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Artificial Lymphatic System

I ran across these articles researching lymphedema and possible treatment processes and found it intriguing. These three abstracts are the only information I could locate on an artificial lymphatic system.

As soon as I can secure further information, I will update the page.

Pat

See also: My Life with Lymphedema and Lymphoma

Use of an Artificial Lymphatic System During Carboplatin Infusion to Improve Canine Osteosarcoma Blood Flow and Clinical Response

2007

Gene R. DiResta, PhD1, Sean W. Aiken, DVM2, Holly K. Brown, MD1, Philip J. Bergman, DVM, PhD2, Ann Hohenhaus, DVM2, E. J. Ehrhart, DVM, PhD3, Keith Baer, DVM2 and John H. Healey, MD1 1 Orthopaedic Surgical Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021-6007 2 The Animal Medical Center, 510 E 62nd Street, New York, New York 10021 3 College of Veterinary Medicine and Biomedical Science, Colorado State University, Ft. Collins, Colorado 80523 Correspondence: Address correspondence and reprint requests to: Gene R. DiResta, PhD; E-mail: direstag@mskcc.org

Background: The artificial lymphatic system (ALS), a mechanical system designed to reduce increased interstitial fluid pressure in solid tumors and enhance the delivery of chemotherapy, was evaluated within a randomized clinical trial treating spontaneously occurring canine appendicular osteosarcoma (OS), a tumor similar to its human OS counterpart.

Methods: An ALS was investigated for its ability to increase OS blood flow and increase uptake of intravenously administered carboplatin.

Results: Blood flow increased by 314% in tumors with active ALS drains versus 126% in control tumors (P < .03). Tumor carboplatin uptake increased by 51% after drain activation (P = .07). Microvascular density (MVD) was measured in tumors after surgical amputation and in corresponding bone regions in a cohort of normal dogs. The OS tumors had equivalent MVD as normal bone, and MVD was higher in the humerus than the femur (P < .03) in both tumor and normal bone. Median survival between the ALS-treated and control cohorts was not different despite increased drug uptake or ALS manipulation. Compared with historic controls, ALS drain insertion into tumors to reduce interstitial fluid pressure did not worsen the prognosis.

Conclusions: The findings in canine spontaneously occurring OS indicate that an ALS may be of value as a chemotherapy adjunct for enhancing the delivery of chemotherapy to tumor interstitium.

Key Words: Osteosarcoma • Carboplatin • Blood flow • Interstitial fluid pressure • Microvessel density • Canine • Artificial lymphatic system

Annals of Surgical Oncology

Enhancing the Uptake of Chemotherapeutic Drugs into Tumors using an “Artificial Lymphatic System”

May, 2000

Gene R. DiResta1, Jongbin Lee2, John H. Healey1, Steven M. Larson2 and Ehud Arbit3 (1) Department of Surgery/Orthopaedic Service, Memorial Sloan Kettering Cancer Centers, USA (2) Nuclear Medicine Research Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY (3) Department of Surgery, Staten Island University Medical Centers, New York, NY

Abstract

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). © 2000 Biomedical Engineering Society. PAC00: 8719Tt, 8719Xx, 8780-y, 8719Uv

Key Words Interstitial fluid pressure - Artificial lymphatic system - Walker 256 - Sarcoma - 3F8 - NMB-7 Neuroblastoma - Doxorubicin - Monoclonal antibody - Cyclophosphamide

Springer Link

Artificial Lymphatic System: A New Approach to Reduce Interstitial Hypertension and Increase Blood Flow, pH and pO2 in Solid Tumors

May, 2000

Gene R. DiResta1, Jongbin Lee2, John H. Healey1, Andrey Levchenko2, Steven M. Larson2 and Ehud Arbit3 (1) Department of Surgery/Orthopaedic Service, Memorial Sloan Kettering Cancer Centers, USA (2) Nuclear Medicine Research Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY (3) Department of Surgery, Staten Island University Medical Centers, New York, NY

Abstract

A mechanical drainage system, the artificial lymphatic system (ALS), consisting of a vacuum source and drain, is evaluated for its ability to aspirate the interstitial fluids responsible for the elevated interstitial fluid pressure (IFP) observed in solid tumors. IFP, pH, and pO2 radial profiles were measured before and after aspiration using wick-in-needle (WIN) probes, needle pH and oxygen electrodes, respectively. Laser Doppler flowmetry measured temporal changes in blood flow rate (BFR) at the tumor surface during aspiration. The WIN probe and IFP profile data were analyzed using numerical simulation and distributed mathematical models, respectively. The model parameter, p E reflecting central tumor IFP, was reduced from 15.3 to 5.7 mm Hg in neuroblastoma and from 13.3 to 12.1 mm Hg in Walker 256, respectively, following aspiration. The simulation demonstrated that spatial averaging inherent in WIN measurements reduced the calculated magnitude of the model parameter changes. IFP was significantly lower (p < 0.05), especially in regions surrounding the drain, and BFR was significantly higher (p < 0.05) following 25 and 45 min of aspiration, respectively; pH and pO2 profiles increased following aspiration. The experimental and mathematical findings suggest that ALS aspiration may be a viable way of reducing IFP and increasing BFR, pO2 and pH and should enhance solid tumor chemo and radiation therapy. © 2000 Biomedical Engineering Society. PAC00: 8719Tt, 8715Vv, 8719Uv, 8780-y, 8719Xx

Key Words Interstitial fluid pressure - Artificial lymphatic system - Walker 256 mammary carcinoma - Monoclonal antibody 3F8 - NMB-7 neuroblastoma - Tumor blood flow - pH and pO2.

Springer Link

Researchers Mimic the Lymphatic System in Animal Alternative Chip

Posted: January 22, 2010

A partnership between Hurel Corp. and L'Oréal has resulted in a chip that may replace skin allergy testing on animals. While the researchers report there is still work to do before the Allergy Test on a Chip is commercially available, they find that it could offer an alternative by late 2011 before the EU ban on animal testing is enforced in 2013.

The chip was designed to replace the local lymph node assay (LLNA), a test often performed on raw materials for cosmetics. In addition to saving animals, the chip is also said to be less expensive than animal testing.

The chip is said to show an allergic reaction similar to the allergic reaction seen in animals. The chip is comprised of an artificial lymph node of cultured cells next to an artificial skin construct made from cultured human cells. The artificial lymph node is connected to the skin with a microfluidic system made of channels filled with a specially maintained chemical gradient. To use the chip, the chemical product being tested would be put into contact with the artificial skin. In an allergic reaction, dendritic cells would migrate toward the artificial lymph node in response to the chemical gradient, where they would stimulate the T-cells

Similarly to when an animal experiences a skin allergy, dendritic cells from the skin migrate to the lymph node through lymphatic fluid. At the lymph node, the dendritic cells stimulate T-cells, thus creating an allergic reaction.

Hurel developed a working microfluidic portion of the chip, with the other portions of the chip remaining. Also, the research team still faces challenges before the chip is ready, such as determining how to measure the allergic response. To do so, it will monitor the response of the T-cells, which could involve monitoring T-cell proliferation, secreted molecules or both.

Further information on the design and use of this animal alternative will be published in Cosmetics & Toiletries magazine's March 2010 issue, “In Sight” interview.

http://www.cosmeticsandtoiletries.com/testing/animalalt/82415027.html?page=1

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artificial_lymphatic_system.txt · Last modified: 2012/10/16 14:40 (external edit)