Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer.

PURPOSE: Mutations in epidermal growth factor receptor (EGFR) can be used to predict the tumor response of patients receiving gefitinib for non-small cell lung cancer (NSCLC). We investigated the association between mutations in EGFR tyrosine kinase domain and tumor response and survival in gefitinib-treated NSCLC patients. EXPERIMENTAL DESIGN: EGFR mutations in exons 18 to 21 were analyzed by DNA sequencing of paraffin-embedded tumor tissues from gefitinib-treated NSCLC patients. The results were correlated with clinical variables. RESULTS: EGFR mutations were found in 61.1% (33 of 54) of cases; response rate and disease control rate were 56.8% and 68.5%, respectively. There was no significant difference in mutation rates between adenocarcinoma (29 of 43) and nonadenocarcinoma (4 of 11; P = 0.085). However, all four nonadenocarcinomas with EGFR mutations had no response to gefitinib. Presence of EGFR mutations was the only independent predictor for disease control (P = 0.003) and tumor response (P = 0.017) in multivariate analysis; positive predictive values were 87.9% and 70.8% and negative predictive values were 61.9% and 69.2%, respectively. In comparison with patients whose tumor was negative for EGFR mutations, patients with EGFR mutations had better progression-free survival (median, 7.6 versus 1.7 months; P = 0.011) and overall survival (median, 14.7 versus 4.7 months; P = 0.046). CONCLUSIONS: Mutations in EGFR tyrosine kinase correlate with treatment response and survival in gefitinib-treated NSCLC patients and can be used as a predictive and prognostic factor. Thus, analysis of EGFR tyrosine kinase mutations in lung adenocarcinoma is of clinical significance, as it can permit the customization of treatment with EGFR tyrosine kinase inhibitors.     

Effect of tissue inhibitor of metalloproteinases-3 genetics polymorphism on clinicopathological characteristics of uterine cervical cancer patients in Taiwan

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. The study included 123 patients with invasive cancer and 97 with precancerous lesions of uterine cervix, and 300 control women. TIMP-3 polymorphisms rs9619311, rs9862 and rs11547635 were checked and their genotypic distributions were determined by real-time polymerase chain reaction. It showed that women with genotypes CT/TT in rs9862 were found to display a higher risk of developing cervical cancer with moderate and poor cell differentiation. Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.     

白蛋白微球作为肝靶向给药载体的研究

用均匀设计方法和计算机技术筛选了乳化化学交联法制备白蛋白微球的六个因素,十二个水平。优化出最佳制备工艺,制备了平均粒径0.41～0.47μm的白蛋白微球。将此工艺制备的¹²⁵I-白蛋白微球做动物体内研究,结果表明微球iv后主要浓集在肝脏,可达注入总剂量的68%,此微球在靶组织肝脏的变化规律可用二室模型契合。     

Uterine leiomyosarcoma metastasis to the breast

BACKGROUND: Uterine leiomyosarcoma is a rare female neoplasm with a high recurrent and metastatic rate. However, only a few cases have been reported on metastasis to the breast. The purpose of this work is to stress the role of follow-up and to increase physicians' awareness of such lesion. case: A 62-year-old female suffered from a breast nodule and multiple metastases six years after resection for uterine leiomyosarcoma. Pathology revealed a rare condition of uterine leiomyosarcoma with breast metastasis. CONCLUSION: The case highlights the important role of long-term follow-up in uterine leiomyosarcoma and implies the necessity of tissue proof in patients with the disease.     

TWO NOVEL MUTATIONS IN PHENYLALANINE HYDROXYLASE GENE AND IN VITRO EXPRESSION ANALYSIS ON MUTATION ARG252GLN

INTRoDUCTIoNPhenylketonuria(PKU)isanautosomalrecessivediseasecausedbythedeficiencyofaliver-specificen-zyme,phenylalaninehydroxylase(PAH).Itisoneofthemostcommoninbornerrorsofmetabolismwithaprevalenceof1in17OOOnewbornChinese(l).Recent-ly,theuseofalternativemolecularapproachesforstudy-ingPKUpatientsfromvariousethnicgroupsworldwidehasrevealedatleast14OdifferentpointmutationsinthehumanPAHgene(2,3),andmorethanl3mutationshavebeenreportedinChinesepopulations(4～9)'Tofurtherinvestigatethemol…     

Antipsychotics: Past and Future: National Institute of Mental Health Division of Services and Intervention Research Workshop, July 14, 1998.

A workshop on "Antipsychotics: Past and Future" was convened by the National Institute of Mental Health (NIMH), Division of Services and Intervention Research (DSIR), on July 14, 1998, to review the results of recent antipsychotic drug research, discuss current standards of treatment, and identify areas needing further study. There has been a proliferation of new antipsychotic medications and a rapid increase in their clinical utilization. The new atypicals are beginning to supplant the older typical neuroleptic antipsychotics, and the scientific and ethical issues raised by this transition prompted the workshop. Given the apparent, albeit not fully defined, advantages of atypical drugs, particularly their safety profiles, the question is whether more comparisons with typical antipsychotics are warranted and whether clinical trial designs warrant (or would be justified in) the inclusion of typical drugs as standard active comparators. Workshop participants--including clinical researchers, patient advocates, bioethicists, and NIMH staff--discussed the conclusions drawn from current data, ethical issues for subjects in clinical trials, funding for ongoing studies using typical agents, and appropriate comparators for trials using atypical agents.     

Radiofrequency Ablation of Hepatic Metastases: Factors Influencing Local Tumor Progression

Background

Although radiofrequency ablation (RFA) of nonresectable hepatic metastases has gained wide acceptance by showing survival benefit in selected patients, scattered reports are available regarding risk factors of local control of percutaneous RFA. The purpose of this study was to prospectively evaluate the factors influencing local tumor progression after percutaneous RFA of hepatic metastases.

Methods

Sixty-nine hepatic metastatic lesions in 54 patients were treated by percutaneous RFA. Efficacy was evaluated by contrast-enhanced computed tomography or magnetic resonance imaging at 1 month after ablation, then at 3-month intervals for the first year and biannually thereafter.

Results

The results of the log-rank test showed that tumor size of <3 cm (p = 0.024) and the absence of tumor contiguous with large vessels (p = 0.002) significantly correlated with local control for hepatic metastases. Cox regression analysis showed that the tumor size <3 cm and the absence of tumor contiguous with large vessels were independent factors (p = 0.055 and 0.009, respectively). The results of the log-rank test showed that neither the threshold post-ablation margin of 1.8 cm (p = 0.064) nor the presence of a tumor with subcapsular location (p = 0.134) correlated with the success of local control.

Conclusions

Percutaneous RFA is more effective in achieving local control in patients with hepatic metastases when the tumor size is <3 cm and not contiguous with large vessels.