-
Veterinary Pathology Apr 2024Histologic diagnosis of less well-differentiated cases of canine extramedullary plasmacytomas (CEMPs) may require immunohistochemical confirmation to discriminate these...
Histologic diagnosis of less well-differentiated cases of canine extramedullary plasmacytomas (CEMPs) may require immunohistochemical confirmation to discriminate these tumors from other round cells tumors including lymphoma, cutaneous histiocytoma, and amelanotic melanomas. CEMPs are characterized by widespread immunoreactivity for multiple myeloma 1 (MUM1) antigen and λ light chains, while the melanocytic marker melan-A has been reported to yield negative results. Here, 33 randomly selected CEMPs, 20 melanocytomas, and 20 malignant melanomas were immunohistochemically tested for MUM1, melan-A, and PNL2. In addition, CEMPs were examined for PAX5, E-cadherin, CD3, CD18, CD20, S100, as well as λ and κ light chain immunoreactivity. All CEMPs were characterized by labeling for MUM1 and λ light chain, as well as variable immunopositivity for the remaining antibodies. Notably, 13 cases of CEMPs (39.4%) exhibited immunolabeling for melan-A. Melanocytic tumors immunolabeled for melan-A (40/40; 100%) and PNL2 (34/40; 85%). An unexpected cytoplasmic immunoreactivity for MUM1 was observed in 2 melanocytic tumors. Summarized, MUM1 or melan-A immunomarkers alone are not sufficient to differentiate between CEMPs and amelanotic melanomas and should be part of a larger immunopanel including λ light chain, CD20, and PNL2.
PubMed: 38642035
DOI: 10.1177/03009858241246979 -
Internal Medicine (Tokyo, Japan) Sep 2023
Topics: Humans; Plasmacytoma; Gallbladder Neoplasms; Multiple Myeloma
PubMed: 36517034
DOI: 10.2169/internalmedicine.1079-22 -
Ophthalmology Nov 2023
PubMed: 37999678
DOI: 10.1016/j.ophtha.2023.10.027 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Jan 2024Extramedullary plasmacytoma (EMP) is a special type of malignant plasmacytosis, which is complex and heterogeneous. Most EMP patients have poor prognosis and lack a...
Extramedullary plasmacytoma (EMP) is a special type of malignant plasmacytosis, which is complex and heterogeneous. Most EMP patients have poor prognosis and lack a stratified prognostic system or ideal treatment strategy supported by evidence-based medical evidence, which cannot meet clinical needs. In order to improve the understanding of this disease entity, Plasma Cell Disease Group, Chinese Society of Hematology, Chinese Medical Association and Chinese Myeloma Committee-Chinese Hematology Association developed the "Chinese Expert Consensus on the diagnosis and treatment of extramedullary plasmacytoma", which aims to standardize the clinical diagnosis and treatment of EMP and ultimately improve the overall survival of patients with plasmacytoma.
Topics: Humans; Plasmacytoma; Consensus; Multiple Myeloma; Prognosis; Paraproteinemias
PubMed: 38527832
DOI: 10.3760/cma.j.cn121090-20231107-00253 -
Veterinary Pathology Nov 2023Microscopic evaluation of hematoxylin and eosin-stained slides is still the diagnostic gold standard for a variety of diseases, including neoplasms. Nevertheless, intra-...
Microscopic evaluation of hematoxylin and eosin-stained slides is still the diagnostic gold standard for a variety of diseases, including neoplasms. Nevertheless, intra- and interrater variability are well documented among pathologists. So far, computer assistance via automated image analysis has shown potential to support pathologists in improving accuracy and reproducibility of quantitative tasks. In this proof of principle study, we describe a machine-learning-based algorithm for the automated diagnosis of 7 of the most common canine skin tumors: trichoblastoma, squamous cell carcinoma, peripheral nerve sheath tumor, melanoma, histiocytoma, mast cell tumor, and plasmacytoma. We selected, digitized, and annotated 350 hematoxylin and eosin-stained slides (50 per tumor type) to create a database divided into training, = 245 whole-slide images (WSIs), validation ( = 35 WSIs), and test sets ( = 70 WSIs). Full annotations included the 7 tumor classes and 6 normal skin structures. The data set was used to train a convolutional neural network (CNN) for the automatic segmentation of tumor and nontumor classes. Subsequently, the detected tumor regions were classified patch-wise into 1 of the 7 tumor classes. A majority of patches-approach led to a tumor classification accuracy of the network on the slide-level of 95% (133/140 WSIs), with a patch-level precision of 85%. The same 140 WSIs were provided to 6 experienced pathologists for diagnosis, who achieved a similar slide-level accuracy of 98% (137/140 correct majority votes). Our results highlight the feasibility of artificial intelligence-based methods as a support tool in diagnostic oncologic pathology with future applications in other species and tumor types.
Topics: Animals; Dogs; Artificial Intelligence; Deep Learning; Eosine Yellowish-(YS); Hematoxylin; Reproducibility of Results; Skin Neoplasms; Machine Learning; Dog Diseases
PubMed: 37515411
DOI: 10.1177/03009858231189205 -
Mayo Clinic Proceedings Jan 2024
Topics: Humans; Plasmacytoma; Larynx; Laryngeal Neoplasms
PubMed: 38176821
DOI: 10.1016/j.mayocp.2023.07.001 -
Indian Journal of Otolaryngology and... Dec 2023Plasmacytomas are localized monoclonal plasma cell lesions with no evidence of systemic involvement which are divided into solitary bone plasmacytoma (SBP) and...
Plasmacytomas are localized monoclonal plasma cell lesions with no evidence of systemic involvement which are divided into solitary bone plasmacytoma (SBP) and extra-medullary plasmacytoma (EMP). The diagnosis of plasmacytomas (PCM) in the oral regions is challenging given the atypical clinical manifestations and low frequency. Here, we report an extremely rare case of plasmacytoma in an elderly male which initially appeared to be arising from the left buccal mucosa on clinical examination but after radiological imaging and intra-operative findings, the epicentre was found to be in the left infratemporal fossa (ITF). The patient underwent en-bloc compartment resection with high clearance of the ITF which proved to be an effective management strategy. It is crucial for the head and neck surgeon to be aware of the solitary bone plasmacytoma in the oral and maxillofacial region in order to identify it early and provide these patients with the best care possible before complications arise.
PubMed: 38027534
DOI: 10.1007/s12070-023-03875-2 -
Biochemical and Biophysical Research... Sep 2023Endothelial dysfunction plays a crucial role in the pathogenesis of vascular disease. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in various...
Endothelial dysfunction plays a crucial role in the pathogenesis of vascular disease. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in various cellular processes and are involved in several vascular endothelial cells (VECs) biological processes, including cell growth, migration, autophagy, and apoptosis. The functions of plasmacytoma variant translocation 1 (PVT1) in VECs have been progressively investigated in recent years, mainly with regard to proliferation and migration of endothelial cells (ECs). However, the mechanism underlying the regulation of autophagy and apoptosis in human umbilical vein endothelial cells (HUVEC) by PVT1 remains unclear. The present study showed that PVT1 knockdown accelerated apoptosis induced by oxygen and glucose deprivation (OGD) through suppression of cellular autophagy. Bioinformatic prediction of PVT1 target miRNAs revealed that PVT1 interacts with miR-15b-5p and miR-424-5p. The study further showed that miR-15b-5p and miR-424-5p inhibit the functions of autophagy related 14 (ATG14) and suppress cellular autophagy. The results showed that PVT1 can function as a competing endogenous RNA (ceRNA) of miR-15b-5p and miR-424-5p and promote cellular autophagy by competitive binding, which down-regulates apoptosis. The results showed that PVT1 can function as a competing endogenous RNA (ceRNA) of miR-15b-5p and miR-424-5p and promote cellular autophagy through competitive binding, which down-regulates apoptosis. The study provides insight into a novel therapeutic target that may be explored in the future for the treatment of cardiovascular disease.
Topics: Humans; Endothelial Cells; MicroRNAs; Autophagy; Cell Proliferation; Apoptosis; Hypoxia; RNA, Long Noncoding; Autophagy-Related Proteins; Adaptor Proteins, Vesicular Transport
PubMed: 37290278
DOI: 10.1016/j.bbrc.2023.06.001 -
Molecular Oncology Dec 2023Synthetic oleanane triterpenoids (SOTs) are small molecules with broad anticancer properties. A recently developed SOT,...
Synthetic oleanane triterpenoids (SOTs) are small molecules with broad anticancer properties. A recently developed SOT, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-2-yl)-1H-imidazole (CDDO-2P-Im or '2P-Im'), exhibits enhanced activity and improved pharmacokinetics over CDDO-Im, a previous generation SOT. However, the mechanisms leading to these properties are not defined. Here, we show the synergy of 2P-Im and the proteasome inhibitor ixazomib in human multiple myeloma (MM) cells and 2P-Im activity in a murine model of plasmacytoma. RNA sequencing and quantitative reverse transcription PCR revealed the upregulation of the unfolded protein response (UPR) in MM cells upon 2P-lm treatment, implicating the activation of the UPR as a key step in 2P-Im-induced apoptosis. Supporting this hypothesis, the deletion of genes encoding either protein kinase R-like endoplasmic reticulum kinase (PERK) or DNA damage-inducible transcript 3 protein (DDIT3; also known as CHOP) impaired the MM response to 2P-Im, as did treatment with ISRIB, integrated stress response inhibitor, which inhibits UPR signaling downstream of PERK. Finally, both drug affinity responsive target stability and thermal shift assays demonstrated direct binding of 2P-Im to endoplasmic reticulum chaperone BiP (GRP78/BiP), a stress-inducible key signaling molecule of the UPR. These data reveal GRP78/BiP as a novel target of SOTs, and specifically of 2P-Im, and suggest the potential broader utility of this class of small molecules as modulators of the UPR.
Topics: Humans; Mice; Animals; Multiple Myeloma; Endoplasmic Reticulum Chaperone BiP; Cell Line, Tumor; Apoptosis; Imidazoles; Unfolded Protein Response
PubMed: 37149844
DOI: 10.1002/1878-0261.13447 -
CNS Neuroscience & Therapeutics Jan 2024This study aimed to investigate the role of plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA, in glioblastoma multiforme (GBM) and its impact on the...
AIMS
This study aimed to investigate the role of plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA, in glioblastoma multiforme (GBM) and its impact on the tumor microenvironment (TME).
METHODS
We assessed aberrant PVT1 expression in glioma tissues and its impact on GBM cell growth in vitro and in vivo. Additionally, we investigated PVT1's role in influencing glioma-associated macrophages. To understand PVT1's role in cell growth and the immunosuppressive TME, we performed a series of comprehensive experiments.
RESULTS
PVT1 was overexpressed in GBM due to copy number amplification, correlating with poor prognosis. Elevated PVT1 promoted GBM cell proliferation, while its downregulation inhibited growth in vitro and in vivo. PVT1 inhibited type I interferon-stimulated genes (ISGs), with STAT1 as the central hub. PVT1 correlated with macrophage enrichment and regulated CX3CL1 expression, promoting recruitment and M2 phenotype polarization of macrophages. PVT1 localized to the cell nucleus and bound to DHX9, enriching at the promoter regions of STAT1 and CX3CL1, modulating ISGs and CX3CL1 expression.
CONCLUSION
PVT1 plays a significant role in GBM, correlating with poor prognosis, promoting cell growth, and shaping an immunosuppressive TME via STAT1 and CX3CL1 regulation. Targeting PVT1 may hold therapeutic promise for GBM patients.
Topics: Humans; Glioblastoma; Cell Line, Tumor; Glioma; Macrophages; Cell Proliferation; RNA, Long Noncoding; Gene Expression Regulation, Neoplastic; MicroRNAs; Tumor Microenvironment; STAT1 Transcription Factor; Chemokine CX3CL1
PubMed: 38287522
DOI: 10.1111/cns.14566