Enhancing the uptake of chemotherapeutic drugs into tumors using an "artificial lymphatic system".
This paper presents findings from uptake studies to evaluate the ability of an "artificial lymphatic system" (ALS) to enhance large and small molecular weight drug transport into solid tumors and the therapeutic effect of the additional drug on their growth. These studies also served to test the effectiveness of an implantable multidrain ALS. Walker 256, Neuroblastoma, and Sarcoma dual-tumor models were used to evaluate the effect of ALS aspiration on the uptake of 3F8 monoclonal antibody, and doxorubicin. A tumor shrinkage experiment using Walker 256 dual tumors was used to evaluate the efficacy of an implantable ALS with cyclophosphamide chemotherapy. Drug uptake significantly increased in all aspirated tumors; 3F8 uptake was enhanced 37.4% in the Walker and 93.1% in the Neuroblastoma tumor lines (p<0.05). Doxorubicin uptake increased 23.2% in Sarcoma tumor (p<0.05). The shrinkage study demonstrated that one-drain aspirated tumors shrank 90% faster (p<0.01) than control tumors, while three-drain aspirated tumors shrank 123% faster than control tumors (p<0.01).
DiResta
G R
GR
Memorial Sloan Kettering Cancer Center's Department of Surgery/Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. direstag@mskcc.org
Lee
J
J
Healey
J H
JH
Larson
S M
SM
Arbit
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001187:Artificial Organs; D001693:Biological Transport, Active; D001698:Biomedical Engineering; D002279:Carcinoma 256, Walker / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008208:Lymphatic System; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D004317:Doxorubicin; D003520:Cyclophosphamide