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Supplementary Table 1 from Cisplatin Depletes TREX2 and Causes Robertsonian Translocations as Seen in TREX2 Knockout Cells

Cisplatin, an anticancer drug, forms DNA interstrand cross-links (ICL) that interfere with replication, whereas TREX2 is a 3′→5′ exonuclease that removes 3′ mismatched nucleotides and promotes cellular proliferation. Here, we show that TREX2 is depleted in human cells derived from cancer after exposure to cisplatin but not other genotoxins including another cross-linking agent, mitomycin C (MMC), indicating a potential role for TREX2 depletion in cisplatin-induced cytotoxicity. To better understand TREX2 cellular function, we deleted TREX2 in mouse embryonic stem (ES) cells by gene targeting and find these cells exhibit reduced proliferation and gross chromosomal rearrangements including Robertsonian translocations (RbT). Quite interestingly, ES cells exposed to cisplatin also exhibit RbTs. By contrast, RbTs are not observed for ES cells exposed to MMC, indicating that RbTs are not caused by ICLs but instead TREX2 depletion by either cisplatin exposure or mutation. Taken together, our results show that cisplatin depletes TREX2 and causes genomic instability that is similarly observed in TREX2-mutant cells. Thus, cisplatin has two potential cytotoxic activities: (a) the generation of ICLs and (b) the depletion of TREX2. [Cancer Res 2007;67(19):9077–83]

This paper introduces the advantages of capillary roof radiant heating system, by using finite element numerical method, the indoor temperature distribution of capillary radiant roof and underfloor supply air composite system is simulated, using the theory of exergy to analysis the energy saving of the system, the result proves that the system can well satisfy indoor comfort requirements, and compared with the floor radiation heating system can saving energy 65.8%, has great research value.

Oil spills are almost constantly present in recent years, which cause ecological disaster of marine environment. It is important to detect the area of oil spill to take rescue measurement in time. The paper took the EnviSat Asar image as example to detect the boundary of oil spills. Firstly, the paper removed speckle noise by Histogram Equalization. Then, image segmentation was carried out by open-close mixed operation in mathematical morphology. At last, the region of oil spill was exacted independently.

TREX2 is an autonomous nonprocessive 3' --5' exonuclease, suggesting that it maintains genome integrity. To investigate TREX2's biochemical and cellular properties, we show that endogenous TREX2 is expressed widely in mouse tissues and human cell lines. Unexpectedly, endogenous human TREX2 is predominantly expressed as a 30-kDa protein (not 26 kDa, as previously believed), which is likely encoded by longer isoforms (TREX2(L1) and/or TREX2(L2)) that possess similar capacity for self-association, DNA binding and catalytic activity. Site-directed mutagenesis analysis shows that the three functional activities of TREX2 are distinct, yet integrated. Mutation of amino acids putatively important for homodimerization significantly impairs both DNA binding and exonuclease activity, while mutation of amino acids (except R163) in the DNA binding and exonuclease domains affects their corresponding activities. Interestingly, however, DNA-binding domain mutations do not impact catalytic activity, while exonuclease domain mutations diminish DNA binding. To understand TREX2 cellular properties, we find endogenous TREX2 is down regulated during G2/M and nuclear TREX2 displays a punctate staining pattern. Furthermore, TREX2 knockdown reduces cell proliferation. Taken together, our results suggest that TREX2 plays an important function during DNA metabolism and cellular proliferation.

ATM (ataxia-telangiectasia-mutated) is a Ser/Thr kinase involved in cell cycle checkpoints and DNA repair. Human Rad9 (hRad9) is the homologue of Schizosaccharomyces pombe Rad9 protein that plays a critical role in cell cycle checkpoint control. To examine the potential signaling pathway linking ATM and hRad9, we investigated the modification of hRad9 in response to DNA damage. Here we show that hRad9 protein is constitutively phosphorylated in undamaged cells and undergoes hyperphosphorylation upon treatment with ionizing radiation (IR), ultraviolet light (UV), and hydroxyurea (HU). Interestingly, hyperphosphorylation of hRad9 induced by IR is dependent on ATM. Ser(272) of hRad9 is phosphorylated directly by ATM in vitro. Furthermore, hRad9 is phosphorylated on Ser(272) in response to IR in vivo, and this modification is delayed in ATM-deficient cells. Expression of hRad9 S272A mutant protein in human lung fibroblast VA13 cells disturbs IR-induced G(1)/S checkpoint activation and increased cellular sensitivity to IR. Together, our results suggest that the ATM-mediated phosphorylation of hRad9 is required for IR-induced checkpoint activation.

Discovery of early-diagnosis biomarkers is the key to improve the early-diagnosis and prognosis of human lung squamous carcinoma (hLSC). In order to identify more exhaustive and systematic protein biomarkers for early-diagnosis of hLSC, we chose LCM purified cells from hLSC tissues and paired normal bronchial epithelia(NBE) tissues and used two methods, the classical 2-DE/MS approach and the new iTRAQ analysis. We found a total of 63 differential proteins, 22 proteins in 2-DE and 59 proteins in iTRAQ analysis, between hLSC and NBE tissues. Among them, 18 proteins were quantified using both methods. The expression level of 15 proteins (68.2%) in 2-DE was consistent with that in iTRAQ analysis. Series of proteins involved in cytoskeleton, chaperone, GTP binding, metabolic process, cell apoptosis, cell proliferation and differentiation, signal transduction, transcription and translation were identified, suggesting their possible role in the emergence of oncogenic pathways leading to carcinogenesis of hLSC. These proteins may make as potential biomarkers for diagnosis of hLSC. The two methods gave us closely related but different information about proteins, suggesting they are complementary or at least supplementary methods at present. Our results show both the usefulness of iTRAQ reagent technology for identification of further potential marker proteins as well as for prevalidation of biomarker.

Cisplatin, an anticancer drug, forms DNA interstrand cross-links (ICL) that interfere with replication, whereas TREX2 is a 3′→5′ exonuclease that removes 3′ mismatched nucleotides and promotes cellular proliferation. Here, we show that TREX2 is depleted in human cells derived from cancer after exposure to cisplatin but not other genotoxins including another cross-linking agent, mitomycin C (MMC), indicating a potential role for TREX2 depletion in cisplatin-induced cytotoxicity. To better understand TREX2 cellular function, we deleted TREX2 in mouse embryonic stem (ES) cells by gene targeting and find these cells exhibit reduced proliferation and gross chromosomal rearrangements including Robertsonian translocations (RbT). Quite interestingly, ES cells exposed to cisplatin also exhibit RbTs. By contrast, RbTs are not observed for ES cells exposed to MMC, indicating that RbTs are not caused by ICLs but instead TREX2 depletion by either cisplatin exposure or mutation. Taken together, our results show that cisplatin depletes TREX2 and causes genomic instability that is similarly observed in TREX2-mutant cells. Thus, cisplatin has two potential cytotoxic activities: (a) the generation of ICLs and (b) the depletion of TREX2. [Cancer Res 2007;67(19):9077–83]

To explore the clinical application of video-assisted thoracoscopic surgery (VATS).We retrospectively analyzed the clinical data of 672 cases of VATS. There were 17 thoracic diseases such as emphysema, bullectomy for spontaneous pneumothorax, massive bullae, benign tumor of mediastinum, cyst of mediastinum, pulmonary benign tumors, hydropericardium, malignant pleural fluid, etc.The mean operation time was 57 minutes and there were no intraoperative complications. The bleeding during the operation was less than 100 mL. Postoperative pneumothorax occurred in 4 patients and among them 2 patients were of relapse after 1 month. The intrathoracic drain in most patients was removed with an average of 2. 5 days. A supplementary incision was needed in 10 cases: Six were due to the adhesion of full pleural cavity and 4 were found with the malignant tumor during the operation.VATS is an alternative approach that provides a safe, less invasive, and effective operation for treating spontaneous pneumothorax, benign tumor of mediastinum, cyst of mediastinum, pulmonary benign tumors, pericardial perfusion, and acute chest trauma patients.

The genesis of lung cancer was associated with mutation or abnormal expression of PTEN, p16, p21, and p53. Tissue microarray provides a high throughout tool for genes expression. But little is reported about expression of PTEN, p16, p21, and p53 in lung cancers with tissue microarray. The aim of this study was to investigate the expression of PTEN, p16, p21, and p53 proteins and to analyze their relationship with the pathogenesis, invasion, and metastasis in lung cancer.The expression of the antioncogene proteins in 100 cases of lung cancer and corresponding adjacent tissues were determined by tissue microarray combined with immunohistochemistry.The positive expression rates of PTEN, p16, p21, and p53 proteins were 31% (31/100), 38% (38/100), 42% (42/100), 53% (53/100) in lung cancer tissues, and were 85% (85/100), 72% (72/100), 80% (80/100), and 23% (23/100) in the adjacent cancer tissues, respectively, showing a low expression of PTEN, p16, p21 in cancer tissues, and high expression of p53 outside of them (P0.05, P0.01). Furthermore, the expression of PTEN, P16, and p53 proteins showed positive correlation with the clinical degrees and pathological stages of lung squamous carcinomas and adenocarcinomas (P0.05,P0.01). In lung cancer with lymph node metastasis, the expression of PTEN, p16, and p21 were low, but the expression of p53 increased significantly (P0.05, P0.01).Tissue microarray provided a useful high-throughout tool for multigene expression in large-scale investigations. There existed low expression of PTEN, p16, p21 proteins and over-expression of mutated p53 protein. Coexpression of these antioncogenes played an important role in invasion and metastasis in lung cancer.