• Clinical and Experimental Pediatrics
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• 제62권12호
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• pp.444-449
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• 2019

Background: Sixty percent of infants with severe neonatal hypoxic-ischemic encephalopathy die, while most survivors have permanent disabilities. Treatment for neonatal hypoxic-ischemic encephalopathy is limited to therapeutic hypothermia, but it does not offer complete protection. Here, we investigated whether hypoxia-inducible factor (HIF) promotes cell survival and suggested neuroprotective strategies. Purpose: HIF-1α deficient mice have increased brain injury after neonatal hypoxia-ischemia (HI), and the role of HIF-2α in HI is not well characterized. Copper-zinc superoxide dismutase (SOD)1 overexpression is not beneficial in neonatal HI. The expression of HIF-1α and HIF-2α was measured in SOD1 overexpressing mice and compared to wild-type littermates to see if alteration in expression explains this lack of benefit. Methods: On postnatal day 9, C57Bl/6 mice were subjected to HI, and protein expression was measured by western blotting in the ipsilateral cortex of wild-type and SOD1 overexpressing mice to quantify HIF-1α and HIF-2α. Spectrin expression was also measured to characterize the mechanism of cell death. Results: HIF-1α protein expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, HIF-2α protein expression increased 30 minutes after HI injury in the wild-type and SOD1 overexpressing mouse cortex and decreased to baseline value at 24 hours after HI injury. Spectrin 145/150 expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, spectrin 120 expression increased in both wild-type and SOD1 overexpressing mouse at 4 hours after HI, which decreased by 24 hours, indicating a greater role of apoptotic cell death. Conclusion: HIF-1α and HIF-2α may promote cell survival in neonatal HI in a cell-specific and regional fashion. Our findings suggest that early HIF-2α upregulation precedes apoptotic cell death and limits necrotic cell death. However, the influence of SOD was not clarified; it remains an intriguing factor in neonatal HI.

• Journal of Korean Neurosurgical Society
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• 제61권5호
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• pp.633-639
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• 2018

Objective : We investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control. Methods : A total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line. Results : After the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%. Conclusion : The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.

• Journal of Gastric Cancer
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• 제21권3호
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• pp.319-324
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• 2021

The abscopal effect refers to the phenomenon in which local radiotherapy is associated with the regression of metastatic cancer that is distantly located from the irradiated site. Here, we present a case of a patient with advanced gastric cancer and brain metastases who was successfully treated with brain radiotherapy and anti-programmed death-1 (PD-1) therapy-induced abscopal effect. Although anti-PD-1 therapy alone could not prevent disease progression, the metastatic lesions in the brain and also in the abdominal lymph node showed a drastic response after brain radiotherapy and anti-PD-1 therapy. To our knowledge, this is the first reported case of successful treatment of advanced gastric cancer with multiple brain and abdominal lymph node metastases, possibly through anti-PD-1 therapy combined with brain radiotherapy-induced abscopal effect. We suggest that the combination of brain radiotherapy and anti-PD-1 therapy may be considered as a therapeutic option for advanced gastric cancer, especially when there is brain metastasis.

• BMB Reports
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• 제35권1호
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• pp.67-86
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• 2002

Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of $Ca^{2+}$ and $Na^+$ that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.

• Journal of Trauma and Injury
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• 제34권4호
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• pp.270-278
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• 2021

Purpose: The purpose of the study is to analyze the results of surgical treatment of patients with brain and torso injury for 5 years in a single regional trauma center. Methods: We analyzed multiple trauma patients who underwent brain surgery and torso surgery for chest or abdominal injury simultaneously or sequentially among all 14,175 trauma patients who visited Dankook University Hospital Regional Trauma Center from January 2015 to December 2019. Results: A total of 25 patients underwent brain surgery and chest or abdominal surgery, with an average age of 55.4 years, 17 men and eight women. As a result of surgical treatment, there were 14 patients who underwent the surgery on the same day (resuscitative surgery), of which five patients underwent surgery simultaneously, four patients underwent brain surgery first, and one patient underwent chest surgery first, four patients underwent abdominal surgery first. Among the 25 treated patients, the 10 patients died, which the cause of death was five severe brain injuries and four hemorrhagic shocks. Conclusions: In multiple damaged patients require both torso surgery and head surgery, poor prognosis was associated with low initial Glasgow Coma Scale and high Injury Severity Score. On the other hand, patients had good prognosis when blood pressure was maintained and operation for traumatic brain injury was performed first. At the same time, patients who had operation on head and torso simultaneously had extremely low survival rates. This may be associated with secondary brain injury due to low perfusion pressure or continuous hypotension and the traumatic coagulopathy caused by massive bleeding.

• 대한의생명과학회지
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• 제12권3호
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• pp.139-143
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• 2006

Jopock (Jpk) has previously been ascertained that induces both bacterial and mammalian cell death. The Escherichia coli cells expressing Glutathion S-transferase (GST) fused Jpk showed elongated phenotype and inhibited cell growth which led eventual cell death. In an attempt to search the genetic suppressor of the lethal protein Jpk in bacterial cells, we constructed a unidirectional protein expression vector inserting tac promoter next to the C-terminus Jpk in pGEX-Jpk. The function of additional tac promoter was confirmed by substituting lac promoter in Plac-TOPO plasmid. The cells harboring plac- TOPO, which regulates $lacZ{\alpha}$ gene expression under lac promoter, formed blue colonies in 5-bromo-4-3 $indolyo-{\beta}-D-galactoside$ (X-gal) plate. When lac promoter was changed to tac promoter, same results were observed. Since the addition of tac promoter did not affect the toxic effect of Jpk, the pGEX-Jpk-ptac could be a useful vector for the screening of suppressor(s) for Jpk, in which GST-Jpk and a putative Jpk-suppressing protein are coexpressing from two unidirectional tac promoters, which response to the same inducer, $isopropyl-{\beta}-D-thiogalactopyranoside (IPTG)$.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.793-796
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• 2014

Background: This study aimed to examine possible effects of implementing a national query program on site-specific cancer mortality rates. Materials and Methods: A total of 2,874 query letters were sent out by the Department of Statistics, Ministry of Health and Welfare of Taiwan between January 2009 and December 2011 to medical certifiers who reported "neoplasm with uncertain nature" on the death certificate asking for more detailed information for coding. Results: Of the 2,571 responses, in 1,398 cases (54%) medical certifiers were still unable to determine the nature of the neoplasm. There were four neoplasm sites for which more than 50% of the responses changed the category to malignant, the gastrointestinal system (73%), urinary system (60%), stomach (55%) and rectum (53%). The liver was the cancer site that showed the largest absolute increase in the number of deaths after the query; however, the brain showed the largest relative increase, at 12%. Conclusions: Different neoplasm sites showed different magnitudes of change in nature after the query. Brain cancer mortality rates exhibited the largest increase.

• Journal of Chest Surgery
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• 제26권7호
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• pp.526-531
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• 1993

Sixty-one consecutive patients with coronary artery bypass graft for myocardial revascularization were retrospectively reviewed to analyze various pattern of postoperative complication and death during hospital stay from Nov. 1988 to Oct. 1992. Fortytwo of the patients were male and nineteen female. The mean age was 56 and 51 years in male and female. Preoperative diagnosises were unstable angina in 14 of patients, stable angina in 28, postmyocardial infarction state in 15, and state of failed percutaneous transluminal coronary angioplasty in 4. 141 stenosed coronary arteries were bypassed with use of 20 pedicled internal mammary artery and 124 reversed saphenous vein grafts. Postoperative complications and perioperative death were as follows: 1. Of 61 patients undergoing operation, peri and postoperative over all complication occured in 15 patients [ 25% ]; newly developed myocardial infarction in 4, intractable cardiac arrhythmia including atrial fibrillation and frequent ventricular premature contraction in 3, bleeding from gastrointestinal tract in 2, persistent vegetative state as a sequele of brain hypoxia in 1, wound necrosis in 1, left hemidiaphragmatic palsy in 3 and poor blood flow through graft in 2. 2. Operative mortality was 8%[5 patients]. 3 out of these died in operating room; 1 patient by bleeding from rupture of calcified aortic wall, 1 by air embolism through left atrial vent catheter, 1 by low cardiac output syndrome. 2 patients died during hospital stay; 1 by acute respiratory distress syndrome with multiuple organ failure, 1 by brain death after delayed diagnosis of pericardial tamponade.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.484-491
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• 2019

Glioblastoma is the most aggressive common brain tumor in adults. Curcumin, from Curcuma longa, is an effective antitumor agent. Although the same proteins control both autophagy and cell death, the molecular connections between them are complicated and autophagy may promote or inhibit cell death. We investigated whether curcumin affects autophagy, which regulates curcumin-mediated tumor cell death in A172 human glioblastoma cells. When A172 cells were incubated with $10{\mu}M$ curcumin, autophagy increased in a time-dependent manner. Curcumin-induced cell death was reduced by co-incubation with the autophagy inhibitors 3-methyladenine (3-MA), hydroxychloroquine (HCQ), and LY294002. Curcumin-induced cell death was also inhibited by co-incubation with rapamycin, an autophagy inducer. When cells were incubated under serum-deprived medium, LC3-II amount was increased but the basal level of cell viability was reduced, leading to the inhibition of curcumin-induced cell death. Cell death was decreased by inhibiting curcumin-induced autophagy using small interference RNA (siRNA) of Atg5 or Beclin1. Therefore, curcumin-mediated tumor cell death is promoted by curcumin-induced autophagy, but not by an increase in the basal level of autophagy in rapamycin-treated or serum-deprived conditions. This suggests that the antitumor effects of curcumin are influenced differently by curcumin-induced autophagy and the prerequisite basal level of autophagy in cancer cells.

• BMB Reports
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• 제35권1호
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• pp.87-93
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• 2002

Neural cell survival is an essential concern in the aging brain and many diseases of the central nervous system. Neural transplantation of the stem cells are already applied to clinical trials for many degenerative neurological diseases, including Huntington's disease, Parkinson's disease, and strokes. A critical problem of the neural transplantation is how to reduce their apoptosis and improve cell survival. Neurotrophic factors generally contribute as extrinsic cues to promote cell survival of specific neurons in the developing mammalian brains, but the survival factor for neural stem cell is poorly defined. To understand the mechanism controlling stem cell death and improve cell survival of the transplanted stem cells, we investigated the effect of plausible neurotrophic factors on stem cell survival. The neural stem cell, HiB5, when treated with PDGF prior to transplantation, survived better than cells without PDGF. The resulting survival rate was two fold for four weeks and up to three fold for twelve weeks. When transplanted into dorsal hippocampus, they migrated along hippocampal alveus and integrated into pyramidal cell layers and dentate granule cell layers in an inside out sequence, which is perhaps the endogenous pathway that is similar to that in embryonic neurogenesis. Promotion of the long term-survival and differentiation of the transplanted neural precursors by PDGF may facilitate regeneration in the aging adult brain and probably in the injury sites of the brain.