Mitochondrial metabolism: a predictive biomarker of radiotherapy efficacy and toxicity

Taghizadeh‐Hesary, Farzad; Houshyari, Mohammad; Farhadi, Mohammad

doi:10.1007/s00432-023-04592-7

Cited by 25 publications

(19 citation statements)

References 239 publications

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“…Within the scope of our current studies on irradiated skin tissue, we observed that mitochondria-associated genes are also strongly modulated by H2A.J. Increasing evidence suggests that an altered mitochondrial metabolism is associated with the onset of resistance to radiotherapy [ 36 ]. However, the precise role of H2A.J in the context of mitochondrial metabolism and tumor response to radiotherapy has to be investigated in appropriate experimental studies.…”

Section: Discussionmentioning

confidence: 85%

Role of Histone Variant H2A.J in Fine-Tuning Chromatin Organization for the Establishment of Ionizing Radiation-Induced Senescence

Al-razaq

Freyter

Isermann

et al. 2023

Cells

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Purpose: Radiation-induced senescence is characterized by profound changes in chromatin organization with the formation of Senescence-Associated-Heterochromatin-Foci (SAHF) and DNA-Segments-with-Chromatin-Alterations-Reinforcing-Senescence (DNA-SCARS). Importantly, senescent cells also secrete complex combinations of pro-inflammatory factors, referred as Senescence-Associated-Secretory-Phenotype (SASP). Here, we analyzed the epigenetic mechanism of histone variant H2A.J in establishing radiation-induced senescence. Experimental Design: Primary and genetically-modified lung fibroblasts with down- or up-regulated H2A.J expression were exposed to ionizing radiation and were analyzed for the formation of SAHF and DNA-SCARS by immunofluorescence microscopy. Dynamic changes in chromatin organization and accessibility, transcription factor recruitment, and transcriptome signatures were mapped by ATAC-seq and RNA-seq analysis. The secretion of SASP factors and potential bystander effects were analyzed by ELISA and RT-PCR. Lung tissue of mice exposed to different doses were analyzed by the digital image analysis of H2A.J-immunohistochemistry. Results: Differential incorporation of H2A.J has profound effects on higher-order chromatin organization and on establishing the epigenetic state of senescence. Integrative analyses of ATAC-seq and RNA-seq datasets indicate that H2A.J-associated changes in chromatin accessibility of regulatory regions decisively modulates transcription factor recruitment and inflammatory gene expression, resulting in an altered SASP secretome. In lung parenchyma, pneumocytes show dose-dependent H2A.J expression in response to radiation-induced DNA damage, therefore contributing to pro-inflammatory tissue reactions. Conclusions: The fine-tuned incorporation of H2A.J defines the epigenetic landscape for driving the senescence programme in response to radiation-induced DNA damage. Deregulated H2A.J deposition affects chromatin remodeling, transcription factor recruitment, and the pro-inflammatory secretome. Our findings provide new mechanistic insights into DNA-damage triggered epigenetic mechanisms governing the biological processes of radiation-induced injury.

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Section: Discussionmentioning

confidence: 85%

Role of Histone Variant H2A.J in Fine-Tuning Chromatin Organization for the Establishment of Ionizing Radiation-Induced Senescence

Al-razaq

Freyter

Isermann

et al. 2023

Cells

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“…Other reports have demonstrated the role of mitochondrial metabolism with cancer cell progression, 16 and PD-L1 blockade has been found to be more effective in cancer cells with higher cellular respiration and adenosine triphosphate (ATP) turnover rate. 17 Therefore, the efficacy of anti-PD-L1 agents may be increased with mitochondria-modulating drugs such as bezafibrate, an agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1α (PGC-1α)/transcription factor complex.…”

Section: Discussionmentioning

confidence: 99%

Metaplastic Carcinoma of the Axillary Breast With Heterologous Mesenchymal (Chondroid) Differentiation: A Difficult Case and Literature Review

Chang,

Lam

2023

Breast Cancer�(Auckl)

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Metaplastic breast carcinoma is an invasive carcinoma with a high differentiation rate of the neoplastic epithelium toward mesenchymal-like epithelium. It comprises of only less than 1% of all breast cancers. Although 80% to 90% of metaplastic breast carcinomas are triple-negative cancers, they usually have worse outcomes than other triple-negative breast cancers (TNBCs). Metaplastic carcinoma is also often refractory to cytotoxic chemotherapy. Here, we reported a case of a 61-year-old female patient, presenting with a solitary and pedunculated mass in the right axillary tail breast tissue, whose biopsy revealed metaplastic breast carcinoma with chondroid differentiation. She had failed neoadjuvant chemotherapy and immunotherapy. Although she received debulking surgery, the tumor regrew even faster before surgery. Despite receiving palliative chemotherapy, the patient died 11 weeks after surgery. This case draws attention to physicians that early recognition and surgery may be more beneficial than chemotherapy in combating metaplastic breast carcinoma.

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“…This approach can improve the efficacy of novel immunotherapeutic agents (such as anti-programmed death protein-1) and radiotherapy by targeting the cancer cells' mitochondria. [135][136][137] 4.1.8 | Graphene and graphene oxide A single honeycomb lattice makes up the 2D substance known as graphene. This substance is electrically conductive with a high surface area (~two times greater than CNTs).…”

Section: Silver Nanoparticlesmentioning

confidence: 99%

“…As a result, a superior system was attained. This approach can improve the efficacy of novel immunotherapeutic agents (such as anti‐programmed death protein‐1) and radiotherapy by targeting the cancer cells' mitochondria 135–137 …”

Section: Nanocarriers To Overcome Mdr In Tumor Microenvironmentmentioning

confidence: 99%

Nanodelivery systems: An efficient and target‐specific approach for drug‐resistant cancers

Ashique,

Garg,

Hussain

et al. 2023

Cancer Medicine

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BackgroundCancer treatment is still a global health challenge. Nowadays, chemotherapy is widely applied for treating cancer and reducing its burden. However, its application might be in accordance with various adverse effects by exposing the healthy tissues and multidrug resistance (MDR), leading to disease relapse or metastasis. In addition, due to tumor heterogeneity and the varied pharmacokinetic features of prescribed drugs, combination therapy has only shown modestly improved results in MDR malignancies. Nanotechnology has been explored as a potential tool for cancer treatment, due to the efficiency of nanoparticles to function as a vehicle for drug delivery.MethodsWith this viewpoint, functionalized nanosystems have been investigated as a potential strategy to overcome drug resistance.ResultsThis approach aims to improve the efficacy of anticancer medicines while decreasing their associated side effects through a range of mechanisms, such as bypassing drug efflux, controlling drug release, and disrupting metabolism. This review discusses the MDR mechanisms contributing to therapeutic failure, the most cutting‐edge approaches used in nanomedicine to create and assess nanocarriers, and designed nanomedicine to counteract MDR with emphasis on recent developments, their potential, and limitations.ConclusionsStudies have shown that nanoparticle‐mediated drug delivery confers distinct benefits over traditional pharmaceuticals, including improved biocompatibility, stability, permeability, retention effect, and targeting capabilities.

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Mitochondrial metabolism: a predictive biomarker of radiotherapy efficacy and toxicity

Cited by 25 publications

References 239 publications

Role of Histone Variant H2A.J in Fine-Tuning Chromatin Organization for the Establishment of Ionizing Radiation-Induced Senescence

Role of Histone Variant H2A.J in Fine-Tuning Chromatin Organization for the Establishment of Ionizing Radiation-Induced Senescence

Metaplastic Carcinoma of the Axillary Breast With Heterologous Mesenchymal (Chondroid) Differentiation: A Difficult Case and Literature Review

Nanodelivery systems: An efficient and target‐specific approach for drug‐resistant cancers

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