Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leiomyomas (fibroids) are benign tumors of the uterus affecting millions of women. Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica), which makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Because dietary intake of lycopene has been associated with a reduced risk of a variety of human cancers, we investigated the effects of lycopene supplementation on the development of leiomyomas in the oviduct of Japanese quail. We also measured serum levels of oxidative stress markers [malondialdehyde (MDA) and homocysteine], lycopene, vitamins C, E, and A, and tissue biomarkers Bcl-2 and Bax expression. One hundred twenty quails (6 mo old) were assigned to 3 treatment groups consisting of 4 replicates of 10 birds in each group. Birds were fed either a basal diet (group C) or the basal diet supplemented with 100 mg (group L1) or 200 mg (group L2) of lycopene per kilogram of diet. The animals were sacrificed after 285 days and the tumors were identified. Lycopene supplementation decreased the number of leiomyomas compared with control subjects (P=0.056). The tumors in lycopene-fed birds were smaller than those found in control birds (P=0.01). There were no significant differences in the expression of tissue Bcl-2 and Bax among the study groups. Serum vitamins C, E, and A increased (P=0.01), whereas MDA and homocysteine concentrations decreased (P=0.01) with lycopene supplementation. No measurable lycopene could be detected in the serum of control birds, whereas a dose-dependent increase was observed in the serum of lycopene-supplemented birds. The results indicate that dietary supplementation with lycopene reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of lycopene supplementation in the prevention and treatment of uterine leiomyoma in humans.
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PMID:Lycopene supplementation prevents the development of spontaneous smooth muscle tumors of the oviduct in Japanese quail. 1562 65

Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica) and laying hens. This makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Genistein has been shown to inhibit the growth of various cancer cells. We investigated the effects of genistein supplementation on the development of fibroid tumors in the oviduct, serum oxidative stress markers [malondialdehyde (MDA), 8-isoprostane, 4-hydroxyalkenal (HAE), 8-hydroxy-2' -deoxyguanosine (8-OHdG) levels], soy isoflavone levels, and tissue biomarkers [Connexin 43 (Cx43), Bcl-2, and Bax and heat shock protein 70 (Hsp70) expression] in Japanese quail. One hundred and fifty quail (12 mo old) were assigned to 3 experimental groups as 5 replicates of pens containing 10 birds in each. Birds were fed either a basal diet or the basal diet supplemented with 400 mg or 800 mg of genistein/kg of diet. The animals were sacrificed after 315 days, and the tumors were identified. Genistein supplementation significantly decreased the incidence of fibroid tumors as compared to control birds (P = 0.04). The tumors in genistein-fed birds were smaller than those found in control birds (P = 0.02). Serum MDA, 8-isoprostane, and HAE levels were lower in treatment groups than in control group (MDA: 2.01 vs. 0.82; 8-isoprostane: 135 vs. 101; HAE: 1.45 vs. 0.73; P <or= 0.01). The concentrations of serum 8-OHdG, which is a marker of oxidative damage, in the groups were 27.5, 22.4, and 21.3 ng/ml, respectively (P = 0.05). The expression of cell cycle regulatory proteins, Bcl-2, was 4.18 and 4.61 in the genistein groups and 6.21 in the control group, and the expression of Bax was 10.93 and 16.78 in the genistein groups and 7.60 in the control group (P < 0.001 for Bax). Cx43 level was 2.56 and 2.40 in the genistein groups compared with 5.15 in the control group. None of the differences in the Cx43 and Bcl-2 of the groups were significant. The expression of heat shock proteins, Hsp60 and Hsp70, were not different between groups, although Hsp70 level of the genistein groups (19.73) was lower than the control group (27.8). The results indicate that dietary supplementation of genistein reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of genistein supplementation in the prevention and treatment of uterine leiomyoma in humans.
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PMID:Genistein suppresses spontaneous oviduct tumorigenesis in quail. 2015 19

The use of levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for management of menorrhagic women with uterine myomas because of reduction in menorrhagia. However, the size of myomas during use of LNG-IUS increased in some but decreased in other instances. This prompted us to characterize the effects of progesterone (P4) on cultured leiomyoma cell growth. Treatment with P4 resulted in increase in epidermal growth factor (EGF) expression in cultured leiomyoma cells, whereas treatment with E2 augmented EGF-R expression in those cells. This indicates that P4 and E2 act in combination to stimulate myoma growth through induction of EGF/EGF-R expression. Bcl-2 expression in leiomyoma cells was up-regulated by P4. Furthermore, P4 augmented proliferating cell nuclear antigen expression in cultured leiomyoma cells but not in cultured normal myometrial cells. This fact let us to examine the effects of progesterone receptor modulator (PRM) on leiomyoma cell proliferation and apoptosis in comparison with normal myometrial cells. Our studies revealed that CDB-2914 inhibits the proliferation, stimulates apoptosis of cultured leiomyoma cells, and inhibits the expression of angiogenic factors (vascular endothelial growth factor and adrenomedullin) and their receptors in cultured leiomyoma cells, without affecting those in cultured normal myometrial cells. We then evaluated the effects of CDB-2914 on extracellular matrix (ECM) components in cultured leiomyoma cells. CDB-2914 increased ECM metalloproteinase inducer, matrix metalloproteinase (MMP)-1, MMP-8 contents and decreased tissue inhibitors of MMP (TIMP)-1, TIMP-2 contents as well as type I and type III collagen contents in cultured leiomyoma cells, without comparable effects on cultured normal myometrial cells. These findings demonstrate that PRM not only inhibits the proliferation and stimulates apoptosis of cultured leiomyoma cells but also suppresses collagen synthesis in a cell-type specific manner. This is meaningful for understanding the molecular mechanism of the usefulness of PRM in the treatment of uterine fibroids.
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PMID:Translational research with progesterone receptor modulator motivated by the use of levonorgestrel-releasing intrauterine system. 2093 17