Gold(III)-Induced Amide Bond Cleavage In Vivo: A Dual Release Strategy via π-Acid Mediated Allyl Substitution.

Selective cleavage of amide bonds holds prominent significance by facilitating precise manipulation of biomolecules, with implications spanning from basic research to therapeutic interventions. However, achieving selective cleavage of amide bonds via mild synthetic chemistry routes poses a critical challenge. Here, we report a novel amide bond-cleavage reaction triggered by Na[AuCl] in mild aqueous conditions, where a crucial cyclization step leads to the formation of a 5-membered ring intermediate that rapidly hydrolyses to release the free amine in high yields.

Zebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancer.

Cancer patients often undergo rounds of trial-and-error to find the most effective treatment because there is no test in the clinical practice for predicting therapy response. Here, we conduct a clinical study to validate the zebrafish patient-derived xenograft model (zAvatar) as a fast predictive platform for personalized treatment in colorectal cancer. zAvatars are generated with patient tumor cells, treated exactly with the same therapy as their corresponding patient and analyzed at single-cell resolution.

Zebrafish Avatars: Toward Functional Precision Medicine in Low-Grade Serous Ovarian Cancer.

Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC).

Relapsed Ovarian Cancer Patients with Ascites and/or Pleural Effusion Still Benefit from Treatment: A Real-Life Study.

(1) Background: Relapsed HGSOC with ascites and/or pleural effusion is a poor-prognostic population and poorly represented in clinical studies. We questioned if these patients are worth treating. In other words, if these patients received the most effective treatment, would it change the course of this disease? To our knowledge this is the first real-life study to evaluate this question in this low-survival population.

Patient-Derived Breast Cancer Tissue Cultures for Anti-Endocrine Drug Assays.

Breast cancer is a complex and heterogeneous pathology, characterized by a variety of histological and molecular phenotypes. The majority of the breast cancers express the estrogen receptor alpha (ER), which plays a pivotal role in the pathobiology of the disease and are therefore classified as ER-positive (ER). In fact, targeting of the ER signaling pathway is the main therapeutic strategy for ER breast cancer.

Zebrafish Patient-Derived Avatars from Digestive Cancers for Anti-cancer Therapy Screening.

Patient-derived xenografts (PDXs), also called "avatars," are generated by the implantation of human primary tumor cells or tissues into a host animal. Given the complexity and unique characteristics of each tumor, PDXs are models of choice in cancer research and precision medicine. In this context, the zebrafish PDX model (zPDX or zAvatar) has been recognized as a promising in vivo model to directly challenge patient cells with anti-cancer therapies in a personalized manner.

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures.

Background: Estrogen receptor α (ERα) signaling is a defining and driving event in most breast cancers; ERα is detected in malignant epithelial cells of 75% of all breast cancers (classified as ER-positive breast cancer) and, in these cases, ERα targeting is the main therapeutic strategy. However, the biological determinants of ERα heterogeneity and the mechanisms underlying therapeutic resistance are still elusive, hampered by the challenges in developing experimental models recapitulative of intra-tumoral heterogeneity and in which ERα signaling is sustained. Ex vivo cultures of human breast cancer tissue have been proposed to retain the original tissue architecture, epithelial and stromal cell components and ERα.

In Vitro and Ex Vivo Models - The Tumor Microenvironment in a Flask.

Experimental tumor modeling has long supported the discovery of fundamental mechanisms of tumorigenesis and tumor progression, as well as provided platforms for the development of novel therapies. Still, the attrition rates observed today in clinical translation could be, in part, mitigated by more accurate recapitulation of environmental cues in research and preclinical models. The increasing understanding of the decisive role that tumor microenvironmental cues play in the outcome of drug response urges its integration in preclinical tumor models.

Zebrafish Avatars towards Personalized Medicine-A Comparative Review between Avatar Models.

Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored according to average response rates. "Omics" approaches are used for patient stratification and choice of therapeutic options towards a more precise medicine.

PREDECT Protocols for Complex 2D/3D Cultures.

PREDECT, a European IMI consortium, has assumed the task to generate robust 2D and 3D culture platforms. Protocols established for 2D and 3D monoculture and stromal coculture models of increasing complexity (spheroid, stirred-tank bioreactor, Matrigel- and collagen-embedded cultures) have been established between six laboratories within academia, biotech, and pharma. These models were tested using three tumor cell lines (MCF7, LNCaP, and NCI-H1437), covering three pathologies (breast, prostate, and lung), but should be readily transferable to other model systems.

3D-3-culture: A tool to unveil macrophage plasticity in the tumour microenvironment.

The tumour microenvironment (TME) shapes disease progression and influences therapeutic response. Most aggressive solid tumours have high levels of myeloid cell infiltration, namely tumour associated macrophages (TAM). Recapitulation of the interaction between the different cellular players of the TME, along with the extracellular matrix (ECM), is critical for understanding the mechanisms underlying disease progression.

Polymethoxylated Flavones from Orange Peels Inhibit Cell Proliferation in a 3D Cell Model of Human Colorectal Cancer.

Polymethoxylated flavones (PMFs) have been recognized to inhibit colorectal cancer proliferation through various mechanisms, however most of these studies have been performed on cells grown as monolayers that present limitations in mimicking the 3D tumor architecture and microenvironment. The main aim of this study was to investigate the anticancer potential of an orange peel extract (OPE) enriched in PMFs in a 3D cell model of colorectal cancer. The OPE was developed by supercritical fluid extraction and the anticancer effect was evaluated in HT29 spheroids cultures in a stirred-tank based system.

Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project.

Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery.

Drug screening in 3D in vitro tumor models: overcoming current pitfalls of efficacy read-outs.

There is cumulating evidence that in vitro 3D tumor models with increased physiological relevance can improve the predictive value of pre-clinical research and ultimately contribute to achieve decisions earlier during the development of cancer-targeted therapies. Due to the role of tumor microenvironment in the response of tumor cells to therapeutics, the incorporation of different elements of the tumor niche on cell model design is expected to contribute to the establishment of more predictive in vitro tumor models. This review is focused on the several challenges and adjustments that the field of oncology research is facing to translate these advanced tumor cells models to drug discovery, taking advantage of the progress on culture technologies, imaging platforms, high throughput and automated systems.

Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery.

Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono- and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437.

Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models.

Currently there is an effort toward the development of in vitro cancer models more predictive of clinical efficacy. The onset of advanced analytical tools and imaging technologies has increased the utilization of spheroids in the implementation of high throughput approaches in drug discovery. Agitation-based culture systems are commonly proposed as an alternative method for the production of tumor spheroids, despite the scarce experimental evidence found in the literature.

Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression.

3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression.

SPIM-fluid: open source light-sheet based platform for high-throughput imaging.

Light sheet fluorescence microscopy has recently emerged as the technique of choice for obtaining high quality 3D images of whole organisms/embryos with low photodamage and fast acquisition rates. Here we present an open source unified implementation based on Arduino and Micromanager, which is capable of operating Light Sheet Microscopes for automatized 3D high-throughput imaging on three-dimensional cell cultures and model organisms like zebrafish, oriented to massive drug screening.