Proteolysis of extracellular matrix by invadopodia facilitates human breast cancer cell invasion and is mediated by matrix metalloproteinases

Breast cancer cell lines vary in invasive behavior and one highly invasive cell line (MDA-MB-231) proteolytically degrades extracellular matrix with invadopodia (Thompson et al. 1992, J Cell Physiol, 150, 534-44; Chen et al 1994, Breast Cancer Res Treat, 31, 217-26). Invadopodial proteolysis of extracellular matrix is thought to be necessary for invasion; however, this has not been demonstrated directly. To obtain such evidence, normal (HBL-100) and malignant (MCF-7, MDA-MB-231) breast cells were evaluated for invadopodial proteolysis of extracellular matrix and invasive behavior. We report that invadopodial proteolysis of immobilized fibronectin is positively correlated with invasion of cells into type I collagen gels. Moreover, reducing the proteolytic activity of invadopodia with the metalloproteinase inhibitor, batimastat (BB-94), also decreases invasion indicating that breast cancer cell invasion is dependent upon proteolytically active invadopodia.     

Multiple myeloma with monoclonal surface immunoglobulin expression: a case report

BACKGROUND: Plasma cells from patients with multiple myeloma have been found to express the immunophenotype of normal plasma cells without surface immunoglobulin expression. CASE: A case occurred of multiple myeloma with monoclonal surface immunoglobulin expression, defined by morphology and flow cytometric immunophenotyping of a fine needle aspiration biopsy of an osteolytic rib lesion and a bone marrow aspirate as well as urine and serum protein electrophoresis with immunofixation. CONCLUSION: The clinical significance of monoclonal surface immunoglobulin expression in rare cases of multiple myeloma is uncertain, and other parameters with clinical significance (CD10 positivity, multiple myeloid antigen expression) will continue to be more useful until additional cases accrue.     

Euthanasia and doctor-assisted suicide: responses by oncologists and non-oncologists

Plasmatic arterial necrosis and microaneurysm of small arteries are preceded by smooth muscle cell loss and the rupture of these arterial lesions is a direct cause of hypertensive intracerebral hemorrhage. The hypertensive brainstem hemorrhage occur exclusively in the pons. To elucidate whether there are differences of underlying arterial lesions between each part of the brainstem or not, small arteries in normal 34 autopsied brainstems were investigated histologically and morphometrically. Histological study revealed the predilection of the occurrence of plasmatic arterial necrosis, microaneurysms and fibronodular arterial lesions in the hypertensive pons. These lesions occurred predominantly in the small arteries 100-300 microns in diameter in the basal part of hypertensive pons, and were rare in the other parts of hypertensive brainstems and in normotensive brainstems. A negative correlation between the ratio of number of smooth muscle cell nuclei to the area of tunica media and age was demonstrated morphometrically. The ratio in the hypertensive group was significantly lower than that of the normotensive group. In addition the mean ratio in the pons was significantly lower than that in the midbrain and the medulla oblongata in the hypertensive group. These results are consistent with the fact that the hypertensive brainstem hemorrhage predominantly occur in the pons and primary bleedings in the other parts of the brainstem are rare.     

Surgical management of ventricular tachycardia

BACKGROUND: Ventricular tachyarrhythmias are the leading cause of death from coronary artery disease. A small percentage of these arrhythmias originate in chronically ischemic myocardium, rather than acutely ischemic myocardium, and can be refractory to medical management. Epicardial mapping and focal cryoablation of foci demonstrating early activation may provide definitive therapy when pharmacologic management fails. We report a series of 42 consecutive patients with refractory ventricular tachycardia (VT) who were treated with open epicardial mapping and focal cryoablation after pharmacologic management failed. METHODS: We retrospectively reviewed the records of patients who underwent surgical treatment of malignant VT. For patients not recently seen in the clinic, we conducted telephone interviews. At the time of operation, epicardial mapping was performed to locate foci of early electrical activation. These foci were then cryoablated, using 2-minute applications of liquid nitrogen-cooled probes. All patients underwent postoperative electrophysiologic studies to test for inducible VT. RESULTS: Of these 42 patients, 34 (81%) were male, 8 (19%) female. Average age was 62.9 +/- 10.6 years; ejection fraction, 0.20 (range, 0.04 to 0.50); and number of foci ablated, 2.1 +/- 1.1 (range, 1 to 6). At the time of cryoablation, all patients underwent additional procedures, including aneurysmectomy, coronary artery bypass, or valve replacement. The 30-day operative mortality was 9.5% (4 of 42). Of the 38 survivors, 36 (94.7%) were clinically free of VT; the remaining 2 had spontaneous or inducible VT. CONCLUSIONS: Open cryoablation of foci propagating VT appears to be safe and effective. It may be the most definitive treatment for malignant VT.     

Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice

The T cell protein tyrosine phosphatase (TC-PTP) is one of the most abundant mammalian tyrosine phosphatases in hematopoietic cells; however, its role in hematopoietic cell function remains unknown. In this report, we investigated the physiological function(s) of TC-PTP by generating TC-PTP-deficient mutant mice. The three genotypes (+/+, +/-, -/-) showed mendelian segregation at birth (1:2:1) demonstrating that the absence of TC-PTP was not lethal in utero, but all homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly, and lymphadenopathy. Homozygous mice exhibited specific defects in bone marrow (BM), B cell lymphopoiesis, and erythropoiesis, as well as impaired T and B cell functions. However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected. BM transplantation experiments showed that hematopoietic failure in TC-PTP -/- animals was not due to a stem cell defect, but rather to a stromal cell deficiency. This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.     

Autologous versus allogeneic T cell-stimulated IL-6 production by dermal fibroblasts

T cells adhere to human dermal fibroblasts (HDF). This cellular interaction leads to a pronounced secretion of the proinflammatory cytokines IL-6 and IL-8 via a juxtacrine stimulation induced by HDF-associated IL-1. Upon stimulation, fibroblasts express various surface proteins such as MCH-I molecules, which may interact with corresponding receptors on T cells. The present study was conducted to further investigate the mechanism of this complex interaction with regard to the secretion of IL-6 in cocultures of T cells and HDF. IL-6 was time- and dose-dependently upregulated in such cocultures. Spatial separation of the cells by microporous membranes resulted in a 90% reduction of IL-6 secretion, but when cells had limited cell contact IL-6 secretion was increased again. Allogeneic cocultures of T cells and HDF showed increased capacity of IL-6 stimulation as compared to autologous cultures. Our results suggest that MHC-I/T cell receptor interaction modulates IL-6 secretion in allogeneic and autologous cocultures.     

Impulsive and self-control choices in opioid-dependent patients and non-drug-using control patients: Drug and monetary rewards.

Delay discounting was investigated in opioid-dependent and non-drug-using control participants. The latter participants were matched to the former on age, gender, education, and IQ. Participants in both groups chose between hypothetical monetary rewards available either immediately or after a delay. Delayed rewards were $ 1,000, and the immediate-reward amount was adjusted until choices reflected indifference. This procedure was repeated at each of 7 delays (1 week to 25 years). Opioid-dependent participants were given a second series of choices between immediate and delayed heroin, using the same procedures (i.e., the amount of delayed heroin was that which could be purchased with $1,000). Opioid-dependent participants discounted delayed monetary rewards significantly more than did non-drug-using participants. Furthermore opioid-dependent participants discounted delayed heroin significantly more than delayed money. (PsycINFO Database Record (c) 2010 APA, all rights reserved)