- Email: [email protected]
Overexpression of vascular endothelial growth factor (VEGF) and receptor in micropapillomatosis, a preneoplastic bronchial lesion
S23
Abstracts
A novel prospective for lung cancer treatment: gemcitabine, a chemotherapeutic drug, es e radiosensitizer Casamassima F, Pacini S, Milan0 F, Pinzani P, Pazzagli M. Dept. of Clin Physiopatol,
Univ. of Florence,
Italy.
Gemcitabine is a nucleoside analogue routinely used in chemotherapy. It has been hypothesized that it can also work as radiosensitizer by enhancing the effects of ionizing radiations in the treatment of non-small cell lung cancer. In order to study the effect of gemcitabine as a radiosensitizer, we studied SK LU 1 cells (human lung adenocarcinoma) treated with non-toxic concentrations of the drug. The radiosensitizing effect was studied by colony forming assay and by measuring variations in ATP intracellular levels. We treated cells with non-toxic concentrations (up to 10 nM) for 3 and 24 h; 24 h after the treatment, cells were irradiated with a linear accelerator for therapeutic usage. Results obtained by measuring the ATP level show that the treatment with concentrations up to 10 nM for 3 h or up to 1 nM for 24 h induces a significant decrease in viability of cells if compared with cells treated with irradiation alone. This effect is best observed with the radiation doses of 50 and 100 cGy; thus, at higher doses the cell damage induced by irradiation itself hides the radiosensitizing effect of drug. These observations are confirmed by the colony forming assay. Our data show that gemcitabine, used at non-cytotoxic concentrations, increases the killing effects of ionizing radiations; therefore, this drug could be proposed as a radiosensitizer in the radiation therapy of non-small cell lung cancer with a clear potentiating effect at low dose irradiation.
Clinical relevance of p53 protein expression in non-smell cell lung cancer (NSCLC) patients (pts) Jassem E, Goidi S*, Jassem J, Urbaniak A*, Kobierska G, Badzio A, Damps I, Skokowski J. Medical University of Gdansk, *Regional
Cancer
Center
in Kielce, Poland.
The aim of this study was to evaluate the clinical value of ~53 protein expression in resectable NSCLC. We analysed paraffin-embedded tumour samples from 95 NSCLC pts: 20 females and 75 males aged 39 to 72 years (mean: 57 years). Pathological diagnosis included squamous cell carcinoma in 53 pts, adenocarcinoma in 29, large cell carcinoma in five and mixed histology in eight. Forty-eight pts were in I stage, nine in II, 35 in IIIa, two in IIIb, and one in IV. The expression of ~53 was assayed immunohistochemically with the use of DO-7 antibodies. Expression was found in 44 tumours (45.2%); in 52.8% squamous cell carcinomas, 44.8% adenocarcinomas, 37.5% mixed tumours and in none of large cell carcinomas (P < 0.05). No association between expression and age, gender, tumour grade and stage was found. Follow-up was available in 89 pts. Median survival was 45 months in pts with ~53 expression and 21 months in those without expression and the 3-year survival rate - 55% and 47%, respectively (P = 0.46). Tumour stage was the only independent prognostic factor for survival in Cox model (P = 0.003). In conclusion: ~53 expression in NSCLC does not carry clinically meaningful information.
Overexpression of vascular endotheliel growth factor (VEGF) and receptor in micropepillometosis, a preneoplestic bronchial lesion Vermylen P, Roufosse C, Ninane V, Sculier JP. Institut Jules Bordet,
Brussels,
Belgium.
Neoangiogenesis is a common feature of solid tumours and has recently been described in the stroma beneath preneoplastic bronchial lesions. We describe a particular morpho logic preneoplastic lesion of the bronchi, characterized by capillary invasion of othetwise hyperplastic, metaplastic or dysplastic bronchial epithelium. We studied 13 micropapillary lesions obtained in vivo, in patients at high risk for lung cancer by using fluorescence bronchoscopy. Control metaplasia, obtained in the same subjects, were available in eight cases. All samples were assessed for VEGF and Flt-1 expression using specific antibodies (Santa-Cruz A-20 and C-171. VEGF was focally expressed in bronchial epithelial cells lining the capillaries in 8/13 micropapillomatous lesions whereas only in 3/8 control metaplasia. Flt-1 expression was, respectively, 7/13 and 2/8 in micropapillomatosis and matched metaplasia. These data suggest that VEGF overexpression may be involved in the genesis of early neoangiogenic preneoplastic lesions of the bronchi. Moreover, concomitant expression of VEGF and IQ-1 was observed in the same lesions. (Supported by FNRS-T&Zvie 9.4587.95, 7.4523.96 and V&ale Fondation). Immunobiology of solid tumors: clinical significance of cytokine secretion Fischer JR. Dept. of Medical Oncology, Thomklinik Heidelberg. Basic and clinical research has revealed, during the last couple of years, that cytokine secretion by immunocompetent cells plays a major role in the clinical course of solid tumors. Several investigations have documented a selective suppression of cytokine secretion in a variety of malignant diseases. Interestingly, suppression of cytokines differs among different tumor entities, possibly indicating different interactions between the tumor and the immune system. Our own results reveal distinct suppression of cytokine secretion in small-cell lung cancer (SCLC) and colon-cancer. Whether the impairment of cytokine secretion is really mediated by the tumor itself, is still under investigation. However, it has been shown that solid tumors secrete molecules with immunosuppressive activity, such as TGF pl, IL-10 and FasLigand. We have earlier reported that SCLC secretes bioactive TGF /31. A possible clinical relevance of this finding is indicated by the fact that TGF pl induces the specific selective cytokine-suppression found in SCLC-patients. In addition, SCLC does not seem to interact with immune defense via FasLigand, although results are still conflicting. Whatever the source of cytokine suppression is, this impairment of immune defense is of major prognostic importance. The initial level of IL-2secretion predicts survival in SCLC. Moreover, long term survival upon complete tumor remission by chemotherapy is only reached by patients with high IL-2-secretion at the time of diagnosis. These data indicate that the level of IL2 partially defines long term survival in SCLC. Based on these data,
Abstracts
A novel prospective for lung cancer treatment: gemcitabine, a chemotherapeutic drug, es e radiosensitizer Casamassima F, Pacini S, Milan0 F, Pinzani P, Pazzagli M. Dept. of Clin Physiopatol,
Univ. of Florence,
Italy.
Gemcitabine is a nucleoside analogue routinely used in chemotherapy. It has been hypothesized that it can also work as radiosensitizer by enhancing the effects of ionizing radiations in the treatment of non-small cell lung cancer. In order to study the effect of gemcitabine as a radiosensitizer, we studied SK LU 1 cells (human lung adenocarcinoma) treated with non-toxic concentrations of the drug. The radiosensitizing effect was studied by colony forming assay and by measuring variations in ATP intracellular levels. We treated cells with non-toxic concentrations (up to 10 nM) for 3 and 24 h; 24 h after the treatment, cells were irradiated with a linear accelerator for therapeutic usage. Results obtained by measuring the ATP level show that the treatment with concentrations up to 10 nM for 3 h or up to 1 nM for 24 h induces a significant decrease in viability of cells if compared with cells treated with irradiation alone. This effect is best observed with the radiation doses of 50 and 100 cGy; thus, at higher doses the cell damage induced by irradiation itself hides the radiosensitizing effect of drug. These observations are confirmed by the colony forming assay. Our data show that gemcitabine, used at non-cytotoxic concentrations, increases the killing effects of ionizing radiations; therefore, this drug could be proposed as a radiosensitizer in the radiation therapy of non-small cell lung cancer with a clear potentiating effect at low dose irradiation.
Clinical relevance of p53 protein expression in non-smell cell lung cancer (NSCLC) patients (pts) Jassem E, Goidi S*, Jassem J, Urbaniak A*, Kobierska G, Badzio A, Damps I, Skokowski J. Medical University of Gdansk, *Regional
Cancer
Center
in Kielce, Poland.
The aim of this study was to evaluate the clinical value of ~53 protein expression in resectable NSCLC. We analysed paraffin-embedded tumour samples from 95 NSCLC pts: 20 females and 75 males aged 39 to 72 years (mean: 57 years). Pathological diagnosis included squamous cell carcinoma in 53 pts, adenocarcinoma in 29, large cell carcinoma in five and mixed histology in eight. Forty-eight pts were in I stage, nine in II, 35 in IIIa, two in IIIb, and one in IV. The expression of ~53 was assayed immunohistochemically with the use of DO-7 antibodies. Expression was found in 44 tumours (45.2%); in 52.8% squamous cell carcinomas, 44.8% adenocarcinomas, 37.5% mixed tumours and in none of large cell carcinomas (P < 0.05). No association between expression and age, gender, tumour grade and stage was found. Follow-up was available in 89 pts. Median survival was 45 months in pts with ~53 expression and 21 months in those without expression and the 3-year survival rate - 55% and 47%, respectively (P = 0.46). Tumour stage was the only independent prognostic factor for survival in Cox model (P = 0.003). In conclusion: ~53 expression in NSCLC does not carry clinically meaningful information.
Overexpression of vascular endotheliel growth factor (VEGF) and receptor in micropepillometosis, a preneoplestic bronchial lesion Vermylen P, Roufosse C, Ninane V, Sculier JP. Institut Jules Bordet,
Brussels,
Belgium.
Neoangiogenesis is a common feature of solid tumours and has recently been described in the stroma beneath preneoplastic bronchial lesions. We describe a particular morpho logic preneoplastic lesion of the bronchi, characterized by capillary invasion of othetwise hyperplastic, metaplastic or dysplastic bronchial epithelium. We studied 13 micropapillary lesions obtained in vivo, in patients at high risk for lung cancer by using fluorescence bronchoscopy. Control metaplasia, obtained in the same subjects, were available in eight cases. All samples were assessed for VEGF and Flt-1 expression using specific antibodies (Santa-Cruz A-20 and C-171. VEGF was focally expressed in bronchial epithelial cells lining the capillaries in 8/13 micropapillomatous lesions whereas only in 3/8 control metaplasia. Flt-1 expression was, respectively, 7/13 and 2/8 in micropapillomatosis and matched metaplasia. These data suggest that VEGF overexpression may be involved in the genesis of early neoangiogenic preneoplastic lesions of the bronchi. Moreover, concomitant expression of VEGF and IQ-1 was observed in the same lesions. (Supported by FNRS-T&Zvie 9.4587.95, 7.4523.96 and V&ale Fondation). Immunobiology of solid tumors: clinical significance of cytokine secretion Fischer JR. Dept. of Medical Oncology, Thomklinik Heidelberg. Basic and clinical research has revealed, during the last couple of years, that cytokine secretion by immunocompetent cells plays a major role in the clinical course of solid tumors. Several investigations have documented a selective suppression of cytokine secretion in a variety of malignant diseases. Interestingly, suppression of cytokines differs among different tumor entities, possibly indicating different interactions between the tumor and the immune system. Our own results reveal distinct suppression of cytokine secretion in small-cell lung cancer (SCLC) and colon-cancer. Whether the impairment of cytokine secretion is really mediated by the tumor itself, is still under investigation. However, it has been shown that solid tumors secrete molecules with immunosuppressive activity, such as TGF pl, IL-10 and FasLigand. We have earlier reported that SCLC secretes bioactive TGF /31. A possible clinical relevance of this finding is indicated by the fact that TGF pl induces the specific selective cytokine-suppression found in SCLC-patients. In addition, SCLC does not seem to interact with immune defense via FasLigand, although results are still conflicting. Whatever the source of cytokine suppression is, this impairment of immune defense is of major prognostic importance. The initial level of IL-2secretion predicts survival in SCLC. Moreover, long term survival upon complete tumor remission by chemotherapy is only reached by patients with high IL-2-secretion at the time of diagnosis. These data indicate that the level of IL2 partially defines long term survival in SCLC. Based on these data,