LIM Kinases in Osteosarcoma Development

Tumorigenesis is a long-term and multistage process that often leads to the formation of metastases. During this pathological course, two major events appear to be crucial: primary tumour growth and metastatic expansion. In this context, despite research and clinical advances during the past decades, bone cancers remain a leading cause of death worldwide among paediatric cancer patients. Osteosarcomas are the most common malignant bone tumours in children and adolescents. Notwithstanding advances in therapeutic treatments, many patients succumb to these diseases. In particular, less than 30% of patients who demonstrate metastases at diagnosis or are poor responders to chemotherapy survive 5 years after initial diagnosis. LIM kinases (LIMKs), comprising LIMK1 and LIMK2, are common downstream effectors of several signalization pathways, and function as a signalling node that controls cytoskeleton dynamics through the phosphorylation of the cofilin family proteins. In recent decades, several reports have indicated that the functions of LIMKs are mainly implicated in the regulation of actin microfilament and the control of microtubule dynamics. Previous studies have thus identified LIMKs as cancer-promoting regulators in multiple organ cancers, such as breast cancer or prostate cancer. This review updates the current understanding of LIMK involvement in osteosarcoma progression.

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Spatial control of actin-based motility through plasmalemmal PtdIns(4,5)P2-rich raft assemblies.

Biochemical Society Symposium ◽

10.1042/bss0720119 ◽

2005 ◽

Vol 72 ◽

pp. 119-127 ◽

Cited By ~ 19

Author(s):

Tamara Golub ◽

Caroni Pico

Keyword(s):

Protein Kinase ◽

Cell Surface ◽

Actin Cytoskeleton ◽

Lipid Rafts ◽

Patch Clustering ◽

Pkc Protein Kinase C ◽

Membrane Bound ◽

And Function ◽

Cytoskeleton Dynamics ◽

Syndrome Protein

The interactions of cells with their environment involve regulated actin-based motility at defined positions along the cell surface. Sphingolipid- and cholesterol-dependent microdomains (rafts) order proteins at biological membranes, and have been implicated in most signalling processes at the cell surface. Many membrane-bound components that regulate actin cytoskeleton dynamics and cell-surface motility associate with PtdIns(4,5)P2-rich lipid rafts. Although raft integrity is not required for substrate-directed cell spreading, or to initiate signalling for motility, it is a prerequisite for sustained and organized motility. Plasmalemmal rafts redistribute rapidly in response to signals, triggering motility. This process involves the removal of rafts from sites that are not interacting with the substrate, apparently through endocytosis, and a local accumulation at sites of integrin-mediated substrate interactions. PtdIns(4,5)P2-rich lipid rafts can assemble into patches in a process depending on PtdIns(4,5)P2, Cdc42 (cell-division control 42), N-WASP (neural Wiskott-Aldrich syndrome protein) and actin cytoskeleton dynamics. The raft patches are sites of signal-induced actin assembly, and their accumulation locally promotes sustained motility. The patches capture microtubules, which promote patch clustering through PKA (protein kinase A), to steer motility. Raft accumulation at the cell surface, and its coupling to motility are influenced greatly by the expression of intrinsic raft-associated components that associate with the cytosolic leaflet of lipid rafts. Among them, GAP43 (growth-associated protein 43)-like proteins interact with PtdIns(4,5)P2 in a Ca2+/calmodulin and PKC (protein kinase C)-regulated manner, and function as intrinsic determinants of motility and anatomical plasticity. Plasmalemmal PtdIns(4,5)P2-rich raft assemblies thus provide powerful organizational principles for tight spatial and temporal control of signalling in motility.

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Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome

Nuklearmedizin ◽

10.1055/s-0038-1625714 ◽

2005 ◽

Vol 44 (03) ◽

pp. 107-117

Author(s):

R. G. Meyer ◽

W. Herr ◽

A. Helisch ◽

P. Bartenstein ◽

I. Buchmann

Keyword(s):

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Primary Tumour ◽

The Other ◽

Haematopoietic Stem Cell ◽

Other Hand ◽

Primary Reduction ◽

The One ◽

Acute Myeloid

SummaryThe prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term diseasefree survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT.This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

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[18F]Fluoride PET Indicates Reduced Bone Formation in Severe Glucocorticoid-induced Osteoporosis

Nuklearmedizin ◽

10.1055/s-0038-1629797 ◽

1998 ◽

Vol 37 (02) ◽

pp. 76-79 ◽

Cited By ~ 8

Author(s):

T. D. Kirchhoff ◽

W. Burchert ◽

J. v. d. Hoff ◽

H. Zeidler ◽

H. Hundeshagen ◽

...

Keyword(s):

Bone Formation ◽

Multiple Organ ◽

High Dose ◽

Multiple Fractures ◽

Glucocorticoid Treatment ◽

Organ Manifestations ◽

Diagnostic Benefit ◽

Sharp Syndrome ◽

18F Fluoride

SummaryA 61-year-old female patient presenting with mixed connective tissue disease (Sharp syndrome), underwent a long-term high dose glucocorticoid treatment because of multiple organ manifestations. Under steroid therapy she developed severe osteoporosis resulting in multiple fractures. A dynamic [18F]fluoride PET study in this patient revealed reduced fluoride influx in non-fractured vertebrae. This finding corresponds to pathogenetic concepts which propose an inhibition of bone formation as major cause of glucocorticoid-induced osteoporosis. In the light of the presented case it seems to be promising to evaluate the diagnostic benefit of [18F]fluoride PET in osteoporosis.

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Antiplatelet Therapy in Acute Coronary Syndromes

European Cardiology Review ◽

10.15420/ecr.2010.6.1.58 ◽

2010 ◽

Vol 6 (1) ◽

pp. 58

Author(s):

Sasha Koul ◽

David Erlinge ◽

◽

Keyword(s):

Platelet Function ◽

Acute Coronary Syndromes ◽

New Drugs ◽

Antiplatelet Drugs ◽

Bleeding Complications ◽

Great Promise ◽

Mortality Data ◽

Poor Responders ◽

Coronary Syndromes

Drugs inhibiting platelet function play a major role in the treatment of acute coronary syndromes (ACS). The first drug used, which is still considered the cornerstone of therapy today, is aspirin. Although very impressive in acutely decreasing rates of myocardial infarction as well as death, long-term data are scarce, despite our current recommendation for lifelong aspirin. The thienopyridines, most notably clopidogrel, are the next line of antiplatelet drugs. Well-documented data support the usage of clopidogrel for non-STEMI-ACS (NSTE-ACS). Although positive mortality data exist regarding clopidogrel and STEMI patients in a medically treated population, including thrombolysis, no larger amounts of randomised data exist in a primary PCI setting. Poor responders to aspirin and/or clopidogrel are a clinical problem, with these individuals constituting a higherrisk group for recurrent ischaemic events. Whereas very little can be done regarding aspirin resistance, clopidogrel resistance might be diminished by increasing the dosage or changing to more potent and newer-generation antiplatelet drugs. The role of glycoprotein IIb/IIIa inhibitors has diminished drastically and instead paved the way for thrombin antagonists (bivalirudin), which have fewer bleeding complications with resulting better long-term mortality. Novel adenosine diphosphate (ADP)-receptor blockers such as prasugrel and ticagrelor have shown increased efficacy over clopidogrel and hold great promise for the future. However, not all patients may benefit from these new drugs and economic constraints may also limit their use. Platelet function tests could possibly help in identifying risk groups in need of stronger platelet inhibition.

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Long-term Effects on the Histology and Function of Livers and Spleens in Rats after 33% Toploading of PEG-PLA-nano Artificial Red Blood Cells

Artificial Cells Blood Substitutes and Biotechnology ◽

10.1080/10731190802554224 ◽

2008 ◽

Vol 36 (6) ◽

pp. 513-524 ◽

Cited By ~ 15

Author(s):

Zun Chang Liu ◽

Thomas M.S. Chang

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Long Term Effects ◽

And Function

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Climate Mobility and Development Cooperation

Population and Environment ◽

10.1007/s11111-021-00387-5 ◽

2021 ◽

Author(s):

Robert Stojanov ◽

Sarah Rosengaertner ◽

Alex de Sherbinin ◽

Raphael Nawrotzki

Keyword(s):

Climate Adaptation ◽

Human Mobility ◽

Climate Impacts ◽

Development Cooperation ◽

Climate Variability And Change ◽

Policy Frameworks ◽

And Migration ◽

And Function ◽

Role And Function

AbstractDevelopment cooperation actors have been addressing climate change as a cross-cutting issue and investing in climate adaptation projects since the early 2000s. More recently, as concern has risen about the potential impacts of climate variability and change on human mobility, development cooperation actors have begun to design projects that intentionally address the drivers of migration, including climate impacts on livelihoods. However, to date, we know little about the development cooperation’s role and function in responding to climate related mobility and migration. As such, the main aim of this paper is to outline the policy frameworks and approaches shaping development cooperation actors’ engagement and to identify areas for further exploration and investment. First, we frame the concept of climate mobility and migration and discuss some applicable policy frameworks that govern the issue from various perspectives; secondly, we review the toolbox of approaches that development cooperation actors bring to climate mobility; and third, we discuss the implications of the current Covid-19 pandemic and identify avenues for the way forward. We conclude that ensuring safe and orderly mobility and the decent reception and long-term inclusion of migrants and displaced persons under conditions of more severe climate hazards, and in the context of rising nationalism and xenophobia, poses significant challenges. Integrated approaches across multiple policy sectors and levels of governance are needed. In addition to resources, development cooperation actors can bring data to help empower the most affected communities and regions and leverage their convening power to foster more coordinated approaches within and across countries.

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Pediatric Antiphospholipid Syndrome: from Pathogenesis to Clinical Management

Current Rheumatology Reports ◽

10.1007/s11926-020-00976-7 ◽

2021 ◽

Vol 23 (2) ◽

Author(s):

Silvia Rosina ◽

Cecilia Beatrice Chighizola ◽

Angelo Ravelli ◽

Rolando Cimaz

Keyword(s):

Antiphospholipid Syndrome ◽

Fluid Phase ◽

Multiple Organ ◽

Clinical Settings ◽

Glycoprotein I ◽

Long Term Follow Up ◽

Pediatric Populations ◽

Cellular Components

Abstract Purpose of Review Elucidating the pathogenic mechanisms mediated by antiphospholipid antibodies (aPL) might exert important clinical implications in pediatric antiphospholipid syndrome (APS). Recent Findings aPL are traditionally regarded as the main pathogenic players in APS, inducing thrombosis via the interaction with fluid-phase and cellular components of coagulation. Recent APS research has focused on the role of β2 glycoprotein I, which bridges innate immunity and coagulation. In pediatric populations, aPL should be screened in appropriate clinical settings, such as thrombosis, multiple-organ dysfunction, or concomitant systemic autoimmune diseases. Children positive for aPL tests often present non-thrombotic non-criteria manifestations or asymptomatic aPL positivity. In utero aPL exposure has been suggested to result in developmental disabilities, warranting long-term follow-up. Summary The knowledge of the multifaceted nature of pediatric APS should be implemented to reduce the risk of underdiagnosing/undertreating this condition. Hopefully, recent pathogenic insights will open new windows of opportunity in the management of pediatric APS.

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Diagnosis, treatment, and misdiagnosis analysis of 28 cases of central nervous system echinococcosis

Chinese Neurosurgical Journal ◽

10.1186/s41016-021-00248-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Guojia Du ◽

Yandong Li ◽

Pan Wu ◽

Xin Wang ◽

Riqing Su ◽

...

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Clinical Features ◽

Multiple Organ ◽

Pathological Examination ◽

Surgical Removal ◽

Surgical Treatments

Abstract Background To explore central nervous system (CNS) involvement in this disease, from the perspectives of diagnosis, treatment, and misdiagnosis Methods Twenty-eight patients with CNS echinococcosis were included in this retrospective study, including 18 males (64.3%) and 10 (35.7%) females. The average age of all the patients were 23.5 years (ranged 4–60 years). Twenty-three (23) patients (82.1%) received the first surgical resection in our hospital. Five (5) patients (17.9%) gave up surgical treatment for multiple-organ hydatidosis and previous surgery history at other hospitals, and albendazole was applied for a long-term (3–6 months) adjunct therapy for the 5 patients. The average follow-up time was 8 years. Results For the 28 patients, 23 cases received surgical treatments, and the diagnosis was confirmed by pathological examinations. The diagnosis of 4 cases of brain echinococcosis and 2 cases of spinal cord echinococcosis could not be confirmed, resulting in a misdiagnosis rate of 21.4% (6/28). For the pathological examination, a total of 17 cases were infected with Echinococcus granulosus (including 2 cases of spinal cord echinococcosis), and 6 cases were infected with Echinococcus alveolaris. Conclusion The diagnosis should be specifically considered in endemic regions. The clinical features of CNS hydatidosis were intracranial space-occupying lesions. For the treatment, the surgical removal of cysts should be necessary. In addition, the adjuvant therapy with drug and intraoperative prophylaxis is also suggested. The misdiagnosis may have resulted from atypical clinical features and radiographic manifestations, as well as the accuracy of hydatid immunologic test.

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Shoulder arthroplasty for juvenile idiopathic arthritis

Journal of Orthopaedic Surgery ◽

10.1177/2309499019890615 ◽

2020 ◽

Vol 28 (1) ◽

pp. 230949901989061

Author(s):

Suroosh Madanipour ◽

Aditya Prinja ◽

Marcus Lee ◽

Abbas Rashid

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Shoulder Arthroplasty ◽

Preoperative Evaluation ◽

Implant Design ◽

Significant Heterogeneity ◽

Post Operative Pain ◽

Inflammatory Arthropathy ◽

Long Term Follow Up ◽

And Function

There is limited literature to guide shoulder surgeons in the management of juvenile idiopathic arthritis (JIA). We aim to help clinicians to formulate an approach to the surgical management of the condition through a review of the available literature on arthroplasty in JIA, general considerations when operating on patients with inflammatory arthropathy and recommendations based on the authors’ experience. Four articles report formal data on arthroplasty in JIA with favourable improvements in post-operative pain and function scores after the long-term follow-up. Significant heterogeneity in treatment and a lack of standardisation in quantitative outcomes highlights the need for further larger scale and higher quality research. The aim of this study is to review the evidence and provide information on preoperative evaluation of surgical candidates, operative techniques, choice of implant design and to evaluate functional outcomes in patients who undergo shoulder arthroplasty.

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