Time and dose dependency of the suppression of pulmonary metastases of rat mammary cancer by amiloride.
Female; Animals; Rats; Drug Administration Schedule; Antineoplastic Agents/*administration & dosage; Neoplasm Transplantation; Amiloride/*administration & dosage; Lung Neoplasms/pathology/*prevention & control/*secondary; Plasminogen Activators/antagonists & inhibitors; Urokinase-Type Plasminogen Activator/antagonists & inhibitors; Dose-Response Relationship; Drug; Mammary Neoplasms; Experimental/*pathology; Inbred F344
Amiloride is an inhibitor of urokinase plasminogen activator (uPA), an essential component of the plasminogen/plasmin enzyme system. Inhibition of uPA prevents the conversion of plasminogen to tumor cell surface bound plasmin which is required for initiation of the metastatic process. MATB rat mammary cancer cells were introduced into the jugular venous system of 80 Fisher 344 female rats. Amiloride at high and low dosages was administered in the drinking water at the time of, prior to or several days following the tumor cell inoculation and continued daily for 10 days post inoculation. Control rats were maintained on water alone. The middle lobe of the right lung was examined microscopically for numbers of metastases. Suppression of metastases was significant at high amiloride dosages in all groups, and at low dosage when administered prior to inoculation. We conclude that amiloride suppresses induced metastases of rat mammary cancer, the effect being dose- and time-dependent.
Evans D M; Sloan-Stakleff K; Arvan M; Guyton D P
Clinical & experimental metastasis
1998
1998-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Reexamination of amphotropic murine leukemia virus neurovirulence: neural stem cell-mediated microglial infection fails to induce acute neurodegeneration.
*Leukemia Virus; *Reassortant Viruses/pathogenicity; Animals; Cell Line; Central Nervous System Diseases/*pathology/virology; Experimental/*pathology; Friend murine leukemia virus/genetics/pathogenicity; Leukemia; Mice; Microglia/pathology/virology; Murine/isolation & purification/pathogenicity; Newborn; Retroviridae Infections/*pathology; Tumor Virus Infections/*pathology; Viral Envelope Proteins/genetics/isolation & purification; Viremia; Virulence
The 4070A amphotropic murine leukemia virus (A-MuLV) has been variably reported to harbor neurovirulence determinants within its env gene. In this report we reexamined this issue by applying two approaches previously demonstrated to amplify murine leukemia virus neurovirulence. The first approach involved introducing the 4070A env gene into the background of Friend virus clone FB29 to enhance peripheral virus replication kinetics and central nervous system entry. The resulting chimeric virus, FrAmE, exhibited widespread vascular infection throughout the central nervous system (CNS); however, parenchymal infection was quite limited. Neither clinical neurological signs nor spongiform neurological changes accompanied FrAmE CNS infection. To overcome this CNS entry limitation, 4070A and FrAmE were delivered directly into the CNS via transplantation of infected C17.2 neural stem cells (NSCs). Significantly, NSC dissemination of either 4070A or FrAmE resulted in widespread, high-level amphotropic virus expression within the CNS parenchyma, including the infection of microglia, the critical target required for inducing neurodegeneration. Despite the extensive CNS infection, no associated clinical neurological signs or acute neuropathological changes were observed. Interestingly, we observed the frequent appearance of circulating polytropic (MCF) virus in the serum of amphotropic virus-infected animals. However, neither peripheral inoculation of an amphotropic/MCF virus mixture nor transplantation of NSCs expressing both amphotropic and MCF viruses induced acute clinical neurological signs or spongiform neuropathology. Thus, the results generated in this study suggest that the 4070A env gene is not inherently neurovirulent. However, the frequent appearance of endogenous MCF viruses suggests the possibility that the interactions of amphotropic viruses with endogenous retroviral elements could contribute to the development of retrovirus-induced neurodegenerative disease.
Traister Russell S; Lynch William P
Virology
2002
2002-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/viro.2001.1299" target="_blank" rel="noreferrer noopener">10.1006/viro.2001.1299</a>