Pseudoxanthoma elasticum and obstetric epidural analgesia: Report of a case

peer reviewedPseudoxanthoma elasticum is a rare inherited disorder of the elastic tissue characterised by multisystem manifestations. Skin, eyes, gastro-intestinal system and cardiovascular system are the major affected systems. We describe the anaesthetic management of a parturient affected by this disease

Reduction of brain metastases in plasminogen activator inhibitor-1-deficient mice with transgenic ocular tumors

Plasminogen activator inhibitor-1 is known to play a paradoxical positive role in tumor angiogenesis, but its contribution to metastatic spread remains unclear. We studied the impact of plasminogen activator inhibitor (PAI)-1 deficiency in a transgenic mouse model of ocular tumors originating from retinal epithelial cells and leading to brain metastasis (TRP-1/SV40 Tag mice). PAI-1 deficiency did not affect primary tumor growth or vascularization, but was associated with a smaller number of brain metastases. Brain metastases were found to be differentially distributed between the two genotypes. PAI-1-deficient mice displayed mostly secondary foci expanding from local optic nerve infiltration, whereas wild-type animals displayed more disseminated nodules in the scissura and meningeal spaces. SuperArray GEarray analyses aimed at detecting molecules potentially compensating for PAI-1 deficiency demonstrated an increase in fibroblast growth factor-1 (FGF-1) gene expression in primary tumors, which was confirmed by reverse transcription-polymerase chain reaction and western blotting. Our data provide the first evidence of a key role for PAI-1 in a spontaneous model of metastasis and suggest that angiogenic factors, such as FGF-1, may be important for primary tumor growth and may compensate for the absence of PAI-1. They identify PAI-1 and FGF-1 as important targets for combined antitumor strategie

Predominant Role of Nuclear Versus Membrane Estrogen Receptor α in Arterial Protection: Implications for Estrogen Receptor α Modulation in Cardiovascular Prevention/Safety

BACKGROUND: Although estrogen receptor α (ERα) acts primarily as a transcription factor, it can also elicit membrane-initiated steroid signaling. Pharmacological tools and transgenic mouse models previously highlighted the key role of ERα membrane-initiated steroid signaling in 2 actions of estrogens in the endothelium: increase in NO production and acceleration of reendothelialization. METHODS AND RESULTS: Using mice with ERα mutated at cysteine 451 (ERaC451A), recognized as the key palmitoylation site required for ERα plasma membrane location, and mice with disruption of nuclear actions because of inactivation of activation function 2 (ERaAF20 = ERaAF2°), we sought to fully characterize the respective roles of nuclear membrane-initiated steroid signaling in the arterial protection conferred by ERα. ERaC451A mice were fully responsive to estrogens to prevent atheroma and angiotensin II-induced hypertension as well as to allow flow-mediated arteriolar remodeling. By contrast, ERαAF20 mice were unresponsive to estrogens for these beneficial vascular effects. Accordingly, selective activation of nuclear ERα with estetrol was able to prevent hypertension and to restore flow-mediated arteriolar remodeling. CONCLUSIONS: Altogether, these results reveal an unexpected prominent role of nuclear ERα in the vasculoprotective action of estrogens with major implications in medicine, particularly for selective nuclear ERα agonist, such as estetrol, which is currently under development as a new oral contraceptive and for hormone replacement therapy in menopausal women

Percutaneous stereotactic en bloc excision of nonpalpable breast carcinoma: a step in the direction of supraconservative surgery

peer reviewedRecently, the advanced breast biopsy instrumentation (ABBI) system has been introduced as an alternative to conventional breast biopsy techniques. This study was prospectively conducted to evaluate the potential of the ABBI method in locoregional management of a consecutive series of patients with nonpalpable mammographically detected breast carcinomas. Sixty-one consecutive patients underwent an ABBI procedure as a first step before possible surgery for nonpalpable breast lesions that would in any case require complete excision. For the 27 patients in whom the ABBI biopsy revealed malignancy further surgery was recommended, including re-excision of the biopsy site and axillary dissection in cases of infiltrating carcinoma. We calculated the probabilities that the ABBI specimen would have tumor-free margins and that a definitely complete excision had been achieved as a function of the mammographic or pathological diameter of the cancer. For cancer with a pathological diameter less than 10 mm, measured on the ABBI specimen, the probability (92%) of obtaining complete resection was significantly better than for larger lesions (P = 0.01, Fisher's exact test). Although the therapeutic perspectives for the ABBI method are limited at present, we suggest that this approach is a first step in the direction of a surgical strategy that is better adapted to the pathological characteristics peculiar to these small tumors, whose incidence is increasing. (C) 2002 Elsevier Science Ltd. All rights reserved

Absence of Host Plasminogen Activator Inhibitor 1 Prevents Cancer Invasion and Vascularization

Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angiogenesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis