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Biomedical subjects

H D Preisler

Publications and source records attributed to H D Preisler.

At least 55 records · Page 3Linked to original sources
PubMed1997

Accuracy of histone H3 messenger RNA in situ hybridization for the assessment of cell proliferation in human tissues.

Histone H3 mRNA in situ hybridization was compared to a reference method, iododeoxyuridine (IdUrd) immunohistochemistry of tissues labeled in vivo, as a means for assessing the proportion of S-phase cells (labeling index, LI) in oral tumor and normal mucosa. Paraffin sections from 16 patients with oral squamous cell carcinoma were studied. Patients received an IdUrd infusion before the biopsy was taken. Tissue sections were coded before counting the percentages of S-phase cells. A high correlation was found between the results obtained by the two techniques. The average histone H3 and IdUrd LIs of the tumors were 28.5 +/- 2.4% and 29.2 +/- 2.7%, respectively (P = 0.85), with a Spearman correlation coefficient r = 0.95 (P < 0. 0001). The histone H3 LI of the basal layer of normal mucosa was 3.1 +/- 0.8%, whereas the IdUrd LI was 2.7 +/- 0.9% (P = 0.74), with r = 0.78 (P = 0.004). In the suprabasal layers, these parameters were 21. 3 +/- 2.3% and 23.9 +/- 3.2%, respectively (P = 0.56), with r = 0.93 (P < 0.0001). In sections stained for both histone H3 and IdUrd, most cells were double labeled, with very few cells containing only one of the labels. In some specimens, large areas of H3-stained cells did not contain IdUrd-labeled cells, suggesting that during the IdUrd infusion, the precursor did not reach these areas. Two specimens were histone H3 negative. They were also negative when hybridized with beta-actin probe, indicating degradation of mRNAs in these samples. The results of this study demonstrate that the histone H3 mRNA in situ hybridization performed in human formalin-fixed, paraffin-embedded tissues provides the same data as does labeling the tumors in vivo with halogenated pyrimidine.

Biopsy↗
PubMed1996

Enzymatic programming of apoptotic cell death.

The phenomenon of 'apoptosis' was recognized in the early seventies. However, most of the mechanistic insights into the process of apoptotic cell death came about only in the last few years. It is now clear that a variety of enzymes constitute the major mediators of this process. The present article reviews the possible interrelationships between these enzymes and proposes a model for enzymatic programming of apoptotic cell death.

Animals↗
PubMed1996

Accuracy of immunohistochemistry and flow cytometry in estimating the proportion of leukemic cells in S phase in chronic myeloid leukemia patients.

We compared the proportion of S phase cells in bone marrow and peripheral blood samples obtained from 17 patients with chronic myeloid leukemia (CML). Before sampling all patients received a one hour i.v. infusion of iododeoxyuridine (IdUrd). The proportion of S phase cells was studied by immunohistochemistry (IHC) in bone marrow biopsies, and by flow cytometry (FCM) in bone marrow aspirates and peripheral blood samples. The IdUrd labelling index (LI) in bone marrow biopsy sections (27.5 +/- 1.8%) was significantly higher than the proportion of IdUrd labelled cells in bone marrow aspirate (15.1 +/- 2.0%). The percentage of S phase cells in peripheral blood was approximately the same as that in the aspirate (12.4 +/- 1.3%) and was correlated with that of bone marrow aspirate indicating a high degree of the aspirate dilution by peripheral blood. It is likely that the differences in % S phase cells in the aspirate and the biopsy result from this dilution. Estimates of the % S phase cells in the peripheral blood study by IHC and FCM were essentially the same. Samples labelled for one hour in vitro resulted in 1.5 fold higher LI than the same samples labelled in vivo. We conclude that estimates of the 8% S phase cells in the bone marrow of patients with CML should be made by infusing patients with IdUrd or BrdUrd with immunohistochemical evaluation of a marrow biopsy. Additionally in vitro labelling is not reflective of the percent S phase cells in vivo in patients.

Antibodies, Monoclonal↗
PubMed1996

Continued malignant cell proliferation in head and neck tumors during cytotoxic therapy.

The effect of cytotoxic therapy on the proliferation of squamous cell carcinoma of the head and neck in vivo in patients was evaluated before and 15-35 days after the start of therapy. To accomplish this, iododeoxyuridine was administered at t = 0, and bromodeoxyuridine was administered 15-35 days later during treatment with a tumor biopsy obtained for study immediately after each pyrimidine infusion. Monoclonal antibodies specific for the halogenated pyrimidines were used to identify cells that were in the S-phase at the time of the infusions. Eleven patients were studied prior to treatment. Of those, the intratreatment biopsy of eight patients contained tumor tissue. In the other three patients, tumor tissue was not present in the second biopsy. Continued precursor incorporation into DNA-synthesizing cells during treatment was detected in six of eight tumor specimens. In two tumor specimens, an increase in the percentage of S-phase cells was noted, in two specimens tumor cells synthesizing DNA were not detected, and in four specimens the percentage of S-phase tumor cells was lower than that in the pretherapy specimen. Patients in whom there were no S-phase cells detected during treatment or in whom no tumor was detected in the second biopsy had a favorable treatment outcome in comparison to those patients in whom continued tumor proliferation during treatment was detected. The number of cells in S-phase prior to the initiation of treatment was not predictive of whether or not proliferation would continue during cytotoxic therapy. Evidence for reentry of kinetically quiescent cells into the cycle during treatment was noted. Additionally, cytotoxic therapy altered the proliferation pattern of normal-appearing mucosa as well. The results of this study demonstrate that tumor cell proliferation does continue in some squamous cell carcinoma of the head and neck during intensive cytotoxic therapy.

Adult↗
PubMed1995

Distribution of cell cycle times amongst the leukemia cells within individual patients with acute myelogenous leukemia.

Seventeen patients with AML received infusions of BrdUrd to permit measurement of the cell parameters of leukemia cells in vivo. The range of S-phase times was measured by using a two color BrdUrd/Pl analysis to determine the range of BrdUrd incorporation into cells which had been in S-phase throughout the entire duration of BrdUrd administration. These data were, in turn, used to calculate the range of cell cycle times amongst the leukemia cells present within individual patients. The range of cell cycle times amongst the leukemia cells present within individual patients differs between patients, with some leukemia cell populations characterized by narrow and others by broad ranges. In general, the longer the mean cell cycle time (between 27 and 112 h) the broader the range of cell cycle times. These differences may help to explain, in part, the differences in response to therapy among patients whose mean leukemia cell kinetic parameters are similar.

Bromodeoxyuridine↗
PubMed1995

Resistance to cytotoxic therapy: a speculative overview.

While most recent studies have focused on the MDR1 gene and other similar types of multidrug resistance, two other phenomena (inhibition of the apoptotic pathway and regrowth resistance) have the potential for producing a much broader type of resistance to cytotoxic therapy. This speculative review discusses the potential contribution of these types of resistance and the possible interrelationships between the various types of resistance to cytotoxic therapy. The need for new approaches to assess the effects of biological agents is discussed.

Cell Division↗
PubMed1995

Regrowth resistance in cancer: why has it been largely ignored?

In drug-sensitive malignancies, treatment failure is a complex phenomenon resulting from both drug resistance and the rapid regrowth of malignant cells in between cycles of chemotherapy. This phenomenon has been referred to as regrowth resistance, and has been identified as a common impediment to the successful treatment of many neoplastic diseases. This phenomenon has received little attention in the past. The administration of maximally tolerated individual dosages of chemotherapeutic agents, combined with the use of biological response modifiers to slow the regrowth between courses of therapy, would be an effective approach to reduce the regrowth resistance. This also could reduce the emergence of drug resistant clones.

Antineoplastic Agents↗
PubMed1995

In vivo labelling with halogenated pyrimidines of squamous cell carcinomas and adjacent non-involved mucosa of head and neck region.

The frequency and distribution of labelled cells were studied immunohistochemically in 37 squamous cell carcinomas (SCC) of head and neck after in vivo infusion of IdUrd and BrdUrd. Tumours were classified according to their labelling patterns. Low and moderate grade SCC consisted of tumour islands separated by interstitial tissue. In some tumours labelled cells only appeared near the basal layer while in others proliferative cells were evenly distributed within the neoplastic island. In anaplastic carcinomas labelled cells were distributed either randomly or around blood vessels (cord structures). While the basal layer in adjacent normal epithelium contained very few labelled cells (LI = 1.6 +/- 0.2%), the LI of basal cells in tumour islands were much higher than the average LI of the tumour (47.2 +/- 2.8% and 23.8 +/- 1.6%, respectively). In patients who had received cytotoxic therapy up to two months before the biopsy, the LI in the basal layer of normal epithelium was 19.0 +/- 3.5%. In sequential biopsies obtained 1-2 weeks after the infusion of IdUrd and BrdUrd some labelled tumour cells were found in necrotic foci and in pearl structures. Additionally, in six tumours, we found areas of cells labelled with IdUrd alone, even though the IdUrd infusion had been followed by a BrdUrd infusion 1 h later. This is in agreement with the phenomenon of intermittent tumour blood flow described earlier in experimental tumours.

Biomarkers, Tumor↗
PubMed1995

Cell kinetics of head and neck cancers.

We measured the tumor cell proliferative rate in 26 patients with head and neck cancer, 22 of which were squamous cell carcinomas (SCCs). Patients received sequential infusions of iododeoxyuridine and bromodeoxyuridine, after which the tumor was biopsied and studied. The percentage of labeled cells [labeling index (LI)] in well-differentiated SCCs was 20.4 +/- 2.7% (mean +/- SE) and 23.8 +/- 2.1% in moderately differentiated SCCs (P = 0.135). The LIs of two poorly differentiated SCCs were 39.4 and 55.9%. The LI was 2.5% in a high-grade lymphoepithelioma and 24.8% in a malignant lymphoma. In one well-differentiated and one poorly differentiated mucoepidermoid tumor, the LIs were 3.0% and 29.1%, respectively. S-phase duration time measurements ranged from 5.1-21.5 h (12.8 +/- 1.5). The calculated potential doubling times ranged from 18.8-84.5 h (47.3 +/- 6.7). The duration of G2 was between 90 and 180 min. To track the fate of labeled cells, in four patients a repeat biopsy was obtained 7-14 days after the iododeoxyuridine/bromodeoxyuridine infusion. These patients did not receive treatment between the biopsies. Due to the dilution of the label, most labeled cells in the second biopsy demonstrated a "fragmented" pattern resulting from repeated cell divisions. In two patients, however, 25% of cells in the second biopsy had undiluted label, suggesting that these cells had not divided after incorporating iododeoxyuridine/bromodeoxyuridine. On Day 7 labeled cells migrated to keratinized parts of tumors and to necrotic foci. Thus, the arrest of cell cycle transition, tumor cell differentiation, and cell death may be major routes of tumor cell loss from the proliferative compartment. This may explain the difference between very short potential doubling times and the actual rate of tumor growth.

Biopsy↗
PubMed1994

Regrowth resistance in leukemia and lymphoma: the need for a new system to classify treatment failure and for new approaches to treatment.

Treatment failure in drug sensitive malignancies is a complex phenomenon resulting from both drug resistance and from the rapid regrowth of malignant cells ('regrowth resistance'). Attempts to overcome regrowth resistance during the treatment of the aggressive lymphomas by increasing the frequency of cytotoxic therapy appears to have failed. An alternative approach of significant potential would be to administer biologically active agents to directly slow the regrowth of neoplastic cells between courses of full dose cytotoxic therapy. To facilitate this approach a new system for classifying treatment failure in the leukemias and lymphomas is needed so that the extent of regrowth resistance and the effects of treatment on regrowth resistance can be directly assessed. Accordingly, a new classification system is proposed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Parallel studies of clonogenic leukaemia cells and the leukaemia cell population as a whole in acute myelogenous leukaemia.

The clonogenic cells in patients with acute myelogenous leukaemia (AML) were evaluated with respect to the relationship between primary and secondary cloning capacity and the proliferative and molecular biological characteristics of the leukaemia cell population as a whole. Secondary cloning capacity was correlated with primary cloning efficiency, and with the ability of the clonogenic cells to produce large sized clones. The cloning capacity of AML cells was unrelated to the cell cycle characteristics of the leukaemia cell population in vivo or to the level of myc, myb, fms, or interleukin (IL)1 beta expression. The sensitivities of the clonogenic cells to cytosine arabinoside and daunorubicin were inversely correlated with the ability of the leukaemia cells to produce large sized clones in vitro. This latter observation may explain the reported relationships between the clonogenic capacity of AML cells and response to chemotherapy.

Cell Cycle↗
PubMed1994

The relationship of the in vivo cell cycle characteristics and treatment outcome in acute myelogenous leukemia to the expression of the FMS and MYC proto-oncogenes.

Fms expression was measured by Northern blot analysis in the pretherapy leukemia cells of 30 patients with acute myelogenous leukemia (AML) who either entered CR or who were shown to have drug resistant disease. High levels of fms expression correlated with a CR outcome and were strongly associated with the fall in the number of leukemia cells during the first six days of remission induction therapy. In contrast, similar studies of myc expression failed to demonstrate any relationship to treatment outcome. Considering those genes whose expression have been measured to date, the level of expression of fms is the one which is most highly correlated with treatment outcome in AML. No significant relationship between the expression levels of these two genes and the cell cycle characteristics of leukemia cells in vivo were detected.

Blotting, Northern↗
PubMed1994

The study of acute leukemia cells by means of acridine orange staining and flow cytometry.

The studies described here explored the staining of acute leukemia cells with acridine orange (AO). The red fluorescence curve of AML specimens was usually bimodal, suggesting the presence of subpopulations of cells which have different RNA contents. In almost every AML specimen, small leukemic blast cells comprised at least part of the "low RNA content" subpopulation. Residual granulocytes and lymphocytes also contributed to this population. Frequently, the green fluorescence, indicative of the binding of AO to DNA, was slightly less in these cells than in the majority of cells present. There was no evidence however, that the leukemia cells with these characteristics represented a G0 or kinetically quiescent population of cells. In ALL specimens, the presence of multiple cytogenetically distinct clones was easily detectable in AO stained specimens. The red fluorescence curve of G0/G1 ALL cells was unimodal.

Acridine Orange↗
PubMed1994

The leukemias.

The leukemias can be divided into acute and chronic varieties, both of which have a myelocytic and lymphocytic type. When untreated, the acute leukemias are associated with a more rapid clinical course than are the chronic leukemias. Paradoxically, to the present time, the acute leukemias have been curable with chemotherapy, whereas the chronic leukemias have not. Until recently the treatment goal for patients with chronic leukemias has been to return the patient's life to normal for as long as possible. With recent advances, it may now be possible to cure some patients with chronic leukemia. Acute leukemias are treated with intensive chemotherapy, which is associated with severe and life-threatening side effects. Although this approach to treatment will cure some patients, the use of bone marrow transplantation has had an increasingly important role in the treatment of younger patients with these diseases.

Acute Disease↗
PubMed1993

Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia.

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1 beta genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1 beta gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy.

Aged↗
PubMed1993

Clonogenic potential of myeloid leukaemia cells in vitro is restricted to leukaemia cells expressing the CD34 antigen.

Cells from patients with acute myeloid leukaemia (AML) or chronic myeloid leukaemia (CML) were separated into CD34-enriched and CD34-depleted subpopulations. The clonogenic capacities of these two subpopulations were then compared to each other and to the original unseparated cell population. In every study, the CD34-enriched subpopulation demonstrated a substantial increase in clonogenicity in vitro in comparison with the original cell population, while the reverse was the case for the CD34-depleted subpopulations. For reasons not clear at present, the enrichment for clonogenic cells far exceeded the enrichment for cells expressing the CD34 antigen. Additionally, the clonogenic potential was found to be unrelated to the level of myc expression in the various cell populations.

Antigens, CD↗
PubMed1993

The serial study of c-myc expression in bone marrow biopsy specimens during treatment for acute myelogenous leukaemia.

The AMEX method of fixation permitted the serial study of c-myc expression in bone-marrow (BM) biopsies obtained from 6 patients with acute myelogenous leukaemia (AML) and one with myelodysplastic syndrome (MDS) during therapy with various cytotoxic and bioactive agents. BM cytotoxic therapy and therapy with bioactive agents was capable of altering c-myc expression in vivo. While cytotoxic therapy was generally associated with a fall in myc expression, it did not produce a dramatic effect on myc expression. Recombinant human granulocyte-macrophage colony-stimulating factor (RhGM-CSF) can increase and retinoic acid/alpha-interferon can decrease c-myc expression in myeloid cells in vivo.

Adult↗