Antimetastatic action of the prostacyclin analogue cicaprost in experimental mammary tumors

Summary In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade and to inhibit the number of lung colonies after i.v.-inoculation of various tumor cell lines. Our data reveal that cicaprost, a metabolically stable and orally active analogue of prostacyclin, has pronounced antimetastatic effects in a series of spontaneously metastasizing rodent tumors. In the SMT 2a and 13762 MTLn3 mammary carcinomas of the rat, cicaprost given daily from the day of tumor implantation strongly inhibits the number of lung metastases as well as lymph node weights without exerting an effect on the primary tumor. Even starting treatment when palpable primary tumors are present gives a pronounced antimetastatic activity. To demonstrate that cicaprost has an effect on metastases already settled in the respective organ, treatment was started after surgical removal of the primary tumor. In the SMT 2a tumor, a strong inhibition of the number of metastases was shown. Interestingly, a perioperative treatment schedule was also effective in both models used. As primary tumor growth in vivo or proliferation in vitro remained unchanged by cicaprost, its mode of action seems to be related to one or more mechanisms of the metastatic process. In tumor cell lines expressing a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In conclusion, cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of action different from cytostatic or antihormonal drugs.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Anti-invasion drugs

Summary Most of the pharmaceuticals in clinical practice today for treatment of breast and other cancers are cytotoxic or cytostatic inhibitors of tumor growth. While this type of drug has found its place, along with surgery and radiotherapy, in treatment of disease, the breast cancer death rate has not decreased. This appears to be the result of rising incidence, resistance to therapy, and metastasis of the disease. Since distant metastasis (usually indicated by lymph node involvement) of breast cancer is related only indirectly to tumor size, it would appear that a concerted effort should be made to discover drugs which directly interfere with this complex process. Metastasis appears to depend upon tumor cell motility, dedifferen-tiation, local invasion, and angiogenesis. Significant progress has been recently made in the creation of new animal models of metastasis and in identifying several new drugs which may be suitable for clinical inhibition of this process. This article reviews current findings on anti-invasion/metastasis drugs with a focus on breast cancer.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Unicentric osteosarcoma of bone with subsequent skeletal metastases

Five cases of unicentric osteosarcoma with subsequent skeletal metastases are reviewed. Skeletal metastases may occur prior to pulmonary metastases in such patients. Initial and periodic bone scanning is therefore justified since early detection of distant bone lesions may have important therapeutic implications. A classification of multiple site osteosarcoma based upon clinical, pathologic, and radiologic characteristics is proposed.     

IL-2活化瘤苗对胃癌术后复发和转移的抑制作用

目的观察用细胞因子活化的特异性瘤苗辅助常规化疗,治疗外科手术后临床Ⅲ～Ⅳ期胃癌患者,抑制肿瘤术后复发、转移的临床疗效。方法于外科术后常规化疗结束后2周,用患者自体肿瘤细胞抗原致敏、IL-2活化的树突状细胞(DC)作为瘤苗给患者四肢皮下多点免疫注射1×106/(ml·次),每周1次,每疗程注射4次,0.5年后强化1次。定期胃镜、影象学和肿瘤标志物检查,随访至手术后第2年,观察生存期和生存率。结果经瘤苗治疗后,患者的免疫功能显著改善。术后24个月,瘤苗联合化疗组患者的生存率为50%,血清中CEA和CA724分别为(10±1.5)ng/ml和(5.5±1.5)U/ml,而单纯化疗组患者的生存率为10%,CEA和CA724的水平分别为(77.0±9.4)ng/ml和(55.0±7.6)U/ml;P<0.001。结论特异性瘤苗免疫治疗,能增强胃癌患者术后的特异性抗肿瘤免疫功能,提高手术后化疗疗效,抑制肿瘤复发和转移,能延长患者生存期,提高生存率。     

Ⅰb-Ⅱb期手术治疗的宫颈腺癌卵巢转移及预后分析

目的　探讨Ⅰb—Ⅱb期手术治疗的宫颈腺癌卵巢转移的高危因素 ,并分析预后因素。方法　回顾性研究 32例Ⅰb—Ⅱb期手术治疗的宫颈腺癌的临床病理特点 ,应用 χ2 检验及logistic回归分析探讨 4例卵巢转移的高危因素 ;应用Kaplan -Meier法及Cox回归模型分析预后因素。结果　单因素分析提示卵巢转移的高危因素是临床分期和盆腔淋巴结转移 ,但多因素分析没有发现有统计学意义的危险因素。Cox回归提示肿瘤大小和盆腔淋巴结转移是独立预后因素。结论　对于有高危因素的宫颈腺癌 ,术中保留卵巢需要慎重。     

肝内胆管癌30例的临床病理特征及预后分析

目的 :探讨肝内胆管癌 (intra hepaticcholangiocarcinoma ,ICC)的临床病理特征及治疗与预后的关系。方法 :回顾性分析 1991～ 1999年山东省立医院、济宁医学院附属医院 3 0例ICC患者病理、临床资料。结果 :ICC比肝细胞癌少见且预后不良 ,手术切除是目前较理想治疗方式 ,影响预后的因素是肿瘤边缘、淋巴结转移与组织病理情况。根治切除术后 1年生存率 5 3 3 % ,3年生存率 3 3 3 %。结论 :根治性切除是最有效的治疗方法。     

大肠癌患者骨髓微转移的基因研究

目的 探讨大肠癌患者骨髓中微转移基因检测的意义。方法 应用聚合酶链式反应－单链构象多态性分析（ＰＣＲ－ＳＳＣＰ）／银染技术,检测５１例大肠癌患者手术前、后不同时间骨髓中ｐ５３和Ｋ－ｒａｓ基因的突变状况。结果 ５１例患者术前骨髓中基因突变阳性者１９例,阳性率３７．２５％。阳性检出与Ｄｕｋｅ’ｓ分期、淋巴转移显著相关。术后经２～３个疗程的化疗后,１９例基因突变阳性的患者中１１例转阴。结论 大肠癌患者骨     

食管癌淋巴结转移的临床病理因素

目的 探讨食管癌淋巴结转移的临床病理相关因素。方法 对204例食管癌根治标本进行统计,分析各主要临床病理改变与淋巴结转移关系。结果 204例食管癌中有淋巴结转移者89例,淋巴结转移率为43.6％。胸中段癌淋巴结转移率为48.0％,胸上段癌和胸下段癌的淋巴结转移率分别为32.0％和26.9％。髓质型和溃疡型淋巴结转移率分别为47.6％和56.0％,除缩窄型外其他类型转移率最高者为21.4％。男性患者淋巴结转移率为54.3％,女性淋巴结转移率为28.4％。浸润至黏膜层和黏膜下层者,未发现淋巴结转移,浸润至浅肌层、深肌层、纤维膜者淋巴结转移率分别为28.6％、45.6％和48.8％。以上四种因素中前后两者间比较差异均有显著性(P<0.05)。淋巴结转移率与年龄无关,也不随肿瘤大小的增加而增加。结论 男性食管胸中段癌患者淋巴结转移率较高,尤其当肿物为髓质型和溃疡型时最为显著。     

喉癌、下咽癌颈廓清组织中转移淋巴结的分布研究

对54侧经临床检查或／和CT扫描确诊为有淋巴结转移而行预廓清的标本进行病理学观察，发现：喉癌、下咽癌淋巴结转移有一定规律可循，即LevelⅡ、Ⅲ有较高的转移率，LevelⅣ、Ⅵ的发生率较低，而LevelⅠ、LevelⅤ很少发生转移。提示：喉癌、下咽癌病人的颈廓清的施术应在颈LevelⅡ～Ⅳ廓清的同时行同侧甲状腺侧叶的切除以将颈中器官周围淋巴结清扫彻底。对LevelⅠ，LevelⅤ的清扫应在临床触诊、CT检查的证实下或术中发现转移时方可进行．以减少颈廓清手术范围、手术时间和术后并发症的发生。