• Radiation Oncology Journal
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• v.12 no.3
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• pp.323-329
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• 1994

Purpose: In supraglottic cancer, radiation therapy is used to preserve the laryngeal function but combined surgery and radiation therapy is required in advanced stage. The authors Present the results of radiation therapy alone and combined surgery Plus Postoperative radiation therapy for supraglottic cancer. Methods and Materials: A retrospective analysis was done for 43 patients with squamous cell carcinoma of the supraglottic larynx who were treated from Feburary 1982 to December 1991, in the Department of Radiation Oncology, Korea University Hospital. Patient distribution according to the AJCC staging system was as follows: I, 3($7.0\%$); II, 7($16.3\%$); III, 17($39.5\%$); IV, 16($37.2\%$). Patients' age ranged from 30 to 72 years(median 62). Follow up durations were from 21 to 137 months(median 27). Seventeen patients($39.5\%$) were treated by radiation therapy alone with radiation doses of 6840-7380 cGy and 26 patients($60.5\%$) were treated with surgery plus postoperative irradiation with doses of 5820-6660 cGy. Results: Overall five-year survival rate for all stage was $51.8\%$, with $100\%$ for Stage I and II, $47.3\%$ for Stage III, and $29.2\%$ for Stage III. The difference of the survival rate by stage was statistically significant(p=0.0152). Five-year survival rates were $100\%$ for locally confined tumor in the supraglottic larynx, $37.5\%$ for transglottic extension, $26.7\%$ for hypopharynx extension, and only two of 5 patients with both transglottic and hypopharynx extension were alive(p=0.0033). Five-year survival rates by neck node status were as follows: $55.0\%$ for NO, $64.3\%$ for N1, $50.0\%$ for N2, and all 2 of N3 were died of disease. Overall survival rate for radiation therapy alone group was $42.8\%$, and it was $56.7\%$ for surgery plus postoperative radiation therapy group with no statistically significant difference(p=0.5215). In Stage I and II, all Patients survived. In Stage III and IV, 5-year survival rate for radiation therapy alone group was $28.5\%$ and $43.4\%$ for surgery plus postoperative irradiation group(p=0.5103). Local control rate was $58.8\%$(10/17) for radiation therapy alone group and $73.1\%$ (19/26) for surgery plus postoperative irradiation group. Three patients from surgery plus postoperative radiation therapy group developed distant metastasis in lungs. Conclusion: Treatment results of radiation therapy alone was excellent in early stage supraglottic cancer. In advanced stage, even the difference was statistically not significant, the result of postoperative radiation therapy group was superior compared with radiation therapy alone group. Since 1992, concomitant chemoradiotherapy with hyperfractionated radiotherapy is being used to improve the result of the treatment and preserve the laryngeal function in advanced stage supraglottic cancer.

• Archives of Pharmacal Research
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• v.20 no.3
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• pp.253-258
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• 1997

Ten, heretofore unreported, $ 5^I-methyl-5^I-[2-(5-substituted uracil-1-yl)ethyl)]-2^I-oxo-3^I$-methylenetetrahydrofurans (H, F, Cl, Br, I, $ CH_3$,$CF_3$,$CH_2CH_3$,$ CH=CH2$, SePh) (7a-j) were synthesized and evaluated against four cell lines (K-562, FM-3A, P-388 and U-937). For the preparation of ${\alpha}$-methylene-${\gamma}$-butyrolactone-linked to 5-substituted uracils (7a-j), the convenient Reformasky type reaction was employed which involves the treatment of ethyl ${\alpha}$-(bromomethyl)acrylate and zinc with the respective 1-(5-substituted uracil-1-yl)-3-butanone (6a-j). The 5-substituted uracil ketones (6a-j) were directly obtained by the respective Michael type reaction of vinyl methyl ketone with the $K_2CO_3$(or NaH)-treated 5-substituted uracils (5a-j) in the presence of acetic acid in the DMF solvent. The .alpha.-methylene-.gamma.-butyrolactone compounds showing the most significant antitumor activity are 7e, 7f, 7h and 7j (inhibitory concentration $(IC_50)$ ranging from 0.69 to $2.9 {\mu}g/ml$), while 7b, 7g and 7i have shown moderate to significant activity. The compounds 7a, 7c and 7d were found to be inactive. The synthetic intermediate compounds 6a-j were also screened and found marginal to moderate activity where compounds 6b and 6g showed significant activity $(IC_50:0.4~2.8 {\mu}g/ml)$.

• Journal of Korean Neurosurgical Society
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• v.30 no.sup1
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• pp.85-90
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• 2001

Objective : DREZotomy is effective for the treatment of deafferentation pain as a consequence of root avulsion, postparaplegic pain, posttraumatic syrinx, postherpetic neuralgia, spinal cord injury, and peripheral nerve injury. We performed microsurgical DREZotomy to the patients with deafferentation pain and relieved pain without any serious complication. The purpose of this study is to evaluate the usefulness of the microsurgical DREZotomy for deafferentation pain. Methods : We evaluated 4 patients with deafferntation pain who were intractable to medical therapy. Two of them were brachial plexus injury with root avulsion owing to trauma, one was axillary metastasis of the squamous cell carcinoma of the left forearm, and the last was anesthesia dolorosa after surgical treatment(MVD and rhizotomy) of trigeminal neuralgia. Preoperative evaluation was based on the neurologic examination, radiologic imaging, and electrophysiological study. In the case of anesthesia dolorosa, we produced two parallel lesions in cephalocaudal direction, 2mm in distance, from the C2 dorsal rootlet to the 5mm superior to the obex including nucleus caudalis, after suboccipital craniectomy and C1-2 laminectomy, with use of microelectrode. In the others, we confirmed lesion site with identification of the nerve root after hemilaminectomy. We performed arachnoid dissection along the posterolateral sulcus and made lesion with microsurgical knife and microelectrocoagulation, 2mm in depth, 2mm in distance, to the direction of 30-45 degrees in the medial portion of the Lissauer's tract and the most dorsal layers of the posterior horn at the one root level above and below the lesion. Results : Compared with preoperative state, microsurgical DREZotomy significantly diminished dosage of the drugs and relieved pain meaningfully. One patient showed tansient ipsilateral ataxia, but recovered soon. There was not any serious complication. Conclusion : It may be concluded that microsurgical DREZotomy is very useful and safe therapeutic modality for deafferentation pain, especially segmentally distributed intermittent or evoke pain. Complete preoperative evaluation and proper selection of the patients and lesion making device are needed to improve the result.

• Journal of Life Science
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• v.32 no.3
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• pp.210-221
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• 2022

This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

• Radiation Oncology Journal
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• v.24 no.2
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• pp.128-137
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• 2006

Purpose: We investigated whether a relationship exists between tumor control dose 50 ($TCD_{50}$) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between $TCD_{50}$, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Materials and Methods: Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used In this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were $8{\sim}12$ weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for $TCD_{50}$, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of $p53,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-X_L,\;Bcl-X_S$, and p34. Correlation analysis was peformed whether the level of RIA were correlated with $TCD_{50}$ or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with $TCD_{50}$, TGD, RIA. Results: The level of RIA showed a significant positive correlation (R=0.922, p=0.026) with TGD, and showed a trend to correlation (R=-0.848), marginally significant correlation with $TCD_{50}$ (p=0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of $p21^{WAF1/CIP1}$ and 34 showed a significant correlation either with $TCD_{50}$ (R=0.893, p=0.041 and R=0.904, p=0.035) or with TGD (R=-0.922, p=0.026 and R=-0.890 p=0.043). The tumors with high constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 were less radiosensitive than those with low expression. Conclusion: Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 can be used as biological markers which predict the radiosensitivity.

• Microbiology and Biotechnology Letters
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• v.41 no.4
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• pp.425-432
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• 2013

Typha orientalis, also known as bulrush or cattail, is a perennial herbaceous plant found in freshwater wetlands and has been widely used in constructed wetlands for wastewater treatment. Recent data has revealed that SH21B, a mixture composed of seven herbs including T. orientalis, exhibited an anti-adipogenic activity by the inhibition of the expression of adipogenic regulators. However, the anti-cancer effect of T. orientalis and its molecular mechanisms remain unclear. In this study, we evaluated the anti-cancer effect and its mechanism in the methanol extract of T. orientalis (METO) on human colon carcinoma HT29 cells. It was found that METO treatment showed cytotoxic activity in a dose-dependent manner, and induced G2/M cell cycle arrest and apoptosis in HT29 cells. The induction of G2/M arrest by METO was associated with the up-regulation of phospho-Cdc2 (Tyr15), an inactive form of Cdc2 and the down-regulation of Cdc25c phosphatase. METO also induced tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. In addition, METO-induced apoptosis was characterized by the proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of death receptor FAS and pro-apoptotic Bax expression. Collectively, these results indicate that the cell cycle inhibition and apoptosis induction of METO in HT29 cells allows for the possibility of its use in anti-cancer therapies.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.226-232
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• 2000

Purpose :This study was performed to find out the prognostic factors affecting local control in early glottic cancer treated with radiation therapy alone. Materials and Methods :We analysed 37 patients of histologically confirmed early glottic cancer treated at Chonnam National University Hospital between July Im and December 1995, retrospectively. Age of patients ranged from 30 to 73 years (median; 59 years). Thirty-five (95$\%$) patients were male. Histological type was all squamous cell carcinoma. According to the staging system of 1997 American Joint Committee on Cancer, 37 patients were restaged as follows: Tla; U (73$\%$), Tlb; 3 (8$\%$), 72: 7 (19$\%$). Radiation therapy was done using 6 MV X-ray of linear accelerator The range of total radiation dose delivered to the glottic lesion was between 5,040 cGy and 7,020 cGy (median; 6,600 cGy). Median follow-up period was U months. local control rates were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of control rates between comparable groups. Multivariate analysis using Cox proportional hazard model was done to find out prognostic factors affecting local control. Results:5 year survival rate of 37 patients was 89$\%$. Local control rate of 37 patients was 74$\%$ in 5 years. We included age, 7-stage, anterior commissure involvement, fraction size, total radiation dose, treatment time of radiotherapy as potential prognostic factors in univariate and multivariate analysis. As a result, treatment time had statistical significance in local control rate in both univariate (p=0.026) and multivariate (p=0.017) analysis. Complication was not recorded except one patient with hypothyroidism. Conclusion :This study revealed that overall treatment time of radiation was a significant factor affecting local control rate.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2043-2049
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• 2015

Background: Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. Materials and Methods: Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. Results: showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). Conclusions: Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.12
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• pp.1708-1716
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• 2016

The Akt/mammalian target of the rapamycin (mTOR) pathway is activated in the majority of human cancers. Activation of the Akt/mTOR pathway confers resistance to many types of cancer therapy. In this study, we evaluated the apoptotic effect of ethanol extract of Artemisia annua L. through down-regulation of Akt signal pathways and the mitochondrial pathway in hepato-carcinoma cells (HepG2). A. annua extract is known as a medicinal herb that is effective against cancer. We evaluated anti-proliferative activity by MTT-based viability assay and apoptotic effect by Annexin-V/PI staining, mitochondrial membrane potential (MMP), and caspase-3/7 activity as determined by flow cytometry. A. annua treatment led to loss of MMP, resulting in cytochrome c-inducible activation of caspase-3/7. Treatment with A. annua extract reduced activities of Akt/mTOR/anti-apoptotic proteins (such as Bcl-2 and $Bcl-X_L$), leading to increased activation of tumor suppressor p53 and pro-apoptotic proteins (such as Bax and Bak). We applied LY294002 (inhibitor of Akt) and rapamycin (inhibitor of mTOR) to determine the relationship between signal transduction of proteins associated with apoptosis. LY294002 and rapamycin significantly reduced cell viability and increased apoptosis. These results indicate that Bcl-2 and caspase-3 are key regulators in A. annua extract-induced apoptosis in HepG2 cells and are controlled through the Akt/mTOR signaling pathway.