A5051415467- Cancer, Hypoxia, and Metabolism
- Hepatocellular Carcinoma Treatment and Prognosis
- Organ Transplantation Techniques and Outcomes
- Liver physiology and pathology
- Pancreatic and Hepatic Oncology Research
- Fibroblast Growth Factor Research
- Liver Disease Diagnosis and Treatment
- Cancer Research and Treatments
- Colorectal Cancer Surgical Treatments
- Neuroendocrine Tumor Research Advances
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Lung Cancer Research Studies
- Liver Disease and Transplantation
- Cardiac Ischemia and Reperfusion
- Diet and metabolism studies
- Neuroblastoma Research and Treatments
- Cancer, Stress, Anesthesia, and Immune Response
- Pelvic and Acetabular Injuries
- Pancreatitis Pathology and Treatment
- Anesthesia and Neurotoxicity Research
- Hernia repair and management
- Congenital heart defects research
- Cancer Immunotherapy and Biomarkers
- Cardiac, Anesthesia and Surgical Outcomes
University Hospital of Zurich
2016-2025
University of Zurich
2013-2024
National Institute for Health Research
2024
University of Birmingham
2024
The University of Texas MD Anderson Cancer Center
2018-2019
Swiss National Science Foundation
2018
To develop a reproducible animal model mimicking novel 2-staged hepatectomy (ALPPS: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy) explore the underlying mechanisms.ALPPS combines portal vein ligation (PVL) with liver transection (step I), followed by resection of deportalized II) within 2 weeks after first surgery. This approach induces accelerated hypertrophy remnant to enable massive tumor load. mechanisms, we designed ALPPS in mice.The group received 90% PVL...
In regenerating liver, hepatocytes accumulate lipids before the major wave of parenchymal growth. This transient, regeneration‐associated steatosis (TRAS) is required for liver recovery, but its purpose unclear. The tumor suppressor phosphatase and tensin homolog (PTEN) a key inhibitor protein kinase B/mammalian target rapamycin axis that regulates growth metabolic adaptations after hepatectomy. quiescent PTEN causes pathological when lost, whereas role in remains unknown. Here, we show...
Remote ischemic preconditioning (RIPC), the repetitive transient mechanical obstruction of vessels at a limb remote to operative site, is novel strategy mitigate distant organ injury associated with surgery. In clinic, RIPC has demonstrated efficacy in protecting various organs against ischemia reperfusion (IR), but common mechanism underlying systemic protection not been identified. Here, we reasoned that may rely on adaptive physiological reponses toward local stress, as incurred through...
Interaction between sinusoidal endothelial cells and hepatocytes is a prerequisite for liver function. Upon tissue loss, both cell populations need to be regenerated. Repopulation occurs in coordinated pattern, first through the regeneration of parenchyme (hepatocytes), which then produces vascular growth factor (VEGF) enable subsequent angiogenic phase. The signals that instruct induce timely VEGF remain unidentified. Given highly vascularized, we reasoned fluctuations oxygenation after...
The aim of this study was to determine whether remote ischemic preconditioning (RIPC) protects aged liver against ischemia reperfusion (IR).The demands for surgery in an aging population are growing. Clamping vessels prevent blood loss is integral surgery, but the resulting IR injury (IRI) augments postoperative complications. More so, sensitivity hepatic IRI increases with age; however, no strategies have been developed that specifically protect old liver. RIPC, a novel protective approach,...
Abstract To explore the general requirement of endothelial mTORC2 during embryonic and adolescent development, we knocked out essential component Rictor in mouse endothelium embryo, adolescence cells vitro . During knockout resulted growth retardation lethality around day 12. We detected reduced peripheral vascularization delayed ossification developing fingers, toes vertebrae this confined midgestational period. did not affect viability, weight gain vascular development further adolescence....
Hypoxia is prominent in solid tumors and a recognized driver of malignancy. Thus far, targeting tumor hypoxia has remained unsuccessful. Myo-inositol trispyrophosphate (ITPP) re-oxygenating compound without apparent toxicity. In preclinical models, ITPP potentiates the efficacy subsequent chemotherapy through vascular normalization. Here, we report results an unrandomized, open-labeled, 3 + dose-escalation phase Ib study (NCT02528526) including 28 patients with advanced primary...
The body is dependent on the exogenous supply of omega-3 polyunsaturated fatty acids (n3-PUFA). These essential are key players in regulating metabolic signaling but also exert anti-inflammatory and anti-carcinogenic properties. liver a major organ involved acid metabolism. Under experimental conditions, n3-PUFA beneficial effect hepatic steatosis, regeneration inflammatory insults such as ischemic injury after surgery. Some these effects have been observed human subjects. However, it...
Abstract Purpose: Tumor hypoxia activates hypoxia-inducible factors (Hifs), which induce a range of malignant changes including vascular abnormalities. Here, we determine whether inhibition the hypoxic tumor response through myo-inositol trispyrophosphate (ITPP), compound with antihypoxic properties, is able to cause prolonged normalization that can be exploited improve standard-of-care treatment. Experimental Design: We tested ITPP on two syngeneic orthotopic mouse models lethal colorectal...
Solid tumors, such as hepato-pancreato-biliary cancer, develop tumor hypoxia with growth. Despite advances in surgery, a majority of these patients are an unresectable condition. At this stage standard cytotoxic chemotherapy regimens applied limited success. Novel biological treatment options based on antiangiogenic mechanism action neglect other mediated mechanisms (e.g. epithelial-mesenchymal transition, Warburg effect, and immunological response) leading to increased invasiveness poor...
The ability of the liver to restore its original volume following tissue loss has been associated with Hippo-YAP1 pathway, a key controller organ size. Yes-associated protein 1 (YAP1)—a growth effector usually restrained by Hippo signaling—is believed be particular importance; however, role in regeneration remains ill-defined. To explore function, we knocked down YAP1 prior standard 70%-hepatectomy (sHx) using hepatocyte-specific nanoformulation. Knockdown was effective during major...
The aim of this study was to assess the effect Ω3 fatty acids (Ω3FA) on and lean liver in hepatic surgery.The global spread energy-dense diets has led an endemic rise disease obesity. Besides metabolic pathologies, steatosis enhances sensitivity ischemia reperfusion (I/R) impedes regeneration (LR). Steatosis limits application surgery, still main curative option for cancer. Ω3FA are known reverse steatosis, but how these lipids affect key factors defining surgical outcomes-that is, I/R, LR,...
// Diego Vicente 1, 2 , Miguel Patino 2, 4 Rebecca Marcus 1 Heather Lillmoe Preparim Limani Timothy Newhook Andy Lee Ching-Wei Tzeng Yun Segraves-Chun David Tweardy 3 Vijaya Gottumukkala Jean-Nicolas Vauthey Thomas Aloia and Juan P. Cata Department of Surgical Oncology, The University Texas MD Anderson Cancer Center, Houston, TX, USA Anesthesiology Oncology Research Group, Molecular Cellular Perioperative Medicine, Correspondence to: Cata, email: jcata@mdanderson.org Keywords: analgesia;...
To investigate the impact of remote ischemic preconditioning (RIPC) on liver regeneration after major hepatectomy.RIPC is a strategy applied at sites to mitigate injury. Unlike other approaches, RIPC spares target organs as it acts via systemic VEGF elevations. In liver, however, an important driver following resection. Therefore, may have pro-regenerative effects.RIPC was C57BL/6 mice through intermittent clamping femoral vessels prior standard 68%-hepatectomy or extended 86%-hepatectomy,...