PubMed · 10029709
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F Reboul, P Vincent, B Chauvet, M Alfonsi, C Berger, D Serin. 1999. [Concurrent chemoradiotherapy update].. https://pubmed.ncbi.nlm.nih.gov/10029709/
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We investigated the role of wild-type p53 and c-myc activity in apoptosis induced by a combination of natural human tumor necrosis factor alpha (TNF-alpha) and natural human interferon alpha (IFN-alpha). Studies were performed with two human non-small-cell lung cancer cell lines, H226b, which has wild-type p53, and H226br, which has a mutant p53. The combination of IFN-alpha and TNF-alpha significantly inhibited cell growth and induced apoptotic cell death of both H226b and H226br, compared with IFN-alpha or TNF-alpha alone. Treatment with one or both cytokines did not affect the expression level of p53 in both cell lines. These results suggest that the combination of IFN-alpha/TNF-alpha induces apoptotic cell death through a p53- independent pathway. The c-myc oncogene is known to be involved in apoptosis induced by TNF. Antisense c-myc oligonucleotides have been reported to modulate cell growth or apoptosis in several cell lines. Antisense oligodeoxynucleotides were added to the culture of H226br cells before the addition of IFN-alpha/TNF-alpha. Antisense c-myc inhibited IFN-alpha/TNF-alpha cytotoxicity and apoptotic cell death. In conclusion, this study provides support for the speculation that TNF-alpha/IFN-alpha induce apoptosis through a c-myc-dependent pathway rather than a p53-dependent pathway. (c)2001 Elsevier Science.
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Residual mediastinal masses are frequently observed in patients with Hodgkin disease (HD) after completed therapy, and the discrimination between active tumor tissue and fibrotic residues remains a clinical challenge. We studied the diagnostic value of metabolic imaging by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting active mediastinal disease and predicting relapse. Twenty-eight HD patients with a residual mediastinal mass of at least 2 cm after initial therapy or after salvage chemotherapy were prospectively assigned to 29 examinations with FDG PET and were evaluated as 29 "subjects." Patients were monitored for at least 1 year after examination and observed for signs of relapse. Median follow-up was 28 months (range, 16 to 68 months). A PET-negative mediastinal tumor was observed in 19 subjects, of whom 16 stayed in remission and 3 relapsed. Progression or relapse occurred in 6 of 10 subjects with a positive PET, whereas 4 subjects remained in remission. The negative predictive value (negative PET result and remission) at 1 year was 95%, and the positive predictive value (positive PET result and relapse) was 60%. The disease-free survival for PET-negative and PET-positive patients at 1 year was 95% and 40%, respectively. The difference was statistically significant. A negative FDG PET indicates that an HD patient with a residual mediastinal mass is unlikely to relapse before 1 year, if ever. On the other hand, a positive PET result indicates a significantly higher risk of relapse and demands further diagnostic procedures and a closer follow-up.