ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer

Jun, Ikhyun,Park, Hyung Soon,Piao, He,Han, Jung Woo,An, Min Ji,Yun, Byeong Gyu,Zhang, Xianglan,Cha, Yong Hoon,Shin, You Keun,Yook, Jong In,Jung, Jinsei,Gee, Heon Yung,Park, Joon Seong,Yoon, Dong Sup,J Nature Publishing Group 2017 The British journal of cancer Vol. No.

<P><B>Background:</B></P><P>Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer.</P><P><B>Methods:</B></P><P>In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated <I>in vitro</I> and <I>in vivo</I> approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer.</P><P><B>Results:</B></P><P>The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of <I>ANO9</I> in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of <I>ANO9</I> in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown <I>of ANO9</I> augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer.</P><P><B>Conclusions:</B></P><P>The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.</P>

The Role of Labour Inspectorates in Tackling the Psychosocial Risks at Work in Europe: Problems and Perspectives

Dimitrios Toukas,Miltiadis Delichas,Chryssoula Toufekoula,Anastasia Spyrouli 한국산업안전공단 산업안전보건연구원 2015 Safety and health at work Vol.6 No.4

Significant changes in the past year have taken place in the world of work that are bringing new challenges with regard to employee safety and health. These changes have led to emerging psychosocial risks (PSRs) at work. The risks are primarily linked to how work is designed, organized, and managed, and to the economic and social frame of work. These factors have increased the level of work-related stress and can lead to serious deterioration in mental and physical health. In tackling PSRs, the European labor inspectorates can have an important role by enforcing preventive and/or corrective interventions in the content and context of work. However, to improve working conditions, unilateral interventions in the context and content of work are insufficient and require adopting a common strategy to tackle PSRs, based on a holistic approach. The implementation of a common strategy by the European Labor Inspectorate for tackling PSRs is restricted by the lack of a common legislative frame with regard to PSR evaluation and management, the different levels of labor inspectors' training, and the different levels of employees' and employers' health and safety culture.

Antibacterial and Antioxidant Properties of the Leaves and Stem Essential Oils of <i> Jatropha gossypifolia</i> L.

Okoh, Sunday O.,Iweriebor, Benson C.,Okoh, Omobola O.,Nwodo, Uchechukwu U.,Okoh, Anthony I. Hindawi Publishing Corporation 2016 BioMed research international Vol.2016 No.-

<P>Antibacterial and antioxidant properties of the leaves and stem essential oils (EOs) of<I> Jatropha gossypifolia</I> and their efficacies against infectious and oxidative stress diseases were studied<I> in vitro</I>. The EOs obtained using Clevenger modified apparatus were characterized by high resolution GC-MS, while their antioxidant and antibacterial properties were examined by spectrophotometric and agar diffusion techniques, respectively. The EOs exhibited strong antibacterial activity against<I> Escherichia coli</I>,<I> Enterococcus faecium, </I>and<I> Staphylococcus aureus</I>. The stem essential oil (SEO) was more active than the leaf essential oil (LEO) against test bacteria with minimum inhibition concentration (MIC) ranging from 0.025 to 0.05 mg/mL and the LEO from 0.05 to 0.10 mg/mL. The SEO was bactericidal at 0.025 and 0.05 mg/mL against<I> S</I>.<I> aureus</I> and<I> E</I>.<I> faecium</I>, respectively, and the LEO was bacteriostatic against the three bacteria at 0.05 and 0.10 mg/mL. The SEO IC<SUB>50</SUB> (0.07 mg/mL) showed that the antiradical strength was superior to LEO (0.32 mg/mL) and <I>β</I>-carotene (1.62 mg/mL) in scavenging 2, 2-diphenyl-1-picrylhydrazyl radicals (DPPH<SUP>•</SUP>). The oils effectively reduced three other oxidants to neutral molecules in concentration dependent manner. Findings from this study suggest that, apart from the traditional uses of the plant extracts, the EOs have strong bioactive compounds with noteworthy antibacterial and antiradical properties and may be good candidates in the search for lead compounds for the synthesis of novel potent antibiotics.</P>

The Effect of Tonsillectomy and Adenoidectomy on Right Ventricle Function and Pulmonary Artery Pressure by Using Doppler Echocardiography in Children

Onur Çağlar Acar,Abdurrahman Üner,Mehmet Fatih Garça,İbrahim Ece,Serdar Epçaçan,Mahfuz Turan,Ferhat Kalkan 대한이비인후과학회 2016 Clinical and Experimental Otorhinolaryngology Vol.9 No.2

Objectives. The purpose of the present study is to emphasize the efficacy of the myocardial performance index and tricuspid annular plane systolic excursion (TAPSE) in the determination of impaired cardiac functions and recovery period following the treatment in children with adenoid and/or tonsillar hypertrophy. Methods. Fifty-three healthy children after routine laboratory, imaging and clinical examinations, with adenoid and/or tonsillar hypertrophy were evaluated before and 3 months after adenotonsillectomy for cardiac functions using M mode and Doppler echocardiography. Results. The mean age of cases was 6.4±3.0 years, 34 (65%) were male, and 19 (35%) were female. Pulmonary hypertension was observed to be mild in 3 patients and moderate in 1 patient preoperatively. When the preoperative and postoperative echocardiographic measurements of the patients were compared, the tricuspid valve E wave velocity, the E/A ratio (E, early diastolic flow rate; A, late diastolic flow rate), and the TAPSE values were determined to be significantly higher postoperatively (P<0.05). The tricuspid valve deceleration time, the isovolumetric relaxation time and the systolic pulmonary artery pressure were found to be significantly lower compared to the preoperative values (P<0.05). Conclusion. Adenoidectomy and/or tonsillectomy may prevent cardiac dysfunctions that can develop in the later periods due to adenoid and/or tonsil hypertrophy in children, before the appearance of the clinical findings of cardiac failure.

Efficacy and safety of sequential neoadjuvant chemotherapy and short-course radiation therapy followed by delayed surgery in locally advanced rectal cancer: a single-arm phase II clinical trial with subgroup analysis between the older and young patients

Ali Mohammad Bananzadeh,Ali Akbar Hafezi,NamPhong Nguyen,Shapour Omidvari,Ahmad Mosalaei,Niloofar Ahmadloo,Mansour Ansari,Mohammad Mohammadianpanah 대한방사선종양학회 2021 Radiation Oncology Journal Vol.39 No.4

Purpose: This study was performed to investigate the efficacy and safety of short-course radiation therapy (SCRT) and sequential chemotherapy followed by delayed surgery in locally advancer rectal cancer with subgroup analysis between the older and young patients.Materials and Methods: In this single-arm phase II clinical trial, eligible patients with locally advanced rectal cancer (T3–4 and/or N1–2) were enrolled. All the patients received a median three sequential cycles of neoadjuvant CAPEOX (capecitabine + oxaliplatin) chemotherapy. A total dose of 25 Gy in five fractions during 1 week was prescribed to the gross tumor and regional lymph nodes. Surgery was performed about 8 weeks following radiotherapy. Pathologic complete response rate (pCR) and grade 3–4 toxicity were compared between older patients (≥65 years) and younger patients (<65 years).Results: Ninety-six patients with locally advanced rectal cancer were enrolled. There were 32 older patients and 64 younger patients. Overall pCR was 20.8% for all the patients. Older patients achieved similar pCR rate (18.7% vs. 21.8; p = 0.795) compared to younger patients. There was no statistically significance in terms of the tumor and the node downstaging or treatment-related toxicity between older patients and younger ones; however, the rate of sphincter-saving surgery was significantly more frequent in younger patients (73% vs. 53%; p=0.047) compared to older ones. All treatment-related toxicities were manageable and tolerable among older patients.Conclusion: Neoadjuvant SCRT and sequential chemotherapy followed by delayed surgery was safe and effective in older patients compared to young patients with locally advanced rectal cancer.

Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model

( Tai Joon An ),( Chin Kook Rhee ),( Ji Hye Kim ),( Young Rong Lee ),( Jin Young Chon ),( Chan Kwon Park ),( Hyoung Kyu Yoon ) 대한결핵 및 호흡기학회 2018 Tuberculosis and Respiratory Diseases Vol.81 No.1

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of T_H2 process and increased T_H1 and/or T_H17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon g, and tumor necrosis factor a in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

IPF와 NSIP에서 MMPs와 TIMPs의 발현

김유진 ( Yu Jin Kim ),김정호 ( Jung Ho Kim ),전효근 ( Hyo Keun Jeon ),김미경 ( Mi Kyeong Kim ),조용찬 ( Young Chan Jo ),경선영 ( Sun Yong Kyung ),안창혁 ( Chang Hyeok An ),이상표 ( Sang Pyo Lee ),박정웅 ( Jung Woong Park ),하승연 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.61 No.5

연구배경: 특발성 폐섬유화증/통상형 간질성 폐렴은 특발성 간질성 폐렴 중 하나로 세포외 기질의 과도한 침착과 기저막 파괴를 통해 섬유모세포/근섬유모세포가 폐포 내로 이동하면서 발생하는 fibroblast foci가 대표적인 병리학적 현상이며, 결국 비가역적인 섬유화로 진행하는 질환이다. 이에 대하여 기질 분해 효소인 MMPs와 그 길항체인 TIMPs의 과발현이 이러한 병태생리의 한 요인으로 설명되고 있다. 본 연구에서는 특발성 폐섬유화증/통상형 간질성 폐렴을 비롯, 비특이성 간질성 폐렴에서 MMPs와 TIMPs의 발현 양상을 살펴보고자 하였다. 연구방법: 특발성 폐섬유화증/통상형 간질성 폐렴, 비특이성 간질성 폐렴의 폐 조직을 이용하여 MMP-1,-2,-9, TIMP-1, -2에 대한 면역조직화학염색 검사와 MMP-2, MMP-9에 대한 gelatin zymography를 시행하였다. 면역조직화학염색 검사는 통상형 간질성 폐렴 22, 비특이성 간질성 폐렴 13례 였으며, gelatin zymography는 통상형 간질성 폐렴9, 비특이성 간질성 폐렴 4례, 정상 대조군5례였다. 연구결과: 면역조직화학 염색 검사 결과 섬유모세포/근섬유모세포 부위에서 TIMP-1, -2, MMP-2,9이 관찰 되었고, 특히 통상형 간질성 폐렴에서 비특이성 간질성 폐렴보다 TIMP-2가 강하게 발현되었다. Gelatin zymography 결과는 MMP-2, MMP-9 모두 통상형 간질성 폐렴에서 비특이성 간질성 폐렴보다 유의하게 높은 소견을 보여 주었다. 결론: 통상형 간질성 폐렴에서 비특이성 간질성 폐렴보다 TIMP-2, MMP-2, MMP-9의 과발현을 관찰할 수 있었으며, 이는 통상형 간질성 폐렴의 비가역적인 섬유화 진행에 관여할 가능성이 있음을 추측해 볼 수 있다. Background: MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects. Method: The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2 ,-9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay. Results: (1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. Particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue. Conclusions: These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be important factors in the irreversible fibrosis of the lung parenchyme (Tuberc Respir Dis 2006; 61: 447-455)

The Role of Labour Inspectorates in Tackling the Psychosocial Risks at Work in Europe: Problems and Perspectives

Toukas, Dimitrios,Delichas, Miltiadis,Toufekoula, Chryssoula,Spyrouli, Anastasia Occupational Safety and Health Research Institute 2015 Safety and health at work Vol.6 No.4

Significant changes in the past year have taken place in the world of work that are bringing new challenges with regard to employee safety and health. These changes have led to emerging psychosocial risks (PSRs) at work. The risks are primarily linked to how work is designed, organized, and managed, and to the economic and social frame of work. These factors have increased the level of work-related stress and can lead to serious deterioration in mental and physical health. In tackling PSRs, the European labor inspectorates can have an important role by enforcing preventive and/or corrective interventions in the content and context of work. However, to improve working conditions, unilateral interventions in the context and content of work are insufficient and require adopting a common strategy to tackle PSRs, based on a holistic approach. The implementation of a common strategy by the European Labor Inspectorate for tackling PSRs is restricted by the lack of a common legislative frame with regard to PSR evaluation and management, the different levels of labor inspectors' training, and the different levels of employees' and employers' health and safety culture.

Integrative epigenomic and genomic analysis of malignant pheochromocytoma

Sandgren, Johanna,Andersson, Robin,Rada-Iglesias, Alvaro,Enroth, Stefan,Akerstrom, Goran,Dumanski, Jan P.,Komorowski, Jan,Westin, Gunnar,Wadelius, Claes Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.7

Epigenomic and genomic changes affect gene expression and contribute to tumor development. The histone modifications trimethylated histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) are epigenetic regulators associated to active and silenced genes, respectively and alterations of these modifications have been observed in cancer. Furthermore, genomic aberrations such as DNA copy number changes are common events in tumors. Pheochromocytoma is a rare endocrine tumor of the adrenal gland that mostly occurs sporadic with unknown epigenetic/genetic cause. The majority of cases are benign. Here we aimed to combine the genome-wide profiling of H3K4me3 and H3K27me3, obtained by the ChIP-chip methodology, and DNA copy number data with global gene expression examination in a malignant pheochromocytoma sample. The integrated analysis of the tumor expression levels, in relation to normal adrenal medulla, indicated that either histone modifications or chromosomal alterations, or both, have great impact on the expression of a substantial fraction of the genes in the investigated sample. Candidate tumor suppressor genes identified with decreased expression, a H3K27me3 mark and/or in regions of deletion were for instance TGIF1, DSC3, TNFRSF10B, RASSF2, HOXA9, PTPRE and CDH11. More genes were found with increased expression, a H3K4me3 mark, and/or in regions of gain. Potential oncogenes detected among those were GNAS, INSM1, DOK5, ETV1, RET, NTRK1, IGF2, and the H3K27 trimethylase gene EZH2. Our approach to associate histone methylations and DNA copy number changes to gene expression revealed apparent impact on global gene transcription, and enabled the identification of candidate tumor genes for further exploration.

Clinical correlation among male infertility and overall male health: A systematic review of the literature

Francesco Del Giudice,Alex M. Kasman,Matteo Ferro,Alessandro Sciarra,Ettore De Berardinis,Federico Belladelli,Andrea Salonia,Michael L. Eisenberg 대한비뇨의학회 2020 Investigative and Clinical Urology Vol.61 No.4

Purpose: Ongoing evidence has suggested the role of male factor infertility as a potential predictor of mortality and general health status. The aim of the present review is to update the current knowledge base regarding the association between male factor infertility and general health through a critical review of the literature. Materials and Methods: A systematic review of the literature was carried out from inception to November 2019 in order to evaluate significant associations between male infertility and adverse health outcomes such as cardiovascular, oncologic, metabolic and autoimmune diseases as well as overall mortality. Results: In all, 27 studies met inclusion criteria and were critically examined. Five studies examined male infertility and cardiovascular disease risk, 11 examined oncologic risk (e.g., overall cancer risk, testis and prostate cancer), 8 examined aggregate chronic medical diseases and 5 infertility related to incidence of mortality, for a total of 599,807 men diagnosed with any male factor infertility covering a period from 1916 to 2016. Conclusions: A man's fertility and overall health appear to be interconnected. Therefore, a diagnosis of male infertility may allow a window into future comorbidity and/or mortality which may help guide clinical decisions and counseling. Several possible etiologies such as genetic, epigenetic, developmental, and lifestyle-based factors need to be further evaluated in order to establish the underlying mechanisms between male infertility and health.