荷VX2移植性乳腺癌兔区域淋巴组织靶向化疗的实验研究

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目的:研究对荷VX2乳腺癌兔实施区域淋巴组织靶向化疗后的局部淋巴结药物浓度及治疗效果。方法:40只雌性新西兰兔随机分为A、B、C、D4组,每组10只,VX2肿瘤组织块悬液注射法建立乳腺癌模型,腋淋巴结最大径达到5mm时开始治疗。A、B组分别给予肿瘤周围皮下注射卡铂活性碳混悬液(carboplatinactivatedcarbonsuspension,CPCH)或卡铂水溶液(carboplatinsolution,CPSol);C、D组分别经耳缘静脉注射CPSol或生理盐水。A、B、C组每次治疗药物剂量5mg/kg,每48h重复给药1次,治疗3次,48h后切除肿瘤、腋窝淋巴结及所有发现的远处转移灶,测量治疗前后肿瘤及淋巴结体积变化,原子吸收光谱法(atomicabsorptionspectrometry,AAS)测定卡铂浓度,常规病理切片观察肿瘤及转移灶坏死情况,RTPCR检测肿瘤组织增殖细胞核抗原(PCNA)。结果:与静脉或局部注射CPSol相比,局部注射CPCH可明显增加淋巴结内的药物浓度,并对淋巴结癌转移灶表现出更为显著的疗效,淋巴结增长减缓,淋巴结转移癌细胞大量死亡,PCNA表达降低。静脉注射CPSol可有效抑制乳腺或远处转移灶内的癌细胞增殖,而局部注射CPSol或CPCH无此效果。结论:区域淋巴组织靶向化疗对乳腺癌淋巴途径转移是一种有效的治疗手段,可辅助用于全身治疗。 Objective: To study the drug concentration and therapeutic effect of regional lymph node after regional lymphoid targeted chemotherapy in VX2 breast cancer rabbits. Methods: Forty female New Zealand rabbits were randomly divided into groups A, B, C, and D4. Each group consisted of 10 rabbits. VX2 tumor tissue suspension injection was used to establish breast cancer model. The maxillary diameter of axillary lymph node reached 5mm. A and B groups were given subcutaneous injection of carboplatin activated carbonspension (CPCH) or carboplatinsolution (CPSol) around the tumor respectively. C and D groups were injected with CPSol or saline via the ear vein respectively. A, B and C groups were treated with 5 mg / kg of each drug and repeated once every 48 hours for 3 times. After 48 hours, the tumors, axillary lymph nodes and all distant metastases were excised and the tumor volume and lymph node volume Changes of atomic absorption spectrometry (atomic absorption spectrometry (AAS) determination of carboplatin concentration, conventional pathological observation of tumor necrosis and metastasis, RTPCR detection of tumor tissue proliferating cell nuclear antigen (PCNA). Results: Compared with intravenous or topical injection of CPSol, local injection of CPCH significantly increased the drug concentration in lymph nodes and showed more significant effect on lymph node metastasis. The lymph node metastasis was slowed down. Large numbers of lymph node metastatic cancer cells died and PCNA expression reduce. Intravenous injection of CPSol effectively inhibited the proliferation of cancer cells in the mammary gland or in distant metastases, whereas local injection of CPSol or CPCH did not. Conclusion: Targeted chemotherapy of regional lymphoid tissue is an effective treatment for lymph node metastasis of breast cancer, which can be used for systemic therapy.
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