Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy

Yi, Hee Jung; Hong, Kyung Sook; Moon, Nara; Chung, Sung-Chong; Lee, Ryung-Ah; Kim, Kwang Ho

doi:10.4174/astr.2016.90.3.179

Cited by 26 publications

(17 citation statements)

References 8 publications

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“…Additionally, similar to the doxorubicin effects on skeletal muscle (43,46),only Fol ri reduced skeletal muscle speci c force (strength per muscle unit area)which may occur through several mechanisms including brosis (15).Together this evidence suggests that signi cant muscle mass loss only occurs after sustained 5FU treatment (15,47),given that 1 week of 5FU was unable to reduce hindlimb muscle weight. We then hypothesize that a loss of water weight is likely to contribute to the observed body weight loss as anorexia and dehydration with 5FU has been reported (48,49).However, pathologies that occur early in the treatment regimen may provide insight into the etiology of muscle mass and strength losses with 5FU. To this end, 5FU-induced anemia and leukopeniaare likely to contribute to the observed functional pathologies that occur late with 5FU treatment.…”

Section: Discussionmentioning

confidence: 89%

The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

VanderVeen

Sougiannis

Velázquez

et al. 2020

Preprint

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Abstract Background: 5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g. colon, breast, head & neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical setting and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis through both the removal of damaged or old materials and coordinate repair and remodeling. Whether 5FU-induced leukopenia extends beyond circulation toimpact resident and infiltrating skeletal muscle immune cells had not been examined. The purpose of the study was to examine the acute effects of 5FU on resident and infiltrating skeletal muscle monocytes and inflammatory mediators. Methods: Male C57BL/6 mice were given a physiologically translatable dose (35mg/kg) of 5FU, or PBS, i.p. once daily for 5 days to recapitulate 1 dosing cycle. Results: Our results demonstrate that 5FU reduced circulating leukocytes, erythrocytes, and thrombocytes while inducing significant body weight loss (>5%). Flow cytometry analysis of the skeletal muscle indicated a reduction in total CD45+ immune cells with a corresponding decrease in total CD45+CD11b+ monocytes. There was a strong relationship between circulating leukocytes and skeletal muscle CD45+ immune cells. Skeletal muscle Ly6cHigh activated monocytes and M1-like macrophageswere reduced with 5FU treatment while total M2-like CD206+CD11c-macrophageswere not changed with 5FU. Interestingly, 5FU reduced bone marrow CD45+ immune cells and CD45+CD11b+ monocytes.Conclusions: Our results demonstrate that 5FU induced body weight loss and decreased skeletal muscle CD45+ immune cells in associated with a reduction in infiltrating Ly6cHigh monocytes. Interestingly, the loss of skeletal muscle immune cells occurred with bone marrow cell cycle arrest.Together our results highlight that skeletal muscle is sensitive to the cytotoxic effects of 5FU which disrupts both circulating and skeletal muscle immune cells.

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Section: Discussionmentioning

confidence: 89%

The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

VanderVeen

Sougiannis

Velázquez

et al. 2020

Preprint

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“…Therefore, colorectal cancer is one of the diseases seriously threating health (2,3). For patients with advanced colorectal cancer, tumor resection is not feasible and chemotherapy and biotherapy have become the only strategies for treatment (4,5). Unfortunately, however, these treatments are mostly ineffective because of the development of chemoresistance in cancer patients (6).…”

Section: Introductionmentioning

confidence: 99%

miR-20a-directed regulation of BID is associated with the TRAIL sensitivity in colorectal cancer

et al. 2016

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MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in cancer processes. Although miR-20a has been reported to be altered in a range of cancers, the role of miR-20a in colorectal cancer is not fully characterized, and the relationship between miR-20a dysregulation and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity is not defined. In the present study, we demonstrated significant upregulation of miR-20a in the serum of colorectal cancer patients, tumor tissues and cell lines by quantitative RT-PCR analysis. Furthermore, we found that the TRAIL-induced apoptosis was associated with the expression level of miR-20a in colorectal cancer. The knockdown of miR-20a by inhibitors increased the antitumor effect of TRAIL via caspase-8 dependent pathway. BID, which is a pro-apoptotic member of the Bcl-2 family, was found to be directly regulated by miR-20a in SW480 cells. The knockdown of miR-20a inhibited the translocation of tBID to the mitochondria, which induced the mitochondrial pathway of apoptosis. Notably, we found that the knockdown of miR-20a also reversed the resistance of TRAIL in established TRAIL-resistant SW480 cells by tBID-mitochondria pathway. Therefore, our results suggest that miR-20a acts as a tumor promoter in colorectal cancer, and the understanding of the miR-20a might be a potential therapeutic target for colorectal cancer.

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“…Inhibition of the tricarboxylic acid cycle also induces the metabolism of pyruvate to lactate, resulting in lactic acidosis. The second hypothesis proposes that a deficiency in dihydropyrimidine dehydrogenase, which is responsible for the degradation of 85% of 5-FU, leads to an increase in blood concentrations of 5-FU and its metabolite ammonia (7). In the third hypothesis, loss of appetite due to chemotherapy results in reduced thiamine uptake.…”

Section: Discussionmentioning

confidence: 99%

Severe Encephalopathy, Lactic Acidosis and Hyperammonaemia With FOLFIRI Plus Aflibercept After Two-stage Hepatectomy: A Case Report

Hara

Miyamoto

Hiyoshi

et al. 2019

In Vivo

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Background/Aim: Recent advances in chemotherapy have increased the possibility of conversion hepatectomy for patients with initially unresectable liver metastases. Although long-term chemotherapy and subsequent extensive hepatectomy are becoming more common, the toxicities of such chemotherapies are unclear. Patients and Methods: We present a case report of a patient with metastatic colorectal cancer who developed severe encephalopathy with lactic acidosis and hyperammonaemia caused by 5-fluorouracil-based chemotherapy. Administration of vitamin B1 and continuous haemodiafiltration rapidly improved the patient's symptoms. Conclusion: Intensive treatment of metastatic colorectal cancer patients with 5fluorouracil can induce rare adverse events. 563

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Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy

Cited by 26 publications

References 8 publications

The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

miR-20a-directed regulation of BID is associated with the TRAIL sensitivity in colorectal cancer

Severe Encephalopathy, Lactic Acidosis and Hyperammonaemia With FOLFIRI Plus Aflibercept After Two-stage Hepatectomy: A Case Report

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