• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.98-98
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• 2003

${\beta}$-(1,3)-D-Glucans have been known to exhibit antitumor and antimicrobial activities. The presence of dectin-1,${\alpha}$, ${\beta}$-glucan receptor of dendritic cell, on macrophage has been controvertial. RT-PCR analysis led to the detection of dectin-1${\alpha}$ and ${\beta}$ in murine macrophage Raw264.7 cell line. Among the various organs of mouse, dectin-1${\alpha}$ and ${\beta}$ were detected in the thymus, lung, spleen, stomach and intestine. To analyze gene expression modulated by ${\beta}$-glucan treated murine Raw264.7 macrophage, total mRNA was applied to cDNA microarray to interrogate the expression of 7,000 known genes. cDNA chip analysis showed that ${\beta}$-glucan of P. osteatus increased gene expressions of immunomodulating genes, membrane antigenic proteins, chemokine ligands, complements, cytokines, various kinases, lectin associated genes and oncogenes in Raw 264.7 cell line. When treated with ${\beta}$-glucan of P. osteatus and LPS, induction of gene expression of TNF-${\alpha}$ and IFN-R1 was confirmed by RT-PCR analysis. Induction of TNF-R type II expression was confirmed by FACS analysis. IL-6 expression was abolished by EDTA in ${\beta}$-glucan and LPS treated Raw264.7 cell line, indicating that ${\beta}$-glucan binds to dectin-l in a Ca$\^$＋＋/ -dependent manner. To increase antitumor efficacy of ${\beta}$-glucan, ginsenoside Rh2 (GRh2) was co-treated with ${\beta}$-glucan in vivo and in vitro tests. IC$\sub$50/ values of GRh2 were 20 and 25 $\mu\textrm{g}$/$m\ell$ in SNU-1 and B16 melanoma F10 cell line, respectively. Co-treatment with ${\beta}$-glucan and GRh2 showed synergistic antitumor activity with cisplatin and mitomycin C both in vitro and in vivo. Single or co-treatment with ${\beta}$-glucan and GRh2 increased tumor bearing mouse life span. Co-treatment with ${\beta}$-glucan and GRh2 showed more increased life span with mitomycin C than that with cisplatin. Antitumor activities were 67% and 72 % by co-injection with ${\beta}$-glucan and GRh2 in the absence or presence of mitomycin C, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6139-6144
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• 2012

Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4335-4340
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• 2016

Background: Bone metastasis is a single condition but presents with various patterns and severities. Skeletal-related events (SREs) deteriorate overall performance status and reduce quality of life. However, guidelines for early detection and management are limited. This study includes a survey of the prevalence of bone metastasis in cases with common cancers in Thailand as well as a focus on survival patterns and SREs. Materials and Methods: A retrospective cohort analysis was conducted using a database of the Chiang Mai Cancer Registry and the Musculoskeletal Tumor Registry of the OLARN Center, Chiang Mai University. The prevalence of bone metastasis from each type of primary cancer was noted and time-to-event analysis was performed to estimate cancer survival rates after bone metastasis. Results: There were 29,447 cases of the ten most common cancers in Thailand, accounting for 82.2% of the entire cancer registry entries during the study period. Among those cases, there were 2,263 with bone metastases, accounting for 7.68% of entries. Bone metastasis from lung, liver, breast, cervix and prostate are common in the Thai population, accounting for 83.4% of all positive cases. The median survival time of all was 6 months. Of the bone metastases, 48.9% required therapeutic intervention, including treatment of spinal cord and nerve root compression, pathological fractures, and bone pain. Conclusions: The frequency of the top five types of bone metastasis in Thailand were different from the frequencies in other countries, but corresponded to the relative prevalence of the cancers in Thailand and osteophilic properties of each cancer. The results of this study support the establishment of country specific guidelines for primary cancer identification with skeletal lesions of unknown origin. In addition, further clinical studies of the top five bone metastases should be performed to develop guidelines for optimal patient management during palliative care.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5057-5061
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• 2012

Purpose: Chemotherapy-induced anemia (CIA) is one of the most important causes of anemia in cancer patients. This study was conducted to describe the prevalence and characteristics of CIA in solid cancer patients in the Chinese population, and to explore the relationship of white blood cell (WBC) or platelet decrease with CIA. Methods: Data on age, gender, tumor diagnosis, anti-cancer treatment and blood cell analyses were available from 220 untreated non-anemic cancer patients who received at least 2 cycles of chemotherapy, and the data were analyzed to assess their relationship with CIA or its severity. Results: 139 patients (63.2%) presented anemia, most being Grade 1 or 2. Esophageal and lung cancers were associated with a high prevalence. G3/4 leucopenia and decrease of platelets were identified as independent risk factors for the occurrence of CIA. Moreover, G3/4 leucopenia, decrease of platelet and G3/4 thrombocytopenia were found to be also associated with the severity of CIA. Cisplatin-containing regimens were a main potential factor in causing CIA, although significant association was only found on univariate analysis. Conclusion: Anemia or decrease in hematoglobin are common in Chinese cancer patients receiving chemotherapy. Cisplatin-containing regimens might be an important factor influencing the occurrence of CIA. Our analysis firstly described some risk factors, such as decrease of platelets or WBCs, severity of leucopenia or thrombocytopenia, associated with the occurrence and severity of CIA.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.34 no.1
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• pp.71-75
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• 2012

Renal cell carcinoma (RCC) is the most frequent urological malignant tumor in adults and it occurs mostly between the fifth and the sixth decades of life. The male-female ratio is 3:1 and it is more common in smokers. It accounts for approximately 3% of adult malignancies; 90~95% of neoplasms of the kidney. The classic triad of presenting symptoms of RCC is hematuria, back pain and a mass in the flank. More than 50% of RCCs show metastasis to breast, lung and regional lymph nodes, and 15% present in the orofacialmaxillary region. This case is about a 66 year-old man who was treated for painless swelling in the left masseteric area. The mass was surgically excised and sent for biopsy. It was diagnosed as RCC and two weeks later nephronectomy of the left kidney was performed. Metastasis to other organs was detected and the patient received radiation therapy. In this case we were able to find the primary lesion by the metastatic lesion.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.3
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• pp.143-154
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• 2013

Purpose: This study was to find efficacy of integrin alpha2 (${\alpha}_2$) and epidermal growth factor receptor (EGFR) as tumor marker of oral squamous cell carcinoma (SCC) and clarify the selective cell death effect of anti-integrin ${\alpha}_2$ and anti-EGFR on SCC cells, additionally testify conjugated gold nanoparticles (GNP) with air plasma for selective cell death of oral SCC. Methods: Expression of integrin ${\alpha}_2$, EGFR on human SCC cells (SCC25) were examined by western blot. SCC25 cells were treated with anti-integrin ${\alpha}_2$, anti-EGFR and analysed by Hemacolor staining, immunoflorescence staining, FACS flow cytometry. Conjugated GNP with integrin ${\alpha}_2$, EGFR antibody were treated by air plasma on SCC cells. Results: Integrin ${\alpha}_2$ and EGFR were over-expressed on SCC25 cells than normal lung WI-38 cells. The cell viability rate of SCC25 cells treated with anti-integrin ${\alpha}_2$, anti-EGFR was lower than WI-38 cells. The concentration changes of nucleus, releasing cytochrome c and apoptosis inducing factor (AIF) from mitochondria to cytosol were observed. The changes of proteins related with apoptosis were observed. Increase of bax, bcl-xL, activation of caspase-3, -7, -9, and fragmentation of PARP, DFF45 and decrease of lamin A/C in SCC25 cells were observed. In FACS, increase of sub-$G_1$ and S phase was observed. Cell cycle related proteins, Such as cyclin D1, cyclin dependent kinase (CDK) 4, cyclin A, cyclin E, CDK 2, p27 were decreased. After SCC25 cells treated with conjugatged GNP-Integrin ${\alpha}_2$, GNP-EGFR, additionally air plasma, the cell death rate was significantly increased. Conclusion: Integrin ${\alpha}_2$, EGFR were over-expressed in oral SCC cells. Anti-integrin ${\alpha}_2$, anti-EGFR in SCC25 cells induced apoptosis selectively. When GNP-anti integrin ${\alpha}_2$, GNP-anti EGFR were treated with air plasma on SCC25 cells, cancer cells were died more selectively. GNP-anti integrin ${\alpha}_2$, GNP-anti EGFR with air plasma could be treatment choice of oral SCC.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2005.04a
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• pp.59-63
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• 2005

Respiration motion causes movement of internal structures in the thorax and abdomen, making accurate delivery of radiation therapy to tumors in those areas a challenge. Accounting for such motion during treatment, therefore, has the potential to reduce margins drawn around the clinical target volume (CTV), resulting in a lower dose to normal tissues (e.g., lung and liver) and thus a lower risk of treatment induced complications. Among the techniques that explicitly account for intrafraction motion are breath-hold, respiration gating, and 4D or tumor-tracking techniques. Respiration gating methods periodically turn the beam on when the patient's respiration signal is in a certain part of the respiratory cycle (generally end-inhale or end-exhale). These techniques require acquisition of some form of respiration motion signal (infrared reflective markers, spirometry, strain gauge, thermistor, video tracking of chest outlines and fluoroscopic tracking of implanted markers are some of the techniques employed to date), which is assumed to be correlated with internal anatomy motion. In preliminary study for the respiratory gating radiation therapy, we performed to measurement of this respiration motion signal. In order to measure the respiratory motion signals of patient, respiration measurement system (RMS) was composed with three sensor (spirometer, thermistor, and belt transducer), 4 channel data acquisition system and mobile computer. For two patients, we performed to evaluation of respiratory cycle and shape with RMS. We observed under this system that respiratory cycle is generally periodic but asymmetric, with the majority of time spent. As expected, RMS traced patient's respiration each other well and be easily handled for application.

• Radiation Oncology Journal
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• v.5 no.2
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• pp.111-117
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• 1987

From March, 1983 to March, 1987, 16 patients with esophageal steno-obstruction due to nonesophageal tumors were treated in the Division of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. The patient characteristics, effect of radiotherapy (XRT) on esophageal steno-obstruction and survival were evaluated. The most common primary tumor was lung cancer (14/16) and the middle third of the esophagus was most frequently involved (14/16). Improved clinical response was observed in $80\%$ of the patients who finished the planned courses of XRT. The mean radiation dose evoking the improvement of dysphagia was 2,993 cGy given over a period of 3 to 4 weeks. The Kaplan-Meier estimates of survival at 15 and 30 weeks of follow-up were $60\%$ and $46\%$, respectively. In the completed group who finished the whole planned courses of XRT, survival rates were $77\%\;and\;51\%$, respectively. Four patients were alive over 90 weeks with normal passage of food.

• The Korean Journal of Nuclear Medicine
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• v.29 no.4
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• pp.526-532
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• 1995

Introduction : $^{99m}Tc$-(V)-DMSA is a tumor seeking agent that has been used to image medullary carcinoma of thyroid, soft tissue sarcoma and lung cancer. This study was designed to assess the clinical role of $^{99m}Tc$-(V)-DMSA in the diagnosis of head and neck cancers. We has evaluated the diagnostic efficacy of planar and SPECT imaging using $^{99m}Tc$-(V)-DMSA. Patients and Method : Sixty-eight patients with head and neck mass were included in this study. All subjects were diagnosed by biopsy or surgery. Planar and SPECT images were obtained at 2 or 3 hour after intravenous injection of 740 MBq(20 mCi) $^{99m}Tc$-(V)-DMSA. Seventeen patients also underwent SPECT in aging using dual head camera. Result : The diagnostic sensitivity of $^{99m}Tc$-(V)-DMSA planar and SPECT imaging was 65% and 90%, and specificity was 80% and 66%, respectively. The sensitivity of planar imaging in squamous cell carcinoma was similar to overall sensitivity Six metastatic lesion were first diagnosed by scintigraphy. But benign lesions such as Kikuchi syndrome, tuberculous lymphadenitis also revealed increased uptake. Conclusion : $^{99m}Tc$-(V)-DMSA imaging seems to be a promising method in the evaluation of patients with head and neck mass. We recommend SPECT imaging to delineate anatomic localization of the lesion.