In Vivo Electron Paramagnetic Resonance Molecular Profiling of Tumor Microenvironment upon Tumor Progression to Malignancy in an Animal Model of Breast Cancer

Eubank, Timothy D.; Bobko, Andrey A.; Hoblitzell, E. Hannah; Gencheva, Marieta; Driesschaert, Benoit; Khramtsov, Valery V.

doi:10.1007/s11307-023-01847-0

Cited by 3 publications

(2 citation statements)

References 75 publications

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“…This important finding implies that metastasis is potentially a systemic disorder associated with dysregulated phosphate metabolism—providing an alternative to the seed and soil theory that proposes that metastasis spreads to secondary sites as cancer cells escape from a tumor [ 88 ]. More recently in 2023, the West Virginia University researchers used the same in vivo technique in a mouse breast-cancer model to investigate cancer biomarkers within the tumor microenvironment, including oxygen concentration and extracellular pH [ 89 ]. The researchers found that only interstitial Pi, a biomarker of deviated metabolic status, was consistently elevated during all stages of tumorigenesis up to and including malignancy.…”

Section: Dysregulated Phosphate Metabolism and Tumorigenesismentioning

confidence: 99%

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate

Brown

2024

Cancers

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Tumors that spontaneously shrink from unknown causes in tumor regression, and that return to normal cells in tumor reversion, are phenomena with the potential to contribute new knowledge and novel therapies for cancer patient survival. Tumorigenesis is associated with dysregulated phosphate metabolism and an increased transport of phosphate into tumor cells, potentially mediated by phosphate overload from excessive dietary phosphate intake, a significant problem in Western societies. This paper proposes that reduced dietary phosphate overload and reregulated phosphate metabolism may reverse an imbalance of kinases and phosphatases in cell signaling and cellular proliferation, thereby activating autophagy in tumor regression and reversion. Dietary phosphate can also be reduced by sickness-associated anorexia, fasting-mimicking diets, and other diets low in phosphate, all of which have been associated with tumor regression. Tumor reversion has also been demonstrated by transplanting cancer cells into a healthy microenvironment, plausibly associated with normal cellular phosphate concentrations. Evidence also suggests that the sequestration and containment of excessive phosphate within encapsulated tumors is protective in cancer patients, preventing the release of potentially lethal amounts of phosphate into the general circulation. Reducing dietary phosphate overload has the potential to provide a novel, safe, and effective reversion therapy for cancer patients, and further research is warranted.

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Section: Dysregulated Phosphate Metabolism and Tumorigenesismentioning

confidence: 99%

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate

Brown

2024

Cancers

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“…The need of in vivo assessment of tumor pH has prompted the development of several imaging methods and pH-responsive probes for measuring the tumor pH [40]. Among the different imaging modalities, Magnetic Resonance Imaging (MRI) can provide accurate assessment of the anatomy and of other microenvironmental properties of the mammary glands [41][42][43][44][45]. More recently, the MRI-Chemical Exchange Saturation Transfer (MRI-CEST) technique has been demonstrated as a robust approach for an accurate determination of tumor pH by exploiting the exchange of saturated mobile protons of pH-sensitive agents with the bulk water pool for generating an MRI-visible pH-dependent contrast [46][47][48][49][50][51][52].…”

Section: Introductionmentioning

confidence: 99%

Assessing the Therapeutic Efficacy of Proton Transport Inhibitors in a Triple-Negative Breast Cancer Murine Model with Magnetic Resonance Imaging—Chemical Exchange Saturation Transfer Tumor pH Imaging

Dhakan,

Anemone,

Ventura

et al. 2023

Metabolites

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Proton transporters play a key role in maintaining the acidic tumor microenvironment; hence, their inhibition has been proposed as a new therapeutic treatment, although few methods can accurately assess their effect in vivo. In this study, we investigated whether MRI-CEST (Magnetic Resonance Imaging—Chemical Exchange Saturation Transfer) tumor pH imaging can be a useful tool to evaluate in vivo the therapeutic efficacy of several Proton Pump Inhibitors (PPIs) in breast cancer. Cell viability and extracellular pH assays were carried out in breast cancer cells cultured at physiological pH (7.4) or acid-adapted (pH of 6.5 and 6.8) following the exposure to inhibitors of V-ATPase (Lansoprazole, Esomeprazole) or NHE1 (Amiloride, Cariporide) at several concentrations. Next, triple-negative breast cancer 4T1 tumor-bearing mice were treated with Lansoprazole or Amiloride and MRI-CEST tumor pH imaging was utilized to assess the in vivo efficacy. Only Lansoprazole induced, in addition to breast cancer cell toxicity, a significant inhibition of proton extrusion. A significant reduction in tumor volume, prolonged survival, and increase in extracellular tumor pH after 1 and 2 weeks were observed after Lansoprazole treatment, whereas no significant changes were detected upon Amiloride treatment. Our results suggested that MRI-CEST tumor pH imaging can monitor the therapeutic efficacy of PPIs in breast cancer murine models.

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Sensitive simultaneous measurements of oxygenation and extracellular pH by EPR using a stable monophosphonated trityl radical and lithium phthalocyanine

Buyse,

Mignion,

Joudiou

et al. 2024

Free Radical Biology and Medicine

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In Vivo Electron Paramagnetic Resonance Molecular Profiling of Tumor Microenvironment upon Tumor Progression to Malignancy in an Animal Model of Breast Cancer

Cited by 3 publications

References 75 publications

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate

Assessing the Therapeutic Efficacy of Proton Transport Inhibitors in a Triple-Negative Breast Cancer Murine Model with Magnetic Resonance Imaging—Chemical Exchange Saturation Transfer Tumor pH Imaging

Sensitive simultaneous measurements of oxygenation and extracellular pH by EPR using a stable monophosphonated trityl radical and lithium phthalocyanine

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