Hypoxia plays a major role in the induction of angiogenesis during tumor development. One mechanism by which tumor cells respond to a reduced oxygen level is via the activation of hypoxia-inducible factor-1 (HIF-1). HIF-1 is an oxygen-dependent transcriptional activator that plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and the highly regulated HIF-1 alpha subunits. The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, phosphorylation and sumoyaltion. Therefore, HIF-1alpha interacts with several protein factors including PHD, pVHL, ARD-1, SUMO and p300/ CBP. Under normoxia, the HIF-1alpha subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)-mediated ubiquitin/proteasome pathway. The association of pVHL and HIF-1alpha under normoxic conditions is triggered by the hydroxylation of prolines and the acetylation of lysine within a polypeptide segment known as the oxygen-dependent degradation (ODD) domain. On the contrary, under the hypoxia condition, the HIF-1alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Under hypoxic conditions, HIF-1 eventually acts as a master regulator of numerous hypoxia-inducible genes. The target genes of HIF-1 are especially related to angiogenesis, cell proliferation and survival, and to glucose and iron metabolism. Moreover, it was reported that the activation of HIF-1alpha is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1alpha itself or the blocking of HIF-1alpha interacting proteins inhibits tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. Therefore, this review summarizes the molecular mechanism of HIF-1alpha stability, the biological functions of HIF-1 and its potential applications for cancer therapies.
Acetylation ; Anoxia ; Cell Proliferation ; Genes, Tumor Suppressor ; Glucose ; Hydroxylation ; Iron ; Lysine ; Metabolism ; Oxygen ; Phosphorylation ; Protein Processing, Post-Translational ; Transcription Factors

PURPOSE: To report a case of globe perforation and linear retinal tear after periocular acupuncture therapy which resulted in persistent temporal field defect with normal retinal function evidenced by multifocal electroretinogram (MERG). CASE SUMMARY: A 42-year-old female presented with decreased visual acuity and pain in her right eye after a periocular acupuncture therapy for blepharospasm. At initial presentation, the best corrected visual acuity (BCVA) was 0.08 in the injured eye and the intraocular pressure was 15 mmHg. Ultrasonography showed minimal vitreous hemorrhage and fundus examination revealed a linear retinal tear in the posterior pole sparing the macula. Consequently, barrier laser photocoagulation was performed around the lesion. The patient suffered from metamorphopsia and persistent decreased visual acuity even after 3 months. On fundus examination, epiretinal membrane with macular pucker was observed on the macula. Spectral domain optical coherence tomography (SD-OCT) revealed retinal nerve fiber layer defect with a full-thickness posterior wall tear. Multifocal electroretinogram showed normal retinal function; however, Humphrey visual field test demonstrated field defect corresponding to the injury. A 25-gauge pars plana vitrectomy was performed with membranectomy and ILM peeling. One month postoperatively, improvement in BCVA and metamorphopsia was achieved; however, the scotomata remained unchanged. CONCLUSIONS: Ocular perforation or retinal tear caused by an acupuncture needle is a rare condition that has not been reported previously in Korea. Furthermore, no case of traumatic visual field defect with preserved retinal function has been reported elsewhere. Hence, the authors present a case of isolated visual field defect without retinal dysfunction following full-thickness retinal tear caused by an acupuncture needle.
Acupuncture ; Acupuncture Therapy ; Adult ; Blepharospasm ; Disaccharides ; Epiretinal Membrane ; Eye ; Female ; Humans ; Intraocular Pressure ; Korea ; Light Coagulation ; Needles ; Nerve Fibers ; Retinal Perforations ; Retinaldehyde ; Tomography, Optical Coherence ; Vision Disorders ; Visual Acuity ; Visual Field Tests ; Visual Fields ; Vitrectomy ; Vitreous Hemorrhage

BACKGROUND/AIMS: Mirizzi syndrome is a rare complication of longstanding gallstone disease which resulting in obstructive Jaundice. It is benign stricture of common hepatic duct because of stone impacted with in the cystic duct or Hartmann pouch of the gallbladder. The aim of this study is to evaluate our experience of Mirizzi syndrome and consider its surgical treatment. METHODS: During the years 1994 to 2001 at Asan medical center, 23 cases of Mirizzi syndrome were diagnosed on the basis of preoperative and postoperative findings and they were retrospectively reviewed. RESULTS: There were 12 patients with Csendes type I, 6 patients with type II, and 5 patients with Type III. Average age was 61 years (range: 31 to 83 years) For preoperative evaluation Endoscopic retrograde cholangiopancreatography (ERCP) and Ultrasonography were performed in all cases. Laparoscopic cholecystectomy was tried in 7 type I cases. 5 were successfully treated and 2 conversions were reported, all because of unclear anatomy. In 6 type II cases open cholecystrctomy, CHD repair and T tube insertion were performed. 5 patients with type III were required hepaticojejunostomy. CONCLUSIONS: High index of suspicion is required for diagnosis of Mirizzi syndrome and laparoscopic approach is permissible in specialized center especially in the case of suspected Mirizzi type I, under the recognition of biliary anatomy through preoperative imaging studies. If there is fistula or unclear anatomy, we recommend open operative techniques for the safety and the efficiency.
Cholangiopancreatography, Endoscopic Retrograde ; Cholecystectomy, Laparoscopic ; Chungcheongnam-do ; Constriction, Pathologic ; Cystic Duct ; Diagnosis ; Fistula ; Gallbladder ; Gallstones ; Hepatic Duct, Common ; Humans ; Jaundice, Obstructive ; Mirizzi Syndrome* ; Retrospective Studies ; Ultrasonography

No abstract available.
Cranial Irradiation ; Leukoencephalopathies* ; Parkinsonian Disorders*

Background: Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT). Methods: A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens. Results: We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression. Conclusions This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by abnormally expanded CAG repeats in the huntingtin gene. The huntingtin gene mutation leads to the progressive degeneration of striatal GABAergic medium spiny neurons (MSN) and reduces the level of brain-derived neurotrophic factor (BDNF) in HD patient’s brain. BDNF is an essential neurotrophic factor for the cortico-striatal synaptic activity and the survival of GABAergic neurons. In this study, we transplanted BDNF-overexpressing human neural stem cells (HB1.F3.BDNF) into the contra-lateral side of unilateral quinolinic acid (QA)-lesioned striatum of HD rat model. The results of in vivo transplantation were monitored using various behavioral tests, 4.7 T animal magnetic resonance imaging (MRI) and immunohistochemical staining. We observed that the QA-lesioned rats receiving HB1.F3.BDNF cells exhibited significant behavioral improvements in the stepping, rotarod and apomorphine-induced rotation tests. Interestingly, contralaterally transplanted cells were migrated to the QA-lesioned striatum and the size of lateral ventricle was reduced. Histological analyses further revealed that the transplanted cells, which had migrated to the QA lesion site, were differentiated into the cells of GABAergic, MSN-type neurons expressing DARPP-32, and neural networks were established between the transplanted cells and the host brain, as revealed by retrograde tracing. Finally, there was a significant reduction of inflammatory response in HB1.F3.BDNF-transplanted HD animal model, compared with vehicle-transplanted group. Taken together, these results suggest that HB1.F3.BDNF can be an effective therapeutic strategy to treat HD patients in the future.

Necrotizing fasciitis caused by Vibrio vulnificus can rapidly progress to septic shock and death. Hence, early surgical debridement of the involved tissue is vital. However, this can be a challenging task due to the coagulopathy and unstable conditions often associated with these patients. Herein, we present a patient with necrotizing fasciitis caused by V. vulnificus who received extracorporeal membrane oxygenation (ECMO) support for refractory hypotension. After initiating ECMO, his vital signs stabilized, and lactate, C-reactive protein, and procalcitonin levels continued to decrease. He underwent several rounds of surgical debridement and vacuum-assisted drainage on both lower legs. On ECMO day 15, he was successfully weaned off the device and his condition was uneventful for several days. However, on the 24th day of intensive care unit (ICU), he was again placed on ECMO due to clinical deterioration. On ICU day 32, he underwent bilateral below-knee amputations due to delayed wound healing. Unfortunately, he subsequently developed multi-organ failure and died. Nonetheless, this case is instructive regarding the potential use of ECMO. We suggest that ECMO could provide the necessary time for sepsis patients to undergo aggressive medical and surgical interventions.
Amputation ; C-Reactive Protein ; Debridement ; Drainage ; Extracorporeal Membrane Oxygenation* ; Fasciitis ; Fasciitis, Necrotizing ; Humans ; Hypotension ; Intensive Care Units ; Lactic Acid ; Leg ; Sepsis* ; Shock, Septic ; Vibrio vulnificus* ; Vibrio* ; Vital Signs ; Wound Healing

BACKGROUND AND OBJECTIVES: Ischemic stroke caused by middle cerebral artery occlusion (MCAo) is the major type of stroke, but there are currently very limited options for cure. It has been shown that neural stem cells (NSCs) or neural precursor cells (NPCs) can survive and improve neurological deficits when they are engrafted in animal models of various neurological diseases. However, how the transplanted NSCs or NPCs are act in vivo in the injured or diseased brain is largely unknown. In this study, we utilized magnetic resonance imaging (MRI) techniques in order to understand the fates of human NSCs (HB1.F3) following transplantation into a rodent model of MCAo. METHODS AND RESULTS: HB1.F3 human NSCs were pre-labeled with ferumoxides (Feridex(R))-protamine sulfate complexes, which were visualized and examined by MRI up to 9 weeks after transplantation. Migration of the transplanted cells to the infarct area was further confirmed by histological methods. CONCLUSIONS: Based on these observations, we speculate that the transplanted NSCs have the extensive migratory ability to the injured site, which will in turn contribute to functional recovery in stroke.
Brain ; Dextrans ; Humans ; Infarction, Middle Cerebral Artery ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; Models, Animal ; Neural Stem Cells ; Rodentia ; Stroke ; Track and Field ; Transplants

BACKGROUND: Data on noninvasive ventilation (NIV) use in intensive care units (ICUs) are very limited in South Korea. METHODS: A prospective observational study was performed in 20 ICUs of university-affiliated hospitals from June 2017 to February 2018. Adult patients (age>18 years) who were admitted to the ICU and received NIV treatment for acute respiratory failure were included. RESULTS: A total of 156 patients treated with NIV were enrolled (mean age, 71.9±11.6 years). The most common indications for NIV were acute hypercapnic respiratory failure (AHRF, n=89) and post-extubation respiratory failure (n=44). The main device for NIV was an invasive mechanical ventilator with an NIV module (61.5%), and the majority of patients (87.2%) used an oronasal mask. After the exclusion of 32 do-not-resuscitate patients, NIV success rate was 68.5% (85/124); ICU and hospital mortality rates were 8.9% and 15.3%, respectively. However, the success rate was lower in patients with de novo respiratory failure (27.3%) compared to that of patients with AHRF (72.8%) or post-extubation respiratory failure (75.0%). In multivariate analysis, immunocompromised state, de novo respiratory failure, post-NIV (2 hours) respiratory rate, NIV mode (i.e., non-pressure support ventilation mode), and the change of NIV device were significantly associated with a lower success rate of NIV. CONCLUSION: AHRF and post-extubation respiratory failure were the most common indications for NIV in Korean ICUs. Overall NIV success was achieved in 68.5% of patients, with the lowest rate in patients with de novo respiratory failure.
Adult ; Critical Care ; Hospital Mortality ; Humans ; Intensive Care Units ; Korea ; Masks ; Multivariate Analysis ; Noninvasive Ventilation ; Observational Study ; Prospective Studies ; Respiratory Insufficiency ; Respiratory Rate ; Ventilation ; Ventilators, Mechanical

BACKGROUND: Data on noninvasive ventilation (NIV) use in intensive care units (ICUs) are very limited in South Korea. METHODS: A prospective observational study was performed in 20 ICUs of university-affiliated hospitals from June 2017 to February 2018. Adult patients (age>18 years) who were admitted to the ICU and received NIV treatment for acute respiratory failure were included. RESULTS: A total of 156 patients treated with NIV were enrolled (mean age, 71.9±11.6 years). The most common indications for NIV were acute hypercapnic respiratory failure (AHRF, n=89) and post-extubation respiratory failure (n=44). The main device for NIV was an invasive mechanical ventilator with an NIV module (61.5%), and the majority of patients (87.2%) used an oronasal mask. After the exclusion of 32 do-not-resuscitate patients, NIV success rate was 68.5% (85/124); ICU and hospital mortality rates were 8.9% and 15.3%, respectively. However, the success rate was lower in patients with de novo respiratory failure (27.3%) compared to that of patients with AHRF (72.8%) or post-extubation respiratory failure (75.0%). In multivariate analysis, immunocompromised state, de novo respiratory failure, post-NIV (2 hours) respiratory rate, NIV mode (i.e., non-pressure support ventilation mode), and the change of NIV device were significantly associated with a lower success rate of NIV. CONCLUSION AHRF and post-extubation respiratory failure were the most common indications for NIV in Korean ICUs. Overall NIV success was achieved in 68.5% of patients, with the lowest rate in patients with de novo respiratory failure.