• BMB Reports
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• v.41 no.9
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• pp.615-625
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• 2008

Over a last decade, intense interest has been focused on biomarker discovery and their clinical uses. This interest is accelerated by the completion of human genome project and the progress of techniques in proteomics. Especially, cancer biomarker discovery is eminent in this field due to its anticipated critical role in early diagnosis, therapy guidance, and prognosis monitoring of cancers. Among cancers, lung cancer, one of the top three major cancers, is the one showing the highest mortality because of failure in early diagnosis. Numerous potential DNA biomarkers such as hypermethylations of the promoters and mutations in K-ras, p53, and protein biomarkers; carcinoembryonic antigen (CEA), CYFRA21-1, plasma kallikrein B1 (KLKB1), Neuron-specific enolase, etc. have been discovered as lung cancer biomarkers. Despite extensive studies thus far, few are turned out to be useful in clinic. Even those used in clinic do not show enough sensitivity, specificity and reproducibility for general use. This review describes what the cancer biomarkers are for, various types of lung cancer biomarkers discovered at present and predicted future advance in lung cancer biomarker discovery with proteomics technology.

• Radiation Oncology Journal
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• v.37 no.4
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• pp.302-308
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• 2019

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain's distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient's tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms of headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient's CNS metastases improved significantly within weeks of her therapy. The patient's non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

• Journal of Korean Neurosurgical Society
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• v.52 no.4
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• pp.334-338
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• 2012

Objective : We compared the survival time between patients with multiple gamma knife radiosurgery (GKRS) and patients with a single GKRS plus whole brain radiation therapy (WBRT), in patients with multiple metachronous brain metastases from lung cancer. Methods : From May 2006 to July 2010, we analyzed 31 patients out of 112 patients who showed multiple metachronous brain metastases. 20 out of 31 patients underwent multiple GKRS (group A) and 11 patients underwent a single GKRS plus WBRT (group B). We compared the survival time between group A and B. Kaplan-Meier method and Cox proportional hazards were used to analyze relationship between survival and 1) the number of lesions in each patient, 2) the average volume of lesions in each patient, 3) the number of repeated GKRS, and 4) the interval of development of new lesions, respectively. Results : Median survival time was 18 months (range 6-50 months) in group A and 6 months (range 3-18 months) in group B. Only the average volume of individual lesion (over 10 cc) was negatively related with survival time according to Kaplan-Meier method. Cox-proportional hazard ratio of each variable was 1.1559 for the number of lesions, 1.0005 for the average volume of lesions, 0.0894 for the numbers of repeated GKRS, and 0.5970 for the interval of development of new lesions. Conclusion : This study showed extended survival time in group A compared with group B. Our result supports that multiple GKRS is of value in extending the survival time in patients with multiple metachronous brain metastases, and that the number of the lesions and the frequency of development of new lesions are not an obstacle in treating patients with GKRS.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7401-7407
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• 2013

Aim: To compare survival outcomes after whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and WBRT plus SRS combination therapy in Korea, by performing a quantitative systematic review. Materials and Methods: We searched 10 electronic databases for reports on Korean patients treated with WBRT or SRS for brain metastases published prior to July 2010. Independent reviewers screened all articles and extracted the data. When a Kaplan-Meier survival curve was available, median survival time and standard errors were calculated. Summary estimates for the outcomes in each study were calculated using the inverse variance random-effects method. Results: Among a total of 2,761 studies, 20 studies with Korean patients (n=1,053) were identified. A combination of 12 studies (n=566) with WBRT outcomes showed a median survival time of 6.0 months (95%CI: 5.9-6.2), an overall survival rate of 5.6% (95%CI: 1-24), and a 6-month survival rate of 46.5% (95%CI: 37.2-56.1). For nine studies (n=412) on SRS, the median survival was 7.9 months (95%CI: 5.1-10.8), and the 6-month survival rate was 63.1% (95%CI: 49.8-74.8). In six studies (n=75) using WBRT plus SRS, the median survival was 10.7 months (95%CI: 4.7-16.6), and the overall and 6-month survival rates were 16.8% (95%CI: 6.2-38.2) and 85.7% (95%CI: 28.3-96.9), respectively. Conclusions: WBRT plus SRS showed better 1-year survival outcome than of WBRT alone for Korean patients with metastatic brain tumors. However, the results of this analysis have to be interpreted cautiously, because the risk factors of patients were not adjusted in the included studies.

• Genomics & Informatics
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• v.10 no.1
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• pp.33-39
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• 2012

High-throughput genomic technologies (HGTs), including next-generation DNA sequencing (NGS), microarray, and serial analysis of gene expression (SAGE), have become effective experimental tools for cancer genomics to identify cancer-associated somatic genomic alterations and genes. The main hurdle in cancer genomics is to identify the real causative mutations or genes out of many candidates from an HGT-based cancer genomic analysis. One useful approach is to refer to known cancer genes and associated information. The list of known cancer genes can be used to determine candidates of cancer driver mutations, while cancer gene-related information, including gene expression, protein-protein interaction, and pathways, can be useful for scoring novel candidates. Some cancer gene or mutation databases exist for this purpose, but few specialized tools exist for an automated analysis of a long gene list from an HGT-based cancer genomic analysis. This report presents a new web-accessible bioinformatic tool, called CaGe, a cancer genome annotation system for the assessment of candidates of cancer genes from HGT-based cancer genomics. The tool provides users with information on cancer-related genes, mutations, pathways, and associated annotations through annotation and browsing functions. With this tool, researchers can classify their candidate genes from cancer genome studies into either previously reported or novel categories of cancer genes and gain insight into underlying carcinogenic mechanisms through a pathway analysis. We show the usefulness of CaGe by assessing its performance in annotating somatic mutations from a published small cell lung cancer study.

• Journal of Korean Neurosurgical Society
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• v.61 no.3
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• pp.376-385
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• 2018

Recent discoveries of brain tumor-related genes and fast advances in genomic testing technologies have led to the era of molecular diagnosis of brain tumor. Molecular profiling of brain tumor became the significant step in the diagnosis, the prediction of prognosis and the treatment of brain tumor. Because traditional molecular testing methods have limitations in time and cost for multiple gene tests, next-generation sequencing technologies are rapidly introduced into clinical practice. Targeted sequencing panels using these technologies have been developed for brain tumors. In this article, focused on pediatric brain tumor, key discoveries of brain tumor-related genes are reviewed and cancer panels used in the molecular profiling of brain tumor are discussed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.269-273
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• 2016

Presently, the world population of the elderly is growing. By improving health hygiene and welfare indicators, mortality and birth rates decrease and life expectancy increases, making the present century the century of elderly. Aging is one of the main risk factors for development of cancer, which itself is the second cause of death in old people. This study was conducted to assess the prevalence of cancer in the elderly covered by the Islamic Republic of Iran Broadcasting (IRIB) insurance program and to obtain suitable programs for cancer screening and early detection, increase patient survival, improve elderly care and to reclaim the cost of treatment in comparison to the national and international statistics. This is a cross-sectional study conducted on all elderly patients diagnosed with malignancy based on their pathology reports. In this study, of the total 75,500 patients covered by IRIB insurance, 17.2% belonged to the elderly group, males accounting for 53.3%. The most common cancers in old men were prostatic cancer (61.3%), colon cancer (10.3%) cancer of the hematologic system, bladder cancer (9.6%), lung cancer (9.1%), thyroid cancer (3.9%) and brain tumors (1.3%). In the elderly women, the most common cancers were breast cancer (80.1%), colon cancer (5.1%), thyroid cancers (4.4%), bladder and hematologic system malignancies (3.6), lung cancer (2.9%) and brain tumors (0.7%). In addition, the prevalence of cancer was almost the same as national and international statistics. With the exception of non-melanoma skin cancer no difference was shown in prevalence of cancer between IRIB elderly patients and the other groups of cancer patients in Iran.

• Korean Journal of Head & Neck Oncology
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• v.28 no.2
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• pp.143-145
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• 2012

Follicular thyroid cancer(FTC) accounts for about 10-15% of thyroid cancer. Distant metastasis is common, usually to lung, bone and brain. 71-years-old man visited neurosurgery outpatient department. He complained of recent 6kg weight loss, left upper extremity pain with weakness and back pain. The radiologic findings showed multiple bone metastasis including thoracic spine and left scapular resulting from FTC. There was a probable brain metastatic lesion on right temporal fossa. The core biopsy of thyroid and thoracic spine(T11) confirmed metastatic follicular carcinoma. Radioactive iodine therapy and radiotherapy was done following total thyroidectomy. We report a unique case of multiple bone metastasis from follicular carcinoma of thyroid with literature review.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.325-328
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• 2012

Objective: Glutathione S-transferases (GSTs) are important enzymes that are involved in detoxification of environmental carcinogens. Molecular epidemiological studies have been conducted to investigate the association between GSTM1 and GSTT1 homozygous deletion polymorphisms and brain tumours but results have been conflicting. The aim of this study was to clarify this problem using a meta-analysis. Methods: A total of 9 records were identified by searching the PubMed and Embase databases. Fixed- and random-effects models were performed to estimate the pooled odds ratios. Results: No significant association was found between the GSTM1 and GSTT1 homozygous deletion polymorphisms and risk of brain tumours, including glioma and meningioma. Similar negative results were also observed in both population-based and hospital-based studies. Conclusion: These findings indicate that the GSTM1 and GSTT1 polymorphisms may not be related to the development of brain tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1575-1578
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• 2012

Objectives: To obtain permeability surface (PS) values using multi-slice helical CT perfusion imaging and to evaluate the spatial distribution correlation between PS values and vascular endothelial growth factor (VEGF) expression in solitary brain metastases. Methods: Imaging was performed on 21 patients, PS values being calculated from the central, border and peripheral parts of tumours. VEGF expression was determined by immunohistochemical staining. Results: Rim enhancement was found in 16 cases, the border of the tumour featuring PS elevation with high VEGF expression in 13 cases. In the 5 cases with nodular enhancement, the border and the central part had high permeability and VEGF expression was high in all cases, the correlation being significant (P<0.01). Conclusion: VEGF expression in brain metastases positively correlates with PS values from CT perfusion imaging, so that the latter can be used in the surveillance of angiogenic activity in brain metastases.