Monoclonal anti-CEA antibody: factors affecting localization in a preclinical study

131I-labelled anti-CEA monoclonal antibody was tested in an animal model to evaluate: influence of antibody type (whole versus F(ab')2 fragments), administration route (i.v. versus i.p.), dose of tracer (100 microCi versus 1000 microCi), growth site (s.c. versus i.p.) and size of tumor. Athymic mice bearing CEA-producing human colon carcinoma (HT-29) or human melanoma as an irrelevant tumor (MeWo) received tracer and immunoscintigraphy and the localization ratios (LR) were compared. In HT-29 bearing animals F(ab')2 fragments localized better than the whole antibody. The LR were higher after i.p. administration of the tracer, independently of the tumor characteristics or the injected dose. The highest values were achieved when the radioactivity remaining in the whole body was below 2% of the injected dose. The images were negative when the i.p. injected dose was low or tumor growth was i.p. but positive in the other conditions (i.v. administration, high tracer dose, s.c. tumor growth). In the animals bearing melanoma, images scored positive or negative when the tumor weight was respectively above or below 400 mg, but the LR were always low.     

Study of a soluble tumor-associated marker composed of CEA related molecules recognized by three monoclonal antibodies.

Three MAbs, MLuC2, MLuC8 and MLuC9, directed against a molecule that is produced and secreted by carcinoma cells were studied with the aim of developing a double-determinant immunoradiometric assay (DDIRMA). We demonstrated by means of immunoblotting, immunodepletion and DDIRMA techniques, that MLuC9 reacted against the CEA molecule, whereas MLuC2 and MLuC8 reacted against a 90 Kd molecule related to CEA. The DDIRMA performed with the anti-CEA as a catcher MAb and the anti-90 Kd as a tracer MAb was found to be positive with the HT29 soluble extract, which suggests the existence of CEA/90 Kd dimeric molecules. The same reactivity was found when sera from patients with lung carcinomas were tested, which excludes that this molecule could be an artefact due to the cell solubilization procedures. The association between CEA and the 90 Kd molecule was further confirmed by immunodepletion experiments in which the immunoprecipitation with one MAb not only removed the recognized molecule, but also partially immunodepleted the material from the other.     

不同训练负荷太极拳运动对早中期帕金森病患者康复疗效

目的 通过对比对照组和太极拳运动组，评价太极拳运动在早中期帕金森病患者康复作用。方法 45例帕金森病患者随机分为：对照组（n=15），不接受干预；太极拳1组（n=15）采用24式简化太极拳练习，40 min/次，3次/周；太极拳2组（n=15）采用24式简化太极拳练习，60 min/次，3次/周。在基线、12周、24周运动后采用患者跌倒功效量表（FES）、起立-行走计时测试（TUGT）、Berg平衡量表评分（BBS）、统一帕金森病评定量表（UPDRS） Ⅲ评分、汉密尔顿焦虑抑郁量表评分（HAMD、HAMA）、匹兹堡睡眠质量指数评分（PSQI）进行评估。结果 太极拳1组，24周对比基线在TUGT、BBS评分的改善上有统计学意义（P<0.05）。太极拳2组，24周对比基线在TUGT、 BBS评分的改善上有统计学意义（P<0.05）,24周对比12周在TUGT的改善上有统计学意义（P<0.05）。结论 太极拳运动可以改善早中期帕金森病患者的平衡障碍，可降低跌倒风险。     

Production of monoclonal antibodies against a new carcinoma-associated marker in view of developing a serological test.

By immunizing a mouse with human metastatic breast tumor cells from patient effusions and infiltrated lymph nodes, a monoclonal antibody (MLuC2), which identifies a new carcinoma-associated marker, was raised. The reactivity of this reagent was studied by immunohistochemistry on live and fixed cells from tumor cell lines and on frozen sections from surgical specimens. Besides reacting with 73% of breast carcinomas, MLuC2 also reacted with 93% of non-small cell lung carcinoma (NSCLC) and with a few normal tissues. The MLuC2-recognized molecule (CaMLuC2), whose MW was 90 KDa according to immunoblotting experiments, was found to be detectable in the serum and could therefore be of particular interest for serological diagnostic applications. Since the CaMLuC2 epitope was not polyexpressed on the bearing molecule, we produced a new generation of MAbs in order to define epitopes coexpressed with CaMLuC2 on the same 90 kDa molecule, and which are therefore suitable to develop a double-determinant immunoradiometric assay (DDIRMA) for the detection of this marker in the sera of lung carcinoma patients. Different analyses by immunohistochemistry, binding inhibition tests and DDIRMA, proved that the two new reagents developed, MLuC8 and MLuC9, recognize the same or closely related epitopes, which are however different from CaMLuC2, but which are all present on the same molecule. Preliminary immunoradiometric tests performed on sera from lung cancer and control patients showed a good specificity but a low sensitivity. In fact, only 42% of the 28 tested sera samples from NSCLC patients scored positive despite the fact that more than 90% of the NSCLC expressed the relevant antigen.