Publications by authors named "Carl L Alden"
The ICH initiated talks in June 2012 to revise regulatory guidance for carcinogenicity assessment of pharmaceutical products, stimulated in part by a proposal called Negative for Endocrine, Genotoxicity, and Chronic Study Associated Histopathologic Risk Factors for Carcinogenicity in the Rat (NEGCARC) from the Pharmaceutical Research and Manufacturing Association (PhRMA). The 2012 STP Town Hall Meeting focused on the need for change in carcinogenicity assessment strategies for pharmaceuticals. Dr.
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- Exposure to p38alpha MAPK inhibitors in Beagle dogs leads to acute toxicity characterized by symptoms like decreased activity, diarrhea, and fever, alongside severe lymphoid tissue damage and hemorrhages.
- The earliest noticeable changes include lymphocyte death in gut-associated lymphoid tissue, progressing to inflammation and additional tissue damage in lymph nodes and spleen.
- These toxic effects were specific to dogs, as similar observations were not found in other tested species like mice, rats, or monkeys, highlighting the unique response to p38alpha MAPK inhibition in dogs.
GT-1 murine neuronal cells exposed to an experimental proteasome inhibitor (EPI) for 24h showed increased cell death via a non-apoptotic mechanism, as assessed by TUNEL and DNA fragmentation assays. Immunofluorescence staining demonstrated that EPI induced reorganization and relocation of non-ubiquinated actin microfilaments and microtubules to the perinuclear region in EPI treated cells. Immunohistochemistry analysis also demonstrated that other non-cytoskeletal proteins became ubiquitinated and/or upregulated including ubiquitin and other stress proteins.
View Article and Find Full Text PDFHepatic enzyme inducers such as phenobarbital are often nongenotoxic rodent hepatocarcinogens. Currently, nongenotoxic hepatocarcinogens can only be definitively identified through costly and extensive long-term, repeat-dose studies (e.g.
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- * Researchers are exploring quicker, more cost-effective methods by using transcription profiling in a 5-day study with various chemicals to identify potential early biomarkers for cancer risk.
- * The study revealed several candidate molecular markers linked to nongenotoxic carcinogenicity, suggesting that these markers could help predict cancer risk in humans earlier in the drug development process.
The Tg rasH2 transgenic mouse has been developed as an altemative to the lifetime mouse bioassay to predict the carcinogenic potential of chemicals. Unlike the p53+/- mouse, the Tg rasH2 mouse is sensitive to both genotoxic and nongenotoxic carcinogens. The Tg rasH2 mouse, officially designated CB6F1-TgN (RasH2), contains multiple copies of the human c-Ha-ras oncogene and promoter within its genome.
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