Biomarker-driven molecular imaging probes in radiotherapy

Theranostics, Journal Year: 2024, Volume and Issue: 14(10), P. 4127 - 4146

Published: Jan. 1, 2024

Biomarker-driven molecular imaging has emerged as an integral part of cancer precision radiotherapy. The use probes, including nanoprobes, have been explored in radiotherapy to precisely and noninvasively monitor spatiotemporal distribution biomarkers, potentially revealing tumor-killing mechanisms therapy-induced adverse effects during radiation treatment.

Language: Английский

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Curcumin nanoparticles alleviate brain mitochondrial dysfunction and cellular senescence in γ-irradiated rats

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 31, 2025

Despite the diverse applications of γ radiation in radiotherapy, industrial processes, and sterilization, it causes hazardous effects on living organisms, such as cellular senescence, persistent cell cycle arrest, mitochondrial dysfunction. This study evaluated efficacy curcumin nanoparticles (CNPs) mitigating dysfunction senescence induced by rat brain tissues. Four groups male Wistar albino rats (n = 8 per group) were included: (Gr1) control group; (Gr2) CNPs group (healthy receiving oral administration at a dose 10 mg/kg/day, three times week for eight weeks); (Gr3) irradiated (rats exposed to single Gy head irradiation); (Gr4) + (irradiated treated with CNPs). The data obtained demonstrated that weeks attenuated oxidative stress γ-irradiated lowering brain's lipid peroxidation level [malondialdehyde (MDA)] enhancing antioxidant markers [superoxide dismutase (SOD), reduced glutathione (GSH), total capacity (TAC)] (P < 0.05). In addition, significantly increased function improving complex I, II, ATP production levels compared group. rats, also showed anti-neuroinflammatory reducing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-ĸB) Moreover, administered β-galactosidase activity expression p53, p21, p16 genes 0.05) while concurrently inducing significant increase AMPK mRNA conclusion, ameliorated neurotoxicity hold promise novel agent delay via their combined antioxidant, anti-inflammatory, mitochondrial-enhancing properties.

Language: Английский

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Epigenetic regulations of cellular senescence in osteoporosis

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102235 - 102235

Published: Feb. 16, 2024

Language: Английский

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Radiotherapy‐Induced Astrocyte Senescence Promotes an Immunosuppressive Microenvironment in Glioblastoma to Facilitate Tumor Regrowth

Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)

Published: Feb. 11, 2024

Abstract Accumulating evidence suggests that changes in the tumor microenvironment caused by radiotherapy are closely related to recurrence of glioma. However, mechanisms which such radiation‐induced involved regrowth have not yet been fully investigated. In present study, how cranial irradiation‐induced senescence non‐neoplastic brain cells contributes glioma progression is explored. It observed senescent facilitated enhancing peripheral recruitment myeloid inflammatory glioblastoma. Further, it identified astrocytes one most susceptible populations and they promoted chemokine secretion via senescence‐associated secretory phenotype. By using senolytic agents after eliminate these substantially prolonged survival time preclinical models. The findings suggest tumor‐promoting role irradiated emphasize translational relevance for efficacy gliomas.

Language: Английский

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Selective targeting of dipeptidyl‐peptidase 4 (DPP‐4) positive senescent chondrocyte ameliorates osteoarthritis progression

Aging Cell, Journal Year: 2024, Volume and Issue: 23(7)

Published: March 31, 2024

Abstract Senescent cells increase in many tissues with age and induce age‐related pathologies, including osteoarthritis (OA). chondrocytes (SnCs) are found OA cartilage, the clearance of those prevents progression. However, targeting SnCs is challenging due to absence a senescent chondrocyte‐specific marker. Therefore, we used flow cytometry screen select chondrocyte surface markers cross‐validated published transcriptomic data. Chondrocytes expressing dipeptidyl peptidase‐4 (DPP‐4), selected marker, had multiple senescence phenotypes, such as increased senescence‐associated‐galactosidase, p16, p21, senescence‐associated secretory phenotype expression, showed phenotypes. To examine effects DPP‐4 inhibition on DPP‐4+ SnCs, sitagliptin, inhibitor, was treated vitro. As result, selectively eliminates without affecting DPP‐4‐ chondrocytes. assess vivo therapeutic efficacy three known senolytics (ABT263, 17DMAG, metformin) sitagliptin were comparatively verified DMM‐induced rat model. Sitagliptin treatment specifically effectively eliminated compared other senolytics. Furthermore, Intra‐articular injection model collagen type II proteoglycan expression physical functions decreased cartilage destruction, subchondral bone plate thickness MMP13 leading amelioration Collectively, OARSI score lowest group. Taken together, marker for suggested that selective could be promising strategy prevent

Language: Английский

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Development of Machine Learning Models for Predicting Radiation Dermatitis in Breast Cancer Patients using Clinical Risk Factors, Patient-Reported Outcomes, and Serum Cytokine Biomarkers

Clinical Breast Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Radiation dermatitis (RD) is a significant side effect of radiotherapy experienced by breast cancer patients. Severe symptoms include desquamation or ulceration irradiated skin, which impacts quality life and increases healthcare costs. Early identification patients at risk for severe RD can facilitate preventive management reduce symptoms. This study evaluated the utility subjective objective factors, such as patient-reported outcomes (PROs) serum cytokines, predicting in The performance machine learning (ML) logistic regression-based models were compared. Data from 147 who underwent was analyzed to develop prognostic models. ML algorithms, including neural networks, random forest, XGBoost, regression, employed predict clinically Grade 2+ RD. Clinical PROs, cytokine biomarkers incorporated into Model using nested cross-validation with separate loops hyperparameter tuning calculating metrics. Feature selection identified 18 predictors smoking, boost, reduced motivation, cytokines interleukin-4, interleukin-17, interleukin-1RA, interferon-gamma, stromal cell-derived factor-1a. Incorporating these predictors, XGBoost model achieved highest an area under curve (AUC) 0.780 (95% CI: 0.701-0.854). not significantly improved over regression model, demonstrated AUC 0.714 0.629-0.798). levels provide complementary information undergoing radiotherapy. comparable AUC>0.70.

Language: Английский

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Therapy-induced senescence as a component of tumor biology: Evidence from clinical cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(6), P. 188994 - 188994

Published: Oct. 6, 2023

Language: Английский

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Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation‐induced premature aging mice

Aging Cell, Journal Year: 2023, Volume and Issue: 22(11)

Published: Aug. 31, 2023

Abstract Radiotherapy destroys cancer cells and inevitably harms normal human tissues, causing delayed effects of acute radiation exposure (DEARE) accelerating the aging process in most survivors. However, effective methods for preventing premature induced by ionizing are lacking. In this study, mice DEARE model was established after 6 Gy total body irradiation (TBI). Then therapeutic mechanism nicotinamide riboside on were evaluated. The results showed that TBI hematopoietic system mice. Nicotinamide treatment reversed spleen phenotypes inhibiting cellular senescence ameliorated serum metabolism profiles. Further demonstrated supplementation alleviated myeloid bias stem temporarily restored regenerative capacity probably mitigating reactive oxygen species activated GCN2/eIF2α/ATF4 signaling pathway. study firstly indicate shows potential as a agent radiation‐exposed populations patients who received radiotherapy.

Language: Английский

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Noninvasive morpho-molecular imaging reveals early therapy-induced senescence in human cancer cells

Science Advances, Journal Year: 2023, Volume and Issue: 9(37)

Published: Sept. 13, 2023

Anticancer therapy screening in vitro identifies additional treatments and improves clinical outcomes. Systematically, although most tested cells respond to cues with apoptosis, an appreciable portion enters a senescent state, critical condition potentially driving tumor resistance relapse. Conventional protocols would strongly benefit from prompt identification monitoring of therapy-induced (TIS) their native form. We combined complementary all-optical, label-free, quantitative microscopy techniques, based on coherent Raman scattering, multiphoton absorption, interferometry, explore the early onset progression this phenotype, which has been understudied unperturbed conditions. identified TIS manifestations as 24 hours following treatment, consisting substantial mitochondrial rearrangement increase volume dry mass, followed by accumulation lipid vesicles starting at 72 hours. This work holds potential affect anticancer treatment research, offering rapid, accurate method identify initial cells.

Language: Английский

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Autophagy and senescence facilitate the development of antiestrogen resistance in ER positive breast cancer

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: March 18, 2024

Estrogen receptor positive (ER + ) breast cancer is the most common diagnosed annually in US with endocrine-based therapy as standard-of-care for this subtype. Endocrine includes treatment antiestrogens, such selective estrogen modulators (SERMs), downregulators (SERDs), and aromatase inhibitors (AIs). Despite appreciable remission achievable these treatments, a substantial cohort of women will experience primary tumor recurrence, subsequent metastasis, eventual death due to their disease. In cases, cells have become resistant endocrine therapy, resistance identified major obstacle medical oncologist patient. To combat development resistance, options ER , HER2 negative now include CDK4/6 used adjuvants antiestrogen treatment. addition dysregulated activity CDK4/6, plethora genetic biochemical mechanisms been that contribute resistance. These mechanisms, which by lab-based studies utilizing appropriate cell animal models cancer, clinical gene expression profiles identify candidate genes, are subject review. addition, we discuss molecular targeting strategies utilized conjunction or target cells. Of approaches currently being explored improve efficacy patient outcome, two adaptive survival autophagy, “reversible” senescence, considered targets. Autophagy and/or senescence induction response treatments often induced inhibitors. Unfortunately, effective pathways not yet successfully developed. Thus, there an urgent need continued interrogation autophagy clinically relevant long-term goal identifying new targets improved cancer.

Language: Английский

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