• Archives of Pharmacal Research
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• v.25 no.1
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• pp.93-101
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• 2002

The extract of European mistletoe ( Viscum album, L) has been used in adjuvant chemotherapy of cancer and mistletoe lectins are considered to be major active components. The present work was performed to investigate the effects of Korean mistletoe lectin (Viscum album L. coleratum agglutinin, VCA) on proliferation and apoptosis of human hepatoma cells as well as the underlying mechamisns for these effects. We showed that VCA induced atoptosis in both SK-Hep-1 and Hep 3B (p53-negative) cells through p53- and p21 -independent pathways. VCA induced apoptosis by down-regulation of Bcl-2 and by up-regulation of Bax functioning upstream of caspase-3 in both cell lines. In addition, we observed down-regulation of telomerase activity in both VCA-treated cells. Our results provide direct evidence of the anti-tumor potential of this biological response which comes from inhibition of telomerase and consequent inducing apoptosis. VCA-induced apoptosis is regulated by mitochondria controlled pathway independently of p53. These findings are important for the therapy with preparation of mistletoe because they show that telomerase-dependent mechanism can be targeted by VCA in human hepatocarcinoma. Taken together, our results suggest that the VCA, considered as a telomerase-inhibitor, can be envisaged as a candidate for enhancing sensitivity of conventional anticancer drugs.

• Molecules and Cells
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• v.37 no.5
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• pp.357-364
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• 2014

Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma.

• Progress in Medical Physics
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• v.23 no.3
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• pp.169-176
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• 2012

Frameless method in brain radiosurgery has advantages relative to rigid head-frame method in terms of patient friendly and flexible application of multi-fractionation. However, it has also disadvantages and the most negative point is that it cannot control the patient motion during treatment as lowly as the level of the frame-based radiosurgery, which could affect to the treatment accuracy. In the present study, we analyzed the geometric uncertainty of the intra-fraction motion using the actual treatment records of 294-CyberKnife treatments for brain tumors. Based on the analysis, we statistically presented the magnitude of intra-fraction motion in frameless radiosurgy. The result could provide the quantitative information to determine the adequate treatment margins to compensate the intra-fraction movements.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.9-15
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• 1999

Purpose : This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer, Materials and Methods : Firty-six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deli- ver 44 Gy using 1 OMV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylaetic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. Results : The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved En 30 (65$\%$) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50$\%$), anemia in 17 (37$\%$), thrombo- cytopenia in nine (20$\%$), alopecia in nine (20$\%$), nausea/vomiting in five (11$\%$), and peripheral neuropathy in one (2$\%$). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24$\%$) out of the total 246 cycles. No radiation esophagitis over grade 111 was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The overall and progression-free survival rates were 79$\%$ and 55$\%$ in 1 year, and 45'/) and 32% in 2 years, respectively, and the median survival was 23 months. Conclusion : Relatively satisfactory local control and suwival rates were achieved after the combined chemotherapy and radiation therapy with mild to moderate acute morbidities in limited disease small cell lung cancer.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.113-117
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• 2012

FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5913-5916
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• 2015

Gestational trophoblastic neoplasia (GTN) is the malignant form of gestational trophoblastic disease. In non-metastatic GTN, the outcomes of treatment are impressive with methotrexate (MTX) or actinomycin D. We retrospectively reviewed the outcomes of non-metastatic GTN treated at our center from January, 1999 to December, 2013. One hundred and nine patients were recruited to the study. The median age was 33.1 years and over 90% were referral cases. Abnormal vaginal symptoms developed in 37.6% while 56.4% were asymptomatic. The most common antecedent pregnancy was a complete mole (92.7%) with the median interval time from antecedent pregnancy to GTN development being 2.0 months. The median pretreatment B-hCG was 5,624 mIu/ml. The most common first line treatment was methotrexate (MTX) and folinic acid (91.7%) followed by weekly MTX (4.6%), etoposide+ MTX+actinomycin D (EMA) (2.8%), and actinomycin D (0.9%), with the median number of cycles at 5.0. The positive response to first line chemotherapy was 73.8%. The patients were given subsequent chemotherapeutic regimens after resistance to the first line therapy and showed a final remission rate of 89.9%.The significant factor that was frequently found in patients who were non-responders to the first line treatment was a hysterectomy procedure. Two patients developed lung metastasis and brain metastasis at one and four years after the first treatment, respectively. In conclusion, the outcomes of non-metastatic GTN were excellent. However, the patients need long term follow up due to the possibility of developing multiple organ metastases.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.1013-1024
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• 1989

One hundred and seventy two patients of primary lung cancer, confirmed by tissue diagnosis at the Dept. of Thoracic and Cardiovascular Surgery in Korea University Hospital between June 1973 and August 1988, were evaluated and restaged with New International TNM classification, and the actuarial survival rate was obtained using Kaplan-Meier equation. The results of analysis were as follows. 1. Male to female ratio was 3.8:1, and prevalent age groups were sixth and seventh decades [76.4 %]. 2. The most common subjective symptom was cough [55.2 %], and 67.4 % of all patients were visited to hospital less than 6 months of symptoms. 3. Positive rates for tissue diagnosis were 100% in open chest or metastatic lymph node biopsy, 80 % in mediastinoscopic biopsy, 60 % in pleural biopsy, 59 % in pleural fluid cytology, 36% in bronchoscopic biopsy, and 22 % in sputum cytology. 4. The order of frequency of cell type was squamous cell carcinoma [53.0%], adenocarcinoma [22.0 %], small cell carcinoma [14.5 %], and so on. 5. Operability and resectability were 44% and 62% respectively, but they were improved recently. 6. Open and closure was done in 44 % of operated patients, uni or bilobectomy in 38 % and pneumonectomy in 24 %. 7. Overall operative mortality rate was 2.6 %. 8. The order of frequency of stage level was S3b [42.0 %], S3a [25.1 %], S1 [15.6%], and so on. 9. Distant metastasis, i.e. stage 4, was noted in 9.5 % of cases, and the sites of frequency were bone, brain, skin, and so on. 10. Actuarial survival rate was 1 year 48.2%, 2 year 36.9%, 3 year 31.2%, and 5 year 20.8%. According to above listed factors, 5 year survival rate was highest in squamous cell carcinoma, lobectomized cases, stage 1, NO in TNM system, and resectable cases. But T factor in TNM system and radiation therapy in nonresectable cases did not show statistical significance in life expectancy.

• Journal of Hospice and Palliative Care
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• v.10 no.2
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• pp.74-77
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• 2007

Purpose: We evaluated how many patients received radiotherapy and how many those of them could not complete radiation therapy in Hospice Ward. Methods: We retrospectively reviewed the general characteristics in 33 patients who began to receive palliative radiation therapy, and radiation dose and reasons of not-completing radiation therapy in Hospice Ward of St. Vincent's Hospital. Results: Thirty three (8.2%) among 404 patients who had been admitted from November 2003 and October 2005 received palliative radiation therapy. The main indications of radiation therapy included brain metastasis, painful bone metastasis, painful tumor mass, and obstructive shortness of breath. Forty five percent of these patients could not complete. And 20% could receive less than 1/3 of planned radiation dose. They failed to complete the treatment often due to poor general rendition. Conclusion: Although palliative radiation therapy had been used frequently for patients with advanced cancer in Hospice Ward of St. Vincent's Hospital, but it was often not completed. With appropriate selection criteria of patients and shorter modification of radiation treatment period, more patients would be benefited with palliative radiation therapy in Hospice Ward.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.873-876
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• 2016

Background: Studies of quality of life (QoL) of oncological patients is carried out using questionnaires approved in many international clinical studies. The European Organization for Research and Treatment of Cancer EORTC QLQ-C30 (Quality of Life Questionnary-Core 30) and its special brain cancer module EORTC QLQ-BN20 are widely used in the world neurooncologic practice. They are available in more than 80 official versions of 30 languages of the world. Previously we used the official versions in Russian, which often causes difficulty in understanding for native Kazakh language speakers, who comprise more than 60% of our respondents. This was the reason for creating a version of Kazakh language. Therefore, in 2014 for the first time the process of adaptation of questionnaires to the Kazakh language was initiated. Materials and Methods: The translation process of questionnaires to Kazakh language was held in accordance with the requirements of the European Organization for Research and Treatment of Cancer EORTC on QoL and consisted of the following stages: preparation - translation - pilot testing - approval. The official permission of authors and "Guideline on translation" was obtained which was developed by the working group of the EORTC on QoL. The pilot testing of EORTC QLQ-C30 and QLQ-BN20 questionnaires was conducted on the basis of the Department of Central Nervous System Pathology of the "National Centre for Neurosurgery" in patients with malignant tumors of the central nervous system. Results: The official versions of the EORTC QLQ-C30 and QLQ-BN20 questionnaires in Kazakh language were introduced and adapted in practical neurosurgical operations in Kazakhstan. Conclusions: The approved versions of the questionnaires in Kazakh language are now available for mainstream use on the official website EORTC.com. The versions of these questionnaires can be used in domestic cohort studies and clinical practice in the Republic of Kazakhstan. The use of these tools for assessing QoL will help professionals in the planning of individual treatment strategies and selection of the necessary therapy.

• Journal of radiological science and technology
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• v.36 no.4
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• pp.327-335
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• 2013

This study investigates the case of clinical application for TomoDirect 3D-CRT(TD-3D) and TomoHelical 3D-CRT(TH-3D) with evaluating dose distribution for clinical application in each case. Treatment plans were created for 8 patients who had 3 dimensional conformal radiation therapy using TD-3D and TH-3D mode. Each patients were treated for sarcoma, CSI(craniospinal irradiaion), breast, brain, pancreas, spine metastasis, SVC syndrome and esophagus. DVH(dose volume histogram) and isodose curve were used for comparison of each treatment modality. TD-3D shows better dose distribution over the irradiation field without junction effect because TD-3D was not influenced by target length for sarcoma and CSI case. In breast case, dosimetric results of CTV, the average value of D 99%, D 95% were $49.2{\pm}0.4$ Gy, $49.9{\pm}0.4$ Gy and V 105%, V 110% were 0%, respectively. TH-3D with the dosimetric block decreased dose of normal organ in brain, pancreas, spine metastasis case. SCV syndrome also effectively decreased dose of normal organ by using dose block to the critical organs(spinal cord <38 Gy). TH-3D combined with other treatment modalities was possible to boost irradiation and was total dose was reduced to spinal cord in esophagus case(spinal cord <45 Gy, lung V 20 <20%). 3D-CRT using Tomotherapy could overcomes some dosimetric limitations, when we faced Conventional Linac based CRT and shows clinically proper dose distribution. In conclusion, 3D-CRT using Tomotherapy will be one of the effective 3D-CRT techniques.