• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Journal of Chest Surgery
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• v.39 no.2 s.259
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• pp.106-110
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• 2006

Background: Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignancy of the lung, and it accounts for $2{\~}14\%$ of all pulmonary malignancies. According to World Health Organization (WHO) categorisation, BAC is a subtype of adenocarcinoma. The current definition of BAC includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, and neoplastic cells growing along the alveolar septa. Previous reports had demonstrated a better prognosis following surgery for patients affected by BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse Asan Medical Center experiences of BAC. Material and Method: Between 1990 and 2002, 31 patients were received operations for BAC. We analyse retrosepectively sex, age, disease location, preoperative clinical stage, postoperative pathologic stage & complications, survival according to medical record. Result: There were 12 men and 19 women, the average age was 61.09$\pm$10.63 ($31{\~}79$) years. Tumor locations were 7 in RUL, 1 in RML, 4 in RLL, 8 in LUL, 11 in LLL. Operations were 28 lobectomies, 2 pneumonectomies. Postoperative pathologic stage were 12 T1N0M0, 15 T2N0M0, 1 T1N1M0, 1 T1N2M0, 1 T2N2M0, 1 T1N0M1. Mortality were 4 cases ($12.9\%$) and there were no early mortality. Cancer free death was 1 cases, other 3 were cancer related deaths. All of them were affected by distal metastasis and received chemotherapy and each metastatic locations were right rib, brain, and both lung field. The average follow up periods were 50.87$\pm$24.77 months. The overall 3, 5-year survival rate among all patients was $97.1\%,\;83.7\%$, stage I patients overall 2, 5year survival rate was $96.3\%$. The overall disease free 1, 2, 5-year survival rate among all patients was $100\%,\;90\%,\;76\%$ and 2, 5-year survival rate in cases of stage I was $96.4\%,\;90.6\%$. 7 cases ($22.58\%$) were chemotherapies, 1 case ($3.22\%$) was radiation therapy, and 2 cases ($6.45\%$) were chemoradiation therapies. Metastatic locations were 3 cases in lung, 1 case in bone, 1 cases in brain. Conclusion: BAC has a favourable survival and low recurrence rate compare with reported other NSCLC after operative resections.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.1-10
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• 2004

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development on distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases,, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach Improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of locally advanced NSCLC continues to evolve. The current issues in the multidisciplinary management of locally advanced NSCLC will be reviewed in this report.

• Tuberculosis and Respiratory Diseases
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• v.55 no.6
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• pp.589-596
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• 2003

Background : The solitary pulmonary nodule(SPN) presents a diagnostic dilemma to the physician and the patients in the our nation with high incidence of tuberculoma. We could not exclude whether the SPN was benign or malignant by the change of the size at chest radiograph and findings of chest CT. Recently, positron emission tomography(PET) have been tried as the differential diagnostic method of SPN. We evaluated the efficacy of PET for differentiating malignant from benign SPN and the relationship between standardized uptake values(SUV) of PET and serum glucose. Method : Between January 2001 and July 2002, sixty-one patients with pulmonary nodule were examined by the chest CT and PET. The SPN has been finally diagnosed by the transthorasic needle aspiration and biopsy, bronchoscopic biopsy, and open lung biopsy. Results : Forty eight patients had a malignant nodule(23 squamous cell lung carcinoma, 16 adenocarcinoma, 9 small cell lung cancer) and thirteen patients had a benign nodule(3 tuberculoma, 9 inflammatory granuloma, 1 cryptococcosis). The mean size of malignant and benign nodule was 40.6 mm and 20.0 mm, respectively. All malignant nodules showed a marked increase in 18 fluorodeoxyglucose (FDG) uptake. Mean SUV of malignant was $9.52{\pm}5.20$ and benign nodule was $1.61{\pm}3.60$. There were false positive cases with an increase in 18-FDG uptake (2 tuberculoma, 1 inflammatory granuloma). The SUV of malignant nodule in diabetes patients has no difference in non diabetes patients($9.10{\pm}4.51$ vs $9.65{\pm}5.46$). The sensitivity and specificity of the PET scan for SPN were 100%, 77%, respectively. The positive and negative predictive values were 94% and 100%. Conclusion : PET scanning showed highly accurate result in differentiating the malignant and benign SPN. There were no significant differences between the SUV and serum glucose in the patients with lung cancer.

• Journal of Yeungnam Medical Science
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• v.7 no.2
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• pp.151-158
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• 1990

We reviewed 30 cases of superior vena cava syndrome in adult patients who were seen at the Yeungnam University Hospital from January 1985 to June 1990. The results were as follows : 1. The male-to-female ratio was 6.5:1, and the most patients were in the age group between the sixth and seventh decades. 2. The most common symptoms were dyspnea (87%) and followed by cough (63%), facial swelling (63%) and chest pain (44%) and the physical signs were dilated neck vein (97%), facial edema (93%) and facial flushing (45%) in order of frequency. 3. The simple chest x-ray findings were superior mediastinal widening (90%), right hilar mass (77%) and pleural effusion (31%). 4. Diagnosis was made by history and physical examination (100%), chest C-T scan (100%), simple chest x-ray (97%), bronchoscopy with biopsy (40%) and so on. 5. 21 cases of patients were confirmed by histology : 14 cases (46%) of bronchogenic ca. 4 cases (14%) of lymphoma, 3 cases (10%) of metastic lung ca. Of bronchogenic ca. small cell ca was 7 cases (23%), squamous cell ca, 5 cases (17%), and unclassified ca was 2 cases (6%). 6. In response of treatment, the clinical improvement was achieved in 18 cases with radiotherapy alone. 1 case with chemotherapy only, and 6 cases with radio-chemotherapy.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.506-512
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• 2010

Background: This study was designed to evaluate the FDG uptake ratio of mediastinal node and primary tumors using integrated PET/CT imaging combined with Glut-1 expression of the primary tumor in order to predict the N2 status more accurately in NSCLC patients. Material and Method: Patients who underwent integrated PET/CT scanning with a detectable mSUV for both primary tumors and mediastinal lymph nodes were eligible for this study. The FDG uptake ratio between the mediastinal node and the primary tumor was calculated. Result: The average mSUV of primary tumors and mediastinal nodes were, respectively, $7.4{\pm}2.2$ and $4.2{\pm}2.2$ in N2-positive patients and $7.6{\pm}3.7$ and $2.8{\pm}6.9$ in N2-negative patients. The mean FDG uptake ratio of mediastinal node to primary tumor were $0.58{\pm}0.23$ for malignant N2 lymph nodes and $0.45{\pm}0.20$ for benign lymph nodes (p<0.05). Models which combined Glut-1 expression with an FDG ratio have better diagnostic power than models that use the FDG uptake ratio alone. Conclusion: In some patients with a previous history of pulmonary tuberculosis or other inflammatory lung diseases, an FDG uptake ratio combined with Glut-1 expression may be useful in diagnosing mediastinal node metastasis more exactly.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.433-440
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• 1998

Purpose : Although small ceil lung cancer (SCLC) has high response rate to chemotherapy and radiotherapy (RT), the prognosis is dismal. The authors evaluated survival and failure patterns according to the prognostic factors in SCLC patients who had thoracic radiation therapy with chemotherapy. Materials and Methods : One hundred and twenty nine patients with SCLC had received thoracic radiation therapy from August 1985 to December 1990. Seventy-seven accessible patients were evaluated retrospectively among 87 patients who completed RT. Median follow-up period was 14 months (2-87months). Results : The two years survival rate was 13$\%$ with a median survival time of 14 months. The two year survival rates of limited disease and extensive disease were 20$\%$ and 8$\%$, respectively, with median survival time of 14 months and 9 months, respectively. Twenty two patients (88$\%$) of limited disease showed complete response (CR) and 3 patients (12$\%$) did partial response (PR). The two year survival rates on CR and PR groups were 24$\%$ and 0$\%$, with median survival times of 14 months and 5 months. respectively (p=0.005). No patients with serum sodium were lower than 135 mmol/L survived 2years and their median survival time was 7 months (p=0.002). Patients whose alkaline phophatase lower than 130 IU/L showed 26$\%$ of 2 year survival rate and showed median survival time of 14 months and those with alkaline phosphatase higher than 130 IU/L showed no 2 year survival and median survival time of 5 the months, respectively (p=0.019). No statistical differences were found according to the age, sex, and performance status. Among the patients with extensive disease, two rear survivals according to the metastatic sites were 14$\%$, 0$\%$, and 7$\%$ in brain, liver, and other metastatic sites, respectively, with median survival time of 9 months, 9 months, and 8 months, respectively (p>0.05). Two year survivals on CR group and PR group were 15$\%$ and 4$\%$, respectively, with a median survival time of 11 months and 7 months, respectively (p=0.01). Conclusion : For SCLC, complete response after chemoradiotherapy was the most significant prognostic tactor. To achieve this goal. there should be further investigation about hyperfractionation, dose escalation, and compatible chemo-radiation schedule such as concurrent chemo-radiation and early radiation therapy with chemotherapy.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.428-437
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• 2000

Background : Five year survival rate of postoperative stage I non-small cell lung cancer(NSCLC) reaches to 66%. In the remaining one third of patients, however, cancer recurs and the overall survival of NSCLC remains dismal. To evaluate clinical and pathologic characteristics of recurred NSCLC, the patterns and factors for postoperative recurrence in patients with staged I and II NSCLC were studied. Method : A retrospective analysis was performed in 234 patients who underwent radical resection for pathologic stage I and II NSCLC. All patients who were followed up for at least one year were included in this study. Results : 1) There were 177 men and 57 women The median age was 63. The median duration of the follow up period was 732 days (range 365~1,695 days). The overall recurrence rate was 26.5%, and the recurrence occurred $358.8{\pm}239.8$ days after operation. 2) The ages of recurred NSCLC patients were higher ($63.2{\pm}8.8$ years) than those of non-recurred patients ($60.3{\pm}9.8$ years)(p=0.043). The recurrence rate was higher in stage II (46.9%) than in stage I (18.8%) NSCLC p<0.001. The size of primary lung mass was larger in recurred ($5.45{\pm}3.22\;cm$) than that of non-recurred NSCLC ($3.74{\pm}1.75\;cm$, p<0.001). Interestingly, there were no recurrent cases when the resected primary tumor was less than 2cm. 3) Distant recurrence was more frequent than locoregional recurrence (66.1% vs. 33.9%). Distant recurrence rate was higher in females and in cases of adenocarcinoma. Brain metastasis was more frequent in patients with adenocarcinoma than in those with squamous cell carcinoma (p=0.024). Conclusion: The tumor size and stage were two important factors for determining the possibility of a recurrence. Because distant brain metastasis was more frequent in patients with adenocarinoma, a prospective study should be conducted to evaluate the effectiveness of preoperative brain imaging.

• Journal of Microbiology and Biotechnology
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• v.26 no.11
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• pp.1881-1890
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• 2016

Manganese superoxide dismutase (MnSOD) is a vital enzyme that protects cells from free radicals through eliminating superoxide radicals ($O^{2-}$). Hirudin, a kind of small active peptide molecule, is one of the strongest anticoagulants that can effectively cure thrombus diseases. In this study, we fused Hirudin to the C terminus of human MnSOD with the GGGGS linker to generate a novel dual-feature fusion protein, denoted as hMnSOD-Hirudin. The hMnSOD-Hirudin gene fragment was cloned into the pET15b (SmaI, CIAP) vector, forming a recombinant pET15b-hMnSOD-Hirudin plasmid, and then was transferred into Escherichia coli strain Rosetta-gami for expression. SDS-PAGE was used to detect the fusion protein, which was expected to be about 30 kDa upon IPTG induction. Furthermore, the hMnSOD-Hirudin protein was heavily detected as a soluble form in the supernatant. The purification rate observed after Ni NTA affinity chromatography was above 95%. The hMnSOD-Hirudin protein yield reached 67.25 mg per liter of bacterial culture. The identity of the purified protein was confirmed by western blotting. The hMnSOD-Hirudin protein activity assay evinced that the antioxidation activity of the hMnSOD-Hirudin protein obtained was $2,444.0{\pm}96.0U/mg$, and the anticoagulant activity of the hMnSOD-Hirudin protein was $599.0{\pm}35.0ATU/mg$. In addition, in vitro bioactivity assay showed that the hMnSOD-Hirudin protein had no or little cytotoxicity in H9c2, HK-2, and H9 (human $CD_4{^+}$, T cell) cell lines. Transwell migration assay and invasion assay showed that the hMnSOD-Hirudin protein could suppress human lung cancer 95-D cell metastasis and invasion in vitro.