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Biomedical subjects

H D Preisler

Publications and source records attributed to H D Preisler.

At least 73 records · Page 4Linked to original sources
PubMed1993

Proliferative advantage rather than classical drug resistance as the cause of treatment failure in chronic myelogenous leukemia.

This presentation discusses the role that proliferative advantage plays in making both the chronic and blastic phases of CML resistant to therapy. A case is made for the addition of "regrowth" inhibitors between courses of chemotherapy as a means of increasing the efficacy of therapy by suppressing or reducing the proliferative advantage that the target cells enjoy over those cells which one would like to repopulate the hematopoietic system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Long-term outcome of patients with acute myelogenous leukemia: the role of maintenance therapy, consolidation therapy and the predictive value of two in vitro assays.

Three successive strategies used to treat acute myelogenous leukemia (AML) patients who entered complete remission are compared with respect to their long term efficacy (> 5 years). Additionally, the ability of two in vitro assays to identify patients who would be long term remitters was assessed. With respect to the proportion of patients in long term remission, 5 years of maintenance therapy, intensive consolidation therapy plus 3 years of additional therapy, and 4 courses of consolidation therapy produced equivalent results with 18 to 22% of patients in remission at 7 years. Patients whose leukemia cells retained high levels of cytosine arabinoside triphosphate (araCTP) and who received maintenance therapy were less likely to experience early relapse than comparably treated patients whose leukemia cells failed to retain araCTP. The failure of leukemia cells to clone in vitro was also associated with a lower early relapse rate for patients who received maintenance therapy. Neither the ability of leukemia cells to retain araCTP nor their ability to clone in vitro were of prognostic significance for patients treated with 4 courses of intensive consolidation therapy.

Arabinofuranosylcytosine Triphosphate↗
PubMed1993

CD34+ cell selection: focus on immunomagnetic beads and chymopapain.

The aim of the present study was to develop immunoadsorption techniques for purifying CD34+ cells from the peripheral blood (PB) and the bone marrow (BM). First, we compared two methods for isolating CD34+ cells from patients with acute non-lymphocytic leukemia. Twenty-two samples (17 PB, 5 BM) were obtained from 19 patients, were density cut and, after incubation with My10 antibody, were separated by panning or by immunomagnetic beads. Beads allowed a significantly better separation, either in terms of purification of CD34+ cells (85.5% +/- 11.1% vs 55.7 +/- 23.8%, p = 0.003) or in terms of depletion of CD34+ cells from the negative fractions (3.9 +/- 7.6 vs 30.9 +/- 25.1%, p = 0.008). In a second study, 2 BMs from healthy subjects and 1 BM and 2 PBs from chronic myeloid leukemia patients were separated using immunomagnetic beads. The results confirmed the previous study the overall frequency of CD34+ cells in the isolated positive fractions was 85.0 +/- 10.6% (with a recovery of 64.0 +/- 5.7%), while it was only 2.7 +/- 6.6% in the negative fractions. In particular the purity in the two normal BMs was respectively 86 and 97%. According to these results, the great majority of clonogenic cells was separated in the CD34+ fractions. Chymopapain, that was used to detach the beads from the cells, was shown to be non-toxic to the clonogenic cells. Positive selection of CD34+ cells with immunomagnetic beads and chymopapain is a useful method for isolating almost pure progenitors from the PB and the BM for experimental use and is under investigation for clinical applications.

Antigens, CD↗
PubMed1992

Alteration of the proliferative rate of acute myelogenous leukemia cells in vivo in patients.

Ten patients with active acute myelogenous leukemia (AML) received either 13 cis retinoic acid (RA) + alpha interferon (IFN) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 3 days. Cell cycle measurements were performed before and at the conclusion of administration of the bioactive agent(s). The proliferative rate of the leukemia cells in vivo decreased in four of five patients receiving RA+IFN whereas in one patient proliferation accelerated. The proliferative rate of AML cells accelerated in three of the five patients who received rhGM-CSF and slowed in two patients. These data show that while the proliferative rate of AML cells can be altered in vivo, the effect produced by bioactive agents may be the opposite of the desired effect. Furthermore, the studies described here demonstrate the usefulness of marrow biopsies for measuring the percent S-phase cells and the importance of measuring the duration of S phase so that the effects of bioactive agents on the cell cycle time of the leukemia cells can be determined.

Biopsy↗
PubMed1992

Multiparameter assessment of the cell cycle effects of bioactive and cytotoxic agents.

This paper describes the use of the bromodeoxyuridine/propidium iodide method to assess the effects of bioactive and cytotoxic agents on the kinetic characteristics of acute myelogenous leukemia cells. By careful selection of gates, the following parameters can be measured simultaneously using only 50,000 cells: the proportion of cells in S-phase, the distribution of cells within the S-phase compartment, the relative rate of DNA synthesis, the relative distribution of S-phase times, the proportion of S0 cells, and the proportion of cells in G1 and G2/M. This method was used to demonstrate that while retinoic acid, alpha-interferon, and cytosine arabinoside may all "inhibit" DNA synthesis, the actual effects of these agents differ. Retinoic acid appears to arrest cells in G1 without affecting the rate of DNA synthesis, while alpha-interferon and cytosine arabinoside "inhibit" DNA synthesis by reducing the rate of synthesis per se.

Animals↗
PubMed1992

c-myc, c-erbB-2, and Ki-67 expression in normal breast tissue and in invasive and noninvasive breast carcinoma.

c-myc, c-erbB-2, and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas. The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues. Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors, while the level of expression in normal breast tissue was much less than that in breast cancer. Membrane staining of the c-erbB-2 protein was demonstrated in 29% (4 of 14) of noninvasive ductal carcinomas and in 45% (19 of 42) of invasive breast carcinomas. None of the 11 normal breast tissue samples was positive. The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue, 4.57 +/- 1.36% for noninvasive ductal carcinoma, and 12.76 +/- 2.18% for invasive breast cancer. In 42 invasive breast carcinomas, the expression of c-myc, c-erbB-2, and Ki-67 proliferation marker were compared with lymph node status, estrogen receptor status, progesterone receptor status, and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status. We concluded that they might be additional prognostic factors for breast carcinoma.

Breast↗
PubMed1992

The role of emerging technologies in the diagnosis and staging of neoplastic diseases.

The revolution in cell and molecular biology presents an unprecedented opportunity to develop an understanding of neoplastic diseases. The emerging technologies resulting from this revolution also present an opportunity to make the diagnosis and staging of neoplastic diseases more accurate. Unfortunately, the integration of these technologies into current clinical practice is not a simple task. The problems associated with the clinical applications of these technologies include standardization and simplification of the technologies so that they can be established in nonresearch institutions, selection of those technologies which provide clinically meaningful information, and finally, the implementation of large-scale clinical trials which will permit multivariate statistical analyses to determine if performance of the new studies actually add to a physician's ability to diagnose and stage cancer patients. In the future, the staging of patients with neoplastic diseases will include anatomic studies together with morphologic and biologic studies of the tumor cells. Data derived from these studies will be used to assess each patient's risk status regarding the likelihood of local and distant metastases being present. These highly accurate estimates of risk status will lead to an improvement in our ability to make individualized recommendations for therapy.

Forecasting↗
PubMed1992

Protooncogene expression in subpopulations of cells from leukemia patients.

This report describes a method for preserving the light scatter patterns of cells in which myc and myb expression are being measured. Exposure of cells to 1% paraformaldehyde for 72 h prior to antibody staining for myc and myb proteins preserved the light scatter patterns. Using this method, myc and myb expression was found to be highest in lymphocytes and monocytes and lowest in granulocytes. The measurement of differences in the level of expression of these genes in subpopulations of leukemia cells obtained from individual patients is possible as is assessment of the levels of expression amongst normal and leukemia cells present in the same patient.

Bone Marrow↗
PubMed1992

Predicting remission outcome in acute non-lymphocytic leukemia: general principles and their application to residual marrow leukemia.

The objective of this paper is to demonstrate the importance of a rigorous and comprehensive evaluation of predictive tests in acute leukemia, especially when these may influence therapeutic decisions. To illustrate these issues, we have chosen an emerging test, early residual bone marrow leukemia, as the example and we have presented actual data from Leukemia Intergroup Studies of adults with first relapse acute non-lymphocytic leukemia induced with high-dose cytosine arabinoside. We show how the choice of a suitable cut-off value to discriminate between patients predicted to have different remission rates is influenced by several variables including the reasons for remission failure, the estimated efficacy and toxicity of the intervention to be employed, and considerations of resource utilization. We suggest that before applying a new predictive test in practice, clinicians should carefully evaluate its performance, and the consequences of its use in their own clinical settings.

Bone Marrow↗
PubMed1992

Comparison of two methods for concentrating CD34+ cells from patients with acute non-lymphocytic leukemia.

The aim of the present study was to compare two different methods for obtaining CD34+ cells from the peripheral blood or the bone marrow of patients with acute non-lymphocytic leukemia (ANLL). Twenty-two samples, obtained from 19 patients, were density cut (Ficoll-Hypaque 1.077) and, after incubation with My10 antibody, separated by panning or by immunomagnetic beads. Immunomagnetic beads provided a significantly better separation than panning, either in terms of concentration of CD34+ cells (85.5 +/- 11.6% vs. 55.7 +/- 25.0%, p = 0.003) or in terms of depletion of CD34+ cells (3.9 +/- 8.0% vs. 30.9 +/- 26.3%, p = 0.008). This was consistent with the virtually complete depletion of colony forming cells (CFC) in the CD34 negative fraction and the recovery of virtually all the CFC in the positive fraction in the samples separated by immunomagnetic beads. In conclusion, separation by immunomagnetic beads can allow collection of nearly pure CD34+ and CD34- cell populations from patients with ANLL, thereby facilitating the study of the biological characteristics of these cell populations. Moreover the method is less time consuming than panning and is not toxic to the CFC.

Adolescent↗
PubMed1992

Relationship of [3H]Ara-C incorporation and response to therapy with high-dose Ara-C in AML patients: a Leukemia Intergroup study.

Pretherapy bone marrow (BM) aspirates of 143 patients with acute myeloid leukemia (AML) were incubated simultaneously with bromodeoxyuridine (BrdU) and tritiated cytosine arabinoside ([3H]Ara-C) to determine the labeling index (LI) and extent of [3H]Ara-C incorporation. Of 143 AML patients, 121 received high-dose Ara-C (HDAra-C) as a single agent for induction therapy (55 newly diagnosed, 66 in first relapse), whereas 22 received HDAra-C plus mAMSA. The data demonstrate that a subset of patients who will fail HDAra-C remission induction therapy because of drug-resistant disease can be prospectively identified on the basis of the low amount of Ara-C incorporated by their leukemia cells.

Acute Disease↗
PubMed1992

Cell cycle studies in acute myelogenous leukemia.

Since the proliferative characteristics of leukemia cells play an important role in determining response to therapy, one may assume that an alteration of these characteristics could be therapeutically beneficial. To this end appropriate methods should be used to evaluate the effects of bioactive agents on leukemia cells in vivo in patients.

Cell Cycle↗
PubMed1991

Studies of the proliferation and differentiation of immature myeloid cells in vitro: 4: Preculture proto-oncogene expression and the behaviour of myeloid leukemia cells in vitro.

Studies were conducted to determine the relationship between the pretherapy characteristics of leukemia cells and their behaviour during culture in vitro. Leukemia cells which proliferated well in vitro also proliferated well in vivo. Cells which manifested myeloid or monocytic differentiation in vivo tended to manifest differentiation along these lines in vitro. Cells which manifested high levels of expression of c-fms, c-fes, or triose phosphate isomerase prior to culture were likely to differentiate in vitro, with high levels of c-fes expression being related to myeloid maturation. These observations suggest that differentiation at the molecular level prior to culture is a requisite for leukemia cell differentiation in vitro. The same may be true for differentiation in vivo under the influence of exogenously administered agents such as cytotoxic chemotherapy or recombinant growth factors.

Adult↗
PubMed1991

Effects of rGM-CSF on leukemia cell proliferation and on the incorporation of cytosine arabinoside into DNA.

In vitro studies of the effects of recombinant granulocyte macrophage-colony stimulating factor (rGM-CSF) on freshly obtained human leukemia cells were conducted to determine if there is a relationship between the effects of this growth factor on the proliferative characteristics of leukemia cells and on their incorporation of cytosine arabinoside (araC) into DNA. While rGM-CSF was found to be able to stimulate both leukemia cell proliferation and araC incorporation, for individual leukemia specimens there was no consistent relationship among these effects. In some specimens proliferation was stimulated without an increase in araC incorporation. The reverse was also observed. These studies demonstrate the difficulty in identifying assays capable of predicting the clinical effects of growth factors on leukemia cells in patients since the effect in vitro vary with the assay.

Bone Marrow↗