The Expressing Level Of Bradykinin B₂ Receptor On Glioma And Brain Metastases From Lung Cancer And Its Clinical Significance

IntroductionBrain metastases from lung cancer and gliomas are the prevalent type of brain tumor. brain tumor capillaries have a blood - tumor barrier (BTB) that limits adequate delivery of antitumor agents to tumor tissue. So the effect of anti-tumor agents is very tiny. Recently, many scholars devote to the research of biochemical opening of the BTB with vasoactive compounds, the most effective compound opening the BTB is bradykinin or its analog receptor - mediated perme-abilizer - 7 ( RMP - 7). Studies have demonstrated that intracarotid infusion of bradykinin allows enhanced delivery of drugs across the BTB to brain tumors up to 12 times more than saline infusion alone,with no delivery to normal brain. Intracarotid infusion of bradykinin analog , RMP — 7, selectively increases transport of carboplatin into brain tumor, which extends the survival of patients with glioma. Therefore , intracarotid infusion of bradykinin has been used to selectively open the BTB for the delivery of therapeutic drugs. But study suggested that there is very difference of increase of BTB permeability induced by bradykinin in brain tumors. We speculate that the variability in response of tumors to bradykinin is likely related to the expressing level of bradykinin B₂ receptor of tumor. This study used metastases from lung cancer and gliomas samples to determine expressing level of bradykinin B₂ receptor with immunohistochemistry (SP) on those tumors and analyze the difference. The result would provide experimental basis for recognizing the reason for variability in response of brain tumors to bradykinin and clinical application of bradykinin.MethodsBradykinin B2 receptor of 30 patients of glioma and 20 patients of brain me-tastases from lung cancer were examined with immuno - histochemistry ( SP) to analyze the expressing level of bradykinin B2 receptor on gliomas and brain me-tastases from lung cancer.ResultsThere was no expressing of bradykinin B2 receptor on brain metastases from lung cancer . But there was on glioma. Bradykinin B2 receptor localized on tumor cells. In three groups of different pathological grade of glioma. The expressing level of bradykinin B2 receptor expressed as the positive position area ratio of bradykinin B2 recptor, the results, the grade I and gradll (2.51% ± 0.72%vs4.21% ±0.85%,n = 10,t=4.813,P < 0.001), grade I and grade 1(2.51% ±0.72%vs7.77% ±1.66% ,n = 10,t =9. 189,P < 0.001), grade II andgradel(4.21% ±0.85% vs7.77% ± 1.66% ,n = 10,t =6.057,P < 0.001). there was a positive correlation between the positive area ratio of bradykinin B2 receptor and the pathological grade of glioma (r =0. 877 ,p <0. 001). as grade I < grade II < grade IH.ConclusionThere was no expressing of bradykinin B2 receptor on brain metastases from lung cancer, but there was on glioma. Bradykinin B2 receptor localized on tumor cells. There was a positive correlation between the expressing level of bradykinin B2 receptor and pathological grade of gliomas, the difference of the expressing level of different tumors may be the reason of the diverse cure effects of increase of blood tumor barrier permability induced by bradykinin and its analog.