Our observations suggest that the ATP-P2Y receptor system is partially involved in the pathogenesis of ventilator-induced lung injury.

No abstract

Acute lung injury (ALI) is defined as an inflammatory lung condition that is mediated by the interplay between inflammatory cells such as phagocytes, in particular macrophages and neutrophils, and non-immune cells such as alveolar epithelial cells. 1,2) Because the overall risk of mortality for ALI or acute respiratory distress syndrome (ARDS) patients remains unacceptably high, an improved understanding of the pathophysiology is needed to reduce mortality through the development of treatments that will be additive or synergistic with mechanical ventilation strategies using low tidal volumes.3) Recently, the several investigators have proposed that lung epithelial cell death occurs not only through necrotic processes, such as through ischemic change or direct disruption, but also by apoptotic processes. 1,4,5) Apoptosis, a form of programmed cell death characterized by nuclear condensation and endonuclease-mediated DNA fragmentation, is essential to tissue development and preservation of cell membrane integrity. Apoptosis also appears to be important in the pathophysiology of some diseases. [6][7][8][9] The Fas-Fas ligand (FasL) system comprises an important mechanism for regulating apoptotic cell death. The Fas antigen (CD95, APO-1) belongs to a conserved family of membrane receptors known as the tumor necrosis factor (TNF) receptor family, 10) and is expressed on various cells and tissues, including thymus, liver, heart, and lung. FasL is a type II integral membrane protein of the TNF family.11) Membranebound FasL is cleaved by specific matrix metalloproteinases to produce its soluble form.12) Although expression of FasL was originally thought to be limited to cytotoxic T cells, it also has been found in other types of cells.11) Polymorphonuclear neutrophils (PMN) release soluble FasL, which can induce apoptosis in certain Fas bearing cell types, including PMN themselves. 13,14) High levels of preformed FasL are found in the intracellular compartment, and stimulation of monocytic cells by phytohaemagglutinin or superantigen gives rise to the rapid release of soluble FasL. 15)Binding of FasL to Fas antigen causes apoptosis in Fas antigen-bearing cells via an apoptotic pathway that is dependent on the initiator caspase-8.16) Cross-linking of the extracellular domains of Fas by FasL results in Fas trimerization and intracellular recruitment of the adapter molecule Fas-associated death domain protein (FADD) to the receptor cluster. Recruitment is facilitated by homotypic interaction between death domains located in Fas and FADD. Receptorbound FADD oligomerizes and utilizes a second domain, the death effector domain, to recruit procaspase-8, forming the Fas/FADD/procaspase-8 complex known as the death-inducing signaling-complex (DISC).17,18) DISC catalyzes the proteolytic conversion of procaspase-8 into active caspase-8, which activates the downstream effector caspases, triggering cell death. Apoptosis also occurs via a mitochondria-mediated process, which begins with mitochondrial permeability transition, followed...

Estrogen receptor-negative breast cancers generally are highly malignant, resistant to chemotherapy and poorly prognostic. Here we demonstrate that estrogen receptor-negative human breast cancer cell lines highly express Fra-1, c-Fos and c-Jun, components of the transcription factor, activator protein-1 (AP-1). Retrospective observation of breast cancer tissues obtained by core needle biopsy before surgery from stages II and III patients demonstrates that Fra-1 expression is high in estrogen receptor-negative human breast cancers, and negatively correlated to paclitaxel sensitivity. Ascochlorin, which suppresses cellular AP-1 activity, selectively kills estrogen receptor-negative human and mouse breast cancer cell lines, and prolongs the survival time of mice implanted with an estrogen receptor-negative mammary carcinoma. These results suggest that chemotherapy targeting AP-1 activity is a potent strategy for estrogen receptor-negative human breast cancers.

Myoid hamartomas of the breast are extremely rare breast lesions, with a poorly understood pathogenesis. We describe the case of a 38-year-old premenopausal woman who presenting with a mass in the left breast. Mammography revealed an oval mass that was partly indistinct, and ultrasonography showed a hypoechoic mass with a slightly irregular margin. Bilateral breast dynamic magnetic resonance imaging was performed for a more detailed evaluation. The images showed rapid initial enhancement and a microlobulated margin. Because the suspicion of malignancy was strong at that time, core needle biopsy was performed. Histologically, the tumor was identified as fibroadenoma. A case of myoid hamartoma of the breast that proved difficult to diagnose is reported, and discussed with reference to the literature.