A functional genomic approach integrating microarray and proteomic analyses done in our laboratory has identified 14-3-3Z as a putative oncogene whose activation was common and driven by its genomic amplification in lung adenocarcinomas. 14-3-3Z is believed to function in cell signaling, cycle control, and apoptotic death. Following our initial finding, here, we analyzed its expression in lung tumor tissues obtained from 205 patients with various histologic and stage non-small cell lung cancers (NSCLC) using immunohistochemistry and then explored the effects of specific suppression of the gene in vitro and in a xenograft model using small interfering RNA. The increased 14-3-3Z expression was positively correlated with a more advanced pathologic stage and grade of NSCLCs (P = 0.001 and P = 0.006, respectively) and was associated with overall and cancer-specific survival rates of the patients (P = 0.022 and P = 0.018, respectively). Down-regulation of 14-3-3Z in lung cancer cells led to a dose-dependent increased sensitivity to cisplatin-induced cell death, which was associated with the inhibition of cell proliferation and increased G 2 -M arrest and apoptosis. The result was further confirmed in the animal model, which showed that the A549 lung cancer cells with reduced 14-3-3Z grew significantly slower than the wild-type A549 cells after cisplatin treatment (P = 0.008). Our results suggest that 14-3-3Z is a potential target for developing a prognostic biomarker and therapeutics that can enhance the antitumor activity of cisplatin for NSCLC. [Cancer Res 2007;67(16):7901-6]

Purpose: Analysis of molecular genetic markers in biological fluids has been proposed as a powerful tool for cancer diagnosis. We have characterized in detail the genetic signatures in primary non^small cell lung cancer, which provided potential diagnostic biomarkers for lung cancer. The aim of this study was to determine whether the genetic changes can be used as markers in sputum specimen for the early detection of lung cancer. Experimental Design: Genetic aberrations in the genes HYAL2, FHIT, and SFTPC were evaluated in paired tumors and sputum samples from 38 patients with stage I non^small cell lung cancer and in sputum samples from 36 cancer-free smokers and 28 healthy nonsmokers by using fluorescence in situ hybridization. Results: HYAL2 and FHIT were deleted in 84% and 79% tumors and in 45% and 40% paired sputum, respectively. SFTPC was deleted exclusively in tumor tissues (71%). There was concordance of HYAL2 or FHIT deletions in matched sputum and tumor tissues from lung cancer patients (r = 0.82, P = 0.04; r = 0.84, P = 0.03), suggesting that the genetic changes in sputum might indicate the presence of the same genetic aberrations in lung tumors. Furthermore, abnormal cells were found in 76% sputum by detecting combined HYAL2 and FHIT deletions whereas in 47% sputum by cytology, of the cancer cases, implying that detecting the combination of HYAL2 and FHIT deletions had higher sensitivity than that of sputum cytology for lung cancer diagnosis. In addition, HYAL2 and FHIT deletions in sputum were associated with smoking history of cancer patients and smokers (both P < 0.05).Conclusions: Tobacco-related HYAL2 and FHIT deletions in sputum may constitute diagnostic markers for early-stage lung cancer.

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The diagnosis and treatment of unexplained recurrent spontaneous abortion (URSA) is an important and hot topic in the field of obstetrics and gynecology. During our clinical investigation (observation), we have found that URSA patients usually experience recurrent vaginitis or vaginal dysbacteriosis during periods of non-pregnancy, pregnancy, and post-abortion. However, there is no research on vaginal dysbacteriosis's influence on URSA. Using women with normal induced abortion as a control group, and using 16S rRNA sequencing, which helps to screen differentially expressed flora, this study discusses the relevance between differential bacteria at the genus level and the incidence of URSA. Another aim of this study is to determine whether certain pathogenic genera can cause an imbalance in immune tolerance of the maternal and fetal interface through regulatory chemokines, which leads to recurrent spontaneous abortion. This article has explored URSA pathogenesis from the perspective of differentially expressed vaginal flora, which has great theoretical significance for the early diagnosis and treatment of URSA.

Interphase multicolor fluorescence in situ hybridization (IM-FISH) has great promise for improving cancer diagnosis because it can directly visualize multiple changes in chromosomes and gene copy number on a cellto-cell basis. However, no more than four targets can be detected simultaneously by current commercially available IM-FISH protocols, and the DNA probes used are too large to detect the single-gene aberrations that characterize tumorigenesis. As a result, multiple FISH has a low sensitivity in detecting cancer cells. To overcome such limitations, we first developed specific genomic probes for the genes relevant to primary lung cancer. We next designed a multiple FISH array by arranging four different compositions of cocktails of four probes for each gene on a coverslip, which allowed four four-color FISH experiments to be performed in parallel on a single slide. We then tested the multiple FISH array on bronchial brushing samples from lung cancer patients to determine its ability to detect genetic abnormalities. A comparison of the data with the results of cytology and commercial four-color FISH suggested that the multiple FISH array had the highest sensitivity for cancer detection. The technique may thus be a powerful laboratory strategy for cancer prevention and early detection and for improved patient management.