Role of Tumor-Associated Macrophages in Sarcomas
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Uterine Sarcomas: a Review
ARTICLE IN PRESS YGYNO-973334; No. of pages: 9; 4C: 3, 6 Gynecologic Oncology xxx (2009) xxx–xxx Contents lists available at ScienceDirect Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno Review Uterine sarcomas: A review Emanuela D'Angelo, Jaime Prat ⁎ Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Sant Antoni M. Claret, 167, 08025 Barcelona, Spain article info abstract Article history: Objective. Uterine sarcomas are rare tumors that account for 3% of uterine cancers. Their histopathologic Received 29 June 2009 classification was revised by the World Health Organization (WHO) in 2003. A new staging system has been Available online xxxx recently designed by the International Federation of Gynecology and Obstetrics (FIGO). Currently, there is no consensus on risk factors for adverse outcome. This review summarizes the available clinicopathological data Keywords: on uterine sarcomas classified by the WHO diagnostic criteria. Uterine sarcomas Methods. Medline was searched between 1976 and 2009 for all publications in English where the studied Leiomyosarcoma population included women diagnosed of uterine sarcomas. Endometrial stromal sarcoma fi Undifferentiated endometrial sarcoma Results. Since carcinosarcomas (malignant mixed mesodermal tumors or MMMT) are currently classi ed Adenosarcoma as metaplastic carcinomas, leiomyosarcomas remain the most common uterine sarcomas. Exclusion of Carcinosarcoma several histologic variants of leiomyoma, as well as “smooth muscle tumors of uncertain malignant potential,” frequently misdiagnosed as sarcomas, has made apparent that leiomyosarcomas are associated with poor prognosis even when seemingly confined to the uterus. Endometrial stromal sarcomas are indolent tumors associated with long-term survival. Undifferentiated endometrial sarcomas exhibiting nuclear pleomorphism behave more aggressively than tumors showing nuclear uniformity. -
Serum Scd163 As a Biomarker of Adipose Tissue Inflammation in Obstructive Sleep Apnoea Patients: Limits and Perspectives
AGORA | CORRESPONDENCE Serum sCD163 as a biomarker of adipose tissue inflammation in obstructive sleep apnoea patients: limits and perspectives To the Editor: Recently, MURPHY et al. [1] demonstrated, through a challenging animal, cellular and human translational approach, that intermittent hypoxia induces a pro-inflammatory activation of adipose tissue macrophages (ATMs), promoting insulin resistance. They confirmed that intermittent hypoxia lowers insulin-mediated glucose uptake in 3T3-L1 adipocytes, and evidenced the interrelationship between inflammation and insulin resistance in the adipose tissue of mice exposed to intermittent hypoxia. They then measured the concentration of serum soluble CD163 (sCD163), an assumed pro-inflammatory biomarker reflecting macrophage activation, in obstructive sleep apnoea (OSA) patients classified according to their BMI and apnoea/hypopnoea index (AHI). This is the first time serum sCD163 has been evaluated in OSA patients, and its association with AHI is promising. With the aim of enhancing its relevance in further studies, we wish to discuss the following points. 1) Activation of adipose tissue macrophages (ATMs) towards M1 phenotype in OSA patients. MURPHY et al. [1] made the assumption that circulating sCD163 levels in OSA patients reflect the intermittent hypoxia-dependent polarisation of ATMs towards a M1 phenotype. As appropriately cited, KRAČMEROVÁ et al. [2] showed that circulating sCD163 concentrations are associated with both macrophage content in human adipose tissue, and insulin sensitivity. However, the assumption that serum sCD163 reflects such a polarisation based on the ADAM-17-dependent cleavage, as hypothesised by ETZERODT et al. [3], is unconvincing since only shown in HEK293 cells. Human ATMs are characterised by a high expression of CD163 which, in contrast, is weakly expressed in differentiated M1 macrophages [4]. -
Mr Leiomyoma Vs Leiomyosarcoma
2 0 SCBT· MR 1 LEIOMYOMA VS LEIOMYOSARCOMA 5 Susan M. Ascher, MD Professor & Co-Director of Abdominal Imaging Georgetown University Hospital, Washington, DC T2-W MRI: Normal Uterus, Leiomyoma and Leiomyosarcoma NORMAL LEIOMYOMA LEIOMYOSARCOMA LEIOMYOMA or LEIOMYOSARCOMA LEIOMYOMA LEIOMYOSARCOMA LEIOMYOMA or LEIOMYOSARCOMA LEIOMYOMA LEIOMYOSARCOMA LEIOMYOMA or LEIOMYOSARCOMA LEIOMYOMA LEIOMYOSARCOMA DEGENERATED LEIOMYOMA vs LEIOMYOSARCOMA Distinguishing the two can be challenging Laparoscopic Power Morcellators • Hysterectomy • Myommectomy Prognosis is significantly worse in women who had leiomyosarcomas morcellated than women who underwent standard abdominal hysterectomy Park JY, et al. Gynecol Oncol 2011; 122:255-259. Perri T, et al. Int J Gyencol Cancer 2009; 19:257-260 DEGENERATED LEIOMYOMA vs LEIOMYOSARCOMA Distinguishing the two can be challenging 4/17/14: FDA safety warning on LPM for hysterectomy & myomectomy • Prev of unsuspected uterine sarcoma: 1 in 352 • Prev of unsuspected uterine LMS: 1 in 498 • Upstaging sarcoma 1 in 7000 Pritts et al (open source) 7/10 -11/14: FDA OB-GYN Devices Panel FDA: Quantitative Assessment of the Prevalence of Unsuspected Uterine Sarcoma in Women undergoing Treatment of Uterine Fibroids. Summary and Key Findings http://www.fda.gov/downloads/MedicalDevices/Safety/AlertsandNotices/UCM393589. 7.11.14: “Fate of Uterine Device Now in Hands of FDA: Panel's Recommendations Run From Outright Ban to 'Black Box' Warning to Limited Use” Ethicon voluntarily suspend sales and recalls devices worldwide 9.22.14: “Gynecologists Resist FDA Over Popular Surgical Tool: Doctors Continue to Use Morcellators Months After Regulator Warned They Can Spread Undetected Cancer” 11.24.2014: FDA Black Box Warning & IIE “Warning Prompts Shift in Surgeries on Women” A Yale University study found that 84% of gynecological surgeons at large U.S. -
A Rare Presentation of Benign Brenner Tumor of Ovary: a Case Report
International Journal of Reproduction, Contraception, Obstetrics and Gynecology Periasamy S et al. Int J Reprod Contracept Obstet Gynecol. 2018 Jul;7(7):2971-2974 www.ijrcog.org pISSN 2320-1770 | eISSN 2320-1789 DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20182920 Case Report A rare presentation of benign Brenner tumor of ovary: a case report Sumathi Periasamy1, Subha Sivagami Sengodan2*, Devipriya1, Anbarasi Pandian2 1Department of Surgery, 2Department of Obstetrics and Gynaecology, Government Mohan Kumaramangalam Medical College, Salem, Tamil Nadu, India Received: 17 April 2018 Accepted: 23 May 2018 *Correspondence: Dr. Subha Sivagami Sengodan, E-mail: [email protected] Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Brenner tumors are rare ovarian tumors accounting for 2-3% of all ovarian neoplasms and about 2% of these tumors are borderline (proliferating) or malignant. These tumors are commonly seen in 4th-8th decades of life with a peak in late 40s and early 50s. Benign Brenner tumors are usually small, <2cm in diameter and often detected incidentally during surgery or on pathological examination. Authors report a case of a large, calcified benign Brenner tumor in a 55-year-old postmenopausal woman who presented with complaint of abdominal pain and mass in abdomen. Imaging revealed large complex solid cystic pelvic mass -peritoneal fibrosarcoma. She underwent laparotomy which revealed huge Brenner tumor weighing 9kg arising from left uterine cornual end extending up to epigastric region. -
Resistance to Immune Checkpoint Blockade in Uterine Leiomyosarcoma: What Can We Learn from Other Cancer Types?
cancers Review Resistance to Immune Checkpoint Blockade in Uterine Leiomyosarcoma: What Can We Learn from Other Cancer Types? Wout De Wispelaere 1 , Daniela Annibali 1,2 , Sandra Tuyaerts 1,3 , Diether Lambrechts 4,5 and Frédéric Amant 1,6,7,* 1 Department of Oncology, KU Leuven (University of Leuven) and Leuven Cancer Institute (LKI), 3000 Leuven, Belgium; [email protected] (W.D.W.); [email protected] (D.A.); [email protected] (S.T.) 2 Division of Oncogenomics, Antoni Van Leeuwenhoek—Netherlands Cancer Institute (AvL-NKI), 1066 CX Amsterdam, The Netherlands 3 Laboratory of Medical and Molecular Oncology (LMMO), Department of Medical Oncology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium 4 Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven (University of Leuven), 3000 Leuven, Belgium; [email protected] 5 VIB Center for Cancer Biology, Flemish Institute for Biotechnology (VIB), 3000 Leuven, Belgium 6 Centre for Gynecologic Oncology Amsterdam (CGOA), Antoni Van Leeuwenhoek—Netherlands Cancer Institute, University Medical Center (UMC), 1066 CX Amsterdam, The Netherlands 7 Department of Obstetrics and Gynecology, University Hospitals Leuven (UZ Leuven), 3000 Leuven, Belgium * Correspondence: [email protected] Simple Summary: Immune checkpoint blockade (ICB) has emerged as a very promising therapeutic option for patients, demonstrating unprecedented, durable responses in several difficult-to-treat Citation: De Wispelaere, W.; cancers. Despite research indicating a strong potential for ICB in uterine leiomyosarcomas (uLMSs), a Annibali, D.; Tuyaerts, S.; Lambrechts, clinical trial assessing response to ICB monotherapy in uLMSs showed no clinical benefit. Resistance D.; Amant, F. Resistance to Immune to ICB has been studied extensively in a variety of tumor types, but the resistance mechanisms Checkpoint Blockade in Uterine explaining the lack of response to ICB in uLMSs remain largely unexplored. -
Soft Tissue Cytopathology: a Practical Approach Liron Pantanowitz, MD
4/1/2020 Soft Tissue Cytopathology: A Practical Approach Liron Pantanowitz, MD Department of Pathology University of Pittsburgh Medical Center [email protected] What does the clinician want to know? • Is the lesion of mesenchymal origin or not? • Is it begin or malignant? • If it is malignant: – Is it a small round cell tumor & if so what type? – Is this soft tissue neoplasm of low or high‐grade? Practical diagnostic categories used in soft tissue cytopathology 1 4/1/2020 Practical approach to interpret FNA of soft tissue lesions involves: 1. Predominant cell type present 2. Background pattern recognition Cell Type Stroma • Lipomatous • Myxoid • Spindle cells • Other • Giant cells • Round cells • Epithelioid • Pleomorphic Lipomatous Spindle cell Small round cell Fibrolipoma Leiomyosarcoma Ewing sarcoma Myxoid Epithelioid Pleomorphic Myxoid sarcoma Clear cell sarcoma Pleomorphic sarcoma 2 4/1/2020 CASE #1 • 45yr Man • Thigh mass (fatty) • CNB with TP (DQ stain) DQ Mag 20x ALT –Floret cells 3 4/1/2020 Adipocytic Lesions • Lipoma ‐ most common soft tissue neoplasm • Liposarcoma ‐ most common adult soft tissue sarcoma • Benign features: – Large, univacuolated adipocytes of uniform size – Small, bland nuclei without atypia • Malignant features: – Lipoblasts, pleomorphic giant cells or round cells – Vascular myxoid stroma • Pitfalls: Lipophages & pseudo‐lipoblasts • Fat easily destroyed (oil globules) & lost with preparation Lipoma & Variants . Angiolipoma (prominent vessels) . Myolipoma (smooth muscle) . Angiomyolipoma (vessels + smooth muscle) . Myelolipoma (hematopoietic elements) . Chondroid lipoma (chondromyxoid matrix) . Spindle cell lipoma (CD34+ spindle cells) . Pleomorphic lipoma . Intramuscular lipoma Lipoma 4 4/1/2020 Angiolipoma Myelolipoma Lipoblasts • Typically multivacuolated • Can be monovacuolated • Hyperchromatic nuclei • Irregular (scalloped) nuclei • Nucleoli not typically seen 5 4/1/2020 WD liposarcoma Layfield et al. -
Mepact, INN-Mifamurtide
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT MEPACT 4 mg powder for concentrate for dispersion for infusion 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each vial contains 4 mg mifamurtide*. After reconstitution, each mL of suspension in the vial contains 0.08 mg mifamurtide. *fully synthetic analogue of a component of Mycobacterium sp. cell wall. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Powder for concentrate for dispersion for infusion White to off-white homogeneous cake or powder. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications MEPACT is indicated in children, adolescents and young adults for the treatment of high-grade resectable non-metastatic osteosarcoma after macroscopically complete surgical resection. It is used in combination with post-operative multi-agent chemotherapy. Safety and efficacy have been assessed in studies of patients 2 to 30 years of age at initial diagnosis (see section 5.1). 4.2 Posology and method of administration Mifamurtide treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of osteosarcoma. Posology The recommended dose of mifamurtide for all patients is 2 mg/m2 body surface area. It should be administered as adjuvant therapy following resection: twice weekly at least 3 days apart for 12 weeks, followed by once-weekly treatments for an additional 24 weeks for a total of 48 infusions in 36 weeks. Special populations Adults > 30 years None of the patients treated in the osteosarcoma studies were 65 years or older and in the phase III randomised study, only patients up to the age of 30 years were included. -
The Role of Tumor Necrosis Factor-Like Weak Inducer of Apoptosis in Atherosclerosis Via Its Two Different Receptors (Review)
EXPERIMENTAL AND THERAPEUTIC MEDICINE 14: 891-897, 2017 The role of tumor necrosis factor-like weak inducer of apoptosis in atherosclerosis via its two different receptors (Review) HENGDAO LIU1,2, DAN LIN3, HONG XIANG1, WEI CHEN1, SHAOLI ZHAO1,4, HUI PENG1, JIE YANG1, PAN CHEN1, SHUHUA CHEN1 and HONGWEI LU1,2 1Center for Experimental Medical Research; 2Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013; 3Qingdao Center for Disease Control and Prevention, Qingdao, Shandong 266033; 4Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China Received May 3, 2016; Accepted March 31, 2017 DOI: 10.3892/etm.2017.4600 Abstract. At present, it is commonly accepted that athero- 1. Introduction sclerosis is a chronic inflammatory disease characterized by disorder of the arterial wall. As one of the inflammatory cyto- Atherosclerosis remains a major global challenge (1). The kines of the tumor necrosis factor superfamily, tumor necrosis World Health Organization statistics data suggest that, by factor-like weak inducer of apoptosis (TWEAK) participates 2020, atherosclerosis will be the most common cause of death in the formation and progression of atherosclerosis. TWEAK, and morbidity in both developed and developing countries (2). when binding to its initial receptor, fibroblast growth factor Atherosclerosis has long been studied as a chronic inflamma- inducible molecule 14 (Fn14), exerts adverse biological func- tory disorder of the arterial wall, which involves numerous tions in atherosclerosis, including dysfunction of endothelial cytokines. Accumulating data suggests that one of the cyto- cells, phenotypic change of smooth muscle cells and inflam- kines, tumor necrosis factor-like weak inducer of apoptosis matory responses of monocytes/macrophages. -
Macrophage Activation Markers, CD163 and CD206, in Acute-On-Chronic Liver Failure
cells Review Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure Marlene Christina Nielsen 1 , Rasmus Hvidbjerg Gantzel 2 , Joan Clària 3,4 , Jonel Trebicka 3,5 , Holger Jon Møller 1 and Henning Grønbæk 2,* 1 Department of Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus N, Denmark; [email protected] (M.C.N.); [email protected] (H.J.M.) 2 Department of Hepatology & Gastroenterology, Aarhus University Hospital, 8200 Aarhus N, Denmark; [email protected] 3 European Foundation for the Study of Chronic Liver Failure (EF-CLIF), 08021 Barcelona, Spain; [email protected] (J.C.); [email protected] (J.T.) 4 Department of Biochemistry and Molecular Genetics, Hospital Clínic-IDIBAPS, 08036 Barcelona, Spain 5 Translational Hepatology, Department of Internal Medicine I, Goethe University Frankfurt, 60323 Frankfurt, Germany * Correspondence: [email protected]; Tel.: +45-21-67-92-81 Received: 1 April 2020; Accepted: 4 May 2020; Published: 9 May 2020 Abstract: Macrophages facilitate essential homeostatic functions e.g., endocytosis, phagocytosis, and signaling during inflammation, and express a variety of scavenger receptors including CD163 and CD206, which are upregulated in response to inflammation. In healthy individuals, soluble forms of CD163 and CD206 are constitutively shed from macrophages, however, during inflammation pathogen- and damage-associated stimuli induce this shedding. Activation of resident liver macrophages viz. Kupffer cells is part of the inflammatory cascade occurring in acute and chronic liver diseases. We here review the existing literature on sCD163 and sCD206 function and shedding, and potential as biomarkers in acute and chronic liver diseases with a particular focus on Acute-on-Chronic Liver Failure (ACLF). -
Single-Cell RNA Sequencing Demonstrates the Molecular and Cellular Reprogramming of Metastatic Lung Adenocarcinoma
ARTICLE https://doi.org/10.1038/s41467-020-16164-1 OPEN Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma Nayoung Kim 1,2,3,13, Hong Kwan Kim4,13, Kyungjong Lee 5,13, Yourae Hong 1,6, Jong Ho Cho4, Jung Won Choi7, Jung-Il Lee7, Yeon-Lim Suh8,BoMiKu9, Hye Hyeon Eum 1,2,3, Soyean Choi 1, Yoon-La Choi6,10,11, Je-Gun Joung1, Woong-Yang Park 1,2,6, Hyun Ae Jung12, Jong-Mu Sun12, Se-Hoon Lee12, ✉ ✉ Jin Seok Ahn12, Keunchil Park12, Myung-Ju Ahn 12 & Hae-Ock Lee 1,2,3,6 1234567890():,; Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell tran- scriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions. 1 Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea. -
Interleukin-9 Regulates Macrophage Activation in the Progressive Multiple Sclerosis Brain
Donninelli et al. Journal of Neuroinflammation (2020) 17:149 https://doi.org/10.1186/s12974-020-01770-z RESEARCH Open Access Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain Gloria Donninelli1†, Inbar Saraf-Sinik1,2†, Valentina Mazziotti3, Alessia Capone1,4, Maria Grazia Grasso5, Luca Battistini1, Richard Reynolds6, Roberta Magliozzi3,6*† and Elisabetta Volpe1*† Abstract Background: Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating disease of the central nervous system (CNS). Several cytokines are thought to be involved in the regulation of MS pathogenesis. We recently identified interleukin (IL)-9 as a cytokine reducing inflammation and protecting from neurodegeneration in relapsing–remitting MS patients. However, the expression of IL-9 in CNS, and the mechanisms underlying the effect of IL-9 on CNS infiltrating immune cells have never been investigated. Methods: To address this question, we first analyzed the expression levels of IL-9 in post-mortem cerebrospinal fluid of MS patients and the in situ expression of IL-9 in post-mortem MS brain samples by immunohistochemistry. A complementary investigation focused on identifying which immune cells express IL-9 receptor (IL-9R) by flow cytometry, western blot, and immunohistochemistry. Finally, we explored the effect of IL-9 on IL-9-responsive cells, analyzing the induced signaling pathways and functional properties. Results: We found that macrophages, microglia, and CD4 T lymphocytes were the cells expressing the highest levels of IL-9 in the MS brain. Of the immune cells circulating in the blood, monocytes/macrophages were the most responsive to IL-9. We validated the expression of IL-9R by macrophages/microglia in post-mortem brain sections of MS patients. -
Stems for Nonproprietary Drug Names
USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol