Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Фев. 12, 2024

Background Neoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages neo-RT, which typically improves outcomes LARC patients, lack reliable biomarkers that predict response and monitor efficacy therapy, can result application unnecessary aggressive therapy affecting patients’ quality life. Hence, search for molecular assessing radio responsiveness this represents relevant issue. Methods Here, we combined proteomic metabolomic approaches to identify signatures, could discriminate tumors with good poor responses neo-RT. Results The integration data on differentially accumulated proteins metabolites made it possible disrupted metabolic pathways signaling processes connected irradiation, including ketone bodies synthesis degradation, purine metabolism, energy degradation fatty acid, amino acid focal adhesion. Moreover, proposed multi-component panels serve solid base develop monitoring predicting preoperative RT patients. Conclusion We proved an integrated multi-omic approach presents valid look at analysis global treatment from perspective reprogramming.

Язык: Английский

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Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Pharmaceuticals, Год журнала: 2024, Номер 17(6), С. 744 - 744

Опубликована: Июнь 6, 2024

Rarely has a chemical elicited as much controversy dichloroacetate (DCA). DCA was initially considered dangerous toxic industrial waste product, then potential treatment for lactic acidosis. However, the main controversies started in 2008 when found to have anti-cancer effects on experimental animals. These publications showed contradictory results vivo and vitro such that thorough consideration of this compound’s cancer is merited. Despite 50 years experimentation, DCA’s future therapeutics uncertain. Without adequate clinical trials health authorities’ approval, been introduced off-label treatments alternative medicine clinics Canada, Germany, other European countries. The lack well-planned its use by people without medical training discouraged scientific community. There are few studies DCA, many individual case reports. Case reports benefits against increasing recently. Furthermore, it shown synergizes with conventional repurposable drugs. Beyond classic target, pyruvate dehydrogenase kinase, new target molecules also recently discovered. findings renewed interest DCA. This paper explores whether existing evidence justifies further research role may play it.

Язык: Английский

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Chitosan-based nanoarchitectures for siRNA delivery in cancer therapy: A review of pre-clinical and clinical importance

International Journal of Biological Macromolecules, Год журнала: 2024, Номер unknown, С. 137708 - 137708

Опубликована: Ноя. 1, 2024

Язык: Английский

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FASN inhibition shows the potential for enhancing radiotherapy outcomes by targeting glycolysis, AKT, and ERK pathways in breast cancer

International Journal of Radiation Biology, Год журнала: 2025, Номер unknown, С. 1 - 12

Опубликована: Янв. 10, 2025

Purpose Breast cancer ranks as the most prevalent in women, characterized by heightened fatty acid synthesis and glycolytic activity. Fatty synthase (FASN) is prominently expressed breast cells, regulating synthesis, thereby enhancing tumor growth migration, leading to radioresistance. This study aims investigate how FASN inhibition affects cell proliferation, radioresistance cancer, well mechanisms involved.

Язык: Английский

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Decoding MUC1 and AR axis in a radiation-induced neuroendocrine prostate cancer cell-subpopulation unveils novel therapeutic targets

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

Despite initial efficacy of radiotherapy (RT), with or without concurrent androgen-deprivation, in prostate adenocarcinoma (PCa), neuroendocrine cancer (NEPC) emerging from disease progression is a highly aggressive malignancy for which standard therapies are mostly ineffective. Although oncogenic MUC1-C leading driver NEPC and PCa lineage plasticity, its putative role response to RT, including RT-induced transdifferentiation (tNED), has not been explored. We thus aimed explore the interplay between androgen receptor (AR) signaling MUC1 NEPC. Firstly, using radioresistant cell line (22Rv1-RR) we demonstrated that epigenetic suppression AR caused MUC1/MUC1-C upregulation, seems be activated through γSTAT3. activation positively associated increased expression neuroendocrine-related markers, CD56, chromogranin A, synaptophysin INSM transcriptional repressor 1 (INSM1). In tissues comparing adenocarcinoma, was upregulated negatively correlated AR, suppressed. Finally, proteomic analyses revealed upon RT selective pressure led acquisition stemness features, induction epithelial mesenchymal transition, enhancement basal cell-like traits. Notably, knockdown (KD) significantly boosted both 22Rv1-RR DU145 lines. Moreover, AR-induced overexpression PC3 lines entailed downregulation, resulting attenuated (NE) traits radioresistance, as well impaired migration invasion capabilities. Collectively, these results highlight promising radiosensitization target may ultimately help overcome therapy resistance progression.

Язык: Английский

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Unveiling Novel Targets in Lung Tumors for Enhanced Radiotherapy Efficacy: A Comprehensive Review

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(3)

Опубликована: Фев. 23, 2025

ABSTRACT Radiotherapy is a cornerstone of lung cancer management, though its efficacy frequently undermined by intrinsic and acquired radioresistance. This review examines the complexity tumors, highlighting their potential as reservoir novel targets for radiosensitization. Ionizing radiation (IR) primarily exerts effects through oxidative damage DNA double‐strand breaks (DSBs). Lung cells, however, develop mutations that enhance response (DDR) suppress cell death pathways. Additionally, interactions between tumor cells microenvironment (TME) components—including immune stromal molecular mediators such cytokines, chemokines, growth factors—contribute to resistance against IR. Understanding these intricate relationships reveals improve radiotherapy outcomes. Promising include DDR pathways, immunosuppressive molecules, hypoxia, proangiogenic mediators, other key signaling discusses emerging strategies, combining with immunomodulators, hypoxia inhibitors, DDR‐targeting agents, innovative approaches. By offering comprehensive analysis TME, this underscores opportunities effectiveness targeted radiosensitization strategies.

Язык: Английский

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Nutrient transporter-oriented nanoinhibitor counteracts intracellular metabolic reprogramming for RT-resistant HCC treatment

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101608 - 101608

Опубликована: Фев. 25, 2025

Язык: Английский

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Altered Arginine Metabolism Affects Proliferation and Radiosensitivity of Keloids

Experimental Dermatology, Год журнала: 2025, Номер 34(3)

Опубликована: Март 1, 2025

ABSTRACT Keloid is characterised by the reprogramming of cellular metabolism, wherein keloid cells adapt their metabolic pathways to meet demands for energy and biosynthetic precursors. Investigating intricate relationship between metabolism biological behaviour holds potential yield novel therapeutic strategies keloid. To elucidate molecular alterations underlying regulatory mechanisms in keloids, we created comprehensive profiling at pathway level analysing metabolomic, transcriptomic single‐cell RNA‐sequencing data from keloids adjacent skin. Viability assay clonogenic were performed validate function pathway(s) primary fibroblast cells. Integrated analysis revealed an upregulation arginine proline keloids. According RNA‐seq data, elevated expression genes related such as P4HA3, P4HA2, P4HA1, PYCR1, OAT ASS1 , was predominately highly expressed fibroblast‐2. Fibroblast‐2 displayed more obvious phenotypes mesenchymal fibroblast. Critical integrated including PYCR1 AZIN2 metabolites fumaric acid 2‐oxo‐5‐amino‐pentanoic showed prognostic relevance with disease‐free survival Additionally, In vitro study that deprivation therapy (ADT) inhibited radiosensitised proliferation keloid‐derived fibroblasts. conclusion, our thorough multiomics deepens understanding link radiosensitivity. Elevated activity fibroblasts may be a

Язык: Английский

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High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma

Cell Death and Differentiation, Год журнала: 2024, Номер 31(5), С. 683 - 696

Опубликована: Апрель 8, 2024

Язык: Английский

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Anticancer Activity of Rice Callus Suspension Cultures from Aromatic Varieties and Metabolites Regulated in Treated Cancer Cell Lines

Rice Science, Год журнала: 2024, Номер 31(4), С. 449 - 462

Опубликована: Апрель 12, 2024

Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints, for cancer prevention. Rice callus suspension cultures (RCSC) seed extracts prepared from aromatic rice varieties evaluated cytotoxic impact on human colon lung cell lines, as well a normal control line, using Taxol positive control. RCSC two Indian applied at different concentrations treat the lines fibroblasts over varying intervals. Apoptosis was assessed in 1:5 dilution A549 HT-29 treated 72 h, propidium iodide staining flow cytometry. showed more potent effect than minimal contrast Taxol. Confocal microscopy cytometry further confirmed apoptotic RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved cytotoxicity, highlighted altered pathways. is proposed an alternative source development novel anticancer drugs reduced effects.

Язык: Английский

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