Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(1), P. 111 - 111

Published: Jan. 12, 2023

Multiple myeloma is a hematological cancer type. For its treatment, Bortezomib has been widely used. However, drug resistance to this effective chemotherapeutic developed for various reasons. 2D cell cultures and animal models have failed understand the MM disease resistance. It therefore essential utilize new technologies reveal complete molecular profile of disease. In review, we in-depth examined possible mechanisms that cause specifically addressed Moreover, also included use nanoparticles, 3D culture methods, microfluidics, organ-on-chip devices in multiple myeloma. We discussed whether emerging technology offers necessary tools prevent Despite ongoing research activities on MM, related studies cannot provide summary MM. Nanoparticle culturing frequently used number microfluidic application insufficient. By combining siRNA/miRNA with devices, genetic could be revealed. Microfluidic chips should clinically personal therapy point-of-care applications. At least microneedles, it ensured patients can go through treatment process more painlessly. This way, switched curable type list, targeted fewer side effects.

Language: Английский

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Trends in 3D models of inflammatory bowel disease

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(3), P. 167042 - 167042

Published: Jan. 29, 2024

Inflammatory bowel disease (IBD) encompasses a set of chronic inflammatory conditions, namely Crohn's and ulcerative colitis. Despite all advances in the management IBD, definitive cure is not available, largely due to lack holistic understanding its etiology pathophysiology. Several vitro, vivo, ex vivo models have been developed over past few decades order abbreviate remaining gaps. The establishment reliable predictable vitro intestinal inflammation may indeed provide valuable tools expedite validate development therapies for IBD. Three-dimensional (3D) more accurate representation different layers intestine, contributing stronger impact on drug screening research inflammation, bridging gap between research. This work provides critical overview state-of-the-art existing 3D discusses challenges, providing insights possible pathways towards achieving IBD mimetic models. We also address some main challenges faced by implementing cell culture while bearing mind clinical translational aspects.

Language: Английский

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Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells’ Escape from the Bone Marrow Microenvironment

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 889 - 889

Published: Feb. 22, 2024

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population MM survivors exceeding 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized extramedullary disease and dominant proliferative clones, despite these treatments. To build upon advances, it is crucial develop models evolution, particularly focusing on understanding biological mechanisms behind its development outside bone marrow. comprehensive essential devising innovative treatment strategies. review emphasizes role 3D models, specifically addressing marrow microenvironment sites. It explores current state-of-the-art in modelling, highlighting challenges replicating disease’s complexity. Recognizing unique demand for accurate discussion underscores impact advanced combating this heterogeneous still incurable disease.

Language: Английский

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Advance in the application of organoids in bone diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 3, 2024

Bone diseases such as osteoporosis and osteoarthritis have become important human health problems, requiring a deeper understanding of the pathogenesis related development more effective treatments. organoids are three-dimensional tissue masses that useful for drug screening, regenerative medicine, disease modeling because they may mimic structure physiological activities organs. Here, we describe various potential methods culturing bone-related from different stem cells, detailing construction processes highlighting main applications these bone organoid models. The application in skeletal is highlighted, current promising screening medicine well latest technological advancements discussed, while future discussed. Looking forward, it will provide reference constructing with complete structures functions applying them to biomedical research.

Language: Английский

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Selenylated Imidazo [1,2-a]pyridine Induces Apoptosis and Oxidative Stress in 2D and 3D Models of Colon Cancer Cells

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(6), P. 814 - 814

Published: May 30, 2023

Colon cancer incidence rates are increasing annually, a scenario aggravated by genetic and epigenetic alterations that promote drug resistance. Recent studies showed novel synthetic selenium compounds more efficient less toxic than conventional drugs, demonstrating biocompatibility pro-oxidant effects on tumor cells. This study aimed to investigate the cytotoxic effect of MRK-107, an imidazo [1,2- a]pyridine derivative, in 2D 3D cell culture models colon (Caco-2 HT-29). Sulforhodamine B results revealed GI50 2.4 µM for Caco-2, 1.1 HT-29, 22.19 NIH/3T3 cultures after 48 h treatment. Cell recovery, migration, clonogenic, Ki-67 corroborated MRK-107 inhibits proliferation prevents regeneration metastatic transition selectively reducing migratory clonogenic capacity; non-tumor cells (NIH/3T3) re-established 18 h. The oxidative stress markers DCFH-DA TBARS increased ROS generation damage. Caspases-3/7 activated induce apoptosis as main mode death both models, assessed annexin V-FITC acridine orange/ethidium bromide staining. is selective, redox-active compound with pro-apoptotic properties capacity activate antiproliferative pathways, showing promise anticancer research.

Language: Английский

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A High-Throughput Bone Marrow 3D Co-Culture System to Develop Resistance to B Cell Receptor Signaling Targeted Agents in B Cell Non-Hodgkin Lymphoma

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract B cell receptor (BCR) signaling plays a central role in the pathogenesis of lymphomas, making it crucial therapeutic target. The advent BCR-targeted inhibitors, particularly those directed at PI3K and BTK, has revolutionized treatment for non-Hodgkin lymphoma (B-NHL). However, resistance remains significant clinical challenge. Increasing evidence suggests that tumor microenvironment (TME), bone marrow (BM) microenvironment, is driving cancer progression resistance. BM provides specialized niche where cells can evade therapy through interactions with stromal extracellular matrix (ECM) components. Bone (BMSCs) contribute significantly to this In study, we developed an vitro 3D model better understand biology drug mechanisms. We co-cultured lines primary BMSCs fibrin gel using high-throughput automated system. Our results revealed modulate growth reduce their sensitivity inhibitor copanlisib BTK ibrutinib. Furthermore, allowed us identify IGFBP-3, Serpin E1, PTX-3 as potential mediators These findings underscore value co-culture models preclinical settings more accurately study resistance, they closely simulate microenvironment’s complexity than traditional 2D models, thus improving predictive testing lymphomas. Visual

Language: Английский

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Assessing the role of model choice in parameter identifiability of cancer treatment efficacy

Frontiers in Applied Mathematics and Statistics, Journal Year: 2025, Volume and Issue: 11

Published: March 24, 2025

Several mathematical models are commonly used to describe cancer growth dynamics. Fitting of these experimental data has not yet determined which particular model best describes growth. Unfortunately, choice is known drastically alter the predictions both future tumor and effectiveness applied treatment. Since there growing interest in using help predict chemotherapy, we need determine if affects estimates chemotherapy efficacy. Here, simulate an vitro study by creating synthetic treatment each seven fit sets other (“wrong”) models. We estimate ε max (the maximum efficacy drug) IC 50 drug concentration at half effect achieved) effort whether use incorrect changes parameters. find that largely weakly practically identifiable no matter generate or data. The more likely be identifiable, but sensitive model, showing poor identifiability when Bertalanffy either

Language: Английский

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Standardized assays to monitor drug sensitivity in hematologic cancers

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Dec. 1, 2023

Abstract The principle of drug sensitivity testing is to expose cancer cells a library different drugs and measure its effects on cell viability. Recent technological advances, continuous approval targeted therapies, improved culture protocols have enhanced the precision clinical relevance such screens. Indeed, has proven diagnostically valuable for patients with advanced hematologic cancers. However, types behave differently in therefore require optimized screening ensure that their ex vivo accurately reflects responses. For example, primary chronic lymphocytic leukemia (CLL) multiple myeloma (MM) unique microenvironmental stimuli survive culture, while this less case acute myeloid (AML) cells. Here, we present our validated culturing from AML, CLL, MM patients, generic protocol line models. We also discuss designs, reproducibility, quality controls. envision these may serve as community guidelines use interpretation assays monitor cancers thus contribute standardization. read-outs provide insight into tumor biology, identify or confirm treatment resistance real time, ultimately guide decision-making.

Language: Английский

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Long-term in vitro maintenance of plasma cells in a hydrogel-enclosed human bone marrow microphysiological 3D model system

Biofabrication, Journal Year: 2024, Volume and Issue: 16(4), P. 045005 - 045005

Published: July 2, 2024

Abstract Plasma cells (PCs) in bone marrow (BM) play an important role both protective and pathogenic humoral immune responses, e.g. various malignant non-malignant diseases such as multiple myeloma, primary secondary immunodeficiencies autoimmune diseases. Dedicated microenvironmental niches the BM provide PCs with biomechanical soluble factors that support their long-term survival. There is a high need for appropriate robust model systems to better understand biology, develop new therapeutic strategies PCs-related perform targeted preclinical studies predictive value. Most data have been derived from vivo mice, vitro of human are limited due restricted survival functionality conventional 2D cultures do not reflect unique niche architecture BM. We developed microphysiological, dynamic 3D culture system (BM-MPS) based on tissue (femoral biopsies), mechanically supported by hydrogel scaffold casing. While bioinert agarose casing did survival, photo-crosslinked collagen-hyaluronic acid (Col-HA) preserved native allowed up 2 weeks. Further, Col-HA was permissive lymphocyte migration into microphysiological system´s circulation. Long-term related stable presence factors, APRIL, BAFF, IL-6. Increasing immunoglobulins concentrations medium confirm over time. To best our knowledge, this study first report successful maintenance primary-derived . Our innovative suitable in-depth regulation exploration approaches CAR-T cell therapy or biologics.

Language: Английский

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High-throughput formulation of reproducible 3D cancer microenvironments for drug testing in myelogenous leukemia

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 12, 2024

Targeting cancer microenvironment is currently one of the major directions in drug development and preclinical studies leukemia. Despite variety available chronic myelogenous leukemia 3D culture models, reproducible generation miniaturized microenvironments, suitable for high-throughput testing, has remained a challenge. Here, we use microfluidics to generate over ten thousand highly monodisperse leukemic-bone marrow hydrogel microbeads per minute. We employ gelatin methacrylate (GelMA) as model extracellular matrix (ECM) tune concentration biopolymer, well other possible components ECM (fibrin, hyaluronic acid), cell ratio leukemic cells bone within microbeads. This allows achieve optimal viability propensity encapsulated microtissue formation, while also warranting long-term stability culture. administer kinase inhibitor, imatinib, at various concentrations and, via comparing mono- co-culture conditions (cancer alone vs cancer-stroma), find that stroma-leukemia crosstalk systematically protects against drug-induced cytotoxicity, confirming therefore our system mimics physiological stroma-dependent protection. finally discuss applicability (i) studying role direct- or close-contact interactions between embedded on stroma-mediated protection, (ii) screening anti-cancer therapeutics personalized therapies.

Language: Английский

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