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WP 2 – Distribution in breast tissue

WP 2 – Distribution in breast tissue. ISOLATION. HYDROLYSIS. Molecular form Aglycones or conjugated ? ( Gu et al. 2005). Biodistribution Glandular or adipose tissue?. EXTRACTION. Concentration. KWANTIFICATION. Discrepantie tussen in vitro en in vivo resultaten: Tangeritine. Tam

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WP 2 – Distribution in breast tissue

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  1. WP 2 – Distribution in breast tissue ISOLATION HYDROLYSIS Molecularform Aglyconesorconjugated? (Gu et al. 2005) Biodistribution Glandularoradipose tissue? EXTRACTION Concentration KWANTIFICATION

  2. Discrepantie tussen in vitro en in vivo resultaten: Tangeritine.

  3. Tam Tang Tam Tang Contr Bracke M, Depypere H et al. JNCI 2000 Tumor volume (mm3) 1000 weeks 2 4 8 6 10 12 14

  4. Tamoxifen Tamoxif + Tang 1.0 Cum Survival Weeks 0 10 20 30 40 50

  5. Danish sex Hormone Register StudyDaHoRS Hormone therapy and breast cancer Øjvind Lidegaard1, Ellen Løkkegaard2, Anne Helms Andreasen3, Lisbeth Møller3 Carsten Agger3, Torben Jørgensen3 1) Rigshospitalet, Gynaecologic Clinic, 4232 2) Dept. Obstetrics & Gynaecology, Hilleroed Hospital, DK. 3) Research Centre for Prevention and Health, Glostrup, DK

  6. DaHoRS: Principal study design Aim • Assess the influence of OC and HT on • The risk of cardiovascular diseases and cancer Material and methods • A National cohort of 1.8 million women • 15-69 years old January 1, 1995 • Followed from January 1995 through 2002 • Exposures and outcomes from national registers • Details on www.dachre.dk Danish Sex Hormone Register Study (DaHoRS): www.dachre.dk

  7. The impact of progestagen doseLow = 0.5mg NETA or 2.5mg MPA. High = 1mg NETA or 5mg MPA Adjusted RR, 95% CI All continuous combined regimens 51-54 55-59 60-64 65-69 DaHoRS/05

  8. Risk of lethal BC with hormones within five years after diagnosis Adjusted RR, 95% CI Women with BC: 12,831 Dead after diagnosis: 2,347 (18%) Five years follow-up: 1,269 DaHoRS/05

  9. Results (2)

  10. Estrogen only WHI RR 0.77 NHS - duration ? 28 835 women with hysterectomy BMI <25 BMI>25 never 78 1.00 148 1.00 <5 y 45 1.03 (0.69-1.52) 54 0.96 (0.96-1.33) 5-9.9 78 1.17 (0.84-1.62) 66 0.74 (0.55-1.00) 10-14.9 94 1.18 (0.86-1.62) 94 0.97 (0.74-1.28) 15-19.9 66 1.36 (0.97-1.92) 63 1.11 (0.82-1.51) >20 80 1.77 (1.26-2.48) 65 1.25 (0.91-1.71)

  11. Oestrogeen monotherapie (na hysterectomie) is er in gerandomiseerd onderzoek geen verhoging van de incidentie van borstkanker. In de nurses’ studie was er een verhoging na 20 jaar inname van hoge dosis ET bij vrouwen met een laag BMI. Continu gecombineerde (oestrogeen-progestogeen) behandeling die lage dosis bevat en natuurlijke progestagenen was niet geassocieerd met een verhoogde incidentie van borstkanker. Een studie van de insuline spiegels met en zonder hormoon behandeling is gepland. Het in vivo resultaat zal worden teruggekoppeld naar in vitro werk.

  12. Soja produkten kunnen theoretisch een vermindering geven van borstkanker. Er is een grote variabiliteit van opname en metabolisatie. Darmbacteriën spelen een belangrijke rol in de opname en metabolisatie. 8-PN is veruit het sterkste phyto oestrogeen. Xanthohumol heeft duidelijke antitumorale werkingen. Iso xanthohumol kan een precursor zijn van 8-PN.

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