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- Kraggerud, SM, et al.
(författare)
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Alterations of the fragile histidine triad gene, FHIT, and its encoded products contribute to testicular germ cell tumorigenesis
- 2002
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Ingår i: Cancer Research. - 1538-7445. ; 62:2, s. 512-517
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Tidskriftsartikel (refereegranskat)abstract
- The fragile histidine triad (FHIT) gene, located within chromosome arm 3p, is a potential target for testicular tumorigenesis. In the present study, 62 primary testicular germ cell tumors were analyzed for allelic imbalance (AI) at 10 loci mapping to chromosome bands 3p14.1-21.1. Twenty-seven tumors (44%) showed AI at one or more 3p loci. The chromosome 3 copy number was evaluated by fluorescence in situ hybridization with centromere and p-telomere probes onto interphase nuclei from 22 of the tumors. Sixteen of these (73%) presented three or more signals of each probe in at least one-third of the nuclei. The combined fluorescence in situ hybridization and AI results indicated that tumors with AI at all loci, in most cases (five of six), reflected an increased chromosome copy number, whereas tumors presenting AI only at some loci reflected interstitial chromosomal changes. A smallest region of overlapping changes could be delineated from tumors showing interstitial chromosomal changes (n = 16). The smallest region of overlapping changes was flanked by D3S1312 and D3S1234 and included parts of FHIT. In the second part of this study, expression analyses of FHIT were performed. Transcripts of aberrant lengths were found in 7 of 17 (41%) analyzed tumors and were identified by sequencing as splice variants. Three different types of transcripts were found, and all lacked exon 3. Immunohistochemical staining showed reduced Fhit protein expression, compared with normal testicular tissue, in 62% (40 of 65) of the testicular germ cell tumors. Although we found a significant association between FHIT mRNA alterations and AI (P = 0.006), altered protein expression did not correlate with AI. The nonepithelial components of teratomas showed strong association with reduced Fhit protein compared with the epithelial component (P < 0.001). Interestingly, reduced Fhit expression seems to be associated with metastasis in the patient at the time of diagnosis, although the association was not statistically significant.
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| 4. |
- Smeland, S, et al.
(författare)
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Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders
- 2003
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Ingår i: European Journal of Cancer. - 1879-0852. ; 39:4, s. 488-494
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Tidskriftsartikel (refereegranskat)abstract
- From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 muM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome. (C) 2003 Elsevier Science Ltd. All rights reserved.
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