[Up-regulation of DLK1 in non-small cell lung cancer and the relevant molecular mechanism].

OBJECTIVE: To explore the expression of delta-like 1 homolog (DLK1) gene in non-small cell lung cancer (NSCLC) and its regulatory mechanism. METHODS: The expression levels of DLK1 protein in 204 NSCLC tissues were examined by immunohistochemical (IHC) staining, and the correlation between DLK1expression and clinicopathological features was analyzed. Bisulfate sequencing PCR (BSP) of DNA samples from the tumor tissues of 18 NSCLC patients was performed to evaluate the DNA methylation status of CpG island in the DLK1 promoter region, and also compared with the corresponding IHC staining of DLK1 protein in the same samples. RESULTS: Among the 102 squamous cell carcinoma (SCC) tissue specimens and their adjacent normal bronchial epithelia, DLK1 was up-regulated in 72 and 37 samples, respectively (P=0.001), and among 102 adenocarcinomas (ADC) tissues and their adjacent alveolar tissues, DLK1 was up-regulated in 77 and 7 samples, respectively (P<0.001). In addition, overexpression of DLK1 was significantly associated with histological type, clinical stage and tumor size of NSCLC (P<0.05 for all). The expression of DLK1protein was inversely correlated with its promoter methylation (P<0.05). CONCLUSION: DLK1 expression is up-regulated in NSCLCs, which may be due, at least in part, to the DNA hypomethylation in the promoter region of theDLK1 gene.

Diagnostic yield of capsule endoscopy in ulcerative colitis and inflammatory bowel disease of unclassified type (IBDU).

BACKGROUND AND STUDY AIMS: Capsule endoscopy is increasingly reported as an important diagnostic procedure in patients with known or suspected Crohn's disease, but its clinical utility in patients with ulcerative colitis or unclassified type inflammatory bowel disease (IBDU) is unclear. The aim of our study was to determine the diagnostic yield of capsule endoscopy for small-bowel disease in patients with ulcerative colitis and IBDU. PATIENTS AND METHODS: All data from patients with a history of ulcerative colitis or IBDU who underwent capsule endoscopy between October 2001 and August 2005 were analyzed for procedure indications and findings. Images were reviewed by an experienced capsule endoscopist. The finding of multiple ulcerations (three or more) on capsule endoscopy was classified as diagnostic of small-bowel Crohn's disease. RESULTS: 120 patients had undergone 122 capsule endoscopy procedures. Overall, 19 of 120 patients (15.8 %) had capsule endoscopy findings consistent with the diagnosis of Crohn's disease. The proportion of patients with small-bowel disease was significantly higher among patients with a history of colectomy (7 of 21 patients, 33 %) compared with those without colectomy (12/99, 12 %) ( P = 0.04). Among patients with positive findings on capsule endoscopy, 18 had also previously undergone a small-bowel follow-through study and only one showed findings consistent with Crohn's disease. CONCLUSIONS: Many patients with a diagnosis of ulcerative colitis and atypical features or IBDU may have small-bowel findings on capsule endoscopy that are consistent with Crohn's disease. Capsule endoscopy should be considered in ulcerative colitis patients with atypical clinical features particularly after colectomy.

[Preliminary study on the antimutagenesis of vegetables and fruits].

Possible antimutation of 108 preparations of 91 kinds of vegetables and fruits on Salmonella typhimurium TA98 and TA100 mutants was tested. 4-nitroquinoline-N-oxide (4 NQO), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), aflatoxin B1 (AFB1) and benzo (a) pyrene (BaP) were used as mutagens. The results showed that 67 (62%) preparations had antimutagenic action in vitro to different degrees. 9.6% of all preparations showed inhibition action on 4 NQO in TA100 mutant and 12.3%, in TA98, 5% on MNNG in TA100, 38% on AFB1 in TA100 and 45.1% in TA98, 28.9% on BaP in TA100. This experiment provides a scientific basis to the study of food resources as prevention of carcinogenesis.

Genetic alterations in pulmonary epithelioid hemangioendothelioma and epithelioid angiosarcoma.

Epithelioid hemangioendothelioma (EHE) is a low-to-intermediate-grade vascular tumor that occurs in many organs, and epithelioid angiosarcoma (EA) is a subtype of angiosarcoma that is associated with high-grade malignancy. These two types of tumors have different forms of biological behavior. Pulmonary epithelioid hemangioendothelioma (PEH) and epithelioid angiosarcoma (PEA) are both very rare, and genetic studies on them are extremely limited. We examined and compared the cytogenetic characteristics of these two types of lung tumors in two patients utilizing the Array-Comparative Genomic Hybridization (Array-CGH) method. Considerable differences in the cytogenetic characteristics were observed between the two types of tumors. Small fragment gains (<10 MB) were dominant in PEH, whereas large fragment gains and deletions (>10 MB) were dominant in PEA. Some large fragment alterations, such as gains in chromosomes 19q and 19p, and deletions in chromosomes 9p and 13q, involved over half of a chromosome arm. PEH and PEA showed great cytogenetic differences; therefore, further genetic studies on these two types of tumors are warranted.

[Inhibitory effects of N-(4-hydroxylphenol) retinamide on transformed human bronchial epithelial cells in vitro and reconstructed human bronchial epithelium in vivo].

Precancerous lesion is one of most important steps in tumorigenesis. It has been shown that retinoids have reliable effects on controlling many kinds of animal tumor and malignant tumor cell lines in vitro, but there is no laboratory report on the biological effect of retinoids on the precancerous lesion of human lung cancer. In this study the methods including of cell serum-free culture, precancerous model of human bronchial epithelium reconstructed in rat trachea/xenotransplanted in nude mice, flowcytometry, immunohistochemistry, TUNEL and pathological observation have been used to study the biological effects of N-(4-hydroxylphenol) retinamide (4-HPR), one new kind of retinoids, on transformed human bronchial epithelial cells in vitro and premalignant human bronchial epithelium in vivo. The results showed that in the study in vitro, the proliferation of transformed human bronchial epithelial cells, the ratio of cells in S phase, and the percentage of cells that positively react to antibody Ki-67 and mpm-2 were inhibited, but apoptotic cells were induced significantly by 4-HPR exposure. At the experiment in vivo, both growth rates and precancerous grades of the reconstructed human bronchial epithelium were reduced, and apoptotic cells were also observed in epithelium after 4-HPR treatment. The results suggested that 4-HPR is one of hopeful chemopreventive medicines to lung cancer.

Molecular cytogenetic alterations in the early stage at human bronchial epithelial cell carcinogenesis.

Lung carcinogenesis is a multi-step process involving activation of oncogenes and inactivation of tumor suppress genes. Many molecular and cytogenetic alterations occur in the early stages of carcinogenesis. We have developed an effective culture system for human bronchial epithelial cells and lung cancer cells. Four immortalized human bronchial epithelial cell lines were established by transfecting the epithelial cells with plasmid DNA containing the early region of SV40. Some molecular and cytogenetic alterations, such as 3p-, 2q-, 9p-, c-myc translocation t(8;14) (q23; q32), were found in one immortalized bronchial epithelial cell line M when approaching malignant transformation. An increase in cell proliferation and decrease of apoptosis were noted in the late passages of the immortalized cell line M. Some molecular cytogenetic alterations were also observed in human primary non-small cell lung cancers. Molecular cytogenetic alterations during the early stage of carcinogenesis of human bronchial epithelial cells may be useful as biomarkers for both diagnosis and intermediate endpoint of chemoprevention of lung cancer.