Carbon Ion Radiobiology

Cancers, Journal Year: 2020, Volume and Issue: 12(10), P. 3022 - 3022

Published: Oct. 17, 2020

Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons, which have physical advantages compared to X-rays but a similar biological response. In addition ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal ion should lower toxicity in entrance channel (normal tissue) and be exquisitely effective target region (tumor). Carbon been chosen because they represent best combination this direction. Normal tissue toxicities second risk those observed conventional radiotherapy. region, increased relative effectiveness reduced oxygen enhancement ratio X-rays. Some properties densely ionizing carbon so distinct from protons considered as different “drug” oncology, may elicit favorable responses such an immune response angiogenesis metastatic potential. The guide patient selection treatment protocols achieve optimal clinical results.

Language: Английский

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Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Translational Oncology, Journal Year: 2020, Volume and Issue: 13(11), P. 100845 - 100845

Published: Aug. 8, 2020

Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid successful colonization at the distant site. not binary process; recent evidence suggests that partial or hybrid E/M phenotype(s) have enhanced stemness compared those undergoing complete EMT. Moreover, enables collective clusters circulating tumor emboli, further endorsing phenotypes may be 'fittest' for Here, we review mechanisms implications phenotypes, including their reported association with hypoxia. Hypoxia-driven activation HIF-1α drive In addition, cyclic hypoxia, acute chronic shows highest levels active augment aggressiveness greater extent, enriching phenotype. We discuss how metastasis influenced by cell migration, call better understanding interconnections among these mechanisms. known regulators highlight gaps needs filled connecting three axes will increase our dynamics help control it more effectively.

Language: Английский

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The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 8, 2022

Abstract Given that hypoxia is a persistent physiological feature of many different solid tumors and key driver for cancer malignancy, it thought to be major target in treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells tumor microenvironment (TME), which have large impact on development immunotherapy. TAMs massively accumulate within hypoxic regions. represent deadly combination because has been suggested induce pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects polarization, but also an indirect effect by altering communication between macrophages. For example, can influence expression chemokines exosomes, both profound impacts recipient cells. Recently, demonstrated intricate interaction TME relevant poor prognosis increased malignancy. However, there no comprehensive literature reviews molecular mechanisms underlying hypoxia-mediated TAMs. Therefore, this review aim collect all recently available data topic provide insights developing novel therapeutic strategies reducing effects hypoxia.

Language: Английский

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Microfluidic organ-on-chip system for multi-analyte monitoring of metabolites in 3D cell cultures

Lab on a Chip, Journal Year: 2021, Volume and Issue: 22(2), P. 225 - 239

Published: Dec. 1, 2021

An organ-on-chip platform equipped with microsensors for long-term microfluidic cultivation and metabolic monitoring (O 2 , Glu, Lac) of 3D tumour organoid cultures grown from patient-derived single cancer stem cells.

Language: Английский

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Nonsense-mediated RNA decay: an emerging modulator of malignancy

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(8), P. 437 - 451

Published: May 27, 2022

Language: Английский

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The interactions of docetaxel with tumor microenvironment

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 119, P. 110214 - 110214

Published: April 29, 2023

Language: Английский

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Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 30, 2024

Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One the main transcription factors activated by hypoxia hypoxia-inducible factor (HIF), which regulates expression genes involved in various aspects tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, cell migration. This can negatively impact patient outcomes inducing therapeutic resistance. The importance clearly demonstrated continued research into finding clinically relevant biomarkers, hypoxia-targeting therapies. problems lack applicable methods detection, standardisation. Additionally, lot detecting do not take consideration complexity hypoxic tumour microenvironment (TME). Therefore, this needs further elucidation as approximately 50% are hypoxic. ECM important component TME, developed both cancer associated fibroblasts (CAFs) cells. However, it distinguish different roles develop biomarkers novel compounds. Fibronectin (FN), collagen (COL) hyaluronic acid (HA) components that create fibres. These fibres crosslinked specific enzymes lysyl oxidase (LOX) stiffness induces fibrosis. partially regulated HIFs. review highlights understanding role current data shows contradictory results on also indicates needed identifying CAF subtypes exact roles; with some showing pro-tumorigenic capacity others having anti-tumorigenic roles. has made difficult fully elucidate CAFs within TME. clear an area requires unravelling strategies target have resulted worsened prognosis. cells discussed been modulating environment. Which led development immunotherapies PD-L1. hypoxia-induced changes confer resistance conventional therapies, such chemotherapy, radiotherapy, immunotherapy. summarizes knowledge TME its implications for therapy It discusses potential prognostic predictive indictors treatment response, well challenges opportunities targeting clinical trials.

Language: Английский

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Cancer Stem Cell Plasticity – A Deadly Deal

Frontiers in Molecular Biosciences, Journal Year: 2020, Volume and Issue: 7

Published: April 30, 2020

Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that fraction cells within tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting resistance and metastasis. Adding to complexity, recent studies have shown there can be different subpopulations CSCs with varying biochemical biophysical traits varied dissemination drug-resistance potential. Moreover, cancer exhibit high level plasticity or ability dynamically switch between CSC non-CSC statesoramong subsets CSCs. The molecular mechanisms underlying such has been under extensive investigation trans-differentiation process Epithelial Mesenchymal transition (EMT) identified as contributing factor. Besides genetic epigenetic factors, also shaped by non-cell-autonomous effects microenvironment. In review, we discuss developments understanding progression at levels,and latest silico approaches being taken characterizing cell implications improving existing approaches.

Language: Английский

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Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia

Cellular & Molecular Biology Letters, Journal Year: 2020, Volume and Issue: 25(1)

Published: March 13, 2020

Abstract During hypoxic conditions, cells undergo critical adaptive responses that include the up-regulation of hypoxia-inducible proteins (HIFs) and induction unfolded protein response (UPR). While their induced signaling pathways have many distinct targets, there are some important connections as well. Despite extensive studies on both these pathways, exact mechanisms involved determine survival versus apoptosis remain largely unexplained therefore beyond therapeutic control. Here we discuss complex relationship between HIF UPR importance understanding how differ normal cancer cell models.

Language: Английский

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Endothelial Dysfunction Driven by Hypoxia—The Influence of Oxygen Deficiency on NO Bioavailability

Biomolecules, Journal Year: 2021, Volume and Issue: 11(7), P. 982 - 982

Published: July 3, 2021

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The initial stage CVDs is characterized by endothelial dysfunction, defined as limited bioavailability nitric oxide (NO). Thus, any factors that interfere with synthesis or metabolism NO in cells involved CVD pathogenesis. It well established hypoxia both triggering factor accompanying cardiovascular disease, and diminished tissue oxygen levels have been reported to influence bioavailability. In cells, produced synthase (eNOS) from L-Arg, tetrahydrobiopterin (BH4) an essential cofactor. Here, we discuss mechanisms which affects bioavailability, including regulation eNOS expression activity. What particularly important fact contributes depletion cofactor BH4 deficiency substrate thus elicits uncoupling—a state enzyme produces superoxide instead NO. uncoupling resulting oxidative stress major driver dysfunction atherogenesis. Moreover, induces impairment mitochondrial respiration cell activation; thus, inflammation, along hypoxic response, contribute development dysfunction.

Language: Английский

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