Lymphatic metastasis of transplantable animal neoplasms

Résumé L'injection de 5 millions de cellules tumorales RD3 dans la patte du rat, fait apparaître des dépôts métastasique sous forme de ganglions lymphatiques poplitétaux. L'examen histologique détaillé montre qu'ils sont vraies métastases. Des résultats pareils sont apparus dans 2 autres tumeurs qui étaient histologiquement malignes, mais non dans celles qui étaient bénignes. Cette technique semble convenir à étude de la métastase lymphatique.     

Lymphatic metastasis of tumour; persistent transport of cells

Summary A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumou cells was continuou over periods up to 90 min and ranged from 10²–10⁵ cells/min.Acknowledgment. This work was supported by a grant from the National Cancer Institute of Canada to C.R.F. and I.C. We are grateful to Mrs W. Kao and Mr I. Etches for meticulous technical help and to the Photographic Section, Department of Pathology for illustrations. Dr V.S. Gupta of Veterinary Physiology, University of Saskatchewan supplied the tumour for transplantation.     

Lymphatic metastasis of tumour; persistent transport of cells.

A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumour cells was continuous over periods up to 90 min and ranged from 10(2)-10(5) cells/min.     

The plasminogen activation system in tumor growth, invasion, and metastasis

Generation of the serine proteinase plasmin from the extracellular zymogen plasminogen can be catalyzed by either of two other serine proteinases, the urokinase- and tissue-type plasminogen activators (uPA and tPA). The plasminogen activation system also includes the serpins PAI-1 and PAI-2, and the uPA receptor (uPAR). Many findings, gathered over several decades, strongly suggest an important and causal role for uPA-catalyzed plasmin generation in cancer cell invasion through the extracellular matrix. Recent evidence suggests that the uPA system is also involved in cancer cell-directed tissue remodeling. Moreover, the system also supports cell migration and invasion by plasmin-independent mechanisms, including multiple interactions between uPA, uPAR, PAI-1, extracellular matrix proteins, integrins, endocytosis receptors, and growth factors. These interactions seem to allow temporal and spatial reorganizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion. The increased knowledge about the plasminogen activation system may allow utilization of its components as targets for anti-invasive therapy.     

Lymphatic fibrinolysis in rats

Zusammenfassung Ratten zeigen regelmässig zu bestimmten Zeiten nach Ductus-Thoracicus-Kannulierung eine hohe, unter Umständen durch Stress induzierte fibrinolytische Aktivität in der Lymphe; diese Aktivität braucht nicht von einer plasmatischen Fibrinolyse begleitet zu sein.     

Lymphatic drainage of the brain

Zusammenfassung In krassem Gegensatz zur heute herrschenden Auffassung spielt eine Lymphdrainage beim Flüssigkeitskreislauf des Gehirns eine ausschlaggebende Rolle. Werden die zervikalen Lymphbahnen verschlossen, so entsteht eine lymphostatische Enzephalopathie, welche u.a. durch ein Hirnödem, Ganglienzell- und Myelinveränderungen sowie durch Beeinträchtigung der Funktion des Zentralnervensystems gekennzeichnet ist. Es wird ein Durchbruch der Lymphologie in das Gebiet der Neurologie und Neuropathologie gefordert und darauf hingewiesen, dass bei der Pathologie des Hirnödems die Rolle der Lymphzirkulation nicht ausser acht gelassen werden sollte.     

Matrix metalloproteinases in tumor invasion

Controlled degradation of extracellular matrix (ECM) is essential for the growth, invasion, and metastasis of malignant tumors, and for tumor-induced angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all ECM components and they apparently play an important role in all these aspects of tumor development. Furthermore, recent evidence suggests that MMPs also play a role in tumor cell survival. In this review, we discuss the current concept concerning the role of MMPs and their inhibitors in tumor invasion, as a basis for prognosis and targeted therapeutic intervention in cancer.     

Molecular targets of glioma invasion

Glioblastoma multiforme is the most common and lethal primary malignant brain tumor. Although considerable progress has been made in technical proficiencies of surgical and radiation treatment for brain tumor patients, the impact of these advances on clinical outcome has been disappointing, with median survival time not exceeding 15 months. Over the last 30 years, no significant increase in survival of patients suffering from this disease has been achieved. A fundamental source of the management challenge presented in glioma patients is the insidious propensity of tumor invasion into distant brain tissue. Invasive tumor cells escape surgical removal and geographically dodge lethal radiation exposure and chemotherapy. Recent improved understanding of biochemical and molecular determinants of glioma cell invasion provide valuable insight into the underlying biological features of the disease, as well as illuminating possible new therapeutic targets. These findings are moving forward to translational research and clinical trials as novel antiglioma therapies. Received 25 July 2006; received after revision 27 October 2006; accepted 22 November 2006     

The invasion and growth ofBabesia bovis in tick tissue culture

Summary Erythrocytic forms ofBabesia bovis inoculated into cell cultures of the tickBoophilus microplus invaded the tick cells and showed multiplication for up to 48 h after inoculation.Acknowledgment. We thank Mr. G.B. Mirre and Mrs M. Steinhoffer for able technical assistance during the course of the work. We also thank Dr. H.M.D. Hoyte, Parasitology Department, University of Queensland, for the use of an electron microscope. The work was supported by funds from the Australian Meat Research Committee.     

Mechanisms of cellular invasion by intracellular parasites

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world’s population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite–host cell interactions, forming the basis of the parasite’s cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.     

Inhibition of invasion and intraerythrocytic development ofPlasmodium falciparum by kinase inhibitors

We have examined the effects of seven protein kinase inhibitors (staurosporine, genistein, methyl 2,5-dihydroxycinnamate, tyrphostins B44 and B46, lavendustin A and R03) on the erythrocytic cycle of the malaria parasite,Plasmodium falciparum. One (staurosporine) strongly inhibits serine/threonine kinases, but the remainder all exhibit a strong preference for tyrosine kinases. We have been able to discriminate between effects on invasion and on intraerythrocytic development. All reagents impeded development of intraerythrocytic parasites, though at widely differing concentrations, from the sub-micromolar to the millimolar. Several inhibitors, including staurosporine, also reduced invasion. The phosphatase inhibitor, okadaic acid, had a strong inhibitory effect both on invasion and development. The regulation of malaria development by phosphorylation or dephosphorylation reactions at several points in the blood-stage cycle is implied.