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Biomedical subjects

T Tursz

Publications and source records attributed to T Tursz.

At least 181 records · Page 10Linked to original sources

Common multigenic activation in different human neoplasias.

It was previously shown that a common multigenic component, designated as tumor-specific DNA (tsDNA), was transcriptionally active in human lymphoid neoplasias and only slightly active, if at all, in normal lymphoid cells, including the Priess cell line immortalized by Epstein-Barr virus. In the Burkitt lymphoma-derived Raji cell line, tsDNA corresponded to 2500-3000 distinct transcription units, arbitrarily defined as encoding mRNA chains of 1000 kds each. In the present study, radioactive Raji cell tsDNA was isolated by a recycling procedure which eliminates transcribed DNA sequences common to both the Raji cell and the Priess cell, and was used as a probe for homologous transcripts. The major part of this probe could be hybridized to RNAs from all the human neoplasias studied: cultured cell lines derived from leukemias, malignant lymphomas or sarcomas, leukemic cells or solid tumors (sarcomas and carcinomas) recovered from patients. In contrast, only a minor portion of Raji cell tsDNA could be hybridized to RNAs from non-malignant cells, normal human lymphoid cells or fibroblasts grown in culture, fetal and chorioplacental tissues. It is concluded that a common multigenic set is activated in a wide variety of, and perhaps in all, human neoplasias.

Burkitt Lymphoma↗

Protective effects of differentiation inducers on natural killer sensitivity of K 562 cells: Analysis at a single-cell level.

K 562 cells induced to differentiate by sodium butyrate (SB) or 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were studied for their capacities to be bound and killed by large granular lymphocytes (LGL) in a single-cell cytotoxicity assay in agarose. After SB treatment, K 562 cells were less efficient in binding to LGL, whereas the frequency of killer cells among bound LGL was unaffected. When TPA was used to induce K 562 differentiation, the binding of LGL to their target and the lytic efficiency of the bound LGL were both diminished when compared to control K 562 cells. It has been demonstrated that the expression of structures involved in the binding of natural killer (NK) effectors to their targets could be correlated with the target-differentiation stage. It is shown that phorbol-ester treatment can also affect NK target structures involved in the killing step.

Animals↗

Effect of a synthetic thymic factor (facteur thymique serique) on natural killer cell activity in humans.

The effect of the serum thymic factor, FTS, on human NK cells was studied. NK cell activity was measured in a 51Chromium-release assay in which effector cells were peripheral blood lymphocytes (PBL) or bone marrow (BM) lymphocytes from healthy individuals and patients, and targets were K562 cells. When added in vitro in this assay, FTS modulated NK cell activity of normal PBL. Low concentrations of FTS (10(-2) ng/ml) increased NK activity (P less than 0.001) whereas higher concentrations decreased it (P less than 0.01) for 10 and 10(2) ng/ml. FTS exhibited no effect on NK cell activity of BM lymphocytes. When administered in vivo to 4 cancer patients (10 micrograms/kg i.v. every 3 days), FTS progressively increased peripheral NK activity in two patients with low pre-treatment NK values, whereas it decreased NK activity in two patients with previously normal or high NK values. The mechanism by which FTS modulates NK cell activity is still unknown but such modulation suggests that NK cells belong in part to the T-lineage.

Bone Marrow Cells↗

Leukemia cell lines can replace monocytes for mitogen-induced T-lymphocyte responses: this accessory function is dependent upon their differentiation stage.

Highly purified peripheral T lymphocytes do not proliferate in response to phytohemagglutinin A or concanavalin A, unless adherent HLA-DR+ monocytes are added as accessory cells. The accessory function (AF) of monocytes is mediated through the release of interleukin-1 (IL-1). We here report that cells from three human leukemic lines--K562, HL-60, and U-937--could exert AF and efficiently replace monocytes in a 72-hr mitogen-stimulated proliferation assay. This AF was clearly related to precise maturational stages of these cells, since the hematopoietic precursor K562 cells spontaneously exerted high AF but lost this property when treated with differentiation inducers such as sodium butyrate or phorbol 12-myristate 13-acetate (PMA). On the other hand, untreated HL-60 and U-937 cells exhibited no spontaneous AF, but they acquired this function when induced to differentiate either along the granulocytic pathway (dimethyl sulfoxide-treated HL-60 cells) or along the monocytic pathway (PMA-treated HL-60 and U-937 cells). Supernatants from PMA-triggered K562 or HL-60 cells allowed the proliferative response of murine thymocytes to phytohemagglutinin A and were therefore shown to contain IL-1. Analysis of phenotypical markers showed that AF and IL-1 production were not restricted to cells of the monocytic lineage. No HLA-DR antigen could be detected on K562 and HL-60 cells. Thus, the expression of HLA-DR antigens is not required for AF and IL-1 production in response to mitogens. Human leukemia cell lines could provide useful sources of human IL-1.

Cell Differentiation↗

HLA-A, -B, and -DR antigens in North African patients with nasopharyngeal carcinoma.

Seventy-six North African patients (most from Algeria) affected with nasopharyngeal carcinoma (NPC) have been studied for their HLA-A, -B, and -DR phenotypes and compared with a control North African population. Antigens HLA-A3, HLA-B5 and HLA-Bw15 were found more frequently in the NPC group than in the control group (30.3% vs 17.6%, 38.2% vs 24.4% and 9.2% vs 0.8%, respectively). HLA-Aw33, HLA-B14 and HLA-DR4 were less frequent in the patients than in the controls (3.9% vs 16.8%, 1.3% vs 16% and 13.2% vs 29.1%, respectively). After correction for the number of specificities tested, these differences were not statistically significant. They were, however, more striking when compared to normal Kabyles (Algerian Berbers), a major ethnical population in Algeria, with lower incidences of the HLA-B5 antigen and of the HLA-Aw33-B14 haplotype. This could suggest, in North Africa, either the existence of MHC-linked genes of resistance or susceptibility to NPC, in Berbers especially, or a preferential occurrence of NPC in non-Berbers. Antibody titers against the Epstein-Barr virus (EBV) associated early antigen (EA) and viral capsid antigen (VCA) have been measured. No correlation was observed between HLA phenotypes and the anti-EBV serological response of the patients.

Adolescent↗

Low natural killer cell activity in patients with malignant lymphoma.

Natural killer (NK) cell activity was found decreased (mean value: 27.5%) in peripheral blood lymphocytes from 59 untreated patients with malignant lymphoma, when compared to 112 healthy subjects (46.3%) and to 75 cancer patients with nonlymphoid tumors (43.7%) (P less than 0.001). NK cell values were similar in patients with Hodgkin's disease (25.5%) and with non-Hodgkin's lymphoma (28.2%). Decreased NK cell activity was not correlated with age, lymphoma extension or leukocyte counts. A physiological role for NK cells in the immune surveillance against lymphoid neoplasias is discussed.

Cell Line↗

A monoclonal antibody with anti-Burkitt lymphoma specificity. I. Analysis of human haematopoietic and lymphoid cell lines.

38-13 is a hybridoma-produced monoclonal rat IgM which appears to define a Burkitt's lymphoma-associated antigen (BLA). In this paper, we described the reactivity of 38-13 with a panel of human haematopoietic and lymphoid cell lines. In indirect immunofluorescence (IF) assays, 15 of 26 Burkitt's lymphoma (BL) lines studied were clearly stained with 38-13 (from 13 to 100% positive cells) by microscope, with varying numbers of heavily labelled cells. In these positive cell lines, fluorescence-activated cell-sorter (FACS) analysis demonstrated that BLA was actually present on all the cells. Positive BL included Epstein-Barr virus (EBV) genome-carrying lines and EBV-negative ones; thus, BLA is not related to the presence of EBV. Most of the 15 BL cells that reacted with 38-13 contained a typical t(8;14) translocation, but had variant translocations such as t(2;8) and t(8;22). The cells were derived from BL patients of different geographical origins and clinical features. Four BL lines were poorly stained and seven were negative with 38-13 in IF assays. The 32 EBV-positive lymphoblastoid cell-lines (LCL) studied were negative. In three line pairs, consisting of a tumor line and an LCL from the same patient, only the BL line was demonstrated to react with 38-13. A series of non-BL cells, including haematopoietic, lymphoid and solid tumor lines, all failed to react with 38-13. Various attempts to modulate the expression of BLA on BL cells were unsuccessful. However, it cannot be ruled out that BLA is actually a transient B-cell differentiation marker.

Animals↗

[Salvage chemotherapy in resistant malignant lymphomas (author's transl)].

A salvage chemotherapy was used in advanced malignant lymphomas resistant to previous chemotherapy. The chemotherapy schedule consisted by the monthly administration of vindesine and continuous infusions of bleomycins, associated with cis-diammine-dichloro-platinum in Hodgkin's disease (patients resistant to MOPP and ABVD protocols) and with DTIC in non-Hodgkin lymphomas (patients resistant to CHOP or equivalent protocol). In 10 patients with advanced Hodgkin's disease (stages III and IV), one complete remission and four partial regressions were achieved. Five patients are still alive after 6 and 14 months. In 15 non-Hodgkin lymphoma patients, two complete remissions and seven partial regressions were achieved. Eight patients are still alive after 4 to 12 months. Severe toxicities related to the chemotherapy protocol have never been observed. These results demonstrate the efficiency of the described chemotherapy schedules in advanced malignant lymphomas resistant to visual therapy.

Adolescent↗

[Factors of severity in placental choriocarcinoma].

A retrospective study has been carried out on the poor prognostic features of a group of 57 patients. These are: the existence of extra-pelvic and extra-pulmonary metastases and a level of serum HCG above 200000. The most favourable prognostic signs are absence of these two factors in pregnancy that is not normal and a delay between the onset of the first diagnostic elements and treatment of less than 6 months.

Adolescent↗

[Non-Hodgkin lymphomas. New histological, cytological and prognostic correlations (author's transl)].

In a homogenous series of 58 patients with non-Hodgkin lymphoma, clinical, histological, cytological and prognostic correlations were investigated by the same pathologists and clinicians, using Kiel's classification. The survival rate at 3 years was 78% for stage I and II lymphomas and 37% for stage III and IV lymphomas. Nodular forms had a better prognosis. There was good correlation between prognosis and Kiel's classification of cytological forms. The survival rate was 81% in low grade malignancy lymphomas and 28% in high grade malignancy lymphomas with immunoblasts, pure centroblasts and lymphoblasts. The poor survival rate of patients with immunoblastic sarcoma was due to a variety of the disease with totally undifferentiated, highly proliferative cells.

Adolescent↗

[N-Methyl-9 hydroxy-ellipticine (NSC 264-137) in the treatment of malignant metastases. Preliminary results (author's transl)].

In a phase II trial 2 N-Methyl-9-Hydroxy-Ellipticine (NMHE) was administered in weekly infusions of 100mg/m2 over 1 hour to patients with malignant metastases. Prior to injection, the drug was dissolved in 250 ml isotonic glucose. The results were evaluated in 67 patients. Objective regression was observed in 23 (34%) and was superior to 50% in 10 cases. Patients showing signs of regression under treatment were mostly those with breast cancer (10/24 cases), soft tissue sarcoma (3/9 cases) and renal cancer (2/8 cases). The main toxic effect was haemolysis (2 cases), probably due to an immunoallergic mechanism. Attention is drawn to the lack of bone marrow toxicity.

Alkaloids↗

Monoclonal antibody against a Burkitt lymphoma-associated antigen.

A monoclonal antibody, referred to as 38.13, was obtained by fusing murine myeloma cells with Lewis rat splenocytes sensitized with Daudi cells (human Burkitt lymphoma containing Epstein--Barr virus genome but lacking HLA-A, -B, and -C and beta 2-microglobulin molecules at the cell surface). 38.13 antibody was demonstrated to be a rat IgM. By complement-dependent microcytotoxicity and indirect immunofluorescence assays, 38.13 antibody was shown to react specifically with cells derived from Burkitt tumors, including both Epstein--Barr virus genome-carrying and Epstein--Barr virus-negative Burkitt lymphoma. By contrast, Epstein--Barr virus-containing lymphoblastoid cell lines derived from normal B lymphocytes were not recognized by 38.13 antibody. Fresh malignant cells from patients affected with various lymphoproliferative disorders were negative, except 4/8 having abdominal Burkitt-like lymphomas. Normal lymphocytes from peripheral blood, spleen, lymph node, tonsil, and bone marrow and mitogen (phytohemagglutinin, pokeweed mitogen, and concanavalin A)-activated blasts were also negative. Thus, 38.13 antibody apparently recognized a Burkitt-associated antigen that is not related to Epstein--Barr virus. The pattern of reactivity of 38.13 antibody with various Burkitt lymphoma cells appeared quite heterogenous and some Burkitt cells were consistently negative. 38.13 antibody thus defines a subset of Burkitt lymphomas.

Animals↗

Natural killer cell activity in human bone marrow recipients: early reappearance of peripheral natural killer activity in graft-versus-host disease.

Natural killer (NK) cell activity toward K562 target cells and antibody-dependent cell-mediated cytotoxicity (ADCC) toward L1210 cell sensitized with anti-L1210 antisera were sequentially tested in peripheral blood lymphocytes (PBLs) from 24 human bone marrow (BM) recipients. Although consistently decreased before the transplant, NK cell activity was restored in all of the patients tested that argues for a bone marrow origin of NK progenitors in humans. In patients without graft-versus-host disease (GVHD), peripheral NK cell activity remained low during the 1st month after the transplant, then rapidly increased and reached normal values usually between days 30 and 50. By contrast, peripheral ADCC appeared earlier restored (since day 13), suggesting that NK and ADCC are two distinct effector mechanisms. When restored, peripheral NK cell activity remained within normal range, except in seven cases with a drastic fall in NK cell values contemporary with a severe viral infection, mainly with cytomegalovirus (CMV). NK cells are thus suggested to play an important role in the control of viral infections in these deeply immunodepressed patients. In patients with acute GVHD, strikingly high NK values were observed early after the transplant, and during the 1st month a strong correlation did exist between high NK values and acute GVHD occurrence. These results suggest that cells involved in GVHD mechanism are able to exert NK cell activity at some stages of their maturation. The assessment of NK cell activity could be an attractive routine procedure for monitoring the prophylaxis of GVHD in human BM recipients.

Antibody-Dependent Cell Cytotoxicity↗

Characterization of antibodies reacting with husband's lymphocytes in sera from patients with trophoblastic malignancies.

Lymphocytotoxic antibodies reacting with husband's lymphocytes were demonstrated in 24 sera from women with trophoblastic neoplasia studied before any chemotherapy. These antibodies exhibited a maximal cytotoxic activity at +4 degrees C. They reacted mainly with B lymphocytes as assessed by microlymphocytotoxicity assays using B- or T-cell enriched subpopulations and T- or B-cell lines as targets. They could not be absorbed out with platelets or erythrocytes, and did not react with autologous lymphocytes. In one double-labelling immunofluorescence experiment, these antibodies could be stained by rhodamine-conjugated Fab'2 anti-mu fragments and thus appeared to belong to the IgM class. They were shown to react mainly with surface Ig (SIg) bearing lymphocytes, plus a minor SIg negative subset. Studies with panels of allogeneic normal B cells and of HLA homozygous B-cell lines showed that the target antigen(s) recognized by these antibodies is clearly distinct from HLA-D antigens. Corresponding antigens seem to be expressed on placenta, since the lymphocytotoxic antibodies could be absorbed out with trophoblastic homogenates and one serum reacted with JAR cells (cultured choriocarcinoma line). An enhancing role of such antibodies in the growth of trophoblastic malignancies may be suggested.

Antigens, Surface↗

[2 N methyl 9 hydroxy-ellipticine in treatment of metastatic breast cancers (author's transl)].

A phase II trial was conducted in 57 patients with advanced metastatic breast cancer given 2-N-methyl 9-hydroxy-ellipticine (NMHE) as 100 mg/m2 weekly. Evaluation of response, after at least 4 injections, was possible in 46 patients. Two complete regressions (of 3 and 12 months) and 7 regressions of over 50 p. cent were observed, a total regression rate of 19 p. cent. Regression was mainly observed in cutaneous or subcutaneous metastases. No objective regression was noted for pulmonary or hepatic metastases. Bone metastases were not taken in account when assessing response to treatment. Absence of haematological changes must be emphasized. The most frequent side effects were anorexia, nausea +/- vomiting and dryness of mouth. Major toxicity was intravascular haemolysis, observed in 6 of 175 patients receiving NMHE in the Institut Gustave-Roussy, always controlled by symptomatic treatment. This product, of acceptable efficacy in breast cancer treatment, will probably occupy an original place in anti-cancer chemotherapy because of its lack of myelotoxicity.

Alkaloids↗