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Biomedicine & Pharmacotherapy =... Jul 2024Noncoding RNAs (ncRNAs) do not participate in protein-coding. Ferroptosis is a newly discovered form of cell death mediated by reactive oxygen species and lipid... (Review)
Review
Noncoding RNAs (ncRNAs) do not participate in protein-coding. Ferroptosis is a newly discovered form of cell death mediated by reactive oxygen species and lipid peroxidation. Recent studies have shown that ncRNAs such as microRNAs, long noncoding RNAs, circular RNAs, and ferroptosis are involved in the occurrence and development of osteosarcoma (OS). Studies have confirmed that ncRNAs participate in the development of OS by regulating the ferroptosis. However, systematic summary on this topic are still lacking. This review summarises the potential role of ncRNAs in the diagnosis, treatment, drug resistance, and prognosis of OS and the basis for diagnosing, preventing, and treating clinical OS and developing effective drugs. This review summarises the latest research progress on ncRNAs that regulate ferroptosis in OS, attempts to clarify the molecular mechanisms by which ncRNAs regulate ferroptosis in the pathogenesis of OS, and elaborates on the involvement of ferroptosis in OS from the perspective of ncRNAs.
Topics: Ferroptosis; Osteosarcoma; Humans; MicroRNAs; RNA, Long Noncoding; RNA, Circular; Bone Neoplasms; Animals; Gene Expression Regulation, Neoplastic
PubMed: 38876052
DOI: 10.1016/j.biopha.2024.116924 -
JCO Clinical Cancer Informatics Jun 2024Rare cancers constitute over 20% of human neoplasms, often affecting patients with unmet medical needs. The development of effective classification and prognostication...
PURPOSE
Rare cancers constitute over 20% of human neoplasms, often affecting patients with unmet medical needs. The development of effective classification and prognostication systems is crucial to improve the decision-making process and drive innovative treatment strategies. We have created and implemented MOSAIC, an artificial intelligence (AI)-based framework designed for multimodal analysis, classification, and personalized prognostic assessment in rare cancers. Clinical validation was performed on myelodysplastic syndrome (MDS), a rare hematologic cancer with clinical and genomic heterogeneities.
METHODS
We analyzed 4,427 patients with MDS divided into training and validation cohorts. Deep learning methods were applied to integrate and impute clinical/genomic features. Clustering was performed by combining Uniform Manifold Approximation and Projection for Dimension Reduction + Hierarchical Density-Based Spatial Clustering of Applications with Noise (UMAP + HDBSCAN) methods, compared with the conventional Hierarchical Dirichlet Process (HDP). Linear and AI-based nonlinear approaches were compared for survival prediction. Explainable AI (Shapley Additive Explanations approach [SHAP]) and federated learning were used to improve the interpretation and the performance of the clinical models, integrating them into distributed infrastructure.
RESULTS
UMAP + HDBSCAN clustering obtained a more granular patient stratification, achieving a higher average silhouette coefficient (0.16) with respect to HDP (0.01) and higher balanced accuracy in cluster classification by Random Forest (92.7% ± 1.3% and 85.8% ± 0.8%). AI methods for survival prediction outperform conventional statistical techniques and the reference prognostic tool for MDS. Nonlinear Gradient Boosting Survival stands in the internal (Concordance-Index [C-Index], 0.77; SD, 0.01) and external validation (C-Index, 0.74; SD, 0.02). SHAP analysis revealed that similar features drove patients' subgroups and outcomes in both training and validation cohorts. Federated implementation improved the accuracy of developed models.
CONCLUSION
MOSAIC provides an explainable and robust framework to optimize classification and prognostic assessment of rare cancers. AI-based approaches demonstrated superior accuracy in capturing genomic similarities and providing individual prognostic information compared with conventional statistical methods. Its federated implementation ensures broad clinical application, guaranteeing high performance and data protection.
Topics: Humans; Prognosis; Artificial Intelligence; Precision Medicine; Female; Rare Diseases; Male; Deep Learning; Neoplasms; Myelodysplastic Syndromes; Algorithms; Middle Aged; Aged; Cluster Analysis
PubMed: 38875514
DOI: 10.1200/CCI.24.00008 -
Medicine Jun 2024This study aimed to assess hematological diseases next-generation sequencing (NGS) panel enhances the diagnosis and classification of myeloid neoplasms (MN) using the... (Observational Study)
Observational Study
This study aimed to assess hematological diseases next-generation sequencing (NGS) panel enhances the diagnosis and classification of myeloid neoplasms (MN) using the 5th edition of the WHO Classification of Hematolymphoid Tumors (WHO-HAEM5) and the International Consensus Classification (ICC) of Myeloid Tumors. A cohort of 112 patients diagnosed with MN according to the revised fourth edition of the WHO classification (WHO-HAEM4R) underwent testing with a 141-gene NGS panel for hematological diseases. Ancillary studies were also conducted, including bone marrow cytomorphology and routine cytogenetics. The cases were then reclassified according to WHO-HAEM5 and ICC to assess the practical impact of these 2 classifications. The mutation detection rates were 93% for acute myeloid leukemia (AML), 89% for myelodysplastic syndrome (MDS), 94% for myeloproliferative neoplasm (MPN), and 100% for myelodysplasia/myeloproliferative neoplasm (MDS/MPN) (WHO-HAEM4R). NGS provided subclassified information for 26 and 29 patients with WHO-HAEM5 and ICC, respectively. In MPN, NGS confirmed diagnoses in 16 cases by detecting JAK2, MPL, or CALR mutations, whereas 13 "triple-negative" MPN cases revealed at least 1 mutation. NGS panel testing for hematological diseases improves the diagnosis and classification of MN. When diagnosed with ICC, NGS produces more classification subtype information than WHO-HAEM5.
Topics: Humans; High-Throughput Nucleotide Sequencing; Female; Male; Middle Aged; Aged; Myeloproliferative Disorders; Adult; Myelodysplastic Syndromes; Mutation; Aged, 80 and over; Janus Kinase 2; World Health Organization; Leukemia, Myeloid, Acute; Receptors, Thrombopoietin; Calreticulin; Young Adult
PubMed: 38875377
DOI: 10.1097/MD.0000000000038556 -
PloS One 2024Ewing sarcoma is the second most common bone cancer in children, and while patients who present with metastatic disease at the time of diagnosis have a dismal prognosis....
Ewing sarcoma is the second most common bone cancer in children, and while patients who present with metastatic disease at the time of diagnosis have a dismal prognosis. Ewing sarcoma tumors are driven by the fusion gene EWS/Fli1, and while these tumors are genetically homogenous, the transcriptional heterogeneity can lead to a variety of cellular processes including metastasis. In this study, we demonstrate that in Ewing sarcoma cells, the canonical Wnt/β-Catenin signaling pathway is heterogeneously activated in vitro and in vivo, correlating with hypoxia and EWS/Fli1 activity. Ewing sarcoma cells predominantly express β-Catenin on the cell membrane bound to CDH11, which can respond to exogenous Wnt ligands leading to the immediate activation of Wnt/β-Catenin signaling within a tumor. Knockdown of CDH11 leads to delayed and decreased response to exogenous Wnt ligand stimulation, and ultimately decreased metastatic propensity. Our findings strongly indicate that CDH11 is a key component of regulating Wnt//β-Catenin signaling heterogeneity within Ewing sarcoma tumors, and is a promising molecular target to alter Wnt//β-Catenin signaling in Ewing sarcoma patients.
Topics: Sarcoma, Ewing; Humans; Cadherins; Wnt Signaling Pathway; Cell Line, Tumor; beta Catenin; Animals; Bone Neoplasms; Mice; Oncogene Proteins, Fusion; Proto-Oncogene Protein c-fli-1; RNA-Binding Protein EWS
PubMed: 38875295
DOI: 10.1371/journal.pone.0305490 -
Human & Experimental Toxicology 2024Stereotactic body radiation therapy (SBRT) is a targeted form of radiotherapy used to treat early-stage cancers. Despite its effectiveness, the impact of SBRT on...
BACKGROUND
Stereotactic body radiation therapy (SBRT) is a targeted form of radiotherapy used to treat early-stage cancers. Despite its effectiveness, the impact of SBRT on myeloid-derived suppressor cells (MDSCs) is not well understood. In this study, we examined how SBRT affects the differentiation and survival of MDSCs, as well as delved into the molecular mechanisms involved.
METHODS AND RESULTS
SBRT was utilized on bone marrow (BM)-derived MDSCs to investigate its impact on the differentiation and survival of MDSCs using flow cytometry. An animal model of lung cancer was created to assess the anti-cancer properties of SBRT and the role of miR-21 expression in MDSCs. The interplay of miR-21 and Sorbin and SH3 domain-containing protein 1 (SORBS1) in MDSC differentiation was explored through dual luciferase activity assay, RT-qPCR, and Western blot analysis. The findings suggest that SBRT led to an increase in miR-21 levels, inhibited MDSC differentiation, and triggered cell apoptosis in BM cells. Inhibition of miR-21 reversed the effects of SBRT on MDSC differentiation and apoptosis. Additionally, it was revealed that SORBS1 was a downstream target of miR-21 in BM cells, and the miR-21/SORBS1 axis played a role in regulating MDSC differentiation and apoptosis induced by SBRT. Modulating miR-21 levels in vivo impinged on the response to SBRT treatment and the quantity of MDSCs in a mouse model of lung cancer.
CONCLUSION
Our data indicate that the upregulation of miR-21 induced by SBRT may contribute to the inhibition of MDSC expansion in a lung cancer model.
Topics: MicroRNAs; Animals; Myeloid-Derived Suppressor Cells; Radiosurgery; Mice; Lung Neoplasms; Cell Differentiation; Apoptosis; Mice, Inbred C57BL; Adaptor Proteins, Signal Transducing; Cell Line, Tumor
PubMed: 38874389
DOI: 10.1177/09603271241261307 -
Turkish Neurosurgery Aug 2023Intradiploic meningiomas are rare neoplasms, often mistaken for metastases or malignant bone tumors. Surgical management can be challenging, considering their diffusive...
AIM
Intradiploic meningiomas are rare neoplasms, often mistaken for metastases or malignant bone tumors. Surgical management can be challenging, considering their diffusive bony invasion. Two main critical decisions need to be taken: the timing for cranial vault reconstruction and the choice of the adequate material for cranioplasty. We believe that this case underscores the complexity of such lesions, the importance of a prompt devascularization, and the pivotal role of an immediate reconstruction to avoid the additional morbidity of a re-do surgery.
MATERIAL AND METHODS
We report a case of 68-year-old men who presented with slow growing right parietal bone swelling he noted many years before, but for which he didn't seek medical attentions, associated with mild contralateral hemiparesis. Neuroradiological examinations revealed a giant extradural intradiploic tumor affecting the right temporo-parietal bone and conditioning significant compression of the underlying brain. We planned a surgical strategy to deafferent the tumor and to reduce the intraoperative bleeding. At first, a circumferential craniectomy centered upon the lesion was performed, then it was devascularized by means of surgical ligation of the ipsilateral superficial temporal artery (STA) and middle meningeal artery (MMA); these steps allowed a subsequent en block tumor excision, despite its large size, without significant blood loss and respecting the oncological principles. At the end, a contextual calvarial reconstruction was performed using a precurved titanium mesh.
RESULTS
Was discharged seven days after surgery with complete recovery of the left-sided motor deficit. Thereafter, he underwent scheduled outpatient evaluations and radiological exams. After 1 year, the Modified Rankin Scale (MRS) was 1, with no evidence of recurrent disease.
CONCLUSION
Surgical complications can be reduced adopting an optimal preoperative work-up and a tailored surgical strategy focused on early tumor deafferentation. Moreover, an immediate cranial vault reconstruction avoids the risks related to a second procedure.
PubMed: 38874243
DOI: 10.5137/1019-5149.JTN.43641-23.2 -
Frontiers in Immunology 2024A 55-year-old male patient developed a mass in the left inguinal area with left lower limb swelling and first visited a local hospital 3 months earlier because of...
CASE REPORT
A 55-year-old male patient developed a mass in the left inguinal area with left lower limb swelling and first visited a local hospital 3 months earlier because of unrelieved pain. An MRI scan suggested left suprapubic branch and left acetabular bone destruction, abnormal soft tissue signals within the iliopsoas muscle of the anterior edge of the left iliac bone, and enlarged lymph nodes in the left iliac fossa and left inguinal region. The patient subsequently underwent left pelvic lesion open biopsy and inguinal lymph node resection biopsy. According to pathological reports, the left inguinal mass was considered to be a malignant tumor of cutaneous accessory origin (pilomatrix carcinoma) with extensive vitreous changes. The suprapupubis branch mass was considered to be a bone metastatic pilomatrix carcinoma. Immunohistochemistry (IHC) revealed a PDL1 combined positive score (CPS) of 8. DNA next-generation sequencing (NGS) showed L65Rfs*53 mutation. The patient received three cycles of gemcitabine and nedaplatin. However, the lesion progressed.
CONCLUSION
Chemotherapy is not effective for treating pilomatrix carcinoma. PDL1 antibodies and CDK4/6 inhibitors might be treatment options for pilomatrix carcinoma.
Topics: Humans; Male; Middle Aged; Cyclin-Dependent Kinase Inhibitor p16; B7-H1 Antigen; Skin Neoplasms; Pilomatrixoma; Mutation; Hair Diseases
PubMed: 38873609
DOI: 10.3389/fimmu.2024.1337400 -
European Radiology Experimental Jun 2024New immunotherapies activate tumor-associated macrophages (TAMs) in the osteosarcoma microenvironment. Iron oxide nanoparticles (IONPs) are phagocytosed by TAMs and,...
BACKGROUND
New immunotherapies activate tumor-associated macrophages (TAMs) in the osteosarcoma microenvironment. Iron oxide nanoparticles (IONPs) are phagocytosed by TAMs and, therefore, enable TAM detection on T2*- and T2-weighted magnetic resonance images. We assessed the repeatability and reproducibility of T2*- and T2-mapping of osteosarcomas in a mouse model.
METHODS
Fifteen BALB/c mice bearing-murine osteosarcomas underwent magnetic resonance imaging (MRI) on 3-T and 7-T scanners before and after intravenous IONP infusion, using T2*-weighted multi-gradient-echo, T2-weighted fast spin-echo, and T2-weighted multi-echo sequences. Each sequence was repeated twice. Tumor T2 and T2* relaxation times were measured twice by two independent investigators. Repeatability and reproducibility of measurements were assessed.
RESULTS
We found excellent agreement between duplicate acquisitions for both T2* and T2 measurements at either magnetic field strength, by the same individual (repeatability), and between individuals (reproducibility). The repeatability concordance correlation coefficient (CCC) for T2* values were 0.99 (coefficients of variation (CoV) 4.43%) for reader 1 and 0.98 (CoV 5.82%) for reader 2. The reproducibility of T2* values between the two readers was 0.99 (CoV 3.32%) for the first acquisitions and 0.99 (CoV 6.30%) for the second acquisitions. Regarding T2 values, the repeatability of CCC was similar for both readers, 0.98 (CoV 3.64% for reader 1 and 4.45% for reader 2). The CCC of the reproducibility of T2 was 0.99 (CoV 3.1%) for the first acquisition and 0.98 (CoV 4.38%) for the second acquisition.
CONCLUSIONS
Our results demonstrated high repeatability and reproducibility of quantitative T2* and T2 mapping for monitoring the presence of TAMs in osteosarcomas.
RELEVANCE STATEMENT
T2* and T2 measurements of osteosarcomas on IONP-enhanced MRI could allow identifying patients who may benefit from TAM-modulating immunotherapies and for monitoring treatment response. The technique described here could be also applied across a wide range of other solid tumors.
KEY POINTS
• Optimal integration of TAM-modulating immunotherapies with conventional chemotherapy remains poorly elucidated. • We found high repeatability of T2* and T2 measurements of osteosarcomas in a mouse model, both with and without IONPs contrast, at 3-T and 7-T MRI field strengths. • T2 and T2* mapping may be used to determine response to macrophage-modulating cancer immunotherapies.
Topics: Animals; Osteosarcoma; Mice; Magnetic Resonance Imaging; Reproducibility of Results; Mice, Inbred BALB C; Disease Models, Animal; Bone Neoplasms; Female
PubMed: 38872042
DOI: 10.1186/s41747-024-00467-9 -
Cancer Radiotherapie : Journal de La... Jun 2024Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards...
PURPOSE
Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards the end of life, a reliable prediction of survival is needed. The goal of this study was to find new clinical factors in relation to overall survival.
MATERIALS AND METHODS
Prospectively 22 clinical factors were collected from 734 patients. The Kaplan-Meier and Cox regression models were used.
RESULTS
Most patients were diagnosed with lung cancer (29%), followed by prostate (19.8%) and breast cancer (14.7%). Median overall survival was 6.4months. Fourteen clinical factors showed significance in the univariate analyses. In the multivariate analyses 6 factors were found to be significant for the overall survival: Karnofsky performance status, primary tumor, gender, total organs affected, morphine use and systemic treatment options after radiotherapy.
CONCLUSION
Morphine use and systemic treatment options after radiotherapy, Karnofsky performance status, primary tumor, gender and total organs affected are strong prediction factors on overall survival after palliative radiotherapy in patients with bone metastasis. These factors are easily applicable in the clinic.
Topics: Humans; Male; Bone Neoplasms; Female; Palliative Care; Prognosis; Aged; Middle Aged; Prospective Studies; Aged, 80 and over; Karnofsky Performance Status; Adult; Lung Neoplasms; Prostatic Neoplasms; Morphine; Breast Neoplasms; Kaplan-Meier Estimate; Sex Factors; Analgesics, Opioid
PubMed: 38871605
DOI: 10.1016/j.canrad.2023.09.003 -
Frontiers in Medicine 2024The present case studies report malignant neoplastic and traumatic lesions observed on two ancient Egyptian skulls held at the Duckworth Collection (Cambridge...
The present case studies report malignant neoplastic and traumatic lesions observed on two ancient Egyptian skulls held at the Duckworth Collection (Cambridge University). The analysis aims to characterise the lesions and provide a diagnosis using a methodology based on micro-CT scanning and microscopic bone surface analysis. Results pointed towards neoplastic lesions in both cases and healed severe skull trauma in one of them suggesting successful traumatological therapy. Interestingly, our analysis has identified the presence of perimortem cutmarks associated with metastatic lytic lesions in one of the skulls, indicating a potential surgical treatment attempt or postmortem medical exploration. We argue that the two cases, although not contemporary, allow a palaeopathological discussion on oncological and traumatological understanding and management of such conditions in the past. The confrontation of two potential managements represented by two different types of lesions represent a clear boundary in ancient Egyptian medical care and a milestone in the history of medicine.
PubMed: 38868751
DOI: 10.3389/fmed.2024.1371645