Drug Screening Tests Research Articles

Gastric biopsy-derived cell line and its utility in assessing tumor cell drug sensitivity

Gastric cancer (GC) has benefited from treatment improvements such as minimally invasive surgery, molecular-targeted drugs, and immune check point inhibitors. However, the prognosis of advanced GC is still unfavorable. Minimally invasive pre-treatment detection of drug sensitivity (MI-PDDS) has increasing importance in view of improved chemotherapy. Gastric biopsy specimens are obtained with relative ease but have not been considered an appropriate source for generating cell lines because of their minute amounts. We therefore materialized the idea of MI-PDDS using biopsy-derived cell lines obtained from endoscopic biopsy specimens. Here, a cell line designated TCC-GC1-C1 was established from a biopsy specimen of a histologically confirmed adenocarcinoma of the stomach. The cell line showed the ability of forming spheroid with deeply stained nuclei and disturbed cellular morphology indicative of malignancy. Single-nucleotide polymorphism (SNP) genotyping of the cell line revealed a duplication of chromosome19q and a deletion of chromosome 8p. A drug screening test with 221 anticancer drugs showed that the cell line had high sensitivity to the proteasome inhibitor (Carfilzomib) and the fibroblast growth factor receptor inhibitor (Erdafitinib), with a low IC50 value of under 0.1 μM. Our MI-PDDS approach holds promise in making a treatment decision for advanced GC.

Establishment and characterization of a sigmoid colon cancer organoid with spinal metastasis.

Sigmoid colon cancer with spinal metastases is rare in distant metastasis. In addition, the prognosis of colon cancer patients with spinal metastases is extremely poor. In order to find effective therapeutic agents, we need to know the biological characteristics of such patients from related models. We collected sigmoid colon cancer tissue from a young female subject who was diagnosed with sigmoid colon cancer with multiple spinal metastases. We successfully established a sigmoid colon cancer organoid using this tissue and investigated drug screening in the patient. HE staining, immunohistochemistry, and DNA sequencing were utilized to compare the biological characteristics between the original tumor and the organoid. Furthermore, we investigated the drug screening of the sigmoid colon cancer organoid in vitro. A colon cancer organoid from sigmoid colon cancer with spinal metastases was successfully established. The organoid culture maintained the morphological features, histological features, and genomic landscape of the corresponding sigmoid colon cancer cells. Moreover, we performed drug screening tests to evaluate the effects of chemotherapeutic drugs and targeted drugs. The sigmoid colon cancer organoid with spinal metastases was a favorable preclinical model to explore the clinicopathologic characteristics of colon cancer patients with spinal metastases.

Advances in drug screening and toxicity testing: A review on Parkinson's disease using brain-on-a-chip

Abstract. Neurodegenerative diseases like Parkinson's disease (PD) pose substantial challenges to health and well-being. PD is characterized by the progressive degeneration of dopamine-producing neurons in the substantia nigra of the brain, leading to motor dysfunction, cognitive decline, and various non-motor symptoms. Advances in drug screening and toxicity testing have transformed the study of neurodegenerative diseases. Traditional methods often fall short in replicating the intricate environment of the human brain, highlighting the necessity for alternative pre-clinical models. Brain-on-a-chip technology, an innovative in vitro platform, offers a promising solution by simulating the intricate architecture and microenvironment of brain tissue. This microfluidic device incorporates living brain cells within a controlled setting, enabling the examination of neuronal behavior, disorder mechanisms, and pharmacological responses in a physiologically relevant context. This review examines recent advancements in brain-on-a-chip systems for PD research, emphasizes their potential to advance drug discovery and toxicity testing, also discusses the difficulty and limitations of current brain-on-a-chip technologies, for examples, challenges of specific neuron cell selection and incubation, and also restriction of organ-organ connection. By comparing in vitro and in vivo studies, brain-on-a-chip technology shows great promise for accelerating the development of effective therapies for PD, ultimately contributing to improved patient outcomes and a deeper understanding of the disease.

Abstract 315: Intraventricular hemorrhage due to bilateral vertebral artery dissection during treatment in drug intoxication patient: a case report

Introduction A vertebral artery dissection is a possible cause of stroke in young and middle‐aged adults without risk factors for cerebrovascular disease. It often occurs spontaneously for no particular reason, but it can also occur due to trauma or other causes. This study aims to report the treatment experience of bilateral vertebral artery dissection and intraventricular hemorrhage in a patient hospitalized for drug intoxication in our hospital. Methods A fifty‐six‐year‐old woman was found collapsed on the street and visited the emergency department of our hospital, complaining of comatose mentality and hypothermia. The Glasgow Coma Scale score measured at the visit was 3 points, and bradycardia and hypotension were present. A bag of medications prescribed by a psychiatrist was found in the patient's bag, and a drug screen test performed showed benzodiazepines positive. Brain CT performed in the emergency room did not reveal an acute lesion, so the patient was admitted to the intensive care unit at the department of emergency medicine under a drug intoxication impression. After four days of hospitalization, the patient's response started to improve, and on the 7th day, she showed a drowsy mentality. IVH was found in the bilateral lateral ventricles on diffusion MR performed on day 7, and dissection was confirmed in the bilateral distal V4 segment on additional CT angiography. Results Conservative treatment was performed in the intensive care unit, and a follow‐up CT showed that the hemorrhage was resolved. Still, dissecting aneurysms with an increased size was confirmed in both V4 segments. Emergency stent‐assisted coil embolization was performed for left V4 dissecting aneurysm with bleb. There were no complications during the procedure, and the right V4 dissecting aneurysm was decided to do embolization after a follow‐up examination. After the procedure, the patient showed an alert mentality, and there were no acute abnormal findings in the follow‐up examination. In the MRA performed one year after the procedure, the treated area on the left V4 dissecting aneurysm was well maintained. The right V4 dissecting aneurysm showed normal findings due to spontaneous healing. Conclusion In the case of vertebral artery dissection, which rapidly changes shape, careful observation is required, and appropriate treatment is required before new neurological symptoms develop. For treatment, stent‐assisted coil embolization can be a good option, and since spontaneous healing can occur in some cases, it is essential to determine an appropriate treatment method. In addition, appropriate follow‐up tests and identification of the cause are necessary for patients with decreased consciousness for which the cause is unclear.

Biobased hydrogel bioinks of pectin, nanocellulose and lysozyme nanofibrils for the bioprinting of A375 melanoma cell-laden 3D in vitro platforms

Melanoma is one of the most aggressive types of skin cancer, and the need for advanced platforms to study this disease and to develop new treatments is rising. 3D bioprinted tumor models are emerging as advanced tools to tackle these needs, with the design of adequate bioinks being a fundamental step to address this challenging process. Thus, this work explores the synergy between two biobased nanofibers, nanofibrillated cellulose (NFC) and lysozyme amyloid nanofibrils (LNFs), to create pectin nanocomposite hydrogel bioinks for the 3D bioprinting of A375 melanoma cell-laden living constructs. The incorporation of LNFs (5, 10 or 15 wt%) on a pectin-NFC suspension originates inks with enhanced rheological properties (shear viscosity and yield point) and proper shear-thinning behavior. The crosslinked hydrogels mimic the stiffness of melanoma tissues, being stable under physiological and cell-culture conditions, and non-cytotoxic towards A375 melanoma cells. P-NFC-LNFs (10 %) reveals good printability (Pr = 0.89) and printing accuracy (51 ± 2 %), and when loaded with A375 cells (3 × 106 cells mL−1) the bioink originates 3D-constructs with high cell viability (92 ± 1 %) after 14 days. The potential of the constructs as 3D in vitro platforms is corroborated by a drug-screening test with doxorubicin, where cells within the model displayed high sensitivity to the drug.

Psychometric Synthesis of the Drug Abuse Screening Test (DAST) Versions

Problem Statement Among individuals aged 12 years or older, 14.3% (40.0 million) reporting the use of an illicit drug in the previous year. Given the prevalence of drug abuse, it is increasingly important to determine effective screening practices, treatment procedures, and best practices among various subpopulations to identify drug use-related consequences. The DAST is one of the most commonly used and accurate drug screening tests. Method This psychometric synthesis of four versions of the Drug Abuse Screening Test (DAST-10, DAST-20, DAST-28, DAST-A) provided aggregated evidence from 346 articles over 40 years of published literature for score reliability, structure, diagnostic, and convergent validity, and descriptive statistics, all with the goal of informing counseling and medical practice and research. Results Results indicated adequate internal consistency (α = 0.81–0.84 across all four versions) and mostly medium to large effect size convergent correlations with comparison measures. Aggregated diagnostic validity data indicate optimal cutoff scores of 7 for DAST-10, 8 for DAST-20, 10 for DAST-28, and 6 for DAST-A. Discussion The DAST-10 appears the best choice for practical and psychometric reasons. Additional studies of the various DAST versions are needed to expand use across participant demographics. Public Statement of Relevance Drug use continues to be a societal problem and mental health practitioners need effective screening practices, treatment procedures, and best practices among various subpopulations to identify drug use-related consequences. This study synthesized 40 years of research on the four versions of the Drug Abuse Screening Test (DAST-10, DAST-20, DAST-28, DAST-A) and found acceptable levels of score reliability and validity for screening purposes.

Phenibut: A drug with one too many "buts".

Phenibut is a gamma aminobutyric acid derivative with activity at γ-aminobutyric acid (GABA)B, A and β-phenethylamine receptors. It was developed as a drug in the former Soviet Union to overcome anxiety and improve cognitive function in military personnel. In the last decade, it has made inroads into the European and U.S. markets, being marketed for purported nootropic properties. Here, we summarize the current knowledge on phenibut, its toxicology, pharmacology, adverse health effects, and patterns of use. Publications in peer-reviewed journals were searched in PubMed, Web of Science, and Google Scholar databases. Available literature points to adverse side effects associated with intoxication, withdrawal, and addiction to phenibut. Some of these effects can be life-threatening, requiring hospitalization and therapeutic interventions. Supportive efforts are often complicated by a lack of knowledge regarding phenibut's toxicology and pharmacology. Ingestion of phenibut was often associated with concomitant use of other substances of abuse. As control over its online marketing seems unrealistic, current efforts need to be focused on the addition of phenibut to current drug screening tests and the development of generally accepted treatment strategies for phenibut-associated toxicities.

AB091. Establishment and application of brainstem glioma organoids.

Traditional preclinical experiments on brainstem gliomas mainly rely on patient-derived primary cell lines, but there are problems such as low success rate in establishment and inability to preserve tumor heterogeneity, which limit the clinical transformation. As a new type of in vitro tumor model, organoids have similar structure and function to the original tumor, requiring less tissue for cultivation, with short cycle and high success rate, which is particularly suitable for brainstem glioma biopsy. There is currently no precedent for the successful construction of brainstem glioma organoid models. This new established organoid provides us a more robust preclinical tool for comprehending the pathogenesis and conducting drug screening for this kind of disease. Cultivate patient-derived brainstem glioma organoids in vitro, verify the genetic fidelity and consistency of the organoids through morphological experiments as well as sequencing technology. Then explore the evolutionary direction of multiple types of brainstem gliomas through pseudo-time series analysis. Complete drug screening, natural killer (NK) cell co-culture, oncolytic virus therapy, and other treatments based on organoids in vitro, and evaluate the efficacy. Complete co-culture of organoids and Institute of Cancer Research (ICR) mouse brain slices in vitro. Establish patient-derived organoid xenograft (PDOX) mouse models derived from organoids in vivo. The establishment of organoids of all types of brainstem gliomas was completed for the first time in the world, with a total of 41/48 organoid models derived from patients, with a success rate of 85.4%, covering all segments and pathological types. The results of morphological experiments and sequencing showed that the genetic characteristics of organoids were highly consistent with those of tumor tissues. Drug screening tests for temozolomide and panobinostat were completed in vitro, and NK cell co-culture and oncolytic virus therapy testing were achieved. Co-culture of brainstem glioma organoids and mouse brain slices was achieved in vitro. Furthermore, a PDOX model of brainstem glioma was established. Brainstem glioma organoids can be established maturely, stably, and reliably, and can be used for preclinical drug testing for patients. Animal models derived from brainstem glioma organoids have broad preclinical experimental value.

Avenues and Future Prospects of 3D Bioprinting

3D bioprinting has opened numerous avenues in the medical field, particularly advancing biomedical techniques for administration of drugs, fabrication of prostheses, surgical operations and restoration of damaged body parts. In this review we discuss the principles of 3D bioprinting, its applications, advantages over traditional methods, recent advancements and the future prospects of automation within the field.. The review also delves into the creation of more physiologically relevant tissue models for drug screening and toxicity testing. Finally, we also explore more recent advancements showcasing the impact of printing in space, integration of artificial intelligence (AI), and development of 4D bioprinting. Expressing current limitations and challenges, the review underscores the potential of 3D bioprinting in personalized medicine.

A high-throughput flowless microfluidic single and multi-solute concentration gradient generator: Design and parametric study.

Microfluidic concentration gradient generators (μ-CGGs) are critical in various biochemical assays, including cell migration, drug screening, and antimicrobial susceptibility testing. However, current μ-CGGs rely on integration with flow systems, limiting their scalability and widespread adoption owing to limited infrastructure and technical expertise. Hence, there is a need for flowless diffusional gradient generators capable of standalone operation, thereby improving throughput and usability. In this study, we model such a diffusional μ-CGG as an infinite source-sink system to capture two characteristic timescales: (i) gradient generation dictated by the diffusion timescale and (ii) stability determined by the rate of change in reservoir concentrations. Through finite-element simulations, we explored the influence of various geometric parameters such as the channel length, cross-sectional area, node and reservoir volumes, and the solute diffusivity on these timescales, along with experimental confirmation using fluorescent tracer diffusion. Our results show that while the gradient stability strongly depends on the reservoir volumes, diffusion length, and solute diffusion coefficient, they are independent of the node shape or the shape of the channel cross section. However, gradient profiles were found to be the strong functions of the diffusion length, solute diffusivity, and the geometric pattern of the microfluidic grid. Additionally, we showcased the versatility of the design by generating discrete gradient profiles and combinatorial gradients of two and three solutes, thus improving throughput in a wide range of on-chip biological assays. These findings underscore the potential of our microfluidic device as an easy-to-use, inexpensive, efficient, and high-throughput platform for various on-chip biological assays.

DIPG-48. PRECISION GUIDED THERAPY PROVIDES CLINICAL BENEFIT IN H3K27-ALTERED DIFFUSE MIDLINE GLIOMA

Abstract BACKGROUND The utility of precision-guided therapeutic approaches to H3K27-altered diffused midline glioma (DMG) remains uncertain. The Australian Zero Childhood Cancer (ZERO) program combines molecular profiling (whole-genome sequencing (WGS), whole-transcriptome sequencing (RNAseq), and DNA methylation profiling), with in vitro high-throughput drug screening (HTS) and patient-derived xenograft (PDX) drug-efficacy testing in patients with high-risk cancer. METHODS We report on the cohort of patients enrolled with a DMG in the ZERO clinical trial between 2017 and 2023. RESULTS 68 patients were enrolled, predominantly at diagnosis (87%), with pontine lesions (66%) at a mean age of 8.7 years. 59 (87%) patients had WGS + RNAseq successfully performed. Most tumors harbored an H3F3A mutation (n=50), followed by HIST1H3B (n=11), HIST1H3C (n=2), HIST2H3C (n=1) and EZHIP overexpression (n=4). 37 samples were suitable for cell culture, with HTS successfully performed in 25 cases, and PDXs established in 7. Precision-guided therapy (PGT) was recommended by the ZERO multidisciplinary tumor board for 53 patients (78%), including 5 recommendations guided by HTS. PI3K/mTOR inhibitors and MEK inhibitors were the most recommended PGTs. 21 patients (31%), receiving 24 PGTs, were eligible for survival analysis. The clinical benefit rate (per RAPNO) was 52% for patients receiving PGT, with 5 patients exhibiting PR and 6 patients SD >6 months. Notably, the 5 PR included: a PR in a patient with BRAFV600E mutation to dabrafenib/trametinib, a near-CR in a patient with germline BRCA2 mutation to olaparib/durvalumab, a sustained PR in a patient with FGFR1 mutation to trametinib/bevacizumab and 2 patients with PIK3CA mutations who received PGT in the context of recent radiotherapy. Median overall survival of the PGT group was 21.2 months versus 11.8 months for the rest of the cohort (hazard ratio 0.67 [95%CI 0.39-1.1]). CONCLUSIONS These results, for the first time, highlight the potential clinical benefit of PGT in H3K27-altered DMG.

Revolutionizing respiratory health research: “commercially-available lung-on-a-chip and air-liquid interface systems”

Inhalation of ultrafine particles, aerosol contaminants, and cigarette smoke can induce respiratory diseases. As humans are constantly exposed to various exogenous substances, it is crucial to study their impacts on respiratory diseases and airway dysfunction. Recently, organ-on-a-chip technology has been applied in many research studies to understand disease mechanisms, drug screening, and drug testing. The combination of organ-on-a-chip technology and the air-liquid interface (ALI) culture method is emerging as a new platform for realistically mimicking the microenvironment and physiological motions of the human lungs. Breathing motion can be simulated through cyclic stretching, while blood flow can be replicated using channel flow within the chip. The ALI system is critical for mucociliary differentiation, pseudostratified morphology, and epithelial barrier function development. The combination of organ-on-a-chip technology and ALI systems allows the integration of cyclic stretch as a breathing motion and microfluidic channels as circulatory systems. The chip system can also integrate the lung epithelial cells, extracellular matrix, and microstructures, providing microenvironments such as fibroblast, collagen, and immune cells to the epithelial cells. This review discusses chip systems as effective tools for recapitulating human lung environments and how they are applied in biological studies against various pulmonary diseases such as infections or inflammation, fibrosis, and malignancy.

Brain Function and Marijuana: Are there Changes after Abstinence of Consumption? Preliminary Results.

The legalization of cannabis use and false claims about the plant Cannabis sativa to be considered a pharmaceutical product have been found to increase consumption, lower risk perception, and lead to more health problems, without reducing criminal activity. Brain function, typically assessed by neuropsychological tests, shows abnormalities with acute marijuana use, but inconsistent results have been published after abstinence, with a maximum follow-up of 28 days. Our previous research, using neuropsychological tests and brain perfusion single photon emission computed tomography (neuroSPECT), demonstrated consistent abnormalities in brain function among schoolchildren who consume marijuana compared to their non-consuming peers. The aim of this study is to investigate whether brain function changes in 20 adult marijuana users after 6 months of abstinence. Comparison of neuropsychological tests (Rey Complex Figure; Porteus Maze; Four subtests of WAIS-IV Intellectual Tests; STROOP; D2) and perfusion neuroSPECT (functional images), obtained in relation to recent consumption and after 6 months of serial drug-screening test confirmed abstinence. In a one-year period (2020-2021) only five compliant participants were recruited. The COVID-19 pandemic was a limiting factor. Preliminary results of neuropsychological tests, functional brain perfusion images and limited statistical analysis are presented. The results of the neuropsychological tests of the three subjects who completed the abstinence period so far show some improvement in working memory and attention after abstinence. NeuroSPECT shows disorganized hypoperfusion of variable severity in relation to recent consumption, involving areas associated with cognitive function such as the posterior cingulate and temporal lobes, in our five initially enrolled patients, when compared to a normal database. Of these, only two participants have already been re-evaluated with neuroSPECT after 6 months of abstinence, one of whom showed some improvement on the post-abstinence images. We analyze the methodological challenges of this research, including the pandemic, to incorporate the appropriate corrections in the next phase of our investigation. Our final findings may provide clinicians and users with information about the long-term effects of marijuana use on brain function.

Rapid Metabolism of Monthly Extended-Release Buprenorphine Formulation: A Case Report

Background: Medication-assisted treatment constitutes the gold standard management for patients with opioid use disorder. Many factors can alter the response to medications, including genetic variations. In this case report, we discuss the presentation of a patient maintained on subcutaneous extended-release buprenorphine formulation who repeatedly presented objective and subjective signs of opioid withdrawal when he was switched from weekly to monthly formulation. We particularly highlight the role of metabolic pharmacogenes in this presentation. Case Presentation: Mr. Y, a 31-year-old single man, presented to our rehabilitation center seeking assistance for his polysubstance dependence, mainly opioid use disorder. As part of his multidisciplinary treatment plan, he was started on weekly extended-release buprenorphine. After maintenance for several months, he was transitioned to the monthly equivalent formulation. Since the transition, he began to develop severe withdrawal symptoms 1-2 weeks before his next due injection. This was paralleled by a noted decrease in buprenorphine level on his urine drug screening test. As soon as the patient was placed back on the weekly formulation, his symptoms resolved. Conclusion: This is a novel case highlighting the potential role of pharmacogenomics in clinical presentation and response to medications. Switching patients from weekly to monthly extendedrelease buprenorphine formulation might make rapid or ultra-rapid metabolizers at risk of earlyonset withdrawal symptoms. =In such a case, earlier provision of the injection or switching to another formulation or medication can be considered.

Tackling new psychoactive substances through metabolomics: UHPLC-HRMS study on natural and synthetic opioids in male and female murine models

Novel psychoactive substances (NPS) represent a broad class of drugs new to the illicit market that often allow passing drug-screening tests. They are characterized by a variety of structures, rapid transience on the drug scene and mostly unknown metabolic profiles, thus creating an ever-changing scenario with evolving analytical targets. The present study aims at developing an indirect screening strategy for NPS monitoring, and specifically for new synthetic opioids (NSOs), based on assessing changes in endogenous urinary metabolite levels as a consequence of the systemic response following their intake. The experimental design involved in-vivo mice models: 16 animals of both sex received a single administration of morphine or fentanyl. Urine was collected before and after administration at different time points; the samples were then analysed with an untargeted metabolomics LC-HRMS workflow. According to our results, the intake of opioids resulted in an elevated energy demand, that was more pronounced on male animals, as evidenced by the increase in medium and long chain acylcarnitines levels. It was also shown that opioid administration disrupted the pathways related to catecholamines biosynthesis. The observed alterations were common to both morphine and fentanyl: this evidence indicate that they are not related to the chemical structure of the drug, but rather on the drug class. The proposed strategy may reinforce existing NPS screening approaches, by identifying indirect markers of drug assumption.

Synthetic human gonadal tissues for toxicology

The process of mammalian reproduction involves the development of fertile germ cells in the testis and ovary, supported by the surrounders. Fertilization leads to embryo development and ultimately the birth of offspring inheriting parental genome information. Any disruption in this process can result in disorders such as infertility and cancer. Chemical toxicity affecting the reproductive system and embryogenesis can impact birth rates, overall health, and fertility, highlighting the need for animal toxicity studies during drug development. However, the translation of animal data to human health remains challenging due to interspecies differences. In vitro culture systems offer a promising solution to bridge this gap, allowing the study of mammalian cells in an environment that mimics the physiology of the human body. Current advances on in vitro culture systems, such as organoids, enable the development of biomaterials that recapitulate the physiological state of reproductive organs. Application of these technologies to human gonadal cells would provide effective tools for drug screening and toxicity testing, and these models would be a powerful tool to study reproductive biology and pathology. This review focuses on the 2D/3D culture systems of human primary testicular and ovarian cells, highlighting the novel approaches for in vitro study of human reproductive toxicology, specifically in the context of testis and ovary.

Development of a rapid-fire drug screening method by probe electrospray ionization tandem mass spectrometry for human urine (RaDPi-U).

Drug screening tests are mandatory in the search fordrugs in forensic biological samples, and immunological methods and mass spectrometry (e.g., gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry) are commonly used for that purpose. However, these methods have some drawbacks, and developing new screening methods is required. In this study, we develop a rapid-fire drug screening method by probe electrospray ionization tandem mass spectrometry (PESI-MS/MS), which is an ambient ionization mass spectrometrymethod, for human urine, named RaDPi-U. RaDPi-U is carried out in three steps: (1) mixing urine with internal standard (IS) solution and ethanol, followed by vortexing; (2) pipetting the mixture onto a sample plate for PESI; and (3) rapid-fire analysis by PESI-MS/MS. RaDPi-U targets 40 forensically important drugs, which include illegal drugs, hypnotics, and psychoactive substances. The analytical results were obtained within 3min because of the above-mentioned simple workflow of RaDPi-U. The calibration curves of each analyte were constructed using the IS method, and they were quantitatively valid, resulting in good linearity (0.972-0.999) with a satisfactory lower limit of detection and lower limit of quantitation (0.01-7.1ng/mL and 0.02-21ng/mL, respectively). Further, both trueness and precisions were 28% or less, demonstrating the high reliability and repeatability of the method. Finally, we applied RaDPi-U to three postmortem urine specimens and successfully detected different drugs in each urine sample. The practicality of the method is proven, and RaDPi-U will be a strong tool as a rapid-fire drug screening method not only in forensic toxicology but also in clinical toxicology.

Bibliometrics analysis based on the Web of Science: Current trends and perspective of gastric organoid during 2010-2023.

Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing. The use of gastric organoid models holds significant promise for advancing personalized medicine research. However, a comprehensive bibliometric review of this bur-geoning field has not yet been published. To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection (WoSCC) database. This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023, as indexed in the WoSCC. CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors, institutions and keywords related to gastric organoid. Citation, co-citation, and burst analysis methodologies were applied to assess the impact and progress of research. A total of 656 relevant studies were evaluated. The majority of research was published in gastroenterology-focused journals. Globally, Yana Zavros, Hans Clevers, James M Wells, Sina Bartfeld, and Chen Zheng were the 5 most productive authors, while Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the foremost influential scientists in this area. Institutions from the University Medical Center Utrecht, Netherlands Institute for Developmental Biology (Utrecht), and University of Cincinnati (Cincinnati, OH, United States) made the most significant contributions. Currently, gastric organoids are used mainly in studies investigating gastric cancer (GC), Helicobacter pylori-infective gastritis, with a focus on the mechanisms of GC, and drug screening tests. Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques. Major contributions from renowned academic institutions highlight this field's dynamic growth.

Abstract B013: Development of oropharyngeal tumor organoids for disease modeling and high throughput drug screening

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with approximately 550,000 new cases diagnosed each year. The oropharynx is one of the most common sites of occurrence, and disease in this region most often presents in the palatine tonsil, followed by the base of tongue and soft palate. Human papilloma virus (HPV) is a common cause of HNSCC, giving rise to a distinct subset of tumors with a different clinical presentation, disease course, and response to treatment. In order to further characterize HPV+ HNSCC tumors and their therapy response, we have leveraged our high throughput 3D tumor organoid screening platform. Our approach entails seeding tumor cells in extracellular matrix gels deposited around the perimeter of tissue culture wells in ring-like structures, with screening results available within a week from surgery (Phan et al, 2019; Al Shihabi et al, 2022; Nguyen et al, 2022; Al Shihabi et al 2023). We particularly focused on tonsil tumors, and develop organoids from both HNSCC and contralateral normal tonsil tissue. Thus far, we have procured tonsil samples from 31 patients to develop organoids, perform high throughput drug screening, and immunohistochemical characterization including H&E staining, Ki67, p16 and p53 immunohistochemical staining. We have leveraged dynamic optical contrast imaging (DOCI), a label-free tissue autofluorescence imaging method that is being investigated clinically (Kim et al, 2017), to assist in distinguishing tumor organoids from normal tissue organoids. Lastly, given the importance of radiation as a treatment modality for HPV+ HNSCC, we have also optimized a chemoradiation pipeline to test possible combinatorial effects. Taken together, our results demonstrate that 3D organoids of HNSCC generated from patient samples can successfully preserve native tissue characteristics and can be used for high throughput drug screening and radiation de-escalation testing, affording critical insight into the management of HNSCC in patients. Citation Format: Krishna K. Bommakanti, Luda Lin, Yazeed Alhiyari, Andreanne Sannajust, Brandon Mo, Lauran Evans, Peyton Tebon, Maie St. John, Alice Soragni. Development of oropharyngeal tumor organoids for disease modeling and high throughput drug screening [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B013.

Revolutionizing immune research with organoid-based co-culture and chip systems.

The intertwined interactions various immune cells have with epithelial cells in our body require sophisticated experimental approaches to be studied. Due to the limitations of immortalized cell lines and animal models, there is an increasing demand for human in vitro model systems to investigate the microenvironment of immune cells in normal and in pathological conditions. Organoids, which are self-renewing, 3D cellular structures that are derived from stem cells, have started to provide gap-filling tissue modelling solutions. In this review, we first demonstrate with some of the available examples how organoid-based immune cell co-culture experiments can advance disease modelling of cancer, inflammatory bowel disease, and tissue regeneration. Then, we argue that to achieve both complexity and scale, organ-on-chip models combined with cutting-edge microfluidics-based technologies can provide more precise manipulation and readouts. Finally, we discuss how genome editing techniques and the use of patient-derived organoids and immune cells can improve disease modelling and facilitate precision medicine. To achieve maximum impact and efficiency, these efforts should be supported by novel infrastructures such as organoid biobanks, organoid facilities, as well as drug screening and host-microbe interaction testing platforms. All these together or in combination can allow researchers to shed more detailed, and often patient-specific, light on the crosstalk between immune cells and epithelial cells in health and disease.