• Journal of Oral Medicine and Pain
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• 제30권3호
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• pp.287-300
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• 2005

두경부에서 발생하는 편평세포암종은 같은 조직학적 분류, 조직학적 단계 및 임상 단계에 있다하더라도 항암제 투여에 따른 감수성은 환자마다 다양하게 나타난다. 따라서, 본 연구의 목적은 기존에 가장 많이 사용하는 항암제인 5-FU 와 Cisplatin의 감수성을 예측할 수 있는 생물학적 표지자를 찾아 환자에게 맞는 항암제를 선택하기 위해서이다. 5종의 구강 편평암세포암주를 이용하였으며, 5-FU 와 Cisplatin의 항암제 감수성을 측정하기 위해 MTT assay를 시행하였다. 각 세포 주의 전 RNA를 추출하였으며 이어서 cDNA를 합성하였다. 다양한 유전자를 1) 돌연변이 2) 염증(COX pathway) 3) 세포주기 4) 노화 5) 세포외기질 과 관련되게 분류하였고 RT-PCR을 시행하여 유전자의 발현량을 살펴보았다. 결과물은 Scion image 프로그램을 통해 분석하였고, Sigma plot을 이용해 표시하였다. 5-FU의 감수성과 비례하는 유전자들은 XPA, XPC, OGG, APEX, COX-2, PPAR, Cyclin E, Cyclin B1, CDC2, hTERT, hTR, TIMP-3, TIMP-4 및 HSP47이었으며, Cisplatin의 감수성과 비례하는 유전자들은 COX-1, iNOS, eNOS, PCNA, Col-1 및 MMP-9 으로 알 수 있었다. 위 결과는 암환자에게 알맞은 항암제를 선택 시 항암제의 감수성과 관련한 유전자들의 발현 정도를 파악한다면 올바른 항암제를 선택하는데 도움이 되리라 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제50권4호
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• pp.504-509
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• 2001

There are numerous agents with potential toxic effects on the lung. In particular, cytotoxic drugs constitute the largest and most important group of agents associated with lung toxicity. Bleomycin is commonly used, either alone or in combination with other chemotherapeutic agents, in the treatment of squamous cell carcinoma(head and neck, esophagus, and genitourinary tract), lymphoma, and germ cell tumor. One of the therapeutic advantages of bleomycin is its minimal bone marrow toxicity. However, pulmonary toxicity is one of the most serious adverse side effects. Classically, pulmonary toxicity manifests as a diffuse interstitial process or less commonly as a hypersensitivity reaction. This pulmonary toxicity is generally considered to be dose related and can progress to a fatal fibrosis. It is also possible that bronchiolitis obliterans organizing pneumonia(BOOP) is another manifestation of bleomycin induced toxicity. Bleomycin induced BOOP is less common and has a favorable response to steroid therapy. Here we present a case that demonstrates a BOOP, secondary to a relatively small cumulative dose of bleomycin($225mg/m^2$), may be reversible.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권1호
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• pp.83-91
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• 2008

The goal of reconstruction following ablative therapy for intraoral cancer is the restoration of form and function to permit a return to activities of daily life. Traditional reconstruction includes split thickness skin grafts, myocutaneous flaps and, more recently, various free flaps. Free flaps provide higher level of functional recovery relative to that seen with other techniques but require the complexity of the technique and microvascular anastomosis and thus, extended surgical time and occasionally a second team for harvesting. The platysma myocutaneous cervical flap is a possible alternative for intraoral reconstruction. It is thin and pliable like the tissue provided by the radial forearm free flap. It can be harvested with enough tissue to close most head and neck ablative defects. There is virtually no donor site morbidity involved. This study evaluated 7 patients affected by intraoral squamous cell carcinoma (SCC). All patients underwent the resection of intraoral SCC with neck dissection and subsequent intraoral reconstruction with the superiorly based platysma myocutaneous cervical flap. Flap-related complications occurred in 3 patients. Adjuvant radiation therapy was performed in 3 patients. Average follow-up was 24.1 months after surgery, with a range of 8 to 42 months. All patients presented self assessment of discomfort associated with intraoral recipient sites and cervical donor sites. However, the neck function measured by two-inclinometer technique was within the normal range during relatively long term follow-up period. Our study concluded that superiorly based platysma myocutaneous cervical flap is good alternative to free flaps, especially for relatively smaller defects and for the defects appropriate for the rotation arc of the flap.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제38권
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• pp.46.1-46.7
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• 2016

Background: Osteoradionecrosis is the most dreadful complication after head and neck irradiation. Orocutaneous fistula makes patients difficult to eat food. Fibular free flap is the choice of the flap for mandibular reconstruction. Osteocutaneous flap can reconstruct both hard and soft tissues simultaneously. This study was to investigate the success rate and results of the free fibular flap for osteoradionecrosis of the mandible and which side of the flap should be harvested for better reconstruction. Methods: A total of eight consecutive patients who underwent fibula reconstruction due to jaw necrosis from March 2008 to December 2015 were included in this study. Patients were classified according to stages, primary sites, radiation dose, survival, and quality of life. Results: Five male and three female patients underwent operation. The mean age of the patients was 60.1 years old. Two male patients died of recurred disease of oral squamous cell carcinoma. The mean dose of radiation was 70.5 Gy. All fibular free flaps were survived. Five patients could eat normal diet after operation; however, three patients could eat only soft diet due to loss of teeth. Five patients reported no change of speech after operation, two reported worse speech ability, and one patient reported improved speech after operation. The ipsilateral side of the fibular flap was used when intraoral soft tissue defect with proximal side of the vascular pedicle is required. The contralateral side of the fibular flap was used when extraoral skin defect with proximal side of the vascular pedicle is required. Conclusions: Osteonecrosis of the jaw is hard to treat because of poor healing process and lack of vascularity. Free fibular flap is the choice of the surgery for jaw bone reconstruction and soft tissue fistula repair. The design and selection of the right or left fibular is dependent on the available vascular pedicle and soft tissue defect sites.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8247-8252
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• 2016

Background: The ubiquitin-proteasome system (UPS) degrades a variety of proteins which attach to specific signals. The ubiquitination pathway facilitates degradation of damaged proteins and regulates growth and stress responses. This pathway is altered in various cancers, including acute lymphoblastic leukemia, head and neck squamous cell carcinoma and breast cancer. Recently it has been reported that expression of newly characterized human genes, UBE2Q1 and UBE2Q2, putative members of ubiquitin-conjugating enzyme family (E2), has been also changed in colorectal cancer. Epigenetics is one of the fastest-growing areas of science and nowadays has become a central issue in biological studies of diseases. According to the lack of information about the role of epigenetic changes on gene expression profiling of UBE2Q1 and UBE2Q2, and the presence of CpG islands in the promoter of these two human genes, we decided to evaluate the promoter methylation status of these genes as a first step. Materials and Methods: The promoter methylation status of UBE2Q1 and UBE2Q2 was studied by methylation-specific PCR (MSP) in tumor samples of 60 colorectal cancer patients compared to adjacent normal tissues and 20 non-malignant controls. The frequency of the methylation for each gene was analyzed by chi-square method. Results: MSP results revealed that UBE2Q2 gene promoter were more unmethylated, while a higher level of methylated allele was observed for UBE2Q1 in tumor tissues compared to the adjacent normal tissues and the non malignant controls. Conclusions: UBE2Q1 and UBE2Q2 genes show different methylation profiles in CRC cases.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8351-8359
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• 2014

Background: Recent epidemiological data have implicated human papilloma virus (HPV) infection in the pathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected in varied amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tongue carcinogenesis remains ambiguous. Materials and Methods: HPV DNA prevalence was assessed by PCR with formalin fixed paraffin embedded sections (n=167) of oral tongue squamous cell carcinoma patients and the physical status of the HPV16 DNA was assessed by qPCR. Immunohistochemistry was conducted for p16 evaluation. Results: We found the HPV prevalence in tongue cancers to be 51.2%, HPV 16 being present in 85.2% of the positive cases. A notable finding was a very poor concordance between HPV 16 DNA and p16 IHC findings (kappa<0.2). Further molecular classification of patients based on HPV16 DNA prevalence and p16 overexpression showed that patients with tumours showing p16 overexpression had increased hazard of death (HR=2.395; p=0.005) and disease recurrence (HR=2.581; p=0.002) irrespective of their HPV 16 DNA status. Conclusions: Our study has brought out several key facets which can potentially redefine our understanding of tongue cancer tumorigenesis. It has emphatically shown p16 overexpression to be a single important prognostic variable in defining a high risk group and depicting a poorer prognosis, thus highlighting the need for its routine assessment in tongue cancers. Another significant finding was a very poor concordance between p16 expression and HPV infection suggesting that p16 expression should possibly not be used as a surrogate marker for HPV infection in tongue cancers. Interestingly, the prognostic significance of p16 overexpression is different from that reported in oropharyngeal cancers. The mechanism of HPV independent p16 over expression in oral tongue cancers is possibly a distinct entity and needs to be further studied.

• Radiation Oncology Journal
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• 제14권1호
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• pp.9-15
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• 1996

목적 : 국소적으로 진행된 III, IV기 두경부종양의 방사선치료시 항암화학요법을 병행할 경우 방사선에 대한 민감도를 증가시켜 치료효과를 향상시키는 것으로 알려져 있다. 따라서 본 연구는 방사선-항암화학 병용요법이 국소제어율 및 생존율에 미치는 영향을 알아보기 위하여 방사선 단독치료군의 치료결과와 후향적으로 비교분석하였다. 대상 및 방법 : 1983년 11월부터 1994년 3월까지 인제대학교부속 백병원에서 두경부종양으로 진단받고, 추적관찰이 가능했던 III, IV기의 편평상피세포종양 환자 31명(I군: 방사선 단독치료 16명, II군: 방사선-항암화학 병용요법 15명)을 데상으로 하였다. 남녀 비는 I, II군에서 각각 12:4, 15:0 이었고 연령분포는 각각 17-74세(중앙값 64세), 34-71세(중앙값 54세)였다. 병기별 분포는 III기가 각각 5명, 3명, IV기가 11명, 12명이었다 방사선치료는 4MV 선형가속기(LINAC)를 사용하였고 총 방사선 조사선량은 I군 50-77.6Gy(중앙값 70.2Gey), II군 50-75.6Gy(중앙값 70Gy)이었다. 항암화학요법은 cisplatin + 5-FU (7명), methotrexate + leucovorin + 5-FU + cisplatin (혹은 carboplatin) (2명), 방사선민감제로서 clsplatin (6명)이 사용되었다. 결과 : 총 추적관찰기간은 4-134개월(중앙값 16개월)이었다 전체관해율은 I군 $66.6\%$(완전관해 $53.3\%$, 부분관해 $13.3\%$), 11군 $93.3\%$(완전관해 $60\%$, 부분관해 $33.3\%$)였고, 완전관해된 환자에서 2년 종양제어율은 각각 $50\%$, $40\%$이었다. 국소실패율은 I군과 II군에서 각각 $71.5\%$, $72.7\%$이었고, 원격전이율은 $14.4\%$와 $9.1\%$였다. 5년 생존율은 전체 환자에서 $21.5\%$, I군과 II군에서 $23.4\%$, $23.5\%$로 두 군간의 생존율의 차이는 통계학적으로 유의하지 않았다(P>0.05). 3년 무병생존율 역시 $44.5\%$와 $40\%$로 통계학적으로 유의한 차이를 보이지 않았다(P>0.05). 치료에 따른 급성 부작용은 피부독성이 I군 7/16명(RTOG/EORTC 등급 1; 5명, 2; 1명, 3: 1명), II군 5/15명(등급 2: 1명, 3: 4명, 4: 1명), 식도염 및 인두염이 각각 14/16명(등급 1: 7명, 2; 6명, 3이상 1명), 6/15명(등급 2: 1명, 3: 1명), 구강점막염은 각각 6/15명(등급 1: 1명, 2: 2명, 3; 2명, 4: 1명), 9/15명(등급 2: 4명, 4; 5명)으로 두 군간의 차이는 없었으나, 혈액학적 독성은 II군에서만 8/15($53.3\%$)가 관찰되었다. 결론 : 본 연구에서는 방사선-항암화학 병용요법군이 방사선 단독치료군에 비해 종양의 전체관해율은 높았으나, 5년 생존율 및 3년 무병 생존율에서는 두 군간에 통계학적으로 유의한 차이가 없었다(p>0.05). 그러나, 본 연구는 대상환자의 숫자가 제한되어 있어 항암화학요법의 역할을 규명하기 위해서는 앞으로 더 많은 환자를 대상으로 하여 오랜 기간의 추적관찰이 필요하리라 생각된다.

• Radiation Oncology Journal
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• 제10권1호
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• pp.27-34
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• 1992

CIS-PLATINUM (DDP)을 제 3기, 제 4기 두경부종양환자에게 방사선 민감제로 사용한 임상연구 결과를 보고한다. 1984년부터 1987년까지 DDP 20 $mg/M^2$/day를 4일간 방사선 치료와 동시에 투여 하였으며 DDP는 3주 간격으로 반복투여 되었다. 치료는 종양세포 감소시기, 근치시기및 보조 치료 시기로 나누어 시행되었다. 본 논문에서 59명 환자의 치료결과및 합병증에 대하여 보고한다. 근치시기동안27명이 방사선치료45Gy 후 근치적 수술을 시행한 제I치료군으로, 29명이 근치적 방사선치료 65Gy를 시행한 제II치료군으로 분류되고 3명의 환자는 근치시기의 치료를 끝내지 못하였다. 종양세포 감소시기의 치료로 완전관해 $47.5\%$, 부분관해 $47.5\%$로 전체 반응률 $95\%$를 보였다. 근치시기 치료후 전체적으로는 $84\%$(47/56)의 완전 관해를 보였고, 제I치료군에서는 $96\%$(26/27), 제 II치료군에서는 $72\%$(21/29)가 완전 관해를 보였다. 제I치료군에서 원발병소의 $67\%$에서, 임파절 병변의 $70\%$에서 병리소견상 종양이 관찰되지 않았다. 근치시기치료후 완전관해 환자중 $34\%$에서 재발하였으며 재발까지의 평균시간은 8개월이었다. 전체 56명 환자의 4년 무병생존율은 $59\%$였고 근치시기에 완전관해를 보인 환자중 $51\%$(24/47)가 31개월의 평균 추적관찰기간(범위 : $10\~51$개월)동안 무병생존하였다. 제I치료군과 제II치료군사이에 전체생존율, 무병생존율에 있어서 유의한 차이는 보이지 않았다. 종양세포감소시기에 완전관해및 부분관해를 보인 환자들 사이에 생존율에서는 차이가 없었으며 가장 중요한 예후인자는 근치시기 치료로 완전관해 되었는지 여부이었다. 전체대상 환자의 합병증은 일반적인 치료시에 비하여 심하지 않았으며 치료에 잘 적응하였다. 본 연구에서 DDP가 비교적 적은 합병증을 동반한 의미있는 방사선 민감제임을 확인하였으며 치료효과를 증대시키기 위하여 DDP와 방사선치료의 적절한 투여 계획을 결정하는 전향적 연구가 필요하다고 생각한다.

• 대한두경부종양학회지
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• 제17권1호
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• pp.59-62
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• 2001

Objectives: We report an interim result of conformal radiotherapy in a patient with early stage cancer at the base of the tongue, which developed in a previously irradiated area. Materials and Methods: A 64-year-old male patient was diagnosed with T4N0M0 supraglottic cancer. He received 72Gy of radiation therapy from 21 November 1988 to 24 February 1989. He had local failure and underwent a salvage total laryngectomy on 28 August 1989. Subsequently, he did well. In early 1999, he suffered from throat pain. He had a 2.5cm ulcerative mass at the base of his tongue, in the area that had been irradiated previously. Biopsy showed squamous cell carcinoma. After workup, he was diagnosed with base of tongue cancer with T2N0M0. Surgery was not feasible because the morbidity was not acceptable. Since it was difficult to re-irradiate the area with a curable dose using conventional 2D radiation therapy with an acceptable morbidity, we decided to try conformal radiotherapy. We used 7 static beam ports with field sizes from $7x6.4\;to\;8x8cm^2$, using 6 and 10MV photons. The fractionation regimen was 1.8Gy, 5 times per week. He received 64.8Gy in 36 fractions from 9 April 1999 to 1 June 1999. Results: In the 21 months since radiotherapy, the patient has not experienced any acute or chronic complications, such as xerostomia. He experienced relief of pain shortly after the start of radiotherapy, showed a complete response, and is still doing well. Conclusion: Conformal radiotherapy can be used to treat cancer that develops within a previously irradiated field, with curative intent.

• 대한두경부종양학회지
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• 제23권1호
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• pp.3-8
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• 2007

연구목적：국소적 진행성 편도암환자에서 수술적치료와 비수술적치료의 결과를 비교 분석하고자 하였다. 연구방법 : 수술 후 보조방사선요법을 시행한 군과 유도화학요법 시행 유무에 상관없이 근치적 방사선 치료 또는 항암화학-방사선 동시치료를 받은 비수술군의 임상결과를 후향적으로 분석하였다. 연구결과：52.4개월의 중앙 추적기간결과, 대상환자의 중앙 연령은 53세 이었다. 대상 환자 중 병기 Ⅲ, Ⅳ기 환자는 72명(82.8%)이었고, 49명(56.3%)이 수술적 치료를, 38명(43.7%)명이 비수술적 치료를 받았다. 방사선 조사량외에 양군간의 차이는 없었다 (수술군：60.4Gy, 비수술군：70.2Gy, p=0.02). 비수술군의 전체 생존율은 81.6%이었다. 수술군의 8명(16.3%), 비수술군의 6명 (15.8%)에서 재발이 발생하였다. 흥미로운 사실은 원격재발은 2명 모두 수술군에서 발생하였다. 병기 III, IV기의 5년 무병생존율과 전체생존율은 수술군이 각각 82.1%, 86.9%이고, 비수술군이 각각 83.3%, 83.1%이었다(p=0.96, p=0.96). 결론：수술적 치료에 비해 비수술적 치료가 활동능력이 불량한 환자에게 선호되었을 가능성이 있었음에도 불구하고, 치료성적은 비슷하였다. 편도암에서 수술적 치료와 비수술적 치료의 전향적 무작위 비교연구가 필요하다.