• 한국치위생학회지
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• 제15권3호
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• pp.523-529
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• 2015

Objectives: Oropharynx tumors(oral cancer), are caused by tobacco, alcohol consumption, and high-risk human papillomavirus(HPV) infection. Oral squamous cell carcinoma(OSCC) is the most common type of oral cancer and frequently arises from the mucosa of the oropharynx and oral cavity. Despite advances in the diagnosis and treatment(chemotherapy, radiotherapy, and surgery) of oral cancer, over the past two decades, the overall survival rates remains at about 60%. Methods: We pretreated HSC-2 cells with various doses of exposed the cells to eugenol and then we measured cell viability by MTT assay. Results: Cell proliferation was markedly inhibited after eugenol treatment compared to the control. The majority of HSC-2 cells in the control groups showed normal morphology with round regular nuclei. In contrast, apoptotic bodies were seen in the 0.5 mM, 1 mM, 2 mM group. However, the pretreatment with eugenol increased HSC-2 cells apoptosis according to dose-dependency. PI staining quantitatively confirmed the anti-apoptotic effects of propofol. The expression levels of cleaved caspase 3, and Bak significantly increased in HSC-2 cells. Conclusions: These findings indicate that eugenol could be a potential anti-cancer agent for human OSCC and provide valuable data for the development of a novel anticancer strategy.

• Radiation Oncology Journal
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• 제2권1호
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• pp.11-20
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• 1984

The renewed interest in the use of hyperthermia in cancer therapy is bases on radiobiological and clinical evidence indicated that there may be a significant therapeutic advantage with the use of heat alone or combined with radiation or chemotherapy, There are many methods for generating heat for localized tumor as like radiofrequency, microwave, electromagnetic induction and ultrasound. But it is very difficult to be even thermal dose distribution and stable output of power and then the detection of temperature in tumor is difficult to be precise with thermocouples and semiconductor sensors. We designed the microwave heating generator, dipole antenna applicators and autometic temperature controlled thermocouples for localized hyperthermia on skin and in cavities. 1. The microwave generator with 120 W, 2,450MHz magnetron could be heating up to $40^{\circ}C\~50^{\circ}C\;for\;1\~2$ hours in living tissues. 2. The thermal dose distribution in tissue with microwave was described $42^{\circ}C\~44^{\circ}C$ with in 3 cm depth and $2\~6cm$ diameter area. 3. Skin surface heating applicator with spiral 3 times wave length antenna radiated high Power of microwave. 4, Intracavitary heating applicator with dipole antenna with autometic control temperature sensor kept up continuously constant temperature in tissue. 5. For constant thermal distribution, applied two steps power with 10W microwave after $17\~20W$ during first 10 minutes. 6. The cooling rate by blood flew in living tissue was rised as $10\%$ then meats.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5191-5197
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• 2015

A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3541-3546
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• 2014

TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TEL-AML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4853-4858
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• 2013

Objectives: To investigate whether hypoxia has an effect on regulation of multidrug resistance (MDR) to chemotherapeutic drugs in laryngeal carcinoma cells and explore the role of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$). Methods: Laryngeal cancer cells were cultured under normoxic and hypoxic conditions. The sensitivity of the cells to multiple drugs and levels of apoptosis induced by paclitaxel were determined by MTT assay and annexin-V/propidium iodide staining analysis, respectively. HIF-$1{\alpha}$ expression was blocked by RNA interference. The expression of HIF-$1{\alpha}$ gene was detected by real-time quantitative RT-PCR and Western blotting. The value of fluorescence intensity of intracellular adriamycin accumulation and retention in cells was evaluated by flow cytometry. Results: The sensitivity to multiple chemotherapy agents and induction of apoptosis by paclitaxel could be reduced by hypoxia (P<0.05). A the same time, the adriamycin releasing index of cells was increased (P<0.05). However, resistance acquisition subject to hypoxia in vitro was suppressed by down-regulating HIF-$1{\alpha}$ expression. Conclusion: HIF-$1{\alpha}$ could be considered as a key regulator for mediating hypoxia-induced MDR in laryngeal cancer cells via inhibition of drug-induced apoptosis and decrease in intracellular drug accumulation.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2409-2414
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• 2012

Objective: Traditional Chinese herbal medicines have a very long history. Rosa roxburghii Tratt and Fagopyrum cymosum are two examples of plants which are reputed to have benefits in improving immune responses, enhancing digestive ability and demonstrating anti-aging effects. Some evidence indicates that herbal medicine soups containing extracts from the two in combination have efficacy in treating malignant tumors. However, the underlying mechanisms are far from well understood. The present study was therefore undertaken to evaluate anticancer effects and explore molecular mechanisms in vitro. Methods: Proliferation and apoptosis were assessed with three carcinoma cell lines (human esophageal squamous carcinoma CaEs-17, human gastric carcinoma SGC-7901 and pulmonary carcinoma A549) by MTT assay and flow cytometry, respectively, after exposure to extract from Rosa roxburghii Tratt (CL) and extract from Fagopyrum cymosum (FR). $IC_{30}$ of CL and FR were obtained by MTT assay. Tumor cells were divided into four groups : control with no exposure to CL or FR; CL with $IC_{30}$ CL; FR with $IC_{30}$ FR; CL+FR group with 1/2 ($IC_{30}$ CL + $IC_{30}$ FR). RT-PCR and Western blot analysis were used to detect the expression of Ki-67, Bax and Bcl-2 at mRNA and protein levels. Results: Compared with the CL or FR groups, the combination of CL+FR showed significant inhibition of cell growth and increase in apoptosis; the mRNA and protein expression levels of Ki-67 and Bcl-2 in CL+FR group were all greatly decreased, while the expression of Bax was markedly increased. Conclusions: These results indicate that the synergistic antitumor effects of combination of CL and FR are related to inhibition of proliferation and induction of apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1845-1849
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• 2012

Objective: Tissue factor (TF) is expressed abnormally in certain types of tumor cells, closely related to invasion and metastasis. The aim of this study was to construct a human gastric cancer cell line SGC7901 stably-transfected with human TF, and observe effects on oxaliplatin-dependent inhibition of invasion and the apoptosis induction. Methods: The target gene TF was obtained from human placenta by nested PCR and introduced into the human gastric cell line SGC7901 through transfection mediated by lipofectamine. Stably-transfected cells were screened using G418. Examples successfully transfected with TF-pcDNA3 recombinant (experimental group), and empty vector pcDNA3 (control group) were incubated with oxaliplatin. Transwell chambers were used to show change in invasive ability. Caspase-3 activity was detected using a colorimetric method and annexin-V/PI double-staining was applied to detect apoptosis. Results: We generated the human gastric cancer cell line SGC7901/TF successfully, expressing TF stably and efficiently. Compared with the control group, invasion increased, whereas caspase-3 activity and apoptosis rate were decreased in the experimental group. Conclusion: TF can enhance the invasive capacity of gastric cancer cells in vitro. Its increased expression may reduce invasion inhibition and apoptosis-inducing effects of oxaliplatin and therefore may warrant targeting for improved chemotherapy.

• Molecules and Cells
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• 제38권5호
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• pp.416-425
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• 2015

NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor, has recently received a great deal of attention as an important molecule that enhances antioxidative defenses and induces resistance to chemotherapy or radiotherapy. In this study, we investigated the apoptosis-inducing and Nrf2- upregulating effects of quercetin on malignant mesothelioma (MM) MSTO-211H and H2452 cells. Quercetin treatment inhibited cell growth and led to upregulation of Nrf2 at both the mRNA and protein levels without altering the ubiquitination and extending the half-life of the Nrf2 protein. Following treatment with quercetin, analyses of the nuclear level of Nrf2, Nrf2 antioxidant response element-binding assay, Nrf2 promoter-luc assay, and RT-PCR toward the Nrf2-regulated gene, heme oxygenase-1, demonstrated that the induced Nrf2 is transcriptionally active. Knockdown of Nrf2 expression with siRNA enhanced cytotoxicity due to the induction of apoptosis, as evidenced by an increase in the level of proapoptotic Bax, a decrease in the level of antiapoptotic Bcl-2 with enhanced cleavage of caspase-3 and PARP proteins, the appearance of a sub-$G_0/G_1$ peak in the flow cytometric assay, and increased percentage of apoptotic propensities in the annexin V binding assay. Effective reversal of apoptosis was observed following pretreatment with the pan-caspase inhibitor Z-VAD. Moreover, Nrf2 knockdown exhibited increased sensitivity to the anticancer drug, cisplatin, presumably by potentiating the oxidative stress induced by cisplatin. Collectively, our data demonstrate the importance of Nrf2 in cytoprotection, survival, and drug resistance with implications for the potential significance of targeting Nrf2 as a promising strategy for overcoming resistance to chemotherapeutics in MM.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.434-441
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• 2015

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP ($IC_{50}=0.67{\mu}M$) than in DU145 cells ($IC_{50}=1.10{\mu}M$) and PC3 cells ($IC_{50}=5.60{\mu}M$) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권1호
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• pp.1-10
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• 2008

Oral squamous cell carcinoma (OSCC) is the most frequent form of oral cancer and holds the eighth position in the cancer incidence ranking. OSCC patients are treated by classical therapeutic modalities consisting of surgery, radiotherapy, and/or chemotherapy. But OSCC still shows significant mortality rates. Thus, new therapeutic approaches have been investigated and the most promising one is naturally acquired agents with known anti-cancer effects. Genistein is a compound extracted from soy bean. Its anti-cancer effect on breast cancer is well established now and it is investigated whether it has similar effect on OSCC. It inhibited the growth and invasive-ness of OSCC cells in vitro, but these effects did not work in living animals in vivo. Catechin is a compound from green tea and its anti-cancer effect on OSCC is known better than other agents. Catechin showed its anti-cancer effect in vitro via induction of apoptosis, cell cycle arrest, inhibition of growth, and down-regulation of invasion/metastasis. These effects were confirmed in vivo with mouse model. Cordycepin is one of major pharmacologically important components in Cordyceps Militaris and may exert its anti-cancer effect as an adenosine receptor agonist. In recent study, it inhibited the proliferation of OSCC cells via A3 adenosine receptor. But because there is very scarce evidence on this effect, more researches are needed on this theme.