• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1457-1461
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• 2012

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1981-1987
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• 2014

Objective: To establish the prevalence and distribution profile of esophageal squamous cell carcinomas (ESCCs) over a 22-yr period in North China. Methods: Using endoscopy for primary diagnosis and histological analysis for the further confirmation, a total of 74,854 ESCC patients aged 20-89 between January 1985 and December 2006 were investigated to analyze the epidemiological profile including prevalence rates, distribution of age-of-onset, gender and geographical area of ESCC in Luoyang, the highest incidence area of North China. Results: A total of 4092 cases of ESCC were finally diagnosed among 74,854 patients who had their first endoscopies. The prevalence among males was higher than that among females (p<0.01), resulting in an overall male:female OR of 1.2 (95%CI, 1.2-1.3). The prevalence in rural areas was higher than in urban areas (p<0.01), resulting in an overall rural:urban OR of 2.6 (95%CI, 2.4-2.9). The rural:urban ORs and the 95% CI increased continuously from 2.6, 2.3-3.0 to 2.7, 2.2-3.3, respectively, for 4 consecutive periods during the 22-yr study period. Moreover, the median age of onset among females was higher than that among males (p<0.01). For both sexes and in both areas, the prevalence rates declined and the median age of onset rose for 4 consecutive periods in the 22-yrs time frame (p<0.01). Conculsions: These data reveal the epidemiological profile of ESCC in the area of North China, and suggest that urban areas and rural people account for a growing proportion of the ESCC patients although the prevalence of ESCC significantly declined and the median age-of-onset postponed over the 22-yrs period. Moreover, the prevalence status of ESCC in rural areas also underlines the need for public health initiatives aimed at reducing risk factors of this fatal disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5249-5252
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• 2014

Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.

• Smart Structures and Systems
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• v.21 no.5
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• pp.687-694
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• 2018

The problem of wheel tread defects has become a major challenge for the health management of high-speed rail as a wheel defect with small radius deviation may suffice to give rise to severe damage on both the train bogie components and the track structure when a train runs at high speeds. It is thus highly desirable to detect the defects soon after their occurrences and then conduct wheel turning for the defective wheelsets. Online wheel condition monitoring using wheel impact load detector (WILD) can be an effective solution, since it can assess the wheel condition and detect potential defects during train passage. This study aims to develop an FBG-based track-side wheel condition monitoring method for the detection of wheel tread defects. The track-side sensing system uses two FBG strain gauge arrays mounted on the rail foot, measuring the dynamic strains of the paired rails excited by passing wheelsets. Each FBG array has a length of about 3 m, slightly longer than the wheel circumference to ensure a full coverage for the detection of any potential defect on the tread. A defect detection algorithm is developed for using the online-monitored rail responses to identify the potential wheel tread defects. This algorithm consists of three steps: 1) strain data pre-processing by using a data smoothing technique to remove the trends; 2) diagnosis of novel responses by outlier analysis for the normalized data; and 3) local defect identification by a refined analysis on the novel responses extracted in Step 2. To verify the proposed method, a field test was conducted using a test train incorporating defective wheels. The train ran at different speeds on an instrumented track with the purpose of wheel condition monitoring. By using the proposed method to process the monitoring data, all the defects were identified and the results agreed well with those from the static inspection of the wheelsets in the depot. A comparison is also drawn for the detection accuracy under different running speeds of the test train, and the results show that the proposed method can achieve a satisfactory accuracy in wheel defect detection when the train runs at a speed higher than 30 kph. Some minor defects with a depth of 0.05 mm~0.06 mm are also successfully detected.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3267-3272
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• 2015

Purpose: To retrospective assess the potential predictors for relapse and create an effective clinical mode for surveillance after orchidectomy in clinical stage I non-seminomatous germ cell testicular tumors (CSI-NSGCTs). Materials and Methods: We analyzed data for CSI-NSGCTs patients with non-lymphatic vascular invasion, %ECa < 50% (percentage of embryonal carcinoma < 50%), and negative or declining tumor markers to their half-life following orchidectomy (defined as low-risk patients); these patients were recruited from four Chinese centers between January 1999 and October 2013. Patients were divided into active surveillance group and retroperitoneal lymph node dissection (RPLND) group according to different therapeutic methods after radical orchidectomy was performed. The disease-free survival rates (DFSR) and overall survival rates (OSR) of the two groups were compared by Kaplan-Meier analysis. Results: A total of 121 patients with CSI-NSGCT were collected from four centers, and 81 low-risk patients, including 54 with active surveillance and 27 with RPLND, were enrolled at last. The median follow-up duration was 66.2 (range 6-164) months in the RPLND group and 65.9 (range 8-179) months in the surveillance group. OSR was 100% in active surveillance and RPLND groups, and DFSR was 89.8% and 87.0%, respectively. No significant difference was observed between these two groups ($X_2=0.108$, P=0.743). No significant difference was observed between the patients with a low percentage of embryonal carcinoma (<50%) and those without embryonal carcinoma (87.0% and 91.9%, $X_2=0.154$, P=0.645). No treatment-related complications were observed in the active surveillance group whereas minor and major complications were observed in 13.0% and 26.1% of the RPLND group, respectively. Conclusions: Active surveillance resulted in similar DFSR and OSR compared with RPLND in our trial. Patients with low-risk CSI-NSGCTs could benefit from risk-adapted surveillance after these patients were subjected to radical orchidectomy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.775-780
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• 2014

Objectives: TCR-gamma-delta+T cells (${\gamma}{\delta}$ T cells) are non-conventional T lymphocytes that can recognize and eradicate tumor cells. Our previous studies showed that infiltration and function of ${\gamma}{\delta}$ T cells were substantially attenuated in hepatocellular carcinoma (HCC). However, their prognostic value was not clarified. Methods: The association between ${\gamma}{\delta}$ T cells and the clinical outcomes was determined by immunohistochemistry (IHC) in a HCC patient cohort (n = 342). Results:Immunohistochemistry showed decreased infiltration of ${\gamma}{\delta}$ T cells in tumoral tissues compared with paired peritumoral tissues. The counts of ${\gamma}{\delta}$ T cells in peritumoral tissues were negatively correlated with tumor size (P = 0.005). Survival analysis showed that the levels of peritumoral ${\gamma}{\delta}$T cells were related to both time to recurrence (TTR) and overall survival (OS) (P = 0.010 and P = 0.036, respectively) in univariate analysis, and related to TTR in multivariate analysis (P = 0.014, H.R. [95% CI] = 0.682 [0.502-0.927]). Furthermore, the level of peritumoral ${\gamma}{\delta}$ T cells showed independent prognostic value for TTR in Barcelona Clinic Liver Cancer (BCLC) stage A patients (P = 0.038, H.R. [95% CI] = 0.727 [0.537-0.984]). However, tumoral ${\gamma}{\delta}$ T cells did not show independent prognostic value for either TTR or OS in HCC patients. Conclusions: Low counts of ${\gamma}{\delta}$ T cells in peritumoral liver tissue are related to a higher incidence of recurrence in HCC and can predict postoperative recurrence, especially in those with early-stage HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.929-934
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• 2013

Aim: To analyze the significance of different clinical factors for prognostic prediction in diffuse large B-cell lymphoma (DLBCL) patients. Methods: Two hundred and twenty-seven DLBCL patients were retrospectively reviewed. Patients were managed with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen or rituximab plus the CHOP (RCHOP) regimen. Results: Lactate dehydrogenase (LDH), ${\beta}2$-microglobulin (${\beta}2$-M), B symptoms, Ann Arbor stage and genetic subtypes were statistically relevant in predicting the prognosis of the overall survival (OS). In the CHOP group, the OS in patients with germinal center B-cell-like (GCB)(76.2%) was significantly higher than that of the non-GCB group (51.9%, P=0.032). With RCHOP management, there was no statistical difference in OS between the GCB (88.4%) and non-GCB groups (81.9%, P=0.288). Conclusion: Elevated LDH and ${\beta}2$-M levels, positive B symptoms, Ann Arbor stage III/IV, and primary nodal lymphoma indicate an unfavorable prognosis of DLBCL patients. Patients with GCB-like DLBCL have a better prognosis than those with non-GCB when treated with the CHOP regimen. The RCHOP treatment with the addition of rituximab can improve the prognosis of patients with DLBCL.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.4983-4988
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• 2013

Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

• BMB Reports
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• v.41 no.10
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• pp.733-738
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• 2008

Although previous studies have implicated a role for TC1 (C8orf4) in cancer cell proliferation, the molecular mechanism of its action is still largely unclear. In this study, we showed, for the first time, that the mRNA levels of TC1 were upregulated by mitogens (FBS/thrombin) and at least partially, through the ERK1/2 signaling pathway. Interestingly, the over-expression of TC1 promoted the $G_1$- to S-phase transition of the cell cycle, which was delayed by the deficiency of ERK1/2 signaling in fibroblast cells. Furthermore, the luciferase reporter assay indicated that the over-expression of TC1 significantly increased Cyclin D1 promoter-driven luciferase activity. Taken together, our findings revealed that TC1 was involved in the mitogen-activated ERK1/2 signaling pathway and positively regulated $G_1$- to S-phase transition of the cell cycle. Our results may provide a novel mechanism of the role of TC1 in the regulation of cell proliferation.

• Journal of the Korean Regional Science Association
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• v.15 no.2
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• pp.131-153
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• 1999

Since 1980's there have been two trends that obviously developed in the would -- economics globalization and urban internationalization. China, with is reform and opening-up policy and rapid economic growth, keeps pace with these two trends. The term "International City" has no putative standard or definition. If we make an analogue of urban functional hierarchy in the world with a pyramid, the International Citiesa are the few elites on its top. The highest level international cities can be called "World City" or "Global City". In today's new international division of labor, they are diversified leading cities with control capacity on a world scale, like New York, London, and Tokyo. The secondary international cities are either diversified cities with influence and regulative functions on multinational scale or specialized cities on politics, economics, culture, or other aspects with worldwide impact. Judged by different criteria, there is no city that is qualified as International City with the exception of Hong Kong, which was returned to the P.R. of China in 1997. Nevertheless, Some favorable conditions for the development of the international city still exist in China. This country is already the sixth largest economic entity in the world, and the second largest economic entity in the world, and the second largest one if GNP estimated by ppp. Furthermore its import and export value make up for 40% of its GNP, indicating that China is repidly merging into global economy. In this 1, 2 billion-population country, the difference of economic levels between urban and rural, coastal and inland regions is so big that a few metropolises in the coastal region have the possibilities and potentials to develop into international cities regardless of rather low GNP per capita of the whole country. This article will focus on analysis from several perspectives, such as the proportion of foreign trade values in GDP, the proportion of imports and exports by foreign funded enterprises in total foreign trade value; distribution of the 500 largest foreign-funded enterprises; distribution of the 500 enterprises with largest import and export values; distrigbution of foreign computer and telecom companies with offices in China; the number of outward flights per week and the international tourists; the value of foreign capital used in cities and so on. From this analysis, it is predicted that Chinese international cities will surely emergy from the eastern coastal regions and they must be the core cities of metropolitan interlocking regions that have been formed or in the process of forming. Those international cities will arise from south to north in turn : Hong Kong-Guangzhu, Shanghai, Beijing-Tianjin, and perhaps the last one is Dalian-Shenyang. The other side of this issue is that there is a long way for the coming international cities in China except Hong Kong. At least China and these core cities must continually devote to (1) improve the regional composition of foreign capital sources. (2) improve the composition of export commodities. (3) improve the investment environment (including hard and soft environment) to attract more transnational corporations to settle. (4) deepen the reform of state-owned enterprises and establish Chinese own transnational corporations to enter the world market.ons to enter the world market.