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Angiopoietin-1 (Ang1) is an angiogenic growth factor that functions through activation of its endothelium-specific tyrosine kinase receptor Tie2; it mediates the interaction between endothelial and surrounding cells to promote the remodeling, maturation and stabilization of blood vessels. Although Ang1 is expressed constitutively in many adult tissues, its role in tumor growth and metastasis is not clear. Here we describe experiments in which Ang1 expression was inhibited in HeLa cells by an antisense RNA approach. The modified HeLa cells produced significantly less Ang1 protein both in cultured cells and in tumors formed when these cells were injected into immunodeficient mice. The Ang1 antisense tumors grew much more slowly, with significantly reduced tumor angiogenesis compared with control tumors. Furthermore, they also had substantially increased tumor cell apoptosis and decreased tumor necrosis. Our results indicate that the perturbation of Ang1 expression in tumors could be an effective method to control tumor growth by inhibiting tumor angiogenesis and that antisense RNA is an efficient way to inhibit Ang1 protein production in tumor cells., (Copyright 2001 Wiley-Liss, Inc.)

Interstitial pulmonary emphysema is a well-documented complication of assisted mechanical ventilation in premature infants with respiratory distress syndrome. Localized persistent interstitial pulmonary emphysema (LPIPE) confined to a single lobe was incidentally presented in a 4-day-old female infant. This patient was a normal full-term baby with no respiratory distress symptom and no experience of assisted mechanical ventilation. Chest radiograph showed radiolucent area in right lower lobe zone, which needed differential diagnosis from other congenital lesions such as congenital cystic adenomatoid malformation and congenital lobar emphysema. CT scan showed irregular-shaped air cystic spaces and pathologically, cystic walls primarily consisted of compressed lung parenchyma and loose connective tissue intermittently lined by multinucleated foreign body giant cells.

Women with breast cancer who have responded to initial hormonal therapy frequently experience additional remissions upon further endocrine manipulation. We postulate that hypersensitivity to estradiol (E2) may serve as a mechanistic explanation for these secondary responses. We previously provided evidence of hypersensitivity using an in vitro breast cancer model system and demonstrated the role of mitogen-activated protein kinase (MAP kinase) in the process of adaptation to long-term estradiol deprivation. In the present study, we wished to demonstrate that hypersensitivity to E2 could occur under more complex in vivo conditions and that MAP kinase activation is enhanced under these circumstances. We used an MCF-7 breast cancer model system involving long-term estradiol deprived (LTED) cells to produce xenografts in nude mice and an E2 clamp method to precisely control sex steroid levels. The E2 clamp was designed to maintain plasma E2 at a series of doubling doses from 1.25 pg/ml to 20.0 pg/ml in oophorectomized nude mice. As evidence of the validity of the clamp method, a uterine weight bioassay revealed an excellent, linear dose-response relationship between the predicted level of plasma E2 and stimulation of uterine weight. As evidence of hypersensitivity, we found that LTED xenograft tumors grew to a greater extent than wild-type in response to E2 concentrations of 1.25 pg/ml (P = 0.003) and 2.5 pg/ml (P = 0.0002). At the 10.0 and 20.0 pg/ml plasma concentrations, the LTED tumors were stimulated to a lesser extent than the wild-type. This pattern of increased growth at lower concentrations and reduced growth vs. the wild-type at higher concentrations mimics closely the pattern seen for LTED cells in vitro. All LTED cell tumors exhibited enhanced activation of MAP kinase ranging from 18 to 25%, and E2 did not increase this further. In contrast, E2 caused a linear increase in the percentage of activated MAP kinase positive cells (P < 0.0001) in wild-type tumors from basal levels of 2.66% to maximal levels of 6.40%. These observations suggest a dynamic interplay whereby activation of MAP kinase renders cells more sensitive to the proliferative effects of E2. The precise mechanisms for this interplay are unknown but, when further understood, could potentially provide insight into approaches to prevent the evolution of tumors to a hormone insensitive state.

Steroid receptor coactivator-1 (SRC-1) family members interact with steroid receptors, including estrogen receptor alpha (ERalpha) and progesterone receptor (PR), to enhance ligand-dependent transcription. However, the expression of ERalpha and SRC-1 was found to be segregated in distinct subsets of cells within the epithelium of the estrogen-responsive rat mammary gland. This finding was in contrast to the finding for the stroma, where significant numbers of cells coexpressed ERalpha and SRC-1. Treatment of animals with estrogen induced PR expression in the ERalpha-expressing mammary epithelial cells in the absence of detectable SRC-1 and did not affect the segregated pattern of SRC-1 and ERalpha expression. PR was neither expressed nor induced by estrogen treatment in stroma, despite the coexpression of ERalpha and SRC-1. These results suggest that SRC-1 is not necessary for ERalpha-mediated induction of PR in mammary epithelial cells and is also not sufficient for PR induction in stromal cells expressing both ERalpha and SRC-1. Furthermore, the expression of SRC-1 in a subpopulation of mammary epithelial cells distinct from those expressing ERalpha or PR raises the possibility that SRC-1 has cell type-specific functions other than simply to act as coactivator for ERalpha or PR in the mammary epithelium.

-D- is a rare haplotype that determines D without C, c, E or e, and exalted D activity. The extremely rare homozygote propositi (-D-/-D-) are usually ascertained through their immune antibodies, anti-Rh17 (Hro), which react with red cells of all common Rh phenotypes. The authors experienced the first case in Korea of a woman with -D- phenotype. She had a history of spontaneous abortion, therapeutic termination and red cell transfusion, and at her third pregnancy she delivered a baby with severe hemolytic disease of the newborn. In spite of intensive medical intervention, the baby died of hydrops fetalis. An immune antibody to high incidence Rh antigen, namely anti-Rh17(Hro), was demonstrated in the woman's serum. A family study revealed that the -D- gene complex was present in all its members and one of the woman's sisters was also -D- homozygote. In the serum of this sister, anti-Rh17(Hro) was also present.