Anti-angiogenic effects of green tea catechin on an experimental endometriosis mouse model.

BACKGROUND: The development of new blood vessels plays an essential role in growth and survival of endometriosis. Epigallocatechin gallate (EGCG) from green tea has powerful anti-angiogenic properties and our aim was to evaluate these properties in experimental endometriosis. METHODS AND RESULTS: Eutopic endometrium from endometriosis patients was transplanted s.c. to severely compromised immunodeficient mice, randomly treated i.p. with EGCG (anti-angiogenic and -oxidant), Vitamin E (a non-angiogenic antioxidant) or saline for 2 weeks. The endometrial implant, including adjacent host outer skin and subcutaneous layers plus inner abdominal muscle and peritoneum, was collected. New microvessels were determined by species-specific immunohistochemistry. Angiogenic factors in lesions and abdominal muscle were detected by quantitative real-time PCR. Apoptosis was studied by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling and quantitative real-time PCR. In saline control, endometrial implants developed new blood vessels with proliferating glandular epithelium and were tightly adhered to host subcutaneous and abdominal muscle layers. After EGCG, endometriotic lesions were smaller than control (P < 0.05), and glandular epithelium was smaller and eccentrically distributed. Angiogenesis in lesions from the implant and adjacent tissues was under-developed, and microvessel size and density were lower (both P < 0.01) than control. mRNA for angiogenic vascular endothelial growth factor A, but not hypoxia inducible factor 1, alpha subunit, was significantly down-regulated in lesions after EGCG (P < 0.05). In addition, apoptosis in the lesions was more obvious, and nuclear factor kappa B and mitogen activated protein kinase 1 mRNA levels were up-regulated (P < 0.05) after EGCG treatment. No differences were observed with Vitamin E treatment. CONCLUSIONS: EGCG significantly inhibits the development of experimental endometriosis through anti-angiogenic effects.

Uptake and distribution of catechins in fetal organs following in utero exposure in rats.

BACKGROUND: Although catechins are known to be powerful antioxidants, no reports have shown their transport to fetal organs. We investigated the distribution of catechins in fetal rat organs after maternal exposure to green tea extract (GTE). METHODS: GTE (550 mg/kg) or water was fed orally to pregnant dams at 15.5 days of gestation, the dams were sacrificed and fetal organs were dissected 0, 0.5, 1, 2, 3, 5, and 8 h later. Catechins and catechin gallates were determined by high-performance liquid chromatography (HPLC) after solid-phase extraction. RESULTS: In the GTE-treated group, catechins were detected in most of the fetal organs studied, including the brain, eyes, heart, lungs, kidneys and liver but not in the control group. The first peak times (T(max)) were about 0.5-1 h. The maximum concentrations (C(max)) of catechins in the fetal eye were about 2-10 times higher than in the other organs, ranging from 249 pmol/g for epicatechin (EC) to 831 pmol/g for epigallocatechin gallate (EGCG). Catechin gallates were generally more readily taken up by fetal organs than catechins. EGCG had the highest level of uptake according to area under the curve (AUC) plots and the highest C(max) in all organs. CONCLUSIONS: Various fetal organs had low but significant levels of catechins after GTE intake by the dams, and organ levels were found to be related to catechin structure. EGCG could be a potential candidate for antioxidant supplementation of the fetus in utero.

The tumor-sensitive calmodulin-like protein is a specific light chain of human unconventional myosin X.

Human calmodulin-like protein (CLP) is an epithelial-specific Ca(2+)-binding protein whose expression is strongly down-regulated in cancers. Like calmodulin, CLP is thought to regulate cellular processes via Ca(2+)-dependent interactions with specific target proteins. Using gel overlays, we identified a approximately 210-kDa protein binding specifically and in a Ca(2+)-dependent manner to CLP, but not to calmodulin. Yeast two-hybrid screening yielded a CLP-interacting clone encoding the three light chain binding IQ motifs of human "unconventional" myosin X. Pull-down experiments showed CLP binding to the IQ domain to be direct and Ca(2+)-dependent. CLP interacted strongly with IQ motif 3 (K(d) approximately 0.5 nm) as determined by surface plasmon resonance. Epitope-tagged myosin X was localized preferentially at the cell periphery in MCF-7 cells, and CLP colocalized with myosin X in these cells. Myosin X was able to coprecipitate CLP and, to a lesser extent, calmodulin from transfected COS-1 cells, indicating that CLP is a specific light chain of myosin X in vivo. Because unconventional myosins participate in cellular processes ranging from membrane trafficking to signaling and cell motility, myosin X is an attractive CLP target. Altered myosin X regulation in (tumor) cells lacking CLP may have as yet unknown consequences for cell growth and differentiation.

The 'right kind' of pain: talking about symptoms in outpatient oncology consultations.

Despite improvements in cancer management over the past 25 years, unrelieved symptoms continue to be reported. Little is known about how patients' problems and concerns are communicated to professionals during oncology treatment. This qualitative study investigates the process of communication between cancer patients and oncologists during consultations in outpatient clinics of a regional teaching hospital. Data were collected by nonparticipant observation and audiotaping consultations. Analyses were by qualitative content analysis and conversation analysis. An objectives, strategies and tactics model was applied to organize the findings. Seventy-four consultations between cancer patients and 15 doctors were observed and audiotaped. Pain talk is defined and identified as a substantial topic, occurring in 39 out of 74 consultations. Doctor-initiated questions are the predominant discourse feature and are prominent not only in initiating discussions but also in directing further talk (e.g. over three-quarters of doctor-initiated questions are in a closed form which focus narrowly on limited physical aspects of patients' pain). This limited information exchange is used alongside other communication tactics to identify the 'right kind' of pain that may benefit from cancer therapy and to truncate talk of problems perceived to be outside of this specialist remit. Although individualized, holistic care is the expressed philosophy of the clinic, our data show that doctors tightly control the agenda to focus narrowly on pain which was amenable to radiotherapy, chemotherapy, surgery or hormone manipulation. Inadequate exploration of patients' pain is likely to be detrimental to symptom control.

Calcium and low-dose aspirin prophylaxis in women at high risk of pregnancy-induced hypertension.

OBJECTIVE: The objectives of the study were to confirm the validity of using oscillometric measurement of MAP in the left lateral position to identify those at high risk for developing pregnancy-induced hypertension (PIH), and to assess and compare the efficacy of prophylaxis with low-dose aspirin or calcium supplementation in high-risk patients. STUDY DESIGN: A prospective study in pregnancy; 500 normotensive, primigravid Chinese women were recruited in the second trimester of pregnancy on the basis of 80 mm Hg > or = MAP < 106 mm Hg in the antenatal clinic. They were then screened by Dinamap in a research setting, measuring MAP in the left lateral position after rest and using a cutoff value of 60 mm Hg for inclusion in the randomized study. Randomization was divided into three groups: control, low-dose aspirin, and calcium supplementation. After delivery, patients were classified as either having remained normotensive or having developed PIH, with or without proteinuria. RESULTS: The incidence of both proteinuric and nonproteinuric PIH was significantly lower in patients screened out as low risk than in those selected as high risk using a critical value of 60 mm Hg for left lateral MAP (p < 0.05). The incidence of proteinuric PIH was significantly lower in patients given low-dose aspirin than in the control group (p < 0.05). However, the confidence intervals for the effect were wide, comparable with aspirin having no effect or leading to a 16-fold reduction in the risk of preeclampsia. For those given calcium supplementation, the reduction was not significant. There was no significant difference in the incidence of nonproteinuric PIH between the control group and the two groups receiving prophylaxis. CONCLUSION: Oscillometric measurement of second-trimester left lateral MAP is a valid predictor of proteinuric PIH. Low-dose aspirin may offer a degree of protection from proteinuric PIH in these high-risk women. Calcium supplementation was not shown to significantly reduce the incidence of PIH.

Platelet angiotensin II receptor status during pregnancy in Chinese women at high-risk of developing pregnancy-induced hypertension.

OBJECTIVES: The aims of this prospective study were to explore the changes in platelet angiotensin II (A-II) binding in pregnancy amongst Chinese women at high risk of developing pregnancy-induced hypertension (PIH) and the effects of low-dose aspirin and calcium supplementation on A-II binding. METHODS: Platelet A-II binding was assayed in 15 non-pregnant women and in 63 pregnant women determined to be at risk of PIH on the basis of 2nd-trimester mean arterial pressure (MAP). The pregnant patients were randomized into three groups: control, low-dose aspirin, and calcium supplementation. A-II binding was assayed again during the 3rd trimester in half the women and 8 weeks after delivery. RESULTS: A-II binding was negatively correlated with MAP measured in the left lateral position (p < 0.05) but not with MAP measured in the supine position. There were no significant differences between A-II binding in non-pregnant and pregnant women. Neither low-dose aspirin nor calcium supplementation caused significant reductions in A-II binding. CONCLUSION: The measurement of platelet A-II binding is unlikely to provide significant information regarding the risk of PIH over and above that obtained from measurement of 2nd-trimester MAP.