PURPOSE: Estrogen stimulates cell proliferation in breast cancer, the biological effects of which are mediated through two intracellular receptors: estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). However, the actual role of ERs in the proliferative action of estrogen remains to be established. It was recently found that ER activates phosphatidylinositol-3-OH kinase (PI3K), via its binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism, with the subsequent formation of phosphatidylinositol-3, 4, 5-trisphosphate (PIP(3)), which is generated from phosphatidylinositol 4, 5-bisphosphate (PIP(2)) via PI3K activation. The present study has demonstrated that 17b-estradiol (E2) up-regulates PI3K in an ERalpha, but not an ERbeta dependent manner, and also stimulates cell growth in breast cancer cells. METHODS: To study this phenomenon, we treated ER-positive MCF-7 cells and ER-negative MDA-MB-231 cells with 10 nM E2. RESULTS: The treatment of MCF-7 cells with E2 resulted in a marked increase in the expression of PI3K (p85), which was paralleled by increases in the levels of phospho-Akt (Ser-473) and PIP3. These observations were also correlated with increased E2-induced cell proliferation activity. However, no effects of E2 on breast cancer cells were observed in the MDA-MB-231 cell line, indicating the pathway of E2-mediated up-regulation of PI3K/Akt is ERalpha-dependent. CONCLUSION: These results suggest that estrogen activates PI3K/Akt signaling via an ERalpha-dependent mechanism in MCF-7 cells.
Breast Neoplasms* ; Breast* ; Cell Line ; Cell Proliferation ; Estradiol* ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Estrogens* ; MCF-7 Cells ; Metabolism ; Phosphatidylinositol 3-Kinases ; Phosphatidylinositols ; Up-Regulation*

A premenarcheal 10-year-old girl visited our clinic due to a rapidly growing and painless mass of the right breast of three months duration. The breast mass was removed using a wide local excision. The pathological findings revealed the tumor was made up of a phyllodes tumor. A phyllodes tumor, also known as cystosarcoma phyllodes, is a rare fibroepithelial tumor of the breast, which accounts for 0.3 to 1.0 % of all breast neoplasms. They have a greater degree of stromal cellularity than fibroadenomas, with a characteristic leaf-like projection. These tumors can occur between the ages of 9 to 88 years, but are most common in the third and fourth decades of life; therefore, are uncommon in children. A phyllodes tumor in an adolescent patient was first studied by Amerson, in 1970, at which time he reviewed 355 cases from the American literature, and found a five percent incidence in subjects below 20 years old. Because only a few cases have been reported in the literature; here we report a case of a phyllodes tumor in a 10-year-old girl.
Adolescent ; Breast ; Breast Neoplasms ; Child* ; Female* ; Fibroadenoma ; Humans ; Incidence ; Phyllodes Tumor* ; Young Adult

BACKGROUND AND OBJECTIVES: Elevated hs-CRP (high sensitivity C-reactive protein) is well known as a biomarker reflecting the inflammatory process that might evoke the potential for microembolization of an atheromatous plaque, and imparts a poor prognosis in patients with coronary artery disease. We designed this study to evaluate whether the preprocedural hs-CRP level was associated with procedure-related myocardial injury following coronary stenting. SUBJECTS AND METHODS: We obtained the plasma hs-CRP level from angina patient, who underwent coronary stenting, within 24 hours prior to the procedure, and divided the patients into either the normal CRP (hs-CRP <3 mg/L) or elevated CRP groups (hs-CRP > or =3 mg/L). We defined the reduction of TMP (TIMI myocardial perfusion) grade as at least one decrease in the TMP grade following coronary stenting compared with the pre-procedural TMP. We also evaluate the procedure-related myocardial damage by measuring CK-MB leakage after stenting. RESULTS: We enrolled 279 lesions in 226 patients, who were divided into two groups: the normal CRP group (n=137, 1.28+/-0.71 mg/L) and the elevated CRP group (n=89, 6.89+/-4.23 mg/L). A reduction in the TMP grade was significantly more prevalent in the elevated CRP (20 lesions, 17.4%) compared to the normal CRP group (6 lesions, 3.7%, p=0.001). An elevated CRP level was related to an increased CK-MB leakage following stenting (elevated CRP group; 23 patients, 25.8%, normal CRP group; 21 patients, 15.3%, p=0.041). In a multivariable analysis, the only significant predictor of a reduction in the TMP grade following stenting was an elevated CRP level. CONCLUSION: Systemically detectable inflammatory activity, served by the plasma hs-CRP level, is associated with procedure-related microvascular injury, as assessed by a reduction in the TMP grade and CK-MB elevation following coronary stenting.
C-Reactive Protein ; Coronary Artery Disease ; Humans ; Microcirculation ; Plasma ; Prognosis ; Stents* ; Thymidine Monophosphate

Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3+ double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10+Foxp3+ regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10+Foxp3+ regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.

Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3+ double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10+Foxp3+ regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10+Foxp3+ regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.