| 71. |
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| 72. |
- Lindner, P., et al.
(författare)
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Combined treatment with histamine dihydrochloride, interleukin-2 and interferon-alpha in patients with metastatic melanoma
- 2004
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Ingår i: Anticancer Res. - 0250-7005. ; 24:3b, s. 1837-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Histamine inhibits phagocyte-derived production of reactive oxygen species and improves the anti-tumour efficiency of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) in vitro and in tumour-bearing animals. PATIENTS AND METHODS: In a phase-II study, twenty-seven patients with stage IV melanoma received subcutanous injections of histamine dihydrochloride (histamine) 1.0 mg and IL-2 2.4 MIU/m2 twice daily (BID) days 1-5 and 8-12. IFN-alpha 3 MIU once daily was administered throughout a cycle (days 1-28; n=14). Alternatively, bolus doses of IL-2 10 MIU/m2 BID days 1 and 2 and histamine days 1-28 (n=13) were administered. The aim was to study efficiency (survival and tumour response), toxicity and histamine pharmacokinetics. RESULTS: The median survival time was 11.3 (2.5-45) months. One patient achieved a complete response and 3 patients had partial responses. The compounds were safely self-administered with low toxicity. Plasma histamine concentrations significantly increased after an injection of histamine over 10 minutes (3 +/- 1 vs. 63 +/- 27 nmol/l). CONCLUSION: Histamine, IL-2 and IFN-alpha treatment is safe, well-tolerated and tumour responses were observed. The putative efficiency of histamine as an adjunct to cytokine therapy in metastatic melanoma needs to be confirmed in later randomized trials.
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| 73. |
- Liu, Jian-Jun, et al.
(författare)
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Sulindac induces apoptosis, inhibits proliferation and activates caspase-3 in Hep G2 cells
- 2002
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Ingår i: Anticancer research. - 1791-7530. ; 22:1A, s. 263-266
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has recently been reported that sulindac has an apoptotic effect on KYN-2 cells, an undifferentiated hepatoma cell line. The present work investigates whether sulindac also has an apoptotic effect on well-differentiated hepatoma cells and what its potential mechanism might be. Materials and Methods: Hep G2 cells were treated with sulindac at different concentrations. Apoptosis rate, cell proliferation and 3H-thymidine incorporation were measured. The activities of caspase-3, acid and neutral sphingomyelinase and the changes of sphingomyelin content were also assayed. Results: Sulindac dose-dependently induced apoptosis in Hep G2 cells; both sulindac sulfone and sulfide had similar effects. The apoptosis was accompanied by an increase 3 of caspase-3 activity and a decrease of cell proliferation and H-3-thymidine incorporation. No significant change could be observed for the activity of sphingomyelinase and sphingomyelin content. Conclusion: Sulindac induces apoptosis and inhibits proliferation in Hep G2 cells. The effect may, be mediated by, a pathway related to caspase-3 activation but independent of sphingomyelin metabolism.
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| 74. |
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| 75. |
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| 76. |
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| 77. |
- Loden, M, et al.
(författare)
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C-erbB2, p27 and G1/S aberrations in human primary breast cancer
- 2003
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Ingår i: Anticancer research. - 1791-7530. ; 23:3A, s. 2053-2061
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Tidskriftsartikel (refereegranskat)abstract
- Background: C-erbB2 is overexpressed in approximately one-fourth of human breast cancers. In spite of numerous reports suggesting a connection of c-erbB2 overexpression with cell cycle regulation through p27, D cyclins and c-myc. the relationship between c-erbB2 and proliferation through de-regulation of the pRb pathway in primaty breast cancer has not been fully clarified. Materials and Methods: For this purpose we compared the expression of c-erbB2 in a total of 10.5 primary breast tumours with a variety of cell cycle proteins and clinical parameters. Results: GerbB2 was strongly con-elated with down-regulation of p27 and overexpression of c-erbB2 was', as expected, associated with poor survival. However, there was no correlation with proliferation. There was, nevertheless, an association between c-erbB2 and proliferation in certain subtypes of breast cancer, as in oestrogen-receptor-positive e tumours, tumours with high cyclin D1 and in tumours with an overall linear pRb pathway, i.e. tumours with a preserved linearity between cyclin D1, pRb phosphorylation and proliferation. Conclusion: Our results suggest that c-erbB2 may have alternative functions in different subtypes of breast cancer, and further stress that c-erbB2, in addition to promoting proliferation, also functions through other mechanisms in breast cancer.
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| 78. |
- Lundgren-Eriksson, L., et al.
(författare)
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Hypothermic modulation of doxorubicin, cisplatin and radiation cytotoxicity in vitro
- 2001
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Ingår i: Anticancer Res. - 0250-7005. ; 21:5, s. 3275-80
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The influence of hypothermia on doxorubicin, cisplatin and radiation cytotoxicity was investigated in vitro. MATERIALS AND METHODS: A human glioma cell line (251MG) in early exponential growth was exposed to doxorubicin or cisplatin at various concentrations for 4 hours, or X-irradiation at 28 degrees C or 37 degrees C. The cells continued growing in multi-well plates at 37 degrees C and were counted every third day until the end of the logarithmic phase, on day 13. RESULTS: Exposure to doxorubicin 0.05-0.5 microg/ml or cisplatin 1-10 microg/ml caused a dose-dependent inhibition of cell growth with a significantly reduced toxicity when exposed at 28 degrees C as compared to 37 degrees C. Irradiation with 4 Gy also resulted in less toxicity during hypothermia. Chlorpromazine 0.01-10 microg/ml, used to induce hypothermia in vivo (1), neither influenced, cellular growth itself nor interacted with doxorubicin, cisplatin or irradiation. CONCLUSION: Moderate hypothermia (28 degrees C) appears to protect against the cellular insult of doxorubicin, cisplatin and ionising irradiation and their consequences.
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| 79. |
- Lundgren-Eriksson, L., et al.
(författare)
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Radio-and chemotoxicity in mice during hypothermia
- 2001
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Ingår i: Anticancer Res. - 0250-7005. ; 21:5, s. 3269-74
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The influence of hypothermia induced by chlorpromazine (10-15 mg/kg given intra-peritoneally) on the survival from radiation and chemotherapy exposure in C57B1-mice, with or without tumour inoculation, was studied. MATERIALS AND METHODS: The mice were exposed to either whole body irradiation (8 Gy), or doxorubicin (15 or 17.5 mg/kg i.p.), or cisplatin (20 mg/kg i. p.) and followed to ensuing death. The control mice maintained a rectal temperature of 38 degres C while those receiving chlorpromazine developed moderate hypothermia of 28 degrees C or 36 degrees C, dependent on the ambient temperature. RESULTS: Hypothermia of 28 degrees C protected the mice from radiation-induced death and acute doxorubicin toxicity, with males gaining more protection than females. The effects appeared dependent on temperature, not on chlorpromazine. Hypothermia protected the mice from acute cisplatin toxicity and increased the anti-tumour effects in both genders. Chlorpromazine itself did not cause toxicity, neither did it change the natural course of tumour progression. CONCLUSION: Hypothermia of 28 degrees C induced by chlorpromazine profoundly reduces radiation, doxorubicin-and cisplatin-induced toxicity in mice with males benefiting more than females. The hypothermia itself, not the chlorpromazine, was responsible for these effects. The anti-neoplastic activity was not compromised; rather, it was enhanced, particularly for cisplatin.
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| 80. |
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