72株小鼠抗人单抗与5种微生物和3种细菌交叉反应性研究

乳腺癌组织免疫小鼠制备出７２株抗人单抗，它们与５种微生物，３种细胞反应，出现交叉反庆比率依次为金黄色葡萄球菌（３４．７％），Ｎ４细胞（３３．３％）卡介苗（２９．２％），Ｈｅｌａ细胞（１３．９％），乙型溶血性链球菌（１２．５％），大肠杆菌（１２．５％），ＢＨＫ２１细菌（８．３％），痘苗病毒（０％）。８种生物平均反应率为１８．１％，７２株单抗中与这８种生物反应的４９株，占６８．１％。

人血清中一种人单克隆IgM抗体(HA—IA)的定量测定法(文摘)

近年来，人单克隆抗体技术的发展已研制出针对一些抗原的单特异性人单抗，并用于临床治疗。这与使用混合的超免疫血清相比较，人单抗具有安全和易标准化等优点，但较小鼠单抗的抗原性弱。应用人单抗临床治疗需要分析制品的动力学，以制订合理的治疗剂量和给药方案。

治疗性全人单克隆抗体,抗体研发的后起之秀

截至目前,全球共批准上市21个抗体药物,其中治疗性全人单抗药物占据了1/3,全人单抗是所有抗体药物中获批数量、研发速度和研发数量增长最快的一类。

Prediction of uniaxial compressive strength and modulus of elasticity for Travertine samples using regression and artificial neural networks

Uniaxial Compressive Strength (UCS) and modulus of elasticity (E) are the most important rock parameters required and determined for rock mechanical studies in most civil and mining projects. In this study, two mathematical methods, regression analysis and Artificial Neural Networks (ANNs), were used to predict the uniaxial compressive strength and modulus of elasticity. The P-wave velocity, the point load index, the Schmidt hammer rebound number and porosity were used as inputs for both meth-ods. The regression equations show that the relationship between P-wave velocity, point load index, Schmidt hammer rebound number and the porosity input sets with uniaxial compressive strength and modulus of elasticity under conditions of linear rela-tions obtained coefficients of determination of (R2) of 0.64 and 0.56, respectively. ANNs were used to improve the regression re-sults. The generalized regression and feed forward neural networks with two outputs (UCS and E) improved the coefficients of determination to more acceptable levels of 0.86 and 0.92 for UCS and to 0.77 and 0.82 for E. The results show that the proposed ANN methods could be applied as a new acceptable method for the prediction of uniaxial compressive strength and modulus of elasticity of intact rocks.

Effects of monoclonal antibodies against human stathmin 1 combined paclitaxel on proliferation of human hepatocellular carcinoma cell lines

Objective： We investigated the effects of monoclonal antibodies against stathmin 1 combined paclitaxel on the proliferation of HCC cells. Methods： HepG2 cells were treated with monoclonal antibodies against stathmin 1, paclitaxel alone or their combination, with the untreated cells used as the control, 24, 48, 72, 96 h later, the cell growth condition was observed by invert microscope and inhabitation rate was studied by MTT assay; The apoptosis was analyzed by flow cytometry with Annexin V/PI. Results： The population decreased and shape, size changed after treating with different concentration of experimental groups. Monoclonal antibodies against stathmin 1 and paclitaxel used alone or in combination both inhibited the proliferation of HepG2 cells, the inhibition ratio of their combination was more higher （P 〈 0.05）, and a synergistic effect of the two agents was noted in their combined action （P 〈 0.05）. Combined treatment of the cells resulted in significantly higher apoptosis rate than that in the other groups （P 〈 0.05）. Conclusion： Monoclonal antibodies against stathmin 1 and paclitaxel used alone or in combination both can inhibit proliferation of HepG2 cells and induce apoptosis. A synergistic effect is obsewed between the monoclonal antibodies against stathmin 1 and paclitaxel in their inhibition of HepG2 cell proliferation.

αV integrin:A new gastrin target in human pancreatic cancer cells

AIM： To analyse αv integrin expression induced by gas- trin in pancreatic cancer models.METHODS： αv integrin mRNA expression in human pan- creatic cancer cells was analysed using a ＂cancer genes＂ array and confirmed by real-time reverse transcription- polymerase chain reaction （PCR）. Western blotting and semi-quantitative immunohistochemistry were used to examine protein levels in human pancreatic cancer cell lines and pancreatic tissues, respectively, The role of αv integrin on gastrin-induced cell adhesion was examined using blocking anti-αv integrin monoclonal antibodies. Adherent cells were quantified by staining with crystal violet.RESULTS： Using a ＂cancer genes＂ array we identi- fied c^v integrin as a new gastrin target gene in human pancreatic cancer cells. A quantitative real-time PCR approach was used to confirm αv integrin gene expression. We also demonstrate that Src family kinases and the PI 3-kinase, two signalling pathways specifically activated by the CCK-2 receptor （CCK2R）, are involved in gastrin-mediated αv integrin expression. In contrast, inhibition of the ERK pathway was without any effect on αv integrin expression induced by gastrin. Our results also show that gastrin modulates cell adhesion via αv integrins. Indeed, in vitro adhesion assays performed on fibronectin show that gastrin significantly increases adhesion of pancreatic cancer cells. The use of blocking anti-αv integrin monoclonal antibodies completely reversed the increase in cell-substrate adhesion induced by gastrin. In addition, we showed in vivo that the targeted CCK2R expression in the pancreas of Elas-CCK2 mice, leads to the overexpression of αv integrin. This process may contribute to pancreatic turnout development observed in these transgenic animals.CONCLUSION： αv integrin is a new gastrin target in pancreatic cancer models and contributes to gastrin effects on cell adhesion.

Correlativity of lymph node micrometastases detection in follicular carcinoma of thyroid in different risk groups

Objective:The aim of this study was to explore the relationship between follicular carcinoma of thyroid in different risk groups and lymph node micrometastases.Methods:The keratin-19 of negative neck lymph nodes in 83 cases in routine pathological examination,was detected by SP immunohistochemistry using keratin-19 monoclonal antibody to confirm lymph node micrometastases.All of cases are divided into high risk group,middle risk group and low risk group according to factors related prognosis,the relationship between lymph node micrometastases and different risk groups and follow-up visit documents were analyzed.Results:Fifty-eight neck lymph nodes in 16 cases of 83 cases(19.3%) showed positive lymph node micrometastases,and incidence of lymph node micrometastases was 4/39 in low risk group,5/32 in middle risk group and 7/12 in high risk group,respectively.it showed remarkable difference during 3 groups(P < 0.001).Nine patients in 16 cases with positive lymph node micrometastases showed local recurrence and distant metastases,6 patients in 67 cases with negative lymph node micrometastases showed same result(P < 0.001).Conclusion:Lymph node micrometastases in follicular thyroid carcinoma closely correlated to factors related to prognosis.The detection of lymph node micrometastases can directly assistant postoperative treatment and prognosis evaluation to some extent for follicular thyroid carcinoma.

PREPARATION AND CHARACTERIZATION OF MONOCLONAL ANTIBODY AGAINST HUMAN TELOME RASE REVERSE TRANSCRIPTASE

Objective.To develop monoclonal antibodies again st the catalytic subunit of human telomerase reverse transcriptasefor i ts expression detection of human tumors.Methods.A dominant epitope in hTERT was automatically synthesized based on Fmoc method,and was used to immuni ze Balb/c mice.Hybridomas were generated and screened by ELISA for specific mo noclonal antibodies,and the characterization was performed by Western blotting and immunohistochemical staining.The heavy chain variable region of antibody wa s cloned by RT-PCR and sequenced.Results.Antigenic peptide hTERT 7 was synthesized and confirmed by MALDI-TOF-MS and HPLC analysis.One hybr idoma cell line secreting anti-hTERT 7 antibodies designated as M2was established after primary screening and cons equent 3rounds of limited dilution.M2was IgG1in isotyping.The competi-tive assay showed that the M2antibody was hTERT 7-specific,and the affinity constant was about 1×10 6 mol-1 .The antibody reacted with cell extracts from HeLa cancer cells but not wi th those from normal2BS cells in ELISA assay.For in situ staining of immunohis tochemistry,the positive staining presented in the nuclear compartment of HeLa ,while2BS was negative.The heavy chain variable region from M2re-vealed tha t the monoclonal antibody was mouse origin.Conclusions.The developed mouse mon oclonal antibody is hTERT-specific and able to recognize native cellular hTERT in ELISA and immunohistochemistry,which makes the immuno-detection of telom-e rase hTERT expression in cancer cells or tissues possible.

Human Monoclonal Antibodies as Candidate Therapeutics Against Emerging Viruses and HIV-1

More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.

抗体药物的创新之路

抗体药物由于靶向性强、特异性高和毒副作用低等特点,近年来已成为生物药行业中发展最快的分支。截至2017年8月,美国FDA累计批准了69个治疗性抗体药物,其中人单抗和人源化单抗已成主流,双特异性抗体开始崭露头角。我国抗体药物的研究几乎与世界同步。但在抗体功能优化、新抗体研发,特别是抗体规模化生产方面与国外相比有一定差距,目前仍以仿制药为主,抗体药物如何创新是我们面临的巨大挑战。