• BMB Reports
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• 제47권6호
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• pp.299-310
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• 2014

Cohesin is a multi-protein complex composed of four core subunits (SMC1A, SMC3, RAD21, and either STAG1 or STAG2) that is responsible for the cohesion of sister chromatids following DNA replication until its cleavage during mitosis thereby enabling faithful segregation of sister chromatids into two daughter cells. Recent cancer genomics analyses have discovered a high frequency of somatic mutations in the genes encoding the core cohesin subunits as well as cohesin regulatory factors (e.g. NIPBL, PDS5B, ESPL1) in a select subset of human tumors including glioblastoma, Ewing sarcoma, urothelial carcinoma, acute myeloid leukemia, and acute megakaryoblastic leukemia. Herein we review these studies including discussion of the functional significance of cohesin inactivation in tumorigenesis and potential therapeutic mechanisms to selectively target cancers harboring cohesin mutations.

• 생명과학회지
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• 제26권9호
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• pp.1015-1021
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• 2016

Pyrimidine 유도체의 일종인 5-fluorouracil (5-FU)은 광범위하게 사용되는 항암제의 일종으로, thymidylate synthase의 활성을 억제시켜 핵산의 합성 및 대사기능 자애 유발 물질이다. 본 연구에서는 Ewing′s 육종 CHP-100 세포에서 5-FU의 증식억제와 연관된 기전 해석으로 시도하였다. 본 연구의 결과에 의하면, 5-FU 처리 시간의 경과에 따른 CHP-100 세포의 증식억제가 세포주기 G1 arrest 유발에 따른 것임을 알 수 있었다. 5-FU에 의한 CHP-100 세포의 G1 arrest는 retinoblastoma protein (pRB)의 탈인산화에 따른 전사인자 E2F-1 및 E2F-4와의 결합 촉진과 연관성이 있었다. 비록 5-FU 처리가 cyclin-dependent kinases의 발현에는 크게 영향을 주지 않았으나, 정상배지에서 배양된 대조군에 비하여 cyclin A 및 B의 발현이 5-FU 처리 시간 의존적으로 억제되었다. 또한 5-FU에 의한 CHP-100 세포의 G1 arrest는 apoptosis 유도와 연관이 있음을 핵 내 염색질의 응축에 따른 apoptotic body의 형성증가, poly (ADP-ribose) polymerase의 단편화 및 annexin V 염색 등을 통하여 확인하였다. 아울러 5-FU는 pro-apoptotic Bax 단백질의 발현 증가 및 anti-apoptotic Bcl-2의 발현 감소를 통한 mitochondrial membrane potential의 소실을 촉진시켰으며, 이로 인하여 미토콘드리아에서 세포질로의 cytochrome c 유리가 증가시켰음을 알 수 있었다. 따라서 본 연구의 결과는 5-FU에 의한 CHP-100 세포의 증식억제와 연관된 G1 arrest 및 apoptosis 유도에는 pRB의 인산화 억제 및 미토콘드리아 기능의 손상이 최소한 관여하고 있음을 의미하는 것이다.

• Radiation Oncology Journal
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• 제2권1호
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• pp.115-122
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• 1984

Total 125 patinets with primary and metastatic Ewing's sarcoma were treated in various ways between 1963 to 1977. Patients were divided into 3 groups according to the treatment methods. Group 1 was nonprotocol patients with or without chemotherapy. Total 58 patients were entered. Group 1 was divided into 2 subgroups. 33 patients were treated locally without chemotherapy and 25 Patients were treated with local therapy and nonprotocol chemotherapy. Group 2 was treated with local therapy and plus T-2 regimen multiagent chemotherapy. 29 patients were entered. Group 3 was treated with local therapy and T-6 regimen multiagent chemotherapy. 38 patients were entered. Local treatments for primary tumor were surgery and/or radiation therapy. Radiation dose ranged between 2,000 and 8,000 rad. Patients with pulmonary metastases received bilateral pulmonary RT. Local recurrence rate was analyzed according to treatment groups and was $16.8\%$. Local 15 yr survival was $33\%$ and 8 yr survival of T-6 group was $64.9\%$. An analysis of time were pattern of recurrence of each group, and the correlation of with radiation dose with local recurrence done. This study concluded that intensive multiagent chemotherapy RT and/or surgery (T-6 regimen) reduced distant metastases, and produced significant increase in local control and survival.

• Radiation Oncology Journal
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• 제4권1호
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• pp.63-66
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• 1986

흉폐부위에서 발생하는 악성소세포종양은 1979년 Askin이 보고했고 이를 Askin종양이라고 부른다. Askin종양은 상당히 희귀하며 흉벽에 연조직이나 폐가장자리에서 잘 생기며 특히 젊은 층에 호발한다. 임상적, 병리학적으로 Ewing's sarcoma와 Rhabdomyosarcoma와 상당히 흡사하나 정밀한 전자현미경 관찰시 병리학적으로 별개에 종양으로 간주되었다. Askin종양은 국소재발이 많고 전신으로 잘 터지지 않는 경향이 있으나 생존율은 상당히 나쁜 것으로 되어 있다. 임상적으로나 병리학칙으로 Askin종양에 해당되는 24계 환자를 치료결과와 더불어 보고한다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2967-2971
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• 2013

Background: Extraskeletal Ewing sarcoma (EES)/primitive neuroectodermal tumours (PNET) are rare soft tissue sarcomas. Prognostic factors and optimal therapy are still unconfirmed. Materials and Methods: We performed a retrospective analysis on patients to explore the clinic characteristics and prognostic factors of this rare disease. A total of 37 patients older than 15 years referred to our institute from Jan., 2002 to Jan., 2012 were reviewed. The characteristics, treatment and outcome were collected and analyzed. Results: The median age was 28 years (range 15-65); the median size of primary tumours was 8.2 cm (range 2-19). Sixteen patients (43%) had metastatic disease at the initial presentation. Wide surgical margins were achieved in 14 cases (38%). Anthracycline or platinum-based chemotherapy was performed on 29 patients (74%). Radiotherapy was delivered in 13 (35%). At a median follow-up visit of 24 months (range 2-81), the media event-free survival (EFS) and overall survival (OS) were 15.8 and 30.2 months, respectively. The 3-year EFS and OS rates were 24% and 43%, respectively. Metastases at presentation and wide surgical margins were significantly associated with OS and EFS. Tumour size was significantly associated with OS but not EFS. There were no significant differences between anthracycline and platinum based chemotherapy regarding EFS and OS. Conclusions: EES/PNET is a malignant tumour with high recurrence and frequent distant metastasis. Multimodality therapy featuring wide surgical margins, aggressive chemotherapy and adjuvant local radiotherapy is necessary for this rare disease. Platinum-based chemotherapy can be used as an adjuvant therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제38권1호
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• pp.29-37
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• 2012

Introduction: Fibrous-osseous lesions of the jaws are difficult to diagnose precisely until excised biopsy results are found, so they might be confused with malignant lesions. This clinical study focused on the diagnostic aids of lesions that demonstrate different clinical, radiologic, and histological findings. Materials and Methods: A total of 16 patients with benign fibrous-osseous lesions on the jaws (6 fibrous dysplasias, 6 ossifying fibromas, 3 cemental dysplasias, and one osteoblastoma) were reviewed. Nine patients with malignant fibrous-osseous lesions (8 osteosarcomas and one Ewing's sarcoma) were also retrospectively reviewed. Results: Osteosarcoma patients complained of facial swelling and tooth mobility. The radiographic findings showed the irregular resorption of cortical bone and periosteal reactions. Histological features included cellular pleomorphism and atypical mitosis. An Ewing's sarcoma patient complained of tooth mobility and facial swelling. Onion-skin appearance and irregular expansile marginal bony radiolucency were seen in the radiography. Fibrous dysplasia patients complained of facial swelling and asymmetry. The radiographic features were mostly ground-glass radiopacity. Histological findings showed a bony trabeculae pattern surrounded by fibrous ground substances. Ossifying fibroma patients complained of buccal swelling and jaw pains, showing expanded cortical radiolucent lesions with a radiopaque margin. Histological findings were revealed as cellular fibrous stroma with immature woven bones. In cemental dysplasia, most of their lesions were found in a routine dental exam. Well-circumscribed radiopaque lesions were observed in the radiography, and cementum-like ossicles with fibrous stroma were seen in the microscopy. An osteoblastoma patient complained of jaw pain and facial swelling. Radiographic findings were mottled, dense radiopacity with osteolytic margin. Trabeculae of the osteoid with a vascular network and numerous osteoblasts with woven bone were predominantly found in the microscopy. Conclusion: Our study showed similar results as other studies. We suggest the clinical parameters of diagnosis and treatment for malignant and benign fibrous-osseous lesions of the jaws.

• Clinical and Experimental Pediatrics
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• 제56권9호
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• pp.401-406
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• 2013

Purpose: We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors. Methods: We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study. Results: A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 months), respectively. At present, 4 patients are alive and 5 patients who experienced adverse events (2 metastasis, 2 local recur, and 1 progressive disease) survived for a median time of 2.8 months (range, 0.1 to 10.7 months). The 2-year survival after HDCT/autoPBSCT was $44.4%{\pm}16.6%$ and disease status at the time of HDCT/autoPBSCT tended to influence survival ($57.1%{\pm}18.7%$ of cases with CR vs. 0% of cases with non-CR, P=0.07). Conclusion: Disease status at HDCT/autoPBSCT tended to influence survival. Further studies are necessary to define the role of HDCT/autoPBSCT and to identify subgroup of patients who might benefit from this investigational treatment.

• Journal of Chest Surgery
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• 제7권1호
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• pp.61-66
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• 1974

Primary tumors of the chest wall are rare than those of other portions of the body. Soft tissue tumors of the chest wall, though these are benign or malignant, should not be paid special attentions about their management than other soft tissue tumors of the body. Thoracic skeletal tumors, however, have some problems in the treatment because of defect in chest wall leading to herniation of lung and paradoxical movement of thoracic cage. The authors experienced 10 case of primary chest wall tumors at the department of thoracic and cardiovascular surgery, the national medical center, during last 15 years. Five of 10 cases were soft tissue tumors, and they were 2 case of lipoma and each one case of myxosarcoma and leiomyosarcoma. Among 5 bone tumors there no cases of sternal tumor, and their histopathological diagnosis were each one of fibrous dysplasia, giant cell tumor, osteochondroma, Ewing`s sarcoma and osteogenic sarcoma. Wide excision, though it was palliative one in certain case, was performed in 9 cases and only diagnostic incisional biopsy in one case, There were no postoperative deaths during admission to the hospital and all cases were missed during short term follow up after discharge from the hospital.

• Advances in pediatric surgery
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• 제5권1호
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• pp.45-52
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• 1999

Pediatric solid tumors have many histologic similarity. These tumors contained small round cell types, and cause frequent diagnostic problems in pediatric pathology. An important advance in the differentiation of these small round cell tumors has been the identification of consistent chromosomal translocations associated with several types of tumors. Eighteen patients with soft tissue sarcoma were available for review. Seventeen cell lines were also included in this study. The RNA from the specimens were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). PAX3-FKHR fusion was present in four of five alveolar rhabdomyosarcoma and PAX7-FKHR fusion was detected in one of five alveolar rhabdomyosarcoma. None of the specimens expressed more than one chimeric transcript. EWS-FLI1 or EWS-ERG fusions were detected in all seven Ewings' sarcoma. No specimens showed EWS-WT1 fusion. These results corresponded well to the histopathologic diagnosis. There were no differences in the histologic appearances of tumors with the more frequent PAX3-FKHR or EWS-FLI1 fusions compared with those containing the variant PAX7-FKHR or EWS-ERG fusions. RT-PCR assay for chimeric transcript is a useful tool for rapid and objective diagnosis of pediatric solid tumors. Through these tools, we can approach genetically to the differential diagnosis of undifferentiated small round tumors.

• 대한핵의학회지
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• 제29권1호
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• pp.73-78
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• 1995

본 연구는 원발성 악성 골종양의 감별진단에 대한 $^{99m}Tc$-MDP 골스캔의 임상적인 유용성을 알아보기 위해 시행하였다. 골조직검사로 원발성 악성골종양으로 진단받았고 골조직검사 전에 $^{99m}Tc$-MDP 골스캔을 하였던 골육종 22예, 연골 육종 5예, 유잉 육종 4예의 총 31예의 환자들을 대상으로 각각의 악성골종양의 공통적인 소견을 관찰하여 이를 방사선학적 검사와 비교하였고, 골육종에서는 조직학적인 간질조직의 형성에 따라 골아세포성, 연골아세포성, 섬유아세포성, 모세혈관 확장성으로 분류하여 골스캔소견과 비교하였다. 골육종에서 공통적인 소견은 강한 방사능 섭취와 동반된 내부의 불규칙한 방사능감소와 골윤곽의 심한 변형으로 22예 중 16예에서 나타났고 조직학적 분류에 따른 차이점은 발견할 수 없었다. 연골 육종에서 공통적인 소견은 정상보다는 증가되었지만 천장관절보다 약한 방사능섭취와 내부의 불규칙한 방사능증가, 비교적 잘 유지된 골윤곽으로 5예중 3예에서 관찰되었다. 유잉 육종에서 공통적인 소견은 천장관절보다 높은 방사능 섭취와 내부의 균일한 방사능 분포, 중등도의 골윤곽 변형으로 4예중 3예에서 관찰되었다. 결론적으로 악성골종양 3예에서 각각 특징적 소견을 나타내는 경향이 있고 환자의 임상적 정보와 방사선학적 소견을 참고하면 감별진단에 도움이 되었다. 그러므로 이에 대한 관심을 갖고 판독하는 것이 중요하다고 생각된다.