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Biomedical subjects

M Danova

Publications and source records attributed to M Danova.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Interleukin 3 in the treatment of chemotherapy induced thrombocytopenia.

We enrolled 19 cancer patients (11 females, 8 males) with thrombocytopenia after standard dose of chemotherapy to receive IL3 10 mg/kg/day s.c. until hematologic recovery. Therapeutic success was obtained in 69.6% of cycles; a major response in 39.3% and a minor response in 30.3% of cycles. We obtained the best results in case of platelet count <49,000/mm3. The main toxicity was a flu-like syndrome. In two cycles (6%) we registered allergic episodes with flushing and lipothymia. In the 47% of cycles evaluable for toxicity no side effect was registered.

Adult↗
PubMedDate not supplied

Cell cycle status and apoptosis of hematopoietic progenitor cells released into the peripheral blood after taxanes and granulocyte colony-stimulating factor in breast cancer patients.

Paclitaxel and its analogue docetaxel show a significant antitumor activity, particularly evident in breast cancer. Paclitaxel has also been proved to be effective as a peripheral blood progenitor cell (CPC) mobilizing agent. To optimize the use of active, disease-specific drugs as CPC priming, we have evaluated the effects of either paclitaxel or docetaxel both at standard dosages and followed by granulocyte colony-stimulating factor (G-CSF), on circulating CPC release and function in 18 patients with advanced breast cancer who had failed previous anthracycline-based regimens. The reported differences in biological behaviour between bone marrow and blood-derived hematopoietic progenitor cells and the ability of both paclitaxel and docetaxel to induce apoptosis, prompted us to simultaneously evaluate the cell cycle perturbations induced on CD34+ cells. Median CD34+ peaks were 24 microl (range: 10-58) in the paclitaxel-treated patients and 39 microl (range: 17-91), respectively, in the patients who received docetaxel. After paclitaxel, the percentage of CD34+ cells in S-phase was low (bromodeoxyuridine, BrdU, labelling index = 3.4+/-2%) with a concomitant presence of early apoptotic cells (8.1+/-3%). On the contrary, after docetaxel, the percentage of CD34+ cells in S-phase was higher (BrdU labelling index = 14.5+/-4%, p<0.05 vs. paclitaxel), while early apoptotic cells were detected at a similar rate (8. 6+/-3%, p = n.s. vs. paclitaxel). In conclusion, when used at standard dosages, with respect to paclitaxel + G-CSF, docetaxel + G-CSF is a more satisfactory tool to mobilize CPC and to induce them into the cell cycle. These data should be taken into account when combinations of docetaxel with other agents are explored as CPC mobilizing regimens for autografting.

Adult↗
PubMedDate not supplied

Left ventricular function in colon cancer patients receiving adjuvant fluoro-folate chemotherapy: an echocardiographic study.

Cardiotoxicity has been reported with increasing frequency after 5-FU administration. Since 5-FU-based regimens are increasingly used as adjuvant treatment for resected colon cancer patients, this carries a potential increased risk of cardiotoxicity. In the present study, we evaluated if fluoro-folate chemotherapy has any effect on left ventricular (LV) diastolic function in resected colon cancer. Twenty-five resected colon cancer patients receiving adjuvant fluoro-folate chemotherapy, were prospectively studied. Both digitized M-mode and Doppler echocardiography were performed, in order to investigate different aspects of LV diastolic function. None of the studied parameters was influenced by chemotherapy administration. Indeed, values recorded at the end of the 6-month treatment and 6 months later were not statistically different from baseline values. This study suggests that the use of fluoro-folate chemotherapy in otherwise normal subjects carries a very low risk of severe cardiotoxicity.

Aged↗
PubMedDate not supplied

[Topotecan: a new field of use].

Topotecan, a semi-synthetic derivative of the alkaloid camptothecin is an antitumor drug that like other camptothecin derivatives, targets DNA topoisomerase I, an enzyme that is present in cells in concentration relatively independent of the stage in the cell cycle. Topotecan stabilizes the complex formed between topoisomerase I and DNA, leading to DNA strand breakage and cell death. In accordance with preclinical studies, clinical efficacy of topotecan was documented in ovarian carcinoma, in small cell lung cancer and in childhood solid tumors. Myelosuppression is the dose-limiting toxicity and nonhematologic side effects are generally mild. The activity of topotecan against a number of hematological malignancies is now increasingly exploited as well as its role in high-dose chemotherapy programs with stem cell support. In both lymphoblastic and myeloid acute leukemias, topotecan has been widely utilised both as single agent or associated to other cytostatic drugs with proven efficacy in these diseases. Most of the published phase II studies demonstrated that heavily pre-treated, relapsing patients achieve a high percentage of overall responses with manageable toxicity. In myelodisplastic syndromes and acute myelomonocitic leukemias a recently published study shows positive results for the combination of topotecan and cytarabin. Topotecan seems to preferentially affect the abnormal cytogenetic clones and in patients achieving a complete response, a conversion from an aneuploid to a diploid karyotipe was documented. In non-Hodgkin lymphomas, several schedules have been tested in the phase I setting. When utilized alone and at very low dosage, the drug yielded 15% of objective responses and a lack of extrahematologic toxicity. Of particular interest seems to be the association of topotecan with taxanes that needs to be supported by growth factors. In multiple myeloma Topotecan has been utilized as single agent in heavily pre-treated patients. The obtained results show good activity and again myelosuppression as preminent toxicity. The use of topotecan in high-dose chemotherapy regimens for multiple myeloma has been proposed. The utilization of topotecan in high-dose chemotherapy is one of the newer and more interesting applications. Solid tumors (i.e. ovarian cancer and small cell lung cancer) are actually investigated by many authors, who have indicated that this drug can be used preferentially as a part of diversified programs containing overlimit dosages of different cytostatics. Furthermore, topotecan demonstrated to be an effective drug to mobilize CD34+ cells for autografting. A general conclusion is that topotecan is an interesting addition to the actual chemotherapy scenario, both because of its mechanism of action and its toxicity profile. The present review of the new possibility of utilization, give us the idea that topotecan has activity in several hematologic neoplasias; further investigations in these diseases (i.e., induction treatment, combination chemotherapy) are then warranted. The broad spectrum of antitumor activity and the characteristics of toxicity make it also interesting for use in both the circulating progenitor cell mobilization and in the consolidation phase of high-dose chemotherapy programs.

Antineoplastic Agents↗
PubMedDate not supplied

Sequential docetaxel and vinorelbine for patients with advanced breast cancer previously treated with anthracyclines: a phase II study.

With respect to their association, sequential non-cross-resistant cytostatics could be better tolerated and allow a similar antitumor effect. From January, 1998 to July, 1999, 42 consecutive patients with metastatic breast cancer (MBC) previously treated with anthracyclines as adjuvant- or first-line therapy entered a phase II multicenter study where docetaxel (TXT, 100 mg/m2/3 weeks/4 times) was followed by vinorelbine (VNR, 25 mg/m2/10 days/8 times). Median follow-up is 21 months and 22/42 patients have died. Four patients did not complete therapy due to early death, grade 3-4 gastrointestinal mucosytis (2 patients) and grade 3 neurotoxicity during TXT therapy. Overall response rate was 57%, and 5% of patients had stable disease. There were 38% of therapy failures due to non-evaluability (10%) or progressive disease (28%). Median time to progression and survival are 10.1 and 17.1 months. Sequential TXT-VNB is a suitable strategy for MBC patients previously treated with anthracyclines. It avoids haematologic toxicity and allows a good antitumor effect. Careful monitoring of intestinal mucosytis is required.

Adult↗
PubMedDate not supplied

Establishment and characterization of two cell lines derived from human glioblastoma multiforme.

We established and characterized two cell lines derived from glioblastoma multiforme. Both cell lines exhibited tumor cell morphology and growth kinetics and showed variable expression of glial fibrillary acidic protein (GFAP), S-100, fibronectin and vimentin. Cytofluorimetrical analysis of tumor samples showed a diploid DNA distribution, whereas permanent culture cells evolved to the hyperdiploid DNA content. Karyotype studies revealed cytogenetical abnormalities described in glial tumors including gain of chromosome 7, loss of chromosome 10 and presence of double minutes (DMs). Enhanced expression of Ha-ras and c-myc genes resulted from high p-21 and p-62 levels. The contemporary presence of TGF-alpha and EGF-Rc transcripts suggested an autocrine mechanism in the cell lines growth.

Cell Division↗
PubMedDate not supplied

[The in vivo use of bromodeoxyuridine for the study of cell kinetics in squamous tumors of the neck and head. Implications for the radiotherapist].

Cell kinetics in 22 human epidermoid head and neck tumors were studied in vivo using bromodeoxyuridine (BUrD). Patients were infused with 250 mg/m2 of intravenous BUrD in a variety of sites (oral cavity, pharynx, larynx and lip) four/five hours prior to biopsy. BUrD incorporating cells were detected by flow-cytometry using anti-BUrD monoclonal antibodies. Ploidy (DNA index) labelling index (LI%), duration of S-phase (Ts) and potential doubling time (Tpot) could be measured within 12-24 hours from sampling in 77%, 72%, 63 and 63% of cases, respectively. Six failures (few viable cells in biopsy specimen and difficulties in BUrD cell analysis and DNA staining) were recorded. Labelling index values in this study ranged from 2.2% to 28% with a median value of 11%. The median total LI% of diploid tumor (n = 7) was 5% compared to 13% in aneuploid tumors (n = 7). Ts measurement ranged from 6.5 hours to 12 hours, median value being 10.5 hours (euploid tumors: 6.5, aneuploid 12). The calculated potential doubling time ranged from 2.6 to 15 days and the median Tpot was shorter at 5.0 days (euploid tumors: 7 days, aneuploid 4 days). 70% of the tumors had potential doubling time of 5 days or less. Potential doubling time did not correlate with ploidy and tumor or neck nodes status while shorter Tpots were observed in moderate or poorly differentiated tumors. Our data strongly suggest BUrD technique as a useful tool for studying the proliferative behavior of human tumors: the pre-treatment knowledge of individualized potential doubling times for the tumors scheduled for irradiation could help the radiotherapist to choose the more effective fractionation regimen (i.e.: accelerated fractionation for tumors with Tpot less than or equal to 6 days and standard fractionation for tumors with higher values.

Bromodeoxyuridine↗
PubMedDate not supplied

Cell cycle-related proteins and flow cytometry.

Several nuclear and surface proteins are expressed in varying amounts in the different phases of the cell cycle. For some of them the coding gene is not known and changes in their expression could simply be secondary to changes in the proliferative activity of the population. Other proteins are oncogene products, probably having a direct regulatory function in cell proliferation, differentiation and malignant transformation. Studying these proteins may both permit a better understanding of the mechanisms regulating proliferation and differentiation and provide kinetic parameters for describing the cell cycle. Based on antibodies against these proteins, bivariate flow cytometry (FCM) is able to quantitate their expression simultaneously with DNA distribution. This allows protein expression to be related precisely with each cell cycle phase in populations having different proliferative activity. Further advantages of bivariate FCM are that few cells are required for the analysis and the percentage of cells expressing the (onco) gene product can be determined. Several cellular proteins have been investigated with bivariate FCM, and the data are reviewed. Some proteins not coded by oncogenes (such as cyclin, the Ki-67 reactive antigen and DNA polymerase alpha) are expressed in cycling, but not in G0 cells and are of special interest for the kineticist, since they could identify cells which are able to initiate DNA synthesis, i.e. those representing the "growth fraction" of the population. Statin, on the contrary, is apparently expressed only in G0 cells. The expression of some proteins coded by oncogenes, such as p53 and the c-myc product is high in proliferating G1 cells and decreases with differentiation. The expression of the c-ras product is not strictly related to cell cycle phases and increases with differentiation. Technical improvements (allowing, for example, the monitoring of the changes in protein expression following the microinjection of a protein-blocking substance into the cells and the inclusion of phenotype markers into the analysis) will expand the role of bivariate FCM for these research works.

Animals↗
PubMedDate not supplied

Bone marrow morphology and proliferative activity in acquired immunodeficiency syndrome.

Peripheral cytopenia has been reported in a number of patients with the acquired immunodeficiency syndrome (AIDS), but the mechanism of bone marrow (BM) failure is unclear. We have examined the BM morphology and cytokinetics of 16 untreated HIV-positive patients whose clinical condition ranged from asymptomatic (stage 1 WR and II CDC classifications) to overt AIDS (stage 6 WR and IV CDC classifications). BM aspirates and iliac crest threphine biopsies were obtained for myelogram and histologic examination, as well as for propidium iodide flow cytometric (FMC) DNA analysis. FCM data were compared with those from the BM of patients with solid tumors without BM involvement. Four patients had normal peripheral blood counts, 2 were anemic, 2 had granulocytopenia, 2 thrombocytopenia, 4 bicytopenia and 2 pancytopenia. BM cellularity was normal or increased, but only 2/16 patients had normal BM morphology. Ten patients had atypical lymphoid aggregates, relative plasmacytosis and eosinophilia, and 4 had typical myelodysplastic changes. There was no correlation between morphology and WR or CDC grade. The mean proliferative fraction (i.e. the percentage of cells in the S phase of the cell cycle) of the HIV-positive patients was 11% (range 5.5-18.3%). The mean value for the control patients was 15.1% (range 7.7-26.9%) (p less than 0.05). All patients had modal diploid DNA content without aneuploid clones. These data suggest that the mechanism of BM failure in HIV-positive patients lies in a reduced proliferative activity whose exact cause is still unclear.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Hematological values from quantitative buffy coat analysis (QBC II) system: evaluation in a hematological/oncological outpatient section.

The quantitative analysis of the buffy coat (QBC II system) of centrifuged whole blood samples allows one to obtain hematocrit (Ht), platelet (PLT) and white blood cell (WBC) values. We have tested the QBC II system in a hematological/oncological Outpatient Section, where it is necessary to know patient's hematological condition immediately before administering chemotherapy. One hundred ten blood samples from 110 patients with solid or remission hematological tumors were measured in duplicate with the QBC II system and with the counter instrumentation (Sysmex TOA 800) of the Central Laboratory, where samples were sent for emergency determination. Reliable values for Ht and WBC were obtained in all samples, and for PLT in 101 samples. The QBC II System failed to furnish very low and very high PLT counts. The time needed for the QBC II system analysis was shorter than that required to obtain the Central Laboratory data. The QBC II system analysis is a useful means for rapidly evaluating the basis hematological condition in most chemotherapy patients.

Hematocrit↗
PubMedDate not supplied

Simultaneous detection of cellular ras p21 oncogene product and DNA content by two-parameter flow cytometry.

The rapid identification of the expression of oncogene products in specific cell types could be useful to investigate normal and malignant cell proliferation. We have developed a sensitive fixation - permeabilization technique (with 70% ethanol and 0.01% Triton x 100) for the detection of p21 ras oncoprotein and DNA content. Cell suspensions with negligible cell clumping, bright specific immunofluorescent staining were obtained with this method. Bivariate flow cytometry was then used to quantitate simultaneously the distribution of anti p21 ras oncoprotein (with a specific FITC-labeled antibody) and of total DNA (with propidium iodide). The study was carried out in human leukemic cell lines HL-60 and K562, human breast carcinoma cell line MCF-7 and fresh neoplastic cells from human acute leukemia. The p21 ras oncoprotein was found in all phases of cell cycle. The degree of its expression, however, varied widely in diploid (C0/G1) cells from different samples, which could be related to differences in the relative proportion of G0 and G1 cells. Compared to the conventional gel electrophoretic technique, the use of bivariate FCM is feasible, fast, requires fewer cells per sample (2 x 10(6] and allows both the ras oncogene expression in intact cell populations as well as its relationship with cell cycle phases to be studied.

Cell Cycle↗
PubMedDate not supplied

Cell kinetic studies of human intracranial tumors.

The authors report their experience on cell kinetic studies of intracranial tumors. Three methods have been utilized to measure cell kinetic parameters: flow-cytofluorometry, flow-cytofluorometry and "in vivo" administration of bromodeoxyuridine, the monoclonal antibody Ki-67. The results of these studies are reported and the role of each method is discussed.

Adolescent↗