Purpose: Indocyanine green (ICG) is a promising agent for intraoperative visualization of tumor tissues and sentinel lymph nodes in early-stage gynecological cancer. However, it has some limitations, including a short half-life and poor solubility in aqueous solutions. This study aimed to enhance the efficacy of near-infrared (NIR) fluorescence imaging by overcoming the shortcomings of ICG using a nano-drug delivery system and improve target specificity in cervical cancer. Materials and Methods: ICG and poly(lactic-co-glycolic acid) (PLGA) conjugated with polyethylenimine (PEI) were assembled to enhance stability. Hyaluronic acid (HA) was coated on PEI-PLGA-ICG nanoparticles to target CD44-positive cancer cells. The manufactured HA-ICG-PLGA nanoparticles (HINPs) were evaluated in vitro and in vivo on cervical cancer cells (SiHa; CD44+) and human dermal cells (ccd986sk; CD44-), respectively, using NIR imaging to compare intracellular uptake and to quantify the fluorescence intensities of cells and tumors. Results: HINPs were confirmed to have a mean size of 200 nm and a zeta-potential of 33 mV using dynamic light scattering. The stability of the HINPs was confirmed at pH 5.0–8.0. Cytotoxicity assays, intracellular uptake assays, and cervical cancer xenograft models revealed that, compared to free ICG, the HINPs had significantly higher internalization by cervical cancer cells than normal cells (p<0.001) and significantly higher accumulation in tumors (p<0.001) via CD44 receptor-mediated endocytosis. Conclusion This study demonstrated the successful application of HINPs as nanocarriers for delivering ICG to CD44-positive cervical cancer, with improved efficacy in NIR fluorescence imaging.

Purpose: Indocyanine green (ICG) is a promising agent for intraoperative visualization of tumor tissues and sentinel lymph nodes in early-stage gynecological cancer. However, it has some limitations, including a short half-life and poor solubility in aqueous solutions. This study aimed to enhance the efficacy of near-infrared (NIR) fluorescence imaging by overcoming the shortcomings of ICG using a nano-drug delivery system and improve target specificity in cervical cancer. Materials and Methods: ICG and poly(lactic-co-glycolic acid) (PLGA) conjugated with polyethylenimine (PEI) were assembled to enhance stability. Hyaluronic acid (HA) was coated on PEI-PLGA-ICG nanoparticles to target CD44-positive cancer cells. The manufactured HA-ICG-PLGA nanoparticles (HINPs) were evaluated in vitro and in vivo on cervical cancer cells (SiHa; CD44+) and human dermal cells (ccd986sk; CD44-), respectively, using NIR imaging to compare intracellular uptake and to quantify the fluorescence intensities of cells and tumors. Results: HINPs were confirmed to have a mean size of 200 nm and a zeta-potential of 33 mV using dynamic light scattering. The stability of the HINPs was confirmed at pH 5.0–8.0. Cytotoxicity assays, intracellular uptake assays, and cervical cancer xenograft models revealed that, compared to free ICG, the HINPs had significantly higher internalization by cervical cancer cells than normal cells (p<0.001) and significantly higher accumulation in tumors (p<0.001) via CD44 receptor-mediated endocytosis. Conclusion This study demonstrated the successful application of HINPs as nanocarriers for delivering ICG to CD44-positive cervical cancer, with improved efficacy in NIR fluorescence imaging.

In Guillain-Barré syndrome (GBS) and its variant, anti-GQ1b antibody has a pathogenic role for ophthalmoplegia. In addition, anti-GT1a antibody is related with lower cranial nerve involvement. This report describes a 60-year-old male patient with GBS manifesting with initially isolated dysphagia and subsequently developed ophthalmoplegia. Both immunoglobulin G type anti-GQ1b and anti-GT1a antibodies were detected in the patient’s serum. A mechanism regarding subsequent involvement of respective cranial nerves remains to be elucidated.

In Guillain-Barré syndrome (GBS) and its variant, anti-GQ1b antibody has a pathogenic role for ophthalmoplegia. In addition, anti-GT1a antibody is related with lower cranial nerve involvement. This report describes a 60-year-old male patient with GBS manifesting with initially isolated dysphagia and subsequently developed ophthalmoplegia. Both immunoglobulin G type anti-GQ1b and anti-GT1a antibodies were detected in the patient’s serum. A mechanism regarding subsequent involvement of respective cranial nerves remains to be elucidated.

PURPOSE: A soft tissue sarcoma (STS) is a rare type of cancer, accounting for 1% of adult solid cancers. The aim of the present study is to determine the incidence of localized and advanced STS in Korean patients, their treatment patterns, and the survival of patients by disease status. MATERIALS AND METHODS: The STS patient cohort was defined using National Health Insurance Service medical data from 2002 to 2015. Incidence, distribution, anatomical location of tumors, survival rates (Kaplan-Meyer survival function) and treatment patterns were analyzed by applying different algorithms to the STS cohort containing localized and advanced STS cases. RESULTS: A total of 7,813 patients were diagnosed with STS from 2007 to 2014, 4,307 were localized STS and 3,506 advanced STS cases. The total incidence of STS was 2.49 per 100,000 person- years: 1.37 per 100,000 person-years for localized STS and 1.12 per 100,000 person-years for advanced STS. The 5-year survival rate after diagnosis was 56.4% for all STS, 82.4% for localized, and 27.2% for advanced STS. Half of the advanced STS patients (49.98%) received anthracycline-containing chemotherapy as initial treatment after diagnosis. CONCLUSION: This study provides insights into localized and advanced STS epidemiology, treatment patterns and outcomes in Korea, which could be used as fundamental data in improving clinical outcomes of STS patients in the future.
Adult ; Cohort Studies ; Diagnosis ; Drug Therapy ; Epidemiology ; Humans ; Incidence ; Korea ; National Health Programs ; Sarcoma ; Survival Rate

Cholesterol embolization syndrome (CES) usually occurs after endovascular procedures, it may also occurs after using anticoagulants and thrombolytics. We report a case of 66-year-old man with sudden elevation of creatinine after using warfarin due to cortical infarction. Histologic examinations revealed a cholesterol cleft on the arcuate artery. We concluded it as warfarin induced atheroembolic renal disease. Careful observation of kidneys is necessary in the case of renal abnormalities after using anticoagulation, considering the possibility of cholesterol embolism due to anticoagulant therapy.
Aged ; Anticoagulants ; Arteries ; Cholesterol ; Creatinine ; Embolism ; Embolism, Cholesterol ; Endovascular Procedures ; Humans ; Infarction ; Kidney ; Warfarin

T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and GSK3β-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.
Apoptosis ; Astrocytes ; Autism Spectrum Disorder ; Brain ; Calcium ; Calcium Channels ; Calcium Channels, T-Type* ; Cell Death ; Cell Survival ; Embryonic Development ; Female ; Neural Tube Defects ; Neurodevelopmental Disorders ; Neurons ; Pregnancy ; Stem Cells*

Benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea are commonly used preservatives in cosmetics. Recent reports suggested that these compounds may have cellular and systemic toxicity in high concentration. In addition, diazolidinyl urea and imidazolidinyl urea are known formaldehyde (FA) releasers, raising concerns for these cosmetic preservatives. In this study, we investigated the effects of benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea on ROS-dependent apoptosis of rat neural progenitor cells (NPCs) in vitro. Cells were isolated and cultured from embryonic day 14 rat cortices. Cultured cells were treated with 1–1,000 nM benzalkonium chloride, and 1–50 μM diazolidinyl urea or imidazolidinyl urea at various time points to measure the reactive oxygen species (ROS). PI staining, MTT assay, and live-cell imaging were used for cell viability measurements. Western blot was carried out for cleaved caspase-3 and cleaved caspase-8 as apoptotic protein markers. In rat NPCs, ROS production and cleaved caspase-8 expression were increased while the cell viability was decreased in high concentrations of these substances. These results suggest that several cosmetic preservatives at high concentrations can induce neural toxicity in rat brains through ROS induction and apoptosis.
Animals ; Apoptosis* ; Benzalkonium Compounds ; Blotting, Western ; Brain ; Caspase 3 ; Caspase 8 ; Cell Survival ; Cells, Cultured ; Formaldehyde ; In Vitro Techniques ; Rats* ; Reactive Oxygen Species ; Stem Cells* ; Urea

BACKGROUND/AIMS: The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development. METHODS: The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting. RESULTS: Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells. CONCLUSIONS: Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer.
Adenoma ; Animals ; Azoxymethane ; Carcinogenesis* ; Colon* ; Colonic Neoplasms ; Colorectal Neoplasms ; Cyclooxygenase 2 ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Fruit* ; Humans ; Immunoblotting ; In Vitro Techniques ; Incidence ; Interleukin-6 ; Interleukins ; Lymphoma, B-Cell ; Macrophages ; Mice* ; Necrosis ; Peroxidase ; Proliferating Cell Nuclear Antigen ; RAW 264.7 Cells ; Sodium

BACKGROUND/AIMS: This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-L-cysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. METHODS: Sprague-Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanol-only group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor α, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. RESULTS: PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMK-S005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. CONCLUSIONS: These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes.
Animals ; Antioxidants ; Blotting, Western ; Dinoprostone ; Enzyme-Linked Immunosorbent Assay ; Ethanol ; Heme Oxygenase-1 ; Interleukins ; Leukotriene B4 ; Mucus ; Peroxidase ; Rats* ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; Ulcer