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- Li, Li, et al.
(author)
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Induction of apoptosis and G2/M arrest by 2-methoxyestradiol in human cervical cancer HeLaS3 cells.
- 2004
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In: Anticancer Res. - Athens : International institute for anticancer research. - 0250-7005 .- 1791-7530. ; 24:2B, s. 873-80
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Journal article (peer-reviewed)abstract
- BACKGROUND: It has been demonstrated that 2-Methoxyestradiol (2-ME), one of the estrogen metabolites, induces apoptosis in many different tumor cell lines. In the present study, the effects of 2-ME on human cervical cancer HeLaS3 cells and on normal cervical epithelial cells were evaluated. MATERIALS AND METHODS: Acridine orange staining, DNA fragmentation arrays and flow cytometry were used to measure the apoptosis and cell cycle progression. In addition, the effect of 2-ME on expression of iNOS was measured by Western blot. RESULTS: 2-ME inhibited the growth of HeLaS3 cells. This growth inhibition was accompanied by apoptosis and G2/M cell cycle arrest. 2-ME increased the expression of iNOS in parallel with apoptosis. Moreover, apoptosis was prevented by the iNOS inhibitor 1400W. 2-ME treatment resulted in a slight increase of the G2/M population, but no apoptosis, in normal cervical epithelial cells. There was no synergetic effect between E2 and 2-ME. CONCLUSION: 2-ME induced apoptosis via the iNOS pathway and caused G2/M cell cycle arrest in human cervical cancer HeLaS3 cells, but showed only slight effects on normal cervical epithelial cells. These data suggest that 2-ME might be an adjuvant agent in the treatment of cervical cancer.
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- Ödmark, Inga-Stina, 1948-, et al.
(author)
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Long-term effects of two different continuous combined regimens of hormone replacement therapy on well-being
- 2004
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In: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 18, s. 305-317
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Journal article (peer-reviewed)abstract
- Our aim was to compare the effect on well-being of two different continuous combined hormone replacement therapies (HRT) in women starting treatment (‘starters’) and women switching from mainly sequential HRT (‘switchers’). The design was a randomized, double-blind, 1-year, prospective study, including 249 postmenopausal women treated with 0.625 mg conjugated estrogen (CE)/ 5 mg medroxyprogesterone acetate (MPA) or 2 mg estradiol/1 mg norethisterone acetate (NETA) continuously. The main outcome measure was well-being, reported daily on a validated symptom scale during treatment cycles 1, 2, 6 and 13. Both treatment groups, starters and switchers, improved significantly in episodes of sweating during the first 6 months (p50.05). Women treated with estradiol/NETA experienced more breast tenderness compared to women using CE/MPA during the whole study period (p50.001), whereas there were no differences in negative mood symptoms between treatment groups. Starters experienced improved wellbeing during the whole study, whereas switchers experienced a transient improvement during the first 2 months. Overall, negative mood symptoms were more frequently reported by women with a history of premenstrual syndrome (PMS) (p50.05). Progestogen side-effects were more pronounced with estradiol/NETA than with CE/MPA combinations. Individual factors, such as previous PMS and previous HRT use, should be taken into consideration when prescribing HRT.
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- Ödmark, Inga-Stina, 1948-, et al.
(author)
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Well-being at onset of hormone replacement therapy : comparison between two continuous combined regimens
- 2004
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In: Climacteric. - : Informa UK Limited. - 1369-7137 .- 1473-0804. ; 7:1, s. 92-102
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Journal article (peer-reviewed)abstract
- Objectives To compare the effect on well-being of two continuous combined hormone replacement therapies (HRTs) in women starting treatment (‘starters’) and women switching from mainly sequential HRT (‘switchers’). Methods This was a randomized, double-blind, 1-month trial, in which 249 postmenopausal women were treated with either conjugated estrogen plus medroxyprogesterone acetate (CE/MPA 0.625 mg/5 mg) or 17β-estradiol plus norethisterone acetate (E2/NETA 2 mg/1 mg) continuously. Twelve items for measuring climacteric symptoms and well-being were reported daily on a validated symptom scale. Results Women taking CE/MPA reported lower scores for breast tenderness (p = 0.005), depression (p = 0.019), irritability (p = 0.004) and tension (p = 0.048), compared with women taking E2/NETA. Compared with pretreatment, both groups developed side-effects during the first week: breast tenderness, swelling and depression (p < 0.05). Starters, but also switchers, improved in sweats (p < 0.001 and p = 0.030). Compared with pretreatment ratings, switchers reported higher scores for breast tenderness (p < 0.001), depression (p = 0.050) and negative effects on daily life (p < 0.001), whereas starters reported only physical side-effects (p < 0.05). A history of premenstrual syndrome (PMS) predicted high scores for swelling (p = 0.023), depression (p = 0.024), tension (p = 0.009), irritability (p = 0.027), headache (p < 0.001) and negative effects on daily life (p < 0.001). Conclusions CE/MPA 0.625 mg/5 mg is better tolerated than E2/NETA 2 mg/1 mg, and starters react differently from switchers. Side-effects occur more quickly than benefits with HRT, and are more frequent in women with previous PMS.
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