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Role of P14 and MGMT Gene Methylation in Hepatocellular Carcinomas: a Meta-analysis

  • Li, Cheng-Cheng;Yu, Zhuang;Cui, Lian-Hua;Piao, Jin-Mei;Liu, Meng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6591-6596
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    • 2014
  • Background: This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC). Materials and Methods: We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC. Results: Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues. Conclusions: These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.

Proliferative and Inhibitory Activity of Siberian ginseng (Eleutherococcus senticosus) Extract on Cancer Cell Lines; A-549, XWLC-05, HCT-116, CNE and Beas-2b

  • Cichello, Simon Angelo;Yao, Qian;Dowell, Ashley;Leury, Brian;He, Xiao-Qiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4781-4786
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    • 2015
  • Siberian ginseng (Eleutherococcus senticosus) is used primarily as an adaptogen herb and also for its immune stimulant properties in Western herbal medicine. Another closely related species used in East Asian medicine systems i.e. Kampo, TCM (Manchuria, Korea, Japan and Ainu of Hokkaido) and also called Siberian ginseng (Acanthopanax senticosus) also displays immune-stimulant and anti-cancer properties. These may affect tumour growth and also provide an anti-fatigue effect for cancer patients, in particular for those suffering from lung cancer. There is some evidence that a carbohydrate in Siberian ginseng may possess not only immune stimulatory but also anti-tumour effects and also display other various anti-cancer properties. Our study aimed to determine the inhibitory and also proliferative effects of a methanol plant extract of Siberan ginseng (E. senticosus) on various cancer and normal cell lines including: A-549 (small cell lung cancer), XWLC-05 (Yunnan lung cancer cell line), CNE (human nasopharyngeal carcinoma cell line), HCT-116 (human colon cancer) and Beas-2b (human lung epithelial). These cell lines were treated with an extract from E. senticosus that was evaporated and reconstituted in DMSO. Treatment of A-549 (small cell lung cancer) cells with E. senticosus methanolic extract showed a concentration-dependent inhibitory trend from $12.5-50{\mu}g/mL$, and then a plateau, whereas at 12.5 and $25{\mu}g/mL$, there is a slight growth suppression in QBC-939 cells, but then a steady suppression from 50, 100 and $200{\mu}g/mL$. Further, in XWLC-05 (Yunnan lung cancer cell line), E. senticosus methanolic extract displayed an inhibitory effect which plateaued with increasing dosage. Next, in CNE (human nasopharyngeal carcinoma cell line) there was a dose dependent proliferative response, whereas in Beas-2 (human lung epithelial cell line), an inhibitory effect. Finally in colon cancer cell line (HCT-116) we observed an initially weak inhibitory effect and then plateau.

Quantification of Her-2/Neu Gene in Breast Cancer Patients using Real Time-Polymerase Chain Reaction (Q-PCR) and Correlation with Immunohistochemistry Findings

  • Abdul Murad, Nor Azian;Razak, Zuraini Abdul;Hussain, Rosniza Muhammmad;Syed Hussain, Sharifah Noor Akmal;Ching Huat, Clarence Ko;Siti Aishah, Che Md. Ali;Abdullah, Norlia;Muhammad, Rohaizak;Ibrahim, Naqiyah;Jamal, Rahman
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1655-1659
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    • 2013
  • Background: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR). Materials and Methods: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification. Results: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR. Conclusion: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.

Determinants of Choice of Surgery in Asian Patients with Early Breast Cancer in A Middle Income Country

  • Teh, Yew-Ching;Shaari, Nor Elina Noor;Taib, Nur Aishah;Ng, Char-Hong;See, Mee-Hoong;Tan, Gie-Hooi;Jamaris, Suniza;Yip, Cheng-Har
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3163-3167
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    • 2014
  • Background: Breast-conserving surgery (BCS) plus radiotherapy is equivalent to modified radical mastectomy (MRM) in terms of outcome. However there is wide variation in mastectomy rates dependent both on tumour and patient characteristics. Objective: This study aimed to assess the determinants of surgery choice in Asian patients with early breast cancer in a middle-income country. Materials and Methods: 184 patients with early breast cancer treated between Jan 2008 and Dec 2010 were recruited to complete a questionnaire. Chi-square test was used to analyze the association between surgery choice and demographic and tumour factors, surgeon recommendation, family member and partner opinions, fear of recurrence, avoidance of second surgery, fear of disfigurement, interference with sex life, fear of radiation and loss of femininity. Results: 85 (46%) had BCS while 99 (54%) had mastectomy. Age >60, Chinese ethnicity, lower education level, and larger tumour size were significantly associated with mastectomy. Surgeon recommendation was important in surgery choice. Although both groups did not place much importance on interference with sex life, 14.1% of the BCS group felt it was very important compared to 5.1% in the mastectomy group and this was statistically significant. There was no statistical difference between the two groups in terms of the other factors. When analyzed by ethnicity, significantly more Malay and Indian women considered partner and family member opinions very important and were more concerned about loss of femininity compared to Chinese women. There were no statistical differences between the three ethnic groups in terms of the other factors. Conclusions: When counseling on surgical options, the surgeon has to take into account the ethnicity, social background and education level, age and reliance on partner and family members. Decision-making is usually a collective effort rather than just between the patient and surgeon, and involving the whole family into the process early is important.

Capecitabine Pattern of Usage, Rate of Febrile Neutropaenia and Treatment Related Death in Asian Cancer Patients in Clinical Practice

  • Phua, Vincent Chee Ee;Wong, Wei Quan;Tan, Pei Lin;Bustam, Anita Zarina;Saad, Marniza;Alip, Adlinda;Ishak, Wan Zamaniah Wan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1449-1453
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    • 2015
  • Background: Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). Materials and Methods: We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from $1^{st}$ January 2009 till $31^{st}$ June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature > $38.5^{\circ}C$ or two consecutive readings of > $38.0^{\circ}C$ for 2 hours and an absolute neutrophil count < $0.5{\times}10^9/L$, or expected to fall below $0.5{\times}10^9/L$ (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment. Results: Between $1^{st}$ January 2009 and $30^{th}$ June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent. Conclusions: Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.

THE EFFECT OF EXTREMELY LOW FREQUENCY MAGNETIC FIELD (ELF-MF) ON THE FREQUENCY OF MICRONUCLEI IN HUMAN LYMPHOCYTES INDUCED BY BENZO(A)PYRENE

  • Cho, Yoon-Hee;Kim, Su-Young;Chung, Hai-Won
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.178-178
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    • 2001
  • The interaction of extremely low frequency magnetic field (ELF-MF) on the frequency of micronuclei (MN) induced by benzo(a)pyrene (BP) in human lymphocytes was examined. A 60 Hz ELF-MF of 0.8 mT field strength was applied for 24 hours either alone or with the tumour initiator, BP. The frequency of MN induced by BP increased in a dose-dependent manner.(omitted)

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Analysis and quantification of DNA photoadducts by HPLC/ion trap mass spectrometry

  • Zhang, Guangyu;Linscheid, Michael
    • Proceedings of the SCSK Conference
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    • 2003.09b
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    • pp.405-406
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    • 2003
  • DNA is known as the genetic material in cells. Various environmental factors can cause DNA damages. One of them is sunlight. The life on earth depends on the sunlight, but on the other hand, the UV light in sunlight can cause skin DNA damages. When these damages are not fully repaired before replication, they can lead to mutations of oncogenes and tumour suppressor gene and result in photo carcinogenesis, in the end, skin cancer.(omitted)

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Clinical Significance of Axin and β-catenin Protein Expression in Primary Hepatocellular Carcinomas

  • Guan, Cheng-Nong;Chen, Xin-Ming;Lou, Hai-Qing;Liao, Xiang-Hui;Chen, Bao-Ying;Zhang, Pei-Weng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.677-681
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    • 2012
  • The aim of the present research was to investigate clinicopathologic correlations of immunohistochemically-demonstrated axin (axis inhibition) and ${\beta}$-catenin expression in primary hepatocellular carcinomas (HCCs), in comparison with paraneoplastic, cirrhotic and normal liver tissues. Variation in Axin expression across groups were significant (P < 0.01), correlating with alpha fetoprotein (AFP), HBsAg, cancer plugs in the portal vein, and clinical stage of HCCs(P < 0.05); however, there were no links with sex, age, and tumour size (P > 0.05). Differences in cell membrane ${\beta}$-catenin expression were also statistically significant (P < 0.01), again correlated with AFP, HBsAg, cancer plugs in the portal vein, and clinical stage in HCCs (P < 0.05) but not with sex, age, and tumour size (P > 0.05). Axin expression levels in tissues with reduced membrane ${\beta}$-catenin were low (P < 0.05), also being low with nuclear ${\beta}$-catenin expression (P < 0.05). Axin and ${\beta}$-catenin may play an important role in the genesis and progression of HCC via the Wnt signal transmission pathway. Simultaneous determination of axin, ${\beta}$-catenin, AFP, and HBsAg may be useful for early diagnosis, and metastatic and clinical staging of HCCs.

Breastfeeding and its Relationship with Reduction of Breast Cancer: A Review

  • Franca-Botelho, Aline Do Carmo;Ferreira, Marina Carvalho;Franca, Juliana Luzia;Franca, Eduardo Luzia;Honorio-Franca, Adenilda Cristina
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5327-5332
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    • 2012
  • In this review, we describe the patterns of known immunological components in breast milk and examine the relationship between breastfeeding and reduced risk of breast cancer. The top risk factors for breast cancer are a woman's age and family history, specifically having a first-degree relative with breast cancer. Women that have a history of breastfeeding have been shown to have reduced rates of breast cancer. Although the specific cause has not been elucidated, previous studies have suggested that breastfeeding reduces the risk of breast cancer primarily through two mechanisms: the differentiation of breast tissue and reduction in the lifetime number of ovulatory cycles. In this context, one of the primary components of human milk that is postulated to affect cancer risk is alpha-lactalbumin. Tumour cell death can be induced by HAMLET (a human milk complex of alpha-lactalbumin and oleic acid). HAMLET induces apoptosis only in tumour cells, while normal differentiated cells are resistant to its effects. Therefore, HAMLET may provide safe and effective protection against the development of breast cancer. Mothers should be encouraged to breastfeed their babies because the complex components of human milk secretion make it an ideal food source for babies and clinical evidence has shown that there is a lower risk of breast cancer in women who breastfed their babies.

Paris polyphylla Smith Extract Induces Apoptosis and Activates Cancer Suppressor Gene Connexin26 Expression

  • Li, Fu-Rong;Jiao, Peng;Yao, Shu-Tong;Sang, Hui;Qin, Shu-Cun;Zhang, Wei;Zhang, Ya-Bin;Gao, Lin-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.205-209
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    • 2012
  • Background: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. Methods: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Results: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. Conclusion: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.