• Nuclear Medicine and Molecular Imaging
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• 제40권2호
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• pp.82-89
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• 2006

Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life it occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. $^{32}P,\;^{89}SrCl,\;^{153}Sm-EDTMP,\;^{188}Re/^{186}Re-HEDP,\;and\;^{177}Lu-EDTMP$ can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studios, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and jndication/contraindication and follow-up protocol.

• Archives of Reconstructive Microsurgery
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• 제14권2호
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• pp.105-111
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• 2005

Perforator flaps have become increasingly popular in microsurgery nowadays and are being used widely for many cases of reconstruction after trauma and cancer ablation. And thoracodorsal perforator based free flap is one of them having the merits of carrying a large skin paddle with leaving intact innervation and function of the remaining latissimus dorsi muscle. We made a homogeneous thin flap excluding the main muscle with a long vascular pedicle and tried to decrease the donor site morbidity. But, it needs a long learning-curve and we have met marginal flap necrosis frequently. Besides, prolonged operation time for complete perforator dissection may be a tedious job to the microsurgeon. To overcome these disadvantages, we usually included very small portion of the latissimus dorsi muscle during this flap elevation around the pedicled 2-3 thoracodorsal perforators during this flap elevation. We performed 3 cases of thoracodorsal perforator based free flap at Hallym university sacred heart hospital between May and August 2005 for the soft tissue defect of the scalp and feet. The average flap size was $8{\times}14\;cm$. Although it is not a true perforator flap, we can get the reliability for the flap survival with much better blood circulation and save the time of one or two hours to dissect the perforators completely. All cutaneous flaps survived completely without any complication except one fatty female who had the very small superficial fat necrosis due to flap bulkiness. We believe the thoracodorsal perforator based free flap can be extended its versatility and reliability by including the very small portion of the muscle around the perforators.

• Molecules and Cells
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• 제42권2호
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• pp.135-142
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• 2019

OCT4, also known as POU5F1 (POU domain class 5 transcription factor 1), is a transcription factor that acts as a master regulator of pluripotency in embryonic stem cells and is one of the reprogramming factors required for generating induced pluripotent stem cells. The human OCT4 encodes three isoforms, OCT4A, OCT4B, and OCT4B1, which are generated by alternative splicing. Currently, the functions and expression patterns of OCT4B remain largely unknown in malignancies, especially in human glioblastomas. Here, we demonstrated the function of OCT4B in human glioblastomas. Among the isoform of OCT4B, OCT4B-190 ($OCT4B^{19kDa}$) was highly expressed in human glioblastoma stem cells and glioblastoma cells and was mainly detected in the cytoplasm rather than the nucleus. Overexpression of $OCT4B^{19kDa}$ promoted colony formation of glioblastoma cells when grown in soft agar culture conditions. Clinical data analysis revealed that patients with gliomas that expressed OCT4B at high levels had a poorer prognosis than patients with gliomas that expressed OCT4B at low levels. Thus, $OCT4B^{19kDa}$ may play a crucial role in regulating cancer cell survival and adaption in a rigid environment.

• Korean Journal of Radiology
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• 제19권6호
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• pp.1130-1139
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• 2018

Objective: To compare the therapeutic efficacy between conventional transarterial chemoembolization (cTACE) and combined therapy using cTACE and radiofrequency ablation (RFA) in ultrasound (US)-invisible early stage hepatocellular carcinoma (HCC). Materials and Methods: From January 2008 to June 2016, 167 patients with US-invisible early stage HCCs were treated with cTACE alone (cTACE group; n = 85) or cTACE followed by immediate fluoroscopy-guided RFA targeting intratumoral iodized oil retention (combined group; n = 82). Procedure-related complications, local tumor progression (LTP), time to progression (TTP), and overall survival (OS) were compared between the two groups. Multivariate analyses were performed to identify prognostic factors. Results: There was no major complication in either group. The cTACE group showed higher 1-, 3-, and 5-year LTP rates than the combined group; i.e., 12.5%, 31.7%, and 37.0%, respectively, in the cTACE group; compared to 7.3%, 16.5%, and 16.5%, respectively, in the combined group; p = 0.013. The median TTP was 18 months in the cTACE group and 24 months in the combined group (p = 0.037). Cumulative 1-, 3-, and 5-year OS rates were 100%, 93.2%, and 87.7%, respectively, in the cTACE group and 100%, 96.6%, and 87.4%, respectively, in the combined group (p = 0.686). Tumor diameter > 20 mm and cTACE monotherapy were independent risk factors for LTP and TTP. Conclusion: Combined therapy using cTACE followed by fluoroscopy-guided RFA is a safe and effective treatment in US-invisible early stage HCCs. It provides less LTP and longer TTP than cTACE alone.

• 동의생리병리학회지
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• 제34권4호
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• pp.177-183
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• 2020

The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.465-472
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• 2022

Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl₂ is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl₂-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl₂-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl₂ but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl₂, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

• BMB Reports
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• 제55권10호
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• pp.506-511
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• 2022

Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress.

• Journal of Korean Neurosurgical Society
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• 제66권1호
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• pp.95-104
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• 2023

Objective : Hypernatremia is a common complication encountered during the treatment of neurocritically ill patients. However, it is unclear whether clinical outcomes correlate with the severity of hypernatremia in such patients. Therefore, we investigated the impact of hypernatremia on mortality of these patients, depending on the degree of hypernatremia. Methods : Among neurosurgical patients admitted to the intensive care unit (ICU) in a tertiary hospital from January 2013 to December 2019, patients who were hospitalized in the ICU for more than 5 days and whose serum sodium levels were obtained during ICU admission were included. Hypernatremia was defined as the highest serum sodium level exceeding 150 mEq/L observed. We classified the patients into four subgroups according to the severity of hypernatremia and performed propensity score matching analysis. Results : Among 1146 patients, 353 patients (30.8%) showed hypernatremia. Based on propensity score matching, 290 pairs were included in the analysis. The hypernatremia group had higher rates of in-hospital mortality and 28-day mortality in both overall and matched population (both p<0.001 and p=0.001, respectively). In multivariable analysis of propensity score-matched population, moderate and severe hypernatremia were significantly associated with in-hospital mortality (adjusted odds ratio [OR], 4.58; 95% confidence interval [CI], 2.15-9.75 and adjusted OR, 6.93; 95% CI, 3.46-13.90, respectively) and 28-day mortality (adjusted OR, 3.51; 95% CI, 1.54-7.98 and adjusted OR, 10.60; 95% CI, 5.10-21.90, respectively) compared with the absence of hypernatremia. However, clinical outcomes, including in-hospital mortality and 28-day mortality, were not significantly different between the group without hypernatremia and the group with mild hypernatremia (p=0.720 and p=0.690, respectively). The mortality rates of patients with moderate and severe hypernatremia were significantly higher in both overall and matched population. Interestingly, the mild hypernatremia group of matched population showed the best survival rate. Conclusion : Moderate and severe hypernatremia were associated with poor clinical outcomes in neurocritically ill patients. However, the prognosis of patients with mild hypernatremia was similar with that of patients without hypernatremia. Therefore, mild hypernatremia may be allowed during treatment of intracranial hypertension using hyperosmolar therapy.

• Journal of Preventive Medicine and Public Health
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• 제56권1호
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• pp.1-11
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• 2023

In 1945, atomic bombs were dropped on Hiroshima and Nagasaki. Approximately 70 000 Koreans are estimated to have been exposed to radiation from atomic bombs at that time. After Korea's Liberation Day, approximately 23 000 of these people returned to Korea. To investigate the long-term health and hereditary effects of atomic bomb exposure on the offspring, cohort studies have been conducted on atomic bomb survivors in Japan. This study is an ongoing cohort study to determine the health status of Korean atomic bomb survivors and investigate whether any health effects were inherited by their offspring. Atomic bomb survivors are defined by the Special Act On the Support for Korean Atomic Bomb Victims, and their offspring are identified by participating atomic bomb survivors. As of 2024, we plan to recruit 1500 atomic bomb survivors and their offspring, including 200 trios with more than 300 people. Questionnaires regarding socio-demographic factors, health behaviors, past medical history, laboratory tests, and pedigree information comprise the data collected to minimize survival bias. For the 200 trios, whole-genome analysis is planned to identify de novo mutations in atomic bomb survivors and to compare the prevalence of de novo mutations with trios in the general population. Active follow-up based on telephone surveys and passive follow-up with linkage to the Korean Red Cross, National Health Insurance Service, death registry, and Korea Central Cancer Registry data are ongoing. By combining pedigree information with the findings of trio-based whole-genome analysis, the results will elucidate the hereditary health effects of atomic bomb exposure.

• 한국엔터테인먼트산업학회논문지
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• 제4권4호
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• pp.72-76
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• 2010

의료 노모그램은 환자에 대한 임상정보를 축적하고 분석하여 만든 수식적인 임상 의료예측 지식을 그래픽으로 표현한 것을 말한다. 의료 노모그램이 환자 진료에 기여하기 위해서는 가능하면 많은 임상 사례들이 추적되어 이들로부터 의료예측 지식을 추출하는 것이 필요하다. 또한 가용한 사례 데이터들로부터 정확도가 높은 예측 모델을 생성하여 노모그램으로 제공해야 한다. 이러한 노모그램은 환자진료 시점에서 쉽게 활용할 수 있도록 제공하는 것이 바람직하다. 이 논문에서는 이러한 요구조건들을 고려하여 제안한 노모그램 서비스 시스템을 소개한다. 제안한 시스템에서는 가능하면 많은 사례를 활용할 수 있도록 하기 위해 웹기반의 사례정보 데이터베이스 시스템을 포함하고, 임상 사례 데이터들을 활용하여 주기적으로 노모그램을 자동으로 갱신하도록 한다. 그 결과를 임상현장에서 바로 사용할 수 있도록 하기 위하여 앱 프로그램 통하여 스마트 단말기를 활용하도록 한다. 이 앱은 노모그램 서버에 직접 접근하여 가장 최근의 노모그램에 근거한 예측 결과를 제공한다. 끝으로 제안된 서비스 시스템 구조를 적용하여 개발된 방광암 환자의 재발율 및 생존율에 대한 노모그램 서비스 시스템을 소개한다.