• Journal of Gastric Cancer
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• 제6권3호
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• pp.125-131
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• 2006

목적: 위암 환자에서 복강 내 파종은 대부분 장막을 침범한 원발성 암에서 떨어져 나온 복강 내 유리 암세포에 의해 이루어지는 것으로 가장 흔한 재발의 형태이다. 수술 중 이러한 유리 암세포의 존재를 직접 또는 간접적으로 확인할 수 있는 방법이 있다면 위암의 치료 전략을 정하는데 유용할 것이다. 이에 수술을 시행 받은 위암 환자를 대상으로 복강 세척액에서 CEA와 CA19-9의 검출 정도와 종양의 침윤도, 림프절 전이 및 병기 등과의 연관성을 알아보고자 연구를 시행하였다. 대상 및 방법: 2004년 5월부터 2006년 1월까지 건양대학교병원 외과에서 위암을 진단받고 수술을 시행한 130명의 환자를 대상으로 하였고, 모든 환자에서 복강 세척액을 채집하여 CEA, CA19-9를 측정하였다. 위의 비선암종 환자 14명을 대조군으로 하여 복강 세척액을 분석하였다. 결과: 위암 환자의 복강 CEA, CA19-9의 측정치는 종양의 침윤도, 림프절 전이 및 병기와 상관 관계가 있었으며(P<0.05) 복강 CEA 측정치는 비선암종 환자군과도 유의한 차이를 보였다. 결론: 복강 CEA, CA19-9의 증가는 TNM 병기와 부분적으로 평균치의 차이가 있고 복강 CEA는 다른 측정치에 비해 가치 있는 복막 전이 예측인자로서의 가능성을 확인하였다.

• Journal of Gastric Cancer
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• 제9권3호
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• pp.88-95
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• 2009

목적: 세포자멸사의 중요인자인 p53과 bcl-2의 개별발현 및 동시 발현이 갖는 위선암의 예후 인자로서의 역할과 생존율에 미치는 영향을 알아보고자 하였다. 대상 및 방법: 1999년 12월에서 2007년 7월까지 위선암으로 분당제생병원 외과에서 근치적 위절제술을 시행 받은 238명의 환자들을 대상으로 자료의 후향적 분석을 시행하였다. p53과 bcl-2의 발현은 DAKO사의 Envision kit로 면역조직화학 염색을 하여 발현군을 양성으로 정의하였다. 결과: 전체 환자 중 p53은 149예(62.5%)에서 발현되었으며, 다른 임상병리학적 예후 인자와의 상관관계를 조사한 결과 세포분화도(P=0.028), TNM 병기(P<0.001)에서 유의성을 나타냈다. bcl-2은 29예(12.2%)가 발현되었으며, TNM 병기(P=0.005)에서 유의성을 나타냈다. 단변량 생존율 분석을 통해 p53과 bcl-2는 생존율 감소에 영향이 있으며, 다변량 생존율 분석을 통해 p53은 독립적 예후 인자로서의 확인되었다. 또한 두 단백의 동시 발현군도 TNM 병기(P=0.002)와 의미 있는 상관관계를 보였으며, 개별 발현 때보다 동시 발현 시 유의한 생존율 감소를 보였다(P<0.001). 결론: p53과 bcl-2의 개별 발현은 나쁜 예후를 나타내며, 이들의 동시 발현은 더욱 나쁜 예후를 나타냈다. 그러나 bcl-2는 다변량 분석에서 독립 예후인자로서 의미는 부족하여 더 많은 분석을 통해 명확히 할 필요가 있겠다.

• Journal of Gastric Cancer
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• 제3권3호
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• pp.139-144
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• 2003

Purpose: Because of an improving gastric cancer detection program and treatment methods, we can expect improved survival of patients with gastric cancer. Given the longer survival times, the chance of an occurrence of multiple primary malignant tumors other than stomach is increased in the same patients. The purpose of this study is to analyze the clinical characteristrics and the survival of patients with gastric cancer and other malignancies. Materials and Methods: A retrospective study of 3669 patients with gastric cancer observed at our department between January 1994 to December 2002 was conducted. Associated tumors were diagnosed using the Warren and Gates criteria, and included tumors that were not considered to be a metastasis, invasion, or recurrence of the gastric cancer. Results: Of all 3669 patients, $2.07\%$ (n=76) had primary tumors other than gastric cancer, $63\%$ of which were synchronous (n=48) and $37\%$ metachronous (n=28). The mean age of the study group was 64.9 (65.5 in males, 61.8 in females), and the male-to-female ratio was 4.8 : 1. The most common cancer associated with gastric cancer was a hepatocellular carcinoma ($23.7\%$), followed by colorectal cancer ($17.1\%$), esophageal cancer ($10.5\%$), breast cancer ($6.6\%$). Of the 45 patients who had undergone a resection, 14 were in stage I, 12 in stage II, 13 in stage III, and 6 in stage IV. No statistically significant differences were found between the synchronous and the metachronous groups with regard to age, sex ratio, differentiation, and stage. The 5-year survival rates of the metachronous and the resected patients were significantly higher than those of the synchronous and the non resected patients, respectively. Conclusion: Due to increasing length of the follow-up period for patients with gastric cancer, another malignancy may develop in other organs. Therefore, physicians should pay attention to detect other cancers early in these patients, and a surgical resection is recommended as the treatment of choice in the management of multiple primary cancer associated with gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8893-8900
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• 2014

Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRTPCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR-196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6227-6232
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• 2014

Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. The aim of present study was to evaluate the efficacy of novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in terms of their potential to change the VEGF-C expression profile in a rat OSCC model. Materials and Methods: 120 male rats were divided into 8 groups of 15 animals administrated with 4-nitroquinoline-1-oxide to induce OSCCs. Newly formulated doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) and free doxorubicin were IV and orally administered. Results: Results indicated that both oral and IV forms of DOX-MTX-nanoparticle complexes caused significant decrease in the mRNA level of VEGF-C compared to untreated cancerous rats (p<0.05). Surprisingly, the VEGF-C mRNA was not affected by free DOX in both IV and oral modalities (p>0.05). Furthermore, in DOX-MTX NP treated group, less tumors characterized with advanced stage and VEGF-C mRNA level paralleled with improved clinical outcome (p<0.05). In addition, compared to untreated healthy rats, the VEGF-C expression was not affected in healthy groups that were treated with IV and oral dosages of nanodrug (p>0.05). Conclusions: VEGF-C is one of the main prognosticators for lymph node metastasis in OSCC. Down-regulation of this lymph-angiogenesis promoting factor is a new feature acquired in group treated with dual action DOX-MTX-NPs. Beside the synergic apoptotic properties of concomitant use of DOX and MTX on OSCC, DOX-MTX NPs possessed anti-angiogenesis properties which was related to the improved clinical outcome in treated rats. Taking together, we conclude that our multifunctional doxorubicin-methotrexate complex exerts specific potent apoptotic and anti-angiogenesis properties that could ameliorate the clinical outcome presumably via down-regulating dissemination factor-VEGF-C expression in a rat OSCC model.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2995-2999
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• 2016

Background: Triple-negative breast cancer (TNBC) often presents as an interval cancer with short survival upon metastasis and thus represents an important clinical challenge. The present study investigated the clinicopathologic characteristics and long term survival outcome of early and locally advanced TNBC. Materials and Methods: Medical records were reviewed retrospectively for 148 consecutive confirmed cases of TNBC treated in a single unit at our centre. Demographic profile, tumor type, histopathology details, treatment and follow-up information was recorded and immunohistochemistry was performed. Results: Age group >50 years was associated with tumors of clinical stage 3 (53.8%), pathological stage 3 (46.2%), pathological grade 3 (45.7%), presence of extracapsular extension (ECE, 48.5%) and lymphovascular invasion (LVI, 64.9%). Locally advanced breast cancers (LABCs) were characterized by pathological stage 3 (96.2%), presence of ECE (100%) and absence of LVI (46.7%) as compared to early breast cancers (EBCs) which had higher incidence of lower stage tumors (100%), absence of ECE (82%) and presence of LVI (91.9%; p-value <0.001. Better relapse free survival was observed in patients with no axillary involvement (69%; p-value <0.001) and absence of ECE (64%; p-value <0.001). Improved overall survival was seen in patients with EBC (90%; p-value 0.008), clear axilla (86%; p-value <0.001), absence of ECE (87%; p-value <0.001) and negative lymph nodes (90%; p-value 0.006). Conclusions: TNBCs are aggressive tumors which show poor long term survival. Patients with TNBC benefit from chemotherapy, thus better and less toxic treatment options are needed. Identification of newer targets and development of targeted therapies are the need of the hour.

• Journal of Chest Surgery
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• 제37권3호
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• pp.286-291
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• 2004

원발성 지방육종은 종격동에서 매우 드물게 발생하는 악성 종양으로 수술적 절제가 가장 효과적인 치료로 알려져 있다. 24세 남자 환자가 1개월 전부터 시작된 호흡곤란과 흉부 불편감으로 타 병원에서 좌측 혈흉을 의심하여 좌측 흉관삽관술을 시행받았다. 본원 입원 후 흉부 단순촬영에서 종격동 편위소견을 보였고 빈맥이 진행하였으며, 중심정맥압이 상승하는 양상보여 진단 및 혈괴제거를 위해 응급으로 좌측 개흉술을 시행하여 다량의 점액성의 혈성 흉수를 제거하였고, 조직검사 결과 골격계외 점액성 연골육종으로 진단되었다. 2주 후 좌측 개흉술로 횡격막 및 심낭의 일부를 포함하는 흉막외 좌측 전폐적출술과 함께 종격동 종양을 절제하였다. 조직검사에서 점액성/원형세포 지방육종으로 진단되었으며, 입원 54일만에 합병증 없이 퇴원하였다. 술 후 2개월째 1회의 항암화학요법(Ifosfamide+Adriamycin: IA) 후 종격동, 좌측 견갑골 부위 및 종격동 임파선에 재발하여, 약제를 바꾸어 (Etoposide+Ifosfamide+Cisplatin: VIP) 항암화학요법을 시행하였으나 복강전이로 술 후 10개월째 사망하였다. 종격동에 발생하는 원발성 지방육종은 매우 드문 질환으로 수술적 절제 및 항암요법 후 추적관찰한 1예를 문헌고찰과 함께 보고하는 바이다.

• 생명과학회지
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• 제30권5호
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• pp.483-490
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• 2020

유비퀴틴 시스템은 ubiquitin ligases와 deubiquitinases (DUBs)에 의해 타겟 기질의 ubiquitination 유무에 따라 안정화, 활성화, 국소화 및 상호작용을 변화시키고 암 발병의 관여하는 다양한 생물학적 과정을 조절한다. DUBs는 촉매 domain에 따라 6그룹으로 나뉘어지는데, 그 중에서 OTU 그룹 내 대부분의 DUB는 세포의 연속적 신호반응(cell signaling cascade)을 조절할 수 있다. 특이하게도 OTU 그룹에 속하는 otubain 1 (OTUB1)은 정규적(canonical) 활성과 비정규적(non-canonical) 활성을 모두 가지고 있다. 본 보고에서는 OTUB1의 canonical, non-canonical 활성 조절에 있어서 다양한 신호전달경로 및 OTUB1의 역할에 대해 기술하였다. OTUB1은 이 두 종류의 활성 경로를 통하여, OTUB1은 암 관련 신호 전달 체계에 중요한 FOXM1, ERα, KRAS 및 EMT를 조절하고 암세포 증식 및 전이 능력 향상 및 항암제에 대한 내성을 나타낸다. 또한 임상적으로 전이성 및 종양 분화도가 높은 암 조직에서 OTUB1의 발현이 높으며, 이에 따라 환자의 생존율이 감소하는 등 나쁜 예후를 나타낸다. 따라서, 임상적으로 적용할 수 있는 OTUB1 억제제의 개발이 이루어진다면 OTUB1은 종양 치료에 있어 중요한 진단마커이자 치료적인 타겟이 될 수 있다.

• 대한두경부종양학회지
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• 제17권2호
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• pp.205-209
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• 2001

Purpose: Most cases of primary hyperparathyroidism are due to parathyroid adenoma or parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause of hyperparathyroidism. Although the diagnosis of parathyroid carcinoma is usually established by pathologic criteria especially of vascular or capsular invasion, some clinical and biochemical features differentiate it from benign forms of hyperparathyroidism. We under-took a retrospective study in 6 patients with parathyroid carcinoma, with the aim of conveying experience from management for this rare cause of hyperparathyroidism. Methods: Clinical symptoms, biochemical laboratory, radiologic, and intraoperative findings, local recurrence and distant metastasis were analyzed in 6 patients diagnosed pathologically as a parathyroid carcinoma after operation from 1992 to 2001. Results: Mean age was 50.2 years (33.0-60.0 years) and male to female ratio was 1:1. Neck mass was found in 5 patients, multiple bone pain in 3 patients and renal stone in 1 patient. One case has suffered from chronic renal failure for 19 years. Although preoperative laboratory evaluations showed the aspects of hyperparathyroidism in all cases, mean serum calcium level was 11.2mg/dl(10.5-12.1mg/dl), slightly elevated. Laboratory values after surgery were within the normal range in 5 cases. However, in one case with chronic renal failure, serum PTH levels, serially checked, were above the normal range. Any of imaging methods failed to suggest a parathyroid carcinoma preoperatively. Parathyroid adenoma was suspected in 3 cases, thyroid cancer in the other cases before surgery. The extent of resection was radical resection of parathyroid lesion with more than unilateral thyroid lobectomy and central compartment neck node dissection and in 2 cases, the resection of recurrent laryngeal nerve or strap muscles was added. During follow-up period, any local or systemic recurrence were not evident in all the cases. Conclusion: Although parathyroid carcinoma is a rare disease and its preoperative diagnosis, in our experience, could not easily be made, the understanding of characteristic clinical and biochemical feature could help diagnosis at first surgery. Radical resection without remaining residual tumor is most important for the management of the parathyroid cancer.