• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.85-91
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• 2014

Background: Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. Methods: Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. Results: Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. Conclusion: In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.5001-5007
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• 2014

The acetyltransferase inhibitor garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Anti-cancer activity has been suggested but there is no report on its action via inhibiting acetylation against cell proliferation, cell cycle progression, and apoptosis-inhibtion induced by estradiol ($E_2$) in human breast cancer MCF-7 cells. The main purposes of this study were to investigate the effects of the acetyltransferase inhibitor garcinol on cell proliferation, cell cycle progression and apoptosis inhibition in human breast cancer MCF-7 cells treated with estrogen, and to explore the significance of changes in acetylation levels in this process. We used a variety of techniques such as CCK-8 analysis of cell proliferation, FCM analysis of cell cycling and apoptosis, immunofluorescence analysis of NF-${\kappa}B$/p65 localization, and RT-PCR and Western blotting analysis of ac-H3, ac-H4, ac-p65, cyclin D1, Bcl-2 and Bcl-xl. We found that on treatment with garcinol in MCF-7 cells, $E_2$-induced proliferation was inhibited, cell cycle progression was arrested at G0/G1 phase, and the cell apoptosis rate was increased. Expression of ac-H3, ac-H4 and NF-${\kappa}B$/ac-p65 proteins in $E_2$-treated MCF-7 cells was increased, this being inhibited by garcinol but not ac-H4.The nuclear translocation of NF-${\kappa}B$/p65 in $E_2$-treated MCF-7 cells was also inhibited, along with cyclin D1, Bcl-2 and Bcl-xl in mRNA and protein expression levels. These results suggest that the effect of $E_2$ on promoting proliferation and inhibiting apoptosis is linked to hyperacetylation levels of histones and nonhistone NF-${\kappa}B$/p65 in MCF-7 cells. The acetyltransferase inhibitor garcinol plays an inhibitive role in MCF-7 cell proliferation promoted by $E_2$. Mechanisms are probably associated with decreasing ac-p65 protein expression level in the NF-${\kappa}B$ pathway, thus down-regulating the expression of cyclin D1, Bcl-2 and Bcl-xl.

• 만화애니메이션 연구
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• 통권34호
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• pp.197-217
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• 2014

20세기 20~30년대는 중국만화가 제일 번영된 때이고 중국 만화의 "황금시기"이다. 중국의 근대만화는 외세에 의하여 정서불안과 전쟁 등으로 풍자만화가 유행하였고 그중 많은 인기작품들 중에서 영화와 드라마로 제작된 20년대의 <왕 선생>과 30년대의 <삼모 유랑기>를 선택하여 분석하였다. II장에서 20~30년대 중국 민국시기 영화, 소설, 잡지, 패션 등의 소비문화가 확대되었지만 그 중, 통속성과 대중성으로 인기를 끌었던 만화잡지의 역사, 30년대 만화 간행물 등의 만화 "황금시기"에 대하여 역사적인 고찰을 하였다. III장에서는 5.4운동이후 사회 풍자유머만화가 유행하였고 20년대 반제반봉건주의의 내용에서 현실생활화 되었고 사회의 부정적인 면을 묘사한 작품들이 유행하였다. 그 중 작가 엽천여는 <왕 선생>을 통하여 소시민의 일상생활, 관료의 부패, 노동인민에 대한 동정 등의 상해에 대하여 묘사하였고 장락평의 <삼모 유랑기>는 힘없고 불쌍한 고아를 통하여 상해의 부르주아와 프롤레타리아의 불공평한 사회제도, 빈부격차에 대하여 묘사하였다. <왕 선생>은 도덕적인 면에서 <삼모 유랑기>는 경제적인 면에서 현실에 대하여 객관적이면서 익살스럽고 우스꽝스럽게 반영하였다는 것을 알 수 있다. 연구자가 <왕 선생>과 <삼모 유랑기>를 선택하게 된 이유는 하나의 좋은 만화, 좋은 애니메이션 심지어 좋은 영화는 우리 주변에 대한 느낌에서 오는 감정을 자극하기 때문에 친근감을 느끼게 하며 익숙한 내용을 다룬 두 작품을 선택하게 되었다.

• Journal of Acupuncture Research
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• 제24권6호
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• pp.89-96
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• 2007

Objectives : To observe the effect of acupuncture treatment in chronic shoulder pain patients. Methods : 36 voluntary patients were randomly assigned to an acupuncture treatment group(E Group, n=18) and a control group(C Group, n=18). The E Group patients received acupuncture treatment on $LI_{15}$, $TE_{14}$, $GB_{21}$ and Master Dong's acupuncture points, Shin-gwan and Gyun-joong, twice a week for four weeks. The C Group patients received no treatment. All patients in both groups were instructed to practise self exercise in their daily lives. Evaluations were made at baseline and after four weeks of study. The Constant Shoulder Assessment(CSA), Shoulder Pain and Disability Index(SPADI) and the patient's subjective pain was measured by Visual Analogue Scale(VAS). The obtained data was analyzed. Results : The E Group showed significant(p<0.05) improvement in CSA, SPADI and VAS after four weeks of treatment. The C Group showed significant(p<0.05) improvement in CSA, but the change of SPADI and VAS was insignificant(p>0.05). CSA and SPADI of E Group significantly(p<0.05) improved compared to the C Group, but the difference of VAS change in the two groups was insignificant(p>0.05). Conclusions : Four weeks of acupuncture treatment significantly improved CSA, SPADI and VAS. The improvement of CSA and SPADI was significant(p<0.05) compared to untreated patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4331-4338
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• 2014

$N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.413-417
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• 2013

Purpose: This phase II study was undertaken to determine the efficacy and safety of Loubo$^{(R)}$ (Lobaplatin) in combination with pemetrexed in treating patients with metastatic breast cancer who failed to respond to anthracycline or taxanes. Patients and Methods: Metastatic breast cancer cases who had previously received an anthracycline and a taxane in either adjuvant or metastatic settings, were enrolled. All patients were recruited from Jiangsu Cancer Hospital and Research Institute, and were treated with Loubo$^{(R)}$ (Lobaplatin) 35 $mg/m^2$ (intravenous; on day 1) and pemetrexed 500 $mg/m^2$ (intravenous; on day 1) every 21 days. Efficacy and side effects were evaluated after at least two cycles of chemotherapy. Results: All eligible 19 patients completed at least 2 cycles of chemotherapy with pemetrexed and lobaplatin, and were evaluable. Overall, 3 (15.8%) patients achieved partial response, 11 (57.9%) stable disease, 5 (26.3%) progression of disease, with no complete remission. Response rate was 15.8%, disease control rate was 42.1%. The median survival time was 10.3 months. Neutrophil suppression occurred in 36.8% of patients who had grade 2 toxicity, and 26.3% had grade 3, 26.4% had grade 4. Thrombocytopenia was encountered as follows: 21.1% grade 2, 15.8% grade 3 and 5.5% grade 4. Incidences of anemia were 10.5% in grade 2, 5.3% grade 3 and 0% grade 4. Only 5.3% of patients required packed red blood cell transfusion. Grade 3 digestive tract toxicity occurred in 5.5% of patients. Other toxicities included elevated transaminase,oral mucositis and skin rashes. Conclusions: The regimen of lobaplatin and pemetrexed is modestly active in metastatic breast cancer patients who failed anthracycline or taxanes, and the toxicity profile suggesting that the doses of chemotherapy should be further modified.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1715-1720
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• 2013

Background: The discovery that microRNAs (miRNAs) regulate proliferation, invasion and metastasis provides a principal molecular basis of tumor heterogeneity. Microvessel distribution is an important characteristic of solid tumors, with significant hypoxia occurring in the center of tumors with low blood flow. The distribution of miR-374a in breast tumors was examined as a factor likely to be important in breast cancer progression. Methods: Breast tissue samples from 40 patients with breast cancer were classified into two groups: a highly invasive and metastatic group (HIMG) and a low-invasive and metastatic Group (LIMG). Samples were collected from the center and edge of each tumor. In each group, six specimens were examined by microRNA array, and the remaining 14 specimens were used for real-time RT-qPCR, Western blot and immunohistochemical analyses. Correlation analysis was performed for the miRNAs and target proteins. Follow-up was carried out during 28 months to 68 months after surgery, and survival data were analyzed. Results: In the LIMG, the relative content of miR-374a was lower in the center of the tumor than at its edge; in the HIMG, it was lower at the edge of the tumor, and miR-374a levels were lower in breast cancer tissues than in normal tissues. There was no difference between VEGF-A and VCAM-1 mRNA levels at the edge and center of the tumor; however, we observed a significant difference between VEGF-A and VCAM-1 protein expression levels in these two regions. There was a negative correlation between miR-374a and target protein levels. The microvessel density (MVD) was lower in the center of the tumor than at its edge in HIMG, but the LIMG vessels were uniformly distributed. There was a significant positive correlation between MVD and the number of lymph node metastases (Pearson correlation, r=0.912, P<0.01). The median follow-up time was 48.5 months. LIMG had higher rate of disease-free survival (100%, P=0.013) and longer median survival time (66 months) than HIMG, which had a lower rate of 75% and shorter median survival time (54 months). Conclusions: Our data demonstrated miR-374a to be differentially distributed in breast cancer; VEGF-A and VCAM-1 mRNA had coincident distribution, and the distribution of teh respective proteins was uneven and opposite to that for the miR-374a. These data might explain the differences in the distribution of MVD in breast cancer and variation in breast cancer prognosis.

• BMB Reports
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• 제43권6호
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• pp.432-437
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• 2010

LBH is a transcription factor as a candidate gene for CHD associated with partial trisomy 2p syndrome. To identify potential LBH-interacting partners, a yeast two-hybrid screen using LBH as a bait was performed with a human heart cDNA library. One of the clones identified encodes ${\alpha}B$-crystallin. Co-immunoprecipitation and GST pull-down assays showed that LBH interacts with ${\alpha}B$-crystallin, which is further confirmed by mammalian two-hybrid assays. Co-localization analysis showed that in COS-7 cells, ${\alpha}B$-crystallin that is cytoplasmic alone, accumulates partialy in the nucleus when co-transfected with LBH. Transient transfection assays indicated that overexpression of LBH or ${\alpha}B$-crystallin reduced the transcriptional activities of p53 and p21, respectively, Overexpression of both ${\alpha}B$-crystallin and LBH together resulted in a stronger repression of the transcriptional activities of p21 and p53. These results showed that the interaction of LBH and ${\alpha}B$-crystallin may inhibit synergistically the transcriptional regulation of p53 and p21.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3811-3816
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• 2015

Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6299-6303
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• 2012

Insulin-like growth factor-binding protein-3 (IGFBP3) has been identified as a putative tumor suppressor with multifunctional roles in the IGF axis. Recently, there have been a growing body of studies investigating the relation between the IGFBP3 A-202C polymorphism, circulating IGFBP3 and prostate cancer risk, but their outcomes varied leading to controversy. Hence, it is necessary to perform a meta-analysis covering all eligible studies to shed a light on the association of IGFBP3 A-202C and cancer risk. Finally, we included a total of 11 relevant articles between 2003 and 2010 covering 14 case-control studies including 9,238 cases and 8,741 controls for our analysis. Our results showed that A-202C was a marginal risk factor of prostate cancer (allele contrast: OR=1.08, 95% CI :1.01-1.16; dominant model: OR=1.11, 95% CI :1.01-1.22; heterozygote codominant model: OR=1.11, 95% CI :1.03-1.18; homozygote contrast: OR=1.19, 95% CI :1.03-1.37). Stratification analysis revealed that sample size and control source were two major heterogeneous meta-factors especially in the recessive model (source: Population-based control group :p=0.30,I2=16.7%, Hospital-based control group: p=0.20, I2=30.3%; sample size: Small: p=0.22,I2= 32.8%, Medium: p=0.09,I2=48%, Large p=0.60,I2=0.0%); However, contrary to previous findings, no significance was found in racial subgroups. No significant publication bias was found in our analysis. Considering the robustness of the results and the discrepancy among some studies, there might be some unsolved confounding factors, and further more critical large studies are needed for confirmation.