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  1. Abstract Background

    Glioblastoma Multiforme, an aggressive primary brain tumor, has a poor prognosis and no effective standard of care treatments. Most patients undergoing radiotherapy, along with Temozolomide chemotherapy, develop resistance to the drug, and recurrence of the tumor is a common issue after the treatment. We propose to model the pathways active in Glioblastoma using Boolean network techniques. The network captures the genetic interactions and possible mutations that are involved in the development of the brain tumor. The model is used to predict the theoretical efficacies of drugs for the treatment of cancer.

    Results

    We use the Boolean network to rank the critical intervention points in the pathway to predict an effective therapeutic strategy for Glioblastoma. Drug repurposing helps to identify non-cancer drugs that could be effective in cancer treatment. We predict the effectiveness of drug combinations of anti-cancer and non-cancer drugs for Glioblastoma.

    Conclusions

    Given the genetic profile of a GBM tumor, the Boolean model can predict the most effective targets for treatment. We also identified two-drug combinations that could be more effective in killing GBM cells than conventional chemotherapeutic agents. The non-cancer drug Aspirin could potentially increase the cytotoxicity of TMZ in GBM patients.

  2. Free, publicly-accessible full text available June 1, 2023
  3. DNA double-strand breaks (DSBs) occur frequently in eukaryotic cells, and the homologous recombination pathway (HR) is one of the major pathways required to repair these breaks. However, tumor cells that are able to repair DSBs are unlikely to die due to damage incurred by DNA damaging chemotherapies, such as platinum compounds. While platinum-based therapies have been effective in treating various cancers, they also carry harsh side effects, and thus ideally platinum should be used when the probability of treatment resistance is low. HR scores provide a measure for patients’ tumor’s HR capacity and have been shown to predict their chemotherapy response and long-term survival. Calculating this score manually from immunofluorescence microscopy images for each patient is error-prone and time-consuming. Herein, we propose an image processing pipeline that takes as input imaging data from three emission channels (representing nuclei, S-phase cells, and HR-mediated repair in a tumor slice) from an epifluorescence microscope and computes the HR score. Our open-source methodology forms a rationale to develop similar approaches in predicting chemotherapeutic responses and facilitating to make treatment decisions.
    Free, publicly-accessible full text available April 20, 2023
  4. Mohan, Chakrabhavi Dhananjaya (Ed.)
    Background Several studies have highlighted both the extreme anticancer effects of Cryptotanshinone (CT), a Stat3 crippling component from Salvia miltiorrhiza , as well as other STAT3 inhibitors to fight cancer. Methods Data presented in this experiment incorporates 2 years of in vitro studies applying a comprehensive live-cell drug-screening analysis of human and canine cancer cells exposed to CT at 20 μM concentration, as well as to other drug combinations. As previously observed in other studies, dogs are natural cancer models, given to their similarity in cancer genetics, epidemiology and disease progression compared to humans. Results Results obtained from several types of human and canine cancer cells exposed to CT and varied drug combinations, verified CT efficacy at combating cancer by achieving an extremely high percentage of apoptosis within 24 hours of drug exposure. Conclusions CT anticancer efficacy in various human and canine cancer cell lines denotes its ability to interact across different biological processes and cancer regulatory cell networks, driving inhibition of cancer cell survival.