• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6513-6518
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• 2013

Background: To evaluate the treatment outcome and major late complications of all patients with recurrent nasopharyngeal carcinoma (NPC) treated with intracavitary brachytherapy (ICBT) in Hospital Kuala Lumpur. Materials and Methods: This retrospective study was conducted at the Department of Radiotherapy and Oncology, Hospital Kuala Lumpur, Malaysia. All patients with histologically confirmed recurrent NPC in the absence of distant metastasis treated in the period 1997-2010 were included in this study. These patients were treated with ICBT alone or in combination with external beam radiotherapy (EBRT). Treatment outcomes measured were local recurrence free survival (LRFS), disease free survival (DFS) and overall survival (OS). Results: Thirty three patients were eligible for this study. The median age at recurrence was 56 years with a median time to initial local recurrence of 27 months. Majority of patients were staged as rT1-2 (94%) or rN0 (82%). The proportion of patients categorised as stage III-IV at first local recurrence was only 9%. Twenty one patients received a combination of ICBT and external beam radiotherapy while 12 patients were treated with ICBT alone. Median interval of recurrence post re-irradiation was 32 months (range: 4-110 months). The median LRFS, DFS and OS were 30 months, 29 months and 36 months respectively. The 5 year LRFS, DFS and OS were 44.7%, 38.8% and 28.1% respectively. The N stage at recurrence was found to be a significant prognostic factor for LRFS and DFS after multivariate analysis. Major late complications occurred in 34.9% of our patients. Conclusions: Our study shows ICBT was associated with a reasonable long term outcome in salvaging recurrent NPC although major complications remained a significant problem. The N stage at recurrence was a significant prognostic factor for both LRFS and DFS.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3411-3416
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• 2016

Background: Nasopharyngeal carcinoma (NPC), a malignancy arising from the epithelial lining of the nasopharynx, is distinct from others cancers in terms of its epidemiologic features. It is rare in most parts of the world except for a few regions with populations of Mongoloid origin. Objectives: To study the expression pattern of Epstein Barr virus (EBV) encoded oncoproteins EBNA1 and LMP1 in different histological types of NPC and to correlate expression patterns with sex, age and histological types. Materials and Methods: A total of 40 formalin-fixed, paraffin-embedded NPC biopsy samples and tissues from 20 healthy controls were collected to study the expression level of EBNA1 and LMP1 using immunohistochemistry. Results: EBNA1 and LMP1 expression was found in 92.5% and 90% respectively, of the cases and none of the control specimens. The expression patterns of EBNA1 and LMP1 were determined to be statistically significant (p<0.05) when correlated with sex, age and histological distributions. Also immunohistochemistry was found to be a sensitive technique in the detection of EBV. Conclusions: The study reveals that the potent oncoproteins EBNA1 and LMP1 were over expressed in our population cohort. Our findings are to some extent inconsistent with earlier reports as our population showed a higher expression of both EBNA1 and LMP1 compared to other studies.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.383-398
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• 2023

Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROS-mediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.

• Radiation Oncology Journal
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• 제9권1호
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• pp.65-72
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• 1991

1977년 7월부터 1987년 6월까지 10년간 연세대학교 의과대학 치료방사선과에서 방사선 치료를 받았던 135명의 비인강암 환자 중 치료시작 당시 조직학적으로 늑진되지 않았던 환자, 원격전이를 동반하고 있었던 환자 및 방사선 치료를 완료하지 못한 환자 30명을 제외한 105명 환자를 대상으로 원격전이의 빈도, 양상 및 예후를 분석하였다. 원격전이 진단은 임상증상과 방사선 소견으로 하였으며, 대상환자 105명중 원격전이를 보인 환자는26명으로 원격전이율 $24.8\%$였으며, 원격전이의 장기는 이전의 다른보고들에서와 마찬가지로골전이 $(50.0\%)$가 가장 많았고, 다음이 폐 $(19.3\%)$, 간$(11.5\%)$, 뇌 $(7.7\%)$ 순서였다. 원격전이에 영향을 미치는 인자로 연령, 성별, AJC의 T병기, N병기, Ho의 T병기, N병기, 조직 세포유형 및 치료방법등을 분석해 보았으나 Ho의 N병기에서만 NO, N1, N2, N3로 감에따라 원격전이율이 증가하는 양상을 보였다(p<0.05) .원격 전이 발생시기는 환자의 $80.8\%$에서 방사선 치료시작부터 2년이내에 일어나는 것을보여 비교적 조기에 발생함을 알 수 있었다. 원격전이가 발생한 26명의 환자에 있어서, 원격전이후 생존율을 살펴보면 중앙 생존치가 9개월이었고 1년생존율 $60\%$, 2년 생존율 $20\%$를 보여 비인강암 환자에서 일단 원격전이가 발생하면 그 예후가 불량함을 알 수 있었다.

• Radiation Oncology Journal
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• 제18권4호
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• pp.221-225
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• 2000

목적 : 본 연구는 1997년에 개정된 비인강암에 대한 AJCC병기 분류법을 1992년의 분류법과 비교하여 새로운 병기 분류법의 신뢰성을 평가하고자 시행되었다. 재료 및 방법 : 1983년부터 1996년까지 서울대학교 병원 치료방사선과에 방사선 치료를 위해 내원한 185명의 조직학적으로 확진되고 원격전이의 증거가 없는 비인강암 환자들을 대상으로 하였다. 이들 환자들에 대하여 의무 기록과 전산화 단층촬영, 자기공명영상을 검토하여 1992년 병기 분류법과 1997년 병기 분류법에 따라 병기를 분류하였고 각 병기 분류법에 따라 생존율을 산출하였다. 결과 : 1992년 분류법과 1997년 분류법에 따른 5년 생존율은 병기 I에서 각각 100$\%$; 병기 II에서는 100$\%$ 와 68.8$\%$; 병기 III에서는 61.4$\%$ 와 63.8$\%$; 병기 IV에서는 61.1$\%$ 와 63.2$\%$ 였다. 각각의 분류법으로 산출한 5년 생존율은 각각의 병기분류법 내에서 병기에 따라 유의한 차이를 보였으나 양 분류법 간에는 병기 II를 제외하고는 통계학적인 차이는 없었다. 결론 : 새로운 비인강암의 AJCC 병기분류법은 이전의 1992년 분류법과 비교하여 신뢰할 수 있을 것으로 생각되나 더 많은 환자를 대상으로 임상적 연구가 진행되어야 할 것으로 생각된다.

• Radiation Oncology Journal
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• 제21권4호
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• pp.269-275
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• 2003

목적: 비인강암 환자에서 방사선치료 후 재발 양상, 생존율 및 생존율에 미치는 예후인자를 분석평가하기 위해 후향적으로 분석을 하였다. 대상 및 방법: 1984년 1월부터 2000년 6월까지 한양대학병원 치료방사선과에서 방사선치료를 위해 의뢰된 비인강암 49명을 대상으로 후향적 분석을 하였다. 추적기간은 평균 76개월이었고 최소 2년 6개월이었다. 연령분포는 17세부터 78세였고 중앙연령은 52세였다 조직병리상 편평상피세포암이 21예, 미분화암이 25예, 샘모양 낭암종이 3예였다. 미국암합동위원회의 1997년 개정판으로 재분류한 병기로 T1 14예, T2 24예, T3 3예, T4 8예였다. N0 17예, Nl 15예, N2 4예, N3 13예였다 병기군별은 stage I, IIa, IIb, III, IVa IVb가 각각 4예, 7예, 12예, 5예, 8예, 13예였다. 방사선은 원발병소나 임파선전이부위에 58$\~$70 Gy를 조사 시행하였다. 결과: 5년 생존율 및 10년 생존율은 각각 54.5$\%$ 및 47$\%$였다. 5년 무병 생존율 및 10년 무병생존율은 가각 55.7$\%$ 및 45.3$\%$였다. 병기별로 100$\%$, IIa 80$\%$, IIb 59.5$\%$, III 40$\%$, IV 42.2$\%$의 5년 생존율을 보였다. 총 23예의 재발을 보였고 10예(20.4$\%$)에서 국소 재발, 4예(8.2$\%$)에서 임파선재발, 10예(20.4$\%$)에서 원격전이가 있었다. 병기에 따른 국소재발률은 T1 2예(4.3$\%$),T23 예(12.5$\%$), T4 5예(62.6$\%$)로 T병기가 높을수록 재발률이 높았다. 원격전이는 N2-3환자에서 많았다(41.2$\%$). 국소 재발시기는 50$\%$가 2년 이내였고 원격 전이시기는 70$\%$에서 2년 이내였다. 예후로는 여성, 젊은 연령, 조기 T병기 및 조기 전체적인 병기 및 미분화세포가 생존율이 높았으며 그중 조기 T병기 및 전체적인 병기가 통계적인 유의성이 있었다. 결론: 비인강암의 방사선치료결과는 국소 재발률은 T4 병기에 높고 원격전이는 2$\~$3병기에 현저히 높음을 알 수 있었다. 국소재발을 낮추기 위해 특히 T4에서 좀더 많은 양의 방사선이 요구되며 방사선량을 높이기 위해 삼차원적인 치료계획을 이용한 입체조형 방사선 치료나 세기조절 방사선 치료 등이 필요하리라 생각되며 임파선전이환자에서 보다 효과적인 항암제와 방사선의 병용요법의 개발이 필요하리라 생각된다.

• Radiation Oncology Journal
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• 제13권3호
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• pp.215-223
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• 1995

Purpose : The aim of this study was to assess the effectiveness, survival rate and complication of radiation in nasopharyngeal cancer. Materials and Methods : From January 1980 to May 1989. Fifty patients who had nasopharyngeal carcinoma treated with curative radiation therapy at Kosin Medical Center were retrospectively studied. Thirty seven patients($74{\%}$) were treated with radiation therapy alone(Group I) and 13 patients ($26{\%}$) treated with combination of chemotherapy and radiation (Group II). Age distribution was 16-75 years(median : 45.8 years). In histologic type, squamous cell carcinoma was in 30 patients($60{\%}$), undifferentiated carcinoma in 17 patients($34{\%}$), and lymphoepithelioma in 3 patients($6{\%}$). According t AJCC staging system. 4 patients($8{\%}$) were in $T_1$, 13 patients($26{\%}$) in $T_2$. 20 patients($40{\%}$) in $T_3$, 13 patients($26{\%}$) in $T_4$ and 7 patients($14{\%}$) in $N_0$, 6 patients($12{\%}$) $N_1$, 23 patients($46{\%}$) in $N_2$, 14 patients($28{\%}$) in $N_3$. Total radiation dose ranges were 5250-9200cGy(median : 7355 cGy) in Group I and 5360-8400cGy(median : 6758cGy) in Group II Radiotherapy on 4-6MV linear accelerator and/or 6-12MeV electron in boost radiation was given with conventional technique to 26 patients($52{\%}$), with hyperfractionation(115-120cGy/fr., 2times/day) to 16 patients($32{\%}$), with accelerated fractionation(160cGy/fr., 2 times/day) to 8 patients($16{\%}$). In chemotherapy, 5 FU 1000mg daily for 5 consecutive days, pepleomycin 10mg on days 1 and 3, and cisplatin 100mg on day 1 were administered with 3weeks interval, total 1 to 3 cycles(average 1.8cycles) prior to radiation therapy. Follow up duration was 6-140 months(mean : 58 months). Statistics was calculated with Chi-square and Fisher's exact test. Results : Complete local control rates in Group I and II were $75.7{\%},\;69.2{\%} Overall 5 year survival rates in Group I and II were $56.8{\%},\;30.8{\%}$. Five year survival rates by histologic type in Group I and II were $52.2{\%},\;14.3{\%}$ is squamous cell carcinoma and $54.5{\%},\;50{\%}$ in undifferentiated carcinoma. Survival rates in Group I were superior to those of Group II though there were not statistically significant. In both group, survival rates seem to be increased according to increasing total dose of radiation up to 7500cGy, but not increased beyond it. There were not statistically significant differences in survival rates by age, stage, and radiation techniques in both group. Twenty four patients($48{\%}$) experienced treatment failures. Complications were found in 12 patients($24{\%}$). The most common one was osteomyelitis(4 patients, $33.3{\%}$) involving mandible (3 patients) and maxilla(1 patient). Conclusion : Chemotherapy in combination with radiotherapy was found to be not effective to nasopharyngeal cancer and the survival rate was also inferior to that of radiation alone group though it was statistically not significant due to small population in chemotherapy combined group.

• 대한두경부종양학회지
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• 제7권1호
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• pp.40-44
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• 1991

Cystic metastasis in the neck from pharyngeal cancer has often been mistaken for either primary squamous cell carcinoma of branchiogenic origin or branchial cleft cyst. The distinctive histological and clinical features of cystic metastasis reviewed after its correct indentification can lead to the discovery of an unsuspected primary lesion and result in specific treatment options. Recendy, the authors experienced three cases of cystic metastasis in the neck from pharyngeal cancer ; one was from nasopharyngeal squamous cell carcinoma and the other two were from tonsillar squamous cell carcinomas. This report summarizes our experiences and review of the literatures.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4663-4670
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• 2014

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4393-4399
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• 2015

Background: To explore the independent prognostic factors for the recurrence/metastasis of patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods: A total of 604 patients initially diagnosed as LANPC by pathohistology in Fujian Provincial Cancer Hospital were selected to analyze the relationship between the clinical pathological patterns, therapeutic protocols and clinical stages with the recurrence/metastasis of LANPC. Results: The 1-, 3- and 5-year locoregionally recurrent rates of LANPC patients were 2.0%, 9.5% and 12.9% respectively, with average recurrent period being 78 months. Univariate analysis results indicated that clinical stages had certain influence on the recurrent period of LANPC patients. However, COX regression models showed that ages, genders and clinical stages were not the independent prognostic factors influencing the recurrence. The 1-, 3- and 5-year metastatic rates of LANPC patients were 6.6%, 17.5% and 18.8% respectively, with average metastatic period of 73 months. Univariate analysis results demonstrated that ages, N stages, clinical stages, locations of lymph node, retropharyngeal lymph node and extracapsular invasion of lymph node had certain influence on the metastatic period of LANPC patients. Additionally, further COX regression analysis results suggested that T stages, reduction protocols and extracapsular invasion of lymph node were the independent prognostic factors influencing the metastasis of patients with LANPC, in which T stages and extracapsular invasion of lymph node were the pestilent factors while reduction protocols the protective factor. Conclusions: Induction chemotherapy is beneficial to LANPC patients with initial treatment, and the metastatic rate decreases greatly after the application of reduction chemotherapy.