Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

Wu, Bocheng; Sodji, Quaovi H.; Oyelere, Adegboyega K.

doi:10.3390/cancers14030552

Cited by 53 publications

(33 citation statements)

References 293 publications

(305 reference statements)

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“…and proteolytic enzymes cleaving extracellular matrix such as MMP or adamalysins, depletion of antioxidant system Nrf2, activation of growth factors, increased expression of fibrogenic and angiogenic factors resulting into elevated production of MMPs, smooth muscle actin (SMA), collagen, etc. [ 199 , 200 ].…”

Section: Effects Of Egcg In Respiratory Diseasesmentioning

confidence: 99%

Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases?

2022

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(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol of green tea that possesses a wide variety of actions. EGCG acts as a strong antioxidant which effectively scavenges reactive oxygen species (ROS), inhibits pro-oxidant enzymes including NADPH oxidase, activates antioxidant systems including superoxide dismutase, catalase, or glutathione, and reduces abundant production of nitric oxide metabolites by inducible nitric oxide synthase. ECGC also exerts potent anti-inflammatory, anti-fibrotic, pro-apoptotic, anti-tumorous, and metabolic effects via modulation of a variety of intracellular signaling cascades. Based on this knowledge, the use of EGCG could be of benefit in respiratory diseases with acute or chronic inflammatory, oxidative, and fibrotizing processes in their pathogenesis. This article reviews current information on the biological effects of EGCG in those respiratory diseases or animal models in which EGCG has been administered, i.e., acute respiratory distress syndrome, respiratory infections, COVID-19, bronchial asthma, chronic obstructive pulmonary disease, lung fibrosis, silicosis, lung cancer, pulmonary hypertension, and lung embolism, and critically discusses effectiveness of EGCG administration in these respiratory disorders. For this review, articles in English language from the PubMed database were used.

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Section: Effects Of Egcg In Respiratory Diseasesmentioning

confidence: 99%

Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases?

2022

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Section: Discussionmentioning

confidence: 99%

“…Fibrosis is the formation of excess connective tissue that causes thickening and scarring [19,20]. Tumor fibrosis has been recognized to be associated with uncontrolled inflammation [19,21], and characterized by chronic inflammation and aberrant ECM remodeling [22]. This altered tumor micro-environment could affect tissue dynamics as measured by US elastography, indicating tissue stiffness [23].…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Ultrasound Elastography and Fibrotic Focus and Their Association in Breast Cancer

Lee

Jeong

2022

JCM

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(1) Background: Ultrasound (US) elastography is an imaging technology that reveals tissue stiffness. This study aimed to investigate whether fibrotic focus (FF) affects elastographic findings in breast cancer, and to evaluate the clinical significance of US elastography and FF in breast cancer. (2) Methods: In this study, 151 patients with breast cancer who underwent surgery were included. Strain elastography was performed and an elasticity scoring system was used to assess the findings. The elasticity scores were classified as negative, equivocal, or positive. FF was evaluated in the surgical specimens. Medical records were reviewed for all patients. (3) Results: Elastographic findings were equivocal in 30 patients (19.9%) and positive in 121 patients (80.1%). FF was present in 68 patients (46.9%). There was no correlation between elastographic findings and FF. Older age, larger tumor size, lymph node metastasis, and higher tumor stage were associated with positive elastographic results. FF showed a positive correlation with age, postmenopausal status, tumor size, lymphovascular invasion, lymph node metastasis, tumor stage, and intratumoral and peritumoral inflammation. (4) Conclusions: Our study showed that positive elastographic results and FF were associated with poor prognostic factors for breast cancer. FF did not affect the elastographic findings of this study.

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“…Briefly, both the canonical and noncanonical pathways are involved in inflammatory responses, which are early manifestations of fibrosis. 91 The RhoA/ROCK pathway has been shown to be associated with the activation of NF-κB signaling, which leads to various inflammatory responses. 92,93 RhoA/ROCK is a critical upstream regulator of NF-κB, and the inhibition of ROCK pharmacological activity with the ROCK inhibitor Y-27632 contributed to the downregulation of NF-κB p65 phosphorylation and the suppression of nuclear translocation levels, further indicating that ROCK inhibitors attenuate lung injury caused by fibrotic responses.…”

Section: The Relationship Between Rock-mediated Pathway Activation An...mentioning

confidence: 99%

Application and Study of ROCK Inhibitors in Pulmonary Fibrosis: Recent Developments and Future Perspectives

et al. 2023

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Rho-associated coiled-coil-containing kinases (ROCKs), serine/threonine protein kinases, were initially identified as downstream targets of the small GTP-binding protein Rho. Pulmonary fibrosis (PF) is a lethal disease with limited therapeutic options and a particularly poor prognosis. Interestingly, ROCK activation has been demonstrated in PF patients and in animal PF models, making it a promising target for PF treatment. Many ROCK inhibitors have been discovered, and four of these have been approved for clinical use; however, no ROCK inhibitors are approved for the treatment of PF patients. In this article, we describe ROCK signaling pathways and the structure–activity relationship, potency, selectivity, binding modes, pharmacokinetics (PKs), biological functions, and recently reported inhibitors of ROCKs in the context of PF. We will also focus our attention on the challenges to be addressed when targeting ROCKs and discuss the strategy of ROCK inhibitor use in the treatment of PF.

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Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

Cited by 53 publications

References 293 publications

Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases?

Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases?

Clinical Significance of Ultrasound Elastography and Fibrotic Focus and Their Association in Breast Cancer

Application and Study of ROCK Inhibitors in Pulmonary Fibrosis: Recent Developments and Future Perspectives

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