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Biomedical subjects

P Reizenstein

Publications and source records attributed to P Reizenstein.

At least 109 records · Page 6Linked to original sources
PubMed1986

Enzyme markers in acute myeloid leukaemia.

The levels of TdT, AdA, 5'-N, 20 alpha-SDH and TK1 were analyzed in different FAB subgroups of AML. AdA, 5'-N, 20 alpha-SDH and TK1 showed large variations both within and between the different subgroups. It therefore seems unlikely that measurements of these enzymes will be able to aid morphological subclassification of AML. Neither could analysis of these enzymes give prognostic information. TdT was detectable in 46% of AML but the levels were only 1/10-1/100 of those found in ALL. The enzyme was detected in leukaemic granulocytopoietic cells while leukaemic cells of monocytic origin were negative in all but 1 case. In addition, increased TdT activity was positively correlated to the length of survival.

20-Hydroxysteroid Dehydrogenases↗
PubMed1986

Managing minimal residual malignant disease.

So-called complete remission of acute leukemia and other tumors frequently leaves minimal residual disease cells, sometimes causing an inflammatory response and often relapse. Although the remaining cells often have long generation times or may even be in G0 condition, they may form a new tumor mass. This can be explained by cell kinetics alone, or by an escape from immunologic or other control mechanisms, or by a new promoting event. Maintenance chemotherapy beyond the first 6 months seemed only to have an effect where induction chemotherapy was weak and palliative, but not since it has become intensive and sometimes curative: it only increases the relapse incubation time, not the survival. Relapse cells may be refractory to cytostatics previously not given, in part because of alternative metabolic pathways or enzyme induction, in part because of tumor cell progression, and any chemotherapy seems to be able to play a significant role in this progression. The result is a relatively high residual tumor mass and a short duration of rare second remissions. Adjuvant immunotherapy, despite controversies about its results, seems to work in some tumors, but the statistical methods applied and the monitoring have been criticized. The strategy proposed for potentially 'curable' tumors (leukemias, lymphomas, embryomas) with short cell generation times is therefore intensive remission induction aiming at the smallest possible residual disease cell number. It is conceivable that this induction might mean accepting risks comparable to those accepted for transplant patients. Manipulation of the bioimmunological response can be effective even against cells in the G0 phase. New methods are proposed to manage residual disease of solid tumors with long generation times, and only maintenance chemotherapy active on cells with a long generation time is suggested.

Humans↗
PubMed1986

Immunomodulating properties of bestatin in cancer patients. A phase II trial.

Thirty-four patients with cancer (30) or ARC (4) with severe T cell defect or imbalance persisting a long time after completion of any cytostatic treatment were treated by bestatin 30 mg/day 3 days per week during three weeks. The drug has no toxicity of any kind. Reassessment of T cell subsets after completion of bestatin therapy showed a significant improvement of the absolute number of CD4 cells in peripheral blood. CD8 subsets wether initially increased or decreased were modified towards normalisation but the modification reached statistical significance only in the subgroup with initial absolute defect of CD8 cells. CD4/CD8 ratio was significantly increased whether considering all cycles of therapy, or all those given to patients with initially high or normal CD8 subsets. Bestatin appears to have immunomodulating properties which might be useful in cancer patients.

Adjuvants, Immunologic↗
PubMed1986

A phase II trial of immunorestoration with zinc gluconate in immunodepressed cancer patients.

Zinc is an trace metal necessary for T cell differentiation and maturation. Forty-two patients, with Aids Related Complex or malignancy in remission and with severe and stable CD4 lymphoid cells cytopenia were submitted to zinc gluconate, 125 mg twice daily orally for three weeks. Reevaluation of T cell subsets one week after the end of zinc intake showed non significant modification of total lymphocyte counts nor of CD4 subsets. CD8 cells however were significantly increased in absolute number in those patients with initially low counts of the cells while they were significantly reduced in those patients with initially normal or high CD8 cells counts. Zinc gluconate in short courses appear to act as a regulator of CD8 lymphoid cells subsets.

AIDS-Related Complex↗
PubMed1986

Clinical trials of myeloma treatment: a review.

Clinical trials of myeloma treatment are reviewed. 7618 patients are described in nine Tables (some patients appear in more than one). Most randomized trials and trials of non-staged myeloma yield no statistically significant differences between the combinations of alkylators, vinca alkaloids, nitrosoureas, anthracyclines, epipodophyllotoxins, procarbazine and/or steroids used. Intensive combination treatment induces response in an average of 3 months and seems superior to monotherapy in stage III, in which the early mortality is reduced from 45% to 10%. No studies were found showing any evidence for superiority of intensive treatment in stage I. Alternating chemotherapy combinations do not delay refractoriness. No evidence was found that maintenance treatment prolongs survival in responding patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Adriamycin, vincristine, cyclophosphamide and 5-fluorouracil (AVCF) compared with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in premenopausal breast carcinoma. Personal results.

Adjuvant treatment of breast cancer with AVCF gave significantly longer disease-free survival than CMF in the group of patients taken as a whole, in the subgroup with lymph node involvement and in the premenopausal subgroup. No significant difference was found regarding overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Clinical trials of the treatment of minimal residual tumours.

It is well known that even after maximal surgical and/or cytostatic treatment, and even in patients with an apparently complete remission, what is known as minimal residual disease often remains. Adjuvant chemotherapy given for periods longer than six months after the induction of complete remission does not appear, in comparative trials with a five-year follow-up, to improve the final prognosis either in leukaemia or in solid tumours. It is suggested here that the reason may be that minimal residual tumours may consist of cells in the G-O phase. Breast cancer before the menopause may be an exception, since oestrogens present before, but not during, menopause are promotors. This could explain why premenopausal breast cancer seems to be the only tumour transitorily sensitive to adjuvant chemotherapy. Immunotherapy given during complete remission seems to result in longer remission duration and/or overall survival and/or survival after relapse in some but not in all properly conducted trials. It is well known that large tumour masses are not influenced by immunotherapy. In contrast, it is known that cells in G-O, refractory to chemotherapy, may be sensitive to immunotherapy.

Antineoplastic Agents↗
PubMed1986

Ethics and errors of clinical trials and the role and place of different types of trial.

Controlled clinical trials, usually carried out in a multicentre, randomized manner, have become fashionable and popular because they contribute to the general acceptance of the results, particularly when the difference between the treatment arms is small. The present book and the present introduction attempt to discuss when and how this form of trial is appropriate. It is recognized that the discussion may be one-sided in the sense that the undoubted and well-known merits of controlled clinical trials are not reiterated. The focus of the present discussion is on the scientific, practical and ethical problems inherent in such trials and on possibilities for improving their design. In the future clinical trials should be used with more restraint than hitherto. Phase I trials should replace inter-patient by intra-patient dose escalation in order to give each patient a chance to benefit from the treatment. Since such trials frequently cause discomfort, they should be limited to one centre at a time. The number of patients subjected to phase II trials can be appreciably reduced if reasonable statistical measures are taken, as proposed here, to optimize and minimize the trial. Phase III trials must improve the relevance of the questions asked, reporting of errors, patient information and statistical interpretation. They must be based on promising phase II studies with historical controls so that their efficacy is increased.

Antineoplastic Agents↗
PubMed1985

Cells responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers.

Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). Improved survival with Bestatin treatment following chemotherapy has been observed in patients with melanoma Stages 1b and II and in patients with acute nonlymphatic leukemia, where BCG also seems active, although possibly only in patient groups with less than 49% complete remissions.

Adjuvants, Immunologic↗
PubMed1985

Cytotoxicity of monoclonal antibodies against individually immunophenotyped human leukemic cells.

Peripheral blood and bone marrow mononuclear cells from 12 patients with acute myeloid leukemia (AML), 2 patients with acute lymphatic leukemia, and 1 patient with chronic myeloid leukemia in blastic crisis were taken at diagnosis or in relapse. Cells were immunophenotyped with a panel of monoclonal antibodies (Moab) (OKIa, Leu M1, Leu M2, Leu M3, Leu M4, B1, Okt 11, J5) and the same antibodies were used in an in vitro cytotoxicity test. Of the 14 patients, 10 had antibody-binding cells, and the percentage of lysed cells was almost equal to that of blasts. The other 4 patients had few binding cells and little lysis. Acute leukemia with and without preceding myelodysplastic features did not differ in immunophenotype. Mean spontaneous release of 51Cr was 12.7% and complement alone caused an additional average release of 11.8%. Four single antibodies together with complement showed a mean 51Cr release of 0.7-32.4% above that found with complement alone. Combinations of Moabs resulted in 51Cr release at least 10% above the single most efficient Moab in 8 out of 12 patients. Not all blast cells showed antibody binding, nor were all antibody-binding cells susceptible to cytotoxicity. Normal bone marrow growth in vitro seemed to be stimulated by factors in complement and in the Moab. When this stimulation was compensated for by adding fetal calf serum, cytotoxicity tests prior to CFUc assays resulted in a mean decrease of 46% of colonies and 25% of clusters in normal bone marrow. CFUc are thus sensitive to the cytotoxicity, although CFU may also be resistant.

Antibodies, Monoclonal↗
PubMed1985

Decreased retention of vinca alkaloids in chronic lymphatic leukemia cells from refractory patients.

Uptake and retention of vincristine (VCR), vinblastine (VB), and vindesine (VD) in isolated mononuclear cells from six healthy donors and in leukemic cells from 12 patients with chronic lymphatic leukemia (CLL) were studied: Three patients responded to VCR-containing regimens, whereas 4 patients were or became refractory and five patients did not receive VCR. Incubation of leukemic or normal cells with 1 microgram/ml vinca alkaloid for 1-24 h showed a steady state level after 1-2 h. Normal cells both took up and retained significantly more drug than those from patients, both responding and refractory. Cells from VCR-refractory patients had a significantly (P less than 0.01) lower drug retention than those from patients responding to or not receiving VCR. In contrast, the difference in uptake was not statistically significant.

Aged↗
PubMed1985

Folate and iron metabolism in patients with tumors and inflammations.

Reduced serum concentrations of nutrients like iron, zinc and folates and of albumin and cholesterol are found, as well as emaciation, both in malnutrition and in cancer. In patients with leukemia, a depletion of intracellular potassium and hypo-potassemia are found in addition. The use of hyperalimentation in cancer was originally based on the concept that too little food is the cause of these disturbances in the nutrition state. However, there is also a disturbed metabolism of nutrients in patients with tumors and inflammatory disease. In the case of folic acid, the disturbed metabolism could not be normalized by hyperalimentation. The more advanced the disease, the more pronounced is the disturbed nutrient metabolism, and this disturbance is related to the macrophage activity. It is not self-evident, therefore, that hyperalimentation can normalize the nutritional state in cancer. Emaciation in cancer patients is not caused exclusively by malnutrition.

Anorexia↗
PubMed1985

The effect of zinc on normal and neoplastic T-lymphocyte proliferation.

After 24-72 h of PHA-stimulation, T-cells expressed the transferrin receptor. This receptor facilitates zinc uptake. Zinc transferrin stimulated DNA synthesis in pre-activated or activated, but not in resting T-cells. The regulatory nuclear protein matrix fraction increased from 5 to 40% of the total nuclear protein material in lymphocytes simultaneously with the initiation of DNA synthesis. In contrast, optimal concentration (0.1-0.4 mM) of zinc salts induced a mitogenic response in transferrin-receptor negative resting, but not in PHA-activated or leukemic T-cells. Higher concentrations were toxic. These findings can explain earlier reports on the effect of zinc on immunocompetence in zinc deficient mice and enteropathic acrodermatitis as well as present findings of a normalization of the T-suppressor-cell number in immunosuppressed patients.

DNA Replication↗
PubMed1985

Influence of pre-incubation with one antibody on the binding of a second by human lymphocytes.

The reaction was studied of the J5-monoclonal antibody with the common acute leukemia antigen (CALLA) on non-malignant human tonsil lymphatic cells, which were double labelled also with antibodies against the B1 and HLA-DR antigens or the kappa and lambda light chains. There were few cells (mean 0-1.4%) which were positive with J5 but not B1. Other percentages of labelled cells depended on the order in which the antibodies were added. If the J5-antibody was added first, more B1 positive cells are found than if the B1 antibody is added first. Similarly, a significant (p less than 0.01-p less than 0.001) increase (3.3-18.8%) in the percentage of cells positive with J5 was found when the B1, kappa, and HLA-DR antibodies were added first, but not if antibody against lambda chains is added first. This difference was most pronounced and most significant for B1. This difference can be explained inter alia by steric differences between antibody conjugated and non-conjugated antigens followed by unmasking of other antigens. Double labelling is thus not equal to two single labellings.

Adult↗
PubMed1985

Phase I pharmacologic study of a new Vinca alkaloid: navelbine.

Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week.

Adolescent↗