Cell Lung Cancer Xenografts Research Articles

Gefitinib.

Gefitinib (ZD1839) is an orally active selective inhibitor of epidermal growth factor receptor tyrosine kinase, an enzyme that regulates intracellular signalling pathways implicated in the proliferation and survival of cancer cells. In human non-small cell lung cancer (NSCLC) cell lines and xenografts, gefitinib dose-dependently inhibited cellular proliferation and tumour growth, and potentiated the cytotoxic effects of chemotherapy and/or radiation. Gefitinib is orally bioavailable and is cleared via the cytochrome P450 3A4 pathway. In patients receiving gefitinib (50 to 700 mg/day) in phase I trials, steady-state plasma concentration was reached in 7 to 10 days. In patients with advanced NSCLC who had failed one or two prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in approximately 19% of patients in a double-blind trial (n = 210). In another double-blind trial including 216 patients with NSCLC who had failed two or more prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in 11.8 and 8.8% of patients, respectively; approximately 40% showed an improvement in disease-related symptoms. Gefitinib was generally well tolerated and the most common adverse events were mild skin rashes and diarrhoea.

HETEROGENEOUS EXPRESSION OF ONCOGENES IN SMALL-CELL LUNG-CANCER XENOGRAFTS

The analysis of oncogene expression may provide insights into the pathogenesis of small cell lung cancer (SCLC) and may help to predict clinical behavior. The expression of 8 oncogenes (c-myc, N-myc, L-myc, Ha-ras, Ki-ras, N-ras, erbB-2, v-sis) was evaluated in small cell lung cancer (SCLC) xenografts of tumor samples, recentlly transplanted, taken from 17 different patients. Eight of these 17 SCLC lines expressed the L-myc oncogene and 2 SCLC lines expressed the c-myc oncogene. One SCLC line (SCLC-63M) simultaneously expressed the L-myc and c-myc oncogenes. All SCLC lines examined had almost similar high RNA levels of the Ki-ras oncogene, while the expression of Ha- and N-ras oncogenes was not always observed. The N-myc and v-sis oncogenes were expressed in only one tumor and at a very weak level, and no transcript of the erbB-2 oncogene was observed in any of our 17 SCLC lines. These results indicate that oncogene expression in SCLC lines is heterogeneous, with the exception of the Ki-ras oncogene which is constantly overexpressed.

Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts.

Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were examined. All tumours but one expressed both cadherin and NCAM. The tumours expressed one, two or rarely three cadherin bands, and different combinations of two major isoforms of NCAM with M(r)'s of approximately 190,000 and 135,000. Polysialylation of NCAM, a feature characteristic of NCAM during embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression.

Characterisation and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon

Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.

In vivo activity and pharmacokinetic analysis by 19F-magnetic resonance spectroscopy (FMRS) of 2′2′difluorodeoxycyticine (DFDC, gemcitabine) in small cell lung cancer (SCLC) xenografts

In vivo activity and pharmacokinetic analysis by 19F-magnetic resonance spectroscopy (FMRS) of 2′2′difluorodeoxycyticine (DFDC, gemcitabine) in small cell lung cancer (SCLC) xenografts

Expression of adhesion molecules of the cadherin family and of NCAM in small cell lung cancer cell lines and xenografts

Expression of adhesion molecules of the cadherin family and of NCAM in small cell lung cancer cell lines and xenografts

Growth kinetics of small cell lung cancer (SCLC) xenografts grown in nude mice

Growth kinetics of small cell lung cancer (SCLC) xenografts grown in nude mice

Expression of myc family onco-proteins in small cell lung cancer cell lines and xenografts

Expression of myc family onco-proteins in small cell lung cancer cell lines and xenografts

In vitro and In vivo effects of [D-Arg1,D-Phe5,D-Trp7,9,Leu11] substance P (D-Phe5SP) on the growth of human lung cancer cell lines and xenografts

In vitro and In vivo effects of [D-Arg1,D-Phe5,D-Trp7,9,Leu11] substance P (D-Phe5SP) on the growth of human lung cancer cell lines and xenografts