The loss of AP-2 expression seems to be associated with malignant transformation and tumor progression in cutaneous malignant melanoma. This tumor-suppressive action of AP-2 may be mediated through p21 regulation. Furthermore, decreased AP-2 expression is independently associated with elevated risk of subsequent metastatic behavior of stage I cutaneous malignant melanoma.
The cell surface glycoprotein CD44 and its ligand, hyaluronan (HA), enhance growth and metastatic capacity of melanoma cells in vitro, but their clinical significance in primary cutaneous melanoma is still unclear. Therefore, we studied whether the levels of CD44 and HA associate with disease progression and survival of cutaneous melanoma. A series of 292 clinical stage I cutaneous melanomas was analyzed by immunohistochemistry using an anti-CD44H antibody (clone 2C5). HA was demonstrated histochemically using a biotinylated HA-specific affinity probe (bHABC). The reduced staining levels of CD44 and HA were associated with each other and indicators of progressive disease. Reduced CD44 and HA level, high tumor thickness, high pT category, high Clark's level, bleeding, and male gender predicted short univariate recurrence free survival (RFS) and overall survival (OS). In Cox's multivariate analysis (N ؍ 251), the decreased level of CD44, high tumor thickness, and bleeding predicted independently short RFS. High tumor thickness and bleeding were associated with short OS. We conclude that the reduced cell surface CD44 and HA levels associate with poor prognosis in clinical stage I cutaneous melanoma. The notion that the decreased level of CD44 independently predicts short RFS suggests that reduced cell surface CD44 enhances the spreading potential in localized cutaneous melanoma and that quantification of CD44 offers a prognostic tool for its clinical evaluation. (Am J Pathol 2000, 157:957-965)The incidence and mortality of cutaneous malignant melanoma has increased worldwide during past decades among white populations. 1 Local disease is in most cases curable by surgical excision. 2 However, the probability of development of disseminated disease is progressively higher as the depth of the primary melanoma increases. In the worldwide multiinstitutional database of cutaneous melanoma patients, the average 5-year overall survival rate for patients with localized (AJCC stages I and II) melanoma was 79%. 3 Those patients who later develop a metastatic disease have a 2-year survival rate less than 5%. 4 As more effective adjuvant therapies, such as interferon-␣, have become available it is even more important to identify the patients at high risk of developing metastatic disease. 5 More research is also needed to improve our basic understanding on the biology of cutaneous melanoma.CD44 is a structurally variable and multifunctional cell surface glycoprotein expressed on most cell types. 6,7 Many functions of CD44 are mediated through interaction with its ligand hyaluronan (HA), 8 a ubiquitous extracellular polysaccharide. 9 HA is abundant in soft connective tissues, but also in epithelial and neural tissues. 8 HA organizes certain proteoglycans in the extracellular matrix, and facilitates cell migration and proliferation during embryogenesis, inflammation, and wound healing. 8 -11 The interaction of CD44 with HA contributes to tumor cell proliferation, 8,12 migration, 6,8,13-15 invasion, 6,8,16 and formation of meta...
Background-Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery, with an incidence of 20% to 40%. AF is associated with postoperative complications, including increased risk of stroke and need of additional treatment, as well as prolonged hospital stay and increased costs. It has been shown that prophylactic oral administration of -blocker therapy reduces the incidence of postoperative AF after cardiac surgery. However, it is possible that absorption of drugs is impaired after cardiopulmonary perfusion associated with cardiac surgery. The purpose of this prospective, controlled, randomized trial was to study compare intravenous and per oral metoprolol administration in the prevention of AF after cardiac surgery. Methods and Results-240 consecutive patients who were scheduled to undergo their first on-pump coronary artery bypass graft (CABG), aortic valve replacement, or combined aortic valve replacement and CABG were randomized to receive 48-hour infusion of metoprolol or oral metoprolol starting on the first postoperative morning. Patients were excluded if they had contraindications for -blocker or had to stay Ͼ1 day in the intensive care unit. Dosage of metoprolol was adjusted according to heart rate. The dosage was 1 to 3 mg/h in the intravenous group and from 25 mg twice per day to 50 mg 3 times per day in the oral group. The incidence of postoperative AF was significantly lower in the intravenous group than in the oral group (16.8% versus 28.1%, Pϭ0.036). No serious adverse effects were associated with intravenous metoprolol therapy. Conclusions-Our study suggests that intravenous metoprolol is well-tolerated and more effective than oral metoprolol in the prevention of AF after cardiac surgery.
The Finnish Foundation for Cardiovascular Research and the Kuopio University EVO Foundation.
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