Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases.

One of the many features of the malignant phenotype, in vitro and in vivo, is elevated heparanase production and activity. Using in vitro model systems, we examined the capacity of murine (B16B15b) and human (70W) brain-metastatic melanoma cells to degrade the subendothelial matrix produced by endothelial cell monolayer cultures. B16B15b and 70W melanoma cells solubilized sulfated matrix proteoglycans at levels significantly higher than their parental lines (B16F1, MeWo).

Human melanoma cell invasion: selected neurotrophin enhancement of invasion and heparanase activity.

Heparanase is an endo-beta-D-glucuronidase whose enzymatic targets are the glycosaminoglycan chains of heparan sulfate proteoglycans. Elevated levels of heparanase are associated with the metastatic potential of melanoma cells. Treatment of murine and human melanoma cells with the prototypic neurotrophin nerve growth factor (NGF) increases the production of heparanase by melanoma cells.

Heparanase and a synthetic peptide of heparan sulfate-interacting protein recognize common sites on cell surface and extracellular matrix heparan sulfate.

Heparanase is an endo-beta-D-glucuronidase that degrades the glycosaminoglycan chains of heparan sulfate (HS) proteoglycans at specific sites. Elevated levels of heparanase are associated with the metastatic potential of melanoma and other types of tumor cells. We previously reported heparanase degradation of cell surface HS subpopulations of the human adenocarcinoma cell line RL95.

Neurotrophin stimulation of human melanoma cell invasion: selected enhancement of heparanase activity and heparanase degradation of specific heparan sulfate subpopulations.

Heparanase is an endo-beta-D-glucuronidase whose enzymatic targets are the glycosaminoglycan chains of heparan sulfate proteoglycans (50). Elevated levels of heparanase are associated with the metastatic potential of melanoma cells, and treatment of murine and human melanoma cells with the prototypic neurotrophin nerve growth factor (NGF) increases the production of heparanase by melanoma cells. We previously reported that physiological concentrations of NGF increased invasion of early passage human brain-metastatic 70W melanoma cells but not melanoma cells metastatic to other sites or nonmetastatic melanoma cells as measured in Matrigel invasion assays.

Death due to a leiomyosarcoma of the pulmonary artery.

Leiomyosarcomas of the pulmonary arteries are rare neoplasms seldom diagnosed during the patient's lifetime. We report a case of unexpected death in a 44-year-old man due to a leiomyosarcoma originating from the main pulmonary trunk and involving the right and left arteries as far as the lobar ramifications. The patient died after a 2-year history of bronchiectasis and chronic bronchopneumonia with weight loss and occasional episodes of syncope during the last 4 months.

Comparison of capillary blood versus venous blood samples in the assessment of immunity to measles.

Seroepidemiological investigations are essential for assessing the efficacy of measles vaccination programmes. However, when large-scale sampling is needed, a major difficulty is the problem of taking venous blood, especially in children. An alternative method is the collection of capillary blood samples spotted on filter papers.

Left ventricular aneurysm caused by blunt chest trauma.

A case of unexpected death associated with an aneurysm of the left ventricle caused by nonpenetrating chest trauma is described. A review of the more recent literature on the incidence, pathological course, and prognosis of the posttraumatic ventricular aneurysm pointed out the necessity of suspecting cardiac damage in cases of blunt chest trauma especially when major injuries may obscure heart involvement.

IgG avidity in the serodiagnosis of acute Toxoplasma gondii infection: a multicenter study.

OBJECTIVE: To evaluate the validity of the IgG avidity test in the serodiagnosis of acute T. gondii infection; to verify the maturation of IgG avidity during the course of infection; to observe whether the kinetics of IgG maturation could be affected by antibiotic treatment. METHODS: Serial serum samples, collected in three Italian hospitals (Perugia, Treviso and Bologna), from untreated and antibiotic-treated patients with primary toxoplasmic infection, were assayed for IgG avidity, and IgM and IgA positivity.

Neurotrophin stimulation of human melanoma cell invasion: selected enhancement of heparanase activity and heparanase degradation of specific heparan sulfate subpopulations.

Heparanase is an endo-beta-D-glucuronidase, the enzymatic targets of which are the glycosaminoglycan chains of heparan sulfate proteoglycans. Elevated levels of heparanase are associated with the metastatic potential of melanoma cells. Treatment of murine and human melanoma cells with the prototypic neurotrophin nerve growth factor (NGF) increases the production of heparanase by melanoma cells.

Inverse expression of neurotrophins and neurotrophin receptors at the invasion front of human-melanoma brain metastases.

Neurotrophins (NT), such as nerve growth factor (NGF), stimulate the growth and differentiation of several neuronal subpopulations in a distinct yet overlapping manner. Brain-metastatic human melanoma cells overexpress p75(NTR), the low-affinity neurotrophin receptor, and treatment of brain-metastatic cells with NGF stimulates extracellular matrix invasion and production of degradative enzymes in relation to the cellular expression of p75(NTR) Although human melanoma cells express high affinity neurotrophin receptors, such as TrkC (the putative receptor for NT-3), they do not express TrkA, the high-affinity NGF receptor. Using digoxigenin-labeled sense/antisense riboprobes against human p75(NTR) and NGF for in situ hybridization, we determined whether the expression of p75(NTR) and NGF mRNAs are related to brain metastasis of human melanoma.

Abnormal expression of perlecan proteoglycan in metastatic melanomas.

Abnormal expression of proteoglycans has been implicated in cancer and metastasis primarily because these macromolecules are involved in the control of cell growth and matrix assembly. In this report, we have investigated the expression and immunolocalization of perlecan, a major heparan sulfate proteoglycan of basement membranes and pericellular matrices, in human metastatic melanomas. Twenty-six of the 27 tumor samples showed a significant increase (up to 15-fold) in the perlecan mRNA levels when compared with normal tissue.

Tumor metastasis to brain: role of endothelial cells, neurotrophins, and paracrine growth factors.

An important clinical endpoint in patients with cancer is formation of metastases in the brain. Understanding this phenomenon is important in several types of malignancies, including melanoma, lung and breast cancers. Metastatic tumor cells use specific adhesion molecules to home to brain, and there they must attach to microvessel endothelial cells and respond to brain endothelial cell-derived motility factors and brain invasion factors to invade the CNS.

Involvement of neurotrophins and growth factors in brain metastasis formation.

The formation of brain metastases is an important clinical end point in patients with cancer. The brain provides a unique microenvironment enclosed by the skull, lacking lymphatic drainage and maintaining a highly regulated vascular transport barrier. In the brain microcirculation, brain-metastatic tumor cells must attach to endothelial cells, respond to brain-derived invasion factors, and invade the blood-brain barrier.

Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trkA.

Although overexpression of the low-affinity p75 neurotrophin receptor (p75NTR) is frequently associated with advanced stages of human melanoma progression, the functional significance of this finding is unknown. We examined whether the degree of cell surface expression of p75NTR in human melanoma cell variants determines their extent of invasion stimulated by nerve growth factor (NGF). Treatment of MeWo melanoma cells or a metastatic spontaneous wheat germ agglutinin-resistant variant subline (70W) of MeWo cells with 2.

Nerve growth factor effects on human and mouse melanoma cell invasion and heparanase production.

The role of growth factor networks in regulating the progression of human melanocytes towards tumorigenicity and ultimately the malignant phenotype is poorly understood. In particular, the autocrine and paracrine influences that modulate cellular invasion and extracellular matrix degradative enzymes of melanoma cells remain undefined at the molecular level. We report here that nerve growth factor (NGF) can modify some metastasis-associated cellular properties of human and mouse melanoma cells.

Treatment of advanced ovarian carcinoma in the elderly.

This study retrospectively analyzes the treatment of advanced ovarian cancer (Stages III and IV) in elderly patients (> or = 65) compared to that in younger patients (< 65). The purpose of this study was to identify possible treatment bias toward the elderly and to statistically analyze the nature of these differences. Seventy patients were evaluated of which 29 were identified as elderly and 41 as young.

Malignant melanoma metastasis to brain: role of degradative enzymes and responses to paracrine growth factors.

Mouse and human melanoma cells metastatic to the brain express degradative enzyme activities that are used for invasion of brain basement membrane and parenchyma. Compared to poorly metastatic or lung- or ovary-metastatic murine melanoma lines, the brain-metastatic sublines secreted higher levels of a variety of degradative enzymes. Brain-metastatic murine and human melanoma cells also degraded subendothelial basement membrane and reconstituted basement membrane at rates higher than other metastatic melanoma cells.

Ontogeny of high- and low-affinity nerve growth factor receptors in the lumbar spinal cord of the developing chick embryo.

The binding of 125I-labeled nerve growth factor-beta (NGF) to soluble extracts of intact or dissociated embryonic chick lumbar cords was used to investigate the kinetic properties and to quantify the levels of NGF receptors (NGFRs) in the developing chick between Embryonic Day 6 (E6) and E10. Both high-affinity (type I; Kd = 7.4 x 10(-11) M) and low-affinity (type II; Kd = 2.

Ovarian endodermal sinus tumor associated with pregnancy: review of the literature.

Endodermal sinus tumor is the second most common malignant germ cell tumor of the ovary and its reported concurrence with pregnancy is extremely rare. This report is the 10th case of endodermal sinus tumor associated with pregnancy and also reviews the previous literature regarding the subject.

Characterization of nerve growth factor binding to embryonic rat spinal cord neurons.

The binding of iodinated beta-nerve growth factor, [125I]-NGF, to embryonic (E16) rat spinal cord cells, was investigated to characterize the binding properties and cellular distribution of nerve growth factor receptors. Spinal cord cells prepared without trypsin yielded two classes of NGF binding sites with Kd's of 3 x 10(-11) M and 4 x 10(-9) M. Fractionation of the cells by discontinuous gradients composed of 8%, 12%, and 17% metrizamide was used to separate motoneurons from other cell types.

Rescue of motoneurons from cell death by a purified skeletal muscle polypeptide: effects of the ChAT development factor, CDF.

Rat skeletal muscle contains a 22 kd polypeptide that increases the level of choline acetyltransferase (ChAT) activity in cultures of embryonic rat spinal cord neurons and has been purified to homogeneity. The application of this factor, ChAT development factor or CDF, to developing chick embryos during the period of naturally occurring motoneuron cell death significantly increased the survival of motoneurons but did not affect the survival of dorsal root ganglion neurons or sympathetic preganglionic neurons (column of Terni). These results provide the first demonstration that an isolated, skeletal muscle-derived molecule can selectively enhance the survival of motoneurons in vivo and suggest that CDF may function in vivo to regulate the survival and development of motoneurons.

Pelvic radiation in stage I endometrial adenocarcinoma with high-risk attributes.

From 1977 to 1987, 45 patients with FIGO stage I endometrial adenocarcinoma with high-risk attributes and disease confined to the pelvis were prospectively treated with postoperative pelvic radiation. By study design, all patients underwent staging laparotomy with pelvic and paraaortic lymphadenectomy. All patients had either grade 1 or 2 adenocarcinoma and greater than 50% myometrial invasion or grade 3 adenocarcinoma with less than or greater than 50% myometrial invasion.

Nerve growth factor activity and aging in CNS.

This is a discussion of aging in CNS and the influence of the nerve growth factor (NGF) protein. The paper considers neuronal plasticity and neuronotrophic substances, neuronal cell death and the nerve growth factor protein, including its effects, receptors, and model systems for the study of CNS aging.