• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• Tuberculosis and Respiratory Diseases
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• v.77 no.4
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• pp.188-192
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• 2014

We present a case of an unusual infectious complication of a ruptured mediastinal abscess after endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which led to malignant pleural effusion in a patient with stage IIIA non-small-cell lung cancer. EBUS-TBNA was performed in a 48-year-old previously healthy male, and a mediastinal abscess developed at 4 days post-procedure. Video-assisted thoracoscopic surgery was performed for debridement and drainage, and the intraoperative findings revealed a large volume pleural effusion that was not detected on the initial radiographic evaluation. Malignant cells were unexpectedly detected in the aspirated pleural fluid, which was possibly due to increased pleural permeability and transport of malignant cells originating in a ruptured subcarinal lymph node from the mediastinum to the pleural space. Hence, the patient was confirmed to have squamous cell lung carcinoma with malignant pleural effusion and his TNM staging was changed from stage IIIA to IV.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4435-4438
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• 2015

p21 is a cyclin-dependent kinase inhibitor, which can arrest cell proliferation and serve as a tumor suppressor. Though many studies were published to assess the relationship between p21 rs1059234 polymorphism and various cancer risks, there was no definite conclusion on this association. To derive a more precise quantitative assessment of the relationship, a large scale meta-analysis of 5,963 cases and 8,405 controls from 16 eligible published case-control studies was performed. Our analysis suggested that rs1059234 was not associated with the integral cancer risk for both dominant model [(T/T+C/T) vs C/C, OR=1.00, 95% CI: 0.84-1.18] and recessive model [T/T vs (C/C+C/T), OR=1.03, 95% CI: 0.93-1.15)]. However, further stratified analysis showed rs1059234 was greatly associated with the risk of squamous cell carcinoma of head and neck (SCCHN). Thus, larger scale primary studies are still required to further evaluate the interaction of p21 rs1059234 polymorphism and cancer risk in specific cancer subtypes.

• Molecules and Cells
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• v.46 no.12
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• pp.764-777
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• 2023

Recombinant immunotoxins (RITs) are fusion proteins consisting of a targeting domain linked to a toxin, offering a highly specific therapeutic strategy for cancer treatment. In this study, we engineered and characterized RITs aimed at mesothelin, a cell surface glycoprotein overexpressed in various malignancies. Through an extensive screening of a large nanobody library, four mesothelin-specific nanobodies were selected and genetically fused to a truncated Pseudomonas exotoxin (PE24B). Various optimizations, including the incorporation of furin cleavage sites, maltose-binding protein tags, and tobacco etch virus protease cleavage sites, were implemented to improve protein expression, solubility, and purification. The RITs were successfully overexpressed in Escherichia coli, achieving high solubility and purity post-purification. In vitro cytotoxicity assays on gastric carcinoma cell lines NCI-N87 and AGS revealed that Meso(Nb2)-PE24B demonstrated the highest cytotoxic efficacy, warranting further characterization. This RIT also displayed selective binding to human and monkey mesothelins but not to mouse mesothelin. The competitive binding assays between different RIT constructs revealed significant alterations in IC₅₀ values, emphasizing the importance of nanobody specificity. Finally, a modification in the endoplasmic reticulum retention signal at the C-terminus further augmented its cytotoxic activity. Our findings offer valuable insights into the design and optimization of RITs, showcasing the potential of Meso(Nb2)-PE24B as a promising therapeutic candidate for targeted cancer treatment.

• Archives of Plastic Surgery
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• v.39 no.4
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• pp.323-328
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• 2012

Background Among the various methods for correcting nasal deformity, the composite graft is suitable for the inner and outer reconstruction of the nose in a single stage. In this article, we present our technique for reconstructing the ala and columella using the auricular chondrocutaneous composite graft. Methods From 2004 to 2011, 15 cases of alar and 2 cases of columellar reconstruction employing the chondrocutaneous composite graft were studied, all followed up for 3 to 24 months (average, 13.5 months). All of the patients were reviewed retrospectively for the demographics, graft size, selection of the donor site and outcomes including morbidity and complications. Results The reasons for the deformity were burn scar (n=7), traumatic scar (n=4), smallpox scar (n=4), basal cell carcinoma defect (n=1), and scar contracture (n=1) from implant induced infection. In 5 cases of nostril stricture and 6 cases of alar defect and notching, composite grafts from the helix were used ($8.9{\times}12.5$ mm). In 4 cases of retracted ala, grafts from the posterior surface of the concha were matched ($5{\times}15$ mm). For the reconstruction of the columella, we harvested the graft from the posterior scapha ($9{\times}13.5$ mm). Except one case with partial necrosis and delayed healing due to smoking, the grafts were successful in all of the cases and there was no deformity of the donor site. Conclusions An alar and columellar defect can be reconstructed successfully with a relatively large composite graft without donor site morbidity. The selection of the donor site should be individualized according to the 3-dimensional configuration of the defect.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.307-315
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• 1996

Purpose : The authors conducted a retrospective analysis of patients with the carcinoma of uterine cervix treated with curative radiation therapy to evaluate the prognostic factors that would affect the results of the therapy and to get the critical ideas in determining more aggressive treatment schedule. Methods and Materials : From January 1987 to December 1988. Four hundreds and sixty patients with uterine cervical carcinomas treated with radiotherapy at KCCH were registered to this retrospective study. One hundred and three patients were treated with external radiation therapy alone, and 357 patients were treated with external radiation followed by low dose rate intracavitary radiation therapy. The follow-up rate was 88% and median follow-up duration was 48 months. Results : The overall 5 year survival rate of the patients was 67.7%, and when classified by FIGO stages, 5 year survival rates were 81.2%, 76.3%, 73.1%, 50%. 52.3%, 11.5% for stages Ib, IIa, IIb, IIIa, IVa respectively. Tumor size(p=0.0002), endocervical growth pattern(p=0.003), lymph node invasion(p=0.0001), mean hemoglobin level(p=0.0001), and pathologic cell type(p=0.0001) were significant prognostic factors and decrease in survival for young age patient group was marginally important (p=0.03). Conclusion : Significant prognostic factors in the radiation therapy of the uterine cervical carcinoma were tumor size, growth pattern of tumor, lymph node invasion, pathologic cell type, hemoglobin level of patients during treatment and lower survival rate in young age group was obvious, too. Patients with large size tumor(${\geq)$4cm), especially combined with endocervical growth patterns or advanced stages(III or more) need more aggressive treatment to improve the outcome of treatment. And positive feature of lymph node invasion affected the result of therapy, so improvement in the diagnostic and therapeutic trial is essential.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5339-5343
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• 2012

The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.685-694
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• 1995

Introduction: Transthoracic fine needle aspiration biopsy(TNAB) has shown to be a resonably safe, simple, and accurate procedure in diagnosis of intrathoracic lung lesions. We reviewed the results of 1,005 TNAB of chest lesions performed on 930 patients with 20 or 22-gauze needles over a period of 10 years. Methods: From November 1983 to June 1995, 1,005 cases in 930 patients with an undiagnosed lung lesion underwent TNAB at the Hanyang University Hospital: 66% were men and 34% were women. Most of the patients were 40~60 years old and the youngest patient was 3 years of age. Result: 540 patients had various malignant chest lesions and 322 patients had benign pulmonary lesions. The diagnostic accuracy of TNAB was 96.1 percent in malignant diseases with one false positive result and 90.1% in benign diseases. A definitive diagnosis was not obtained in the remaining 68 patients. The most common diagnoses among 519 malignancy chest lesions with TNAB were the following: squamous cell lung carcinoma, 31.7%; adenocarcinoma, 24.7%; small cell lung carcinoma, 16.7%; metastatic cancer, 14.2%; large cell lung carcinoma, 6.2% and so on. Complications included pneumothorax in 12.3% necessitating chest tube drainage in 0.6%. Minor hemoptysis occurred in 3.6%. There was no death directly attributable to the procedure. Conclusion: We concluded that TNAB permits a direct approach to all kinds of localized lung lesions with a high degree of accuracy and without major complications.

• Journal of Chest Surgery
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• v.52 no.4
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• pp.221-226
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• 2019

Background: Accurate mediastinal lymph node staging is vital for the optimal therapy and prognostication of patients with lung cancer. This study aimed to determine the preoperative risk factors for pN2 disease, as well as its incidence and long-term outcomes, in patients with clinical N0-1 non-small cell lung cancer. Methods: We retrospectively analyzed patients who were treated surgically for primary non-small cell lung cancer from November 2005 to December 2014. Patients staged as clinical N0-1 via chest computed tomography (CT) and positron emission tomography (PET)-CT were divided into two groups (pN0-1 and pN2) and compared. Results: In a univariate analysis, the significant preoperative risk factors for pN2 included a large tumor size (p=0.083), high maximum standard uptake value on PET (p<0.001), and central location of the tumor (p<0.001). In a multivariate analysis, central location of the tumor (p<0.001) remained a significant preoperative risk factor for pN2 status. The 5-year overall survival rates were 75% and 22.9% in the pN0-1 and pN2 groups, respectively, and 50% and 78.2% in the patients with centrally located and peripherally located tumors, respectively. In a Cox proportional hazard model, central location of the tumor increased the risk of death by 3.4-fold (p<0.001). Conclusion: More invasive procedures should be considered when preoperative risk factors are identified in order to improve the efficacy of diagnostic and therapeutic plans and, consequently, the patient's prognosis.