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  1. Article ; Online: A mathematical model to study low-dose metronomic scheduling for chemotherapy.

    Arora, Garhima / Bairagi, Nandadulal / Chatterjee, Samrat

    Mathematical biosciences

    2024  Volume 372, Page(s) 109186

    Abstract: Metronomic chemotherapy refers to the frequent administration of chemotherapeutic agents at a lower dose and presents an attractive alternative to conventional chemotherapy with encouraging response rates. However, the schedule of the therapy, including ... ...

    Abstract Metronomic chemotherapy refers to the frequent administration of chemotherapeutic agents at a lower dose and presents an attractive alternative to conventional chemotherapy with encouraging response rates. However, the schedule of the therapy, including the dosage of the drug, is usually based on empiricism. The confounding effects of tumor-endothelial-immune interactions during metronomic administration of drugs have not yet been explored in detail, resulting in an incomplete assessment of drug dose and frequency evaluations. The present study aimed to gain a mechanistic understanding of different actions of metronomic chemotherapy using a mathematical model. We have established an analytical condition for determining the dosage and frequency of the drug depending on its clearance rate for complete tumor elimination. The model also brings forward the immune-mediated clearance of the tumor during the metronomic administration of the chemotherapeutic agent. The results from the global sensitivity analysis showed an increase in the sensitivity of drug and immune-mediated killing factors toward the tumor population during metronomic scheduling. Our results emphasize metronomic scheduling over the maximum tolerated dose (MTD) and define a model-based approach for approximating the optimal schedule of drug administration to eliminate tumors while minimizing harm to the immune cells and the patient's body.
    Language English
    Publishing date 2024-04-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1126-5
    ISSN 1879-3134 ; 0025-5564
    ISSN (online) 1879-3134
    ISSN 0025-5564
    DOI 10.1016/j.mbs.2024.109186
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Targeting metabolic fluxes reverts metastatic transitions in ovarian cancer.

    Arora, Garhima / Banerjee, Mallar / Langthasa, Jimpi / Bhat, Ramray / Chatterjee, Samrat

    iScience

    2023  Volume 26, Issue 11, Page(s) 108081

    Abstract: The formation of spheroids during epithelial ovarian cancer progression is correlated with peritoneal metastasis, disease recurrence, and poor prognosis. Although metastasis has been demonstrated to be driven by metabolic changes in transformed cells, ... ...

    Abstract The formation of spheroids during epithelial ovarian cancer progression is correlated with peritoneal metastasis, disease recurrence, and poor prognosis. Although metastasis has been demonstrated to be driven by metabolic changes in transformed cells, mechanistic associations between metabolism and phenotypic transitions remain ill-explored. We performed quantitative proteomics to identify protein signatures associated with three distinct phenotypic morphologies (2D monolayers and two geometrically distinct three-dimensional spheroidal states) of the high-grade serous ovarian cancer line OVCAR-3. We obtained disease-driving phenotype-specific metabolic reaction modules and elucidated gene knockout strategies to reduce metabolic alterations that could drive phenotypic transitions. Exploring the DrugBank database, we identified and evaluated drugs that could impair such transitions and, hence, cancer progression. Finally, we experimentally validated our predictions by confirming the ability of one of our predicted drugs, the neuraminidase inhibitor oseltamivir, to inhibit spheroidogenesis in three ovarian cancer cell lines without any cytotoxic effects on untransformed stromal mesothelia.
    Language English
    Publishing date 2023-09-28
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108081
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Understanding doxorubicin associated calcium remodeling during triple-negative breast cancer treatment: an

    Arora, Garhima / Ghosh, Sumana / Chatterjee, Samrat

    Exploration of targeted anti-tumor therapy

    2021  Volume 2, Issue 2, Page(s) 208–226

    Abstract: Aim: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with high heterogeneity, rapid progression, and paucity of treatment options. The most effective chemotherapeutic drug used to treat TNBC is doxorubicin (Doxo) ... ...

    Abstract Aim: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with high heterogeneity, rapid progression, and paucity of treatment options. The most effective chemotherapeutic drug used to treat TNBC is doxorubicin (Doxo) which is an anthracycline antibiotic. However, Doxo treatment alters cytosolic calcium dynamics leading to drug-resistance condition. The aim of this study is to capture the alterations in the activity of various calcium channels and pumps during Doxo treatment and their consequences on cytosolic calcium dynamics that ultimately result in drug resistance.
    Methods: In the present study, a mathematical model is proposed to capture the complex dynamical landscape of intracellular calcium during Doxo treatment. This study provides an insight into Doxo remodeling of calcium dynamics and associated drug-resistance effect. The model was first analyzed analytically and then explored through numerical simulation using techniques like global sensitivity analysis, parameter recalibration, etc.
    Results: The model is used to predict the potential combination therapy for Doxo that can overcome Doxo associated drug resistance. The results show targeting the dysregulated Ca
    Conclusions: The investigation highlights the importance of integrating the calcium signaling of various calcium regulating compounds for their effective anti-tumor effects deliverance along with chemotherapeutic agents. The results from this study might provide a new direction to the experimental biologists to explore different combination therapies with Doxo to enhance its anti-tumor effect.
    Language English
    Publishing date 2021-04-30
    Publishing country United States
    Document type Journal Article
    ISSN 2692-3114
    ISSN (online) 2692-3114
    DOI 10.37349/etat.2021.00042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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