• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.3
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• pp.193-201
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• 2006

Squamous cell carcinoma(SCC) of head and neck(SCCHN) is the sixth most common human malignant tumor. However, despite advances in prevention and treatment of SCC, the five-year survival rates for patients remain still low. To improve the outcome for patients with SCCHN, novel treatment strategies are needed. Overexpression of the epidermal growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.

• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.205-210
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• 2010

Purpose: To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. Materials and Methods: Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39~89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0~64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. Results: The median follow-up time was 62 months (2~202 months). The 5-year overall survival, loco regional relapse-free survival, disease-free survival, and colostomy-free survival rates were 86.0%, 71.7%, 71.7%, 78.2%, respectively. Regarding overall survival, the Eastern Cooperative Oncology Group (ECOG) performance status and complete response were found to be significant prognostic factors on univariate analysis. For multivariate analysis, only the ECOG performance status was significant. No significant factor was found for locoregional relapse-free survival or disease-free survival and similarly for treatment response, no significant factor was determined on logistic regression analysis. There were 7 patients who had local or regional recurrences and one patient with distant metastasis. The only evaluable toxicity in all patients was radiation dermatitis of perianal skin (grade 3), which developed in 4 patients (9.5%) and grade 2 in 22 patients (52.4%). Conclusion: This study revealed that patients with a performance score of ECOG 0-1 survived significantly longer than those with a poorer score. Finally, there was no significant predicting factors tested for treatment response.

• Journal of Chest Surgery
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• v.34 no.2
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• pp.148-155
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• 2001

배경: 본 연구는 1987년부터 1997년까지 원자력병원에서 수술을 시행한 500명의 식도암환자를 대상으로 하여 휴향적 방법을 통해 조기 및 장기성적, 재발양상, 예후인자 등을 보고하고자 한다. 대상 및 방법: 대상환자 중에서 발병암이 있는 경우, 인두식도 경계부위나 위식도 경계부위 암, 고식적 우회술 또는 인공식도 삽입예 그리고 시험적 개흉술이나 개복술 만을 시행한 경우는 제외 시켰다. 식도 절제는 대부분 우측 개흉술을 이용한 Ivor Lewis 술식을 사용하였고 대부분의 문합은 stapler를 사용하였다. Extended lymph node dissection은 1994년 8월부터 시행하였고 그 이전에는 standard lymph node dissection을 하였다. 96.8%에서 위를 식도 대체장기로 사용하였고 경부에서 절제 및 재건술을 시행한 경우를 제외한 모든 식도재건은 후종격동을 통해 시행하였다. 결과: 474예(94.8%)가 편평상피 세포암이었고 대부분(58.2%)은 중부식도에 위치하였다. 술후병기는 47.4%가 stage III이었고 25%가 stage IIA이었다. 392예에서 근치적 절제가 가능하였고 74예는 고식적 절제를 시행하였으며, 식도열공을 통한 식도절제술과 경부에서의 유리공장 이식술을 시행한 34예는 위분류에서 제외하였다. 술후 유병율은 38.4%이었고 수술 사망률은 5.8%로 호흡기 감염, 문합부 유출이 주요 원인이었다. 대상환자의 99.8%에서 추적은 가능하였고 수술사망 예를 포함한 전체환자의 1, 2, 5년 생존율은 각각 63.5%, 38.9%, 19.4% 이었다. Standard lymph node dissection 그룹에서의 1, 2, 5년 생존율이 60.7%, 35.9%, 16.9%이었으나 extended lymph node dissection그룹에서는 1, 2, 4년 생존율이 70.2%, 46.5%, 30.9%이었다. 근치적 절제의 경우는 1, 2, 5년 생존률이 69.4%, 43.9%, 21.9%이었고, 고식적 절제의 경우는 37.8%, 17.6%, 7.3%이었다. 수술사망을 제외한 근치적 절제술과 extended lymph node dissection을 함께 시행한 경우의 4년 생존율은 35.6%이었다. 수술후 재발은 226예에서 발견되었고 주로 국소임파절(69%; 경부, 종격동, 복부)이었으며, 전신재발은 간, 폐, 뼈, 뇌 등의 순이었다. 결론: 저자들은 적절한 술후 환자관리가 선행되어야 하지만 근치적 절제와 광범위한 임파절 절제가 장기성적의 향상에 필수적 요소이고, 진행된 식도암에 있어서는 보다 효과적인 보강적 복합치료가 연구되어야 할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.103-110
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• 1999

A thromboembolic event in patients later given a diagnosis of cancer is the result rather than the cause of the cancer. The risk of hidden cancer is significantly higher for patients with recurrent idiopathic thromboembolism compared to those with secondary deep vein thrombosis. Microemboli from hepatic or adrenal metastases and large-sized emboli from the great veins invaded by the tumor are the sources of tumor embolization The intraarterial tumor emboli less likely invade the arterial wall. Thrombus formation and organization may be capable of destroying tumor cells within pulmorlary blood vessels. Therefore, all tumor emboli are not true metastases. The treatment of deep vein thrombosis and pulmonary embolism in patients with cancer consists of anticoagulation with heparin and warfarin, venacaval filters, appropriate anti-neoplastic agents, and surgical methods(embolectomy, thromboendarterectomy). However, considerable literatures suggest that oral anticoagulant such as warfarin is ineffective in the treatment of those. We report a case of primary unknown squamous cell carcinoma incidentally found in the thrombus after pulmonary embolectomy.

• Journal of Chest Surgery
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• v.31 no.12
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• pp.1200-1205
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• 1998

Background: Lung cancer formation is a multistage process involving activation of protooncogene and inactivation of tumor suppressor genes. We evaluate the significance of cyclin D1, p53, bcl-2 gene mutations in patients with curatively resected stage IIIA non-small cell lung cancer(NSCLC). Material and Method: One hundred consecutive cases of stage IIIA lung cancers from patients operated on curatvely between 1990 and 1995 for which adequate paraffin blocks and clinical history were available. Immunohistochemical studies were performed on the representative tissue sections from each case by the labelled streptovidin- biotin method. Sections for cyclin D1, p53, Bcl-2 immunostaining were pretreated in a microwave oven for 10 to 20 minutes in citrate buffer before immunostaining. The overnight incubation with NCL-cyclin D1-GM for cyclin D1, with clone DO-7 for p53, with clone 124 for bcl-2 was done. Mean follow-up was 24.1 months (range 2-84 months) after operation. Result: One hundred cases of lung cancers were composed of 56 cases of squamous cell carcinoma, 37 cases of adenocarcinoma, 5 cases of adenosquamous cell carcinoma, and 2 cases of large cell carcinoma. The 5-year survival was 32.1%. The positive expression rate of cyclin D1 was 35%, p53 was 56%, and bcl-2 was 17%. But there were no correlation between cyclin D1, p53, Bcl-2 protein expression and survival. Conclusion: These observation indicate that cyclin D1, p53, bcl-2 protein overexpression might be implicated in the oncogenesis of non-small cell lung carcinomas but they have no usefulness as a prognostic marker.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.4
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• pp.334-340
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• 1998

Stimulatory effects of epidermal growth factor (EGF) and transforming growth $factor-{\alpha}$($TGF-{\alpha}$) on the growth of squamous cancer cell lines established from human oral cancer tissue with moderate differentiation were studied in vitro. After culturing in serum-free media for 24 hours, growth factors-EGF only, $TGF-{\alpha}$ only and EGF, $TGF-{\alpha}$ together-were added to the media and numbers of cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and compared with the control at 96, 144 hours. Each of EGF and $TGF-{\alpha}$ showed statistically significant stimulatory effects on the growth of cells respectively. Dose-dependent relationship of the stimulatory effects were not clearly demonstrated. The effects of EGF were higher than those of $TGF-{\alpha}$ and combinative administration showed higher effects than those of single uses. In conclusion, EGF may play an important and major role in differentiation and growth of human oral squamous cancer cells. $TGF-{\alpha}$, produced from cells activated by EGF, also can stimulate the cell growth and could be an alternative ligand for EGF receptor.

• Journal of Chest Surgery
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• v.29 no.1
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• pp.43-51
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• 1996

From march 1989 to October 1993, 57 patients were diagnosed and operated for primary non-small cell lung cancer, and evaluated clinically. 1. There were 45 males and 12 females (M:F=3.8:1), and the peak incidence of age was 6th decade of life (45.6%). In the preoperative diagnostic methods and their positive rate, sputum cytology was 11%, bronchial washing cytology 50%, bronchoscopic biopsy 73%, and CT guided percutaneous needle aspiration biopsy 83%. 3. Histopathologically, squamous cell carcinoma was 56.1%, adenocarcinoma 22.8%, bronchioloal veolar cell carcinoma 1%, and undifferentiated large cell carcinoma 1.8%. 4. In the operation, pneumonectomy was 35.1%, lobectomy 38.6%, bilobectomy 3.5%, segmentec tony 7%, and exploratory thoracotomy 15.8%, and overall resectability was 84.2%. 5. In postoperative stagings, stage I was 28.1%, st ge II 22.8%, stage IIIa 31.6% and stage IIIb 17.5%. 6. Postoperative complications were developed in 11 cases (19.3%) and operative mortality was none. 7. One year survival rate in rejectable cases was 87.0%, 2 year 61.6% and 5 year 44.9%. According to stage, 3 year survival rate was 75.8% in stage I, 16.9% in stage II, 60.9% in stage IIIa, 50% in stage IIIb.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.18-22
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• 2002

Background and Objectives: The expression of telomerase, a ribonucleoprotein complex, has been detected in tissues from many human cancers, but not in the majority of normal tissues except germ cell. It is believed that the activation of telomerase is linked to celluar immortality and may playa role in tumorigenesis. Human telomerase reverse transcriptase (hTERT) has been identified as a putative catalytic subunit of human telomerase and its expression is closely correlated with telomease activity. We studied the expression of hTERT in head and neck squamous cell carcinoma (HNSCC) and resection margin by immunohistochemistry for hTERT and evaluate the correlation between hTERT expression and clinical data in HNSCC. Materials and Methods: We performed a immunohistochemistry in 17 cases of HNSCC and 10 cases of resection margins, histologically normal. The correlations between the hTERT expression and the clinical data in HNSCC were analyzed. Result: hTERT immunoreactivities were detected in 14 of 17 (82.4%) HNSCC, 1 of 10 (10%) resection margin. No correlation was observed between clinical data and hTERT expression in HNSCC. Conclusion: hTERT is activated in HNSCC and its expression is independent from clinical data of patients.

• Korean Journal of Head & Neck Oncology
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• v.12 no.2
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• pp.181-187
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• 1996

We have characterized 4 human squamous carcinoma cell lines established from the larynx and hypopharynx area. All the cell lines were cultured in RPMI-1640 medium. During the growth they showed monolayer adherence pattern in culture flask. They showed tonofilament on transmission electromicroscopy which is characteristic of squamous cell epithelium. DNA finger-printing using Hinf-l proved them to be originated from different beings. Flow cytometric analysis revealed them to show aneuploidy. Immunohistochemical staining for cytokeratin was done using CK1, CK8.13, CK19 and CAM5.2 antibody, and produced various patterns of positivity. All the cell lines showed varying degrees of tumorigenecity in athymic nude mice when injected subcutaneously, but only heterotransplanted SNU-1041 cell line showed continuous tumor growth. Histopathologic findings of the heterotransplanted tumors were identical to those of the original tumors of patients. This study suggests that establishment of many different squamous cell lines might bestow great capability in researches of the head and neck cancer.