Sunitinib-Induced Hyperammonemic Encephalopathy in Gastrointestinal Stromal Tumors

2011 ◽  
Vol 45 (10) ◽  
pp. 1309-1309 ◽  
Author(s):  
Na-Ri Lee ◽  
Ho-Young Yhim ◽  
Chang-Yeol Yim ◽  
Jae-Yong Kwak ◽  
Eun-Kee Song
Keyword(s):  
Emergency Department ◽  
Growth Factor ◽  
Tyrosine Kinases ◽  
Ammonia Level ◽  
Hyperammonemic Encephalopathy ◽  
Metastatic Gist ◽  
Imatinib Resistant ◽  
Serum Ammonia Level ◽  
Serum Ammonia ◽  
Endothelial Growth Factor

Objective: To report 2 cases of hyperammonemic encephalopathy induced by sunitinib in patients with metastatic gastrointestinal stromal tumor (GIST). Case Summary: A 58-year-old man with imatinib-resistant metastatic GIST presented to the emergency department with confusion that developed 17 days after the initiation of sunitinib 50 mg/day. His serum ammonia level was markedly elevated (210 μg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. His neurologic status normalized within 24 hours and his serum ammonia level decreased to 64 μg/dL A 68-year-old woman with imatinib-resistant metastatic GIST was admitted into the emergency department with confusion and irritability that developed 10 days after the start of sunitinib therapy. Her serum ammonia level was markedly elevated (389 μg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. Within 24 hours, her mental status was improved and her serum ammonia level was decreased to 116 μg/dL. Sunitinib was reintroduced, and the same symptoms occurred after day 7 of administration. Sunitinib was not prescribed afterward and the woman did not experience any further encephalopathy symptoms. Discussion: Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases such as stem cell factor receptor, vascular endothelial growth factor, and platelet-derived growth factor. It is used as second-line therapy for patients with imatinib-resistant GIST. Hyperammonemic encephalopathy is an uncommon fatal complication of chemotherapy. According to the Naranjo probability scale, sunitinib was a probable cause of hyperammonemic encephalopathy in the patients described here. Although the mechanism of hyperammonemia is unclear, hyperammonemic encephalopathy might be caused by a vascular disorder related to the antiangiogenic properties of sunitinib, and it has ethnic differences associated with genetic polymorphisms. Conclusions: Sunitinib may Induce hyperammonemic encephalopathy in some patients. Although further studies are warranted, clinicians should be aware of this severe adverse event when using sunitinib for treatment of GIST.

scholarly journals Oxaliplatin-Induced Hyperammonemic Encephalopathy in a Patient with Metastatic Pancreatic Cancer: A Case Report

2017 ◽  
Vol 10 (3) ◽  
pp. 885-889 ◽  
Author(s):  
Takatsugu Ogata ◽  
Hironaga Satake ◽  
Misato Ogata ◽  
Yukimasa Hatachi ◽  
Hisateru Yasui
Keyword(s):  
Pancreatic Cancer ◽  
Nutritional Supplement ◽  
Ammonia Level ◽  
High Concentration ◽  
Hyperammonemic Encephalopathy ◽  
Consciousness Disorder ◽  
Serum Ammonia Level ◽  
Branched Chain ◽  
Gcs Score ◽  
Serum Ammonia

Oxaliplatin-based chemotherapy is widely used to treat advanced cancer. Oxaliplatin-induced hyperammonemic encephalopathy is rarely reported. Here, we report a case of oxaliplatin-induced hyperammonemic encephalopathy occurring after gemcitabine plus oxaliplatin (GEMOX) chemotherapy in a patient with pancreatic cancer. A 76-year-old man received GEMOX regimen as first-line treatment for pancreatic adenocarcinoma with peritoneal dissemination. GEMOX consists of gemcitabine (1,000 mg/m2) and oxaliplatin (100 mg/m2) on day 1, repeated every 2 weeks. The second cycle of GEMOX was administered as planned. However, he appeared to have difficulties with daily activities. Two days later, he visited the emergency room complaining of drowsiness. On examination, the patient had a Glasgow Coma Scale (GCS) score of 14 (E4V4M6), and asterixis was not present. Blood examination revealed a serum ammonia level of 202 µg/dL. The levels of serum hepatic enzymes were only mildly elevated, and the hemoglobin level was typical for this patient. Computed tomography, magnetic resonance imaging, lumbar puncture test, and blood culture showed no abnormality. Based on these results, he was diagnosed with oxaliplatin-induced hyperammonemia. One day after hospitalization, GCS score had significantly decreased to 6 (E1V1M4). His consciousness disorder improved after administration of a nutritional supplement containing a high concentration of branched-chain amino acids for 5 days, and the level of serum ammonia improved to 79 µg/dL. He stated that he could not remember the episode. The findings of this case suggest the importance of examining serum ammonia levels in patients receiving an oxaliplatin-containing regimen who develop disordered consciousness.

scholarly journals Quantifying the strength of heterointeractions among receptor tyrosine kinases from different subfamilies: Implications for cell signaling

2020 ◽  
Vol 295 (29) ◽  
pp. 9917-9933 ◽  
Author(s):  
Michael D. Paul ◽  
Hana N. Grubb ◽  
Kalina Hristova
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Eph Receptor ◽  
Vital Cell ◽  
Cell Processes ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Receptor tyrosine kinases (RTKs) are single-pass membrane proteins that control vital cell processes such as cell growth, survival, and differentiation. There is a growing body of evidence that RTKs from different subfamilies can interact and that these diverse interactions can have important biological consequences. However, these heterointeractions are often ignored, and their strengths are unknown. In this work, we studied the heterointeractions of nine RTK pairs, epidermal growth factor receptor (EGFR)–EPH receptor A2 (EPHA2), EGFR–vascular endothelial growth factor receptor 2 (VEGFR2), EPHA2–VEGFR2, EPHA2–fibroblast growth factor receptor 1 (FGFR1), EPHA2–FGFR2, EPHA2–FGFR3, VEGFR2–FGFR1, VEGFR2–FGFR2, and VEGFR2–FGFR3, using a FRET-based method. Surprisingly, we found that RTK heterodimerization and homodimerization strengths can be similar, underscoring the significance of RTK heterointeractions in signaling. We discuss how these heterointeractions can contribute to the complexity of RTK signal transduction, and we highlight the utility of quantitative FRET for probing multiple interactions in the plasma membrane.

scholarly journals Serum ammonia is a strong prognostic factor for patients with acute-on-chronic liver failure

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chenxia Hu ◽  
Kaizhou Huang ◽  
Lingfei Zhao ◽  
Fen Zhang ◽  
Zhongwen Wu ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Liver Failure ◽  
Ammonia Level ◽  
Chronic Liver ◽  
Hbv Reactivation ◽  
Chronic Liver Failure ◽  
Short Term ◽  
Plasma Ammonia ◽  
Serum Ammonia Level ◽  
Serum Ammonia

Abstract Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in acute-on-chronic liver failure (ACLF) is still unknown. We aimed to determine the association between serum ammonia level and short-term prognosis in ACLF. Furthermore, we performed an in-depth evaluation of the independent effect of serum ammonia level on the short-term prognosis of hepatitis B virus (HBV) reactivation-induced ACLF patients. We identified 174 patients as part of prospective observational studies in patients with ACLF. Plasma ammonia levels were measured on admission, and several prognostic scores were used to determine the prognostic effect of ammonia. The 28-day patient survival was determined. Receiver operating characteristic analysis was used to identify the cut-off points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. Plasma ammonia was significantly higher in nonsurvivors (83.53 ± 43.78 versus 67.13 ± 41.77 µmol/L, P = 0.013), and ACLF patients with hyperammonemia had significantly higher 28-day mortality than those without hyperammonemia. Ammonia was also closely related to ACLF grade (P < 0.001) and organ failure, including liver (P = 0.048), coagulation (P < 0.001) and brain (P < 0.001). HBV reactivation serves as the main precipitating factor in the ACLF population. Subgroup analysis showed that ammonia is also a strong prognostic factor in the HBV reactivation-induced ACLF population. Ammonia level is closely correlated with failure of other organs and is an independent risk factor for mortality in ACLF and the special population defined as HBV reactivation-related ACLF. Based on the results from our study, we measured serum ammonia in the population with ACLF, which strongly indicates their prognosis. It serves as an important biomarker and a therapeutic target.

scholarly journals Mammalian Sprouty-1 and -2 Are Membrane-Anchored Phosphoprotein Inhibitors of Growth Factor Signaling in Endothelial Cells

2001 ◽  
Vol 152 (5) ◽  
pp. 1087-1098 ◽  
Author(s):  
Maria-Antonietta Impagnatiello ◽  
Stefan Weitzer ◽  
Grainne Gannon ◽  
Amelia Compagni ◽  
Matt Cotten ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Map Kinase ◽  
Tyrosine Kinases ◽  
Functional Characterization ◽  
Leading Edge ◽  
Growth Factor Signaling ◽  
Kinase Activation ◽  
Rtk Signaling ◽  
Endothelial Growth Factor

Growth factor–induced signaling by receptor tyrosine kinases (RTKs) plays a central role in embryonic development and in pathogenesis and, hence, is tightly controlled by several regulatory proteins. Recently, Sprouty, an inhibitor of Drosophila development-associated RTK signaling, has been discovered. Subsequently, four mammalian Sprouty homologues (Spry-1–4) have been identified. Here, we report the functional characterization of two of them, Spry-1 and -2, in endothelial cells. Overexpressed Spry-1 and -2 inhibit fibroblast growth factor– and vascular endothelial growth factor–induced proliferation and differentiation by repressing pathways leading to p42/44 mitogen-activating protein (MAP) kinase activation. In contrast, although epidermal growth factor–induced proliferation of endothelial cells was also inhibited by Spry-1 and -2, activation of p42/44 MAP kinase was not affected. Biochemical and immunofluorescence analysis of endogenous and overexpressed Spry-1 and -2 reveal that both Spry-1 and -2 are anchored to membranes by palmitoylation and associate with caveolin-1 in perinuclear and vesicular structures. They are phosphorylated on serine residues and, upon growth factor stimulation, a subset is recruited to the leading edge of the plasma membrane. The data indicate that mammalian Spry-1 and -2 are membrane-anchored proteins that negatively regulate angiogenesis-associated RTK signaling, possibly in a RTK-specific fashion.

scholarly journals Fatal Nonhepatic Hyperammonemia in ICU Setting: A Rare but Serious Complication following Bariatric Surgery

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Gyanendra Acharya ◽  
Sunil Mehra ◽  
Ronakkumar Patel ◽  
Simona Frunza-Stefan ◽  
Harmanjot Kaur
Keyword(s):  
Bariatric Surgery ◽  
Normal Liver ◽  
Liver Function Tests ◽  
Altered Mental Status ◽  
Ammonia Level ◽  
Gastric Bypass Procedure ◽  
History Of ◽  
Serum Ammonia Level ◽  
Pedal Edema ◽  
Serum Ammonia

Bariatric surgery is well established in reducing weight and improving the obesity-associated morbidity and mortality. Hyperammonemic encephalopathy following bariatric surgery is rare but highly fatal if not diagnosed in time and managed aggressively. Both macro- and micronutrients deficiencies play a role. A 42-year-old Hispanic female with a history of Roux-en-Y Gastric Bypass Procedure was brought to ED for progressive altered mental status. Physical exam was remarkable for drowsiness with Glasgow Coma Scale 11, ascites, and bilateral pedal edema. Labs showed elevated ammonia, low hemoglobin, low serum prealbumin, albumin, HDL, and positive toxicology. She remained obtunded despite the treatment with Narcan and flumazenil and the serum ammonia level fluctuated despite standard treatment with lactulose and rifaximin. Laboratory investigations helped to elucidate the etiology of the hyperammonemia most likely secondary to unmasking the functional deficiency of the urea cycle enzymes. Hyperammonemia in the context of normal liver function tests becomes diagnostically challenging for physicians. Severe hyperammonemia is highly fatal. Early diagnosis and aggressive treatment can alter the prognosis favorably.

The relationship between serum ammonia level and neurologic complications in patients with acute glufosinate ammonium poisoning: A prospective observational study

2017 ◽  
Vol 37 (6) ◽  
pp. 571-579 ◽  
Author(s):  
YS Cha ◽  
H Kim ◽  
Y Lee ◽  
EH Choi ◽  
HI Kim ◽  
...  
Keyword(s):  
Observational Study ◽  
Prospective Observational Study ◽  
Latency Period ◽  
Ammonia Level ◽  
Control Group ◽  
Neurologic Complication ◽  
Neurologic Complications ◽  
Glufosinate Ammonium ◽  
Serum Ammonia Level ◽  
Serum Ammonia

Glufosinate ammonium poisoning can cause neurological complications even after a symptom-free period. We prospectively investigated the predictors of neurologic complications in acute glufosinate ammonium poisoning and the change of serum ammonia level as a predictor of patient’s presence and recovery of neurologic complication. This prospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between September 2014 and June 2016. Serum ammonia was serially measured. The patients were divided into two groups: the neurologic complication group and the nonneurologic complication group. We also defined 25 other insecticide- or herbicide-poisoned patients as controls. The neurologic complication group included 18 patients (72.0%). The latency period for neurologic complications was within 48-h postingestion. The peak ammonia level was statistically higher in the neurologic complication group than in the control group ( p < 0.001) and the nonneurologic complication groups ( p = 0.001). There was a statistical difference between the nonneurologic complication group and the neurologic complication group ( p = 0.0085) in terms of ingested amount. The peak ammonia was the only predictor for the development of neurologic complications (the optimal cutoff: 90 μg/dL). In patients with mental changes, the mean serum ammonia levels before and after recovery of the mental changes were statistically different ( p = 0.0019). In acute glufosinate ammonium poisoning, serial serum ammonia level measurements are needed and a serum peak ammonia level greater than 90 μg/dL is a predictor of neurologic complications. Also, it is important to treat the hyperammonemia in acute glufosinate ammonium poisoning.

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