Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment

Doornebal, Ewald; Harris, Nicola L.; Riva, Antonio; Jagatia, Ravi; Pizanias, Michail; Prachalias, Andreas; Menon, Krishna; Preziosi, Melissa; Zamalloa, Ane; Miquel, Rosa; Zen, Yoh; Orford, Michael; Eaton, Simon; Heaton, Nigel; Palma, Elena; Srirajaskanthan, Rajaventhan; Chokshi, Shilpa

doi:10.3389/fendo.2022.909180

Cited by 5 publications

(3 citation statements)

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“…The histological, cytological characteristics, as well as the degree of differentiation of the tumor were perpetuated during the ex vivo culture, similar to that observed by different researchers using other tumor tissue slice models [31,35,67]. This study also observes the high proliferation rate during the culture period (Figure 2B), which is consistent with previous reports [68,69], suggesting that both the selected time and the culture conditions are suitable for conducting assays to assess the effects of antineoplastic agents on the tissues.…”

Section: Discussionsupporting

confidence: 83%

Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services

Carranza-Rosales,

Valencia-Mercado,

Esquivel-Hernández

et al. 2023

JPM

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Breast cancer is one of the main causes of death worldwide. Lately, there is great interest in developing methods that assess individual sensitivity and/or resistance of tumors to antineoplastics to provide personalized therapy for patients. In this study we used organotypic culture of human breast tumor slices to predict the experimental effect of antineoplastics on the viability of tumoral tissue. Samples of breast tumor were taken from 27 patients with clinically advanced breast cancer; slices were obtained and incubated separately for 48 h with paclitaxel, docetaxel, epirubicin, 5-fluorouracil, cyclophosphamide, and cell culture media (control). We determined an experimental tumor sensitivity/resistance (S/R) profile by evaluating tissue viability using the Alamar Blue® metabolic test, and by structural viability (histopathological analyses, necrosis, and inflammation). These parameters were related to immunohistochemical expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The predominant histological type found was infiltrating ductal carcinoma (85.2%), followed by lobular carcinoma (7.4%) and mixed carcinoma (7.4%). Experimental drug resistance was related to positive hormone receptor status in 83% of samples treated with cyclophosphamide (p = 0.027). Results suggest that the tumor S/R profile can help to predict personalized therapy or optimize chemotherapeutic treatments in breast cancer.

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Section: Discussionsupporting

confidence: 83%

Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services

Carranza-Rosales,

Valencia-Mercado,

Esquivel-Hernández

et al. 2023

JPM

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“…Collected human liver tissue was kept in sterile University of Wisconsin solution (ViaSpan; Bridge to Life Ltd., London, UK) until slicing. The PCLS (approximately 5 mg in weight, 250 µm thick) were prepared using a Krumdieck tissue slicer (Alabama R&D, Munford, AL, USA) as described previously [ 26 , 60 ]. The time from tissue collection to culture was kept to a minimum (approx.…”

Section: Methodsmentioning

confidence: 99%

Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related Liver Disease

Rastovic,

Bozzano,

Riva

et al. 2023

IJMS

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Alcohol-related liver disease (ALD) encompasses a range of pathological conditions that are complex to study at the clinical and preclinical levels. Despite the global burden of ALD, there is a lack of effective treatments, and mortality is high. One of the reasons for the unsuccessful development of novel therapies is that experimental studies are hindered by the challenge of recapitulating this multifactorial disorder in vitro, including the contributions of hepatotoxicity, impaired lipid metabolism, fibrosis and inflammatory cytokine storm, which are critical drivers in the pathogenesis of ALD in patients and primary targets for drug development. Here, we present the unique characteristics of the culture of human precision-cut liver slices (PCLS) to replicate key disease processes in ALD. PCLS were prepared from human liver specimens and treated with ethanol alone or in combination with fatty acids and lipopolysaccharide (FA + LPS) for up to 5 days to induce hepatotoxic, inflammatory and fibrotic events associated with ALD. Alcohol insult induced hepatocyte death which was more pronounced with the addition of FA + LPS. This mixture showed a significant increase in the cytokines conventionally associated with the prototypical inflammatory response observed in severe ALD, and interestingly, alcohol alone exhibited a different effect. Profibrogenic activation was also observed in the slices and investigated in the context of slice preparation. These results support the versatility of this organotypic model to study different pathways involved in alcohol-induced liver damage and ALD progression and highlight the applicability of the PCLS for drug discovery, confirming their relevance as a bridge between preclinical and clinical studies.

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“…This technique enables the monitoring of acute or chronic disease processes, offering valuable insights into the molecular mechanisms underlying ALD. The PCLS model also serves well as a platform for preclinical drug testing and effectively enables the exploration of acute and chronic scenarios, providing a bridge between preclinical and clinical studies not only in chronic liver diseases but also in liver cancers [206][207][208].…”

Section: Precision-cut Liver Slices (Pcls): a Miniaturized Window Int...mentioning

confidence: 99%

Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression

Osna,

Tikhanovich,

Ortega-Ribera

et al. 2024

Biomolecules

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Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

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Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment

Cited by 5 publications

References 50 publications

Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services

Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services

Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related Liver Disease

Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression

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