Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity,in node-negative breast carcinoma

In a series of 205 node-negative breast cancers (NNBC), we determined staining by the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test its association with other prognostic variables and its prognostic significance. Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples. Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205), with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%). In 107 tumors frozen sections were available to also assess the Ki-67 antibody. Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80% (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%). There was no significant relationship between Ki-S1 and the other two cell kinetic markers. Ki-S1 labeling was significantly associated only with tumor size (p = 0.03).With a median follow-up of 6 years, Ki-S1 had no significant prognostic value for either relapse-free survival (RFS) or overall survival (OS)(Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively). For RFS the following variables had a significant prognostic value: Ki-67 ( 10% vs > 10%; p = 0.037); progesterone receptor (PgR) expression (– vs +/++; p = 0.041); tumor size (pT1 vs pT2–3; p = 0.042) and grading (GI vs GII–III; p = 0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060), and Ki-67 (p = 0.043) were significantly prognostic.In multivariate analysis (final model), only tumor size retained a significant and independent prognostic value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age ( 55 years vs > 55 years; p = 0.041) retained significance in the multivariate model.In conclusion, Ki-S1 does not seem to have prognostic relevance in this series of NNBC. Possible hypotheses to explain this observation are discussed.     

Immunohistochemical analysis of 61 pituitary adenomas with a monoclonal antibody to the neuron-specific β-tubulin isotype

Pituitary adenomas surgically resected from 61 consecutive patients and 9 normal pituitary glands were studied by immunohistochemistry to determine the localization of the class III-tubulin isotype (neuron-specific) which is recognized by the monoclonal antibody TUJ1. In normal pituitary glands only a few cells were weakly immunopositive for TUJ1, whereas, in 43(73%) of 61 adenomas, more than 5% of tumor cells were immunopositive. The result may indicate that this neuron-specific -tubulin isotype may be either expressed de novo or enhanced under the transformation of pituitary acinar cells to tumors.Research fellow of the Department of Pathology, Kitasato University School of Medicine where the work was conducted     

Effects of P-Aminophenyl Dichloroarsine on Reduced High-affinity [3H]Nicotine Binding Sites from Chick Brain: A Covalent,Yet Reversible,Agent for Neuronal Nicotinic Receptors

Neuronal nicotinic acetylcholine receptor (nAChR) α-subunits contain a conserved disulphide that is essential for function. Here, we have examined the effects of sulphydryl redox reagents on [³H]nicotine binding to chick brain nAChR immunoisolated with the monoclonal antibody mAb35. The disulphide reducing agent, dithiothreitol (DTT), inhibited [³H]nicotine binding [50% inhibitory concentration (IC₅₀) = 146 μM] but this effect was reversed (93±1.5%) by subsequent reoxidation with 1 mM dithio-bis(nitrobenzoic acid) (DTNB). The trivalent arsenical, p -aminophenyl dichloroarsine (APA), which reacts with pairs of spatially close sulphydryls, was a potent inhibitor of reoxidation by DTNB (IC₅₀= 35 nM). However, application of the 'anti-arsenical', 2,3-dimercaptopropane sulphonic acid (DMPS), restored agonist binding after APA treatment (50% effective concentration = 120 μM). Paradoxically, DMPS was also found to be a potent oxidizing agent of these receptors. Affinity alkylation of reduced nAChRs with bromoacetylcholine (BAC; 100 μM) irreversibly blocked nicotine binding (>90%). We propose (but have not proven) that APA interacts with the cysteines homologous to Cys192–193 in Torpedo AChRs, since APA pretreatment of reduced neuronal receptors protected against irreversible BAC alkylation, as shown by subsequent reversal of DMPS (2 mM; 20 min). This study illustrates the potent and reversible nature of the arsenical's covalent interaction with an isolated nAChR and suggests that modified arsenicals could be useful nAChR probes.     

鼠和兔中流行性感冒病毒抗体的制备及测定

报道了流行性感冒病毒抗体的制备及其抗体价的检测方法。利用鼠、兔对流行性感冒(IFV)抗原的免疫反应制备抗体；酶联免疫法(ELISA)测定抗体价。结果显示：Freund佐剂与抗原的混合乳液，具有流行性感冒病毒的抗原特异性，且能够增强抗原的免疫原性，并改变宿主的免疫反应原性。     

Use of radiolabeled antibodies in the treatment of childhood acute leukemia

Abstract: Despite advances in therapy for acute leukemia, relapse continues to be the major cause of treatment failure. Hematopoietic stem cell transplant can rescue some patients after relapse, but the ability to escalate the intensity of preparative regimens is limited by toxicity to normal organs. Radiolabeled monoclonal antibodies against hematopoietic antigens have emerged as an alternative to deliver targeted supplemental radiation to sites of leukemic involvement while relatively sparing normal organs. This paper will review the rationale for using this approach, our current experience with radiolabeled anti-CD45 antibody, and the potential challenges encountered in treating children with radiolabeled antibodies.     

Molecular and functional characterization of porcine LFA-1 using monoclonal antibodies to CD11a and CD18

Abstract: We describe in this report the production and characterization of monoclonal antibodies (mAb) to the swine homologues of CD11a and CD18 antigens, and their use for phenotypic and functional analysis of porcine leukocytes. Monoclonal antibodies BL1H8 and BL2F1 precipitated two bands of approximately 170 and 95 kDa, whereas mAb BA3H2 brought down three bands of 170, 155 and 95 kDa, from alveolar macrophage lysates. Clearance of macrophage lysates with mAbs BL1H8 and BL2F1 resulted in complete removal of the 170-kDa band. The cell distribution of the molecules recognized by these mAbs was similar to that of human LFA-1. It was found on all leukocytes, although its expression varied among the different leukocyte subpopulations, with monocytes, granulocytes and a subset of CD8⁺ cells expressing the highest levels. Cross-blocking studies showed that these antibodies recognize different epitopes on porcine LFA-1. Both anti-LFA-1 mAbs strongly inhibited the mitogenic response of PBMC to ConA, whereas the anti-CD18 mAb had no effect. These anti-LFA-1 mAbs also inhibited the mixed lymphocyte reaction (MLR) and the NK cell-mediated lysis of K-562 cells.     

γ—干扰素对喉癌细胞株HEP—2增殖活性的影响

用单克隆抗体Ｋｉ－６７（抗ＰＣＮＡ），以链霉菌素－生物素技术（ＬＳＡＢ）检测喉癌细胞株ＨＥＰ－２增殖细胞核抗原（ＰＣＮＡ）表达。人重组γ－干扰素（ｒｈｕ－ＩＦＮ－γ）抑制ＰＣＮＡ表达（即抗增殖活性）强弱与其剂量有关；雌激素对ｒｈｕ－ＩＦＮ－γ抗增殖作用无影响。提示：ｒｈｕ－ＩＦＮ－γ对喉癌细胞株ＨＥＰ－２有抗增殖作用，因而在喉癌的治疗中具有应用价值的。     

EB病毒VCA-IgA抗体水平与鼻咽癌病人远期疗效关系

目的：分析ＥＢ病毒血清学ＶＣＡ－ＩｇＡ抗体与鼻咽癌病人远期疗效关系，为临床治疗提供参考依据。方法：１９８５年本院病理确诊的５２２例鼻咽癌病人，按治疗前、后ＶＣＡ－ＩｇＡ抗体滴度分为三组：低滴度组（１：５～１：２０）、中滴度组（１：４０～１：８０）和高滴度组（１：１６０以上），随访１０年，比较生存率的异同。结果：治疗前鼻咽癌病人高滴度组１０年生存率低于低滴度组（Ｐ＜０．０５），但和中滴度组差别无显著性（Ｐ＞０．０５）。治疗后三组病人１０年生存率比较，高、中滴度二组差别无显著性（Ｐ＞０．０５），但低于低滴度组。结论：ＥＢ病毒ＶＣＡ－ＩｇＡ抗体水平可以作为估计预后的重要参考依据，与远期疗效有密切关系。     

全人源肝癌噬菌体单链抗体的筛选及特异性鉴定

目的对全人源肝癌噬菌体单链抗体库进行鉴定,筛选肝癌抗体,同时对抗体的活性及特异性进行鉴定。方法PCR鉴定阳性重组菌TG1中人肝癌ScFv的插入率。先以人成纤维细胞吸附后再以体外培养的肝癌细胞SMMC7721为抗原对所建抗体库进行3轮“吸附洗脱扩增”的亲和筛选。将筛选后的ScFv进行PCR鉴定及双酶切鉴定;通过ELISA法及FCM鉴定其与人肝癌细胞及正常细胞的结合活性。结果ScFv基因插入率为70%。在亲和筛选过程中,肝癌噬菌体单链抗体得到富集,收获率逐轮得到提高,第3轮为第1轮的214倍。筛选后的ScFv进行PCR鉴定及双酶切鉴定,均可检测到目的基因。ELISA分析结果显示18个克隆与SMMC7721呈阳性反应,阳性率为90%,15个克隆与成纤维细胞有交叉反应。得到3株肝癌单链抗体。ScFv的FCM鉴定表明,以正常胎肝细胞L02为对照,ScFv与肝癌结合比率为41.3%。特异性鉴定表明,其与肝癌细胞结合活性明显高于正常细胞。结论利用噬菌体抗体库技术结合减数筛选得到了肝癌噬菌体单链抗体及其基因,且筛选后的抗体片段与人肝癌细胞有特异性的结合活性。