• Korean Journal of Head & Neck Oncology
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• v.19 no.1
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• pp.25-33
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• 2003

Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.113-118
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• 2022

Gadolinium neutron capture therapy (Gd-NCT) is a precision radiation therapy that kills cancer cells using the neutron capture reaction that occurs when ¹⁵⁷Gd hits thermal neutrons. ¹⁵⁷Gd has the highest thermal neutron capture cross section of 254,000 barns among stable isotopes in the periodic table. Another stable isotope, ¹⁵⁵Gd, also has a high thermal neutron trapping area (~ 60,700 barns), so gadolinium that exists in nature can be used as a Gd-NCT drug. Gd-NCT is a mixed kinetic energy of low-energy and high-energy ionizing particles, which can be uniformly distributed throughout the tumor tissue, thereby solving the disadvantage of heterogeneous dose distribution in tumor tissue. The Gd complexes of small-sized molecule are widely used as contrast agents for magnetic resonance imaging (MRI) in clinical practice. Therefore, these compounds can be used not only for diagnosis but also therapy when considering the concept of Gd-NCT. This multifunctional trial can look forward to new medical advance into NCT clinical practices. In this review, we introduce gadolinium compounds suitable for Gd-NCT and describe the necessity of image guided Gd-NCT.

• Journal of Korean Neurosurgical Society
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• v.54 no.3
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• pp.261-264
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• 2013

We report a long-term survival case of a primary malignant intracerebral nerve sheath tumor (MINST) occurring in the right frontal lobe of a 13-year old boy. After the gross total resection (GTR), we have performed radiation therapy but it recurred 50 months after the surgery, so the second GTR was performed. Later, second tumor recurrence was found 4 months after the second surgery. Subsequently the third GTR, radiotherapy, and chemotherapy were carried out. At present, the patient has been remaining alive for 77 months without evidence of tumor recurrence. According to the previous reports, the primary MINST is very rare : there are only 8 cases reported. It is also a fast-growing, invasive tumor with poor outcome. This is the first case that had no recurrence for 50 months after the surgery among the reported cases that had been followed up for more than 5 years. It is supposed that a period of recurrence free survival after GTR and low mitotic activity are associated with the patient's prognosis. A GTR followed by adjuvant radiation therapy and chemotherapy will be recommended to patients of MINST.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.39-45
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• 2000

We have investigated the efficacy of liposome encapsulated N-(phosphonacetyl)-L-aspartic acid (PALA) for the treatment of the C-26 murine colon tumor in Balb/c mice, and have compared it in this regard to free PALA. Healthy female Balb/c mice and C-26 tumor inoculated mice were randomized for the maximum tolerated dose (MTD) study and the in vivo therapy study, and the survival was measured after a single intraperitoneal injection of the drug. The maximum tolerated dose for intraperitoneally administered drug was found to be 750 mg/Kg for free PALA, and was greater than the maximum dose possible (150 mg/Kg) for PALA encapsulated in both DSPC and DSPG liposomes. When drug was administered one day after tumor implantation, 150 mg/Kg of PALA in DSPG liposomes increased the percentage of tumor bearing mice surviving at day 36 from 8% (buffer control) to 88%. In contrast, 150 mg/Kg free PALA increased the day 36 surviving percentage to only 25%. A 150 mg/Kg dose of PALA in DSPC liposomes increased the surviving percentage to 50%, while a 75 mg/Kg dose of PALA in sterically stabilized liposomes increased the surviving percentage to 78%. These results show that PALA in negatively charged or sterically stabilized liposomes can exhibit considerably greater potency than free PALA in C-26 tumor bearing mice.

• Biomedical Science Letters
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• v.25 no.4
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• pp.293-301
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• 2019

Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.229-240
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• 1999

Background: The impact of the immune response on cancer gene therapy using viral vectors to deliver a "suicide gene" is currently unclear. A vigrous immune response targeted at viral proteins or transgene may enhance the efficacy of tumor destruction and even augment responses to tumor antigens. These responses may involve the release of cytokines and stimulation of tumor specific cytotoxic T-lymphocytes that enhance therapeutic efficacy. On the other hand, a vigorous rapid cellular immune response may destroy cells expressing the therapeutic gene and attenuate the response to therapy. Furthermore, development of neutralizing antibody responses may prevent readministration of virus, a potentially significant limitation. Evaluating the significance of these limitations in animal models and developing solutions are therefore of obvious importance. Methods: After retroviral transduction of mouse mesothelioma cell line(AB12) with Herpes Simplex Virus thymidine kinase (HSVtk) gene in vitro, subcutaneous flank tumors were established. To study the effect of intact immune system on efficacy of tumor erradication, the ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Balb/c mice, immunodeficient Balb/c-nude and SCID mice, and Balb/c mice immunosuppressed with cyclosporin. Results: Ganciclovir treatment resulted in greater inhibition of tumor growth in Balb/c mice compared with immunodeficient Balb/c-nude mice and SCID mice(in immunodeficient mice, there were no growth inhibition by ganciclovir treatment). Ganciclovir treatment resulted in greater inhibition of tumor growth in noncyclosporin (CSA) treated Balb/c mice compared with CSA treated Balb/c mice. On day 8, mean ganciclovir-treated tumor volume were 65% of control tumor volume in Balb/c mice versus 77% control tumor volume in CSA-treated Balb/c mice. This effect was still evident during therapy (day 11 and 13). On day 13, non-CSA treated tumor volume was 35% of control tumor volume versus 60% of control tumor volume in CSA treated Balb/c mice. Duration of expression of HSVtk was not affected by the immunosuppression with CSA. Conclusion: These results indicate that the immune responses against retrovirally transduced cells enhance the efficacy of the HSVtk/ganciclovir system. These findings have important implications for clinical trials using currently available retrovirus vectors as well as for future vector design.

• Journal of the Korean Society of Radiology
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• v.7 no.6
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• pp.409-414
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• 2013

In this study, we evaluated to the superiority of treatment techniques on prostate cancer, apply to each other treatment techniques-3D conformal therapy versus IMRT-using dose distribution and dose coverages. Obtained 10 patients CT simulation, divided tumor volume and critical organs. Prescription dose was 80 Gy on tumor volume and Each of plans was set by two different plans. As a result, Dose coverage was superior to IMRT. The IMRT's tumor absorbed dose(100.2%) was close to prescription doses. Normal tissue(bladder, rectal, bowel Lt Rt fumoral head) absorbed dose rate was superior. In other words, the radiation therapy of prostate cancer with intensity modulated radiation therapy was better than conformal radiation therapy on dose.

• The Journal of the Korean bone and joint tumor society
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• v.1 no.2
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• pp.210-219
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• 1995

Many different factors which may affect the prognosis of the soft tissue sarcomas have been reported by many authors ; Generally, tumor size, histologic type, surgical margin, and multi modality therapy therapy as the prognostic factors were reported. The objectives of this retrospective study of soft tissue sarcomas are : 1) to define more clearly prognostic variables that have significant predictive value for disease-free and overall survival ; and 2) to evaluate tumor histologic grade based upon extent of tumor necrosis as a means of stratifying more aggressive soft tissue sarcomas(grade II & III) of the extremities. We treated 94 patients who had soft tissue sarcoma of the extremities and trunk from May 1984 to September 1994(average duration of follow-up was 5 years ranging from 2 months to 10 years) and evaluated the prognostic factors of the soft tissue sarcomas; age, sex, depth, size, location, histologic type and grade, stage, therapy modality, surgical margin, local recurrence and distant metastasis. The results were as follows. 1. The patients with poorer prognosis were over the age of fifty, whose mass was deeply located, size of the mass was over 10cm in diameter, grade III in histology, who had local recurrence, metastasis, and received only surgery. 2. Among these prognostic factors, the most significant prognostic factor was histologic grade base upon extent of tumor necrosis.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.147-152
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• 2009

Ascorbate (vitamin C) is a cofactor for a number of metabolic enzymes and is an indisputable essential vitamin C for humans. However, the potential of ascorbate as an anticancer agent has been a topic of controversy. A number of previous reports have addressed both positive aspects and limitations of ascorbate in cancer therapy. In this review, we briefly summarize the potential antitumor effects of ascorbate and its prospects for clinical use.

• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.82-84
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• 2001

An 11 kg, 7-year-old male pug dog with lameness and tumor of the 2-3rd interdigital portion of the right forelimb was referred to the Veterinary Medical Center of the Tokyo University. On the clinical examination findings, the tumor size was $3{\times}3 cm but alopecia and necrosis were not found. On the radiological findings, a bone lysis was found in the phalanges of digit II of the right forelimb but pulmonary metastasis was not found. The mass was removed with metacarpal bone. Histopathological examination of the mass revealed highly differentiated hemangiopericytoma. Two weeks after the operation, the dog was irradiated by orthovoltage radiation. The source of irradiation was 300 kV, 4mA, 4Gy and a focal spot to skin distance of 40 cm using 1.0 Cu, 1.0Al filter. The radiation therapy was performed twice a week for 5 weeks. The dog showed no recurrence and no metastasis. It was thought that the surgery and radiation therapy treatment was quite a useful method to treat a canine heman-giopericytoma.