Environmental Health and Toxicology Resources of the United States National Library of Medicine

Hochstein, Colette; Arnesen, Stacey J.; Goshorn, Jeanne

doi:10.1300/j115v26n03_02

Cited by 9 publications

(3 citation statements)

References 5 publications

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“…Hepatotoxins can come directly from food, such as hepatotoxic mushrooms and fruits, or they can be generated during food processing, such as polycyclic aromatic hydrocarbons (Ref. 11). Fungal mycotoxins (such as aflatoxin B1) can be found in contaminated grains and nuts (Ref.…”

Section: Exposure Of the Liver To Xenobiotic Chemicalsmentioning

confidence: 99%

Molecular mechanisms underlying chemical liver injury

Manautou

2012

Expert Rev. Mol. Med.

267

147

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The liver is necessary for survival. Its strategic localisation, blood flow and prominent role in the metabolism of xenobiotics render this organ particularly susceptible to injury by chemicals to which we are ubiquitously exposed. The pathogenesis of most chemical-induced liver injuries is initiated by the metabolic conversion of chemicals into reactive intermediate species, such as electrophilic compounds or free radicals, which can potentially alter the structure and function of cellular macromolecules. Many reactive intermediate species can produce oxidative stress, which can be equally detrimental to the cell. When protective defences are overwhelmed by excess toxicant insult, the effects of reactive intermediate species lead to deregulation of cell signalling pathways and dysfunction of biomolecules, leading to failure of target organelles and eventual cell death. A myriad of genetic factors determine the susceptibility of specific individuals to chemical-induced liver injury. Environmental factors, lifestyle choices and pre-existing pathological conditions also have roles in the pathogenesis of chemical liver injury. Research aimed at elucidating the molecular mechanism of the pathogenesis of chemical-induced liver diseases is fundamental for preventing or devising new modalities of treatment for liver injury by chemicals.

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Section: Exposure Of the Liver To Xenobiotic Chemicalsmentioning

confidence: 99%

Molecular mechanisms underlying chemical liver injury

Manautou

2012

Expert Rev. Mol. Med.

267

147

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“…Brown, with the needs of occupational safety and health professionals in mind, and includes biological and physical hazards in addition to chemical hazards. 3 Since its start at NLM in 2002, Haz-Map has grown to include over 10,000 chemical and biological agents. Users can rapidly search by occupation, exposure, disease, or signs and symptoms.…”

Section: Haz-map® Http://hazmapnlmnihgov/mentioning

confidence: 99%

What Online Toxicology Resources Are Available at No Cost From the (US) National Library of Medicine to Assist Practicing OEM Physicians?

Downs

Hakkinen

2015

Journal of Occupational &Amp; Environmental Medicine

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“…The constructed models were validated through PROCHECK [29]and ProSA [30]servers. The ligand structure (LY-3023414) was retrieved from the TOXNET's Chem-IDplus database [31]. Sybyl-X 2.0 (Tripos international, USA) [32] was used for the present study.…”

Section: Methodsmentioning

confidence: 99%

Genomic profiling is predictive of response to cisplatin treatment but not to PI3K inhibition in bladder cancer patient-derived xenografts

et al. 2016

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PurposeEffective systemic therapeutic options are limited for bladder cancer. In this preclinical study we tested whether bladder cancer gene alterations may be predictive of treatment response.Experimental designWe performed genomic profiling of two bladder cancer patient derived tumor xenografts (PDX). We optimized the exome sequence analysis method to overcome the mouse genome interference.ResultsWe identified a number of somatic mutations, mostly shared by the primary tumors and PDX. In particular, BLCAb001, which is less responsive to cisplatin than BLCAb002, carried non-sense mutations in several genes associated with cisplatin resistance, including MLH1, BRCA2, and CASP8. Furthermore, RNA-Seq analysis revealed the overexpression of cisplatin resistance associated genes such as SLC7A11, TLE4, and IL1A in BLCAb001. Two different PIK3CA mutations, E542K and E545K, were identified in BLCAb001 and BLCAb002, respectively. Thus, we tested whether the genomic profiling was predictive of response to a dual PI3K/mTOR targeting agent, LY3023414. Despite harboring similar PIK3CA mutations, BLCAb001 and BLCAb002 exhibited differential response, both in vitro and in vivo. Sustained target modulation was observed in the sensitive model BLCAb002 but not in BLCAb001, as well as decreased autophagy. Interestingly, computational modelling of mutant structures and affinity binding to PI3K revealed that E542K mutation was associated with weaker drug binding than E545K.ConclusionsOur results suggest that the presence of activating PIK3CA mutations may not necessarily predict in vivo treatment response to PI3K targeted therapies, while specific gene alterations may be predictive for cisplatin response in bladder cancer models and, potentially, in patients as well.

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Environmental Health and Toxicology Resources of the United States National Library of Medicine

Cited by 9 publications

References 5 publications

Molecular mechanisms underlying chemical liver injury

Molecular mechanisms underlying chemical liver injury

What Online Toxicology Resources Are Available at No Cost From the (US) National Library of Medicine to Assist Practicing OEM Physicians?

Genomic profiling is predictive of response to cisplatin treatment but not to PI3K inhibition in bladder cancer patient-derived xenografts

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