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Wankun Chen, Yajun Xu, Jing Zhong, Huihui Wang, Meilin Weng, Qian Cheng, Qichao Wu, Zhirong Sun, Hui Jiang, Minmin Zhu, Yu Ren, Pingbo Xu, Jiawei Chen, Changhong Miao
Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is a predicted oncoprotein that demonstrates tumorigenic activity in vivo; however, the mechanisms involved are unknown. Macrophages are divided into the pro-inflammatory M1 and anti-inflammatory/protumoral M2 subtypes. Tumor cells can induce M2 polarization of tumor-associated macrophages (TAMs) to promote metastasis; but the underlying pathways require to be elucidated. In this study, we detected a positive association between MFHAS1 expression in TAMs and human colorectal cancer (CRC) TNM stage...
October 21, 2016: Oncotarget
Alexandra Sufit, Alisa B Lee-Sherick, Deborah DeRyckere, Manali Rupji, Bhakti Dwivedi, Marileila Varella-Garcia, Angela M Pierce, Jeanne Kowalski, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Amy K Keating, Douglas K Graham
BACKGROUND: MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines. METHODS: Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database...
2016: PloS One
María Virtudes Céspedes, María José Guillén, Pedro Pablo López-Casas, Francesca Sarno, Alberto Gallardo, Patricia Álamo, Carmen Cuevas, Manuel Hidalgo, Carlos María Galmarini, Paola Allavena, Pablo Avilés, Ramón Mangues
We explored whether the combination of lurbinectedin (PM01183) with the antimetabolite gemcitabine may result in synergistic antitumor effect in pancreatic adenocarcinoma (PDA) models. We also studied the contribution of lurbinectedin to this synergism. This drug presents a dual pharmacological effect that contributes to its in vivo antitumor activity: (i) specific binding to DNA minor groove inhibiting active transcription and DNA repair; and (ii) specific depletion of tumor-associated macrophages (TAMs).We evaluated the in vivo antitumor activity of lurbinectedin, gemcitabine (as single agents) and its combination in SW-1990 and MIA PaCa-2 cell-line xenografts and in patient-derived PDA models (AVATAR)...
October 20, 2016: Disease Models & Mechanisms
Robert I Menzies, Frederick W Tam, Robert J Unwin, Matthew A Bailey
Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function...
October 22, 2016: Kidney International
Jihye Han, Joonbeom Bae, Chang-Yong Choi, Sang-Pil Choi, Hyung-Sik Kang, Eun-Kyeong Jo, Jongsun Park, Young Sik Lee, Hyun-Seuk Moon, Chung-Gyu Park, Myung-Shik Lee, Taehoon Chun
Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation...
October 26, 2016: Autophagy
Kuntal Kanti Goswami, Madhurima Sarkar, Sarbari Ghosh, Akata Saha, Tithi Ghosh, Ipsita Guha, Subhasis Barik, Saptak Banerjee, Soumyabrata Roy, Anamika Bose, Parthasarathi Dasgupta, Rathindranath Baral
Heterogeneous tumor microenvironment (TME), broadly divided into tumor core and peripheral sub-microenvironments, differentially polarize normal macrophages into a different form known as tumor associated M2 macrophages (M2TAMs) to promote tumor growth. In view of the extensive immune-editing role of NLGP, here, we have observed that NLGP is effective to convert M2TAMs (CD11b(+)F4/80(high)) to M1 (CD11b(+)F4/80(low)) more prominently in tumor core, along with downregulation of other M2 associated markers, like, ManR, Ym1, Fizz1...
October 21, 2016: Molecular Immunology
Thanh Tam Tran, Joel Adams-Bedford, Vasoontara Yiengprugsawan, Sam-Ang Seubsman, Adrian Sleigh
INTRODUCTION: Injury and psychological distress are public health priorities because of their high occurrence in the population. This study examines the longitudinal effects of injury characteristics on psychological distress. METHODS: Study participants were enrolled distance learning Thai adults (N = 42,785 at 2013 follow-up) residing nationwide. We analysed 2009 and 2013 data. Injury questions included injury prevalence, causes and levels of severity. Distress was measured using the standard Kessler-6...
2016: PloS One
Joshua H K Tam, M Rebecca Cobb, Claudia Seah, Stephen H Pasternak
The amyloid hypothesis posits that the production of β-amyloid (Aβ) aggregates leads to neurodegeneration and cognitive decline associated with AD. Aβ is produced by sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretase. While nascent APP is well known to transit to the endosomal/ lysosomal system via the cell surface, we have recently shown that APP can also traffic to lysosomes intracellularly via its interaction with AP-3. Because AP-3 interacts with cargo protein via interaction with tyrosine motifs, we mutated the three tyrosines motif in the cytoplasmic tail of APP...
2016: PloS One
Mohamed M Abou Elatta, Foad Assal, Hussam M Basheer, Mazen Mohamed Ibrahim
Volar fracture dislocation is very uncommon, with few series reported in the literature. Patients with such injuries were treated by modified dynamic external fixators. The mean follow-up was 18 months (range, 6 to 92 mo). The mean range of interphalangeal (proximal interphalangeal) joints and distal interphalangeal joints were 90 and 74 degrees, respectively. The total active range of motion (TAM) was excellent (256 degrees). The mean quick disabilities of the arm, shoulder and hand score was 1.2. The advantages of our external fixators are that they are simple, cheap, adjustable, and allow immediate range of motion...
October 21, 2016: Techniques in Hand & Upper Extremity Surgery
Joaquim Carreras, Yara Yukie Kikuti, Sílvia Beà, Masashi Miyaoka, Shinichiro Hiraiwa, Haruka Ikoma, Ryoko Nagao, David Martin-Garcia, Itziar Salaverria, Ai Sato, Ichiki Akifumi, Giovanna Roncador, Juan F Garcia, Kiyoshi Ando, Elias Campo, Naoya Nakamura
AIMS AND METHODS: We aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large B-cell lymphoma (DLBCL(sn) ) in a series of 240 DLBCL(all ()(NOS)()) including DLBCL(sn) training set (n=11) and validation set (n=18), and DLBCL(non-sn) (n=211). RESULTS: In the training set 82% had non-GCB phenotype and 18% were EBER(+) . The genomic profile showed gains((+)) of 1q21.3q31.2 (55%), 10q24.1 (46%), 11q14.1 (46%) and 18q12.1q23 (46%); losses((-)) of 6q26q27 (55%) and 9p21...
October 24, 2016: Histopathology
Magdalena Paolino, Josef M Penninger
The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases...
October 21, 2016: Cancers
Takashi Dejima, Kenjiro Imada, Ario Takeuchi, Masaki Shiota, Jeffrey Leong, Tabitha Tombe, Kevin Tam, Ladan Fazli, Seiji Naito, Martin E Gleave, Christopher J Ong
BACKGROUND: LIM and SH3 domain protein 1 (LASP1) has been implicated in several human malignancies and has been shown to predict PSA recurrence in prostate cancer. However, the anti-tumor effect of LASP1 knockdown and the association between LASP1 and the androgen receptor (AR) remains unclear. The aim of this study is to clarify the significance of LASP1 as a target for prostate cancer, and to test the effect of silencing LASP1 in vivo using antisense oligonucleotides (ASO). METHODS: A tissue microarray (TMA) was performed to characterize the differences in LASP1 expression in prostate cancer treated after hormone deprivation therapy...
October 24, 2016: Prostate
Mathias Wenes, Min Shang, Mario Di Matteo, Jermaine Goveia, Rosa Martín-Pérez, Jens Serneels, Hans Prenen, Bart Ghesquière, Peter Carmeliet, Massimiliano Mazzone
Hypoxic tumor-associated macrophages (TAMs) acquire angiogenic and immunosuppressive properties. Yet it remains unknown if metabolic changes influence these functions. Here, we argue that hypoxic TAMs strongly upregulate the expression of REDD1, a negative regulator of mTOR. REDD1-mediated mTOR inhibition hinders glycolysis in TAMs and curtails their excessive angiogenic response, with consequent formation of abnormal blood vessels. Accordingly, REDD1 deficiency in TAMs leads to the formation of smoothly aligned, pericyte-covered, functional vessels, which prevents vessel leakiness, hypoxia, and metastases...
October 13, 2016: Cell Metabolism
Grace M Mackie, Dorit Samocha-Bonet, Charmaine S Tam
BACKGROUND: There remains common belief in the general community that weight cycling or 'yo-yo dieting' is associated with potential adverse effects on obesity and metabolic risk factors. In 1994, a review by the National Task Force on the Prevention and Treatment of Obesity concluded that weight cycling did not impact metabolism, and that weight loss attempts should not be discouraged. This study is an updated review of the literature published since 1994, to determine if weight cycling is associated with metabolic risk factors for obesity and type 2 diabetes...
October 20, 2016: Obesity Research & Clinical Practice
Angus Baumann, Jane Conway, Hannah Rosenfeld, Tam Le Cong, David J Torpy, Wayne Rankin
No abstract text is available yet for this article.
February 2016: Pathology
Fabio Camacho-Alonso, P Salmerón-Lozano, Y Martínez-Beneyto
The aim of this study was to evaluate the antibacterial effect of photodynamic therapy (PDT), 2 % chlorhexidine (CHX). The teeth were contaminated with 0.1 mL Enterococcus faecalis (3 × 10(8) cell/mL) and randomized into eight treatment groups: Group 1 (2.5 % NaOCl); Group 2 (PDT); Group 3 (2 % CHX); Group 4 (TAM); Group 5 (propolis), Group 6 (ozone), Group 7 (positive control) and Group 8 (negative control). Following treatment, the canal content was sampled. The samples were cultured in triplicate on blood agar plates to determine the number of colony forming units (CFU)/mL...
October 22, 2016: Odontology
Wai Jia Tam, Philip Yap
Approximately two-thirds of the world's older adults live in developing nations. By 2050, as many as 80% of such older people will live in low- and middle-income countries. In sub-Saharan Africa alone, the number of individuals aged 60 and older is projected to reach 163 million. Despite this demographic wave, the majority of Africa has limited access to qualified geriatric health care.(3) Although foreign aid and capacity-building efforts can help to close this gap over time, it is likely that failure to understand the unique context of Africa's older adults, many of whom are marginalized, will lead to inadequacies in service delivery and poor health outcomes...
October 22, 2016: Journal of the American Geriatrics Society
C T Lau, A Kan, N Shek, P Tam, K K Y Wong
BACKGROUND: Congenital pulmonary airway malformation (CPAM) is an increasingly recognized disease with potential mortality. Owing to limited published studies, the true incidence is yet to be determined. We carried out this prospective study with the aim to estimate its true incidence on a population basis. METHODS: An antenatal ultrasonography program was implemented since 2009. Fetuses with suspected intra-thoracic lesions were monitored by regular follow-ups...
October 21, 2016: Pediatric Surgery International
Jinke Xu, Mifong Tam, Sepideh Samadei, Sophie Lerouge, Jake Barralet, Mary M Stevenson, Marta Cerruti
Mucoadhesive drug delivery systems stick to mucosal tissues and prolong the local retention time of drugs. Since the colon is covered by a mucosal layer, mucoadhesive rectal formulations may improve treatment of such diseases as hypertension or colon cancer. Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the colonic mucosa. It is commonly treated with sulfasalazine (SSZ), which is metabolized by the intestinal flora into the therapeutic 5-aminosalicylic acid (5-ASA) and a toxic by-product sulfapyridine (SP)...
October 18, 2016: Acta Biomaterialia
Vivienne H Tam, Chris Sosa, Rui Liu, Nan Yao, Rodney D Priestley
The blood brain barrier (BBB) is a major obstacle to drug delivery for diseases of the central nervous system (CNS). This brief review highlights the current invasive and non-invasive technologies available to address this problem. In particular, nanomedicine has shown much promise as a non-invasive strategy due to its drug loading capabilities, ease of targeting to the BBB, and small size. The versatility of this technology in terms of type of drug and imaging agent, carrier material, and targeting mechanism is highlighted in this review...
October 18, 2016: International Journal of Pharmaceutics
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