• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10937-10941
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• 2015

Pathogenesis of lung cancer is a complicated biological process including multiple genetic and epigenetic changes. Since cigarette smoking is confirmed as the most main risk factor of non-small cell lung cancer (NSCLC), the aim of this study was to determine whether tobacco exposure plays a role in gene methylation. Methylation of the RAR-${\beta}$ gene were detected using methylation-specific polymerase chain reaction in DNA from 167 newly diagnosed cases with NSCLC and corresponding 105 controls. A significant statistical association was found in the detection rate of the promoter methylation of RAR-${\beta}$ gene between NSCLC and controls ($x^2$=166.01; p<0.01), and hypermethylation of the RAR-${\beta}$ gene was significantly associated with smoking status (p=0.038, p<0.05). No relationship was found between RAR-${\beta}$ gene methylation and pathologic staging including clinical stage, cell type, gender and drinking (p>0.05), and the methylation of RAR-${\beta}$ gene rate of NSCLC was slightly higher in stages III+IV (80.0%) than in I+II (70.8%). Similar results were obtained for methylation of the RAR-${\beta}$ gene between squamous cell carcinoma (77.9%) and other cell type lung cancer (73.9%). These results showed that the frequency of methylation increased gradually with the development of clinical stage in smoking-associated lung cancer patients, and tobacco smoke may be play a potential role in RAR-${\beta}$ gene methylation in the early pathogenesis and process in lung cancer, particularly squamous cell carcinoma. Aberrant promoter methylation is considered to be a promising marker of previous carcinogen exposure and cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5557-5563
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• 2014

Background: This study investigated the survival benefit of radiotherapy (RT) of the supra- and infraclavicular lymphatic drainage area in Chinese women with T1-2N1M0 breast cancer receiving mastectomy. Methods: A total of 593 cases were retrospectively reviewed from 1998 to 2007. The relationship between supra- or infraclavicular fossa relapse (SCFR) and post-operative RT at the supra-/infraclavicular lymphatic drainage area was evaluated. Results: The majority of patients (532/593; 89. 8%) received no RT while 61 patients received RT. The median follow-up was 85 months. Among patients without RT, 54 (10. 2%) developed recurrence in the chest wall or ipsilateral SCFR. However, none of the 61 patients who underwent RT demonstrated SCFR. One patient who received RT (1. 6%) experienced recurrence in the chest wall. Univariate analysis revealed that age and molecular subtype (both P < 0. 05) were two prognostic factors related to supraclavicular and infraclavicular fossa relapse-free survival (SFRFS). Multivariate analysis revealed that only Her-2 positive status (P = 0. 011) was an independent predictor of SFRFS. RT had no influence on distant metastasis (P = 0. 328) or overall survival (P = 0. 541). SCFR significantly affected probability of distant metastasis (P < 0. 001) and overall survival (P < 0. 001). Conclusion: Although RT was not significantly associated with SFRFS, postoperative RT was significantly associated with a lower locoregional (i. e., supraclavicular/infraclavicular and chest wall) recurrence rate. SCFR significantly influenced distant metastasis-free survival, which significantly influenced the overall survival of T1-2N1M0 breast cancer patients after mastectomy. Thus, prophylactic RT is recommended in T1-2N1M0 breast cancer patients, especially those who have Her-2 positive lesions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5691-5696
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• 2014

Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.811-816
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• 2013

Background: Pervious studies suggested occupational workers exposure to pentachlorophenol (PCP) might contribute to increased risk of cancer. However, few studies have focused on associations between PCP and cancer risk at the community level. Objective: The present study was to explore the cancer risk for the community population living long-term in a PCP contaminated area. Methods: All the cancer cases diagnosed in 2009-2011 in Tongling City were collected. The cancer patients' residencies were geo-referenced in each district. The historical PCP usage for each district of Tongling was calculated as the PCP pollution index, which was further used to divide into PCP exposure categories. Standardized rate ratios (SRRs) of cancer incidence were applied to detect the cancer risk as exposure grade elevated. Correlation analysis was performed to analyze the relationship between PCP pollution and cancer incidence. Results: A total of 5,288 cancer cases (3,451 male and 1,837 female) were identified. PCP usage was correlated with the incidence of leukemia (r=0.88, P=0.002) for males, and with cancer of the esophagus for males (r=0.83, P=0.008) and females (r=0.71, P=0.020). Compared with the low exposure category, significant SRRs for total cancer sites was obtained for high PCP exposure category (SRR=1.61, 95%CI=1.59-1.62). Most SRR values of the cancer sites were significantly increased as exposure grade elevated and exposure time extended. Conclusion: The present study found that community residents living in the PCP contaminated area had increased risk of cancers. Leukemias, lymphomas and nasopharyngeal and esophageal cancers are most possibly associated with PCP exposure.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.685-689
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• 2013

Objective: To study the effects of down-regulation of HDAC6 expression on proliferation, cell cycling and migration of esophageal squamous cell carcinoma (ESCC) cells and related molecular mechanisms. Methods: ESCC cell line EC9706 cells were randomly divided into untreated (with no transfection), control siRNA (transfected with control siRNA) and HDAC6 siRNA (transfected with HDAC6 small interfering RNA) groups. Effects of HDAC6 siRNA interference on expression of HDAC6 mRNA and protein in EC9706 cells were investigated by semi-quantitative RT-PCR, Western blotting and immunocytochemistry methods. Effects of down-regulation of HDAC6 expression on cell proliferation, cell cycle, and cell migration were studied using a CCK-8 kit, flow cytometry and Boyden chambers, respectively. Changes of mRNA and protein expression levels of cell cycle related factor (p21) and cell migration related factor (E-cadherin) were investigated by semi-quantitative RT-PCR and Western blotting methods. Results: After transfection of HDAC6 siRNA, the expression of HDAC6 mRNA and protein in EC9706 cells was significantly downregulated. In the HDAC6 siRNA group, cell proliferation was markedly inhibited, the percentage of cells in G0/G1 phase evidently increased and the percentage of cells in S phase decreased, and the number of migrating cells significantly and obviously decreased. The mRNA and protein expression levels of p21 and E-cadherin in the HDAC6 siRNA group were significantly higher than those in the untreated group and the control siRNA group, respectively. Conclusions: HDAC6 siRNA can effectively downregulate the expression of HDAC6 mRNA and protein in EC9706 cells. Down-regulation of HDAC6 expression can obviously inhibit cell proliferation, arrest cell cycling in the G0/G1 phase and reduce cell migration. The latter two functions may be closely related with the elevation of mRNA and protein expression of p21 and E-cadherin.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5231-5235
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• 2013

Objective: NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. Materials and Methods: A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo. Results: Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines. Conclusion: Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5219-5223
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• 2013

The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer. The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor in predicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis was based on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008 in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile software and validated by bootstrapping. Patients were then divided into three groups (low-, intermediate-, and high-risk) according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportional hazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log-rank test. The 5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT, pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly different prognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor. Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category, but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore, LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routine clinical decision-making should take the LNR into consideration.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5325-5329
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• 2013

Objectives: Although there are many reports about the risk of breast cancer, few have reported clinical factors including history of breast-related or other diseases that affect the prevalence of breast cancer. This study explores these risk factors for breast cancer cases reported in Beijing in 2009. Materials and Methods: Data were derived from a Beijing breast cancer screening performed in 2009, of 568,000 women, from 16 districts of Beijing, all aged between 40 and 60 years. In this study, multilevel statistical modeling was used to identify clinical factors that affect the prevalence of breast cancer and to provide more reliable evidence for clinical diagnostics by using screening data. Results and Conclusion: Those women who had organ transplants, compared with those with none, were associated with breast cancer with an odds ratio (OR)=65.352 [95% confidence interval (CI): 8.488-503.165] and those with solid breast mass compared with none had OR=1.384 (95% CI: 1.022-1.873). Malignant tendency was strongly associated with increased risk of breast cancer, OR=207.999(95% CI: 151.950-284.721). The risk of breast cancer increased with age, $OR_1$=2.759 (95% CI: 1.837-4.144, 56-60 vs. 40-45), $OR_2$=2.047 (95% CI: 1.394-3.077, 51-55 vs. 40-45), $OR_3$=1.668 (95% CI: 1.145-2.431). Normal results of B ultrasonic examination show a lower risk among participants, OR= 0.136 (95% CI: 0.085-0.218). Those women with ductal papilloma compared with none were associated with breast cancer, OR=6.524 (95% CI: 1.871-22.746). Therefore, this study suggests that clinical doctors should pay attention to these high-risk factors.

• Journal of Korean Medical classics
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• v.29 no.2
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• pp.135-150
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• 2016

Objectives : KangHaiChengZhiLun (亢害承制論; If Excess Brings Harm, Lifing Qi (承氣) Restrains) was originally a theory that explained how the realms of nature remain in harmony and equilibrium. It later became an important theory for clinical trials of Traditional Chinese Medicine, explaining the physiological and pathological mechanism. Methods : The researcher considered all the annotations and the original text of SuWen(素問), LiuWeiZhiDaLun(六微旨大論) and theories of medical practitioners who applied KangHaiChengZhiLun(亢害承制論) to their clinical trials. Results & Conclusions : Wangbing (王氷) went with a theory that phenomena of Lifting Qi (承氣) take place in the realms of nature when Qi (氣) flourishes. In XinJiaoZheng(新校正), he wrote about two theories: one was that Six Kinds of Natural Factors (六氣) first work as the main Qi (本氣) but later bring about Lifting Qi. (終見下承之氣說); the other was that excessive Stagnation Qi (鬱氣) can be exploded and invite another accompanying Qi, Lifting Qi. (甚者兼其下承之氣說) Liuwansu (劉完素) had a theory that if Six Kinds of Natural Factors go disproportionately excessive, it becomes accompanied by imaginary Qi (假象) that conquers self. (反兼勝己之化說) $Wangl{\ddot{u}}$(王履) maintained that Lifting Qi usually works as a means to prevent Six Kinds of Natural Factors (六氣) from becoming rampant; but when Six Kinds of Natural Factors become overly excessive, Lifting Qi restrains them in order to maintain equilibrium. (防之與克勝說) Yutuan explained that since Excessive Qi (亢氣) does damage to the mother of Lifting Qi, Lifting Qi restrains Excessive Qi to protect Original Qi (元氣), its mother. (護救承者之元氣說) Gongtingxian was in favor of two theories: one argued that causes and symptoms of a disease differ from each other. (體用不同說); the other said that diseases are naturally cured if the patient finds out the time when Lifting Qi gains strength. (得承之時自愈說) Mashi (馬蒔) had a theory that Lifting Qi is generated when Six Kinds of Natural Factors are prosperous and reveals itself when its season comes. (極則生承氣 至本位著說) Zhangjiebin (張介賓) asserted that when Six Kinds of Natural Factors are thriving, Lifting Qi, as a restraining force, is generated to disperse the thriving natural factors and leads to a new one. (前之退而後之進說) Zhangqi (張琦)'s argument was that if Lifting Qi restrains the main Qi, a son of the main Qi is generated and every four season goes in harmony. (承氣制則生化說) Hemengyao (何夢瑤) had an argument that a son of the restrained Qi succeeds to its father and later achieves equilibrium by restraining Excessive Qi. (被克承父 制之平衡說).

• BMB Reports
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• v.46 no.6
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• pp.316-321
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• 2013

Gastric cancer remains the main cause of cancer death all around the world, and upregulated activation of the nonreceptor tyrosine kinase c-SRC (SRC) is a key player in the development. In this study, we found that expression of Src is also increased in clinical gastric cancer samples, with the protein level increased more significantly than that at the RNA level. Further study revealed that miR34a and miR203, two tumor suppressive miRNAs, inversely correlate with the expression of Src. Restoration of miR34a and miR203 decreased Src expression in gastric cancer cell lines, which in turn inhibited cell growth and cell migration. In summary, our study here revealed that posttranscriptional regulation of Src contributes to the deregulated cell growth and metastasis in gastric cancer, and targeting Src by miR34a or miR203 mimics would be a promising strategy in therapy.