The efficacy of metastasis-directed external beam radiotherapy for castration-resistant prostate cancer: A retrospective multicenter study.

Background: To assess the efficacy of metastasis-directed external beam radiotherapy (MDT) in patients with castration-resistant prostate cancer (CRPC), we conducted a multicenter retrospective study.

Materials And Methods: We retrospectively analyzed data from patients with metastatic CRPC treated with MDT between January 2013 and July 2023 across 14 hospitals. Patients who received palliative or local radiation therapy or had insufficient clinical data were excluded.

Temporal changes in the urologist's practice behaviour of active surveillance for prostate cancer: analysis of prospective observational study cohort.

Background: To analyse temporal trends and variations in the use of active surveillance (AS) for low- and intermediate-risk prostate cancer in Japan.

Methods: We conducted a retrospective analysis of data from the Prostate Cancer Research International: AS-JAPAN study, a multi-institutional prospective observational cohort study, collected between January 2010 and February 2024. The primary outcomes of interest were temporal trends in characteristics of patients undergoing AS, including risk classification, age at enrollment, patterns of treatment interventions during AS, and reasons for discontinuation of AS.

Considerations for developing CYP induction assays in hepatocytes: Insights from a multilaboratory study.

Cytochrome P450 (CYP) induction studies using primary human hepatocytes (PHH) were conducted across seven laboratories. Standard operating procedures (SOPs) were developed and distributed, ensuring all laboratories used PHH from the same donor and CYP inducers prepared at a single location. In each laboratory, PHH was seeded, cultured, and tested for CYP induction.

3D hepatic spheroids and liver-organ on chip models displayed maintenance of hepatic functions and maturation profile in a long-term culture of the humanized HepaSH cells, a human cell population harvested from chimeric mice.

Long-term functional hepatocyte and reproducible cultures are required in pharmaceutical industries to model chronic liver disorders and to perform associated drug testing. In this frame, we have investigated the behavior of the HepaSH cells when cultivated in liver Biochips, in 3D Spheroids, and in Petri for 20 days. HepaSH is a newly developed humanized hepatocyte harvested from chimeric mice.

Transcriptomic characterization of the synergy between human induced pluripotent stem cells-derived liver- and pancreas-on-chip coculture.

Interactions between the liver and pancreas are key features of the carbohydrate and lipid homeostasis in healthy and pathological patients. To investigate the crosstalk between the two organs, we have developed an organ-on-chip coculture model derived from human induced pluripotent stem cells. The presence of pancreatic-derived tissue in the culture environment contributed to increase the CYP3A4 activity, the glycogen storage, and the expression of genes related to lipids, bile acids and sterol metabolism in the liver derived tissue.

Active Surveillance in Prostate Cancer With Intermediate-Risk Features: The PRIAS-JAPAN Study.

Objectives: To report outcomes of active surveillance (AS) for prostate cancer in men with intermediate-risk features of International Society of Urological Pathology (ISUP) grade group 2 and/or clinical stage T2 compared with ISUP grade group 1 and clinical stage T1 in the PRIAS-JAPAN study.

Methods: Patients with prostate cancer diagnosed between January 2010 and February 2024 were included in this study. PSA test, rectal examination, and re-biopsy were performed regularly.

Add-on or switch to vibegron in patients with overactive bladder insufficiently responding to initial 4-week antimuscarinics: a randomised, parallel-group, multicentre trial () .

Introduction: Overactive bladder (OAB) is a condition characterised by urinary urgency, often accompanied by frequency and nocturia. Antimuscarinics and β3 receptor agonists are first-line therapies that improve urinary symptoms and the quality of life. For insufficient antimuscarinic response, options include dose increase, switching medications or combination therapy.

Bioprinting functional hepatocyte organoids derived from human chemically induced pluripotent stem cells to treat liver failure.

Background: To treat liver failure, three-dimensional (3D) bioprinting is a promising technology used to construct hepatic tissue models. However, current research on bioprinting of hepatic tissue models primarily relies on conventional single-cell-based bioprinting, where individual functional hepatocytes are dispersed and isolated within hydrogels, leading to insufficient treatment outcomes due to inadequate cell functionality.

Objective: Here, we aim to bioprint a hepatic tissue model using functional hepatocyte organoids (HOs) and evaluate its liver-specific functions and .

Advancements in Microphysiological systems: Exploring organoids and organ-on-a-chip technologies in drug development -focus on pharmacokinetics related organs.

This study explored the evolving landscape of Microphysiological Systems (MPS), with a focus on organoids and organ-on-a-chip (OoC) technologies, which are promising alternatives to animal testing in drug discovery. MPS technology offers in vitro models with high physiological relevance, simulating organ function for pharmacokinetic studies. Organoids composed of 3D cell aggregates and OoCs mimicking in vivo environments based on microfluidic platforms represent the forefront of MPS.

Modeling vascular dynamics at the initial stage of endochondral ossification on a microfluidic chip using a human embryonic-stem-cell-derived organoid.

Vascular interactions play a crucial role in embryogenesis, including skeletal development. During endochondral ossification, vascular networks are formed as mesenchymal cells condense and later invade skeletal elements to form the bone marrow. We and other groups developed a model of endochondral ossification by implanting human embryonic stem cell (hESC)-derived sclerotome into immunodeficient mice.

A computational model of the crosstalk between hepatocyte fatty acid metabolism and oxidative stress highlights the key enzymes, metabolites, and detoxification pathways in the context of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as NAFLD) is a common liver disease worldwide and carries the risk of progressing to severe liver conditions, such as fibrosis and liver cancer. In the context of MASLD, evaluating fat accumulation in the liver and the subsequent production of oxidative stress is essential to understand the disease propagation. However, clinical studies using human patients to investigate the fat accumulation and the onset of oxidative stress in MASLD face ethical and technical challenges, highlighting the importance of alternative methods.

From to : xenotransplantation and vascularization of mouse embryonic kidneys in a microfluidic chip.

Organoids are emerging as a powerful tool to investigate complex biological structures . Vascularization of organoids is crucial to recapitulate the morphology and function of the represented human organ, especially in the case of the kidney, whose primary function of blood filtration is closely associated with blood circulation. Current microfluidic approaches have only provided initial vascularization of kidney organoids, whereas transplantation to animal models is problematic due to ethical problems, with the exception of xenotransplantation onto a chicken chorioallantoic membrane (CAM).

Transplantation of pancreatic beta-cell spheroids in mice non-swellable hydrogel microwells composed of poly(HEMA--GelMA).

Pancreatic islet transplantation is an effective treatment for type I diabetes mellitus. However, many problems associated with pancreatic islet engraftment remain unresolved. In this study, we developed a hydrogel microwell device for islet implantation, fabricated by crosslinking gelatin-methacryloyl (GelMA) and 2-hydroxyethyl methacrylate (HEMA) in appropriate proportions.

Establishment of human induced pluripotent stem cell-derived hepatobiliary organoid with bile duct for pharmaceutical research use.

In vitro models of the human liver are promising alternatives to animal tests for drug development. Currently, primary human hepatocytes (PHHs) are preferred for pharmacokinetic and cytotoxicity tests. However, they are unable to recapitulate the flow of bile in hepatobiliary clearance owing to the lack of bile ducts, leading to the limitation of bile analysis.

Vascularization of kidney organoids: different strategies and perspectives.

Kidney diseases such as glomerulopathy and nephron dysfunction are estimated to grow to more than 900 million cases by 2030, in 45% of which kidney transplantation will be required, representing a major challenge for biomedicine. A wealth of progress has been made to model human diseases using induced pluripotent stem cells (iPSCs) differentiated to a variety of organoids, including kidney organoids, and in developing various microfluidics-based organ-on-a-chip (OoC) systems based on them. With the combination of targeted gene editing capacities, relevant polymorphic genetic variants can be established in such organoid models to advance evidence-based medicine.

Transcriptomic profiling analysis of the effect of palmitic acid on 3D spheroids of β-like cells derived from induced pluripotent stem cells.

Type 2 diabetes (T2D) is posing a serious public health concern with a considerable impact on human life and health expenditures worldwide. The disease develops when insulin plasma level is insufficient for coping insulin resistance, caused by the decline of pancreatic β-cell function and mass. In β-cells, the lipotoxicity exerted by saturated free fatty acids in particular palmitate (PA), which is chronically elevated in T2D, plays a major role in β-cell dysfunction and mass.

Dynamic, IPSC-derived hepatic tissue tri-culture system for the evaluation of liver physiology.

Availability of hepatic tissue for the investigation of metabolic processes is severely limited. While primary hepatocytes or animal models are widely used in pharmacological applications, a change in methodology towards more sustainable and ethical assays is highly desirable. Stem cell derived hepatic cells are generally regarded as a viable alternative for the above model systems, if current limitations in functionality and maturation can be overcome.

A highly efficient cell culture method using oxygen-permeable PDMS-based honeycomb microwells produces functional liver organoids from human induced pluripotent stem cell-derived carboxypeptidase M liver progenitor cells.

Recent advancements in bioengineering have introduced potential alternatives to liver transplantation via the development of self-assembled liver organoids, derived from human-induced pluripotent stem cells (hiPSCs). However, the limited maturity of the tissue makes it challenging to implement this technology on a large scale in clinical settings. In this study, we developed a highly efficient method for generating functional liver organoids from hiPSC-derived carboxypeptidase M liver progenitor cells (CPM+ LPCs), using a microwell structure, and enhanced maturation through direct oxygenation in oxygen-permeable culture plates.

Mechanobiological stimulation in organ-on-a-chip systems reduces hepatic drug metabolic capacity in favor of regenerative specialization.

Hepatic physiology depends on the liver's complex structural composition which among others, provides high oxygen supply rates, locally differential oxygen tension, endothelial paracrine signaling, as well as residual hemodynamic shear stress to resident hepatocytes. While functional improvements were shown by implementing these factors into hepatic culture systems, direct cause-effect relationships are often not well characterized-obfuscating their individual contribution in more complex microphysiological systems. By comparing increasingly complex hepatic in vitro culture systems that gradually implement these parameters, we investigate the influence of the cellular microenvironment to overall hepatic functionality in pharmacological applications.