• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Journal of Chest Surgery
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• v.56 no.1
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• pp.25-32
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• 2023

Background: We reviewed the clinical outcomes of patients with oligometastatic (OM) non-small cell lung cancer (NSCLC) who received multimodal therapy including lung surgery. Methods: We retrospectively analyzed 117 patients with OM NSCLC who underwent complete resection of the primary tumor from 2014 to 2017. Results: The median follow-up duration was 2.91 years (95% confidence interval, 1.48-5.84 years). The patients included 73 men (62.4%), and 76 patients (64.9%) were under the age of 65 years. Based on histology, 97 adenocarcinomas and 14 squamous cell carcinomas were included. Biomarker analysis revealed that 53 patients tested positive for epidermal growth factor receptor, anaplastic lymphoma kinase, or ROS1 mutations, while 36 patients tested negative. Metastases were detected in the brain in 74 patients, the adrenal glands in 12 patients, bone in 5 patients, vertebrae in 4 patients, and other locations in 12 patients. Radiation therapy for organ metastasis was performed in 81 patients and surgical resection in 27 patients. The 1-year overall survival (OS) rate in these patients was 82.8%, and the 3- and 5-year OS rates were 52.6% and 37.2%, respectively. Patients with positive biomarker test results had 1-, 3-, and 5-year OS rates of 98%, 64%, and 42.7%, respectively. These patients had better OS than those with negative biomarker test results (p=0.031). Patients aged ≤65 years and those with pT1-2 cancers also showed better survival (both p=0.008). Conclusion: Surgical resection of primary lung cancer is a viable treatment option for selected patients with OM NSCLC in the context of multimodal therapy.

• Clinical and Experimental Pediatrics
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• v.51 no.1
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• pp.78-83
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• 2008

Purpose : Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Although survival rate of osteosarcoma patients has markedly improved, about 20-30% of patients still have a relapse. This study was aimed to find factors that influence postrelapse survival of osteosarcoma in childhood and adolescents. Methods : Between 1985 and 2004, of 461 patients who were diagnosed and treated as osteosarcoma in Korean Cancer Center Hospital, 180 patients with recurrent osteosarcoma were retrospectively reviewed. We examined survival rates and analyzed prognostic factors, such as relapse site, post-relapse treatment methods, pathologic response to neoadjuvnat chemotherapy, metastasis at first diagnosis, and relapse free interval. Results : The overall recurrence rate of patients with osteosarcoma was 39%. The 5-year and 10-year postrelapse survival rates in the recurrent osteosarcoma were 13% and 4%, respectively. The 5-year post-relapse survival rate was influenced by site of relapse (lung, 39%; local, 0%; lung & bone, 25%; others, 12%; P<0.05), relapse-free interval (<12 months, 13%; ${\geq}12$ months, 44%, P<0.05), and post-relapse treatment methods (with surgery, 38%; without surgery, 11%; P<0.05). Conclusion : The survival rate of recurrent case is very low after 10 years, so new second-line chemotherapy and active treatment is needed to increase survival. Aggressive surgery with the removal of recurrence sites combined with multi-agent chemotherapy could either cure patients with recurrent osteosarcoma or significantly prolong their survival.

• The Journal of the Korean bone and joint tumor society
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• v.6 no.1
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• pp.1-9
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• 2000

Purpose : Spine is one of the most common sites of the metastatic bone tumors. Conservative management such as chemotherapy or radiotherapy has been preferred in most cases. However, the neurologic deficit has not been usually improved, and the quality of life was poor. The purpose of this study was to show the efficacy of the surgical treatments for metastatic spinal tumors in terms of postoperative improvements of neurologic deficit and survival time. Materials and Methods : Authors have reviewed the literatures and analyzed 14 patients of metastatic spinal tumors who were received operative treatments between August 1991 and June 1999 at the our department of orthopaedic surgery. Results : The most frequent primary tumor was breast cancer in women and lung cancer in men. The thoracic region was the most common site. There was a preponderance of females over males, and the age ranged between 4th and 8th decade. The indications of surgical treatment comprised instability, progressive neurologic findings, resistance to radiotherapy, pathological fracture, long life expectancy( >6weeks), isolated metastasis and need for pathological diagnosis. The degree of preoperative neurological deficit might influence on the improvement of clinical symptoms after surgery. Conclusion : The surgical treatment reduced the neurological deficit and pain regardless of the operative methods. In the early stage of neurological deficit, the surgical treatment was important for better prognosis. Recently early active operative treatment was performed for metastatic spinal tumor to minimize the intractable pain and to prevent the progression of the neurologic deficit. Early intervention can improve the quality of life and long term survival.

• The Journal of the Korean bone and joint tumor society
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• v.12 no.1
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• pp.1-8
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• 2006

Purpose: To analyze the clinical outcome of stage IIB osteosarcomas arisen in the long bones. Materials and Methods: Since February 1993, 58 Enneking stage IIB osteosarcomas arisen in long bones were managed and followed at least one year at our four university hospitals. There were 48 wide resections, 2 marginal resections and 8 amputations. The mean follow up period was 4.1years (up to 12.2years). Local recurrence, distant metastasis, complication, survival rate, and oncologic and functional results were evaluated. Results: At the last follow up, 35 patients were CDF, 9 were NED, 5 were AWD, 7 were DOD and the remained 2 died with unrelated disease. Eight local recurrences (13.8%) and 18 distant metastases (31.0%) were occurred. Nine infections were developed after 48 reconstructions (18.8%). Overall functional outcome was 24.3 (81.%). The 5 year overall survival rate was 84.6% and the continuous disease-free survival rate was 68.7% at 5 years and 42.3% at 10 years. Conclusion: Forty-six of 58 stage IIB osteosarcomas arisen in long bones (79.3%) showed CDF or NED at an average 4.1 year follow up. Overall 5-year survival rate was 84.6% and overall functional outcome score was 24.3, which were comparable to those of other studies.

• The Journal of the Korean bone and joint tumor society
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• v.16 no.1
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• pp.1-7
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• 2010

Purpose: With advances in various treatment modalities, limb salvage surgery has been commonly used in osteosarcoma of extremities. An alternative method for skeletal reconstruction is reimplantation of the tumor bearing bone following extracorporeal irradiation (ECI). We report the long-term results of ECI autograft in aspect of the oncological and functional outcomes, and complications. Materials and Methods: We retrospectively reviewed 31 osteosarcoma patients who underwent reconstruction with ECI between July 1995 and January 2006. There were 24 males and 7 females with a mean age of 24 (7-74 years) and a mean follow-up of 117 months (17-177 months). Twenty-five cases were reconstructed with ECI autograft, 6 cases with ECI autograft-prosthesis composite. The pathologic subtypes were conventional in 29 cases, periosteal in 1 case, and parosteal in 1 case. The most common location of tumor was distal femur (15 cases) followed by humerus (3), proximal fibula (3) and proximal tibia (3). Musculoskeletal Tumor Society (MSTS) score was used for functional evaluation. The overall survival rate, local recurrence, complications were analyzed. Results: The overall survival rate was 80.6% and the disease-free survival rate was 64.5%. Five patients died of distant metastasis. One patient required above-knee amputation due to local recurrence. All of them, twenty-three complications occurred, which included nonunion in 7 cases, deep infection in 5 cases, joint instability in 4 cases, metal failure in 2 cases, Limb-length discrepancy (LLD) in 2 cases, periprosthetic fracture in 1 case, epiphyseal collapse in 1, local recurrence in 1 case. The mean MSTS functional score was 62.5%. Conclusion: Extracorporeal irradiated autograft can be achieved relatively good result in aspect of oncological and functional aspect, but is needed to be additional research about occurring many complications. The reconstruction with ECI after intercalary or fragmentary resection is effective reconstruction in aspect of oncological and functional result, complications.

• Journal of Yeungnam Medical Science
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• v.22 no.1
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• pp.72-80
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• 2005

Background: Nasopharyngeal cancer is a rare disease with a relatively poor prognosis because it tends to be diagnosed at an advanced stage. The aim of this study was to establish the clinical characteristics of nasopharyngeal cancer. Materials and Methods: The medical records of 54 patients with nasopharyngeal cancer from January 1993 to December 2002 were reviewed retrospectively. Forty one cases were male (75.9%) and thirteen were female (24.1%). The average age was of 46.9 (range 16 to 78 years) years. The majority of patients (79.6%) were diagnosed in the advanced stage. The most common complaints were a neck mass (55.5%) and the WHO type III (53.7%) was the most frequent histological type. Results: The cumulative survival rate for a 5-year period was 46.5% and the T stage, N stage, pathologic type, and clinical stage were not significantly related to the survival rate. Sixteen of 54 (31.5%) cases presented with a distant metastasis of the bone, lung, brain, spine, and liver, and six cases (11.1%) presented with a locoregional recurrence. Conclusion: TNM staging is not appropriate for predicting survival rate of nasopharyngeal carcinoma patients. Therefore, a newer staging system, which includes new factors, is needed to predict the prognosis.

• Korean Journal of Head & Neck Oncology
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• v.10 no.1
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• pp.13-24
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• 1994

Despite optimal local therapy such as surgery and/or radiotherapy, the long term outcome is poor for patients with advanced squamous cell carcinomma of head and neck, due to frequent loco-regional recurrence and distant metastases. We studied to determine whether the combination chemotherapy, especially as an adjuvant chemotherapy, would improve the survival of these patients. Between January, 1986 and December, 1992, 57 patients with previously untreated, locally advanced squamous cell arcinoma of head and neck were assigned to receive 2-3 cycles of induction chemotherapy consisting of 5-fluorouracil(F) and cisplatin(P) every 3 weeks and standard local therapy such as surgery and/or radiotherapy followed by adjuvant chemotherapy with the same FP regimens. Of the 57 enroled patients, 45 patients were evaluable. The obtained results were as following: 1) Among 45 evaluable patients, 18 patients finished all treatment protocol including adjuvant chemotherapy and 27 patients had no adjuvant chemotherapy. The difference of age, sex, performance status, disease stage, and tumor differentiation was not significant statistically between adjuvant chemotherapy group and no-adjuvant chemotherapy group. 2) After induction chemotherapy, 7/45(15.4%), 30/45(67%) achieved complete remission and partial remission respectively with 82.4% overall response rates in entire patients. 3) The 4year progression free survival was 43.3% in adjuvant chemotherapy group and 24.1% in no-adjuvant chemotherapy group(p>0.05). The 4year overall survival was 56.9% and 25.5% respectively(p>0.05). There was no significant different in the patterns of local recurrence and distant metastasis between the two groups. 4) Adverse reactions from combination chemotherapy included nausea, vomiting, mucositis, diarrhea and hematologic bone marrow depression. These were mild and tolerated by patients, and these was no episode of any life threatening toxicities. In conclusion, adjuvant chemotherapy after induction chemotherapy and local therapy did not show statistically significant survival improvement, but there was trend of prolongation of survival when compared to no adjuvant chemotherapy. Thus, large scale phase III randomized controlled studies are strongly recommended.

• The Journal of the Korean bone and joint tumor society
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• v.14 no.1
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• pp.33-43
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• 2008

Purpose: To evaluate the clinical usability of reconstructive methods, and how to select flap after wide excision of malignant soft tissue tumor in ankle and foot. Materials and Methods: The 15 cases shown in the 14 patients (In case of a male patient, reconstruction was performed two times due to local recurrence.) with malignant soft tissue tumor in ankle and foot, who underwent reconstruction after wide excision from March 2000 until March 2007. Oncologic, surgical and functional results were evaluated. Results: The method of reconstruction used were anterolateral thigh perforator flap (5cases), Reversed superficial sural artery flap (4 cases), dorsalis pedis flap (3 cases), local flap (3cases). The defect, mean size was $5.5{\times}5.7\;cm$, was reconstructed with rotation flap or free flap, mean size was $5.9{\times}6.0\;cm$, skin graft for remnant. The mean operation time was 310 minutes (120~540 minutes); it took 256 minutes to reconstruct by rotation flap, and 420 minutes by free flap. As oncologic results, 7 patients were no evidence of disease, 6 patients were alive with disease and 1 patient was expired by pulmonary metastasis at the time of the last follow-up. 4 patients had local recurrence and 4 pateints had distant metastases. As functional results, 14 patients were evaluated with average score of 68.8% using the system of the Musculoskeletal Tumor Society. Conclusion: The dorsalis pedis and reverse superficial sural artery rotation flap which is easy procedure, has less complication and takes short operation time, can be primarily considered to reconstruct a small defect. And the anterolateral thigh perforator flap is suitable for coverage of a large defects after wide excision of malignant soft tissue tumor in ankle and foot.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.1
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• pp.1-11
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• 2003

Purpose: To analysis of the result of the treatment of metastatic diaphyseal fracture of the humerus with closed interlocking intrameduallry nailing. Materials and Methods: Among surgically treated 29 patients with pathologic or impending fracture of diaphysis of the humeurs, 13 patients (16 cases) treated with closed intramedullary interlocking nail were selected for the study. The final result of pain relief and functional recovery was evaluated by modified rating system of Perez et al. Results: Primary cancer was diagnosed after fracture was developed in 2 patients and pathologic or impending fracture was occurred average period of 28.9 months after primary cancer was diagnosed. The main primary malignancies were multiple myeloma, lung cancer and breast cancer. Mean survival after humeral metastasis was 11.7 months. The final result was superior to fair in 13 of 16 cases, and poor in 3 cases with progression of tumor spread or distant dissemination to the ipsilateral fingers. Except the latter 3 patients and other 3 patients, who died before 3 months postoperatively, bony union was achieved in 10 cases. There were no complications related to surgery. Conclusion: Closed interlocking intrameduallry nailing is accomplished with brief operative time, small amount of bleeding and provides immediate stability with resultant early return of function to the arm. Additionally it allows early postoperative irradiation. However, some of our cases shows that intramedullary nailing can accelerate tumor spread and metastases elsewhere, so that serious consideration must be given in planning this treatment. In conclusion, the functional status before fracture, life expectancy, type of tumor and extent of involvement should be carefully considered to decide operative treatment of metastatic disease.