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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 -
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 -
Diagnostic Pathology Jun 2024Intravascular papillary endothelial hyperplasia (IPEH) represents an uncommon reactive endothelial hyperplastic proliferation. A 46-year-old man experienced increased... (Review)
Review
Intravascular papillary endothelial hyperplasia (IPEH) represents an uncommon reactive endothelial hyperplastic proliferation. A 46-year-old man experienced increased volume in the right maxilla, elevation of the nasal ala, and swelling of the hard palate with a reddish hue for 3 months. Computed tomography revealed an expansive hypodense region and cortical bone destruction associated with an impacted supernumerary tooth and an endodontically treated tooth. Under the differential diagnoses of a radicular cyst, dentigerous cyst, and ameloblastoma, an exploratory aspiration and incisional biopsy were performed. This revealed the formation of blood vessels of various diameters lined by endothelium, forming intravascular papillae positive for CD-34. The definitive diagnosis was IPEH, and the patient was treated by embolization and surgery. Histological analysis confirmed the presence of IPEH associated with an odontogenic cyst. After 12 months of follow-up, no recurrence was observed. Also, we reviewed case reports of IPEH affecting the maxilla and mandible. Fourteen intraosseous cases were reported in the maxilla and mandible, with a preference for males and affecting a wide age range. Complete surgical excision was the treatment of choice, and recurrences were not reported. The pathogenesis of IPEH is controversial and may originate from trauma or inflammatory processes. To the best of our knowledge, this is the first report of an association of IPEH with an odontogenic cyst. The importance of IPEH in the differential diagnosis of intraosseous lesions in the jaws is emphasized, and preoperative semiotic maneuvers are needed to prevent surgical complications.
Topics: Humans; Male; Middle Aged; Odontogenic Cysts; Hyperplasia; Diagnosis, Differential; Maxilla; Biopsy; Treatment Outcome; Tomography, X-Ray Computed; Maxillary Diseases; Embolization, Therapeutic
PubMed: 38867285
DOI: 10.1186/s13000-024-01505-1 -
BMC Complementary Medicine and Therapies Jun 2024This study was conducted to determine the effect of music on the pain, anxiety, and comfort levels of patients who underwent bone marrow aspiration and biopsy. (Clinical Trial)
Clinical Trial
AIM
This study was conducted to determine the effect of music on the pain, anxiety, and comfort levels of patients who underwent bone marrow aspiration and biopsy.
METHODS
This study was conducted on patients with hematological malignancies. Music was used with the intervention group. Patients' pain, anxiety, and comfort levels were measured. In addition, qualitative data were obtained through in-depth interviews with patients.
RESULTS
A significant difference (p < 0.05) was found between the experimental and control groups regarding pain, comfort and anxiety levels following the application of music. It was found that there was a negative correlation between comfort and pain (r=-0.442 p < 0.001) and between comfort and anxiety (r=-0.544 p < 0.001). As a result of qualitative interviews, patients mentioned the relaxing effect of music and the reduction of anxiety and pain levels. They also stated that music can be utilized as an alternative method.
CONCLUSION
According to the results of the present study, music reduced the pain and anxiety levels of the patients in bone marrow aspiration and biopsy and increased their comfort levels. We can say that music can be used in the clinic as a non-pharmacological method for pain, anxiety and comfort.
CLINICAL TRIALS NUMBER
NCT05895357 (Date:08/06/2023).
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Anxiety; Biopsy; Bone Marrow; Hematologic Neoplasms; Music Therapy; Pain; Pain Management; Pain Measurement; Patient Comfort; Turkey
PubMed: 38867235
DOI: 10.1186/s12906-024-04531-0 -
Scientific Reports Jun 2024This study proposes the beta-emitting radioisotope Pr as a promising candidate for palliative treatment of metastatic bone pain due to its desirable physical decay...
This study proposes the beta-emitting radioisotope Pr as a promising candidate for palliative treatment of metastatic bone pain due to its desirable physical decay characteristics. An optimized process was developed for the production and purification of non-carrier-added Pr using a medium flux research reactor. Calculations were performed to determine the optimal irradiation time and cooling period for irradiating 1 mg of natural cerium oxide to indirectly produce Pr through the decay of Ce. Following irradiation and cooling, extraction chromatography was employed to efficiently isolate Pr from the irradiated target material. A column containing Ln-resin was used along with nitric acid as the mobile phase and an optional oxidation step with NaBrO/ascorbic acid to separate Pr from impurities such as Ce and Ce. Radionuclidic purity of over 99.995% was achieved as confirmed through gamma spectroscopy, demonstrating effective separation of Pr. Additional quality control analyses established the chemical and radiochemical purity of the purified Pr nitrate product. With a half-life of 13.6 days and maximum beta energy of 0.937 MeV, Pr exhibits favorable properties for palliative bone pain therapy. This study therefore provides a viable method for producing high-purity Pr through the optimized irradiation and purification processes described. Further investigation is warranted to explore potential clinical applications of Pr for palliation of metastatic bone cancer pain.
Topics: Bone Neoplasms; Palliative Care; Humans; Cancer Pain; Radiopharmaceuticals; Radioisotopes
PubMed: 38866894
DOI: 10.1038/s41598-024-64321-z