• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.441-452
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• 2002

Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.265-279
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• 1996

Damage produced by radiation elicits a complex response in mammalian cells, including growth rate changes and the induction of a variety of genes associated with growth control and apoptosis. At doses of 10,000 cGy or greater, the exposed individual was killed in a matter of minutes to a couple of days, with symptoms consistent with pathology of the central nervous system(CNS) including degenerative changes. The nature of the damage in irradiated cells underlies the unique hazards of ionizing radiation. Radiation injury to CNS is a rare event in clinical medicine, but it is catastrophic for the patient in whom it occurs. The incidence of cerebral necrosis has been reported as high as 16% for doses greater than 6,000 cGy. In this study, the effect of radiation on brain tissue was studied in vivo. Jun and p53 genes in the rat brain were induced by whole body irradiation of rat with 600Co in doses between 1 Gy and 100 Gy and analyzed for expression of jun and p53 genes at the postirradiation time up to 6 hours. Northern analyses were done using 1.8 Kb & 0.8 Kb-pGEM-2-JUN/Eco RI/Pst I fragments, 2.0 Kb-php53B/Bam HI fragment and ,1.1 Kb-pBluescript SK--ACTIN/Eco RI fragment as the digoxigenin or [${\alpha}^{32}P$] dCTPlabeled probes for Jun, p53 and ${\beta}$-actin genes, respectively. Jun gene seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 1 hour after irradiation of $^{60}$Co in dose of 30 Gy. Jun was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in doses of 1 Gy and 10 Gy. After irradiation of $^{60}$Co in dose between 20 Gr and 100 Gy, the expression of Jun was however increased to peak in 2 hours and decreased thereafter. p53 gene in this study also seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 6 hours after irradiation of $^{60}$Co in dose of 1 Gy, p53 was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in dose between 1 Gy and 40 Gy. After irradiation of $^{60}$Co in doses of 50 Gy and 100 Gy, the expression of p53 was however increased to peak in 2 hours and decreased thereafter. The expression of Jun and p53 genes was not correlative in the brain tissue from rats. It seemed to be very important for the establishment of the optimum conditions for the animal studies relevant to the responses of genes inducible on DNA damage to ionizing radiation in mammalian cells. But there are many limitations to the animal studies such as the ununiform patterns of gene expression from the tissue because of its complex compositions. It is necessary to overcome the limitations for development of in situ Northern analysis.

• Research in Plant Disease
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• v.17 no.1
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• pp.19-24
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• 2011

It was identified as a sharp eyespot (Rhizoctonia cerealis) that the isolates from abnormal symptoms in wheat that showed yellowing leaves, necrotic spot on stem base and dead tillers. These isolates have slower growth property and fewer mycelia than Rhizoctonia solani AG-1(1A) (KACC 40106). They showed binuclear cell, same media cultural and DNA characteristics to R. cerealis. They caused same symptoms on leaves and stem base appeared in artificial inoculation test, comparing to diseased wheat fields and also affect to maturing of kernels. They have optimal growth temperature and acidity on the artificial media as $20{\sim}25^{\circ}C$ and pH 5~7, respectively. In the investigation of varietal resistance of Korean winter cereal crops to sharp eyespot, there was no resistant in wheat cultivars that all materials infected over 20% diseased ratio. 12 cultivars including 'Anbaekmil', however, considered to moderate resistance with 20 to 30% infection ratio. The others crops using in feeding, whole crop barley, oat, rye and triticale were resistant below 15% diseased degree except the rye that showed over 50% infection rate. It was the first evaluation to sharp eyespot resistance for the Korean feeding crop cultivars. Most tested Korean barley cultivars for malting and food were moderate and susceptible to the sharp eyespot. Only 3 hulled barley, 'Tapgolbori', 'Albori' and 'Seodunchalbori', showed resistance with less than 10% diseased ratio. All tested naked barley cultivars showed susceptible response to the disease.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.177-183
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• 2004

Purpose: Authors would report the results of sequential CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisone) and involved field radiotherapy (IFRT) for early stage nasal natural killer/T-cell Iymphoma (NKTCL). Materials and Methods: Fourteen among 17 patients, who were registered at the Samsung Medical Center tumor registry with stage I and II nasal NKTCL from March 1995 to December 1999 received this treatment protocol. Three to four cycles of CHOP chemotherapy were given at 3 weeks' interval, which was followed by local IFRT including the known tumor extent and the adjacent draining lymphatics. Results: Favorable responses after chemotherapy (before IFRT) were achievable only in seven patients (5 CR's+2 PR's: 50%), while seven patients showed disease progression. There were six patients with local failures, two with distant relapses, and none with regional lymphatic failure. The actuarial overall survival and progression-free survival at 3 years were 50.0% and 42.9%. All the failures and deaths occurred within 13 months of the treatment start. The factors that correlated with the improved survival were the absence of 'B' symptoms, the favorable response to chemotherapy and overall treatment, and the low risk by international prognostic index on univariate analyses. Conclusion: Compared with the historic treatment results by IFRT either alone or followed by chemotherapy, the current trial failed to demonstrate advantages with respect to the failure pattern and survival. Development of new treatment strategy in combining IFRT and chemotherapy is required for improving outcomes.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.208-216
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• 2004

Purpose: DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase consisting of a 470 kDa catalytic subunit (DNA-PKcs) and a heterodimeric regulatory complex, called Ku, which is composed of 70 kDa(Ku 70) and 86 kDa (Ku 80) proteins. The DNA-PK has been shown to play a pivotal role in rejoining DNA double-strand-breaks (dsb) in mammalian cells. The purpose of this study is to examine the relationship between the level of Ku expression and radiation sensitivity. Methods and Materials: Nine head and neck, cancer cell lines showed various intrinsic radiation sensitivities. Among the nine, AMC-HN-3 cell was the most sensitive for X-ray irradiation and AMC-HN-9 cell was the most resistance. The most sensitive and resistant cell lines were selected and the test sensitivity of radiation and expression of Ku were measured. Radiation sensitivity was obtained by colony forming assay and Ku protein expression using Western blot analysis. Results: Ku80 increased expression by radiation, wheres Ku70 did not. Overexpression of Ku80 protein increased radiation resistance in AMC-HN9 cell line. There was a correlation between Ku8O expression and radiation resistance. Ku80 was shown to play an important role in radiation damage response. Conclusion: Induction of Ku80 expression had an important role in DNA damage repair by radiation. Ku80 expression may be an effective predictive assay of radiosensitivity on head and neck cancer.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Journal of Life Science
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• v.26 no.1
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• pp.101-108
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• 2016

The aim of this study was to evaluate the relationships between the expression of Heat shock protein70 (HSP70), Raf-1 and Bcl-2-associated athanogene-1 (BAG1) protein in diffuse type gastric carcinoma and examine association of HSP70, Raf-1 and BAG1 expression with various clinic-pathological factors and survival. Heat shock protein70 is induced in the cells in response to various stress conditions, including carcinogens. Overexpression of heat shock protein 70 has been observed in many types of cancer. The proto-oncoprotein Raf is pivotal for mitogen-activated protein kinase (MAPK) signaling, and its aberrant activation has been implicated in multiple human cancers. Overexpression of BAG1 protein has been documented in some type of human cancer. BAG1 has been reported to interact with protein involved with a variety of signal pathway, and regulation of cell differentiation, survival and apoptosis. These interaction partners include HSP70 and Raf-1. The percentage of tumors exhibiting HSP70 positivity was significantly in cases of positive lymph node metastasis (64.9%) compared to cases without lymph node metastasis (35.1%, p=0.007). HS70 expression was correlated with pathological N-stage (p=0.006). Expression of BAG1 was detected in the majority of diffuse type gastric carcinoma tissues (71.7%), especially in younger patients (80% vs 52.6%, p=0.035). Furthermore BAG1 expression was correlated with tumor size (p=0.020). Raf-1 expression was found to be significantly associated with tumor size (p=0.005). The result indicate that HSP70 was significantly correlated the progression of diffuse type gastric cancer. Expression of BAG1 and Raf-1 may be used as diagnostic markers for gastric carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.5
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• pp.373-384
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• 2001

Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

• Journal of Dental Rehabilitation and Applied Science
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• v.25 no.2
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• pp.125-137
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• 2009

There are many reports that these implant surface treatments may affect to cellular reaction in the surface of implant. This study was done by installing the 8 type implant with the variable surface treatment, used or developed, in the mandible of the mature dog to evaluate how the method of surface treatment of the implant can affect to the bone healing by analyzing histologically and histomorphometrically and find out bone healing appearance periodically after installing implant. By using the 8 type implants which have the different surface treatment, 72 implants were installed on the mandible of 9 mature dogs, and 3 dogs were sacrificed on every 2, 4, 8 weeks. After making bone fragment by cutting and managing, we analyzed histologically, then compared with BIC(Bone to implant contact) for the histomorphometrical analysis. In the result of histological analysis, there was large amount of bone formation in good state on the adjacent area of implant in the 2 weeks testing group. At 4 weeks, although there was general bone formation, the new bone was separated with the basal bone. At 8 weeks, the new bone became matured and connected tightly to the basal bone. There was no difference in the each surface of 8 implants. In the result of histomorphometrical analysis, 2 weeks group had considerably lower value than 4 and 8 weeks group, and there was no difference between 4 and 8 weeks group. There was no difference in the each surface treatment of implants.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.253-264
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• 2002

Background : It has been reported that the expression of protein which influences on the cell cycle is significantly involved in the development, progress, treatment response, and survival of cancer, and also that the degree of expression of p27 and CDK4 is related to the prognosis. Recent research has revealed that uteroglobin, tumor suppressor gene, is related to cell cycle. This study is focused on the relations between expression of proteins related to cell cycle and clinical index of and survival of NSCLC. Methods : We examined immunohistochemically specimens of 110 surgically resected NSCLCs for expression of p27, CDK, Uteroglobin. Tissue array slide were obtained from 110 surgically resected NSCLCs. Immunohistochemical staining was performed by immuno-peroxidase technique using avidin-biotinylated horseradish peroxidase complex. Results : In 110 patients with resected NSCLCs, the ratio of male to female was 87:13, the median age was $56.43{\pm}9.41$ yrs. The positive staining of p27 was detected in 75% of the cases. A non-statistically significant trend toward increased p27 expression was observed in smoker and squamous cell cancer. The positive staining of CDK4 was detected in 89%, which was the highest expression of protein among 3 types. The survival ratio of CDK4 negative staining group was higher than that of positive staining group, which was significant diffrernce(P<0.05). There was no association between p27 or uteroglobin expression and survival. Conclusion : The expression degree of CDK4 is related to the prognosis. This findings suggests that the measurement of CDK4 may be useful in identifying patient at high risk for disease recurrence and survival.