From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9463 - 9463

Опубликована: Авг. 30, 2024

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance treatment approaches. This article provides comprehensive review our current understanding CRC epidemiology, risk factors, pathogenesis, management strategies. We also present intricate cellular architecture colonic crypts their roles intestinal homeostasis. carcinogenesis multistep processes are described, covering conventional adenoma-carcinoma sequence, alternative serrated pathways, influential Vogelstein model, which proposes sequential

Язык: Английский

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MiRNAs as new potential biomarkers and therapeutic targets in brain metastasis

Non-coding RNA Research, Год журнала: 2024, Номер 9(3), С. 678 - 686

Опубликована: Фев. 23, 2024

Brain metastases represent a formidable challenge in cancer management, impacting significant number of patients and contributing significantly to cancer-related mortality. Conventional diagnostic methods frequently fall short, underscoring the imperative for non-invasive alternatives. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) long non-coding (lncRNAs), present promising avenues exploration. These ncRNAs exert influence over prognosis treatment resistance brain metastases, offering valuable insights into underlying mechanisms potential therapeutic targets. Dysregulated have been identified originating from various primary cancers, unveiling opportunities intervention prevention. The analysis ncRNA expression bodily fluids, such as serum cerebrospinal fluid, provides noninvasive means differentiate tumors. NcRNAs, particularly miRNAs, assume pivotal role orchestrating immune response within microenvironment. MiRNAs exhibit promise diagnosing effectively distinguishing between normal cells, pinpointing tissue origin metastatic manipulation miRNAs holds substantial treatment, prospect reducing toxicity enhancing efficacy. Given limited options threat patients, RNAs, especially emerge beacons hope, serving both tools Further clinical studies are validate specificity sensitivity ncRNAs, potentially reshaping approaches tackle this elevate outcomes affected patients.

Язык: Английский

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Insights on the Role of Polyphenols in Combating Cancer Drug Resistance

Biomedicines, Год журнала: 2023, Номер 11(6), С. 1709 - 1709

Опубликована: Июнь 14, 2023

Chemotherapy resistance is still a serious problem in the treatment of most cancers. Many cellular and molecular mechanisms contribute to both inherent acquired drug resistance. They include use unaffected growth-signaling pathways, changes tumor microenvironment, active transport medicines out cell. The antioxidant capacity polyphenols their potential inhibit activation procarcinogens, cancer cell proliferation, metastasis, angiogenesis, as well promote inhibition or downregulation efflux transporters, have been linked reduced risk epidemiological studies. Polyphenols also ability alter immunological responses inflammatory cascades, trigger apoptosis cells. discovery relationship between abnormal growth signaling metabolic dysfunction cells highlights importance further investigating effects dietary polyphenols, including boost efficacy chemotherapy avoid multidrug (MDR). Here, it summarized what known regarding effectiveness natural polyphenolic compounds counteracting that might develop drugs result variety different mechanisms.

Язык: Английский

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Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Окт. 3, 2023

Successful clinical methods for tumor elimination include a combination of surgical resection, radiotherapy, and chemotherapy. Radiotherapy is one the crucial components cancer treatment regimens which allow to extend patient life expectancy. Current cutting-edge radiotherapy research focused on identification that should increase cell sensitivity radiation activate anti-cancer immunity mechanisms. Radiation activates various cells microenvironment (TME) impacts growth, angiogenesis, immunity. was shown regulate signaling functions TME immune vasculature components, including tumor-associated macrophages, dendritic cells, endothelial cancer-associated fibroblasts (CAFs), natural killers, other T subsets. Dual effects radiation, metastasis-promoting activation oxidative stress, have been detected, suggesting triggers heterogeneous targets. In this review, we critically discuss angiogenesis during used strengthen novel immunotherapy. Intracellular, genetic, epigenetic mechanisms manipulations responses stress by are accented. findings indicate be considered as supporting instrument immunotherapy limit cancer-promoting TME. To cancer-free survival rates, it recommended combine personalized therapy with TME-targeting drugs, checkpoint inhibitors.

Язык: Английский

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Integrins and Integrin-Driven Secretory Pathways as Multi-dimensional Regulators of Tumor-Associated Macrophage Recruitment and Reprogramming in Tumor Microenvironment

Matrix Biology, Год журнала: 2024, Номер 135, С. 55 - 69

Опубликована: Дек. 5, 2024

Язык: Английский

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Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 7, 2024

Abstract Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated spatiotemporal heterogeneity molecular expression during transformation. It was found that although both tight (TJs) gap (GJs) were involved maintaining microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), TJ molecules consistently decreased normal-cancer is a potential oncogenic factor. For fibroblasts (mesenchymal GJs increased In addition, profiles TJs used to stratify colorectal cancer (CRC) patients, where subtypes characterized high GJ levels low enhanced mesenchymal signals. Importantly, propose leiomodin 1 (LMOD1) biphasic, with features GJs. LMOD1 not only promotes activation cancer-associated (CAFs) but also inhibits Epithelial–mesenchymal transition (EMT) program conclusion, these findings demonstrate provide new insights into further understanding TME heterogeneity. Graphical

Язык: Английский

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Nucleic acid coated photothermal nanoregulator for multiple therapy of drug-resistant breast cancer

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 308, С. 142592 - 142592

Опубликована: Март 29, 2025

Язык: Английский

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Stimuli-responsive smart nanomaterials for theranostics of urological cancers

Coordination Chemistry Reviews, Год журнала: 2025, Номер 539, С. 216745 - 216745

Опубликована: Май 1, 2025

Язык: Английский

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Tie2 activity in cancer associated myofibroblasts serves as novel target against reprogramming of cancer cells to embryonic-like cell state and associated poor prognosis in oral carcinoma patients

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Май 10, 2025

Abstract Background Myofibroblastic cancer-associated fibroblasts (CAF) in tumor stroma serves as an independent poor prognostic indicator, supporting higher stemness oral cancer; however, the underlying biology is not fully comprehended. Here, we have explored crucial role of Tunica Interna Endothelial Cell Kinase (Tie2/TEK) signaling transition and maintenance myofibroblastic phenotype CAFs, possible link with prognosis head neck squamous cell carcinoma (HNSCC) patients. Methods Bulk single RNA-sequencing (scRNAseq) methods in-depth bioinformatic analysis were applied for CAF cancer cells co-culture studying molecular relationships. In vitro 3D-spheroid-forming ability, expression markers, vivo formation ability zebrafish embryo syngeneic mouse allografts was conducted to test stemness, upon targeting CAF-specific Tie2 activity by gene silencing or small molecule inhibitor. Immunohistochemistry performed locate distribution αSMA primary tumors carcinoma. Prognosis HNSCC patient cohort from The Cancer Genome Atlas (TCGA) study analysed based on sample set enrichment score (ssGSEA) Kaplan–Meier analysis. Results Autocrine exogenous TGFβ-induction led recruitment histone deacetylase 2 (HDAC2) promoter Tie2-antagonist, Angiopoietin-2 (ANGPT2), resulting its downregulation, leading phosphorylation (Y992) subsequent activation SRC (Y418). This SRC/ROCK mediated αSMA-positive stress-fiber gain myofibroblast phenotype. Tie2-signaling responsible producing embryonic-like state co-cultured cells; enhanced initiating ability. exerted dynamic reprogramming, upregulation ‘cell migration’ downregulation ‘protein biosynthesis’ related gene-regulatory-network modules malignant cells. AUCell scores calculated signatures derived these showed significant concordance independently reported scRNAseq studies association cohort. Conclusions may serve direct stromal-target against plasticity Overall, our work has provided wider applicability Tie2-specific functions biology, along known endothelial cell-specific function.

Язык: Английский

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Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis

Cells, Год журнала: 2025, Номер 14(10), С. 732 - 732

Опубликована: Май 17, 2025

Drug delivery to solid tumors is challenged by multiple physiological barriers arising from the tumor microenvironment, including dense extracellular matrix, cellular heterogeneity, hypoxic gradients, and elevated interstitial fluid pressure. These features hinder uniform distribution accumulation of therapeutics, reducing treatment efficacy. Despite their widespread use, conventional two-dimensional monolayer cultures fail reproduce these complexities, contributing poor translational predictability many preclinical candidates. Three-dimensional multicellular spheroids have emerged as more representative in vitro models that capture essential architecture, stromal interactions, microenvironmental resistance mechanisms. Spheroids exhibit spatially organized regions proliferation, quiescence, hypoxia, can incorporate non-tumor cells mimic tumor–stroma crosstalk. Advances spheroid analysis now enable detailed evaluation drug penetration, migration, cytotoxic response, molecular gradients using techniques such optical confocal imaging, large-particle flow cytometry, biochemical viability assays, microfluidic integration. By combining relevance with analytical accessibility, support mechanistic studies transport efficacy under tumor-like conditions. Their adoption into routine workflows has potential improve accuracy while reliance on animal models.

Язык: Английский

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