PMCID string | Title string | Sentences string |
|---|---|---|
PMC12852540 | Choosing the right animal model for sarcoma research | One study investigated the role of NOX2-derived reactive oxygen species (ROS) in the development and immune response of chemically induced sarcomas using MCA-induced model. |
PMC12852540 | Choosing the right animal model for sarcoma research | Genetically engineered mice with either a homozygous or heterozygous mutation in the NCF1 gene that disrupts NOX2 functionality were used. |
PMC12852540 | Choosing the right animal model for sarcoma research | The aim was to determine whether NOX2-driven ROS production influences sarcoma development, immune cell recruitment and response to therapies. |
PMC12852540 | Choosing the right animal model for sarcoma research | MCA was injected intramuscularly into mice to induce sarcoma formation over 70 to 160 days. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumours were characterised histologically and immune cell infiltration was assessed. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumour cells were isolated to establish cell lines which were then tested for proliferation, invasion and resistance to chemotherapy (cisplatin) and radiotherapy. |
PMC12852540 | Choosing the right animal model for sarcoma research | The rate and incidence of sarcoma development was not significantly affected by NOX2 mutation status. |
PMC12852540 | Choosing the right animal model for sarcoma research | MCA-induced tumours increased populations of immunosuppressive cells, such as Tregs and MDSCs, in both mutant and control mice. |
PMC12852540 | Choosing the right animal model for sarcoma research | However, this accumulation was independent of NOX2-derived ROS. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumour-infiltrating T cells showed activation and memory phenotypes, but their functionality was similar regardless of NOX2 functionality. |
PMC12852540 | Choosing the right animal model for sarcoma research | In vitro tests showed no differences in tumour growth, invasion or resistance to chemoradiotherapy between NOX2-deficient and NOX2-competent cell lines. |
PMC12852540 | Choosing the right animal model for sarcoma research | The model used in the study has some advantages, for example it better reflects the slow progression and immune dynamics of human tumours than transplantable tumour models. |
PMC12852540 | Choosing the right animal model for sarcoma research | It provides insights into the interactions between tumour development and the immune system, particularly in the context of chronic inflammation and immunosuppression. |
PMC12852540 | Choosing the right animal model for sarcoma research | It provides a basis for studying the effects of immune cell populations such as Tregs and MDSCs in tumour biology. |
PMC12852540 | Choosing the right animal model for sarcoma research | However, the model has limitations, including the dependence of tumorigenesis on chemical carcinogenesis, which introduces extensive DNA damage and variability, making results less specific to innate tumour processes. |
PMC12852540 | Choosing the right animal model for sarcoma research | The lack of a strong role for NOX2 in this model limits its relevance to cancers where oxidative stress is central to tumour progression or immune evasion. |
PMC12852540 | Choosing the right animal model for sarcoma research | Taken together, these findings suggest that NOX2-derived ROS do not play a critical role in MCA-induced sarcoma development or in shaping the immune microenvironment. |
PMC12852540 | Choosing the right animal model for sarcoma research | This challenges the notion that NOX2-derived ROS are universally important in tumour biology and highlights the importance of context-dependent mechanisms. |
PMC12852540 | Choosing the right animal model for sarcoma research | Interestingly, a recent study found that MCA-induced carcinogenesis was mitigated by an innate foreign body response that led to encapsulation of the carcinogen within fibrotic tissue. |
PMC12852540 | Choosing the right animal model for sarcoma research | Mice were injected intramuscularly with various doses of MCA to induce sarcoma formation. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumour development was monitored over time (up to 80 weeks) with comparisons between IFN-γR-deficient and competent mice. |
PMC12852540 | Choosing the right animal model for sarcoma research | Histological and immunohistochemical methods were used to analyse tissue repair responses, fibrosis and DNA damage at MCA injection sites. |
PMC12852540 | Choosing the right animal model for sarcoma research | These experiments demonstrated that IFN-γR expression by either bone marrow-derived or non-bone marrow-derived cells was sufficient to inhibit MCA-induced tumour formation, suggesting a multifaceted role of IFN-γ in controlling carcinogenesis. |
PMC12852540 | Choosing the right animal model for sarcoma research | DNA breaks in surrounding cells were measured using the TUNEL assay, providing direct evidence of the protective effect of IFN-γ in limiting mutagenic activity. |
PMC12852540 | Choosing the right animal model for sarcoma research | IFN-γR-deficient mice showed higher tumour incidence and earlier onset of sarcoma compared to IFN-γR-competent mice. |
PMC12852540 | Choosing the right animal model for sarcoma research | MCA encapsulation was more effective in IFN-γR-competent mice, correlating with reduced DNA damage and tumour development. |
PMC12852540 | Choosing the right animal model for sarcoma research | The study identified a robust tissue repair response in IFN-γR-competent mice, characterised by fibroblast accumulation and collagen deposition around the MCA. |
PMC12852540 | Choosing the right animal model for sarcoma research | This model links the effects of environmental carcinogens to the role of the immune system in preventing tumours, providing a new understanding of how tissue repair and the immune response work together to prevent tumour formation. |
PMC12852540 | Choosing the right animal model for sarcoma research | It highlights how the surrounding tissue environment, including scarring and structural changes, plays a crucial role in the development and growth of sarcomas. |
PMC12852540 | Choosing the right animal model for sarcoma research | Other carcinogens include asbestos, which causes DNA damage through chronic inflammation and oxidative stress, modelling environmentally induced sarcomas such as radiation-associated osteosarcoma or hepatic angiosarcoma from vinyl chloride exposure; asbestos itself leads classically to malignant mesothelioma, which, while not a sarcoma, exemplifies exposure-driven oncogenesis. |
PMC12852540 | Choosing the right animal model for sarcoma research | Aflatoxins, produced by moulds, are primarily associated with liver cancer, but are also used to study the systemic effects of dietary carcinogens and their role in sarcoma [35–37]. |
PMC12852540 | Choosing the right animal model for sarcoma research | Vinyl chloride, often associated with hepatic angiosarcoma, has been used in soft tissue sarcoma research to study the effects of industrial carcinogens . |
PMC12852540 | Choosing the right animal model for sarcoma research | Ethylnitrosourea (ENU), a highly mutagenic compound, induces a wide range of tumours and is ideal for identifying genetic drivers of sarcoma through mutagenesis screens .Carcinogens allow researchers to create models that mimic real-world tumour progression, helping to study the biology of sarcomas and test therapeutic strategies. |
PMC12852540 | Choosing the right animal model for sarcoma research | However, many of these models rely on unspecific, widespread mutagenesis, which can obscure the understanding of individual genetic pathways . |
PMC12852540 | Choosing the right animal model for sarcoma research | The primary advantage is their ability to reproduce the entire process of carcinogenesis, including its initiation, promotion, and progression, which closely mirrors the pathogenesis of many human cancers. |
PMC12852540 | Choosing the right animal model for sarcoma research | This makes them invaluable for studying the early events of tumourigenesis, such as DNA damage and mutation, as well as later processes, such as tumour growth and metastasis. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumours generated in these models often share histological and molecular features with human sarcomas, making them highly relevant for translational research. |
PMC12852540 | Choosing the right animal model for sarcoma research | For example, N-nitrosodiethylamine (DENA)-induced liver tumours and MCA-induced sarcomas share patterns of genetic instability and progression with human malignancies although some features can happen distinctly in chemically induced models for example an unique antigen on BALB/c Meth A sarcoma described in 1977. |
PMC12852540 | Choosing the right animal model for sarcoma research | These models are also relatively easy to establish, requiring only simple methods such as injections or dietary administration of carcinogens, making them cost-effective and accessible. |
PMC12852540 | Choosing the right animal model for sarcoma research | Their ability to generate multifocal and sometimes metastatic lesions further extends their utility, allowing researchers to study both the biology of the primary tumour and mechanisms underlying metastatic spread. |
PMC12852540 | Choosing the right animal model for sarcoma research | The primary limitation of these models is the unpredictability and variability of tumour development, which can lead to significant challenges in terms of experimental consistency. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumours induced by chemical carcinogens often vary widely in timing, location, size, and progression within individual animals, making it difficult to standardise studies or make comparisons between groups . |
PMC12852540 | Choosing the right animal model for sarcoma research | This inherent heterogeneity complicates the evaluation of therapeutic response and biomarkers. |
PMC12852540 | Choosing the right animal model for sarcoma research | In addition, the time required for tumour formation can be substantial, with latency periods often lasting weeks to months, making these models impractical for the rapid screening of drugs or treatments. |
PMC12852540 | Choosing the right animal model for sarcoma research | Another limitation is the broad, non-specific mutational effects of chemical carcinogens. |
PMC12852540 | Choosing the right animal model for sarcoma research | While this is useful for studying the general mechanisms of tumourigenesis, it often masks the specific genetic alterations that define certain human sarcoma subtypes, such as the EWS-FLI1 fusion in Ewing sarcoma or the SS18-SSX fusion in synovial sarcoma . |
PMC12852540 | Choosing the right animal model for sarcoma research | In addition, these models typically require invasive techniques or animal sacrifice to assess tumour burden and progression, particularly for internal or visceral tumours, such as those in the liver or lung . |
PMC12852540 | Choosing the right animal model for sarcoma research | Although advances in imaging technologies, such as MRI, have improved the ability to monitor tumor growth and therapeutic response noninvasively, these methods are expensive and not widely available . |
PMC12852540 | Choosing the right animal model for sarcoma research | Despite these challenges, chemically induced models remain important tools for understanding the complex processes of carcinogenesis, and their value is enhanced when combined with other approaches, such as genetically engineered or patient-derived models, to provide a more complete picture of sarcoma biology and treatment. |
PMC12852540 | Choosing the right animal model for sarcoma research | As genotype-to-phenotype mapping is obscured by widespread random mutagenesis, effective regimens identified in these models often lack a genotype-based rationale and therefore do not consistently translate to human subtypes. |
PMC12852540 | Choosing the right animal model for sarcoma research | Human tumour xenografts are the most prevalent among the animal models employed in cancer research. |
PMC12852540 | Choosing the right animal model for sarcoma research | Cell line-derived (CDX) xenografts are primarily used as rapid, scalable platforms for in vivo pharmacology, allowing dose and schedule optimisation, target engagement studies and early resistance mapping, albeit at the cost of reduced histological and molecular fidelity to primary sarcomas . |
PMC12852540 | Choosing the right animal model for sarcoma research | The procedure involves the implantation of tumour cells into immunocompromised mice, either subcutaneously or into the same organ type of origin as stated previously. |
PMC12852540 | Choosing the right animal model for sarcoma research | Athymic nude mice, severe combined immunodeficient (SCID) mice, or other immunocompromised mice can readily accept xenografts . |
PMC12852540 | Choosing the right animal model for sarcoma research | CDXs can be generated using established cell lines or patient-derived cells, providing flexibility for different research objectives. |
PMC12852540 | Choosing the right animal model for sarcoma research | Established cell lines are cancer cells that have been grown and maintained in the laboratory over time, ensuring their consistency and availability .These cells can be genetically modified to mimic specific mutations or engineered to express drug resistance, allowing researchers to study the effects of these changes on tumour behaviour or therapeutic response. |
PMC12852540 | Choosing the right animal model for sarcoma research | mCDXs (mouse CDXs) derived from such cell lines are widely used in basic research to understand cancer biology and in translational studies to test the efficacy of drugs before advancing to clinical trials . |
PMC12852540 | Choosing the right animal model for sarcoma research | To generate mCDXs, 1–5 million sarcoma cells are injected into each mouse, usually subcutaneously or into an organ that matches the tumour’s origin . |
PMC12852540 | Choosing the right animal model for sarcoma research | This creates a growing tumour that can be monitored for several months, making it ideal for long-term studies. |
PMC12852540 | Choosing the right animal model for sarcoma research | The important tool in choosing the right CDX model is Cellosaurus (https://www.cellosaurus.org) is a comprehensive database of over 140,000 cell lines used in biomedical research. |
PMC12852540 | Choosing the right animal model for sarcoma research | It provides detailed information on each cell line, including species (e.g. human, mouse), tissue of origin (e.g. liver, lung), disease association (e.g. HeLa for cervical cancer) and contamination issues . |
PMC12852540 | Choosing the right animal model for sarcoma research | Each cell line is assigned a unique identifier (e.g. CVCL_0030 for HeLa) and cross-referenced to resources such as PubMed and ATCC. |
PMC12852540 | Choosing the right animal model for sarcoma research | This database supports reproducibility and helps researchers find validated cell lines for experiments. |
PMC12852540 | Choosing the right animal model for sarcoma research | Currently the database lists 1,197 cell lines associated with sarcoma, a group of cancers that originate in connective tissues such as bone, cartilage, fat, muscle or blood vessels. |
PMC12852540 | Choosing the right animal model for sarcoma research | These cell lines represent different sarcoma subtypes, including osteosarcoma (e.g. U-2 OS, CVCL_0042), Ewing’s sarcoma (e.g. RD-ES, CVCL_2183) and liposarcoma (e.g. SW 872, CVCL_0547). |
PMC12852540 | Choosing the right animal model for sarcoma research | several cell lines listed in the Cellosaurus database have seen limited use in laboratory research and lack annotations for the fusion gene, including SYN-1, SYNb-1, SYNb-2, STSAR-198, STSAR-84, SW1045, A1095, HS 192.T, HS197.T, Hs431.T, Hs 701.t, hSS-005R, HSS-84, and RIT-3p . |
PMC12852540 | Choosing the right animal model for sarcoma research | Several studies have explored CDX models to evaluate targeted therapy and oncogenic activity in soft tissue sarcomas (STSs) . |
PMC12852540 | Choosing the right animal model for sarcoma research | For example, Floris et al. . |
PMC12852540 | Choosing the right animal model for sarcoma research | investigated a xenograft model derived from the IM-sensitive GIST882 cell line (bearing a KIT exon 13 mutation) and patient-derived tumor biopsies carrying KIT exon 9 and KIT exon 11 mutations into athymic NMRI nude mice. |
PMC12852540 | Choosing the right animal model for sarcoma research | This study was the first to use a nude mouse xenograft model to assess the effects of the histone deacetylase inhibitor (HDACi) panobinostat alone or in combination with Imatinib on human gastrointestinal stromal tumours (GISTs) with different oncogenic KIT mutations. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumours were passaged multiple times to establish consistent and reproducible models and maintained by subcutaneous transplantation until they reached a volume of approximately 0.7–1.7 cc before being harvested for analysis. |
PMC12852540 | Choosing the right animal model for sarcoma research | In the study, 36 mice were divided into four treatment groups, including an untreated control, a group receiving panobinostat intraperitoneally at 10 mg/kg daily, another receiving imatinib orally at 150 mg/kg twice daily, and a final group receiving combination therapy with both drugs at the same dose and schedule. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumour volume was monitored using calipers and histological analysis was performed to assess tumour response. |
PMC12852540 | Choosing the right animal model for sarcoma research | Endpoints included tumour growth, apoptosis, cell proliferation and histone acetylation, while immunohistochemistry and Western blot analysis were used to assess the molecular effects of the treatments on KIT signalling and histone acetylation in the harvested tumours. |
PMC12852540 | Choosing the right animal model for sarcoma research | Panobinostat induced significant tumour regression in GIST882 and KIT exon 11 tumours, but was less effective in KIT exon 9 tumours. |
PMC12852540 | Choosing the right animal model for sarcoma research | Combination therapy showed enhanced effects, with the highest tumour regression observed in KIT exon 11 tumours. |
PMC12852540 | Choosing the right animal model for sarcoma research | Panobinostat treatment caused increased necrosis, apoptosis and fibrosis in tumours, particularly in KIT exon 11 and GIST882 xenografts. |
PMC12852540 | Choosing the right animal model for sarcoma research | Combination therapy further increased apoptotic activity and histone acetylation. |
PMC12852540 | Choosing the right animal model for sarcoma research | Panobinostat increased histone H3 and H4 acetylation, disrupted chromatin structure and induced apoptosis. |
PMC12852540 | Choosing the right animal model for sarcoma research | Combination treatment resulted in a synergistic effect, with significant reductions in tumour volume and increases in molecular markers of apoptosis. |
PMC12852540 | Choosing the right animal model for sarcoma research | The use of established cell lines and patient-derived tumour material allowed the controlled study of drug effects on specific genetic backgrounds. |
PMC12852540 | Choosing the right animal model for sarcoma research | Subcutaneous transplantation ensured uniform tumour growth across mice, allowing consistent measurement of therapeutic responses. |
PMC12852540 | Choosing the right animal model for sarcoma research | The models provided a platform to study the molecular mechanisms of panobinostat and imatinib, in particular their effects on histone acetylation and KIT signalling. |
PMC12852540 | Choosing the right animal model for sarcoma research | Moreover, another study using CDX focused on the feasibility of a short-term, three-dimensional (3D) culture-based drug sensitivity test (DST) for malignant bone tumours. |
PMC12852540 | Choosing the right animal model for sarcoma research | Two osteosarcoma (OS) cell lines, KCS8 and KCS9, derived from metastatic lung tumours of OS patients, were used. |
PMC12852540 | Choosing the right animal model for sarcoma research | These cell lines were characterised by genetic and immunohistochemical analysis and then implanted subcutaneously into immunodeficient mice to establish CDX models. |
PMC12852540 | Choosing the right animal model for sarcoma research | Tumours from these models replicated osteosarcoma characteristics, including atypical cell morphology and osteoid formation. |
PMC12852540 | Choosing the right animal model for sarcoma research | The CDX tumours and derived cell lines were subjected to DST in a 3D collagen gel environment. |
PMC12852540 | Choosing the right animal model for sarcoma research | Sixty drugs were tested in all cell lines before and after xenotransplantation and in CDX tumour samples, including those depleted of non-tumour bearing mouse cells. |
PMC12852540 | Choosing the right animal model for sarcoma research | Drug sensitivity varied slightly between in vitro cell lines and in vivo CDX tumours, but a significant correlation in drug sensitivity was observed. |
PMC12852540 | Choosing the right animal model for sarcoma research | CDX tumours reflected the influence of the tumour microenvironment, although differences in drug sensitivity between cell line and CDX samples highlighted the influence of in vivo factors. |
PMC12852540 | Choosing the right animal model for sarcoma research | Clinical tumour samples from six patients (four with OS and two with Ewing sarcoma) were similarly subjected to 3D-DST. |
PMC12852540 | Choosing the right animal model for sarcoma research | These tests identified unique drug sensitivity profiles for each tumour, with proteasome inhibitors (bortezomib and carfilzomib) and the kinase inhibitor CEP-701 showing potential efficacy in all samples. |
PMC12852540 | Choosing the right animal model for sarcoma research | Genetic analysis of the clinical samples identified specific mutations, such as PIK3CA in one case, which correlated with sensitivity to targeted drugs such as mTOR/AKT inhibitors. |
PMC12852540 | Choosing the right animal model for sarcoma research | The study demonstrated that 3D-DST can be applied to CDX models and clinical samples of bone sarcomas. |
PMC12852540 | Choosing the right animal model for sarcoma research | The method requires small sample sizes, accommodates tumours with limited viability, and captures both tumour cell-specific and microenvironmental drug responses. |
PMC12852540 | Choosing the right animal model for sarcoma research | Notably, in myxoid liposarcoma, serially transplantable FUS–DDIT3-positive xenografts in athymic NCr-nu/nu mice were developed that retained the histology, fusion transcript and clinical chemosensitivity profile of round-cell and high-grade tumours; these models showed that trabectedin induced profound tumour regression, adipocytic differentiation and durable disease control at exposures comparable to the 24-h q3w schedule used clinically .Together with mechanistic work demonstrating anti-inflammatory and macrophage-targeting effects in myxoid liposarcoma and other sarcoma xenografts – including depletion and reprogramming of tumour-associated macrophages and up-regulation of thrombospondin-1 and TIMP-1/−2 in both tumour and host compartments [58–60]. |
PMC12852540 | Choosing the right animal model for sarcoma research | These models helped justify both histotype-restricted trials in myxoid liposarcoma and the choice of prolonged infusions and correlative microenvironmental endpoints in neoadjuvant and metastatic trabectedin studies. |
PMC12852540 | Choosing the right animal model for sarcoma research | Moreover, in myxoid liposarcoma, the first-generation CDK4/6 inhibitor PD-0332991 (palbociclib) was shown to produce deep, durable G1 arrest and tumour regression across multiple human tumour xenografts, with schedule-dependent effects related to the duration of target suppression . |
PMC12852540 | Choosing the right animal model for sarcoma research | These observations – together with the near-universal CDK4 amplification in well-differentiated and dedifferentiated liposarcoma – informed the design of early phase studies that restricted eligibility to CDK4-amplified WD/DD liposarcoma, used intermittent dosing to balance myelosuppression against continuous Rb hypophosphorylation, and selected 12-week progression-free survival as the primary endpoint. |
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