• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.261-267
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• 2012

Purpose: The relationship between thymidylate synthase (TS) expression and outcomes in gastric cancer (GC) patients remains controversial, although most studies reported poor survival and reduced response to fluoropyrimidine were related to high TS in tumors. We carried out a systematic review of the literature with meta-analysis to estimate the predictive value of TS expression from published studies. Methods: We indentified 24 studies analysing the outcome data in gastric cancer stratified by TS expression. Effect measures of outcome were hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS), or the odds ratio (OR) for overall response rate (ORR). HRs and ORs from these eligible studies were pooled using random-effects meta-analysis. Results: Fifteen studies investigated outcomes in a total of 844 patients with advanced GC, and nine studies investigated outcomes in a total of 1,235 patients with localized GC undergoing adjuvant therapy. Meta-analysis of estimates showed high TS expression was significantly associated with poor OS in the advanced setting (HR: 1.43, 95%CI: 1.08 - 1.90), and poor EFS in the adjuvant setting (HR: 1.53, 95%CI: 1.01 - 2.32). Subgroup analysis demonstrated TS expression to haves even greater value in predicting OS, EFS and ORR in advanced GC patients treated with fluoropyrimidine monotherapy (HR for OS: 2.32, 95%CI: 1.53 - 3.50; HR for EFS: 1.76, 95%CI: 1.19 - 2.60; OR for ORR: 0.32, 95%CI: 0.11 - 0.95). Conclusion: High levels of TS expression were asssociated with a poorer OS for advanced GC patients compared with low levels. In the adjuvant setting, high TS expression was also associated with a worse EFS. Additional studies with consistent methodology are needed to define the precise predictive value of TS.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5505-5510
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• 2012

Objective: The aim of this retrospective study is to analyze the clinical and pathological factors related to the prognosis of Chinese patients with stage Ib to IIb cervical cancer. Methods and Results: 13 clinical pathological factors in 255 patients with stage Ib to IIb cervical cancer undergoing radical hysterectomy and systematic lymphadenectomy were analyzed to screen for factors related to prognosis. The cumulative 5-year survival of the 255 patients was 75.7%. The result of the univariate analysis suggested that clinical stage, cell differentiation, depth of cervical stromal invasion, parametrial tissue involvement, and lymph node metastasis were prognostic factors for patients with stage Ib to IIb cervical cancer (P<0.05). Compared with cases with involvement of iliac nodes, obturator nodes, or inguinal lymph nodes, cases with metastasis to the common iliac lymph nodes had a poorer prognosis (P<0.05). Cases with involvement of four or more lymph nodes had a poorer prognosis than those with involvement of three or fewer lymph nodes (P<0.05). Using multivariate Cox proportional hazards model regression analysis, non-squamous histological type, poor differentiation, parametrial tissue involvement, and outer 1/3 stromal invasion were found to be independently related to patients poor prognosis (P<0.05). Conclusion: Non-squamous histological type, poor cell differentiation, parametrial tissue involvement, and outer 1/3 stromal invasion are the independent poor prognostic factors for patients with stage Ib to IIb cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.33-35
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• 2012

To evaluate the relationship between abortions and risk of breast cancer, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The results have revealed that induced abortion was related to increased risk of breast caner. Premenopausal women who had ${\geq}3$ times of induced abortion were at increased crude OR (2.41, 95%CI: 1.09-5.42) and adjusted-OR (1.55, 95%CI: 1.15-5.68). Postmenopausal women with a previous induced abortion were at increased crude OR (2.04, 95%CI: 1.48-2.81) and adjusted-OR (1.82, 95%CI: 1.30-2.54), and there was a significant increase trend in OR with number of induced abortions (p for trend: 0.0001). Overall, spontaneous abortion did not significantly alter the risk of breast cancer, but postmenopausal women who had history of spontaneous abortion were at increased OR. These results suggested that relationship between breast cancer and abortions may depend on menopausal status and induced abortion may played an important role in the development of breast cancer in Jiangsu' women of China.

• Geomechanics and Engineering
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• 제11권2호
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• pp.253-267
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• 2016

The stability of surrounding rock will be poor when the tunnel is excavated through nearly horizontal stratum. In this paper, the instability mechanism of local nearly horizontal stratum in super-large section and deep buried tunnel is revealed by the analysis of the macro failure and micro fracture. A structural model is proposed to explain the mechanics of surrounding rock collapse under the action of stress redistribution and shed light on the macroscopic analytical approach of the stability of surrounding rock. Then, some highly effective formulas applied in the tunnel engineering are developed according to the theory of mixed-mode micro fracture. And well-documented field case is made to demonstrate the effectiveness and accuracy of the proposed analytical methods of mixed-mode fracture. Meanwhile, in order to make the more accurate judgment about yield failure of rock mass, a series of comprehensive failure criteria are formed. In addition, the relationship between the nonlinear failure criterion and $K_I$ and $K_{II}$ of micro fracture is established to make the surrounding rock failure criterion more comprehensive and accurate. Further, the influence of the parameters related to the tension-shear mixed-mode fracture and compression-shear mixed-mode fracture on the propagation of rock crack is analyzed. Results show that ${\sigma}_3$ changes linearly with the change of ${\sigma}_1$. And the change rate is related to ${\beta}$, angle between the cracks and ${\sigma}_1$. The proposed simple analytical approach is economical and efficient, and suitable for the analysis of local nearly horizontal stratum in super-large section and deep buried tunnel.

• BMB Reports
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• 제40권4호
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• pp.571-576
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• 2007

Three anti-apoptosis genes, Ls-iap2, iap3 and p49 were found in Leucania separata multiple nuclear polyhedrovirus. Amino acid sequence homology of Ls-IAP2 and Ls-IAP3 with Op-IAP2 and Op-IAP3 from Orgyia pseddotsugata MNPV were 20% and 42%, while that of Ls-P49 is 28% with Sl-P49 from Spodoptera littorolis MNPV. Ls-IAP2 contains one baculoviral IAP repeat (BIR) domain followed by a RING domain, while Ls-IAP3 contains two BIRs and a RING. Ls-P49 contains a reactive site loop, predicted cleavage site (KKLD$^{74}{\downarrow}$G) that is different from Sl-P49 (TVID$^{94}{\downarrow}$G). Expressed Ls-iap3 or Ls-p49 under presence of actinomycin D in SF9 cells, DNA ladder assayrevealed that Ls- IAP3 or Ls-P49 could block the apoptosis of SF9 cells induced by actinomycin D. Replication of p35 deficient-mutant Autographa californica MNPV in SF9 cells was also rescued when Ls-iap3 or Ls-p49 was expressed transiently. No anti-apoptotic activity was observed for Ls-IAP2. The results showed that both of Ls-IAP3 and Ls-P49 were functional apoptotic suppressors in SF9 cells.

• Molecules and Cells
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• 제27권1호
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• pp.39-45
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• 2009

Ligand-dependent or independent oligomerization of receptor protein tyrosine kinase (RPTK) is often an essential step for receptor activation and intracellular signaling. The novel oncogene with kinase-domain (NOK) is a unique RPTK that almost completely lacks an ectodomain, expresses intracellularly and activates constitutively. However, it is unknown whether NOK can form oligomer or what function oligomerization would have. In this study, two NOK deletion mutants were generated by either removing the ectodomain ($NOK{\Delta}ECD$) or including the endodomain (NOK-ICD). Co-immunoprecipitation demonstrated that the transmembrane (TM) domain of NOK was essential for its intermolecular interaction. The results further showed that NOK aggregated more closely as lower order oligomers (the dimer- and trimer-sized) than either deletion mutant did since NOK could be crosslinked by both Sulfo-EGS and formaldehyde, whereas either deletion mutant was only sensitive to Sulfo-EGS. Removing the NOK TM domain (NOK-ICD) not only markedly promoted higher order oligomerization, but also altered the subcellular localization of NOK and dramatically elevated the NOK-mediated constitutive activation of extracellular signal-regulated kinase (ERK). Moreover, NOK-ICD but not NOK or $NOK{\Delta}ECD$ was co-localized with the upstream signaling molecule RAS on cell membrane. Thus, TM-mediated intermolecular contacting may be mainly responsible for the constitutive activation of NOK and contribute to the autoinhibitory effect on RAS/MAPK signaling.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2897-2901
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• 2012

Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin. Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (FAK) and JNK in CHG-5 and CHG-hS cells. The migration ability of CHG-hS cells was significantly higher than that of CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925 sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 site was not changed. Phosphorylated Src, JNK and Akt levels in CHG-hS cells were also significantly upregulated. Phosphorylation of JNK and Akt were abolished by the specific inhibitors SP600125 and LY294002, respectively, and the migration ability of CHG-hS cells was decreased, indicating that the JNK and PI3K/Akt pathways play important roles in regulating mda-9/syntenin-induced human brain glioma migration. Our results indicate Mda-9/syntenin overexpression could activate FAK-JNK and FAK-Akt signaling and then enhance the migration capacity of human brain glioma cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4897-4902
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• 2014

Purpose: To investigate the anticancer effects and underlying mechanisms of parthenolide on HepG2 human hepatocellular carcinoma cells. Materials and Methods: Cell viability was assessed by MTT assay and cell apoptosis through DAPI, TUNEL staining and Western blotting. Monodansylcadaverin(MDC) and AO staining were used to detect cell autophagy. Cell proliferation was assessed by Ki67 immunofluorescence staining. Results: Parthenolide induced growth inhibition in HepG2 cells. DAPI and TUNEL staining showed that parthenolide could increase the number of apoptotic nuclei, while reducing the expression of the anti-apoptotic protein Bcl-2 and elevating the expression of related proteins, like p53, Bax, cleaved caspase9 and cleaved caspase3. Parthenolide could induce autophagy in HepG2 cells and inhibited the expression of proliferation-related gene, Ki-67. Conclusions: Parthenolide can exert anti-cancer effects by inducing cell apoptosis, activating autophagy and inhibiting cell proliferation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.5055-5061
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• 2014

In this study, an anti-oxidant and anti-tumor protein Latcripin-3 of Lentinula edodes C91-3 was expressed in Escherichia coli. for the first time. According to the cDNA library, the full-length gene of Latcripin-3 was cloned by the methods of 3'-full rapid amplification of cDNA Ends (RACE) and 5'-full RACE. The structural domain gene of Latcripin-3 was inserted into the pET32 a(+). The functional protein of Latcripin-3 was expressed in Rosetta-gami (DE3) E. coli, evaluated by Western blotting and mass spectrometry. DPPH testing showed that the protein Latcripin-3 can scavenge free radicals remarkably well. The activity of functional protein Latcripin-3 on A549 cells was studied with flow cytometry and the MTT method. The MTT assay results showed that there was a decreases in cell viability in a dose-dependent and time-dependent manner in protein Latcripin-3 treated groups. Flow cytometry demonstrated that Latcripin-3 can induce apoptosis and block S phase dramatically in human A549 lung cancer cells as compared to the control group. At the same time, the cell ultrastructure observed by transmission electron microscopy supported the results of flow cytometry. This research offers new insights and advantages for identifying anti-oxidant and anti-tumor proteins.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7501-7508
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• 2013

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.