Severe Cholestatic Hepatitis due to Temozolomide

Grieco, Antonio; Tafuri, Maria Antonietta; Diletto, B.; Napoli, Nicola; Balducci, Nicola; Vecchio, Fabio Maria; Miele, Luca

doi:10.1097/md.0000000000000476

Cited by 13 publications

(10 citation statements)

References 11 publications

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“…However, chemoresistance and TMZ-induced side effects (anemia, lymphopenia, neutropenia, severe thrombocytopenia [ 3 , 28 , 29 , 30 ] and liver injury [ 31 , 32 ]) represent a big challenge in the management of oncological patients.…”

Section: Discussionmentioning

confidence: 99%

Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

et al. 2017

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Despite multimodal treatments comprising, radiation therapy (RT) and chemotherapy with temozolomide (TMZ), the prognosis of glioblastoma multiforme (GBM) remains dismal and consolidated therapy yields a median survival of 14.6 months.Blood Brain Barrier (BBB) mediated chemoresistance and high dose related toxicity make necessary the development of new therapeutic approach to sensitize GBM to TMZ.The aim of the present study was to investigate the potential of the treatment morphine plus TMZ metronmic doses (1,77 and 0,9 mg/kg) in GBM therapy.The effect of morphine, on tumor cell growth and P-glycoprothein (P-gp) activity, was investigate in in vitro models.The results demonstrated that GBM cells growth is not influenced by morphine treatment and, for the first time, we show that morphine is an inhibitor of the activity of P-gp efflux transporter who is markedly expressed on BBB.In vivo, response to the treatments TMZ plus morphine was investigated in an orthotopic nude mice model of GBM.Animals treated with TMZ metronomic doses showed a significant tumor growth inhibition compared to untreated mice and association with morphine appears to improve TMZ efficacy.Moreover, the combination of morphine with lower dose of TMZ result in a cytostatic effect on tumor growth over the period of the pharmacological treatments.In conclusion this novel approach could be a successful strategy to overcome chemoresistance and side effects TMZ mediated, reducing drug dosage and improving long term response, in GBM therapy.

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Section: Discussionmentioning

confidence: 99%

Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

et al. 2017

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“…Three of the recent case reports concern temozolomide, an anti-neoplastic alkylating agent mainly used in the treatment of gliomas (51–53). Temozolomide mainly causes cholestatic patterns of injury, spanning from acute cholestasis to cholestatic hepatitis to chronic cholestasis with ductopenia.…”

Section: Recent Reports Of Histological Injury Patterns In Dilimentioning

confidence: 99%

Recent Advances in the Histopathology of Drug-Induced Liver Injury

Kleiner

2018

Surgical Pathology Clinics

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Drug-induced liver injury (DILI) is constantly changing as new drugs are approved and as new herbals and dietary supplements (HDS) reach the market. The pathologist plays a key role in the evaluation of DILI by classifying and interpreting the histologic findings considering patients' medical history and drug exposure. The liver biopsy findings may suggest alternative explanations of the injury and additional testing that should be performed to exclude non-DILI causes. Recent reports of iatrogenic liver injury are reviewed with attention to immunomodulatory and antineoplastic agents as well as reports of injury associated with HDS use.

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“…The combined treatment based on radiotherapy and temozolomide is considered to be the optimal treatment for patients with glioblastoma, which doubles the 2-year survival rate to 27%. However, the efficacy of temozolomide is limited due to its drug resistance and toxic side effects 30 31 . Thus, it is crucial to develop new chemotherapeutic agents for treating patients with glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

“…It’s well known that multiple upstream signaling pathways are involved in the induction of autophagy, including beclin-1 (atg6), AMPK/mTOR, calcium signaling, endoplasmic reticulum-stress and Ras/Raf/MAPK pathway 42 . Among them, AMPK/mTOR plays a central role in the regulation of autophagy by integrating and coordinating different sensory inputs from upstream factors and then phosphorylating Atg proteins 31 43 . In our study, it’s noticeable that VOA induced autophagy via AMPK/mTOR signaling pathway in A172 cells but independently of mTOR inhibition in U251 cells.…”

Section: Discussionmentioning

confidence: 99%

Volatile Oil of Acori Graminei Rhizoma-Induced Apoptosis and Autophagy are dependent on p53 Status in Human Glioma Cells

Chen

Jiang

et al. 2016

Sci Rep

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Acori Graminei Rhizoma is well known for the beneficial effects on CNS disorders in traditional medicine. Though it is frequently prescribed in formulations for brain tumors, the anti-glioma effect has not been examined. We used volatile oil of Acori Graminei Rhizoma (VOA) and human glioblastoma multiforme (GBM) cells in this study. We found that VOA exhibited greater growth suppression in p53 wild-type cells than p53 mutant cells and very low effect on fibroblasts and human glial HEB cells. Apoptosis was triggered by VOA with a caspase-dependent way in p53 wild-type A172 cells, while a caspase-independent way in p53 mutant U251 cells. Meanwhile, both A172 and U251 cells treated by VOA displayed autophagic features. Furthermore, p53 decrease was observed along with VOA-induced apoptosis and autophagy in A172 cells. VOA-induced autophagy was mediated through a p53/AMPK/mTOR signaling pathway in A172 cells, while an mTOR-independent signaling pathway in U251 cells. Finally, blockage of autophagy potentiated the proapoptotic effect in both A172 and U251 cells, indicating a protective role of autophagy in VOA-induced cell death. Together, VOA exhibited anti-tumor activity in human GBM cells and induced apoptotic cell death and protective autophagy, which is cell type specific and dependent on p53 status.

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Severe Cholestatic Hepatitis due to Temozolomide

Cited by 13 publications

References 11 publications

Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

Recent Advances in the Histopathology of Drug-Induced Liver Injury

Volatile Oil of Acori Graminei Rhizoma-Induced Apoptosis and Autophagy are dependent on p53 Status in Human Glioma Cells

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