• 대한골관절종양학회지
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• 제2권1호
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• pp.38-46
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• 1996

The traditional methodology in Ewing's sarcoma was chemotherapy and radiotherapy. Recently surgery is reemerging as an important therapeutic tool and some paper report increased survival with it. The purpose of this nonrandomized study is to evaluate our result of Ewing's sarcoma with surgery, retrospectively. We experienced 30 cases for seven years and among them 6 were extraskeletal. In location, axial was 10 cases and peripheral was 20. By Enneking's classification, state IIB was 26 cases and IIIB was 4. Eighteen patients took operation, chemotherapy and/or radiotherapy, and remaining twelve took chemotherapy and/or radiotherapy only. Type of operation was limb salvage in 16 cases and amputation 2. Average dosage of radiation was 45.1Gy. Six kinds of chemotherapeutic regimen were used, but among them main protocols were Ifosfamide-Adriamycin(17 cases) and IESS(Cytoxan, Adriamycin, Methotrexate, Vincristine:8 cases). Complications were as follows. In operation group, there were 3 local recurrence and one case of nonunion. In nonoperated group, one local recurrence and one pancytopenia resulting in death. Average follow up was 29.7 months. Kaplan-Meier's ten year actuarial survival rate for the whole 30 cases was 26.8%. Significant difference in survival exists between central and peripheral lesions(p=0.05, by log rank test). Types of chemotherapy and surgery itself showed no significance. But surgery is important in function and local control. More intensive chemotherapeutic regimen to prevent distant metastasis and combined surgery and radiotherapy may be needed in Ewing's sarcoma.

• 대한골관절종양학회지
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• 제2권1호
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• pp.27-32
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• 1996

Recent advances in imaging techniques, surgery and combination anti-cancer chemotherapy have brought high survival rates in osteosarcoma. To investigate the survival rate, local recurrence and complications in treatment, we analysed 25 osteosarcoma cases who had been treated with preoperative neo-adjuvant chemotherapy, surgery and post operative chemotherapy at Department of Orthopedic Surgery, Catholic University. From May 1988 to April 1995, 42 cases of stage IIB osteosarcoma were admitted in Department of Orthopedic Surgery. Among them, 17 cases who didn't follow our treatment guidance were excluded in this study. The average age were 19 years. There were 21 males and 4 females. The involved sites were 4 humerus, 10 femur, 10 tibia and 1 talus. Eleven cases had received intraarterial cisplatin and intravenous adriamycin chemotherapy, and 7 T-10 protocol and 7 intravenous ifosfamide, ADR, methotrexate, cisplatin. Twenty-three cases were treated with limb salvage surgery, and 2 amputation. The average follow-up was 35 months(3~82). There were 14 cases of continuous disease free, 9 cases of died of disease, 1 case of alive with disease, and 1 case of no evidence of disease at final follow-up. There were three cases of local recurrence at 6,8 and 12 months after operation. The estimated Kaplan-Meier's 5 year survival rates for all, ADR-cisplatin group, T-10 protocol group, and ifosfamide regimen group were 6%, 73%, 44% and 72%, respectively.

• Journal of Korean Neurosurgical Society
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• 제58권1호
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• pp.1-8
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• 2015

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

• Journal of Korean Neurosurgical Society
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• 제59권6호
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• pp.590-596
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• 2016

Objective : Rheumatoid arthritis (RA) is a systemic disease that can affect the cervical spine, especially the atlantoaxial region. The present study evaluated the risk factors for atlantoaxial subluxation (AAS) development and progression in patients who have undergone surgical treatment. Methods : We retrospectively analyzed the data of 62 patients with RA and surgically treated AAS between 2002 and 2015. Additionally, we identified 62 patients as controls using propensity score matching of sex and age among 12667 RA patients from a rheumatology registry between 2007 and 2015. We extracted patient data, including sex, age at diagnosis, age at surgery, disease duration, radiographic hand joint changes, and history of methotrexate use, and laboratory data, including presence of rheumatoid factor and the C-reactive protein (CRP) level. Results : The mean patient age at diagnosis was 38.0 years. The mean time interval between RA diagnosis and AAS surgery was $13.6{\pm}7.0$ years. The risk factors for surgically treated AAS development were the serum CRP level (p=0.005) and radiographic hand joint erosion (p=0.009). The risk factors for AAS progression were a short time interval between RA diagnosis and radiographic hand joint erosion (p<0.001) and young age at RA diagnosis (p=0.04). Conclusion : The CRP level at RA diagnosis and a short time interval between RA diagnosis and radiographic hand joint erosion might be risk factors for surgically treated AAS development in RA patients. Additionally, a short time interval between RA diagnosis and radiographic hand joint erosion and young age at RA diagnosis might be risk factors for AAS progression.

• The Korean Journal of Physiology and Pharmacology
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• 제24권3호
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• pp.213-221
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• 2020

Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]-22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.

• Journal of Yeungnam Medical Science
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• 제33권1호
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• pp.64-67
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• 2016

We report on a 64-year-old man with leptomeningeal metastasis (LM) from an epidermal growth factor receptor (EGFR)-mutated adenocarcinoma of the lung. He was treated with paclitaxel, cisplatin. After completion of chemotherapy, he complained of headache, nausea, and vomiting. EGFR-mutated tumor cells were identified from the cerebrospinal fluid (CSF). Second-line therapy with gefitinib, methotrexate was started. After receiving gefitinib for 4 weeks, he had no more headaches or vomiting. Eleven months after initiation of gefitinib, he developed headache and nausea. Chest computed tomography showed aggravation of bone metastasis. Third-line therapy was started with gemcitabine and carboplatin. Two weeks later, he experienced disorientation. After a fourth relapse within the central nervous system, the therapy was switched to erlotinib and significant improvement of LM was achieved. This case shows that LM can be diagnosed by detecting EGFR mutation in CSF and EGFR tyrosine kinase inhibitors are effective for LM from EGFR mutant non-small cell lung cancer.

• Journal of Microbiology and Biotechnology
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• 제23권8호
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• pp.1176-1184
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• 2013

Anti-hepatocyte growth factor (anti-HGF) monoclonal antibodies (mAbs) are potential therapeutics against various cancers. Screening for high-producer clones is a time-consuming and complex process and is a major hurdle in the development of therapeutic mAbs. Here, we describe an efficient approach that allows the selection of high-producer Chinese hamster ovary (CHO) cell lines producing the novel anti-HGF mAb SFN68, which was generated previously by immunizing HGF bound to its receptor c-Met. We selected an SFN68-producing parental cell line via transfection of the dihydrofolate reductase-deficient CHO cell line DG44, which was preadapted to serum-free suspension culture, with an SFN68-expression vector. Subsequent gene amplification via multiple passages of the parental cell line in a methotrexate-containing medium over 4 weeks, followed by clonal isolation, enabled us to isolate two cell lines, 2F7 and 2H4, with 3-fold higher specific productivity. We also screened 72 different media formulated with diverse feed and basal media to develop a suboptimized medium. In the established suboptimized medium, the highest anti-HGF mAb yields of the 2F7 and 2H4 clones were 842 and 861 mg/l, respectively, which were about 10.5-fold higher than that of the parental cell line in a non-optimized basal medium. The selected CHO cell lines secreting high titers of SFN68 would be useful for the production of sufficient amounts of antibodies for efficacy evaluation in preclinical and early clinical studies.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6519-6524
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• 2014

The aim of this study was to evaluate the clinical outcomes of radical cystectomy (RC) and concurrent chemoradiotherapy (CRT) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with locally advanced bladder cancer (BC). From December 2000 to February 2012, 72 patients with locally advanced BC (T3-4a, N0 or N+, M0) received either RC or CRT. RC with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the CRT group received one cycle of MVAC followed by radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Standard fractionation at a daily dose of 1.8-2.0 Gy was used, with a median total dose of 50 Gy (range, 45-60 Gy). The 3-year progression-free survival (PFS) rates in the RC and CRT groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Multivariate Cox proportional hazards regression analysis with application of a propensity score indicated that RC was a significant predictor of PFS (p=0.033) but not of OS (p=0.291). Among patients with locally advanced BC, PFS was significantly prolonged in the RC group compared with the CRT group. However, RC was not a significant predictor of OS. Although the sample size in this study was small, the results suggest that patient background and postoperative quality of life should be considered when choosing treatment strategy for locally advanced BC.

• Radiation Oncology Journal
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• 제30권4호
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• pp.165-172
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• 2012

Purpose: To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Materials and Methods: Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. Results: With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. Conclusion: In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9355-9360
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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. In this study, we evaluate the efficacy of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting HER2 expression profile in OSCC model in rat. Results: DOX-MTX- nanoparticle complexes caused significant decrease in mRNA level of HER2 compared to untreated cancers (p<0.05) and this finding was more pronounced with the IV mode (p<0.000). Surprisingly, HER2 mRNA was not affected in DOX treated as compared to the control group (p>0.05). On the other hand, in the DOX-MTX NP treated group, fewer tumors characterized with advanced stage and decreased HER2 paralleled improved clinical outcome (P<0.05). Moreover, the effectiveness of the oral route in the group treated with nanodrug accounted for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Furthermore, there was no significant difference in mRNA level of HER2 (p>0.05). Conclusions: Influence of HER2 gene expression is a new feature and mechanism of action observed only in dual action DOX-MTX-NPs treated groups. Down-regulation of HER2 mRNA as a promising marker and prognosticator of OSCC adds to the cytotoxic benefits of DOX in its new formulation. Both oral and IV application of this nanodrug could be used, with no preferences in term of their safety or toxicity. As HER2 is expressed abundantly by a wide spectrum of tumors, i DOX-MTX NPs may be useful for a wide-spectrum of lesions. However, molecular mechanisms underlying HER2 down regulation induced by DOX-MTX NPs remain to be addressed.