• Biomolecules & Therapeutics
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• 제30권1호
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• pp.19-27
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• 2022

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wild-type EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2083-2087
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• 2016

A new compound namely (13-(3,3-dihydroxypropyl)-1,6-dihydroxy-3,4-dihydro-1H-isochromen-8(5H)-one (1) was isolated from an ethyl acetate extract of the borne fungi Screlotium rolfsii. Its chemical structure was elucidated by spectroscopic analysis. Screlotiumol 1 were evaluated for their effects on the reversion of multidrug resistant (MDR) mediated by P-glycoprotein (P-gp) of the soil borne fungi. The multidrug resistant P-glycoprotein is a target for chemotherapeutic drugs in cancer cells. In the present study rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma which showed excellent MDR reversing effect in a dose dependent manner against mouse T-lymphoma cell line. Moreover, molecular docking studies of compound-1 also showed better results as compared with the standard. Therefore the preliminary results obtained from this study suggest that screlotiumol 1 could be used as a potential agent for the treatment of cancer.

• 구강회복응용과학지
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• 제18권2호
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• pp.113-118
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• 2002

Long bridge가 필요한 구강암종환자에게 자기공명영상을 촬영하여야 하는 경우, fiber reinforced polymer ceramics로 잠정보철물을 제작해준 경우 충분한 파절 저항성과 심미성을 얻을 수 있었다. 하지만, 여기에 대한 장기간의 연구와 관찰이 필요하리라 사료된다.

• 대한핵의학회지
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• 제30권3호
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• pp.325-331
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• 1996

$^{99m}Tc$-pertechnetate를 이용하여 두경부암 환자에서 이하선과 악하선의 방사선 조사 전후 및 추적 검사에서 방사선 조사로 인한 타액선의 기능 변화, 기능저하의 회복 여부, 이하선과 악하선의 방사선에 대한 감수성 차이, 그리고 구강건조증이 있던 환자와 없던 환자 사이의 기능 저하 차이를 객관적으로 평가하고자 하였다. 방사선 치료를 받는 두경부암 환자중 방사성 동위원소를 이용하여 이하선과 악하선 기능 검사를 시행한 19명의 환자를 대상으로 하였다. $^{99m}Tc$-pertechnetate를 이용한 이하선과 악하선 기능 검사는 측정된 방사능치에 의한 섭취 곡선과 구연산으로 자극하였을 때의 평균 배출율에 의한 배출 곡선을 포함하였다. 이하선과 악하선의 섭취 곡선에서는 방사선 치료전보다 치료 1주후에서 증가하였고 치료 2주후와 3주후 그리고 치료 종료시에서는 치료 전과 비슷하거나 약간 증가하였으며 방사선 치료 후에서는 시간이 지날수록 점점 감소하였다. 이하선과 악하선의 배출 곡선에서는 방사선 치료 시작부터 종료시까지는 급격히 감소하였고 방사선 치료 후 1년까지의 검사에서는 배출율이 회복되지 않았다. 이하선과 악하선의 방사선에 대한 감수성 차이는 나타나지 않았고 구강건조증을 호소하는 환자와 호소하지 않는 환자 사이의 이하선과 악하선의 평균 배출율 차이는 발견되지 않았다. $^{99m}Tc$-pertechnetate를 이용한 이하선과 악하선기능 검사로 방사선 치료에 따른 이하선과 악하선의 기능 변화를 객관적으로 평가할 수 있고, 방사선 치료후 1년까지는 이하선과 악하선의 기능 회복이 없어 방사선 치료를 받은 두경부암 환자의 타액선 기능에 관한 예후추정에 도움이 되리라 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1121-1126
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• 2013

Background: Palliative chemotherapy with cisplatin/5-fluorouracil (5FU) is the commonest regimen employed for metastatic and recurrent head and neck squamous cell carcinoma (SCCHN) and nasopharyngeal carcinoma (NPC). However, this regimen is cumbersome requiring 5 days of admission to hospital. Carboplatin/5FU may be an alternative regimen without compromising survival and response rates. This study aimed to compare the efficacy and toxicity of carboplatin/5FU regimen with the cisplatin/5FU regimen. Materials and Methods: This retrospective study looked at patients who had palliative chemotherapy with either cisplatin/5FU or carboplatin/5FU for metastatic and recurrent SCCHN and NPC. It included patients who were treated at UKMMC from $1^{st}$ January 2004 to $31^{st}$ December 2009 with either palliative IV cispaltin 75 $mg/m^2$ D1 only plus IV 5FU 750 $mg/m^2$ D1-5 infusion or IV Carboplatin AUC 5 D1 only plus IV 5FU 500 $mg/m^2$ D1-2 infusion plus IV 5FU 500 $mg/m^2$ D1-2 bolus. The specific objectives were to determine the efficacy of palliative chemotherapy in terms of overall response rate (ORR), median progression free survival (PFS) and median overall survival (OS) and to evaluate the toxicities of both regimens. Results: A total of 41 patients were eligible for this study. There were 17 in the cisplatin/5FU arm and 24 in the carboplatin/5FU arm. The ORR was 17.7 % for cisplatin/5FU arm and 37.5 % for carboplatin/5FU arm (p-value=0.304). The median PFS was 7 months for cisplatin/5FU and 9 months for carboplatin/5FU (p-value=1.015). The median OS was 10 months for cisplatin/5FU arm and 12 months for carboplatin/5FU arm (p-value=0.110). There were 6 treatment-related deaths (6/41=14.6%), four in the carboplatin/5FU arm (4/24=16.7%) and 2 in the cisplatin/5FU arm (2/17=11.8%). Grade 3 and 4 hematologic toxicity was also more common with carboplatin/5FU group, this difference being predominantly due to grade 3-4 granulocytopenia (41.6% vs. 0), grade 3-4 anemia (37.5% vs. 0) and grade 3-4 thrombocytopenia (16.6% vs. 0). Conclusions: Carboplatin/5FU is not inferior to cisplatin/5FU with regard to its efficacy. However, there was a high rate of treatment-related deaths with both regimens. A better alternative needs to be considered.

• 대한핵의학회지
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• 제39권5호
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• pp.269-277
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• 2005

목적: 두경부암 환자에서 경부림프절 전이의 진단에서의 $^{18}F-FDG$ PET/CT의 유용성을 알아보고자 하였다. 대상 및 방법: 환자들을 수술 전 병기 결정을 위해 PET/CT을 촬영한 환자 46명(수술 전 환자군, 남: 38명, 여: 8명, 평균나이: 54.54세)과 1차 치료 후 재발 병소의 병기 결정을 위해 PET/CT를 시행한 환자 20명(재발 환자군, 남: 15명, 여: 5명, 평균나이: 49.5세)의 두군으로 분류하였다. PET/CT에서 FDG 섭취를 보인 경부림프절을 병소 대 병소로 조직검사 소견과 후향적으로 비교하였다. 결과: 수술 전 환자 15명의 PET/CT에서 21개의 FDG 섭취 증가를 보이는 림프절이 관찰되었다. 이 중 20개가 조직학적으로 림프절 전이로 확진되었고 평균 최대 SUV는 5.84 (2.05-20.39)였다. 나머지 하나의 림프절은 조직 검사에서 염증성 병소로 진단되었고 최대 SUV는 2.75였다. 7개의 림프절전이가 조직검사에서만 발견되었다 민감도는 74.0%, 특이도는 99.6%, 양성 예측도는 95.2% 그리고 음성 예측도는 97.3%였다. 수술 후 환자 9명에서 11개의 림프절전이가 PET-CT에서 관찰되었고, 이 중 8개가 전이로 확진되었고 평균 최대 SUV는 5.65 (3.02-9.84)였다. 나머지 3개의 림프절들은 염증성 병소였고 평균 최대 SUV는 2.87였다. 1개의 위음성의 림프절이 발견되었다. 민감도는 88.8%, 특이도는 97.7%, 양성 예측도는 72.7% 그리고 음성 예측도는 92.9%였다. 결론: FDG-PET/CT은 두경부암 환자의 경부 림프절 전이를 평가하는데 수술 전 환자군에서는 보다 높은 양성 예측도를, 재발 환자군에서는 보다 높은 민감도를 보였다. 그러므로 PET/CT는 두경부암 환자에서 수술 전 환자와 재발 환자의 경부 림프절 전이의 진단에 유용하였다.

• 대한두경부종양학회지
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• 제30권2호
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• pp.53-61
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• 2014

Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

• Molecules and Cells
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• 제41권6호
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• pp.515-522
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• 2018

Patients with head and neck cancer are treated with therapeutic irradiation, which can result in irreversible salivary gland dysfunction. Because there is no complete cure for such patients, stem cell therapy is an emerging alternative for functional restoration of salivary glands. In this study, we investigated in vitro characteristics of primarily isolated epithelial cells from human salivary gland (Epi-SGs) and in vivo formation of acini-like structures by Epi-SGs. Primarily isolated Epi-SGs showed typical epithelial cell-like morphology and expressed E-cadherin but not N-cadherin. Epi-SGs expressed epithelial stem cell (EpiSC) and embryonic stem cell (ESC) markers. During long-term culture, the expression of EpiSC and ESC markers was highly detected and maintained within the core population with small size and low cytoplasmic complexity. The core population expressed cytokeratin 7 and cytokeratin 14, known as duct markers indicating that Epi-SGs might be originated from the duct. When Epi-SGs were transplanted in vivo with Matrigel, acini-like structures were readily formed at 4 days after transplantation and they were maintained at 7 days after transplantation. Taken together, our data suggested that Epi-SGs might contain stem cells which were positive for EpiSC and ESC markers, and Epi-SGs might contribute to the regeneration of acini-like structures in vivo. We expect that Epi-SGs will be useful source for the functional restoration of damaged salivary gland.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6649-6655
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• 2014

Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.

• 대한두경부종양학회지
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• 제14권1호
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• pp.54-60
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• 1998

Objectives: We'd like to give help in diagnosis and treatment of children's thyoid tumor through our clinical experiences and reference consideration. Materials and Methods: The authors report their experiences with 33 cases of thyroid tumor in patients younger than 16 years of age who were treated at Presbyterian Medical Center from 1979 to 1995. Results: 1) Girls were more predominant than boys by a ratio of 5.6:1. The peak incidence was in the 15 years old of age. 2) The final diagnosis in the 33 patients were thyroid carcinoma in 12 cases, nodular goiter in 6 cases, adenoma in 6 cases, Graves disease in 4 cases, Hasimoto's disease in 4 cases and cyst in 1 case. 3) All of 12 patients with thyroid cancer had nodular tumor. 4) In 5 of 6 patients with palpable cervical lymphadenopathy, the final diagnosis was thyroid carcinoma. 5) Delayed diagnosis arose in 6 of 12 thyroid carcinomas which were treated for long periods as benign disease. 6) The surgical procedures were total thyroidectomy in 3 cases, subtotal thyroidectomy in 13 cases and thyroid lobectomy in 17 cases. 7) 11 of 12 patients with thyroid carcinoma had subtotal or total thyroidectomy with lymphnode dissection and only one had lobectomy. 8) The overall rate of postoperative complication was 3%(1 of 33 patient). 9) Postoperative $^{131}I$ therapy was done in 7 case because of recurrence and distant metastasis in six and severe local invasion in one. 10) In thyroid cancer, the metastatic rate of lymph node at initial surgery was 81%(9/11) and rate of recurrence was 50%(6/12). 11) Patients with thyroid carcinoma were followed up for a mean of 12 years but only one died as a result of thyroid carcinoma 3.5 years later. Conclusion: The authors suggest that thyroid tumors in childhood should receive the benifit of joint management by endocrine pediatrician and experianced surgeons with an agreed protocol of diagnosis and management. We, also, recommend aggressive surgical and $^{131}I$ treatment as the most effective regimen for children with thyroid carcinoma.