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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-4-18
pubmed:abstractText
Matrix metalloproteinases (MMPs) have been implicated in the growth and invasiveness of primary and metastatic tumors. Hypothesizing that MMP inhibition would slow cancer growth, the MMP inhibitor BB-94 (batimistat) was evaluated in an orthotopic animal model of human pancreatic carcinoma. Ten million human pancreatic cancer cells were surgically implanted into the pancreata of 30 athymic nu/nu mice. Intraperitoneal administration of 30 mg/kg BB-94 or vehicle control began 7 days after tumor implantation (13 mice with confirmed implantations in each group) and continued daily for 21 days, and then three times weekly until death or sacrifice at day 70. Representative tumors harvested from mice in each group were analyzed for presence and activity of MMP-2 and MMP-9. Animal weights were significantly higher in the BB-94-treated group at sacrifice (mean 58.4 +/- 7.9 g vs. 39.8 +/- 6.2 g; P < 0.05, Student's t test). The likelihood of survival to 70 days was significantly higher in the treated group (4 of 13 vs. 0 of 13, P < 0.05, Z-test for end points) than in the control group as was overall survival (P = 0.03, Wilcoxon test). Nine mice in the control group developed metastases to the liver, peritoneum, abdominal wall, or local lymph nodes, whereas only two mice in the BB-94 group had evidence of metastatic disease (P < 0.02, Fisher's exact test), in both instances confined to the abdominal wall. Tumors from treated mice manifested lower MMP activity than those from control animals. These reports support the use of MMP inhibitors alone or as an adjunct in the treatment of pancreatic cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1091-255X
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
614-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11307097-Adenocarcinoma, pubmed-meshheading:11307097-Animals, pubmed-meshheading:11307097-Biopsy, Needle, pubmed-meshheading:11307097-Confidence Intervals, pubmed-meshheading:11307097-Disease Models, Animal, pubmed-meshheading:11307097-Humans, pubmed-meshheading:11307097-Immunohistochemistry, pubmed-meshheading:11307097-Metalloendopeptidases, pubmed-meshheading:11307097-Mice, pubmed-meshheading:11307097-Mice, Nude, pubmed-meshheading:11307097-Neoplasms, Experimental, pubmed-meshheading:11307097-Pancreatic Neoplasms, pubmed-meshheading:11307097-Phenylalanine, pubmed-meshheading:11307097-Reference Values, pubmed-meshheading:11307097-Statistics, Nonparametric, pubmed-meshheading:11307097-Survival Rate, pubmed-meshheading:11307097-Thiophenes, pubmed-meshheading:11307097-Treatment Outcome
pubmed:articleTitle
Matrix metalloproteinase inhibition improves survival in an orthotopic model of human pancreatic cancer.
pubmed:affiliation
Department of Surgical Oncology, Ohio State University, Columbus, Ohio 43210, USA.
pubmed:publicationType
Journal Article, Comparative Study