Gas Tensions in Cardiac Lymph as a Reflection of the Interstitial Space of the Heart

Palmer, Arthur; Miller, Albert J.; Davis, Cornelius A.; Greene, R. R.

doi:10.1177/000331979804901005

Cited by 7 publications

(10 citation statements)

References 2 publications

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“…The extracellular acid-base status of most normal tissue in vivo is, under physiological, wellperfused conditions, maintained relatively stable and close to that of blood (1). Accordingly, interstitial pH of normal tissue is usually in the range 7.3 to 7.4, but under some conditions, it fluctuates substantially, such as in epithelia (e.g., pancreas, colon, ventricle) during intense acid or base secretion (2) and in skeletal muscle during physical activity (3).…”

Section: Composition Of the Tumor Microenvironmentmentioning

confidence: 99%

“…Accordingly, interstitial pH of normal tissue is usually in the range 7.3 to 7.4, but under some conditions, it fluctuates substantially, such as in epithelia (e.g., pancreas, colon, ventricle) during intense acid or base secretion (2) and in skeletal muscle during physical activity (3). A number of noncancer disease conditions, such as inflammatory states, ischemia, and systemic respiratory or metabolic disturbances, are also associated with interstitial acidosis (1,(4)(5)(6).…”

Section: Composition Of the Tumor Microenvironmentmentioning

confidence: 99%

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The Acidic Tumor Microenvironment as a Driver of Cancer

Boedtkjer

Pedersen

2020

Annu. Rev. Physiol.

742

495

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Acidic metabolic waste products accumulate in the tumor microenvironment because of high metabolic activity and insufficient perfusion. In tumors, the acidity of the interstitial space and the relatively well-maintained intracellular pH influence cancer and stromal cell function, their mutual interplay, and their interactions with the extracellular matrix. Tumor pH is spatially and temporally heterogeneous, and the fitness advantage of cancer cells adapted to extracellular acidity is likely particularly evident when they encounter less acidic tumor regions, for instance, during invasion. Through complex effects on genetic stability, epigenetics, cellular metabolism, proliferation, and survival, the compartmentalized pH microenvironment favors cancer development. Cellular selection exacerbates the malignant phenotype, which is further enhanced by acid-induced cell motility, extracellular matrix degradation, attenuated immune responses, and modified cellular and intercellular signaling. In this review, we discuss how the acidity of the tumor microenvironment influences each stage in cancer development, from dysplasia to full-blown metastatic disease.

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Section: Composition Of the Tumor Microenvironmentmentioning

confidence: 99%

Section: Composition Of the Tumor Microenvironmentmentioning

confidence: 99%

The Acidic Tumor Microenvironment as a Driver of Cancer

Boedtkjer

Pedersen

2020

Annu. Rev. Physiol.

742

495

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“…) and will at least locally reflect interstitial deviations (Palmer et al. ). The tested degrees of acidification are well‐within the range of local pH disturbances observed during pathologies, for instance, malignancies (Vaupel et al.…”

Section: Discussionmentioning

confidence: 99%

“…; Takaori and Tosaki ; Palmer et al. ). Severe acidification of thoracic duct lymph occurs during hemorrhagic and endotoxin shock (Berman et al.…”

Section: Introductionmentioning

confidence: 99%

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Acidosis inhibits rhythmic contractions of human thoracic ducts

2019

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Lymph vessels counteract edema by transporting interstitial fluid from peripheral tissues to the large veins and serve as conduits for immune cells, cancer cells, and pathogens. Because edema during inflammation and malignancies is frequently associated with acidosis, we tested the hypothesis that acid‐base disturbances affect human thoracic duct contractions. We studied, by isometric and isobaric myography, the contractile function of human thoracic duct segments harvested with written informed consent from patients undergoing esophageal cancer surgery. Human thoracic ducts produce complex contractile patterns consisting of tonic rises in tension (isometric myography) or decreases in diameter (isobaric myography) with superimposed phasic contractions. Active tone development decreases substantially (~90% at 30 vs. 7 mmHg) at elevated transmural pressure. Acidosis inhibits spontaneous as well as noradrenaline‐ and serotonin‐induced phasic contractions of human thoracic ducts by 70–90% at extracellular pH 6.8 compared to 7.4 with less pronounced effects observed at pH 7.1. Mean tension responses to noradrenaline and serotonin – averaged over the entire period of agonist exposure – decrease by ~50% at extracellular pH 6.8. Elevating extracellular [K + ] from the normal resting level around 4 mmol/L increases overall tension development but reduces phasic activity to a level that is no different between human thoracic duct segments investigated at normal and low extracellular pH . In conclusion, we show that extracellular acidosis inhibits human thoracic duct contractions with more pronounced effects on phasic than tonic contractions. We propose that reduced phasic activity of lymph vessels at low pH attenuates lymph propulsion and increases the risk of edema formation.

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Employing Noble Metal–Porphyrins to Engineer Robust and Highly Active Single‐Atom Nanozymes for Targeted Catalytic Therapy in Nasopharyngeal Carcinoma

Wang,

Gao

et al. 2023

Advanced Materials

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Single‐atom nanozymes (SANzymes) emerge as promising alternatives to conventional enzymes. However, chemical instability limits their application. Here, a systematic synthesis of highly active and stable SANzymes is presented by leveraging noble metal–porphyrins. Four noble metal–porphyrins are successfully synthesized to mimic the active site of natural peroxidases through atomic metal–N coordination anchored to the porphyrin center. These noble metal–porphyrins are integrated into a stable and biocompatible Zr‐based metal–organic framework (MxP, x denoting Ir, Ru, Pt, and Pd). Among these, MIrP demonstrates superior peroxidase‐like activity (685.61 U mg−1), catalytic efficiency, and selectivity compared to horseradish peroxidase (267.71 U mg−1). Mechanistic investigations unveil heightened catalytic activity of MIrP arises from its robust H2O2 adsorption capacity, unique rate‐determining step, and low energy threshold. Crucially, MIrP exhibits remarkable chemical stability under both room temperature and high H2O2 concentrations. Further, through modification with (−)‐Epigallocatechin‐3‐Gallate, a natural ligand for Epstein–Barr virus (EBV)‐encoded latent membrane protein 1, targeted SANzyme (MIrPHE) tailored for EBV‐associated nasopharyngeal carcinoma is engineered. This study not only presents an innovative strategy for augmenting the catalytic activity and chemical stability of SANzymes but also highlights the substantial potential of MIrP as a potent nanomedicine for targeted catalytic tumor therapy.

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Gas Tensions in Cardiac Lymph as a Reflection of the Interstitial Space of the Heart

Cited by 7 publications

References 2 publications

The Acidic Tumor Microenvironment as a Driver of Cancer

The Acidic Tumor Microenvironment as a Driver of Cancer

Acidosis inhibits rhythmic contractions of human thoracic ducts

Employing Noble Metal–Porphyrins to Engineer Robust and Highly Active Single‐Atom Nanozymes for Targeted Catalytic Therapy in Nasopharyngeal Carcinoma

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