presented in this study provide a strong argument for using the Ber-H2 mAb as a carrier for delivering cytotoxic agents (isotopes or toxins) to neoplastic cells of HD refractory to conventional therapy.
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PMID:In vivo targeting of Hodgkin and Reed-Sternberg cells of Hodgkin's disease with monoclonal antibody Ber-H2 (CD30): immunohistological evidence. 132 18

The murine monoclonal antibody HRS-3 (Ab1; isotype IgG1-Kappa), that defines the CD30 antigen (m.w. 120,000) expressed by Hodgkin-Reed Sternberg cells was used to generate monoclonal anti-idiotype antibodies (Ab2) in syngeneic BALB/c mice. Ab2 were selected on the basis of their binding to HRS-3 immunoglobulin and F(ab')2 fragments and lack of reactivity with the whole immunoglobulin or F(ab')2 fragments of unrelated monoclonal antibodies of the same isotype and allotype. Such a putative anti-idiotypic Ab2, was designated antibody 12D3 and further characterized. 12D3 bound to the paratope of HRS-3, as determined by a 85% inhibition of binding of biotinylated HRS-3 to the cell surface of the CD30 positive Hodgkin cell line L450, and to semipurified CD30 positive cell lysates thereof at a concentration as low as 50 ng/well. These results demonstrate that 12D3 binds at or near the binding site of HRS-3 to the CD30 antigen. Purified 12D3 was coupled to keyhole limpet hemocyanine and used to immunize BALB/c mice and rabbits in order to obtain an Ab3 which binds to the CD30 antigen. These immune sera inhibited the binding of biotinylated 12D3 with HRS-3. Moreover, they showed binding activity with the CD30 positive L540 Hodgkin cell line as well as with the L540 cell lysates, indicating that an anti-anti-idiotopic antibody (Ab3) shares idiotopes with Ab1 (HRS-3). These data suggest that antibody 12D3 may be useful in the generation of an anti-idiotype vaccine against Hodgkin's lymphomas.
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PMID:Idiotype vaccine against Hodgkin's lymphoma: generation and characterization of an anti-idiotypic monoclonal antibody against the Hodgkin-associated (anti-CD 30) monoclonal antibody HRS-3. 165 53

Three monoclonal antibodies which strongly bind to Hodgkin and Reed-Sternberg cells and two corresponding Fab' fragments were linked to deglycosylated ricin A chain (dg A) to evaluate their potential as immunotoxins for the treatment of Hodgkin's disease. Two of the antibodies, Ber-H2 and HRS-3, were shown to bind to the same epitope on the CD30 antigen, whereas the third antibody, IRac, bound to a different antigen. None of the antibodies significantly cross-reacted with normal human tissues as judged by indirect immunofluorescence and immunoperoxidase analyses on frozen sections from 28 normal tissues. All three antibodies formed potent and specific immunotoxins. They inhibited protein synthesis of the L540 Hodgkin's disease cell line in vitro by 50% at concentrations of 1 x 10(-11) M for IRac.dgA, 9 x 10(-11) M for HRS-3.dgA, and 2 x 10(-10) M for Ber-H2.dgA. HRS-3 Fab' and IRac Fab' immunotoxins were 7.8- and 60-fold less cytotoxic, respectively, than their intact counterparts in vitro. In vivo, a single i.v. injection of a dose of Ber-H2.dgA, HRS-3.dgA, or IRac.dgA corresponding to 40% of the LD50 induced lasting complete remissions in 38, 44, and 50%, respectively, of mice with solid s.c. L540 tumors of 60 to 80 mm3 size (0.5-cm diameter). At equivalent dosage (40% of the LD50), the HRS-3 Fab'.dgA and the IRac Fab'.dgA both induced lasting complete remissions in 25% of the mice, although the HRS-3 Fab'.dgA was significantly superior to IRac Fab'.dgA at retarding tumor growth in the remaining animals. The effectiveness of the immunotoxins depended on the size of the tumor at the time of injection, since IRac.dgA treatment induced complete remissions in 100% of mice with small tumors (10 to 20 mm3, approximately 0.3 cm in diameter) but only 13% of mice with larger tumors of 400 to 600 mm3 (approximately 1 cm in diameter). Tumors which regrew after IRac.dgA treatment mainly consisted of antigen-deficient mutants having reduced sensitivity to IRac.dgA but normal sensitivity to HRS-3.dgA. It is concluded that HRS-3.dgA, HRS-3 Fab'.dgA, and IRac.dgA are candidates for the treatment of Hodgkin's disease in humans.
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PMID:Antitumor effects of ricin A chain immunotoxins prepared from intact antibodies and Fab' fragments on solid human Hodgkin's disease tumors in mice. 169 51

The CD30 antigen is a characteristic phenotypic feature of Sternberg-Reed and Hodgkin cells and is also found in a subset of large cell non-Hodgkin's lymphomas. The finding of CD30 positive cells in some centroblastic/centrocytic (cb/cc) follicular lymphomas prompted us to characterize the presence and distribution of CD30 positive cells in this type of lymphoma, using the monoclonal antibody BerH2. CD30 positive cells were present in 17/19 of the cases studied, located mainly at the edge of the neoplastic follicles, but also in some cases in perinodular or T-cell areas. This distribution resembles that found in reactive tonsils and lymph nodes. The majority of these CD30 positive cells in cb/cc lymphoma seem to be B-cells, as suggested by their reactivity with B-cell markers demonstrated by double immunostaining. The nature of these CD30 positive cells is unclear, but they should be taken into consideration in the differential diagnosis of cb/cc lymphoma with lymphocyte predominance Hodgkin's disease.
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PMID:CD30 expression in follicular lymphoma. 184

The soluble form of the CD30 antigen (sCD30), an 88-kd glycoprotein that is released by Hodgkin's-derived cell lines in vitro, can be detected in patients with Hodgkin's lymphoma, adult (HTLV-1+) T-cell leukemia, rare cases of non-Hodgkin's lymphoma, and acute infectious mononucleosis (anti-EBV-IgM+). In a prospective study of 90 consecutive untreated patients with newly diagnosed Hodgkin's disease who were treated according to the protocols of the German Hodgkin Study group, 22% had detectable levels of sCD30 in their serum. sCD30 was only detected in patients with B symptoms (20 of 44 or 45%), and maximum sCD30 levels (88 U/mL) were found in stage IVB. Of 87 patients evaluable for response, sCD30+ patients had significantly lower rates of complete remission (9 of 20 or 45% v 60 of 67 or 90%; P less than .001) and higher rates of progressive disease (9 of 20 or 45% v 6 of 67 or 9%; P less than .001) than CD30+ patients. Similarly, freedom from treatment failure curves were significantly worse for CD30+ patients (P = .0003). sCD30 disappeared after successful treatment, but increased in patients with progressive disease. It was never detected in patients in complete remission or in healthy controls. We conclude that sCD30 is a valuable marker for disease activity and has prognostic significance in Hodgkin's disease.
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PMID:Clinical significance of soluble CD30 antigen in the sera of patients with untreated Hodgkin's disease. 185 Mar 8

Five monoclonal CD30 antibodies and two Fab' fragments were linked to deglycosylated ricin A chain (dgA), and their potential as immunotoxins for the treatment of Hodgkin's disease was evaluated. Cross-blocking experiments demonstrated that HRS-1, HRS-3, HRS-4, and Ber-H2 recognize the same epitope on the CD30 antigen and that Ki-1 binds to a different epitope. Scatchard analyses showed that HRS-3, HRS-4, and Ber-H2 bound strongly to L540 Hodgkin cells (Kd 15, 7, and 14 nM, respectively), whereas HRS-1 and Ki-1 bound more weakly (Kd 160 and 380 nM, respectively). The different affinities of the antibodies correlated closely with their cytotoxic potency as immunotoxins. HRS-3.dgA, HRS-4.dgA, and Ber-H2.dgA inhibited the protein synthesis of L540 cells by 50% at concentrations of 0.9-2.0 x 10(-10) M, whereas HRS-1.dgA and Ki-1.dgA were about 100 times less potent with 50% inhibitory concentrations of 0.8-1.0 x 10(-8) M. The most effective immunotoxins, HRS-3.dgA and HRS-4.dgA, were only 15 times less toxic than ricin itself. HRS-3 Fab'.dgA and HRS-4 Fab'.dgA were 7.8 and 3 times less potent than their IgG.dgA counterparts with 50% inhibitory concentrations of 7 x 10(-10) and 3 x 10(-10) M, respectively. Staining of human tissues revealed an unexpected cross-reactivity of HRS-4 with pancreatic cells of malignant and nonmalignant origin. HRS-1, HRS-3, Ber-H2, and Ki-1 showed very little cross-reactivity with any normal human tissues. It is concluded that HRS-3.dgA and HRS-3 Fab'.dgA are the immunotoxins of choice for in vivo therapy.
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PMID:Evaluation of ricin A chain-containing immunotoxins directed against the CD30 antigen as potential reagents for the treatment of Hodgkin's disease. 215 74

Using a sandwich enzyme-linked immunosorbent assay (ELISA) we were able to detect a soluble form of the CD30 antigen (CD30s) in the supernatant of cell lines expressing membrane-bound CD30 and in T and B cells after transformation with human T-cell leukemia virus (HTLV-I) and Epstein-Barr-Virus (EBV). While CD30s was not found in 250 healthy controls, it was detected in the sera of patients with Hodgkin's disease (23/100), anaplastic large-cell (6/9), angioimmunoblastic (2/2) and one unclassified high-grade non-Hodgkin's lymphoma (NHL), as well as in 18/20 patients with acute adult T-cell leukemia (ATL, HTLV-I-positive). It was absent in a large number of patients with other high-grade NHL, all low-grade NHLs, acute or chronic leukemias and solid tumors. The only non-malignant disease with detectable levels of CD30s was infectious mononucleosis (9/10). The membrane-bound form of CD30 has a molecular weight of 120 kDa. Western blot analysis revealed that CD30s in the serum of patients has a molecular weight of 88 kDa, identical to the antigen released by cell lines in vitro. CD30s disappeared in all originally positive cases after successful treatment and reappeared in relapsing patients. Thus, CD30s may be useful as a specific marker for disease activity of certain types of lymphoma and ATL.
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PMID:Detection of a soluble form of the CD30 antigen in sera of patients with lymphoma, adult T-cell leukemia and infectious mononucleosis. 215 38


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