• Radiation Oncology Journal
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• v.17 no.2
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• pp.151-157
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• 1999

Purpose : By sequencing the Erpressed Sequence Tags of human 걸ermal papilla CDNA library, we identified a clone named K872 of which the expression decreased during differentiation of HL6O cell line. Materials and Methods : K872 plasmid DNA was isolated according to QIA plasmid extraction kit (Qiagen GmbH, Germany). The nucleotide sequencing was performed by Sanger's method with K872 plasmid DNA. The most updated GenBank EMBL necleic acid banks were searched through the internet by using BLAST (Basic Local Alignment Search Tools) program. Nothern bots were performed using RNA isolated from various human tissues and cancer cell lines. The gene expression of the fusion protein was achieved by His-Patch Thiofusicn expression system and the protein product was identified on SDS-PAGE. Results : K872 clone is 1006 nucleotides long, and has a coding region of 675 nucleotides and a 3' non-coding region of 280 nucleotides. The presumed open reading frame starting at the 5' terminus of K872 encodes 226 amino acids, including the initiation methionine residue. The amino acid sequence deduced from the open reading frame of K872 shares $70\%$, identity with that of rat glutathione 5-transferase kappa 1 (rGSTKl). The transcripts were expressed in a variety of human tissues and cancer cells. The levels of transcript were relatively high in those tissues such as heart, skeletal muscle, and peripheral blood leukocyte. It is noteworthy that K872 was found to be abundantly expressed in coloreetal cancer and melanoma cell lines. Conclusion : Homology search result suggests that K872 clone is the human homolog of the rGSTK1 which is known to be involved in the resistance of cytotoxic therapy. We propose that meticulous functional analysis should be followed to confirm that.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.35-44
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• 2008

Purpose: To evaluate the incidence and prognostic factors of treatment-related pneumonitis in non-small-cell lung cancer(NSCLC) patients treated with intensity modulated radiation therapy(IMRT). Materials and Methods: One-hundred-five patients with NSCLC treated with IMRT between 1 August 2004 and 30 November 2006 were analyzed retrospectively. The mean age of patients was 62.9 years, and squamous carcinomas were confirmed in 81 patients(77%). Sixty-six patients(62.9%) were classified as stage III, and 59 patients had lesions in the right lung. Twenty-seven patients were treated with a dose of 3,060 cGy preoperatively, and 10 patients were given a dose of 5,040 cGy postoperatively. Sixty-eight patients received a dose of 7,020 cGy for curative intent. Sixty-eight patients were treated with the use of the CORVUS planning system and 37 patients were treated with the use of the ECLIPSE planning system. Results: Of 105 patients, 21 patients(20%) had abnormal radiological findings, but only seven patients(6.7%) required treatment for radiation pneumonitis. Six of the seven patients had other serious lesions, including a bronchioesophageal fistula(one patient), recurrence in the treatment field(two patients), brain metastasis(one patient) and lung-to-lung metastasis(two patients); all of these patients died within 19 months after radiation treatment. Sixteen patients(23.5%) that received planning with the CORVUS system had abnormal lung findings. Five patients(13.5%) had abnormal lung findings with the use of the ECLIPSE planning system. Other prognostic factors such as perioperative radiation therapy, a volume over 10% of the V20 volume in the right lung, were also statistically significant. Conclusion: This retrospective analysis suggests that IMRT could be a beneficial treatment modality for the reduction of radiation pneumonitis in NSCLC patients. However, the higher incidence of abnormal radiological findings in perioperative patients treated with relatively lower doses($3,060{\sim}5,040$ cGy) suggest the need for judicious treatment planning in preoperative or postoperative treatment.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.4
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• pp.205-210
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• 2006

Purpose: FDG uptake on positron omission tomography (PET) has been considered a prognostic indicator in non-small cell lung cancer (NSCLC). The aim of this study was to assess the clinical significance of maximum value of SUV (maxSUV) in recurrence prediction in patients with surgically resected NSCLC. Materials & methods: NSCLC patients (n=42, F:M =14:28, age $62.3{\pm}12.3$ y) who underwent curative resection after FDG-PET were enrolled. Twenty-nine patients had pathologic stage 1, and 13 had pathologic stage II. Thirty-one patients were additionally treated with adjuvant oral chemotherapy. MaxSUVs of primary tumors were analyzed for correlation with tumor recurrence and compared with pathologic or clinical prognostic indicators. The median follow-up duration was 16 mo (range, 3-26 mo). Results: Ten (23.8%) of the 42 patients experienced recurrence during a median follow-up of 7.5 mo (range, 3-13 mo). Univariate analysis revealed that disease-free survival (DFS) was significantly correlated with maxSUV (<7 vs. $\geq7$, p=0.006), tumor size (<3 cm vs. $\geq3$ cm, p=0.024), and tumor tell differentiation (well/moderate vs. poor, p=0.044). However, multivariate Cox proportional analysis identified maxSUV as the single determinant for DFS (p=0.014). Patients with a maxSUV of $\geq7$(n=10) had a significantly lower 1-year DFS rate (50.0%) than those with a maxSUV of <7 (n=32, 87.5%). Conclusion: MaxSUV is a significant independent predictor for recurrence in surgically resected NSCLC. FDG uptake can be added to other well-known factors in prognosis prediction of NSCLC.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.42 no.5
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• pp.597-603
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• 1997

Orostachys japonicus, Wasong as herb medicine, has been artificially cultivated as an anti-tumor medicinal. The experiment was carried out to examine the effect of natural daylength as control or night-break treatment (NB) imposed at June 20, July 18 or Aug. 15 on its growth, dry weights of leaf and bract, stem, floret and root, and morphological characters including bolting and floret flowering. After a plant was grown in a 15cm plastic pot containing a 2 : 1 soil : peat moss mixture on May 23, three treatments with above differing night-break had been imposed around midnight up to Nov. 7. The plants were sampled 3 times at the same day forced to night-break and then done 6 times by 2-week interval after the final NB. Plant height and inflorescence length of all the NB increased with delayed NB but declined in comparison with the natural daylength. No. of leaves including bracts showed similar response to plant height although NB given before July 18 showed less leaves and bracts. Stem diameters of NB were continuously increased to middle Sept. to middle Oct. while that of natural daylength decreased after middle Oct. Natural daylength or NB given on Aug. 15 had greater fraction, shoot and total dry weights resulting from increment of leaf and bract up to Aug. or of floret, stem and root after Sept. The earlier NB, the later formation of florets and the less number of flowering florets whereas in natural daylength florets on inflorescence begun to be formed from middle Sept. were sharply increased up to middle Oct. when all the plants were flowered. Bolting was not formed in the plant of the earliest NB of June 20, and thereby no anthesis of florets up to early Nov. It was concluded that year-round cultivation of Orostachys japonicus plants was possible through controlling the NB timing because its bolting and flowering of florets separately occurred.

• Journal of Life Science
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• v.26 no.1
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• pp.23-33
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• 2016

Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. The purpose of this study was to develop methods to maximize the stability of Pexa-Vec. In short-term instability testing, viral activity was rapidly decreased both at 4℃ and at room temperature (RT), but it was completely restored after sonication followed by vortex. Long-term stability testing of Pexa-Vec in the following liquid formulations was performed: (A) 30 mM Tris/pH 7.6, (B) 30 mM Tris/pH 8.6, (C) 30 mM Tris/pH 7.6, 150 mM NaCl, 15% sucrose, (D) 30 mM Tris/pH 7.6, 15% sucrose, and (E) 30 mM Tris/pH 8.6, 15% sucrose. Viral activity decreased less than 2 log10 at 4℃, and RT was observed in 3 days in B, while viral activity was not decreased even after 4–8 weeks at 4℃ and at 1 week in RT in A, suggesting that neutral pH may be essential to maintain virus stability. The addition of 15% sucrose into A (D) significantly increased viral stability at −20℃, 4℃, or RT, and it was also observed at pH 8.6 (E). The addition of 150 mM NaCl into D (C) significantly increased viral stability in addition to the sucrose effect at 4℃ or RT. Accordingly, the viral activity in formulation C was maintained for 1.5 years at 4℃, and for 1-2 weeks in RT. In conclusion, we propose that formulation C can provide the most adequate condition for the proper storage of vaccinia oncolytic virus.

• Journal of Life Science
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• v.27 no.2
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• pp.149-154
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• 2017

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.275-284
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• 2002

Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.164-170
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• 2006

[ $\underline{Purpose}$ ]: This study identified the result of postoperative radiation therapy and the prognostic factors to affect survival rates in cancer patients. $\underline{Materials\;and\;Methods}$: One hundred and thirty three patients with cervical cancer who were treated with postoperative radiation therapy following surgery at our institution between June 1985 and November 2002 were retrospectively analyzed. One hundred and thirteen patients had stage IB disease, and 20 patients had stage IIA disease. Histological examination revealed 118 squamous cell carcinoma patients and 15 adenocarcinoma patients. Sixty seven patients were noted to have stromal invasion greater than 10 mm, and 45 patients were noted to have stromal Invasion 10 mm or less. Positive lymphovascular invasion was found in 24 patients, and positive pelvic lymph nodes were noted in 39 patients. Positive vaginal resection margin was documented in 8 patients. All of the patients were treated with external beam radiation therapy to encompass whole pelvis and primary surgical tumor bed. Intracavitary radiation therapy was added to 19 patients who had positive or close surgical margins. $\underline{Results}$: Actuarial overall and disease-free survival rates for entire group of the patients were 88% and 84% at 5 years, respectively. Five-year disease-free survival rates for patients with stromal invasion greater than 10 mm and 10 mm or less were 76% and 97%, respectively (p<0.05). Also there was a significantly lower survival in patients with positive pelvic lymph nodes compared with patients with negative pelvic lymph nodes (p<0.05). However, lymphovascular invasion, positive vaginal resection margins were not statistically significant prognostic factors. Addition of neoadjuvant chemotherapy or type of surgery did not affect disease-free survival. $\underline{Conclusion}$: Postoperative radiation therapy appears to achieve satisfactory local control with limited morbidity in cervical cancer patients with high pathologic risk factors. Distant metastasis was a dominant failure pattern to affect survival in cervical cancer patients after radical surgery and radiation and more effective systemic treatment should be investigated in these high-risk patients.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.613-618
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• 2005

This study was carried out to examine the effects of gamma irradiation on the cytotoxicity and multidrug-resistance reversing activity of methanol extracts from Coix lachryma-jobi L. var. me-yuen Stapf seed. The seed was irradiated with doses of 1, 4, 8, 16, 32 and 64 Gy of the gamma radiation, and then extracted by methanol. The extracts were examined for cytotoxicity on the human cancer cell lines, MCF-7 (human breast adenocarcinoma pleural effusion), Calu-6 (human pulmonary carcinoma) and SNU-601 (human gastric carcinoma) cells, and investigated for multidrug-resistance reversing activity using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. The growth inhibitory activity of irradiated seed extracts on human cancer cell lines was higher than that of the control. In the case of Calu-6 cell line, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. $IC_{50}$ value in the MCF-7 cell line was measured in the only 8 Gy extract. And in the SNU-601 cell line as Calu-6, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. But the extracts of gamma-irradiated seed over 32 Gy showed little growth inhibitory effect against human cancer cell lines. In this result, 8 Gy extract had significant growth inhibitory in all human cancer cell lines $(Calu-6:\;633\;{\mu}g/mL,\;MCF-7:\;653\;{\mu}g/mL\;and\;SNU-601:\;683\;{\mu}g/mL)$. The extracts of 4, 8 and 16 Gy strongly potentiated vincristine cytotoxicity in AML-2/D100 cells. The reversal fold (RF) of 4, 8 and 16 Gy extracts was 1.7, 1.8 and 1.6, respectively. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. These results indicate that the above samples would contain some principles which have cytotoxicity and multidrug-resistance reversing activity. Irradiation technology can be applied to promote physiological activities of medicinal plant seeds.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.776-784
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• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.