A novel early-stage orthotopic model for ovarian cancer in the Fischer 344 rat.

The purpose of our study was to ascertain the progression of metastases in a novel ovarian cancer model designed to mimic early-stage disease by utilizing an orthotopic injection technique. Female Fischer 344 rats were injected with either 10(4) or 10(5) NuTu-19 cells by intraperitoneal or orthotopic injection. Peritoneal washings and histologic specimens were examined to correlate the incidence and extent of tumor growth. In a second phase, orthotopic injections of 10(2) and 10(3) cells were compared to that of 10(4) cells. Progression of ovarian cancer was observed by gross and microscopic examinations in both intraperitoneal and orthotopic models. Pelvic extension and abdominal adhesions uniquely characterized the orthotopically injected animals. Numbers of identifiable metastases declined with lower cell inocula, confirming that early-stage disease was extended to at least 14 days with 10(2) NuTu-19 cells. The orthotopic ovarian cancer model emulates early disease with the initiation of a primary tumor that is localized within the inherent microenvironment. The orthotopic model offers a clinically relevant alternative for future cancer research that allows for the investigation of therapeutic strategies against early stages of the disease process.

Maximum effect of urokinase plasminogen activator inhibitors in the control of invasion and metastasis of rat mammary cancer.

Experimentally induced pulmonary metastases of mammary cancer in the Fisher 344 rat can be suppressed by the inhibition of urokinase plasminogen activator (uPA). The inhibition of uPA with amiloride or B428 has been shown to be dose dependent. Increased dosage levels of inhibitors might be expected to enhance levels of suppression of metastases. The use of each of these inhibitors at equipotent concentrations that exceeded the doses administered in previous studies failed to eliminate pulmonary metastases. These results demonstrate that a maximum limit is attained for the inhibitory capacities on cells during in vitro invasion or in vivo metastasis. At increased levels, uPA inhibitors continue to suppress, but do not eradicate, experimental pulmonary metastases of MATB cell rat mammary cancer.