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Biomedical subjects

F Mauro

Publications and source records attributed to F Mauro.

At least 55 records · Page 3Linked to original sources
PubMed1986

Flow cytometrically determined DNA content of breast carcinoma and benign lesions: correlations with histopathological parameters.

The relative DNA content of cellular samples from 54 patients affected by breast carcinomas and 20 affected by benign breast lesions (including 11 fibroadenomas) was measured by flow cytometry. All normal tissue samples and 17/20 (85%) specimens from benign lesions exhibited a cytometrically diploid DNA distribution, 3/20 (15%) benign lesions an abnormal DNA content, and 35/54 (65%) carcinomas at least one aneuploid cell subpopulation. Furthermore, 9/54 (17%) tumors were characterized by the presence of more than one aneuploid cell subpopulation. The results also indicate that flow cytometry can be used to recognize lymph nodes infiltrated by aneuploid cells. Statistically significant correlations were evidenced between the occurrence of aneuploidy or the ploidy level measured as DNA index and the nodal infiltration status. The percentage of S cells can also be extracted from DNA content distribution histograms. Statistically significant differences (p less than 0.01) were also observed for the percentage of S cells between normal tissues (6.2 +/- 3.2 SD) and benign lesions (11.1 +/- 6.6 SD), normal tissues (6.2 +/- 3.2 SD) and aneuploid tumors (19.7 +/- 10.3 SD), benign lesions (11.1 +/- 6.6 SD) and aneuploid tumors (19.7 +/- 10.3 SD), and diploid (7.9 +/- 4.0 SD) and aneuploid tumors (19.7 +/- 10.3 SD).

Adult↗
PubMed1986

Flow cytometry as a tool for the prognostic assessment of human neoplasia.

Flow cytometry permits the quantitative description of neoplastic cell populations from the point of view of their cytogenetic and cytokinetic features. The advances in preparation of cellular monodispersed samples allow the examination not only of in vitro and hematological, but also of surgical, biopsy, endoscopic, and lavage specimens. The analysis of cytometric DNA content has evidenced the importance of (aneu)ploidy as a remarkable tumor marker. Tumors of different sites and, in some cases, stages and/or grades are characterized by a differential occurrence of diploid vs. aneuploid cell subpopulations and by the eventual presence of different stem cell lines within the same tumor. For certain classes of neoplasms, these parameters can be used for the early recognition of neoplasia and related to disease evolution and dissemination and to the results of therapy. Flow cytometry can also be used to evaluate the fraction of (cycling) cells in the S-phase and of proliferating cells (growth fraction). The percent of S cells can be extracted from cytometric DNA content histograms. Furthermore, the method of Bromodeoxyuridine (BrdUrd) incorporation has been recently introduced into flow cytometry. BrdUrd labeling in cycling cells can be detected either by the induction of quenching or enhancement of specific DNA-dye fluorescence or by fluorescent anti-BrdUrd monoclonal antibodies. This approach has been confirmed by preliminary comparative tests on cultured cells, normal and malignant bone marrow, and human solid tumor specimens. These parameters, together with other cytometric parameters of potential importance for the cellular characterization of malignancy, offer a reliable and real time-saving tool for the prognostic assessment of human tumors and the predicting and monitoring of the results of therapy.

Aneuploidy↗
PubMed1986

Considerations in the design of possible cell cycle effective drugs.

Antineoplastic agents are known to induce differential cytotoxic and cytostatic effects throughout the cell cycle. Many drugs have greater toxicity for cycling cells and act selectively at one or more phases of the cycle and may cause partial synchrony of surviving cells. However, these observations have been generally carried out on in vitro systems only and present a variety of complexities and pitfalls. Furthermore, human tumours are often characterized by a relatively low fraction of proliferating cells and present a large cellular heterogeneity as far as their cytogenetic, cytokinetic, and clonogenic features and their responses to drugs are concerned. Therefore, resistance to chemotherapy is due to various factors characterizing, in some instances, each individual tumour. In spite of the advent of technological advances such as flow cytometry, it is still difficult to design kinetic-orientated therapies especially for the treatment of solid tumours. Consequently, it is also difficult to design protocols based on cell cycle effective drugs. The possibility remains, at least for the moment, to stratify tumours according to their cellular heterogeneity. Different protocols could then be assigned to classes of tumours. Such an approach could be completed by further advances in the cellular monitoring of individual tumours.

Alkylating Agents↗
PubMed1984

Cytometrically determined relative DNA content as an indicator of neoplasia in gastric lesions.

Cellular samples from human gastric endoscopic biopsies were analysed in order to detect possible DNA content alterations as markers of cancerous and precancerous lesions of the digestive tract. Samples were derived from the stomach of normal donors (17 cases), and from patients clinically classified as affected by stomach adenocarcinoma (18 cases), chronic atrophic gastritis (20 cases), or other nonneoplastic lesions (17 cases). Sample processing was performed by mechanical and enzymatic treatment to obtain monodispersed cells. Staining for flow cytometric analysis was achieved with ethidium bromide and mithramycin. Samples from normal donors constantly exhibited a single cell population with diploid DNA content. All but three neoplastic specimens exhibited both a diploid and an aneuploid cell subpopulation, with the DNA index of the aneuploid peak ranging from 1.10 to 1.85 (except a single instance with a value of 3.13). The presence of a recognizable aneuploid subpopulation was also observed in 9 out of 20 chronic atrophic gastritis specimens. Such aneuploidy is similar to that observed for the adenocarcinoma, even if the fraction of aneuploid cells appears to be generally higher in the tumor than in the gastritis cases. All other cases of gastritis and of nonneoplastic disease exhibited diploid cells only. The meaning of aneuploidy in some gastritis specimens is a phenomenon not yet fully explained. Still, aneuploidy appears to be a useful marker for recognizing the presence of suspect malignant cells in gastric lesions.

Adenocarcinoma↗
PubMed1983

MOPP treatment of resistant Hodgkin's disease following ABVD failure.

Fourteen patients with Hodgkin's disease resistant to ABVD were treated with MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone). Complete remission was obtained in 6 patients (43%). Four of the 6 complete responders are disease free after 5, 20, 23, 35 months. The actuarial median survival after MOPP of all patients is 20 months. These data confirm that there is no "cross-resistance" among the drugs included in the two schedules.

Adolescent↗
PubMed1983

Bone marrow involvement at onset of Hodgkin's disease.

Bilateral trephine bone marrow biopsies of 370 patients with Hodgkin's disease first seen at the Institute of Hematology, University of Rome, between 1970 and 1981, revealed tumor involvement of the bone marrow in 18 cases. The histologic type was mixed cellularity in 7 cases, lymphocytic depletion in 4 cases, nodular sclerosis in 4 cases, and lymphocytic prevalence in 1 case. Anemia with less than 10 g/dl of hemoglobin was observed in 5 patients; white blood cells were less than 4.0 X 10(9)/liter in 2 patients; platelets were less than 12.0 X 10(9)/liter in 1 case; a pancytopenic condition was observed in only 1 case. B symptoms were present in 14 of the 18 patients. All patients who underwent laparosplenectomy presented spleen involvement, 4 also had liver involvement. All patients were treated with chemotherapy; MOPP regimen was employed in 11 cases, ABVD in 5 patients, and PROVECIP in 1 case. Of the 13 patients evaluable for therapeutic response, 11 achieved complete remission, with a median actuarial relapse-free survival of 15 months. The actuarial survival curve showed that 50% of all patients are projected alive at 47 months with a follow-up ranging from 1 to 109 months.

Adult↗
PubMed1983

Non-small-cell lung carcinoma: tumor characterization on the basis of flow cytometrically determined cellular heterogeneity.

Some 150 tumor specimens from 49 patients with non-small-cell carcinoma of the lung (23 epidermoid, 14 adenocarcinoma, 12 large-cell carcinoma) and three with nonneoplastic lung disease were analysed for cellular DNA content by flow cytometry. Monodispersed cells were stained with ethidium bromide and mithramycin. Normal specimens and samples from patients with nonneoplastic disease constantly yielded a single cell population with diploid DNA content. Twenty of 23 epidermoid carcinomas exhibited one or more than one aneuploid subpopulation. Ten of 12 large-cell carcinomas were characterized by one aneuploid clone and 2/12 by two aneuploid clones. Adenocarcinoma exhibited multiclonal cell subpopulations (one to five aneuploid clones). Further information has been obtained on the differential presence of clones in various tumor areas and in infiltrated lymph nodes. These tumors appear characterized by a remarkable degree of cellular heterogeneity. The cytometric ploidy level(s) and the cell population multiclonal structure yield, in comparison with, and in addition to, pathology, indications of possible clinical interest. A correlation between the clonal DNA content and a prognostic parameter such as the tumor mass doubling time has been demonstrated.

Adenocarcinoma↗
PubMed1983

Tumor control and therapeutic gain with different schedules of combined radiotherapy and local external hyperthermia in human cancer.

Tumor control and therapeutic gain have been evaluated in a series of studies on patients with multiple lesions employing different protocols of combined radiotherapy (RT) and local external hyperthermia (HT). Tumor response has been evaluated during a follow-up ranging 6 to 18 months. Therapeutic enhancement factor (TEF) was defined as the ratio of thermal enhancement (TE) of tumors to TE of skin, where TE was clinically evaluated as the ratio of percent response (i.e., complete tumor clearance and moist desquamation, respectively) after combined modality to percent response after RT alone. Local tumor control was constantly better in lesions treated with any combined modalities in comparison with RT alone. The use of high RT dose per fraction appeared to increase tumor control only in the combined modalities groups, the immediate (so called "simultaneous") schedule (HT at 42.5 degrees C/45 min, applied immediately after each RT fraction, twice a week) being more effective than the delayed (so called "sequential") treatment (HT at 42.5 degrees C/45 min, delivered 4 h after each RT fraction, twice a week). The combination of high RT dose per fraction with high temperature HT (45 degrees C for 30 min) achieved the best tumor control. No increased radiation skin reaction was observed when a conventional fraction size of RT was used (3 daily fractions of 1.5-2 Gy, 4 h interval between fractions) in association with HT (42.5 degrees C/45 min, every other day, immediately after the second daily RT fraction). A remarkable enhancement of skin reaction was observed, however, when using high RT doses per fraction in association with 42.5 degrees C HT, especially with the immediate treatment schedule. No enhancement of skin reaction was obtained after high RT doses per fractions and 45 degrees C HT because an active skin cooling by means of circulating cold water was used in these cases. Consequently, a good TEF (1.58) was obtained when conventional RT doses per fraction were used in association with 42.5 degrees C HT. TEF values of 1.40 and 1.15 were observed when high RT doses per fraction were employed in association with the delayed and immediate 42.5 degrees C HT, respectively. HT at 45 degrees C can be safely employed only when tumors can be heated selectively or at least preferentially in comparison with normal tissue; in the lesions treated with such a schedule a TEF of 2.10 was obtained.

Diathermy↗
PubMed1982

Cytometric evidence of cytogenetic and proliferative heterogeneity of human solid tumors.

Flow cytometry is a widely recognized method of rapidly assessing the ploidy and proliferation status of experimental and solid tumors. In the present work, a variety of human cancers from various sites (lung, head and neck, etc.), of traditional interest in our laboratory, have been analyzed. In agreement with a number of recent reports, a general heterogeneity of human solid tumors can be evidenced. In particular: (a) solid tumors are characterized by a variable degree of aneuploidy; (b) the internal structure of solid tumors is highly heterogeneous especially with respect to the fraction of aneuploid malignant cells and their distribution through the cycle phases; and (c) some solid tumors are also characterized by the presence, to a variable extent, in the tumor of mass of multiple cell clones. Static fluorimetry of Feulgen-stained (mitotic) single cells offers a way to confirm this kind of observations.

Aneuploidy↗
PubMed1981

Reduction of 1-beta-D-arabinofuranosylcytosine and adriamycin cytotoxicity following cell cycle arrest by anguidine.

The protein synthesis inhibitor anguidine induced a frozen cell cycle state in exponentially growing Chinese hamster ovary cells, as demonstrated by serial DNA flow cytometric measurements in the absence and presence of Colcemid as a stathmokinetic agent. The minimally effective concentration of anguidine for induction of cell cycle arrest was 0.1 microgram/ml. As demonstrated by tritiated thymidine labeling index and DNA flow cytometric investigations in the presence of Colcemid, a 4-hr exposure of Chinese hamster ovary cells to greater than or equal to 4 micrograms of anguidine per ml effected a greater than or equal to 12-hr cycle perturbation at no cytotoxic expense. Preincubation of exponentially growing Chinese hamster ovary cells for 4 hr with 5 micrograms of anguidine per ml reduced the cytotoxicity from Adriamycin (1 hr; 0.1 to 10 micrograms/ml) and from 1-beta-D-arabinofuranosylcytosine treatment (18 hr; 5 to 50 micrograms/ml) by 10- to 100-fold. Further investigation of the concentration dependence and time course of this protective effect of anguidine revealed a plateau at 1 microgram of anguidine per ml and lack of protection in case of anguidine exposure subsequent to Adriamycin and 1-beta-D-arabinofuranosylcytosine treatment. Prolongation of the treatment-free interval between initial anguidine exposure and 1-hr Adriamycin treatment demonstrated partial recovery of DNA synthesis associated with some loss in cytoprotection. Our results indicate that the largely indiscriminate interference with cycle progression by anguidine under noncytotoxic conditions affords significant protection against 1-beta-D-arabinofuranosylcytosine and Adriamycin-related cytotoxicity, the degree of which appears to be related to the extent of reduction in cycle traverse rate. Thus, anguidine may serve as a useful probe to study in detail drug-induced lethal injury as a function of cycle traverse rate.

Animals↗
PubMed1980

Multiple daily fractionation (MDF) radiotherapy in association with hyperthermia and/or misonidazole: experimental and clinical results.

Several modalities involving a Multiple Daily Fractionation (MDF) course in combination with hyperthermia and/or the hypoxic sensitizer misonidazole have been tested on a mouse tumor system and then applied, with the proper sequencing, to a group of patients with multiple (N2-N3) neck node metastases from H&N cancers. Different lesions of the same patients underwent different modalities. The clinical results indicate the effectiveness, in respect to a historical series of patients treated with conventional fractionation (200 rads/day, five days/week), of either MDF alone (200 + 150 + 150 rads/day, five days/week) or MDF + hyperthermia (500 MHz, 42-43 C, 45 min., after 2nd daily fraction, on day 1, 3, and 5 of each week) or MDF + misonidazole (1.2 g/m2 daily, 2 hours before 1st fraction, up to a maximum dose of 12 g/m2), or MDF + hyperthermia + misonidazole. The latter modality appears to be possibly the most effective at inducing a complete local tumor response lasting longer in time (follow-up to a minimum of four months). The pharmacology of misonidazole has been monitored in the patients to avoid undesired excessive drug plasma level. No neurological symptoms have been observed. Oropharyngeal mucositis has been observed only in patients treated with misonidazole and radiation through two cross-firing portals. The problem of selecting individual patients for a particular modality is discussed.

Animals↗