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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical trials of radioimmunotherapy (RIT) of lymphoma have produced frequent tumor regressions and remissions, but it has been difficult to determine to what extent these tumor responses have been due to antibody-specific targeted radiation, nontargeted radiation, and/or cytotoxicity mediated by the carrier monoclonal antibody (MoAb). In this report, RIT was studied in athymic nude mice bearing s.c. Raji human Burkitt's lymphoma xenografts using two different pan-B-cell MoAbs, MB-1 (anti-CD37) and anti-B1 (anti-CD20), which differ in isotype (and thus the potential for interaction with host effector mechanisms) and isotype-matched control antibodies either in the unlabeled state or labeled with 131I. When a single i.p. injection of 300 microCi 131I-labeled MB-1 (IgG1) was compared to treatment with unlabeled MB-1 or 300 microCi 131I-labeled MYS control IgG1 MoAb, an antibody-specific targeted radiation effect of RIT was seen. 131I-labeled MB-1 produced a 44 +/- 19% (SEM) reduction in tumor size at 3 weeks posttreatment, while unlabeled MB-1 or 300 microCi 131I-labeled MYS control IgG1 antibody treatment resulted in continued tumor growth over this period of time. In vitro studies demonstrated that MB-1 was incapable of mediating antibody-dependent cellular cytotoxicity using Raji tumor cell targets and human peripheral blood mononuclear cells. Similar to the MB-1 studies, treatment with 300 microCi 131I-labeled anti-B1 produced a 64% reduction in mean tumor size, while 300 microCi of control antibody resulted in a 58% increase in tumor size over the same 3-week period. In contrast to MB-1, however, unlabeled anti-B1 (an IgG2a MoAb which in vitro studies showed to be capable of antibody-dependent cellular cytotoxicity) also had a substantial antitumor effect. Indeed, 300 microCi 131I-labeled anti-B1 and unlabeled anti-B1 treatment (using an equivalent amount of total protein in the treatment dose) produced a similar specific reduction in tumor size. Increasing the radionuclide dose of anti-B1 to 450 microCi in another experiment did not produce a significant difference in tumor regression compared to a 300-microCi dose. These results suggest that the antitumor effects of 131I-labeled anti-B1 treatment were dominated by antibody-mediated cytotoxicity mechanisms, such that an antibody-specific targeted radiation effect could not be distinguished. In contrast, antibody-specific targeting of radiation was the dominant mechanism of tumor killing with 131I-labeled MB-1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Therapy with unlabeled and 131I-labeled pan-B-cell monoclonal antibodies in nude mice bearing Raji Burkitt's lymphoma xenografts. 142 95

Placental ferritin is a tumour associated antigen present in the serum of patients with active Hodgkin's and non-Hodgkin's lymphoma, and the serum values fall during remission of the disease. There is no correlation between placental and total blood ferritin values. Because of the strong association between coeliac disease and lymphoma, 19 children with active and 25 with inactive coeliac disease were screened for the presence of placental ferritin. Thirty two children with other intestinal disorders served as controls. Placental ferritin was identified by using a monoclonal antibody in an ELISA procedure. The mean (SEM) placental ferritin value in the control serum was 12.6 (2.4) while the values in serum of patients with active and inactive coeliac disease were 117 (22.8) and 43.8 (10.2) U/ml respectively. Patients with active coeliac disease differed significantly from both control subjects (p = 0.0004) and those with inactive disease (p = 0.03). Peripheral blood lymphocytes contained no placental ferritin. It was present, however, in lamina propria lymphocytes of intestinal biopsy specimens from active coeliacs. Placental ferritin was also found in some of the better differentiated malignant cells in two patients with adult onset enteropathy associated lymphoma. Placental ferritin is known to have an immunosuppressive effect, and this may be one of the necessary steps in the development of malignancy associated with coeliac disease. Gluten free diet, by reversing this state, may have a role in the prevention of lymphoma.
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PMID:Placental ferritin in coeliac disease: relation to clinical stage, origin, and possible role in the pathogenesis of malignancy. 191 5

A high false negative rate from endoscopic forceps biopsy is well-known in gastric carcinoma. The initial aim of the present study was to determine whether possible thickening of adjacent nontumorous mucosa by nonspecific or specific trophic factors could contribute to this observation; 167 gastrectomy specimens (77 carcinomas, 14 lymphomas, 76 gastric ulcers) were examined and mucosal thickness measured. Mean thickness of uninvolved mucosa near carcinoma (1.4 +/- 0.08 mm, mean +/- SEM) and near lymphoma (1.5 +/- 0.1 mm) was in each case significantly greater than mucosal thickness near ulcer (1.14 +/- 0.05 mm) or at a distance in the same specimen (P less than 0.01 for each comparison). A subset of specimens representing 20% of carcinomas, showed marked mucosal thickening (2.01 +/- 0.05 mm) above the control mean. Immunohistochemical evaluation for intratumoral epidermal growth factor content (EGF) correlated with mucosal thickness in all groups examined (R = 0.67). Immunostaining for EGF receptor showed similar patterns of expression to those of EGF. EGF and EGF receptor contents were also correlated with depth of invasion when possible. In conclusion, the mucosal thickening adjacent to gastric malignancy may well contribute to the insensitivity of endoscopic forceps biopsy. More importantly, the higher tumor EGF and EGF-receptor contents seen in these lesions may prove to be a useful marker of biologic behavior and predictor of prognosis in these tumors.
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PMID:Mucosal thickening adjacent to gastric malignancy: association with epidermal growth factor. 278 75

Amniotic fluid prolactin is a product of maternal decidualized endometrium that is derived by translocation of the hormone across the reflected fetal membranes. Amniotic fluids from 26 second-trimester (14 to 23 weeks) and 75 third-trimester (29 to 40 weeks) normal singleton pregnancies were evaluated for prolactin content by radioimmunoassay and bioassay with the Nb2 rat lymphoma cell line. The relative bioactivity was calculated as the ratio of bioassay to radioimmunoassay for each fluid. Data segregated by gestational age and fetal genetic sex identified a highly significant difference (p = 0.0004) in amniotic fluid prolactin radioimmunoassay concentrations (mean +/- SEM) that surround male (682 +/- 49, n = 42) versus female (440 +/- 39, n = 33) fetuses of third-trimester age. Paired bioassay values were significantly lower (p = 0.002) than radioimmunoassay values among males (626 +/- 52) but equivalent (p = 0.1066) among females (464 +/- 44). The bioassay/radioimmunoassay ratios of third-trimester fetal female-associated amniotic fluid prolactin were significantly higher (p = 0.0004) than those of third-trimester males and second-trimester males and females. The results suggest a fetal gender-related factor is associated with both the production and the biologic activity of the maternally derived hormone. Thus the fetus appears to have some control over the dynamics of uterine prolactin production.
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PMID:Fetal control of maternal prolactin production and bioactivity in utero. 291 13

Rat reticulocytes contain a cytosol activator protein (RCAP) that augments catecholamine-sensitive adenylate cyclase activity in reticulocyte membranes. A highly purified preparation of RCAP, obtained by Sephacryl S-200 chromatography, was used to elucidate further its mechanism of action. The specific activity of the S-200 fraction to augment isoproterenol responsiveness was increased approximately 1,100-fold over the starting material, from 1.2 to 1,300 nmol cAMP formed per mg RCAP. The mol wt of RCAP is approximately 20,000. The effect of RCAP to enhance isoproterenol responsiveness was apparent within 20 sec, virtually abolishing the normal lag time of hormone-activated adenylate cyclase. In addition to its effects on catecholamine-responsive adenylate cyclase, RCAP significantly increased basal [21 +/- 3 (+/- SEM) to 41 +/- 4 pmol/mg protein X 30 min; P less than 0.02], guanyl-5'-yl-imidodiphosphate-associated (3173 +/- 213 to 4339 +/- 365 pmol/mg X 30 min; P less than 0.03), and fluoride-associated (5152 +/- 64 to 5807 +/- 58 pmol/mg X 30 min; P less than 0.05) adenylate cyclase activities. RCAP also altered the characteristics of agonist binding to the beta-adrenergic receptor of reticulocyte membranes, causing an increase in the apparent IC50 for isoproterenol from 0.7 +/- 0.2 to 7.9 +/- 1.6 microM (P less than 0.001). Similar to its effects on reticulocytes, RCAP enhanced isoproterenol- and prostaglandin E2-sensitive adenylate cyclase activity in the wild-type S49 lymphoma cell and shifted the binding isotherm for isoproterenol rightward. In cyc-, the mutant that lacks the stimulatory guanine nucleotide-binding protein (Ns) and in UNC, the mutant in which receptors are uncoupled from N, RCAP was ineffective. Moreover, RCAP decreased agonist affinity for the beta-adrenergic receptor in wild-type S49 cells, but not in cyc- or UNC cells. These observations suggest that RCAP requires a functional Ns unit for its effects on hormone-sensitive adenylate cyclase activity.
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PMID:Cytosol activator protein from rat reticulocytes requires the stimulatory guanine nucleotide-binding protein for its actions on adenylate cyclase. 298 18

Human T-T hybridomas were developed as a strategy for obtaining lymphokines that alter T-lymphocyte motility. Mitogen-stimulated human T lymphocytes were fused with cells of the human CEM lymphoma line and the supernatants derived from these fusion products were assessed for chemoattractant activity in a modified Boyden chamber assay. Supernatants from hybridoma 41B2 enhanced lymphocyte migration to 198 +/- 13% (mean +/- SEM) of control. Characterization by Sephadex G-100 molecular sieve chromatography revealed a single peak of chemoattractant activity corresponding to a molecular weight (MW) of 56,000. This activity eluted from a Sephadex QAE anion-exchange column at 4-6 mS. Subsequent isoelectric focusing in sucrose revealed an isoelectric point of 9.0-9.2. Fractions with activity after sequential molecular sieve and anion-exchange chromatography were concentrated, radiolabeled with 125I, and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography revealed a band which corresponded to a MW of 14,000 (representing four similar monomeric chains) and to the region from which chemoattractant activity could be detected in eluates from slices of unstained gels run in parallel. The biological activity of this hybridoma-derived lymphocyte chemoattractant was abolished by treatment with trypsin and neuraminidase but was unaffected by heating to 56 degrees C. We conclude that certain human T-T-cell hybridomas constitutively elaborate a lymphocyte chemoattractant that appears to be physicochemically identical to a previously described human lymphokine, lymphocyte chemoattractant factor.
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PMID:A human T-T-cell hybridoma-derived lymphocyte chemoattractant factor. 309 96

The effects of all-trans retinoic acid (RA) were tested on the growth in vitro of myeloid progenitors from peripheral blood or bone marrow, in 25 patients with chronic myeloid leukemia (CML), ten of whom were either in accelerated or blastic phase, and in nine patients with myeloproliferative disease (MPD). The responses were compared with 12 normal bone marrow controls obtained from patients with lymphoma. Clonal growth in CML blastic and accelerated phase was inhibited to the greatest degree (mean 49 +/- 9% (SEM) of control at 0.3 microM RA). The responses in CML chronic phase and MPD were more heterogeneous, but significant inhibition was seen at higher concentrations of RA (50 +/- 12% CML chronic phase, 58 +/- 26% MPD at 3.0 microM RA). At 0.3 microM and 1.0 microM RA there were significant differences between the CML chronic phase and the CML blastic phase patients (p less than 0.02 and p less than 0.05 respectively). At these concentrations there was no significant inhibition on normal bone marrow myeloid progenitors. Inhibition was independent of the proportions of progenitors in S phase, as assessed by tritiated thymidine suicide. Preincubation of cells from selected patients with RA for 48 hours before culture in agar resulted in a significant degree of inhibition (48 +/- 8% of control). Inhibition was prevented by delaying the addition of RA from 24 to 48 hours from the beginning of the culture, indicating that RA exerts an early direct effect on myeloid progenitors.
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PMID:Inhibition by retinoic acid of myeloid progenitors in chronic myeloid leukemia and myeloproliferative disease: increased sensitivity in blastic phase of chronic myeloid leukemia. 316 96

Twenty-one male homosexuals were followed up by repeated lymph node biopsy for a mean (+/- SEM) follow-up of 99 +/- 18 weeks. Four histologic patterns were seen on biopsy: explosive follicular hyperplasia (EFH), follicular involution (FI), a mixed pattern of EFH with FI in the same node, and lymphocyte depletion. Patients with FI and lymphocyte depletion had mean survival times that were significantly less than those for the subjects with EFH. The percentage of lymph node follicles with suppressor cell clusters (T8) in EFH lymph nodes was significantly higher (43% vs 8%) than in nodes from patients without risk for human immunodeficiency virus infection. Helper/suppressor T-cell ratios in control nodes were 1.6; in EFH nodes, 0.97; and in FI nodes, 0.88. A remarkable 33% of patients in this lymphadenopathy group ultimately developed large-cell (B-cell) lymphoma, suggesting that the follicular stimulation noted histologically played a role in the development of this neoplasm. These data show that there is a progressive destruction of lymph node follicles that correlates with the progression of the disease and that lymph node histologic features may provide important prognostic information.
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PMID:Lymph node biopsy in patients with human immunodeficiency virus infections. 317 83

We treated 73 patients with hematologic malignancies in first complete remission (acute lymphoblastic leukemia = 23 patients; acute non-lymphoblastic leukemia = 25 patients; chronic myelogenous leukemia in first chronic phase = 20 patients, and high grade lymphoma = five patients) with a uniform preparative regimen consisting of fractionated total body irradiation (1,320 cGy) and high dose cyclophosphamide (100 mg/kg), followed by allogeneic bone marrow transplantation. By radiation dosimetry we demonstrated that the calculated doses were delivered accurately and reproducibly. Actuarial survival rates (+/- SEM) in complete remission were as follows: Acute lymphoblastic leukemia = 74 +/- 9%; acute nonlymphoblastic leukemia = 50 +/- 11%; and chronic myelogenous leukemia = 55 +/- 11%. Actuarial relapse rates for these three diagnoses were 19 +/- 9%, 17 +/- 11%, and 0% respectively. Three of the five lymphoma patients are alive in complete remission at 22+, 28+, and 54+ months. Overall probability of survival for the 73 patients was 59 +/- 7%. Interstitial pneumonia, usually associated with cytomegalovirus infection and graft-versus-host disease, and relapse of the underlying malignancy were the major causes of death.
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PMID:Fractionated total body irradiation and high dose cyclophosphamide: a preparative regimen for bone marrow transplantation for patients with hematologic malignancies in first complete remission. 329 91

Dissemination of neoplastic cells within the body involves invasion of blood vessels by tumor cells. Since platelets have been shown to contribute to this process, we studied the interaction in vitro of platelets and malignant cells with the vascular endothelium and its underlying basement membrane-like ECM. A metastatic subline (ESb) of the methylcholanthrene-induced DBA/2 T-lymphoma invaded the vascular endothelium at a higher rate than its parental nonmetastatic (Eb) subline. ESb cells also exhibited a much higher ability to degrade the proteoglycan scaffold of the ECM by means of a specific HS degrading endoglycosidase (heparanase). The interaction of platelets with this ECM was associated with platelet activation, aggregation, and degradation of HS by means of the platelet heparanase. Degradation of ECM-HS was facilitated by proteolytic activity that produced a more accessible substrate for further cleavage by heparanase. A similar enhancement was exerted by plasminogen via the activity of the tumor cells or ECM associated PAs. Heparin and chemically modified heparins that lack anticoagulant activity inhibited degradation of the ECM-HS by heparanase. Interaction of platelets and lymphoma cells with ECM covered with vascular endothelial cells was investigated by SEM and by determination of ECM-HS degradation products. SEM studies demonstrated that platelets may adhere to minor gaps between adjacent endothelial cells and degrade the ECM-HS. Platelets were also shown to recruit lymphoma cells into these interendothelial gaps, suggesting that by binding to ECM and release of heparanase, platelets may play an active role in tumor cell invasion and metastasis. Our observation that nonanticoagulant heparins may interfere with heparanase-mediated degradation of ECM-HS suggests a potential therapeutic use for such heparins in neoplastic disorders.
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PMID:Role of heparanase in platelet and tumor cell interactions with the subendothelial extracellular matrix. 332 38


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