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Biomedical subjects

M Andreeff

Publications and source records attributed to M Andreeff.

At least 253 records · Page 14Linked to original sources
PubMed1983

Cell survival kinetics in peripheral blood and bone marrow during total body irradiation for marrow transplantation.

Cell survival kinetics in both peripheral blood and in bone marrow have been studied over the time course of hyperfractionated total body irradiation (TBI) for bone marrow transplantation. Our unique TBI regimen allows the study of the in vivo radiation effect uncomplicated by prior cyclophosphamide, since this agent is given after TBI in our cytoreduction scheme. Peripheral blood cell concentrations were monitored with conventional laboratory cell counts and differentials. Absolute bone marrow cell concentrations were monitored by measuring cell concentrations in an aspirate sample and correcting for dilution with blood by a cell cycle kinetic method using cytofluorometry. In the entire group of patients, time to engraftment with donor marrow was found to be 16.6 +/- 4.4 days and more rapid when a nucleated donor cell dose of greater than or equal to 4.0 X 10(8) cells/kg was given. For lymphocytes in peripheral blood in patients in remission, the effective D0 ranged from 373 rad in 10 children less than or equal to 10 y old, to 536 rad in the four patients between 11-17 y old, while n = 1.0 in all groups. There was no trend observed according to age. Granulocytes had a much higher effective D0, approximately 1000 rad in vivo. Absolute nucleated cell concentration in marrow dropped slowly initially, due to an increased lymphocyte concentration in marrow during a concurrent drop in lymphocyte concentration in peripheral blood, but eventually fell on the last day of TBI ranging from 7-44% of the initial marrow nucleated cell concentration. Marrow myeloid elements, however, dropped continuously throughout the course of TBI.

Adolescent↗
PubMed1983

Biosynthesis of ferritin subunits from different cell lines of HL-60 human promyelocytic leukaemia cells and the release of acidic isoferritin-inhibitory activity against normal granulocyte-macrophage progenitor cells.

Biosynthesis of acidic isoferritins was investigated in human promyelocytic HL-60 cells, characterized by diploid (2C), tetraploid (4C) and mixed diploid--tetraploid (2C-4C) DNA cell lines. The three cell lines were studied for the biosynthesis of ferritin and its subunits and for the release of acidic isoferritin-inhibitory activity against normal CFU-GM before and after addition of DMSO. While the tetraploid and mixed diploid--tetraploid cell lines synthesized more H-(Mr = 21) than L-subunits (Mr = 19) after induction, the tetraploid line synthesized more H-subunit before and after induction, compared to the diploid line. The release of acidic isoferritin-inhibitory activity was greater before than after induction in both cell lines, but the tetraploid cell line released more acidic isoferritin-inhibitory activity consistent with its greater production of Mr = 21 subunit. However, after induction no inhibitory activity could be detected from the diploid cells and much less activity was detected with the tetraploid cells, suggesting that differentiation caused a decrease in production of acidic isoferritin-inhibitory activity.

Animals↗
PubMed1983

[Comparison of the therapeutic efficacity of 2 induction protocols in acute myeloid leukemia using exact quantification of bone marrow cellularity].

Using a recently developed technique for the determination of the pure bone marrow cell count per mm3 bone marrow, two different induction regimens for AML were compared for their efficacy, i.e. the therapy induced cytoreduction. In both protocols cytosine arabinoside, daunorubicin and 6-thioguanine were applied at comparable doses but different schedules. In both regimens a blast cell reduction of more than 2.0 log10 within the first 5 to 6 days of therapy strongly correlated (p less than 0.001) with the achievement of an adequate blast clearance in the marrow and complete remission (n = 18), while an inadequate blast cell reduction was revealed in all patients with a cell kill of less than 2.0 log10 (n = 9). Total cytoreduction on day 5 or 6 of therapy was comparable for both protocols. However, on one protocol a continuous logarithmic blast cell reduction was found while the cell kill followed a biphasic function on the other regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Sodium azide enhancement of interleukin-2 production.

The production of large quantities of Interleukin-2 (IL-2) from normal human lymphocytes has been limited by the short production and release period, as well as its absorption by the responsive cell population. We report the utilization of sodium azide (NaN3, 0.01% final concentration) to allow continued production of IL-2 as long as 72-96 hr and thereby increase the yield significantly. Cell cycle analysis performed by flow cytometry indicates that NaN3 blocks cells at the G0-G1 transition and the G1-S transition, depending on the time of addition of NaN3 to the cultures.

Animals↗
PubMed1982

Characterization of two newly established human cell lines from patients with large-cell anaplastic lung carcinoma.

Two permanent cell lines, designated LU-65 and SK-Luci-6, were established from large-cell anaplastic lung cancers of two patients. Both cell lines grew as solid tumors in nude mice. The histologic pattern of the tumors in the nude mouse resembled that of the primary lung cancers in that the xeno-transplanted tissues showed no distinctive features indicative of cell type, a finding consistent with origin from a large-cell anaplastic lung cancer. Cells from both lines formed clones in semisolid agar. Flow cytometric analysis of SK-Luci-6 showed a hypertriploid stemline with a very high RNA-index. Line LU-65 had a hyperdiploid stemline evolving into a hypertriploid stemline with a high RNA-index. Chromosome analysis showed aneuploidy with abnormalities and marker chromosomes in both tumor cell lines. The isoenzyme pattern of LU-65 and Sk-Luci-6 indicated that they were of human origin and distinct from HeLa cells or another common contaminating line. Both cell lines released biologically active agents that could have caused the neutrophilia and hypercalcemia seen in the patients.

Adult↗
PubMed1982

Cell kinetics in acute leukemia: a critical reevaluation based on new data.

The current study was undertaken to compare biopsy and aspiration sampling techniques for reliable cell kinetic analysis in acute leukemia and to reevaluate the clinical significance of cell kinetic data in this disease. Ad 1: One hundred forty-three paired simultaneously taken marrow aspirates and Jamshidi biopsies from 61 patients with acute nonlymphocytic leukemia (ANLL) were compared by means of flow cytometry (FCM) for cellular DNA and RNA measurements, autoradiography for 3H-TdR labeling index and liquid scintillation counting for 3H-TdR uptake. Aspirates were found unreliable for pretreatment evaluation and for monitoring of drug induced cell kinetic perturbations due to contamination with peripheral blood. Aspiration should, therefore, be replaced by marrow biopsy which provides reliable sampling of bone marrow for cell kinetic studies. Ad 2: FCM S-phase index determined from biopsy material was not found predictive for therapeutic response in 43 patients with ANLL treated with two different induction regimens. In one of the two protocols, changes in FCM S-phase index after 48 hours continuous infusion of cytosine arabinoside correlated significantly with clinical response and nonresponse, respectively.

Biopsy↗
PubMed1982

Induction of in vitro proliferation and maturation of human aneuploid myelogenous leukemic cells.

Human leukemic cells were induced to proliferate and mature to macrophage-like cells in primary cultures supplemented with conditioned medium (CM) from phytohemagglutinin and alloantigen-stimulated normal T lymphocytes. Blast and promyelocyte-enriched preparations, isolated after depletion of adherent phagocytic cells and lymphoid cells from samples of myelogenous leukemia patients, were suspended in liquid cultures with 30% CM. Cell cycle analysis was performed throughout the course of induced cellular maturation. Within 24 h of exposure to CM, cells with macrophage-like morphology were identified among the developing adherent cells. Approximately 15-30% of the cells in culture suspensions also developed macrophage-like morphology and esterase reactivity with alpha-napthyl acetate after incubation for 2 d. The number of these nonproliferating cells increased and became predominant in the later culture period. Flow cytometric measurement of DNA content showed that these mature cells had the same aneuploid stemline as the undifferentiated leukemic cells, indicating that genetically abnormal leukemic cells can be induced to differentiate. Reduction in the total RNA content of the macrophage-like cells was also determined by flow cytometry. Reduction in RNA and development of adherent cells served as early markers of maturation, in addition to the later acquisition of complement receptors and phagocytic capacity. Cell cycle analysis showed that CM stimulated the proliferation of immature cells. This initial proliferation may precede intertwined events of proliferation and concurrent maturation of immature cells. Later in the culture period, cellular proliferation decreased, leading to termination of the cultures.

Adult↗
PubMed1982

Bone marrow biopsy instead of 'marrow juice' for cell kinetic analysis. Comparison of bone marrow biopsy and aspiration material.

Since cell kinetic bone marrow studies have so far exclusively been carried out on aspiration material and have yielded inconsistent or even contradictory results, we investigated the adequacy and reliability of aspirates for cell kinetic analyses in comparison to biopsies. Paired samples of bone marrow (133) were taken simultaneously by aspiration and Jamshidi biopsy from 48 patients with acute leukemias and 67 patients with non-leukemic disorders. Cell kinetic analysis by (1) flow cytometry (FCM) of cellular DNA and RNA content, (2) autoradiography for [3H]TdR pulse labelling indices and (3) liquid scintillation counting of [3H]TdR uptake revealed significantly higher values in biopsies (p less than 0.001) exceeding the corresponding results from aspirates on average by factors of 1.65 for FCM S-phase index, 1.90 for G0/1 cells with high RNA content, 1.82 for [3H]TdR LI and 1.90 for [3H]TdR uptake. In more than 70% of all samples results from biopsies were 1.1-11.4 times higher, indicating that aspirates were equivalent to biopsies in fewer tan 30% of cases. Cell kinetic analysis in vitro blood/biopsy mixtures and measurements of DNA synthesis rate in corresponding aspirates and biopsies revealed that these discrepancies are due to the contamination of aspirates with non-proliferating nucleated blood cells. Biopsy, however, was found to provide representative and reproducible sampling of marrow for cell kinetic studies and should replace the presently used aspirate already characterized as "unreliable marrow juice" by Dameshek et al. in 1937 [18].

Acute Disease↗
PubMed1982

Bone marrow cell count per cubic millimeter bone marrow: a new parameter for quantitating therapy-induced cytoreduction in acute leukemia.

A new technique is introduced for determining the number of bone marrow cells per cubic millimeter marrow, providing an accurate and objective means for quantitating therapy-induced cytoreduction. The method requires a correction for admixed peripheral blood in bone marrow aspirates to measure the fraction of remaining pure marrow. While cell kinetic differences between blood, aspirates, and biopsies identify the proportion of contaminating blood cells, the ratio of red cell hematocrits in blood and aspirate gives the volume of trapped blood. By combining both procedures, bone marrow cell counts per unit volume pure marrow result (BMC/cu mm BM), which were found highly reproducible. Blast cell counts (BMBC/cu mm BM) were obtained by additional morphological differentiation. BMC and BMBC/cu mm BM were monitored in 16 patients with acute nonlymphoblastic leukemia treated with daunorubicin, cytosine arabinoside, and 6-thioguanine in combination and in 4 patients with end-stage acute leukemias and non-Hodgkin's lymphomas during high-dose thymidine therapy. Total and daily therapy-induced cytoreduction rates were significantly greater (P less than 0.01) in responders than nonresponders to either regimen. Changes in BMC/cu mm BM were also found representative for changes in BMBC/cu mm BM, since the majority of bone marrow cells were blasts. In acute leukemia. BMC/cu mm BM thus provides accurate and objective measurements of treatment efficacy in vivo and after short periods of drug exposure. Differences in cytoreduction rates within the group of responders also suggest possible prognostic implications.

Acute Disease↗
PubMed1981

Acute myeloblastic leukemia following non-Hodgkin lymphoma in an adolescent. A report of a case with preleukemic syndrome, and review of the literature.

Reports of acute nonlymphoblastic leukemia occurring after successful treatment of Hodgkin and non-Hodgkin lymphoma (NHL) are appearing with increasing frequency. Two years after completion of LSA2-L2 therapy for stage III, poorly differentiated lymphocytic lymphoma, a 16-year-old boy developed a preleukemic state characterized by a refractory macrocytic anemia with excess blasts, dyshematopoiesis, abnormal cluster:colony ratio on in vitro bone marrow culture, and acquired deficiencies of erythrocyte pyruvate kinase, triose phosphate isomerase, and adenylate kinase. Four months later acute myeloblastic leukemia was evident. The RNA index determined by flow cytofluorometry was increased. Four marker chromosomes were found and involved complex translocation of chromosomes 11 and 17 (t11;l17) in 100% of the cells, and chromosomes 4 (t4q;4) in 10% of the cells. A thorough literature search uncovered four other reports of acute nonlymphoblastic leukemia occurring in children treated for NHL and a total of 58 cases in the adult and pediatric age groups. Over 50% of the patients had AML, were mean over 50 years of age, and were treated with radiotherapy and chemotherapy. It is anticipated that additional cases of second malignancies will be reported in this population of patients whose outlook for the curability of the primary malignancy is 75%.

Adolescent↗
PubMed1981

Multiparameter flow cytometry. Part II. application in hematology.

The application of flow cytometry to hematology is emerging as an important new technique in experimental and clinical leukemic research. In addition to the described methods to determine DNA, RNA, and esterase content and the stability of DNA in situ, quantitation of immunofluorescence using antibody techniques has greatly elucidated the hematopoietic cell system. Hence, flow cytometry provides new perspective for determining the origin, diagnosis, classification, staging and treatment scheduling of normal hematopoietic and malignant cell populations.

Aneuploidy↗
PubMed1981

Detection of luxol-fast-blue positive cells in human promyelocytic leukemia cell line HL-60.

Differentiation of HL-60 cells toward the eosinophilic series has not been reported previously. Eosinophil granule specific staining with Luxol-fast-blue was used to determine if HL-60 cells could differentiate into the eosinophilic lineage. The specificity of the Luxol-fast-blue stain for cells of the eosinophilic series was substantiated by comparison of the staining of cells from a patient with an eosinophilic syndrome by Wright-Giemsa and Luxol-fast-blue. Luxol-fast-blue positivity was most notable in cells found in colonies formed from HL-60 clonogenic cells in semisolid agar medium. Colony and cluster formation was spontaneous but in the presence of medium conditioned by either human placental cells or the human monocyte-like cell line, GCT, Luxol-fast-blue positive colonies and clusters were detected at a higher frequency.

Cell Line↗