[Relationship between UGT1A1 gene polymorphisms and irinotecan-induced severe adverse events].

Objective: To investigate the relationship between UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A1*93 polymorphisms and irinotecan-induced severe adverse reactions(grade 3-4 delayed diarrhea and neutropenia) in Chinese cancer patients. Methods: A total of 141 cancer patients treated with irinotecan were enrolled in this study. Peripheral venous blood was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A1*93 were analyzed by PCR and direct sequencing. The adverse reactions during chemotherapy were observed and recorded. The incidence of severe adverse reactions was compared among patients with different genotypes. Results: Among 141 patients, the cases with UGT1A1*6 GG, GA and AA genotypes were 71, 54 and 16, while those with UGT1A1*28 TA6/6, TA6/7 and TA7/7 genotypes were 105, 33 and 3, respectively. The cases with UGT1A1*60 AA, AC and CC genotypes were 52, 80 and 9, while those with UGT1A1*93 GG, GA and AA genotypes were 105, 32 and 4, respectively. The patients with grade 3-4 delayed diarrhea and neutropenia were 23 and 56, respectively. Multivariate logistic regression analysis showed that UGT1A1*6 and UGT1A1*60 genetic polymorphisms were independent factors influencing the occurrence of grade 3-4 delayed diarrhea. The risk of grade 3-4 delayed diarrhea in homozygous AA carriers of UGT1A1*6 increased 3.79 times compared with that in wild-type GG carriers (95%CI: 1.35-10.67). Moreover, the risk of grade 3-4 delayed diarrhea in homozygous CC carriers of UGT1A1*60 was 20.42 times compared with that in wild-type AA carriers (95%CI: 3.52-118.33). In addition, UGT1A1*28 genetic polymorphism was an independent factor of the occurrence of grade 3-4 neutropenia. The patients with homozygous TA7/7 carriers of UGT1A1*28 had an 1.61 times higher risk of grade 3-4 neutropenia compared with those with wild-type TA6/6 carriers (95%CI: 1.44-12.65). There was no correlation between UGT1A1*93 genetic polymorphism and severe adverse reactions caused by irinotecan. Conclusion: The cancer patients who carried UGT1A1*6, UGT1A1*28 and UGT1A1*60 gene polymorphisms have high risk of severe adverse events caused by irinotecan-based chemotherapy.

[A new melanoma antigen-encoding gene subfamily in human chromosome X].

A lot of studies have been focused on the tumor-related genes. We have cloned a new melanoma antigen-encoding gene (MAGE) from human fetal liver of third trimester and subsequently found that it represented a new MAGE gene subfamily, named MAGE-D. The MAGE-D subfamily contained three orthologs including human MAGE-D1, rat SNERG-1 and mouse DLXIN-1, and two paralogs including human MAGE-D and human KIAA1114. All human members of MAGE-D subfamily are located in human chromosome Xp11.21-p11.23. Moreover, MAGE-D subfamily stands out from other known subfamilies MAGE-A, -B and -C of MAGE family in view of typical features such as exon/intron organization, absence of tumorspecific antigens, evolutionarily divergent in sequences. The identification of MAGE-D subfamily will be helpful in understanding the genesis of tumor.

[Construction of fusion recombinant plasmid coding for RGD peptide and urokinase B chain, its expression in Escherichia coli and preliminary characterization of its biological activity].

A synthetic RGD (Arg-Gly-Asp) peptide-coding sequence was fused with urokinase B-chain cDNA and then cloned into the prokaryotic expression vector pBV220. The fused gene was expressed in E. coli DH5 alpha under the control of PRPL promoter by 42 degrees C induction. The expression level of the fusion protein was over 9.2% of the total bacterial proteins as a or of inactive inclusion body. The purified fusion protein was obtained with similar antigenicity as urokinase shown by Western blotting. Its in vitro fibrinolysis and anti-platelet aggregation activity was also evaluated by bioassay.

Some opinions on byssinosis in China.

On the basis of some study results in China and reports from abroad, a conclusion should be drawn that leads to the recognition of a pneumoconiosis-like lesion of interstitial fibrosis. This disease is called "cotton pneumoconiosis" and we may classify these occupational lesions into four types: 1) byssinosis; 2) chronic obstructive pulmonary disease (COPD); 3) cotton fever; and 4) cotton pneumoconiosis. Byssinosis, COPD, cotton fever and cotton pneumoconiosis may be different types of responses due to the different duration of exposure, the different parts of bronchial tree (upper respiratory tract, small airway, and respiratory part) where deposition occurs, and the different components of cotton dust (broken cotton fibers, bracts, pericarps, bacteria, and fungi). These responses, which include histaminelike reaction, allergy, and stimulation of foreign material, happen in different symptoms of the syndrome among cotton mill workers. But no matter whether responses caused by inhalation of dust are inflammation or allergic reaction, cotton dust is foreign stimulation on deposited sites, causing lung fibrosis after lung stimulation. For the health of cotton workers, we must pay attention not only to the acute effects but also to the chronic lesions. We therefore suggest that these four types of occupational lung disorders caused by inhalation of cotton dust may be called by the joint name, "Byssinosis syndrome."