The Characterization of Mass Transfer Factors in Neuroblastoma Implanted in Immunosuppressed Nude Rats

면역결핍누드쥐에 이식된 neuroblastoma에서의 물질전달에 미치는 인자의 특성

  • ;
  • G.R
  • Published : 1994.03.01

Abstract

The chemotherapy using macromolecules, i.e., monoclonal antibodies loaded with anticancer agents hasn't been successful in delivering therapeutic amount of the conjugates. The comprehensive evaluation of mass transfer factors in tumor is prerequisite for the development of the effective chemotherapy. Characterization of neuroblastoma implanted in immunosuppressed athymic nude rats was performed. Its growth kinetics, glucose metabolic rate (GMR) were measured along with the interstitial fluid pressure (IFP), blood perfusion rate (BPR) and pH distribution throughtout the tumor radius. Volume doubling time and GMR were 8.1 days(SD 0.44 day), 23.53 mg/min/100 g(SD 3.54 mg/min/100 g), respectively. The IFP in tumor center was increased with tumor volume, and approached to 3 mmHg (SD 2.6 mmHg) when the tumor was 3 cm high. The radial distribution of IFP, BPR and pH in 2 cm high tumors showed that BPR and pH were decreased, while IFP was increased as the ~ensors moved toward the tumor center. The elevated IFP, decreased BPR and pH in tumor center suggested that the delivery of conjugates might be increased by properly manipulating mass transfer factors.

단세포군항체(monoclonal antibody)를 이용한 항암제치료법이 다각적인 방면으로 실험되고 있으나, 환자에 주입된 단세포군항체중에서 실제의 암전달량은 언제나 기대치에 미치지 못하고 있다. 그러므로, 효과적인 항암제치료와 조기암진단을 위하여 암내부에서의 물질전달에 미치는 인자들의 포괄적인 측정이 필요하였다. 본 실험에서는 면역결핍누드쥐에 이식된 neurobastoma의 물질전달환경을 이해하기 위하여 성장특성과 포도당대사속도(GMR)를 측정하였으며, 세포간체액압력(IFP), 국부혈액속도(BPR)와 pH를 높이 2cm의 암에서 반경방향으로 측정하였다. 성장특성으로써 체적배가시간을, 세포활동성으로써 GMR를 측정하였더니, 각각 8.1일 (SD 0.44일), 23.53 mg/min/100g(SD 3.54 mg/min/100 g)이었다. 암중심 IFP는 암부피가 커짐에 따라 증가하여 높이 3cm의 암에서는 12.3mmHg(SD 2.6mmHg)이 되었다. 반경방향에 따른 IFP, BPR, pH를 특정한 결과, 암중심에 접근할수록 IFP는 증가되었고, 반면에 BPR과 pH는 감소되었다. 이로써 암내부에서의 증가된 IFP, 감소된 BPR과 pH가 단세포군항체와 그 공합체의 내부전달을 저해하는 원인으로 작용할 수 있다는 사실이 제시되었으며, 이들 인자들을 적당한 기술로 조절하여 더 많은 단세포군항체를 암내부로 전달시킬 수 있을 것으로 판단된다.

Keywords

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