• Title/Summary/Keyword: critical cancer

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Pak1/LIMK1/Cofilin Pathway Contributes to Tumor Migration and Invasion in Human Non-Small Cell Lung Carcinomas and Cell Lines

  • Jang, In-Seok;Jeon, Byeong-Tak;Jeong, Eun-Ae;Kim, Eun-Jin;Kang, Da-Won;Lee, Jong-Sil;Jeong, Baek-Geun;Kim, Jin-Hyun;Choi, Bong-Hoi;Lee, Jung-Eun;Kim, Jong-Woo;Choi, Jun-Young;Roh, Gu-Seob
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.3
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    • pp.159-165
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    • 2012
  • Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the major histological types of non-small cell lung carcinoma (NSCLC). Although both SCCs and ACs have been characterized histologically and clinically, the precise mechanisms underlying their migration and invasion are not yet known. Here, we address the involvement in NSCLC of the p21-associated kinase1 (Pak1)/LIM kinase1 (LIMK1)/cofilin pathway, which recently has been reported to play a critical role in tumor migration and invasion. The Pak1/LIMK1/cofilin pathway was evaluated in tumors from SCC (n=35) and AC (n=35) patients and in SCC- and AC-type cell lines by western blotting, immunohistochemistry, and in vitro migration and invasion assays. The levels of phosphorylated Pak1, LIMK1, and cofilin in lung tumor tissues from SCC patients were increased as compared to normal tissues. In addition, immunohistochemistry showed greater expression of phosphorylated cofilin in SCC tissues. Expression of phosphorylated Pak1 and LIMK1 proteins was also significantly higher in SCC-type cells than in AC-type cells. Moreover, migration and invasion assays revealed that a higher percentage of SCC type cells exhibited migration and invasion compared to AC type cells. Migration was also decreased in LIMK1 knockdown SK-MES-1 cells. These findings suggest that the activation of the Pak1/LIMK1/cofilin pathway could preferentially contribute to greater tumor migration and invasion in SCC, relative to that in AC.

Increased Risk of Severe Gastric Symptoms by Virulence Factors vacAs1c, alpA, babA2, and hopZ in Helicobacter pylori Infection

  • Lee, Dong-Hae;Ha, Jong-Hun;Shin, Jeong-Ih;Kim, Kyu-Min;Choi, Jeong-gyu;Park, Seorin;Park, Jin-Sik;Seo, Ji-Hyeun;Park, Ji-Shook;Shin, Min-Kyoung;Baik, Seung-Chul;Lee, Woo-Kon;Youn, Hee-Shang;Cho, Myung-Je;Kang, Hyung-Lyun;Jung, Myunghwan
    • Journal of Microbiology and Biotechnology
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    • v.31 no.3
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    • pp.368-379
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    • 2021
  • Two virulence factors of Helicobacter pylori, cagA and vacA, have been known to play a role in the development of severe gastric symptoms. However, they are not always associated with peptic ulcer or gastric cancer. To predict the disease outcome more accurately, it is necessary to understand the risk of severe symptoms linked to other virulence factors. Several other virulence factors of H. pylori have also been reported to be associated with disease outcomes, although there are many controversial descriptions. H. pylori isolates from Koreans may be useful in evaluating the relevance of other virulence factors to clinical symptoms of gastric diseases because the majority of Koreans are infected by toxigenic strains of H. pylori bearing cagA and vacA. In this study, a total of 116 H. pylori strains from Korean patients with chronic gastritis, peptic ulcers, and gastric cancers were genotyped. The presence of virulence factors vacAs1c, alpA, babA2, hopZ, and the extremely strong vacuolating toxin was found to contribute significantly to the development of severe gastric symptoms. The genotype combination vacAs1c/alpA/babA2 was the most predictable determinant for the development of severe symptoms, and the presence of babA2 was found to be the most critical factor. This study provides important information on the virulence factors that contribute to the development of severe gastric symptoms and will assist in predicting clinical disease outcomes due to H. pylori infection.

Luminescence Properties of Europium-doped NaSr(PO3)3 Phosphor (Europium이 첨가된 NaSr(PO3)3형광체의 형광특성)

  • Yoon, Changyong;Park, Cheolwoo
    • Journal of the Korean Society of Radiology
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    • v.13 no.4
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    • pp.645-652
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    • 2019
  • Phosphor with phosphorus doped with rare earth ions was investigated by searching Sr and Eu phosphors suitable for substitution of Eu ions with similar ionic radius to polyphosphate host. The $NaSr(PO_3)_3$ phosphor was synthesized by the solid state method and the $NaSr(PO_3)_3:Eu^{2+}$ phosphor was prepared by the carbon thermal reduction method. Both of the phosphors were identified by X - ray diffraction. The excitation and emission spectra of $NaSr(PO_3)_3:Eu^{3+}$ increased fluorescence intensity and intensity quenching with increasing $Eu^{3+}$ concentration. The higher the $Eu^{3+}$ concentration in the emission spectrum, the higher the local symmetry of $Eu^{3+}$ environment. The mechanism of concentration quenching, in which fluorescence decreases due to the energy transfer between $Eu^{2+}$ ions with the closest critical distance between $Eu^{2+}$ ions with increasing $Eu^{2+}$ ion concentration, was confirmed in the emission spectrum of $NaSr(PO_3)_3:Eu^{2+}$ concentration. It is possible to change the fluorescent region through the post-processing of single rare earth ion added phosphors, and it is possible to change the fluorescence by applying the energy transfer and concentration quenching mechanism according to the local symmetry of $Eu^{3+}$ will be used for high phosphor development.

Risk Factors of Predicting Intensive Care unit Transfer in Deteriorating Ward Patients (병동 급성악화 환자의 중환자실 전동 위험요인 분석)

  • Lee, Ju-Ry
    • Journal of Digital Convergence
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    • v.19 no.4
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    • pp.467-475
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    • 2021
  • Purpose: When a patient with acute deterioration occurs in a ward, the decision to transfer to intensive care unit (ICU) is critical to improve the patient's outcomes. However, when available ICU resources limited, it is difficult to determine which of the deteriorating ward patients to transfer to the ICU. Therefore the purpose of this study was to identify risk factors in predicting deteriorating ward patients transferred to intensive care unit (ICU). Methods: We reviewed retrospectively clinical data of 2,945 deteriorating ward patients who referred medical emergency team. Data were analyzed with multivariate logistic regression. Results: The solid cancer that diagnosed at hospitalization (odds ratio[OR] 0.39; 95% confidence interval [CI] 0.32-0.47), when the cause of deterioration was respiratory problem (1.51; 95% CI 1.17-1.95), high MEWS (1.22; 1.17-1.28) and SpO2/FiO2 score (2.41; 2.23-2.60) were predictive of ICU transfer. Conclusion: These findings suggest that early prediction and treatment of patients with high risk of ICU transfer may improve the prognosis of patients.

Estimation of Multi-Route Exposure and Aggregated Risk Assessment for Cadmium and Lead (카드뮴과 납의 다경로 노출량 추정 및 통합 위해성 평가)

  • Yu, Changwoo;Kwon, Hoonjeong
    • Journal of Food Hygiene and Safety
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    • v.35 no.6
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    • pp.587-601
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    • 2020
  • Exposure to hazardous substances occurs through multiple pathways. Aggregated risk assessment, which includes all potential exposure pathways to a single toxicant, is necessary to prevent exposure to harmful substances. We aimed to estimate cadmium and lead exposure through various media, such as food, water, air, smoking, cosmetics, and female hygiene products. This study covered 10,733 subjects from the Seventh Korea National Health and Nutrition Examination Survey(2016, 2017). Dietary exposure was estimated using 24-hour recall data. For water and inhalational exposure, regional variations were considered. Water was classified as tap, bottled, and public water. Inhalational exposure was estimated using the '2014 Time Use Survey' based on daily lifestyle and social status. The frequency and volume of cosmetic usage were randomly approximated by sex and age. Post-menarcheal and premenopausal women were assumed to use feminine hygiene products. Non-carcinogenic aggregated risks were estimated using the Aggregate Risk Index from EPAs and the Total Exposure Hazard Index from Korean government guidelines. For carcinogenic risk assessment, excessive cancer risk was estimated. Ingestion, especially food, was the major route for both cadmium and lead exposure. Smoking was also associated with high cadmium exposure. Exposure to lead from cosmetics was remarkable but not critical. In aggregate risk assessments, median cadmium and lead exposure did not exceed the reference value. Sex, age, smoking status, and income affected exposure levels, unlike to regional variations.

Bioactive Lipids and Their Derivatives in Biomedical Applications

  • Park, Jinwon;Choi, Jaehyun;Kim, Dae-Duk;Lee, Seunghee;Lee, Bongjin;Lee, Yunhee;Kim, Sanghee;Kwon, Sungwon;Noh, Minsoo;Lee, Mi-Ock;Le, Quoc-Viet;Oh, Yu-Kyoung
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.465-482
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    • 2021
  • Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.

EID3 Promotes Glioma Cell Proliferation and Survival by Inactivating AMPKα1

  • Xiang, Yaoxian;Zhu, Lei;He, Zijian;Xu, Lei;Mao, Yuhang;Jiang, Junjian;Xu, Jianguang
    • Journal of Korean Neurosurgical Society
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    • v.65 no.6
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    • pp.790-800
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    • 2022
  • Objective : EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. Methods : A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. Results : EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. Conclusion : Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.

Folate: 2020 Dietary reference intakes and nutritional status of Koreans (엽산: 2020 영양소 섭취기준과 한국인의 영양상태)

  • Han, Young-Hee;Hyun, Taisun
    • Journal of Nutrition and Health
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    • v.55 no.3
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    • pp.330-347
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    • 2022
  • Folate, a water-soluble vitamin, acts as a coenzyme for one-carbon metabolism in nucleic acid synthesis and amino acid metabolism. Adequate folate nutritional status during the periconceptional period is known to prevent neural tube defects. In addition, insufficient folate intake is associated with various conditions, such as anemia, hyperhomocysteinemia, cardiovascular disease, cancer, cognitive impairment, and depression. This review discusses the rationale for the revision of the 2020 Korean dietary reference intakes for folate, and suggestions for future revisions. Based on the changes in the standard body weight in 2020, the adequate intake (AI) for infants (5-11 months) and the estimated average requirements (EARs) for 15-18 years of age were revised, but there were no changes in the recommended nutrient intakes (RNIs) and tolerable upper intake levels (ULs) for all age groups. Mean folate intake did not reach RNI in most age groups and was particularly low in women aged 15-29 years, according to the results of the 2016-2018 Korea National Health and Nutrition Examination Survey (KNHANES). The percentages of folate intake to RNI were lower than 60% in pregnant and lactating women, but serum folate concentrations were higher than those in other age groups, presumably due to the use of supplements. Therefore, total folate intake, from both food and supplements, should be evaluated. In addition, the database of folate in raw, cooked, and fortified foods should be further expanded to accurately assess the folate intake of Koreans. Determination of the concentrations of erythrocyte folate and plasma homocysteine as well as serum folate is recommended, and quality control of the analysis is critical.

Kinesin superfamily member 15 knockdown inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma

  • Yi Cai;Qianyue Lai;Xuan Zhang;Yu Zhang;Man Zhang;Shaoju Gu;Yuan Qin;Jingshen Hou;Li Zhao
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.5
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    • pp.457-470
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    • 2023
  • The aim of this study was to investigate the role of kinesin superfamily member 15 (KIF15) in nasopharyngeal carcinogenesis (NPC) and explore its underlying mechanisms. We employed various assays, including the CCK-8 assay, flow cytometry, the Transwell and scratch assay, Western blotting, and nude mice transplantation tumor, to investigate the impact of KIF15 on NPC. Our findings demonstrate that KIF15 plays a critical role in the proliferation, apoptosis, migration, and invasion of NPC cells. Furthermore, we discovered that silencing KIF15 inhibits cell proliferation, migration, and invasion while promoting apoptosis, and that KIF15's effect on NPC cell growth is mediated through the PI3K/AKT and P53 signaling pathways. Additionally, we showed that KIF15 promotes nasopharyngeal cancer cell growth in vivo. Our study sheds light on the significance of KIF15 in NPC by revealing that KIF15 knockdown inhibits NPC cell growth through the regulation of AKT-related signaling pathways. These findings suggest that KIF15 represents a promising therapeutic target for the prevention and treatment of NPC.

Emergent Esophagectomy in Patients with Esophageal Malignancy Is Associated with Higher Rates of Perioperative Complications but No Independent Impact on Short-Term Mortality

  • Yahya Alwatari;Devon C. Freudenberger;Jad Khoraki;Lena Bless;Riley Payne;Walker A. Julliard;Rachit D. Shah;Carlos A. Puig
    • Journal of Chest Surgery
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    • v.57 no.2
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    • pp.160-168
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    • 2024
  • Background: Data on perioperative outcomes of emergent versus elective resection in esophageal cancer patients requiring esophagectomy are lacking. We investigated whether emergent resection was associated with increased risks of morbidity and mortality. Methods: Data on patients with esophageal malignancy who underwent esophagectomy from 2005 to 2020 were retrospectively analyzed from the American College of Surgeons National Surgical Quality Improvement Program database. Thirty-day complication and mortality rates were compared between emergent esophagectomy (EE) and non-emergent esophagectomy. Logistic regression assessed factors associated with complications and mortality. Results: Of 10,067 patients with malignancy who underwent esophagectomy, 181 (1.8%) had EE, 64% had preoperative systemic inflammatory response syndrome, sepsis, or septic shock, and 44% had bleeding requiring transfusion. The EE group had higher American Society of Anesthesiologists (ASA) class and functional dependency. More transhiatal esophagectomies and diversions were performed in the EE group. After EE, the rates of 30-day mortality (6.1% vs. 2.8%), overall complications (65.2% vs. 44.2%), bleeding, pneumonia, prolonged intubation, and positive margin (17.7% vs. 7.4%) were higher, while that of anastomotic leak was similar. On adjusted logistic regression, older age, lower albumin, higher ASA class, and fragility were associated with increased complications and mortality. McKeown esophagectomy and esophageal diversion were associated with a higher risk of postoperative complications. EE was associated with 30-day postoperative complications (odds ratio, 2.39; 95% confidence interval, 1.66-3.43; p<0.0001). Conclusion: EE was associated with a more than 2-fold increase in complications compared to elective procedures, but no independent increase in short-term mortality. These findings may help guide data-driven critical decision-making for surgery in select cases of complicated esophageal malignancy.