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The BE (2)-M17 neuroblastoma cell line: revealing its potential as a cellular model for Parkinson's disease.

Parkinson's disease is a pathology with a wide range of in vivo and in vitro models available. Among these, the SH-SY5Y neuroblastoma cell line is one of the most employed. This model expresses catecholaminergic markers and can differentiate and acquire various neuronal phenotypes. However, challenges persist, primarily concerning the variability of growth media, expression of dopaminergic markers, and a wide variety of differentiation protocols have been reported in the literature without direct comparison between them. This lack of standardized differentiation conditions impacts result repro

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… immortalized neuronal progenitor cell line (CSM14.1), mouse neuroblastoma (N2A) pheochromocytoma cells derived from the rat adrenal medulla (PC12), Human neuroglioma cells (H4), Immortalized human embryonic kidney cells (HEK 293), Lund human mesencephalic (LUHMES), primary neuronal cell cultures, iPSCs and organoids …

HDAC3: A Multifaceted Modulator in Immunotherapy Sensitization.

Histone deacetylase 3 (HDAC3) has emerged as a critical epigenetic regulator in tumor progression and immune modulation, positioning it as a promising target for enhancing cancer immunotherapy. This work comprehensively explores HDAC3's multifaceted roles, focusing on its regulation of key immune-modulatory pathways such as cGAS-STING, ferroptosis, and the Nrf2/HO-1 axis. These pathways are central to tumor immune evasion, antigen presentation, and immune cell activation. Additionally, the distinct effects of HDAC3 on various immune cell types-including its role in enhancing T cell activation,

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… In an organoid-based study of breast cancer, the use of adenovirus to block the interaction of HDAC3 with nuclear receptor co-repressor 2 (NCOR2) was found to up-regulate the expression of interferon regulatory factor 1 (IRF-1) and interferon-γ (IFN-γ) factors. … Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity Nat. Cancer 2022 3 734 752 10.1038/s43018-022-00375-0 35618935 PMC9246917 16. Xiao Y. Hale S. Awasthee N. Meng C. Zhang X. Liu Y. Ding H. Huo Z. Lv D. …

The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.

Bone tumors, encompassing heterogeneous primary and metastatic lesions, are driven in their initiation, progression, and metastasis by dysregulation of the bone microenvironment (BME). Clinically manifested by localized pain, pathological fractures, and neurological deficits, these malignancies substantially threaten patient survival. Radiographic patterns (osteolytic, osteoblastic, mixed) directly reflect pathogenic BME-tumor interactions, particularly involving osteoblast-osteoclast imbalance. The BME-a specialized niche of bone-resident cells (osteocytes, osteoblasts, osteoclasts), immune c

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… Inhibiting PI3K signaling can downregulate the expression of brachyury in U-CH2, a chordoma cell line, leading to the suppression of cell proliferation. [ 140 ] High-throughput screening of chordoma patient-derived organoids reveals PI3K/mTOR inhibitors as the most effective targeted therapies, further …

Cancer immunotherapies: A hope for the uncurable?

The use of cancer immunotherapies is not novel but has been used over the decades in the clinic. Only recently have we found the true potential of stimulating an anti-tumor response after the breakthrough of checkpoint inhibitors. Cancer immunotherapies have become the first line treatment for many malignancies at various stages. Nevertheless, the clinical results in terms of overall survival and progression free survival were not as anticipated. Majority of cancer patients do not respond to immunotherapies and the reasons differ. Hence, further improvements for cancer immunotherapies are cruc

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… This Fc-fusion peptide was also shown to activate effector mechanisms of both an IgG1 and IgA1 which resulted in higher tumor killing in vitro, in vivo and in patient-derived organoids. 2.1.3.9 Fc-fusion peptides Antibodies are large complexes which make them very hard to diffuse into large tumors … Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro , in vivo and with patient-derived tumor organoids . J. Immunother. …

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… The 3D organoids maintain the cellular and genetic heterogeneity of in vivo tissues and haves proved to be so far the best ex vivo model of human cancers. … We introduced Apc mutation into wild type murine small intestinal organoids by CRISPR-Cas9. Results : We found that in CRC patient-derived organoid cultures, small EVs were preferentially secreted. …

Lung cancer immunotherapy: progress, pitfalls, and promises.

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are

A prognostic model for anoikis-related genes in pancreatic cancer.

Anoikis, a distinct form of programmed cell death, is crucial for both organismal development and maintaining tissue equilibrium. Its role extends to the proliferation and progression of cancer cells. This study aimed to establish an anoikis-related prognostic model to predict the prognosis of pancreatic cancer (PC) patients. Gene expression data and patient clinical profiles were sourced from The Cancer Genome Atlas (TCGA-PAAD: Pancreatic Adenocarcinoma) and the International Cancer Genome Consortium (ICGC-PACA: Pancreatic Ductal Adenocarcinoma). Non-cancerous pancreatic tissue gene expressio

Neuropsychiatric manifestations following chimeric antigen receptor T cell therapy for cancer: a systematic review of clinical outcomes and management strategies.

BACKGROUND: Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative modality in the treatment of patients with cancer. However, it is increasingly evident that this therapeutic approach is not without its challenges. The unique nature of CAR-T cells as living drugs introduces a distinct set of side effects. As the application of CAR-T cell therapy expands to treat a broader range of diseases, it becomes increasingly important to devise effective strategies for handling the associated toxicities. Challenges in treating patients with CAR-T cells include addressing complica

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… This European consortium is dedicated, among others, to refining current preclinical models specifically for CAR-T cell therapies, addressing the intricate challenges associated with toxicity prediction. 59 60 Moreover, the project strives to foster the emergence of ex vivo human models, notably organoids …

Functional genomics for breast cancer drug target discovery.

Breast cancer is a heterogeneous disease that develops through a multistep process via the accumulation of genetic/epigenetic alterations in various cancer-related genes. Current treatment options for breast cancer patients include surgery, radiotherapy, and chemotherapy including conventional cytotoxic and molecular-targeted anticancer drugs for each intrinsic subtype, such as endocrine therapy and antihuman epidermal growth factor receptor 2 (HER2) therapy. However, these therapies often fail to prevent recurrence and metastasis due to resistance. Overall, understanding the molecular mechani

Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease.

UNLABELLED: Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregula

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… In addition, it has been shown by Hans Clevers’ group that self-renewing intestinal crypt organoids can be generated in vitro by induction of Wnt signaling in isolated intestinal stem cells [ 30 ]. …

Подстегнутая стрессом связь с нанотрубкой в глиальных клетках CNS: последствия провокационного демиэлирования и отказа в ремонте.

Множественные склерозы и связанные с ними воспалительные расстройства центральной нервной системы, включая расстройство спектра нейромиелита, расстройство спектра и болезнь миэлина олигодендроцита гликопротеина, связанные с антителами, характеризуются повреждениями имунной ткани, глиальной дисфункцией, метаболическим стрессом и неполным ремонтом. Хотя периферическая иммунная инфильтрация и антителные механизмы объясняют многие аспекты образования острых повреждений, они не в полной мере учитывают стойкую активность повреждения, метаболическую нестабильность или отказ от ремиэлирования в местно

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… Patient-derived iPSC co-cultures, organoids, and glial–neurovascular assembloids may provide useful intermediate models between conventional culture and human tissue. Third, biological relevance requires quantitative assessment. …

A bibliometric and knowledge-map analysis of bispecific antibodies in cancer immunotherapy from 2000 to 2023.

BackgroundBispecific antibody (BsAb)-based cancer immunotherapy has provided new avenues for the treatment of various malignancies. The approval of Blinatumomab has encouraged further investigation into these treatments, and a series of preclinical and clinical trials have been conducted, together with the publication of numerous articles. Here, the knowledge structure of BsAb-based cancer immunotherapy is summarized using bibliometric analysis to provide in-depth insight into current research trends and foci.MethodsThe studies included in the bibliometric analysis of BsAbs in cancer immunothe

B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease.

Targeting the B-cell lymphoma 2 (Bcl-2) family proteins has been the backbone for hematological malignancies with overall survival improvements. The Bcl-2 family is a major player in apoptosis regulation and, has captured the researcher's interest in the treatment of solid tumors. Sarcomas are a heterogeneous group of diseases, comprising several entities, with high morbidity and mortality and with few specific therapies available. The treatment for sarcomas is based on platinum regimens, with variable results and poor outcomes, especially in advanced lesions. The high number of different sarc

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… Tumor suppressive role of miR-342-5p in human chondrosarcoma cells and 3D organoids. Int J Mol Sci. 2021;22:5590. doi: 10.3390/ijms22115590. 104. …

CXCL12/CXCR4 axis supports mitochondrial trafficking in tumor myeloma microenvironment.

Mesenchymal stromal cells (MSCs) within the protective microenvironment of multiple myeloma (MM) promote tumor growth, confer chemoresistance and support metabolic needs of plasma cells (PCs) even transferring mitochondria. In this scenario, heterocellular communication and dysregulation of critical signaling axes are among the major contributors to progression and treatment failure. Here, we report that myeloma MSCs have decreased reliance on mitochondrial metabolism as compared to healthy MSCs and increased tendency to deliver mitochondria to MM cells, suggesting that this intercellular exch

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… Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids. Biochem J. 2021;478:21–39. doi: 10.1042/BCJ20200710. 16. Mahrouf-Yorgov M, Augeul L, Da Silva CC, Jourdan M, Rigolet M, Manin S, et al. …

The Application Progress of Patient-Derived Tumor Xenograft Models After Cholangiocarcinoma Surgeries.

Surgical treatment is the only possible cure for cholangiocarcinoma (CCA) at present. However, the high recurrence rate of postoperative CCA leads to a very poor prognosis for patients, effective postoperative chemotherapy is hence the key to preventing the recurrence of CCA. The sensitivity of CCA to cytotoxic chemotherapy drugs and targeted drugs varies from person to person, and therefore, the screening of sensitive drugs has become an important topic after CCA surgeries. Patient-Derived tumor Xenograft models (PDX) can stably retain the genetic and pathological characteristics of primary t

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… Applications of Patient-Derived Tumor Xenograft Models and Tumor Organoids. J Hematol Oncol (2020) 13(1):4. 10.1186/s13045-019-0829-z 23. Murayama T, Gotoh N. Patient-Derived Xenograft Models of Breast Cancer and Their Application. Cells (2019) 8(6):621. 10.3390/cells8060621 24. …

Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.

The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA changes, often precede genetic mutations and are critical in cancer progression. In this study, we explore how liquid biopsy, combined with epigenetic markers, can provide early detection of lung cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges of targeting epigenetic regulators, which could disrupt cellul

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… Organoids as a systems platform for SCLC brain metastasis . Front Oncol . 2022 ; 12 : 881989 . 35574308 10.3389/fonc.2022.881989 PMC9096159 4 Gridelli C , Rossi A , Carbone DP , et al. Non‐small‐cell lung cancer . … Genotype‐phenotype mapping of a patient‐derived lung cancer organoid biobank identifies NKX2‐1‐defined Wnt dependency in lung adenocarcinoma . Cell Rep . 2023 ; 42 ( 3 ): 112212 . 36870059 10.1016/j.celrep.2023.112212 37 Jin C , Wang T , Zhang D , et al. …

Current Landscape and Future Directions in Cancer Immunotherapy: Therapies, Trials, and Challenges.

Cancer remains a leading global health challenge, placing immense burdens on individuals and healthcare systems. Despite advancements in traditional treatments, significant limitations persist, including treatment resistance, severe side effects, and disease recurrence. Immunotherapy has emerged as a promising alternative, leveraging the immune system to target and eliminate tumour cells. However, challenges such as immunotherapy resistance, patient response variability, and the need for improved biomarkers limit its widespread success. This review provides a comprehensive analysis of the curr

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… For example, the generation of patient-derived organoids for drug testing and therapy development presents logistical challenges. … Although organoids can closely mimic the tumour microenvironment, their limited availability and the time-consuming processes required for their expansion make high-throughput screening impractical [ 228 ]. …

Trials and Tribulations of MicroRNA Therapeutics.

The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Cons

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… For example, miR-3622b-5p, when paired with cisplatin, not only enhances apoptosis but also sensitizes ovarian tumor organoids to cisplatin [ 192 ], suggesting the potential of miRNAs in combination with chemotherapy to address cancer treatment and counteract drug resistance. 5.2. …

Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination.

The stromal microenvironment regulates mammary gland development and tumorigenesis. In normal mammary glands, the stromal microenvironment encompasses the ducts and contains fibroblasts, the main regulators of branching morphogenesis. Understanding the way fibroblast signaling pathways regulate mammary gland development may offer insights into the mechanisms of breast cancer (BC) biology. In fact, the unregulated mammary fibroblast signaling pathways, associated with alterations in extracellular matrix (ECM) remodeling and branching morphogenesis, drive breast cancer microenvironment (BCM) rem

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… Evidence shows that FGF2 and FGF9 signaling in primary mammary fibroblasts, co-cultured with 3D epithelial organoids, sustains the branching of the mammary epithelium ( Figure 2 A) [ 60 ]. … Humana Press Inc.; Totowa, NJ, USA: 2017. 3D coculture of mammary organoids with fibrospheres: A model for studying epithelial–stromal interactions during mammary branching morphogenesis; pp. 107–124. 3. Polyak K., Kalluri R. …

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.

The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor progn

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… Moreover, Gli interacts with the promoter of ABCG2 and regulates its expression in gastric cancer stem cells. 367 Accordingly, targeting HH signaling pathway may improve GC chemosensitivity. 368 , 369 Koh et al. investigated PDL-1 expression mediated by Gli in gastric cancer organoids, which may relate …