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Isolated limb perfusion

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https://www.readbyqxmd.com/read/27890347/isolated-limb-perfusion-for-the-management-limb-threatening-soft-tissue-sarcomas-the-role-of-histological-type-on-clinical-outcomes
#1
M Rastrelli, S Mocellin, R Stramare, A Brunello, M Maruzzo, U Basso, G Scarzello, M S Buzzaccarini, P Pilati, L M Saadeh, S P Del Fiore, A Tosi, C Montesco, L G Campana, S Tropea, C R Rossi
BACKGROUND: Hyperthermic isolated limb perfusion (HILP) is an effective neoadjuvant treatment to avoid amputation in patients with locally advanced extremity soft tissue sarcomas (STS). We aimed to investigate whether STS histological type plays a role in predicting clinical outcomes. METHODS: This study reports a retrospective analysis of 125 patients with limb threatening STS (liposarcoma, n = 41; malignant peripheral nerve sheath tumor, n = 20; leiomyosarcoma, n = 20; miscellany, n = 44), who underwent HILP from 1990 through 2015 at our institution...
November 18, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27859767/mechanisms-for-the-control-of-local-tissue-blood-flow-during-thermal-interventions-influence-of-temperature-dependent-atp-release-from-human-blood-and-endothelial-cells
#2
Kameljit K Kalsi, Scott T Chiesa, Steven J Trangmar, Leena Ali, Makrand D Lotlikar, José González-Alonso
Local tissue perfusion changes with alterations in temperature during heating and cooling, but the thermosensitivity of the vascular ATP signalling mechanisms for control of blood flow during thermal interventions remains unknown. Here we tested the hypotheses that the release of the vasodilator mediator ATP from human erythrocytes, but not from endothelial cells or other blood constituents, is sensitive to both increases and reductions in temperature and that increasing intravascular ATP availability with ATP infusion would potentiate thermal hyperaemia in limb tissues...
November 17, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27832863/endothelial-progenitor-cells-from-human-fetal-aorta-cure-diabetic-foot-in-a-rat-model
#3
Wan-Ni Zhao, Shi-Qing Xu, Jian-Feng Liang, Liang Peng, Hong-Lin Liu, Zai Wang, Qing Fang, Meng Wang, Wei-Qin Yin, Wen-Jian Zhang, Jin-Ning Lou
OBJECTIVE: Recent evidence has suggested that circulating endothelial progenitor cells (EPCs) can repair the arterial endothelium during vascular injury. However, a reliable source of human EPCs is needed for therapeutic applications. In this study, we isolated human fetal aorta (HFA)-derived EPCs and analyzed the capacity of EPCs to differentiate into endothelial cells. In addition, because microvascular dysfunction is considered to be the major cause of diabetic foot (DF), we investigated whether transplantation of HFA-derived EPCs could treat DF in a rat model...
December 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27783991/oncolytic-vaccinia-virus-combined-with-radiotherapy-induces-apoptotic-cell-death-in-sarcoma-cells-by-down-regulating-the-inhibitors-of-apoptosis
#4
Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27752734/investigating-the-involvement-of-trpv1-ion-channels-in-remote-hind-limb-preconditioning-induced-cardioprotection-in-rats
#5
Puneet Kaur Randhawa, Amteshwar Singh Jaggi
Remote ischemic preconditioning (RIPC) treatment strategy is a breakthrough in the field of cardiovascular pharmacology as it has the potential to attenuate myocardial ischemia-reperfusion injury. However, the underlying intracellular pathways have not been widely explored. The present study intends to explore the possible role of TRPV1 channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 cycles in succession) was delivered by tying the blood pressure cuff at the inguinal level of the rat...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27746000/supplementing-essential-amino-acids-with-the-nitric-oxide-precursor-l-arginine-enhances-skeletal-muscle-perfusion-without-impacting-anabolism-in-older-men
#6
W Kyle Mitchell, Bethan E Phillips, Daniel J Wilkinson, John P Williams, Debbie Rankin, Jonathan N Lund, Kenneth Smith, Philip J Atherton
Postprandial limb blood flow and skeletal muscle microvascular perfusion reduce with aging. Here we tested the impact of providing bolus essential amino acids (EAA) in the presence and absence of the nitric oxide precursor, l-Arginine (ARG), upon skeletal muscle blood flow and anabolism in older men. Healthy young (YOUNG: 19.7 ± 0.5 y, N = 8) and older men (OLD, 70 ± 0.8 y, N = 8) received 15 g EAA or (older only) 15 g EAA +3 g ARG (OLD-ARG, 69.2 ± 1.2 y, N = 8). We quantified responses in muscle protein synthesis (MPS; incorporation of (13)C phenylalanine into myofibrillar proteins), leg and muscle microvascular blood flow (Doppler/contrast enhanced ultrasound (CEUS)) and insulin/EAA in response to EEA ± ARG...
October 6, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27739318/-hyperthermic-isolated-limb-perfusion-combined-with-tasonermin-a-perfusion-leakage-monitoring-technique
#7
J Trnka, M Špaček, V Šírová, P Mitáš, G Hodková, J Kubinyi, R Špunda, J Lindner
BACKGROUND: Hyperthermic isolated limb perfusion is used to treat irresectable extremity malignancies. It is based on the following principle - the perfusion of the extremity is isolated from systemic circulation and connected to an extra-corporal circuit via which a very high concentration of a chemotherapeutic agent is administered into the blood compartment of the extremity. In some cases, treatment efficiency can be improved using tasonermin (a TNF-α agent). By itself, tasonermin can cause severe health complications in patients if leakage into systemic circulation results in a level that exceeds the maximally tolerated dose...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27684571/effect-of-dose-on-intra-articular-amikacin-sulfate-concentrations-following-intravenous-regional-limb-perfusion-in-horses
#8
Alison Harvey, Isabelle Kilcoyne, Barbara A Byrne, Jorge Nieto
OBJECTIVE: To compare synovial concentrations of amikacin following intravenous regional limb perfusion (IVRLP) with two different doses, and to compare their ability to reach target concentrations for bacterial isolates from common orthopedic conditions. STUDY DESIGN: Randomized crossover experiment. ANIMALS: Six adult horses. METHODS: Horses received IVRLP with 2 and 3 g of amikacin in the cephalic vein of alternate limbs (20 minutes tourniquet application and ≥14 days washout period)...
September 29, 2016: Veterinary Surgery: VS
https://www.readbyqxmd.com/read/27681558/vasopressin-lowers-renal-epoxyeicosatrienoic-acid-levels-by-activating-soluble-epoxide-hydrolase
#9
Christin Boldt, Tom Röschel, Nina Himmerkus, Allein Plain, Markus Bleich, Robert Labes, Maximilian Blum, Hans Krause, Ahmed Magheli, Torsten Giesecke, Kerim Mutig, Michael Rothe, Steven M Weldon, Duska Dragun, Wolf-Hagen Schunck, Sebastian Bachmann, Alexander Paliege
Activation of the thick ascending limb (TAL) Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) by the antidiuretic hormone arginine vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here, we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5 ng/h, 3 days) significantly lowered renal EET levels (-56 ± 3% for 5,6-EET, -50 ± 3...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27680682/preclinical-validation-of-a-single-treatment-infusion-modality-that-can-eradicate-extremity-melanomas
#10
Minhyung Kim, Nickolay Neznanov, Chandler D Wilfong, Daria I Fleyshman, Andrei A Purmal, Gary Haderski, Patricia Stanhope-Baker, Catherine A Burkhart, Katerina V Gurova, Andrei V Gudkov, Joseph J Skitzki
Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an effective treatment option for extremity in-transit melanoma but is toxic and technically challenging to deliver locoregionally. CBL0137 is an experimental clinical drug with broad anticancer activity in animal models, owing to its ability to bind DNA in a nongenotoxic manner and inactivate the FACT chromatin modulator essential for tumor cell viability. Here, we report that CBL0137 delivered by ILP in a murine melanoma model is as efficacious as melphalan, displaying antitumor activity at doses corresponding to only a fraction of the systemic MTD of CBL0137...
September 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27680210/therapeutic-angiogenesis-induced-by-human-umbilical-cord-tissue-derived-mesenchymal-stromal-cells-in-a-murine-model-of-hindlimb-ischemia
#11
Ana Rita S Pereira, Teresa F Mendes, Augusto Ministro, Mariana Teixeira, Mariana Filipe, Jorge M Santos, Rita N Bárcia, J Goyri-O'Neill, Fausto Pinto, Pedro E Cruz, Helder J Cruz, Susana Constantino Rosa Santos
BACKGROUND: Mesenchymal stem cells derived from human umbilical cord tissue, termed UCX®, have the potential to promote a full range of events leading to tissue regeneration and homeostasis. The main goal of this work was to investigate UCX® action in experimentally induced hindlimb ischemia (HLI). METHODS: UCX®, obtained by using a proprietary technology developed by ECBio (Amadora, Portugal), were delivered via intramuscular injection to C57BL/6 females after unilateral HLI induction...
September 29, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27660293/restoration-of-hydrogen-sulfide-production-in-diabetic-mice-improves-reparative-function-of-bone-marrow-cells
#12
Zhongjian Cheng, Venkata Naga Srikanth Garikipati, Emily Nickoloff, Chunlin Wang, David J Polhemus, Jibin Zhou, Cynthia Benedict, Mohsin Khan, Suresh K Verma, Joseph E Rabinowitz, David Lefer, Raj Kishore
BACKGROUND: Bone marrow cell (BMC)-based treatment for critical limb ischemia in diabetic patients yielded a modest therapeutic effect resulting from cell dysfunction. Therefore, approaches that improve diabetic stem/progenitor cell functions may provide therapeutic benefits. Here, we tested the hypothesis that restoration of hydrogen sulfide (H2S) production in diabetic BMCs improves their reparative capacities. METHODS: Mouse BMCs were isolated by density-gradient centrifugation...
November 8, 2016: Circulation
https://www.readbyqxmd.com/read/27651800/umbilical-cord-derived-mesenchymal-stem-cells-relieve-hindlimb-ischemia-through-enhancing-angiogenesis-in-tree-shrews
#13
Cunping Yin, Yuan Liang, Jian Zhang, Guangping Ruan, Zian Li, Rongqing Pang, Xinghua Pan
Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27600523/reconstituted-high-density-lipoproteins-promote-wound-repair-and-blood-flow-recovery-in-response-to-ischemia-in-aged-mice
#14
Tania Tsatralis, Anisyah Ridiandries, Stacy Robertson, Laura Z Vanags, Yuen Ting Lam, Joanne T M Tan, Martin K C Ng, Christina A Bursill
BACKGROUND: The average population age is increasing and the incidence of age-related vascular complications is rising in parallel. Impaired wound healing and disordered ischemia-mediated angiogenesis are key contributors to age-impaired vascular complications that can lead to amputation. High-density lipoproteins (HDL) have vasculo-protective properties and augment ischemia-driven angiogenesis in young animals. We aimed to determine the effect of reconstituted HDL (rHDL) on aged mice in a murine wound healing model and the hindlimb ischemia (HLI) model...
2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27572153/regular-exercise-reduces-endothelial-cortical-stiffness-in-western-diet-fed-female-mice
#15
Jaume Padilla, Francisco I Ramirez-Perez, Javad Habibi, Brian Bostick, Annayya R Aroor, Melvin R Hayden, Guanghong Jia, Mona Garro, Vincent G DeMarco, Camila Manrique, Frank W Booth, Luis A Martinez-Lemus, James R Sowers
We recently showed that Western diet-induced obesity and insulin resistance promotes endothelial cortical stiffness in young female mice. Herein, we tested the hypothesis that regular aerobic exercise would attenuate the development of endothelial and whole artery stiffness in female Western diet-fed mice. Four-week-old C57BL/6 mice were randomized into sedentary (ie, caged confined, n=6) or regular exercise (ie, access to running wheels, n=7) conditions for 16 weeks. Exercise training improved glucose tolerance in the absence of changes in body weight and body composition...
November 2016: Hypertension
https://www.readbyqxmd.com/read/27507404/resolvin-d2-enhances-postischemic-revascularization-while-resolving-inflammation
#16
Michael J Zhang, Brian E Sansbury, Jason Hellmann, James F Baker, Luping Guo, Caitlin M Parmer, Joshua C Prenner, Daniel J Conklin, Aruni Bhatnagar, Mark A Creager, Matthew Spite
BACKGROUND: Resolvins are lipid mediators generated by leukocytes during the resolution phase of inflammation. They have been shown to regulate the transition from inflammation to tissue repair; however, it is unknown whether resolvins play a role in tissue revascularization following ischemia. METHODS: We used a murine model of hind limb ischemia (HLI), coupled with laser Doppler perfusion imaging, microcomputed tomography, and targeted mass spectrometry, to assess the role of resolvins in revascularization and inflammation resolution...
August 30, 2016: Circulation
https://www.readbyqxmd.com/read/27338249/co-dependence-of-the-neural-and-humoral-pathways-in-the-mechanism-of-remote-ischemic-conditioning
#17
Jack M J Pickard, Sean M Davidson, Derek J Hausenloy, Derek M Yellon
The cardioprotection afforded by remote ischaemic conditioning (RIC) is mediated via a complex mechanism involving sensory afferent nerves, the vagus nerve, and release of a humoral blood-borne factor. However, it is unknown whether release of the protective factor depends on vagal activation or occurs independently. This study aimed to evaluate the co-dependence of the neural and humoral pathways of RIC, focussing on the vagus nerve and intrinsic cardiac ganglia. In the first study, anesthetised rats received bilateral cervical vagotomy or sham-surgery immediately prior to RIC (4 × 5 min limb ischemia-reperfusion) or sham-RIC...
July 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27269515/isolated-limb-perfusion-as-a-treatment-option-for-rare-types-of-tumours
#18
Valerio Belgrano, Ilan Ben-Shabat, Peter Bergh, Roger Olofsson Bagge
BACKGROUND: Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours. METHODS: Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively...
September 2016: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/27237868/intralesional-pv-10-for-in-transit-melanoma-a-single-center-experience
#19
Jocelyn Lippey, Rhiannon Bousounis, Cori Behrenbruch, Bartholomew McKay, John Spillane, Michael A Henderson, David Speakman, David E Gyorki
BACKGROUND AND OBJECTIVES: Patients with in-transit melanoma metastasis have longer median survival than patients with distant metastatic disease. Furthermore, local disease control is an important endpoint for symptom management. The treatment of unresectable loco-regional recurrence or in-transit disease has been historically managed with a combination of treatments including surgery, radiotherapy, isolated limb infusion or perfusion as well as systemic therapies. Intralesional PV-10 has been used at Peter MacCallum Cancer Centre since 2010, and the current report presents a retrospective analysis of patient outcomes, reporting the response rates, durability of responses, and observed toxicities...
September 2016: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27197621/role-of-isolated-limb-perfusion-with-recombinant-human-tumor-necrosis-factor-%C3%AE-and-melphalan-in-locally-advanced-extremity-soft-tissue-sarcoma
#20
REVIEW
Jens Jakob, Peter Hohenberger
The management of locally advanced extremity soft tissue sarcoma of the limbs is challenging, particularly for recurrent tumors and those adjacent to neurovascular bundles and joints. Typically, the tumors are large, below the fascia, and high-grade (T2b or stage III according to the American Joint Committee on Cancer) and thus require multimodal therapy. Treatment options must be tailored to patient and tumor characteristics. Isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan (TNF-ILP) adds a therapeutic option to radiation therapy (RT) and systemic chemotherapy...
September 1, 2016: Cancer
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