• 생약학회지
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• 제45권1호
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• pp.1-10
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• 2014

Ginsenoside Rg3 (G-Rg3) is one of protopanaxadiol ginsenosides characteristic of red ginseng, steamed and dried ginseng (Panax ginseng), which has recently attracted much attention for its antitumor properties in vitro and in vivo animal models. Experimental studies have demonstrated that it could promote cancer cell apoptosis, inhibit cancer cell growth, the apoptosis of cancer cells, adhesion, invasion and metastasis, and also prevent an angiogenetic formation in prostate, breast, ovarian, colorectal, gastric, liver and lung cancer etc. It has shown the antitumor activities by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (vascular endothelial growth factor), tumor suppressors (p53 and p21), cell death mediators (caspases, Bcl-2, Bax), inflammatory response molecules ($NF-{\kappa}B$ and COX-2), protein kinases (JNK, Akt, and AMP-activated protein kinase) and Wnt/${\beta}$-catenin signaling. In addition, the combination of Rg3 and chemotherapeutic agents have synergistically enhanced therapeutic efficacy and reduced antagonistically side effects. Furthermore, it can reverse the multidrug resistance of cancer cells, prolong the survival duration and improve life quality of cancer patients. Taken together, accumulating evidences could provide the potential of G-Rg3 in the treatment of cancers and the feasibility of further randomized placebo controlled clinical trials.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3983-3988
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• 2016

Background: Cervical cancer though preventable is still the leading cause of cancer death among women secondary to breast cancer. Persistent infection with HPV has been causally linked to the disease. A school based HPV vaccination program was introduced in late 2010 in Malaysia and nurse support is essential for its success. Objectives: To determine nurses knowledge and attitudes about HPV infection and its vaccines, and factors associated with their knowledge. Materials and Methods: This cross-sectional study was conducted among nurses working at primary health clinics in Kelantan from mid-June till the end of July 2014. Its involved 330 nurses selected through multistage random sampling. A validated self-administered questionnaire consisting of 11 items for the knowledge domain and eight items for the attitude domain was used. Results: The response rate of the study was 93.7%. The mean knowledge and mean attitude (SD) scores were 5.37 (1.76) and 29.8 (3.51) respectively. Only 24% knew that HPV is the most common sexually transmitted infection and 67% correctly answered that Gardasil vaccine can protect against four types of HPV. Nearly 60% of participants wrongly answered that HPV vaccines cannot be offered to sexually active women. Likewise, 70.9% participants were not aware that HPV vaccine may be appropriate for females aged 9 through 26 years. Though 90% of participants believed that the vaccine is safe, nearly half of them were unsure about efficacy. From multiple linear regression analysis, among the factors tested only participant's level of education showed a statistically significant association with the HPV knowledge score (p <0.001). Conclusions: This study indicates nurses have favorable attitudes towards HPV vaccination; however they have significant knowledge deficit and major misunderstanding in critical knowledge items. Among the factors tested, nursing qualification is the only factor that is significantly associated with the nurses knowledge score.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6073-6076
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• 2012

Discovery of anticancer drugs that kill or disable tumor cells in the presence of normal cells without undue toxicity is a potential challenge for therapeutic care. Several papers in the literature have emphasized the potential implications of marine products such as seaweeds which exhibit antitumor activity. Study attempts to screen the antitumor effect of Sargassum sp, against chosen cell lines such as MCF-7 (Breast cancer) and Hep-2 (Liver Cancer). Ethanol extract of Sargassum sp. was concentrated using a Soxhlet apparatus and dissolved in DMSO. In vitro cytotoxic activity of Sargassum sp at various concentrations ($100{\mu}g/ml-300{\mu}g/ml$) screened for antitumor effect against the chosen cell lines using MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole). The study documented that the percentage of cell viability has been reduced with increased concentration, as evidenced by cell death. Sargassum sp extract shows potential cytotoxic activity ($P{\leq}0.05$) with $IC_{50}$ of $200{\mu}g/ml$ and $250{\mu}g/ml$ against Hep-2 and MCF-7 cell lines respectively. The ethanol fraction of Sargassum sp induced cell shrinkage, cell membrane blebbing and formation of apoptotic bodies with evidence of bioactive components as profound influencing factors for anti-tumor effects. Further research need to be explored for the successful application of Sargassum sp as a potent therapeutic tool against cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1553-1556
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• 2012

Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.

• Molecules and Cells
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• 제43권3호
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• pp.236-250
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• 2020

Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy. For this purpose, we initially investigated the inhibitory role of TRIP-Br1/XIAP in necroptosis, a regulated form of necrosis, under nutrient/serum starvation. Our data showed that necroptosis was significantly induced in all tested 9 different types of cancer cell lines in response to prolonged serum starvation. Among them, necroptosis was induced at a relatively lower level in MCF-7 breast cancer line that was highly resistant to apoptosis than that in other cancer cell lines. Interestingly, TRIP-Br1 oncogenic protein level was found to be very high in this cell line. Up-regulated TRIP-Br1 suppressed necroptosis by repressing reactive oxygen species generation. Such suppression of necroptosis was greatly enhanced by XIAP, a potent inhibitor of apoptosis. Our data also showed that TRIP-Br1 increased XIAP phosphorylation at serine87, an active form of XIAP. Our mitochondrial fractionation data revealed that TRIP-Br1 protein level was greatly increased in the mitochondria upon serum starvation. It suppressed the export of CypD, a vital regulator in mitochondria-mediated necroptosis, from mitochondria to cytosol. TRIP-Br1 also suppressed shikonin-mediated necroptosis, but not TNF-α-mediated necroptosis, implying possible presence of another signaling pathway in necroptosis. Taken together, our results suggest that TRIP-Br1/XIAP can function as onco-proteins by suppressing necroptosis of cancer cells under nutrient/serum starvation.

• 생명과학회지
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• 제29권4호
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• pp.499-508
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• 2019

암줄기세포는 전이와 재발의 주요한 요인이 되는 자가재생능력, 분화할 수 있는 능력, 치료에 대한 저항성 및 암 형성 능력의 특성을 가진다. WNT/${\beta}$-catenin, Hedgehog, Notch, BMI1, BMP 및 TGF-${\beta}$와 같은 암줄기세포의 특성을 획득 및 유지할 수 있는 신호기전의 연구 결과가 존재하지만, 현재까지 선택적으로 암줄기세포를 표적할 수 있는 치료 전략은 미미하다. 최근, 면역관문억제제인 CTLA-4, PD-1/PD-L1 단일클론항체는 흑색종, 폐암, 췌장암 및 혈액암에 괄목할만한 임상 시험 결과를 나타냈으며, 긴 항암지속효과와 적은 부작용은 기존 항암제보다 개선 된 모습을 보였다. 또한 두경부편평상피암, 흑색종, 유방암 줄기세포를 선택적으로 제거 하였다. 위의 결과를 종합하면, 면역관문억제제는 이전 항암제에 비해 효과적인 항암전략이며, 동시에 암줄기세포를 선택적으로 제거할 수 있는 가능성을 시사한다. 따라서 본 리뷰에서는 암줄기세포와 면역관문억제제의 이해를 통해, 면역관문억제제의 암줄기세포 표적 가능성에 대해 고찰하고자 한다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.228.1-228.1
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• 2003

Sphingolipid metabolites have been implicated as an important component of cell signalling, such as cell proliferation, differentiation and apoptosis. But the roles of phytoceramide and its deraivatives are very poorly understood. even though they are abundant in plants, yeasts and animals including humans. We investigated the effects of N-acetyl-C2-phytosphingosine(NAPS) and the analogue of N.N-dimethylsphingosine(DMS), N,N-dimethylphytosphytosphingosine(DMPS), on cell growth inhibition and apoptosis. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9739-9745
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• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5839-5843
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• 2014

Objective: The Zhejiang Provincial Cancer Prevention and Control Office collected cancer registration data during 2000 to 2009 from 6 cancer registries in Zhejiang province of China in order to analyze the cancer incidence. Methods: Descriptive analysis included cancer incidence stratified by sex, age and cancer site group. The proportions and cumulative rates of 10 common cancers in different groups were also calculated. Chinese population census in 1982 and Segi's population were used for calculating age-standardized incidence rates. The log-linear model was used for fitting to calculate the incidence trends. Results: The 6 cancer registries in Zhejiang province in China covered a total of 60,087,888 person-years during 2000 to 2009 (males 30,445,904, females 29,641,984). The total number of new cancer cases were 163,104 (males 92,982, females 70,122). The morphology verified cases accounted for 69.7%, and the new cases verified only by information from death certification accounted for 1.23%. The crude incidence rate in Zhejiang cancer registration areas was $271.5/10^5$ during 2000 to 2009 (male $305.41/10^5$, female $236.58/10^5$), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were $147.1/10^5$ and $188.2/10^5$, the cumulative incidence rate (aged from 0 to 74) being 21.7%. The crude incidence rate was $209.6/10^5$ in 2000, and it increased to $320.20/10^5$ in 2009 (52.8%), with an annual percent change (APC) of 4.51% (95% confidence interval, 3.25%-5.79%). Age-specific incidence rate of 80-84 age group was achieved at the highest point of the incidence curve. Overall with different age groups, the cancer incidences differed, the incidence of liver cancer being highest in 15-44 age group in males; the incidence of breast cancer was the highest in 15-64 age group in females; the incidences of lung cancer were the highest in both males and females over the age of 65 years. Conclusions: Lung cancer, digestive system malignancies and breast cancer are the most common cancers in Zhejiang province in China requiring an especial focus. The incidences of thyroid cancer, prostate cancer, cervical cancer and lymphoma have increased rapidly. Prevention and control measures should be implemented for these cancers.

• Journal of Korean Neurosurgical Society
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• 제61권5호
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• pp.633-639
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• 2018

Objective : We investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control. Methods : A total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line. Results : After the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%. Conclusion : The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.