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Biomedical subjects

W Zoli

Publications and source records attributed to W Zoli.

46 records · Page 3Linked to original sources

N-nitroso compound precursors and gastric cancer: preliminary data of a study on a group of farm workers.

An epidemiological research on gstric cancer mortality rates carried out in the town of Forì is reported. The results are significant as regards the relation between the urban and rural areas, and show a higher risk for gastric cancer in the rural area. Salivary nitrite measurement in 92 farm workers showed particularly high values (over 30 ppm in 4 individuals). Analysis of histological findings in biopsies performed during endoscopy in 46 persons of the group studied showed a great number of CAG and CAG + IM in asymptomatic individuals.

Adult↗

An efficient method for culturing human breast carcinoma to evaluate antiblastic drug activity in vitro: experience on 136 primary cancers and on 116 recurrences.

The feasibility of techniques developed for isolating and culturing human mammary epithelial cells of malignant origin was confirmed in 136 primary breast cancers, 116 hypodermal metastases, and 8 metastatic lymph nodes. In 115 (84%) primary breast cancers and in 81 (70%) hypodermal recurrences we observed a good in vitro cellular proliferation. These proliferating cells, at the second passage, were used for a clonal assay suitable for quantitating drug sensitivity. With this clonal assay median cloning efficiencies of 14% and 6% were obtained respectively in primaries and in skin recurrences. We examined the in vitro response to different drugs and confirmed the test's ability to detect heterogeneity in response to same drugs (doxorubicin, 4'-epidoxorubicin, vinblastine, cis platinum, and idarubicinol) among the different breast carcinoma cultures as well as heterogeneity among subpopulations within a single carcinoma.

Antineoplastic Agents↗

Correlation between p53 gene mutations and p53 protein accumulation evaluated by different methodologies.

Mutations in the p53 gene are the most common genetic alterations in many tumour histotypes. Many of these mutations induce conformational changes resulting in p53 protein stabilisation and consequently an accumulation detectable with immunochemical methods. Available data on the correlation between p53 gene alterations and p53 overexpression widely vary. In this study we analysed the correlation between p53 gene alterations detected by DGGE, SSCP and sequencing and protein expression detected by flow cytometric and immunohistochemical approaches by using PAb 1801 antibody. The study was performed on 21 bladder tumours and 10 cell lines derived from different tumour histotypes as representative of different methodologic problems which can be met starting from different types of biological material. The best correlation (81%) was observed between p53 mutations and FCM results, using a double evaluation criterion for the latter which includes the percentage of positive cells and "delta values", evaluated as the difference between the mean values of Pab 1801 stained cells and isotypic control. The high correlation obtained between results from this FCM double criterion and p53 gene mutations is a good starting point for the analysis on large series of tumours and for a multiparameter FCM analysis including p53 protein levels.

Carcinoma, Transitional Cell↗

Simultaneous determination of apoptosis and surface antigen expression in tumor adherent cells.

Apoptosis is a physiological, gene-directed form of cell death aimed at controlling cell proliferation in several biological conditions. It plays a crucial role in modulating tissue growth during embryonic development, cell turnover in adult life, and it seems to be the most frequent mechanism of tumor cell deletion by chemotherapy. Flow cytometry is a widely-used technique for checking apoptosis, permitting a multiparametric analysis. It is possible to follow the alterations occurring in the nucleus, mitochondria and plasmatic membrane during the different apoptotic stages using probes such as LDS-751, JC-1 or Annexin V. The potential of these probes to identify the early or late stages of apoptosis has been widely investigated in cells growing in suspension. In order to assess apoptosis in adherent cells, we tested a combination of fluorescein diacetate (FDA), a substrate for non specific esterase whose activity decreases during the early phase of apoptosis, and trypan blue in MCF-7 human breast cancer cells. Apoptotic cells showed a decrease in the green fluorescence emitted by fluorescein, the product of FDA hydrolysis, whereas necrotic cells emitted a red fluorescence due to the trypan blue staining. FDA-trypan blue double-staining was used to investigate the different kinetics of apoptosis induced by taxol, camptothecin and UV-B irradiation in MCF-7 cells. This method is rapid and simple, and can be used for monitoring the process of apoptosis from early stages in adherent cells, for the physical separation of apoptotic and live cells, and for immunophenotyping, including Fas expression.

Annexin A5↗

Inhibition of growth of breast cancer cells in vitro by the ribosome-inactivating protein saporin 6.

The antiproliferative activity of Saporin 6, a Ribosome-inactivating protein purified from the seeds of Saponaria officinalis has been tested on human breast cancer cells in vitro by the analysis (a) of colony formation in cells from surgical specimens from 27 patients bearing primary breast cancer and (b) of protein synthesis inhibition in the MCF/7 cell line. Results indicate a very high sensitivity of breast cancer cells from most patients to a short-term treatment with Saporin 6 at concentrations (10(-9) M), until now found effective only in acellular systems or after conjugation with monoclonal antibodies. On the contrary, the treatment of the human cell line MCF/7 indicate a very reduced sensitivity compared to fresh human neoplastic cells, with the necessity of a long lag for the effect to begin.

Antineoplastic Agents, Phytogenic↗

In vitro potentiation by lonidamine of the sc-RIP saporin 6 effect in a human metastatic breast cancer cell line.

The ability of Lonidamine (LND), an energolytic derivative of indazole-carboxylic acid, to modulate the antiproliferative effect of the single-chain ribosome-inactivating protein Saporin 6 (SO 6) was investigated in the human MAST breast cancer cell line, recently established from an ascitic effusion of a ductal carcinoma, by analysis of protein synthesis inhibition and of colony formation in vitro. Different schedules were tested varying with regard to time of exposure (0-24 h), concentration of the drugs (0.01- > 10 micrograms/ml SO 6; 25-100 micrograms/ml LND) and sequence of administration (LND- > SO 6; SO 6- > LND; SO 6+LND). Results indicate that the marginal activity exerted here by each drug when tested independently is highly potentiated by the combination treatments, the cytotoxicity becoming significantly greater than that expected from an additive effect between the two drugs. In particular, a strong synergistic effect is obtained when SO 6 preceedes LND, with a reduction of the SO 6 IC 50 from 1.3 x 10(-7) M to 2.6 x 10(-9) M.

Antineoplastic Agents↗

In vitro antiproliferative activity of docetaxel (Taxotere), paclitaxel (Taxol) and cisplatin against human tumour and normal bone marrow cells.

The in vitro antiproliferative effect of docetaxel (Taxotere), paclitaxel (Taxol) and cisplatin was assessed in a range of human tumour types, including 25 tumour cell lines and 35 primary cultures. Additionally, 12 human normal bone marrow samples were analyzed. Seven laboratories, all members of the EORTC Preclinical Therapeutic Models Group (PTMG), have performed these tests, using their own individual assay procedures. In all comparisons docetaxel and paclitaxel were much more potent than cisplatin with IC50 values of the taxoids being in the nanomolar range. Docetaxel generally was two- to four-fold more cytotoxic than paclitaxel. The sensitivity profile of the cell lines, which was based on the IC50 values, indicated a certain degree of cross-sensitivity between paclitaxel and docetaxel (linear regression analysis; r = 0.73, p < 0.001). On the other hand, the sensitivity profile of cisplatin was different from the ones seen for docetaxel and paclitaxel, indicating that no cross-sensitivity exists between cisplatin and both taxoids.

Antineoplastic Agents, Phytogenic↗

GM-CSF production in human adenocarcinoma cell lines.

We describe the production of human granulocyte-macrophage colony-stimulating factor (hGM-CSF), by cell lines established from patients with different stages of breast, lung and colon adenocarcinoma. GM-CSF expression has been identified by immunocytochemistry determination, quantified on conditioned medium with specific ELISA procedure and evaluated by means of proliferation and differentiation of normal human monocytic and granulocytic progenitors. The growth of cell lines after incubation with exogenous GM-CSF and antibody-antiGM-CSF was not modified. To better understand the patho-physiologic role of hGM-CSF in vivo we also estimated its serum levels at diagnosis in 75 patients with breast lung and colon adenocarcinoma and in 69 healthy person. Only two patients showed detectable GM-CSF levels. The lack of growth modulation observed in vitro with exogenous GM-CSF and antibody anti-GM-CSF suggests a non autocrine secretion by adenocarcinoma cells. The serum investigation evidences that the leukocytosis observed in adenocarcinoma patients is unrelated to a GM-CSF constitutive tumor production in vivo.

Adenocarcinoma↗