| 121. |
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| 122. |
- Tomasetti, M, et al.
(författare)
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α-tocopheryl succinate and TRAIL selectively synergise in induction of apoptosis in human malignant mesothelioma cells
- 2004
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 90:8, s. 1644-1653
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Tidskriftsartikel (refereegranskat)abstract
- Malignant mesothelioma (MM) is a fatal type of neoplasia with poor therapeutic prognosis, largely due to resistance to apoptosis. We investigated the apoptotic effect of α-tocopheryl succinate (α-TOS), a strong proapoptotic agent, in combination with the immunological apoptogen TNF-related apoptosis-inducing ligand (TRAIL) on both MM and nonmalignant mesothelial cells, since MM cells show low susceptibility to the clinically intriguing TRAIL. All MM cell lines tested were sensitive to α-TOS-induced apoptosis, and exerted high sensitivity to TRAIL in the presence of subapoptotic doses of the vitamin E analogue. Neither TRAIL or α-TOS alone or in combination caused apoptosis in nonmalignant mesothelial cells. Isobologram analysis of the cytotoxicity assays revealed a synergistic interaction between the two agents in MM cells and their antagonistic effect in nonmalignant mesothelial cells. TRAIL-induced apoptosis and its augmentation by α-TOS were inhibited by the caspase-8 inhibitor Z-IETD-FMK and the pan-caspase inhibitor Z-VAD-FMK. Activation of caspase-8 was required to induce apoptosis, which was amplified by α-TOS via cytochrome c release following Bid cleavage, with ensuing activation of caspase-9. Enhancement of TRAIL-induced apoptosis in MM cells by α-TOS was also associated with upregulation of the TRAIL cognate death receptors DR4 and DR5. Our results show that α-TOS and TRAIL act in synergism to kill MM cells via mitochondrial pathway, and are nontoxic to nonmalignant mesothelial cells. These findings are indicative of a novel strategy for treatment of thus far fatal MM.
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| 123. |
- Tynninen, O, et al.
(författare)
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Tumour microvessel density as predictor of chemotherapy response in breast cancer patients
- 2002
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 86:12, s. 1905-1908
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the predictive value of intratumoural microvessel density in breast cancer. We studied immunohistochemically primary tumours of 104 patients with metastasised breast cancer who took part in a randomised multicentre trial comparing docetaxel to sequential methotrexate and 5-fluorouracil. Vessels were highlighted with factor VIII staining and counted microscopically. Microvessel density was compared with clinical response to chemotherapy and patient survival. The microvessel density of the primary tumour was not significantly associated with patient's response to chemotherapy, time to progression or overall survival in the whole patient population or in the docetaxel or methotrexate and 5-fluorouracil groups. However, disease-free survival was longer in patients with low microvessel density (P=0.01). These findings suggest that microvessel density of the primary tumour cannot be used as a predictive marker for chemotherapy response in advanced breast cancer.
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| 124. |
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| 125. |
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| 126. |
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| 127. |
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| 128. |
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| 129. |
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| 130. |
- Westerdahl, J, et al.
(författare)
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Risk of cutaneous malignant melanoma in relation to use of sunbeds : further evidence for UV-A carcinogenicity
- 2000
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 82:9, s. 1593-1599
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based, matched, case-control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma and 913 healthy controls aged 16-80 years, the association between sunbed use and malignant melanoma was evaluated. A total of 250 (44%) cases and 372 (41%) controls reported ever having used sunbeds. A significantly elevated odds ratio for developing malignant melanoma after regular exposure to sunbeds was found, adjusted for hair colour, raised naevi, skin type and number of sunburns (odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2-2.7). A dose-response relationship between total number of sunbed uses and melanoma risk was only found up to the level of 250 times. The OR was higher in individuals younger than age 36 years (adjusted OR 8.1, 95% CI 1.3-49.5 for regular vs. never use). The association seemed to be true only for subjects with black/dark brown or light brown hair and among females. Lesions of the extremities showed the strongest association of increased risk with sunbed use. An increased risk was related to commercial exposure and to exposure during the winter. The results substantiate the hypothesis that exposure to sunbeds might increase the risk of developing malignant melanoma.
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