Asta Literature Retrieval: Pathophysiology and clinical mechanisms of choroid plexus carcinoma. Core disease mechanisms, molecular and cellular...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 20
• Snippets retrieved: 20

Relevant Papers

[1] Molecular insights into malignant progression of atypical choroid plexus papilloma

• Authors: M. Yankelevich, J. Finlay, Hamza S. Gorsi, W. Kupsky, D. Boue et al.
• Year: 2021
• Venue: Cold Spring Harbor Molecular Case Studies
• URL: https://www.semanticscholar.org/paper/e8f50e986cb5fd975d5f2ede4aee715afa5d9bdb
• DOI: 10.1101/mcs.a005272
• PMID: 33608379
• PMCID: 7903885
• Citations: 11
• Influential citations: 2
• Summary: Choroid plexus tumors are rare pediatric neoplasms ranging from low-grade papillomas to overtly malignant carcinomas and the chromosomal loss that occurred resulted in the losses of two critical tumor suppressor genes, RB1 and BRCA2, which might play a possible role in the observed malignant transformation.
• Evidence snippets:
• Snippet 1 (score: 0.510) > Choroid plexus tumors are rare pediatric neoplasms ranging from low-grade papillomas to overtly malignant carcinomas. They are commonly associated with Li–Fraumeni syndrome and germline TP53 mutations. Choroid plexus carcinomas associated with Li–Fraumeni syndrome are less responsive to chemotherapy, and there is a need to avoid radiation therapy leading to poorer outcomes and survival. Malignant progression from choroid plexus papillomas to carcinomas is exceedingly rare with only a handful of cases reported, and the molecular mechanisms of this progression remain elusive. We report a case of malignant transformation of choroid plexus papilloma to carcinoma in a 7-yr-old male with a germline TP53 mutation in which we present an analysis of molecular changes that might have led to the progression based on the next-generation genetic sequencing of both the original choroid plexus papilloma and the subsequent choroid plexus carcinoma. Chromosomal aneuploidy was significant in both lesions with mostly gains present in the papilloma and additional significant losses in the carcinoma. The chromosomal loss that occurred, in particular loss of Chromosome 13, resulted in the losses of two critical tumor suppressor genes, RB1 and BRCA2, which might play a possible role in the observed malignant transformation.

[2] Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier

• Authors: N. Strazielle, J. Ghersi-Egea
• Year: 2016
• Venue: Current Pharmaceutical Design
• URL: https://www.semanticscholar.org/paper/23ab05b8885941339250b7c09706e0a3f4bba00f
• DOI: 10.2174/1381612822666160726112115
• PMID: 27464721
• PMCID: 5421134
• Citations: 82
• Influential citations: 5
• Summary: Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers, and the choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery.
• Evidence snippets:
• Snippet 1 (score: 0.451) > The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates.

[3] Molecular and cellular characteristics of cerebrovascular cell types and their contribution to neurodegenerative diseases

• Authors: F. J. García, Myriam Heiman
• Year: 2025
• Venue: Molecular Neurodegeneration
• URL: https://www.semanticscholar.org/paper/651ecb2269ae562236345f2451cab13e3d495216
• DOI: 10.1186/s13024-025-00799-z
• PMID: 39881338
• PMCID: 11780804
• Citations: 6
• Summary: The current understanding of cerebrovasculature structure, function, and cell type diversity and its role in the mechanisms underlying various neurodegenerative diseases is described.
• Evidence snippets:
• Snippet 1 (score: 0.443) > The cerebrovasculature represents one of several major interfaces between the blood and the brain. Although not as extensively studied as the cerebrovasculature, the choroid plexus and the meninges also both provide essential roles in supporting brain function. In recent years, studies focusing on each of these barriers have now extensively characterized the diversity of cell type composition and function as well as their roles in diseased states. In addition, the importance of the glycocalyx as the first interface with transport mechanisms at the BBB and its role in neurodegenerative diseases is becoming increasingly understood. Although much is still unknown regarding the mechanisms underlying their functions, it is clear that these structures and their relevance to neurodegenerative diseases is more important than previously appreciated. > The blood-cerebrospinal fluid (CSF) barrier is provided by the choroid plexus, a structure composed of specialized epithelial cells that secrete CSF into the ventricles that fills the subarachnoid space surrounding the brain. Humans produce between 400-600mL of CSF a day, which allows the brain to exist in a buoyant state for protection from physical injuries and also clear waste products. The rich composition of CSF biomolecules has been extensively studied and thus the interest in accessing CSF both for identifying biomarkers of disease and as a drug delivery route have received considerable attention [193]. Recently, the interest in understanding molecular profiles of cell types that comprise the choroid plexus has been investigated [194]. Interestingly, distinct gene expression patterns were found within each of the choroid plexus regions, both for the epithelial cells as well as the embedded mesenchymal cells, consistent with prior work demonstrating differential developmental trajectories for each region [195]. Whether these gene expression patterns are conserved in human choroid plexus or whether additional specific-specific adaptations are present, however, remains unknown. Most recently, multi-modal approaches including TRAP have shown diurnal fluctuations in gene expression within the mouse choroid plexus including the highly expressed epithelial marker Ttr [196].

[4] Cerebrospinal fluid hypersecretion in pediatric hydrocephalus.

• Authors: J. Karimy, Daniel Duran, Jamie Hu, Charuta Gavankar, Jonathan R Gaillard et al.
• Year: 2016
• Venue: Neurosurgical focus
• URL: https://www.semanticscholar.org/paper/ddbf660603e6ef871916e3dd83000190b275bb25
• DOI: 10.3171/2016.8.FOCUS16278
• PMID: 27798982
• Citations: 62
• Influential citations: 2
• Summary: Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence.
• Evidence snippets:
• Snippet 1 (score: 0.434) > Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

[5] A Rare Case of Concurrent Intraventricular Meningioma and Choroid Plexus Papilloma: A Case Report

• Authors: Daniel Markov, K. Bechev, Usman Khalid, V. Aleksiev, G. Markov et al.
• Year: 2024
• Venue: Medicina
• URL: https://www.semanticscholar.org/paper/7d547e6c3263d41cae0f8e81d34fc33a4a7e6ae8
• DOI: 10.3390/medicina60122100
• PMID: 39768979
• PMCID: 11679289
• Summary: A rare case of concurrent choroid plexus papilloma and ventricular meningioma, manifesting as a single tumor mass is described, manifesting as a single tumor mass.
• Evidence snippets:
• Snippet 1 (score: 0.422) > Data suggest that type II neurofibromatosis should manifest at a younger age, whereas in our patient at 66 years old, the disease was potentially rooted in genetic mutations triggered by hormonal influences or ionizing radiation, which acted as primary risk factors in tumorigenesis. > The combination of choroid plexus papilloma and meningioma in a single tumor mass can complicate the diagnosis during pathological examinations. The diagnostic workflow consists of clinical, cross-sectional imaging and histological studies. Key histologic differential diagnoses encompass a spectrum of tumors, including papillary meningioma, papillary ependymoma and metastatic carcinoma with papillary features [5,11]. The perivascular pseudopapillary pattern accounts for the majority of papillary meningioma, with the diagnosis of papillary meningioma being definitive once supported by an aggressive clinical presentation alongside high-grade histologic features [12]. Despite both papillary ependymomas and choroid plexus papillomas having a papillary structure with a fibrovascular core, the finger-like growth projection lined by single or multiple layers of cuboidal cells with smooth contiguous surface is a key histologic finding of papillary ependymomas [11]. Furthermore, the rough hobnail appearance of a choroid plexus papilloma coupled with a lack of extensive glial fibrillary acidic protein immunoreactivity holds value in further differentiating the two tumors [4,13]. > The mechanism behind the occurrence of primary brain tumors colliding at the same site, particularly those with mixed components of choroid plexus papilloma and meningioma, remains unclear. Various theories have been proposed to explain the presence of concurrent primary intracranial tumors [5,11]. Several theories have been suggested: (1) distinct tumors may collide at the same location; (2) an initial tumor might stimulate local growth factors, leading to a secondary tumor; (3) bidirectional differentiation from common progenitor cells could result in mixed tumor elements; and (4) commonly occurring tumors might coincidentally develop together.

[6] Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

• Authors: W. Tulalamba, T. Janvilisri
• Year: 2012
• Venue: International Journal of Cell Biology
• URL: https://www.semanticscholar.org/paper/307cb9186444d9dad6e2e3b53763be0de76de186
• DOI: 10.1155/2012/594681
• PMID: 22500174
• PMCID: 3303613
• Citations: 93
• Influential citations: 5
• Summary: The molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression and the important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.
• Evidence snippets:
• Snippet 1 (score: 0.417) > In the pregenomic eras, highly integrated and complex circuitry of molecular signaling in NPC pathogenesis was only partially understood. Over the past decade, the knowledge of the molecular mechanisms in NPC carcinogenesis has been rapidly accumulated. Dysregulation and abnormal protein expression of molecules in certain signaling pathways involved in cellular functions including proliferation, adhesion, survival, and apoptosis has been demonstrated in the NPC cells. Detailed information on the complex network in signaling pathway leading to a coordinated pattern of gene expression and regulation in NPC will undoubtedly provide important clues to develop novel prognostic and therapeutic strategies for this cancer. Refining molecular markers into clinically relevant assays may assist in the detection of NPC in asymptomatic patients, as well as stage classification and monitoring disease progression and treatments. Furthermore, selective regulation of particular proteins targeting cancer cell proliferation, invasion, and apoptosis is a hopeful prospect for future anticancer therapy that slow disease progression and improve survival.

[7] Pathological Alteration in the Choroid Plexus of Alzheimer’s Disease: Implication for New Therapy Approaches

• Authors: A. Krzyzanowska, E. Carro
• Year: 2012
• Venue: Frontiers in Pharmacology
• URL: https://www.semanticscholar.org/paper/86354fbedbed94bda6b38feb27c87942bbe624b0
• DOI: 10.3389/fphar.2012.00075
• PMID: 22563316
• PMCID: 3342675
• Citations: 66
• Influential citations: 3
• Summary: The data suggest that the significantly altered functions of the choroid plexus contribute to the multiparametric pathogenesis of late-onset AD.
• Evidence snippets:
• Snippet 1 (score: 0.416) > Alzheimer's disease is characterized by the production and accumulation of β-amyloid (Aβ) species in the form of oligomers, fibrils, and large aggregates called Aβ deposits leading to classical senile plaques in the brain, and vascular deposits (amyloid angiopathy) in brain and meningeal blood vessels (Gentile et al., 2004). Recent advances have led to a better understanding of the cellular and molecular pathways of AD. Although amyloid cascade theory as the primary cause of the disease is actually a controversy, pathological mechanisms in this cascade involve neurotoxic effects of amyloid peptides probably producing oxidative damage and apoptosis in brain cells, including choroid plexus epithelial cells (Perez-Gracia et al., 2009;Vargas et al., 2010b). However, there are alternative proposed processes or hypotheses which might be involved in pathological development of AD. > Recently, emphasis has focused on comorbidity of AD and the deficient clearance of Aβ across the blood-brain barrier (BBB; Deane et al., 2004;Tanzi et al., 2004;Zlokovic, 2004) and the blood-CSF barrier (BCSFB; Zlokovic et al., 1996). The traditional role ascribed to the choroid plexus has been to provide physical protection to the brain and to facilitate removal of brain metabolites through bulk drainage of CSF. However, recent studies suggest that the choroid plexus-CSF system plays a much more active role in AD (Weller, 1998;Stopa et al., 2001;Carro et al., 2006;Maurizi, 2010;Vargas et al., 2010b). > The choroid plexus is subject to morphological and physiological changes that produce a wide range of effects. In AD the choroid plexus develops abnormalities similar to those observed with aging, although greatly enhanced. Epithelial atrophy is significantly accentuated: a decrease in cell height is observed compared to age-matched controls (Serot et al., 2000).

[8] Localized proteomic differences in the choroid plexus of Alzheimer's disease and epilepsy patients

• Authors: D. Leitner, E. Kanshin, A. Faustin, Manon Thierry, D. Friedman et al.
• Year: 2023
• Venue: Frontiers in Neurology
• URL: https://www.semanticscholar.org/paper/812779b4f485009c5e472089bc820a5fac7aa0b2
• DOI: 10.3389/fneur.2023.1221775
• PMID: 37521285
• PMCID: 10379643
• Citations: 13
• Influential citations: 3
• Summary: Altered signaling pathways in the choroid plexus of severe AD cases and many correlated changes in the protein expression of cell metabolism pathways in AD and epilepsy cases are found and could inform novel therapeutic strategies to prevent disease progression or restore normal function.
• Evidence snippets:
• Snippet 1 (score: 0.416) > We and others have identified AD protein changes in multiple brain regions over the disease course (46). These include glial proteins (47), Aβ, and tau levels that correlate with spliceosome activity (48)(49)(50), synaptic dysfunction (51, 52), and tau interacting proteins involved in ubiquitination and phagosome maturation (29,53). In epilepsy, we identified protein changes associated with increased translation and decreased oxidative phosphorylation and synaptogenesis (54). The molecular mechanisms in the choroid plexus of AD and epilepsy are not well-understood. Limited proteomic studies in AD choroid plexus (55) and CSF revealed protein changes in CSF, indicating altered astrocyte/microglial and sugar metabolism (56), neuroinflammation, cerebrovascular dysfunction, and apoptosis (57, 58). There are no proteomics studies in human epilepsy choroid plexus. With most AD clinical trials failing (59-66) and drug-resistant epilepsy rates stable for decades (67,68), proteomics approaches may reveal unbiased comprehensive datasets to identify shared druggable protein targets. Identifying these mechanisms can inform therapeutic strategies to improve network function, limit disease progression, and potentially reverse functional and pathological changes.

[9] Atypical choroid plexus papilloma: Diagnosis and differentials: A case report

• Authors: H. Andour, S. Ben El Hend, C. Mandour, M. Allaoui, A. Fikri
• Year: 2024
• Venue: SAGE Open Medical Case Reports
• URL: https://www.semanticscholar.org/paper/5d7107cb7f0f9cc5b7dafea1baceebe02e747f67
• DOI: 10.1177/2050313X241254000
• PMID: 38764919
• PMCID: 11102693
• Citations: 3
• Summary: The case of a 4-year-old female presenting with headaches and altered mental status revealed a right lateral ventricular mass with some atypical characteristics, which were confirmed on pathological examination as an atypical choroid plexus papilloma.
• Evidence snippets:
• Snippet 1 (score: 0.411) > In children, clinical presentation may include an increase in head circumference and refusal to feed. The mechanism of hydrocephalus in CPP, similar to other choroid plexus tumors (CPTs), results from the combination of obstruction, hyperproduction, and impairment of reabsorption. Consequently, there is no correlation between the tumor size and the severity of hydrocephalus, unlike other intraventricular tumors. 11 Moreover, blockage of CSF absorption in the arachnoid granulations following hemorrhage or disruption of CSF dynamics by the tumor itself can lead to a reduction in "glymphatic clearance" worsening the disease. 12 t is now well recognized that similar to the peripheral lymphatic system, the CNS has its own "glymphatic system" composed of glial cells with various barrier systems responsible for maintaining homeostasis. Disorders in this system are implicated in various diseases, making it a target for various treatment pathways. This significance has led imaging techniques to explore it, yielding promising results. These include perfusion through arterial spin labeling (ASL), contrast injection through magnetic resonance lymphography, and metabolic sequences such as contrast exchange saturation transfer (CEST). Taking CPTs as an example, ASL can aid in differentiating tumoral from seeding areas from normal plexus choroid structures. CEST, as metabolic sequences, are more sensitive than spectroscopy in detecting both small exogenous and endogenous compounds. Consequently, amide proton transfer weighted imaging can better predict carcinoma with higher amounts of protein compared to plexus choroid papilloma. 13 everal genetic abnormalities are reported to be associated with the development of CPP in the pediatric population. These include Aicardi syndrome, hypomelanosis of Ito, constitutional 9p duplication, and Von-Hippel-Lindau syndrome. The germline mutation in the TP53 tumor suppressor, which is the origin of Li-Fraumeni syndrome, is more commonly associated with CPC.

[10] The Role of Targeted Therapy in Metastatic Renal Cell Carcinoma

• Authors: J. Unnithan, B. Rini
• Year: 2007
• Venue: The Scientific World Journal
• URL: https://www.semanticscholar.org/paper/d5d6d3155431806aa44bbc5391b25cad4f4ed412
• DOI: 10.1100/tsw.2007.149
• PMID: 17619763
• PMCID: 5901264
• Citations: 6
• Summary: The biological pathways involved in the development of RCC and the results of clinical trials using targeted therapy in metastatic RCC are described.
• Evidence snippets:
• Snippet 1 (score: 0.403) > Renal cell carcinoma has historically been a treatment resistant tumor. Association of renal cell carcinoma with inherited VHL syndrome and the subsequent elucidation of relevant biological pathways in clear cell RCC have changed the approach to systemic therapy. Drugs targeting the VEGF and related pathways have robust clinical activity. Ongoing clinical trials are exploring multiple options such as combining molecular targets with cytokines and combining targeting agents directed against different proteins in the same or different molecular pathways. The emergence of active agents in RCC has generated several needs within the RCC clinical research arena. One pressing need is a pre-clinical model that can replicate the phenotype of disease and treatment with these drugs to better understand mechanisms of response and resistance. Predictive clinical and molecular markers also require investigation to most appropriately target these agents. In addition, standard CT scans and RECIST criteria are often inadequate to evaluate response and progression with VEGF-targeted therapy. Investigation of newer imaging modalities and evaluation criteria is warranted. A new era of treatment in metastatic RCC has emerged, however, where rational therapeutic targeting has lead to substantial clinical advances.

[11] Breakthroughs in choroid plexus and CSF biology from the first European Choroid plexus Scientific Forum (ECSF)

• Authors: Laura Pellegrini, V. Silva-Vargas, Annarita Patrizi
• Year: 2024
• Venue: Fluids and Barriers of the CNS
• URL: https://www.semanticscholar.org/paper/ef559b8d884c5fa286fd1a8d8269402439d3cfc3
• DOI: 10.1186/s12987-024-00546-4
• PMID: 38773599
• PMCID: 11106960
• Citations: 1
• Summary: New findings in this expanding field, innovative approaches, animal models and 3D in vitro models were showcased to encourage further investigation into choroid plexus and cerebrospinal fluid roles.
• Evidence snippets:
• Snippet 1 (score: 0.399) > The recent advancements in research methodologies have significantly enhanced our understanding of ChP diseases.Notably, the application of the Stable Isotope Labelling Kinetic (SILK) method [29] in patients with normal pressure hydrocephalus has been pivotal in monitoring changes in the dynamics of CSF biomarkers, such as Transthyretin (TTR).Furthermore, the development of ChP organoids that can reach mature stages offers an innovative way to mimic CSF secretion and replicate the protein turnover dynamics of disease-relevant biomarkers.Lastly, the exploration of new techniques to target this barrier for drug delivery, particularly through investigating mechanisms of transcytosis, is underway.This research holds great promise for yielding less invasive and more effective treatments, leveraging the ChP's strategic location and its influential role in CSF signaling.These developments mark a significant step forward in the pursuit of advanced treatments for ChP-related conditions. > Another key point discussed is how to increase patient involvement in choroid plexus tumor research.Due to the rarity of this tumor entity, a few strategies were discussed, such as the establishment of an interdisciplinary research networks and an international platform to coordinate and organise patients worldwide expanding the, already existing, International SIOP-CPT Registry coordinated by Dr. med.Denise Obrecht, at the University Medical Centre Hamburg-Eppendorf.The SIOP-CPT registry is involved with the choroid plexus carcinoma guidance (lead by Dr. Jenny Adamski; SIOPE-CPT-BTG) within the European Reference Network for Paediatric Cancer diseases (ERN PaedCan) and the PNOC-CPT trial plans (lead by Prof. Dr. Sabine Müller) It is important to devise a multimodal approach to ensuring effective coordination with patients for improved clinical outcomes and sample collection.Patient education, involvement and constant communication are crucial throughout the process, from the beginning by giving rigorous ethical consent, to patient support, and follow-up, including updates on research progress.Together these can foster a sense of contribution and improve clinical engagement always complying with legal and ethical standards.Finally, establishing a feedback mechanism for patients to express concerns or inquire about the research would also enhance trust and transparency.

[12] Outcomes of the 2019 hydrocephalus association workshop, "Driving common pathways: extending insights from posthemorrhagic hydrocephalus"

• Authors: J. Karimy, Jessie Newville, C. Sadegh, Jill A. Morris, E. Monuki et al.
• Year: 2023
• Venue: Fluids and Barriers of the CNS
• URL: https://www.semanticscholar.org/paper/d52f08890df91091713a05768360f9343b4fe851
• DOI: 10.1186/s12987-023-00406-7
• PMID: 36639792
• PMCID: 9838022
• Citations: 3
• Summary: Three cell types that are targets for new hydrocephalus interventions: choroid plexus epithelial cells, ventricular ependymal cells, and immune cells (macrophages and microglia) are presented.
• Evidence snippets:
• Snippet 1 (score: 0.398) > The workshop expanded on discussions held at the 2016 Hydrocephalus Association PHH Workshop, which was held at the National Institutes of Health [4]. Recent publications have shown significant overlap between mechanisms implicated in PHH and other etiologies of hydrocephalus [5][6][7][8][9][10][11]. However, despite the apparent overlaps, much of this research has been siloed. > The pathophysiology of hydrocephalus can be incredibly multifactorial, with common genes, molecular pathways, and cellular alterations. The goal of this workshop was therefore to provide a small group setting in which researchers could (1) challenge preconceptions, (2) explore commonalities and differences between hydrocephalus etiologies, (3) identify potential treatments and therapies applicable to multiple etiologies, and (4) build collaborations. By bringing researchers together who study similar mechanisms in different models and species, collaborations can be developed to validate drug targets across etiologies and increase the potential impact of this research. > The workshop began with overviews on clinical research and overlapping disease mechanisms. Day One sessions were focused on the choroid plexus, cilia, brain development, and microglia. Day Two began with an overview of neuroinflammation and drug targets followed by a session focused on ependyma and ending with an exploration of opportunities in cell therapies. The workshop closed with a discussion focused on opportunities and next steps. The full agenda can be found here: > https:// www. hydro assoc. org/ spons ored-resea rch-events/. > This report reviews the presented research and major themes discussed during the Driving Common Pathways: Extending Insights from Posthemorrhagic Hydrocephalus workshop (Figure 1). The views and recommendations in this report were developed by the listed authors based on workshop discussions and integrated into the report.

[13] Genetic profiling and pathway analysis in bladder carcinoma: Implications for therapeutic targeting

• Authors: Sampara Vasishta, U. Adiga, Alfred J Augustine
• Year: 2025
• Venue: Turkish Journal of Surgery
• URL: https://www.semanticscholar.org/paper/405be9f362a5373a199f2dab695c9f0bf33d4e85
• DOI: 10.47717/turkjsurg.2025.2025-3-33
• PMID: 40726145
• PMCID: 12687403
• Summary: Comprehensive insights into the molecular underpinnings of bladder carcinoma are provided, highlighting interconnected pathways and potential therapeutic targets that could be exploited for therapeutic intervention.
• Evidence snippets:
• Snippet 1 (score: 0.397) > Objective Bladder carcinoma represents a significant challenge in oncology due to its heterogeneous molecular nature. This study aimed to identify key genetic factors and molecular pathways involved in bladder carcinoma pathogenesis to facilitate the development of targeted therapies. Material and Methods The top 30 genes associated with bladder carcinoma were retrieved from the disease gene network database. Comprehensive bioinformatic analysis was performed using various enrichment tools, including gene ontology biological process, cellular component, molecular function analyses, and pathway mapping through WikiPathways and metabolite associations through human metabolome database. Drug interactions were evaluated using DrugMatrix data. Results Gene ontology analysis revealed significant enrichment of cancer-related biological processes, cellular components, and molecular functions. Pathway analysis identified strong associations with head and neck squamous cell carcinoma, cancer pathways, pleural mesothelioma, endometrial cancer, and bladder cancer pathways. Key genes including CDKN2A, PTEN, EGFR, PIK3CA, HRAS, FGFR3, and TP53 were implicated across multiple pathways. Metabolite analysis showed significant associations with phosphatidylinositol derivatives, highlighting the importance of the PI3K pathway. Drug interaction analysis revealed potential modulatory effects of several compounds including sertraline, valproic acid, and hydroxyurea on gene expression patterns in bladder carcinoma. Conclusion This study provides comprehensive insights into the molecular underpinnings of bladder carcinoma, highlighting interconnected pathways and potential therapeutic targets. The significant overlap with other cancer types suggests common oncogenic mechanisms that could be exploited for therapeutic intervention. Further validation of these findings in clinical samples may facilitate the development of personalized treatment approaches for bladder carcinoma patients.

[14] Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules

• Authors: Daniel O. Dodd, Sabrina Méchaussier, P. Yeyati, Fraser McPhie, Jacob R. Anderson et al.
• Year: 2024
• Venue: Science (New York, N.Y.)
• URL: https://www.semanticscholar.org/paper/5ee9bc4e645721f92ca68e0408820717bd1c08be
• DOI: 10.1126/science.adf5489
• PMID: 38662826
• PMCID: 7616230
• Citations: 31
• Influential citations: 2
• Summary: It is shown that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies, as well as identifying de novo mutations in the β-tubulin TUBB4B associated with patients with classic PCD.
• Evidence snippets:
• Snippet 1 (score: 0.397) > Cilia on the choroid plexus are dramatically remodelled during development from motile to sensory/immotile (44) and then lost gradually with age (45). Our work suggests that defects in choroid plexus function could underlie hydrocephaly phenotypes more broadly in PCD patients, rather than defects in ependymal cells, which have been largely accepted to be the culprit. The exact function of what choroid plexus cilia do remains unclear but it has been suggested choroid plexus cilia regulate fluid transcytosis and their motility could help cilia sample CSF (46). In a rapidly growing body of evidence for non-genetic causes of hydrocephaly, the importance of the choroid plexus in triggering innate immune and CSF secretory responses to drive hydrocephaly has been linked to insult-induced cilia loss in choroid plexus epithelial cells (47,48). Moreover, in PCD patients with RGMC phenotypes, like Multicilin variants, MRI imaging revealed fully penetrant hydrocephaly with choroid plexus hyperplasia (49). Future studies will be required to understand the mechanisms by which cilia loss regulates CSF secretion and homeostasis in the choroid plexus. > Our study raises an intriguing question of how a cell expressing different tubulin isotypes preferentially creates specific isotype-enriched microtubule structures with different proportions of available isotypes. One possibility is regulation by the large class of microtubule-associated proteins, which can interact with tubulin and microtubules to affect their dynamic and physical properties (50). To dissect this would require our in vivo approaches, which preserve both the endogenous network of regulatory factors and tubulin balance. Our endogenously tagged Tubb4b ALFA model allows us to monitor in development and disease isotype-specific functions sensitively during the organization of different cellular microtubule arrays. Such approaches are necessary to understand the molecular mechanisms leading to isotype-specific differences in the intracellular microtubule networks which support bespoke cell functions.

[15] Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer

• Authors: M. G. de Matos, Mafalda Pinto, A. Gonçalves, Sule Canberk, M. J. Bugalho et al.
• Year: 2025
• Venue: PeerJ
• URL: https://www.semanticscholar.org/paper/655de68f1a7e8137dcba8a2046f14dee4f07594d
• DOI: 10.7717/peerj.18801
• PMID: 39850836
• PMCID: 11756370
• Citations: 4
• Summary: The knowledge of genetic and molecular biomarkers has achieved a high level of complexity, and the difficulties related to its applicability determine that their implementation in clinical practice is not yet a reality.
• Evidence snippets:
• Snippet 1 (score: 0.393) > Knowledge of molecular mechanisms implicated in thyroid carcinogenesis has been attained in recent years. Thyroid neoplasm result from alterations in gene expression patterns, which occur due to a gradual accumulation of genetic and epigenetic events. These changes are associated with specific tumor phenotypes and are implicated in disease etiology. Molecular alterations induce the activation of different signaling pathways, such as the mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K/AKT/mTOR), which are involved in and promote carcinogenesis (Hsiao & Nikiforov, 2014). In a few years, the knowledge of molecular mechanisms implicated in thyroid carcinogenesis changed from understanding signaling pathways and identification of a few genes mutations to the knowledge of the main genes implicated in thyroid carcinogenesis, reviewed by De Leo et al. (2024). Genetic changes in thyroid neoplasms were divided in early/driver molecular alterations and late/progression events. Late/ progression events may be associated with early/driver molecular alterations and represent the evolution from well-differentiated to high-grade and undifferentiated carcinoma, being (Pozdeyev et al., 2018). Most frequent gene mutations present in follicular-cell derived thyroid tumors are BRAF, RAS, and TERTp mutations, associate with clinically relevant clinicopathologic features, as shown in Table 3.

[16] ‘Breast Cancer Resistance Likelihood and Personalized Treatment Through Integrated Multiomics’

• Authors: S. Mehmood, Muhammad Faheem, Hammad Ismail, S. M. Farhat, Mahwish Ali et al.
• Year: 2022
• Venue: Frontiers in Molecular Biosciences
• URL: https://www.semanticscholar.org/paper/c542ec176c594aeddb3790bb3d10767598b86ae4
• DOI: 10.3389/fmolb.2022.783494
• PMID: 35495618
• PMCID: 9048735
• Citations: 19
• Influential citations: 1
• Summary: This review has summarized therapeutic resistance associated with BC and the techniques used for its management, and identifies the biomarkers of disease progression and treatment progress by collective characterization and quantification of pools of biological molecules within and among the cancerous cells.
• Evidence snippets:
• Snippet 1 (score: 0.391) > Breast cancer is a very complex and heterogeneous disorder with unique molecular and morphological features relative to a disease which involves only a single gene or protein in a simple signaling pathway contributing toward the progression of disease in an independent and autonomous manner (Organization 2019). Various studies had represented BC heterogeneity through the differential response of the same type of BC patients to treatment and risk of developing side effects. One of the major clinical complications in the treatment of breast carcinoma patients is the development of therapeutic resistance (Luque-Bolivar et al., 2020). Recently drug resistance in BC treatment is not properly addressed, rather to focus on molecular pathways deeply; an alternative strategy of using a different drug is commonly applied. In order to reduce the adverse effects of BC treatment including drug resistance, a profound understanding of the molecular mechanism of the disease and the response to the drug is needed. Multidrug resistance (MDR) and consequent relapse on therapy are prevalent issues related to breast carcinoma as our understanding is incomplete related to the molecular mechanism of breast carcinoma disease (Waks and Winer, 2019a). Therefore, elucidating the molecular mechanisms involved in drug resistance is critical. For the management of breast cancers, the treatment decision not only depends on the Treatment with exemestane alone or in combination with an mTOR inhibitor such as everolimus (Carlini et al., 2007Chin et al., 2007Geisler et al., 2008Bahrami et al. (2020) ER+/ HER2- assessment of prognosis factors but also on the evaluation of pathological and clinical factors. Integrated data assessments of these multiple factors of breast carcinoma through multiomics can provide significant insight and hope for making therapeutic decisions (Parsons and Francavilla 2020). Major BC treatment strategies rely on the tumor subtype, immunohistochemical evaluation of prognostic elements, and seek new genetic markers to improve the diagnostic strategies and to enhance treatment outcomes with minimal side effects.

[17] Choroid plexus enlargement in acute neuroinflammation is tightly interrelated to the tyrosine receptor signalling

• Authors: F. Luessi, Julia Schiffer, G. González-Escamilla, Vinzenz Fleischer, Sinah Engel et al.
• Year: 2024
• Venue: bioRxiv
• URL: https://www.semanticscholar.org/paper/5cd1620e6bfe35eada7ed32eea663b9947196a4e
• DOI: 10.1101/2024.03.09.583615
• Citations: 1
• Summary: This work provides conclusive new evidence for the role of ChP in the context of neuroinflammation and neurodegeneration, demonstrating the intriguing relationships between ChP enlargement, CSF dynamics, and the development of neuroinflammatory and neurodegenerative diseases.
• Evidence snippets:
• Snippet 1 (score: 0.389) > The choroid plexus (ChP) plays a crucial function in neuroinflammation of the central nervous system and in the immune response of the brain during neurodegeneration. Recent studies described a massive ChP enlargement in patients with multiple sclerosis (MS) and active disease courses, but also in several other neuroinflammatory and neurodegenerative conditions. Nevertheless, the exact basis and pathophysiology behind ChP hypertrophy remains unclear. This study was designed to evaluate the association of cerebrospinal fluid (CSF) proteomic spectra with brain MRI-derived volumetric measures of ChP in two independent cohorts of MS patients, and to translationally validate the related molecular mechanisms in the transcriptomic analysis of the ChP properties in a mouse model of experimental autoimmune encephalomyelitis (EAE). Our analysis revealed five enriched proteins (NTRK2, ADAM23, SCARB2, CPM, CNTN5) significantly associated with the ChP volumes in both of the MS cohorts. These proteins relate closely to mechanisms of cellular communication, function (e.g. transmembrane tyrosine receptor signalling (RTK) and vascular endothelial growth) and pathways involved in the regulation of cellular plasticity (e.g. neuron differentiation, axonal remodelling and myelin regulation) as depicted by molecular function analysis and validation of the results in the transcriptome from ChP tissue specific for EAE. This work provides conclusive new evidence for the role of ChP in the context of neuroinflammation and neurodegeneration, demonstrating the intriguing relationships between ChP enlargement, CSF dynamics, and the development of neuroinflammatory and neurodegenerative diseases. Our results are encouraging for the development of new therapeutic avenues (i.e. targeting RTK signalling). One sentence summary Tyrosine receptor signalling is tightly associated with choroid plexus enlargement and is key in CSF dynamics during a neuroinflammatory attack in MS

[18] Skin Development and Disease: A Molecular Perspective

• Authors: Iasonas Dermitzakis, Despoina Chatzi, Stella Aikaterini Kyriakoudi, Nikolaos Evangelidis, E. Vakirlis et al.
• Year: 2024
• Venue: Current Issues in Molecular Biology
• URL: https://www.semanticscholar.org/paper/3b0d602b335c265102e2a9f169bab20f51343212
• DOI: 10.3390/cimb46080487
• PMID: 39194704
• PMCID: 11353016
• Citations: 15
• Influential citations: 1
• Summary: By delving into the molecular mechanisms implicated in developmental processes, as well as in the pathogenesis of diseases, a comprehensive understanding of these aspects paves the way for developing innovative targeted therapies and personalised treatment approaches for various skin conditions.
• Evidence snippets:
• Snippet 1 (score: 0.386) > Understanding the molecular mechanisms underlying congenital skin diseases and cancer has significantly advanced in recent years, providing crucial insights into the pathogenesis of these conditions. Researchers have uncovered key genetic mutations, signalling cascades, and cellular interactions that drive the development and progression of these disorders by unravelling the intricate molecular pathways affected. This section emphasises that the various molecular signals involved in embryonic development are also implicated in the pathophysiology of certain congenital skin diseases and types of cancer. Analysing these connections provides valuable insights into the molecular mechanisms underlying both skin development and the pathogenesis of skin cancers, such as basal cell and squamous cell carcinoma. Skin cancers often stem from disruptions in essential biological pathways that are also involved in normal skin development. Therefore, identifying these specific molecules can pave the way for developing new targeted therapies through laboratory-based interventions.

[19] BIOL-02. MODELING BRAIN TUMORS IN VIVO AND WITH HUMAN ORGANOIDS

• Authors: L. Tiberi
• Year: 2023
• Venue: Neuro-Oncology
• URL: https://www.semanticscholar.org/paper/e312a4869b2623c974835d45d91185b116fc97bb
• DOI: 10.1093/neuonc/noad073.021
• PMCID: 10259887
• Summary: This work has recently developed a human IPSCs-derived organoid model of pediatric medulloblastoma and pediatric high-grade glioma that overcome the limitations of using animal models and pave the way to gaining unprecedented new knowledge into the development of brain cancer in a human system.
• Evidence snippets:
• Snippet 1 (score: 0.386) > Matilde de Almeida Duarte, Richard Gilbertson, Jessica Taylor, Amir Jassim, Linda Hu; University of Cambridge -Cancer Research UK Cambridge Institute, Cambridge, United Kingdom Choroid plexus carcinomas (CPCs) are rare, aggressive malignant tumours of the central nervous system occurring mainly in children under the age of one. While advances in clinical and molecular stratification have enabled risk-adapted treatment planning and improvements in outcome for many types of childhood brain tumours, there has not been equivalent progress for children with CPC. This has largely been due to the low incidence, leading treatment strategies to be mostly based on case series and a "standard of care" has yet to be established. In order to elucidate a coordinated therapeutic strategy for children with CPC, it is imperative to develop in vitro and in vivo models to improve our understanding of the mechanisms underlying tumorigenesis. We hypothesised that we could develop a genetically engineered mouse model (GEMM) to recapitulate patient CPCs, allowing for an early age of onset and high penetrance rate for accurate and efficient preclinical studies. To develop this GEMM of CPC, we utilized Cre-Lox technology to target CPC cells of origin. We crossed mice that conditionally expressed Tp53 flx/flx ; Rb flx/flx ; Pten flx/flx with mice harbouring a Tg (Ttr-cre/Esr1*)1Vco allele, as it drives selective Cre-recombination in the early embryonic choroid plexus. Using this methodology, we have managed to produce CPCs within 90 days and with a 95% penetrance rate which we characterised using our laboratory's tumour characterisation pipeline comprising histological evaluation, transcriptome analysis and imaging. We then used this model to investigate the transformation of the choroid during tumorigenesis and test novel therapeutic approaches to improve outcomes for patients affected by CPC. Not only are we looking for a "standard of care" that is currently inexistent for CPC, but we are also looking for one that will have minimal side effects and, therefore, not jeopardise the future of these children.

[20] Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation

• Authors: Hao Xiong, Jinsheng Guo
• Year: 2025
• Venue: Pharmaceuticals
• URL: https://www.semanticscholar.org/paper/76e92127053136900f7e3f10e2c9278251ced5d2
• DOI: 10.3390/ph18040507
• PMID: 40283943
• PMCID: 12030350
• Citations: 8
• Summary: HSC-targeted approaches using specific surface markers and receptors may enable the selective delivery of drugs, oligonucleotides, and therapeutic peptides that exert optimized anti-fibrotic and anti-HCC effects.
• Evidence snippets:
• Snippet 1 (score: 0.385) > Significant progress has been made in elucidating the cellular and molecular mechanisms of liver fibrosis; however, only a few findings have been successfully translated into clinical applications. Firstly, the high cost of drug development and target validation necessitates prolonged timelines and substantial financial investment. Secondly, as regulatory requirements become more stringent, there is an increasing demand for drugs with well-defined clinical efficacy and safety profiles. Moreover, the efficacy observed in animal models often fails to fully translate to clinical settings due to differences in pharmacokinetics, extracellular matrix (ECM) cross-linking, and disease pathophysiology. Despite advancements in anti-fibrotic drug development, accurately identifying ideal noninvasive biomarkers for fibrotic activity and establishing consensus on optimal clinical endpoints remain significant challenges [113,114]. > Currently, addressing the underlying cause remains the only proven strategy to halt or reverse liver fibrosis progression, while the development of effective anti-fibrotic therapies continues to pose a major challenge in liver disease management. Over the past few decades, substantial progress has been made in elucidating the cellular and molecular mechanisms underlying liver fibrosis. Liver fibrosis is a complex pathological change involving multiple cells, factors, and pathways, and the study of the cellular and molecular mechanisms of its occurrence and development provides an important theoretical basis and therapeutic target for clinical drug development. It is anticipated that improved animal models and well-designed clinical trials will facilitate the successful translation of anti-fibrotic research into effective clinical treatments in the near future.

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.