Wistar rats were inoculated with purified YWK-I antibody. The anti-idiotypie antibodies were isolated from rat sera by successive passage over affinity chromatography columns of YWK-I mAb and normal mouse Igs. Specifi...Wistar rats were inoculated with purified YWK-I antibody. The anti-idiotypie antibodies were isolated from rat sera by successive passage over affinity chromatography columns of YWK-I mAb and normal mouse Igs. Specificity of anti-Id antibody was established by ELISA. The 84 kD protein inhibited the binding of anti-Id to YWK-I mAb, but failed to repress antibody against normal mouse Ig binding to YWK-I mAb. In competitive inhibition assay, 84 kD protein had shown the ability to compete with anti-Id binding to YWK-I mAb in a dose-dependent manner. Crude sperm extract showed a lower competitive ability. No effeet was found with the irrelevant 36 kD sperm protein. The antisera from the Ba1b/e mice immunized with AId contained Ab3 that reacted with 84 kD sperm protein. The binding of anti-Id to YWK-I mAb was inhibited by Ab3 in a dose-dependent fashion and Ab3 was shown to be able to induce human sparm agglutination. These results indicate that anti-Id which may mimio an epitope of the 84 kD protein could be exploited as an antigen to raise antibodies against sperm protein.展开更多
The heavy chain variable region genes of 5 human polyreactive mAbs generated in our laboratory have been cloned and sequenced using polymerase chain reaction (PCR) technique. We found that 2 and 3 mAbs utilized genes ...The heavy chain variable region genes of 5 human polyreactive mAbs generated in our laboratory have been cloned and sequenced using polymerase chain reaction (PCR) technique. We found that 2 and 3 mAbs utilized genes of the VHIV and VHIII families, respectively. The former 2 VH segments were in germline configuration. A common VH segment, with the best similarity of 90.1 % to the published VHIII germline genes, was utilized by 2 different rearranged genes encoding the V regions of other 3 mAbs. This strongly suggests that the common VH segment is a unmutated copy of an unidentified germline VHIII gene. All these polyreactive mAbs displayed a large NDN region (VH-D-JH junction). The entire H chain V regions of these polyreactive mAbs are unusually basic. The analysis of the charge properties of these mAbs as well as those of other poly- and mono- reactive mAbs from literatures prompts us to propose that the charged amino acids with a particular distribution along the H chain V region,especially the binding sites (CDRs), may be an important structural feature involved in antibody polyreactivity.展开更多
Objective： Invasion and metastasis are the most significant and intrinsic biological characteristics of cancers, also which are main factors of malignant tumor causing treatment failure and death. Recent studies have...Objective： Invasion and metastasis are the most significant and intrinsic biological characteristics of cancers, also which are main factors of malignant tumor causing treatment failure and death. Recent studies have found that Fra-1 plays an important role on cell migration, invasion, and maintaining malignant phenotype of transformed cells. But there are few stud- ies about the expression and location of Fra-1 in breast tissues and cells being reported .This study just aims to discuss the expression and location of transcription factor Fra-1 in benign and malignant human breast tissues. Methods： The expression of Fra-1 was investigated by immunohistochemistry in neoplastic breast diseases ranging from benign fibroadenoma to very aggressive undifferentiated carcinoma. The correlations of Fra-1 expression with other indicators of breast carcinoma prog- nosis （ER, PR and ErbB2 receptors） were analyzed. Results： All neoplastic breast tissues, either benign or malignant breast tissues, were nuclear immunoreactive for Fra-l-recognizing antibody. In 85% of benign tumors （17/20）, the immunoreactive for Fra-l-recognizing antibody as exclusively restricted to the nuclei. In three cases （3/20, 15%）, focal unequivocal cytoplas- mic staining was also exhibited. Strong positive nuclear staining for Fra-1 was easily seen in all types of breast carcinomas. However the nucleaflcytoplasmic concomitant immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization was noticed in 90.2% （37/41） of breast carcinomas. No inverse relationship between Fra-1 and ER and PR protein levels was noticed in malignant tumors. The relative expression level of Fra-1 was not correlated with the expression of ErbB2. Conclusion： The overall expression, pattern and intensity of Fra-1 proteins were correlated with breast oncogenesis. Overexpression of Fra-1, leading to a persistent high cytoplasmic accumulation, may play a role in the process of breast carcinogenesis.展开更多
Crizotinib is a mesenchymal-epithelial transition/anaplastic largecell kinase （MET/ALK） multi-targeted receptor tyrosine kinase inhibitor and has been rapidly and successfully developed as an inhibitor in ALK-rearra...Crizotinib is a mesenchymal-epithelial transition/anaplastic largecell kinase （MET/ALK） multi-targeted receptor tyrosine kinase inhibitor and has been rapidly and successfully developed as an inhibitor in ALK-rearranged NSCLC （non-small cell lung cancer）. Lung cancer is the major cause of cancer-related mortality, accounting for over one quarter of cancer deaths. Lung cancers are generally divided into two main categories： SCLC （small cell lung cancer） and NSCLC. NSCLC accounts for approximately 85% of all lung cancers. ALK gene rearrangements are identified and targeted resulting in promising response rates for NSCLC in early studies. Considering the significance of Crizotinib in the treatment of NSCLC, the synthesis, pharmacodynamics, pharmacokinetics, therapeutic trials and adverse events are briefly overviewed in order to make more scholars, medical workers and patients have a more clear and comprehensive recognition on Crizotinib.展开更多
文摘Wistar rats were inoculated with purified YWK-I antibody. The anti-idiotypie antibodies were isolated from rat sera by successive passage over affinity chromatography columns of YWK-I mAb and normal mouse Igs. Specificity of anti-Id antibody was established by ELISA. The 84 kD protein inhibited the binding of anti-Id to YWK-I mAb, but failed to repress antibody against normal mouse Ig binding to YWK-I mAb. In competitive inhibition assay, 84 kD protein had shown the ability to compete with anti-Id binding to YWK-I mAb in a dose-dependent manner. Crude sperm extract showed a lower competitive ability. No effeet was found with the irrelevant 36 kD sperm protein. The antisera from the Ba1b/e mice immunized with AId contained Ab3 that reacted with 84 kD sperm protein. The binding of anti-Id to YWK-I mAb was inhibited by Ab3 in a dose-dependent fashion and Ab3 was shown to be able to induce human sparm agglutination. These results indicate that anti-Id which may mimio an epitope of the 84 kD protein could be exploited as an antigen to raise antibodies against sperm protein.
文摘The heavy chain variable region genes of 5 human polyreactive mAbs generated in our laboratory have been cloned and sequenced using polymerase chain reaction (PCR) technique. We found that 2 and 3 mAbs utilized genes of the VHIV and VHIII families, respectively. The former 2 VH segments were in germline configuration. A common VH segment, with the best similarity of 90.1 % to the published VHIII germline genes, was utilized by 2 different rearranged genes encoding the V regions of other 3 mAbs. This strongly suggests that the common VH segment is a unmutated copy of an unidentified germline VHIII gene. All these polyreactive mAbs displayed a large NDN region (VH-D-JH junction). The entire H chain V regions of these polyreactive mAbs are unusually basic. The analysis of the charge properties of these mAbs as well as those of other poly- and mono- reactive mAbs from literatures prompts us to propose that the charged amino acids with a particular distribution along the H chain V region,especially the binding sites (CDRs), may be an important structural feature involved in antibody polyreactivity.
文摘Objective： Invasion and metastasis are the most significant and intrinsic biological characteristics of cancers, also which are main factors of malignant tumor causing treatment failure and death. Recent studies have found that Fra-1 plays an important role on cell migration, invasion, and maintaining malignant phenotype of transformed cells. But there are few stud- ies about the expression and location of Fra-1 in breast tissues and cells being reported .This study just aims to discuss the expression and location of transcription factor Fra-1 in benign and malignant human breast tissues. Methods： The expression of Fra-1 was investigated by immunohistochemistry in neoplastic breast diseases ranging from benign fibroadenoma to very aggressive undifferentiated carcinoma. The correlations of Fra-1 expression with other indicators of breast carcinoma prog- nosis （ER, PR and ErbB2 receptors） were analyzed. Results： All neoplastic breast tissues, either benign or malignant breast tissues, were nuclear immunoreactive for Fra-l-recognizing antibody. In 85% of benign tumors （17/20）, the immunoreactive for Fra-l-recognizing antibody as exclusively restricted to the nuclei. In three cases （3/20, 15%）, focal unequivocal cytoplas- mic staining was also exhibited. Strong positive nuclear staining for Fra-1 was easily seen in all types of breast carcinomas. However the nucleaflcytoplasmic concomitant immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization was noticed in 90.2% （37/41） of breast carcinomas. No inverse relationship between Fra-1 and ER and PR protein levels was noticed in malignant tumors. The relative expression level of Fra-1 was not correlated with the expression of ErbB2. Conclusion： The overall expression, pattern and intensity of Fra-1 proteins were correlated with breast oncogenesis. Overexpression of Fra-1, leading to a persistent high cytoplasmic accumulation, may play a role in the process of breast carcinogenesis.
文摘Crizotinib is a mesenchymal-epithelial transition/anaplastic largecell kinase （MET/ALK） multi-targeted receptor tyrosine kinase inhibitor and has been rapidly and successfully developed as an inhibitor in ALK-rearranged NSCLC （non-small cell lung cancer）. Lung cancer is the major cause of cancer-related mortality, accounting for over one quarter of cancer deaths. Lung cancers are generally divided into two main categories： SCLC （small cell lung cancer） and NSCLC. NSCLC accounts for approximately 85% of all lung cancers. ALK gene rearrangements are identified and targeted resulting in promising response rates for NSCLC in early studies. Considering the significance of Crizotinib in the treatment of NSCLC, the synthesis, pharmacodynamics, pharmacokinetics, therapeutic trials and adverse events are briefly overviewed in order to make more scholars, medical workers and patients have a more clear and comprehensive recognition on Crizotinib.
