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We tested the sensitivity to doxorubicin (DXR) and cisplatin (DDP) of multicellular tumor spheroids (MTS) developed from 2 human lung cancer cell lines; PC-10 squamous cell carcinoma and PC-6 small cell carcinoma. DDP was able to maintain its efficacy in MTS: PC-10 MTS were only 3-fold more resistant to DDP than in monolayer and in PC-6 cells DDP induced cell lethality was essentially unchanged irrespective of cells being in a monolayer or MTS. Atomic absorption spectrometry revealed that DDP uptake was essentially identical, irrespective of cells being in monolayer or MTS. DDP's efficient cell kill effects in MTS seems to be explained by its good penetration into the MTS core. In contrast to DDP, these 2 types of cells responded differently to DXR. Thus, PC-10 MTS became progressively more resistant to DXR when their size increased, whereas the susceptibility of PC-6 MTS tended to increase when the MTS grew larger. Fluorescent microscopic study revealed that prominent DXR fluorescence was observed only at the outer layer of PC-10 MTS. In PC-6 MTS, however, DXR fluorescence was diffusely seen in the entire MTS at low concentrations; nevertheless, owing to PC-6 cells' high sensitivity DXR was able to exert cell lethality. The differences in distribution of DXR fluorescence between PC-10 and PC-6 MTS were corroborated by flow cytometric analysis.

The authors calculated the uptake ratio to evaluate the degree of Tl-201 uptake in the primary tumor. This ratio was compared with survival time and other prognos-1 Department of Respiratory Medicine, Nikko tic factors. Memorial Hospital, Muroran, Japan. RESULTS.The authors studied 152 patients (125 men and 27 women). The group 2 Department of Nuclear Medicine, School of of patients with the low Tl-201 uptake ratio survived longer than the group of Medicine, Hokkaido University, Sapporo, Japan.patients with the high Tl-201 uptake ratio (median survival, 58 weeks vs. 33 weeks; P Å 0.0138 by the log rank test). The multivariate analysis confirmed that the Tl-3 Department of Medical Information Services, Nikko Memorial Hospital, Muroran, Japan.201 uptake ratio was an independent prognostic factor for survival. CONCLUSIONS. These results suggest that the Tl-201 uptake ratio provides indepen-4 First Department of Medicine, School of Medident and objective prognostic information for patients with lung carcinoma. Cancine, Hokkaido University, Sapporo, Japan.

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