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.     

The vascular ‘sunburst’ appearance of osteosarcoma: A new angiographic finding

The angiographic analogue of the sunburst, (right angle) periosteal new bone formation in osteogenic sarcoma is described. The angiographic findings in this tumor and their relationship to the pathologic appearance are discussed.     

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。     

人结直肠癌平滑肌组织毒蕈碱受体特性的变化

随着受体理论和研究技术的发展 ,人们开始从受体的变化去探寻疾病发生和发展的根源 ,并从受体水平诊治疾病。最近人们发现ＭＡＣｈ Ｒ与肿瘤之间关系密切。一方面 ,ＭＡＣｈ Ｒ过度活化可导致细胞增殖、恶性转化及肿瘤发生[1] ;另一方面 ,在肿瘤状态下ＭＡＣｈ Ｒ的特性也发生变化。本文主要探讨肿瘤状态下ＭＡＣｈ Ｒ特性的变化。1　材料与方法1.1　临床资料　结直肠癌病人 10例 ,男 6例 ,女 4例。中国医科大学附属第一医院肿瘤科提供。1.2　标本采集　结直肠癌患者手术切除的标本 ,分别取癌、癌旁及正常组织各一块。癌旁组织取距癌灶约 2…     

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。     

透明质酸在宫颈上皮及宫颈癌组织中的表达

目的 :探讨透明质酸 (HA)在正常宫颈上皮及宫颈癌中的表达及其与肿瘤发生发展的关系。方法 :用免疫组化法检测 5 9例宫颈浸润癌、35例宫颈上皮内瘤样病变 (CIN)及11例正常宫颈组织中HA和CD4 4v6的表达。结果 :正常宫颈上皮不表达HA。慢性炎症者上皮底层细胞以及细胞间质表达HA ,随病变加重及CIN发生 ,HA表达增强。癌旁组织的上皮细胞HA呈强阳性表达 ,伴有基质HA强阳性染色。癌细胞HA阳性率为 6 7.2 7% ,与病理类型有关 ,角化癌高表达 ,而腺癌不表达 ,在低分化鳞癌中多见不规则灶性HA阴性区。宫颈鳞癌的肿瘤基质HA表达普遍增强。肿瘤基质的HA表达与CD4 4v6呈正相关。结论 :正常宫颈上皮不表达HA ,但炎症与致瘤因素可促使HA表达 ,HA的代谢失衡可能与宫颈癌的发生及浸润行为有关     

血清CA125检测在子宫内膜癌中的价值

目的探讨血清CA125在子宫内膜癌中的价值.方法选取1992年3月～2002年3月在北京大学第一附属医院、北京大学人民医院住院经手术治疗的子宫内膜癌患者141例,术前及随访中用放射免疫法测定血清CA125水平,CA125≥35 U/ml 为阳性结果.对其中14例行子宫内膜癌组织CA125免疫组化方法检测.收集患者的临床病理资料,分析CA125与这些资料的关系以及复发患者复发前后CA125变化.结果 CA125免疫组化检测14例均呈阳性,阳性细胞着色率与血清CA125之间无明显相关.141例患者术前血清CA125阳性32例(22.7%), Ⅰ、Ⅱ、Ⅲ和Ⅳ期患者血清CA125阳性(阳性率)分别为11例(12.1%)、6例(31.6%)、12例(46.2%)和3例(60.0%). 血清CA125阳性率随子宫内膜癌期别的增加而升高.深肌层浸润、宫颈受累、附件转移、腹腔洗液细胞学阳性、盆腔淋巴结转移及宫内肿瘤病灶≥2 cm者,血清CA125阳性率增加.随访中13例复发,其中9例术前血清CA125＞35 U/ml者复发时均伴血清CA125水平升高,而另4例术前血清CA125正常者,复发后血清CA125水平仍正常.结论子宫内膜癌患者术前血清CA125的测量有助于了解肿瘤的侵犯范围.术前血清CA125水平异常的子宫内膜癌患者,术后定期复查血清CA125水平,将有助于子宫内膜癌病情的监测.     

层粘连蛋白、基质金属蛋白酶-9在卵巢粘液性肿瘤中的表达及其意义

目的 :探讨层粘连蛋白 (LN)、基质金属蛋白酶 9(MMP 9)在卵巢粘液性肿瘤中的表达以及与临床病理因素和预后的关系。方法 :应用免疫组织化学方法检测 43例卵巢粘液性肿瘤LN、MMP 9的表达情况。结果 :LN、MMP 9的表达 ,在卵巢粘液性肿瘤从良性、交界性到恶性发展中 ,LN的表达级别和MMP 9的表达阳性率逐渐增高 ;LN的表达程度与卵巢粘液性囊腺癌的组织学分级有关 (P =0 0 0 0 ) ;MMP 9的表达与卵巢粘液性囊腺癌的组织学分级 (P =0 0 48)、FIGO分期 (P =0 0 47)、术后复发和死亡 (P =0 0 30 )有关。在卵巢粘液性囊腺癌中 ,LN的表达程度在MMP 9阳性组与MMP 9阴性组之间差异有显著性 (P =0 0 0 8) ,并呈正相关。结论 :LN、MMP 9在卵巢粘液性肿瘤的浸润转移中起重要作用 ,是卵巢粘液性肿瘤的恶性指标之一 ,可望作为交界性粘液性囊腺瘤及粘液性囊腺癌的诊断和分级的客观指标 ;MMP 9可协助临床估计预后。