TH-4000, a hypoxia-activated pan-HER inhibitor, shows excellent preclinical efficacy for the treatment of HER2 < sup > + < /sup > breast cancer
Arch Toxicol. 2024 Mar;98(3):865-881. doi: 10.1007/s00204-023-03670-6. Epub 2024 Jan 11.ABSTRACTHuman epidermal growth factor receptor 2-positive (HER2+) breast cancer is correlated with poor prognosis, the current treatment of which is still based on surgery and adjuvant targeted therapy with monoclonal antibody. Problems of drug resistance hinder the use of monoclonal antibodies. Subsequently, tyrosine kinase inhibitors (TKIs) have been noticed, TKIs have the advantages of multi-targets and reduced drug resistance. However, TKIs that target HER family proteins often cause adverse effects such as liver damage and diarrhea...
Source: Archives of Toxicology - January 11, 2024 Category: Toxicology Authors: Xinyi Shao Dawei Yang Liuqun Shan Xueqin Yan Di Xu Lei Li Yidan Sun Qiang Yu Honglei Zhou Yongbin Ding Jinhai Tang Source Type: research
Cytotoxicity of Prymnesium parvum extracts and prymnesin analogs on epithelial fish gill cells RTgill-W1 and the human colon cell line HCEC-1CT
Arch Toxicol. 2024 Mar;98(3):999-1014. doi: 10.1007/s00204-023-03663-5. Epub 2024 Jan 11.ABSTRACTHarmful algal blooms kill fish populations worldwide, as exemplified by the haptophyte microalga Prymnesium parvum. The suspected causative agents are prymnesins, categorized as A-, B-, and C-types based on backbone carbon atoms. Impacts of P. parvum extracts and purified prymnesins were tested on the epithelial rainbow trout fish gill cell line RTgill-W1 and on the human colon epithelial cells HCEC-1CT. Cytotoxic potencies ranked A > C > B-type with concentrations spanning from low (A- and C-type) to middle (B-type) nM r...
Source: Archives of Toxicology - January 11, 2024 Category: Toxicology Authors: Elisabeth Varga H élène-Christine Prause Matthias Riepl Nadine Hochmayr Deniz Berk Eva Attakpah Endre Kiss Nikola Medi ć Giorgia Del Favero Thomas Ostenfeld Larsen Per Juel Hansen Doris Marko Source Type: research
Development of an adverse outcome pathway network for nephrotoxicity
This study utilised established criteria to develop an AOP network that connects thirteen individual AOPs associated with nephrotoxicity (as sourced from the AOP-Wiki) to identify several key events (KEs) linked to various adverse outcomes, including kidney failure and chronic kidney disease. Analysis of the modelled AOP network and its topological features determined mitochondrial dysfunction, oxidative stress, and tubular necrosis to be the most connected and central KEs. These KEs can provide a logical foundation for guiding the selection and creation of in vitro assays and in silico tools to substitute for animal-based...
Source: Archives of Toxicology - January 10, 2024 Category: Toxicology Authors: D A Barnes J W Firman S J Belfield M T D Cronin M Vinken M J Janssen R Masereeuw Source Type: research
Reply on the comments of Ulla Vogel and colleagues on their recently published paper entitled "Re-evaluation of the occupational exposure limit for ZnO is warranted. Comments on 'Systemic inflammatory effects of zinc oxide particles: is a re-evaluation of exposure limits needed?' by Christian Mons é et al."
Arch Toxicol. 2024 Mar;98(3):1023-1024. doi: 10.1007/s00204-023-03668-0. Epub 2024 Jan 10.NO ABSTRACTPMID:38197914 | PMC:PMC10861704 | DOI:10.1007/s00204-023-03668-0 (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 10, 2024 Category: Toxicology Authors: Christian Mons é Rolf Merget Dirk Pallapies Thomas Br üning J ürgen Bünger Source Type: research
Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma
Arch Toxicol. 2024 Mar;98(3):985-997. doi: 10.1007/s00204-023-03669-z. Epub 2024 Jan 8.ABSTRACTChronic infection with Hepatitis B virus (HBV) significantly increases the risk of hepatocellular carcinoma (HCC), particularly in Eastern Asia. However, only a subset of individuals with chronic HBV infection develop HCC, suggesting the role for genetic factors in HCC etiology. Despite genome-wide association studies (GWASs) identifying multiple single nucleotide polymorphisms (SNPs) associated with HBV-related HCC susceptibility, the underlying mechanisms and causal genetic polymorphisms remain largely unclear. To address this,...
Source: Archives of Toxicology - January 8, 2024 Category: Toxicology Authors: Linyu Han Yanfei Huo Linying Huang Yanxiu Zheng Xinyuan Yu Nasha Zhang Ming Yang Source Type: research
Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma
Arch Toxicol. 2024 Jan 8. doi: 10.1007/s00204-023-03669-z. Online ahead of print.ABSTRACTChronic infection with Hepatitis B virus (HBV) significantly increases the risk of hepatocellular carcinoma (HCC), particularly in Eastern Asia. However, only a subset of individuals with chronic HBV infection develop HCC, suggesting the role for genetic factors in HCC etiology. Despite genome-wide association studies (GWASs) identifying multiple single nucleotide polymorphisms (SNPs) associated with HBV-related HCC susceptibility, the underlying mechanisms and causal genetic polymorphisms remain largely unclear. To address this, we de...
Source: Archives of Toxicology - January 8, 2024 Category: Toxicology Authors: Linyu Han Yanfei Huo Linying Huang Yanxiu Zheng Xinyuan Yu Nasha Zhang Ming Yang Source Type: research
Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma
Arch Toxicol. 2024 Jan 8. doi: 10.1007/s00204-023-03669-z. Online ahead of print.ABSTRACTChronic infection with Hepatitis B virus (HBV) significantly increases the risk of hepatocellular carcinoma (HCC), particularly in Eastern Asia. However, only a subset of individuals with chronic HBV infection develop HCC, suggesting the role for genetic factors in HCC etiology. Despite genome-wide association studies (GWASs) identifying multiple single nucleotide polymorphisms (SNPs) associated with HBV-related HCC susceptibility, the underlying mechanisms and causal genetic polymorphisms remain largely unclear. To address this, we de...
Source: Archives of Toxicology - January 8, 2024 Category: Toxicology Authors: Linyu Han Yanfei Huo Linying Huang Yanxiu Zheng Xinyuan Yu Nasha Zhang Ming Yang Source Type: research
27-Hydroxycholesterol inhibits trophoblast fusion during placenta development by activating PI3K/AKT/mTOR signaling pathway
This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes.PMID:38180513 | DOI:10.1007/s00204-023-03664-4 (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 5, 2024 Category: Toxicology Authors: Xiaoyan Zhao Xiaxia Cai Haiyan Zhu Qinyu Dang Qian Yang Yandi Zhu Yadi Zhang Mengling Zhang Xinyin Jiang Zhuo Hu Yuchen Wei Rong Xiao Huanling Yu Source Type: research
Hepatic glucuronidation of tetrabromobisphenol A and tetrachlorobisphenol A: interspecies differences in humans and laboratory animals and responsible UDP-glucuronosyltransferase isoforms in humans
Arch Toxicol. 2024 Jan 5. doi: 10.1007/s00204-023-03659-1. Online ahead of print.ABSTRACTTetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA), bisphenol A (BPA) analogs, are endocrine-disrupting chemicals predominantly metabolized into glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in humans and rats. In the present study, TBBPA and TCBPA glucuronidation by the liver microsomes of humans and laboratory animals (monkeys, dogs, minipigs, rats, mice, and hamsters) and recombinant human hepatic UGTs (10 isoforms) were examined. TBBPA glucuronidation by the liver microsomes followed the Michaelis-Menten m...
Source: Archives of Toxicology - January 5, 2024 Category: Toxicology Authors: Nobumitsu Hanioka Takashi Isobe Keita Saito Kenjiro Nagaoka Yoko Mori Hideto Jinno Susumu Ohkawara Toshiko Tanaka-Kagawa Source Type: research
Metabolic effects of nuclear receptor activation in vivo after 28-day oral exposure to three endocrine-disrupting chemicals
In conclusion, the observed changes on metabolic health parameters were modest, suggesting that a standard repeated dose 28-day oral toxicity test is not a sensitive method for the detection of the metabolic effect of EDCs.PMID:38182912 | DOI:10.1007/s00204-023-03658-2 (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 5, 2024 Category: Toxicology Authors: Brecht Attema Outi Kummu Sini Pitk änen Jonna Weisell Taina Vuorio Erika Pennanen Maria Vorimo Jaana Rys ä Sander Kersten Anna-Liisa Levonen Jukka Hakkola Source Type: research
The role of ferroptosis in cardio-oncology
Arch Toxicol. 2024 Jan 5. doi: 10.1007/s00204-023-03665-3. Online ahead of print.ABSTRACTWith the rapid development of new generations of antitumor therapies, the average survival time of cancer patients is expected to be continuously prolonged. However, these therapies often lead to cardiotoxicity, resulting in a growing number of tumor survivors with cardiovascular disease. Therefore, a new interdisciplinary subspecialty called "cardio-oncology" has emerged, aiming to detect and treat cardiovascular diseases associated with tumors and antitumor therapies. Recent studies have highlighted the role of ferroptosis in both ca...
Source: Archives of Toxicology - January 5, 2024 Category: Toxicology Authors: Kai Hou Lin Liu Zhi-Hui Fang Wei-Xing Zong Daqiang Sun Zhigang Guo Lu Cao Source Type: research
27-Hydroxycholesterol inhibits trophoblast fusion during placenta development by activating PI3K/AKT/mTOR signaling pathway
This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes.PMID:38180513 | DOI:10.1007/s00204-023-03664-4 (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 5, 2024 Category: Toxicology Authors: Xiaoyan Zhao Xiaxia Cai Haiyan Zhu Qinyu Dang Qian Yang Yandi Zhu Yadi Zhang Mengling Zhang Xinyin Jiang Zhuo Hu Yuchen Wei Rong Xiao Huanling Yu Source Type: research
Hepatic glucuronidation of tetrabromobisphenol A and tetrachlorobisphenol A: interspecies differences in humans and laboratory animals and responsible UDP-glucuronosyltransferase isoforms in humans
Arch Toxicol. 2024 Jan 5. doi: 10.1007/s00204-023-03659-1. Online ahead of print.ABSTRACTTetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA), bisphenol A (BPA) analogs, are endocrine-disrupting chemicals predominantly metabolized into glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in humans and rats. In the present study, TBBPA and TCBPA glucuronidation by the liver microsomes of humans and laboratory animals (monkeys, dogs, minipigs, rats, mice, and hamsters) and recombinant human hepatic UGTs (10 isoforms) were examined. TBBPA glucuronidation by the liver microsomes followed the Michaelis-Menten m...
Source: Archives of Toxicology - January 5, 2024 Category: Toxicology Authors: Nobumitsu Hanioka Takashi Isobe Keita Saito Kenjiro Nagaoka Yoko Mori Hideto Jinno Susumu Ohkawara Toshiko Tanaka-Kagawa Source Type: research
The role of ferroptosis in cardio-oncology
Arch Toxicol. 2024 Jan 5. doi: 10.1007/s00204-023-03665-3. Online ahead of print.ABSTRACTWith the rapid development of new generations of antitumor therapies, the average survival time of cancer patients is expected to be continuously prolonged. However, these therapies often lead to cardiotoxicity, resulting in a growing number of tumor survivors with cardiovascular disease. Therefore, a new interdisciplinary subspecialty called "cardio-oncology" has emerged, aiming to detect and treat cardiovascular diseases associated with tumors and antitumor therapies. Recent studies have highlighted the role of ferroptosis in both ca...
Source: Archives of Toxicology - January 5, 2024 Category: Toxicology Authors: Kai Hou Lin Liu Zhi-Hui Fang Wei-Xing Zong Daqiang Sun Zhigang Guo Lu Cao Source Type: research
Metabolic effects of nuclear receptor activation in vivo after 28-day oral exposure to three endocrine-disrupting chemicals
In conclusion, the observed changes on metabolic health parameters were modest, suggesting that a standard repeated dose 28-day oral toxicity test is not a sensitive method for the detection of the metabolic effect of EDCs.PMID:38182912 | DOI:10.1007/s00204-023-03658-2 (Source: Archives of Toxicology)
Source: Archives of Toxicology - January 5, 2024 Category: Toxicology Authors: Brecht Attema Outi Kummu Sini Pitk änen Jonna Weisell Taina Vuorio Erika Pennanen Maria Vorimo Jaana Rys ä Sander Kersten Anna-Liisa Levonen Jukka Hakkola Source Type: research
