Pathobiology : journal of immunopathology, molecular and cellular biology最新文献

{"title":"Erythroid predominance in bone marrow biopsies of AML patients after decitabine treatment correlates with mutation profile and complete remission.","authors":"Francesca Tiso, K. Hebeda, Saskia M C Langemeijer, A. D. de Graaf, Joost H A Martens, Thessa N. Koorenhof-Scheele, Ruth Knops, L. Kroeze, B. A. van der Reijden, J. Jansen","doi":"10.1159/000538953","DOIUrl":"https://doi.org/10.1159/000538953","url":null,"abstract":"INTRODUCTION\u0000Acute myeloid leukemia (AML) patients may receive hypomethylating agents (HMAs) such as decitabine (DAC) as part of their treatment. Not all patients respond to this therapy, and if they do the clinical response may occur only after 3 to 6 courses of treatment. Hence, early biomarkers predicting response would be very useful.\u0000\u0000\u0000METHODS\u0000We retrospectively analyzed a cohort of 22 AML patients who were treated with DAC. Histology of the bone marrow biopsy, pathogenic mutations and methylation status were related to the treatment response.\u0000\u0000\u0000RESULTS\u0000In 8/22 (36%) patients, an erythroid dominant response (EDR) pattern, defined as a ratio of myeloid cells/erythroid cells < 1, was observed. In the remaining 14 cases a myeloid predominance was preserved during treatment. No difference in the hypomethylating effect of DAC treatment was observed in patients with and without EDR, as global 5-methylcytosine levels dropped similarly in both groups. Mutational analysis by NGS using a panel of commonly mutated genes in AML, showed that patients with an early EDR harbored on average less mutations, with U2AF1 mutations occurring more frequently, whereas RUNX1 mutations were underrepresented compared to non-EDR cases. Interestingly, the development of an EDR correlated with complete remission (7/8 cases with an EDR versus only 2/14 cases without an EDR).\u0000\u0000\u0000CONCLUSION\u0000We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":"11 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140681339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colonic tubular adenoma with clear cell change - case report with whole exome sequencing and updated review of the literature.","authors":"Ádám Ferenczi, Levente Kuthi, I. Sejben, Anita Sejben","doi":"10.1159/000538705","DOIUrl":"https://doi.org/10.1159/000538705","url":null,"abstract":"INTRODUCTION\u0000Colorectal tubular adenomas displaying clear cell change are rare entities, with unknown clinical relevance, prognosis, immunohistochemical, and molecular features.\u0000\u0000\u0000CASE PRESENTATION\u0000Hereby we report a case of a 43-year-old female patient with a rectosigmoid polyp. Histologically, conventional dysplasia was visible with scattered areas displaying clear cell change. Whole exome sequencing (WES) was carried out and revealed high tumour mutation burden, and 7 pathogenic mutations, including TP53, APC, FGFR4, EHBP1, IL4R, TYR, and ACTN3.\u0000\u0000\u0000CONCLUSION\u0000Clear cell change may only be present in less than 0,1% of adenomas. Aetiology is not well understood, additionally, few authors suggest autolysis or fixation problems. Our WES resulted in newly found pathogenic mutations, and high mutation burden, proving the lesion's neoplastic origin. Hitherto, neither special stainings, nor immunohistochemical markers proved to be useful in the diagnostic process. From a differential diagnostic perspective, enteroblastic differentiation, primary and secondary clear cell adenocarcinoma has to be excluded.","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140744147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Lipopolysaccharide Mutant Re-LPS Is a Useful Tool for Detecting LPS Contamination in Rheumatoid Synovial Cell Cultures.","authors":"Hiroki Kohno,&nbsp;Kazuhisa Ouhara,&nbsp;Sho Mokuda,&nbsp;Tadahiro Tokunaga,&nbsp;Tomohiro Sugimoto,&nbsp;Hirofumi Watanabe,&nbsp;Michinori Ishitoku,&nbsp;Yusuke Yoshida,&nbsp;Noriyoshi Mizuno,&nbsp;Tatsuhiko Ozawa,&nbsp;Masatoshi Kawataka,&nbsp;Shintaro Hirata,&nbsp;Hiroyuki Kishi,&nbsp;Eiji Sugiyama","doi":"10.1159/000520022","DOIUrl":"https://doi.org/10.1159/000520022","url":null,"abstract":"<p><strong>Introduction: </strong>Lipopolysaccharide (LPS) contamination of commercially available proteins has seriously impeded research on citrullinated fibrinogen (cit-Fb) in rheumatoid synovial cells (RSCs).</p><p><strong>Methods: </strong>RSCs obtained from 4 rheumatoid arthritis patients who underwent full knee arthroplasty were cultured, stimulated with cit-Fb, and cytokine expression levels were measured. We then evaluated polymyxin-B (PMB), heat inactivation, and rough (R)-type LPS mutants for rapid detection of LPS contamination.</p><p><strong>Results: </strong>cit-Fb induced expression of CXCL10 and IFNB in RSCs via the toll-like receptor. PMB inhibited cit-Fb-mediated CXCL10 gene expression but not protein expression induced by 20 μg/mL cit-Fb. Heat inactivation did not affect LPS-mediated CXCL10 or IL-6 induction; however, cit-Fb-mediated CXCL10expression was inhibited. Wild-type LPS from Escherichia coli (WT-LPS) strongly induces CXCL10 expression, but induction by Ra-LPS was weak, and induction by Rc- and Re-LPS was minimal. Re-LPS suppression of WT-LPS-mediated CXCL10 induction in RSCs and peripheral blood monocytes (PBMs) was dose dependent. Furthermore, Re-LPS completely suppressed cit-Fb-mediated CXCL10 induction in RSCs and PBMs.</p><p><strong>Conclusion: </strong>To easily identify LPS contamination during routine experiments, our results suggest that Re-LPS is a better tool for rapid detection of LPS contamination compared to PMB and heat treatment.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"92-100"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39752842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Possible Pathogenic Role of IgG4-Producing Plasmablasts in Stricturing Crohn's Disease.","authors":"Omar Bushara,&nbsp;David Joseph Escobar,&nbsp;Samuel Edward Weinberg,&nbsp;Leyu Sun,&nbsp;Jie Liao,&nbsp;Guang-Yu Yang","doi":"10.1159/000521259","DOIUrl":"https://doi.org/10.1159/000521259","url":null,"abstract":"<p><strong>Background: </strong>Crohn's disease (CD) is a condition on the spectrum of inflammatory bowel disease that affects up to 20 people per 100,000 in the US annually, and with incidence increasing. One of the most significant sources of morbidity in CD is the formation of strictures, with resultant intestinal blockage a common indication for hospitalization and surgical intervention in these patients. The pathophysiology of stricture formation is not fully understood. However, the fibroplasia that leads to fibrostenotic stricture formation may have shared pathophysiology with IgG4-related fibrosis.</p><p><strong>Summary: </strong>Initial intestinal inflammation recruits innate immune cells, such as neutrophils, that secrete IL-1β and IL-23, which induces a type 17 CD4+ T-helper T-cell (Th17)-mediated adaptive immune response. These CD4+ Th17 T cells also contribute to inflammation by secreting proinflammatory cytokines such as IL-17 and IL-21. IL-21 recruits and stimulates CD4+ T follicular helper (Tfh) cells, which secrete more IL-21. This causes ectopic germinal center formation, recruiting and stimulating naïve B cells. The IL-17 and IL-21 produced by Th17 cells and Tfh cells also induce IgG4 plasmablast differentiation. Finally, these IgG4-producing plasmablasts secrete platelet-derived growth factor (PDGF), which activates local PDGF-receptor expressing fibroblasts and myofibroblasts, resulting in uncontrolled fibroplasia.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"187-197"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39818852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic Differences of CD103+ Tissue-Resident Memory T Cells Associated with Various Cancers.","authors":"Hye Seon Park,&nbsp;Yeonjin Jeon,&nbsp;Hyun Lee,&nbsp;Heejae Lee,&nbsp;Young-Ae Kim,&nbsp;In Ah Park,&nbsp;Won Seon Bang,&nbsp;Miseon Lee,&nbsp;Young Jin Cho,&nbsp;Jihyeong Kim,&nbsp;Gyungyub Gong,&nbsp;Hee Jin Lee","doi":"10.1159/000518972","DOIUrl":"https://doi.org/10.1159/000518972","url":null,"abstract":"<p><strong>Background/aims: </strong>The presence and clinical importance of tissue-resident memory T (TRM) cells have been recently described in association with various cancer types. However, the frequency and the traditional naïve-effector-memory phenotypic characteristics of TRM cells are largely unknown.</p><p><strong>Methods: </strong>We analyzed single-cell populations of colorectal cancer (CC, n = 18), stomach cancer (SC, n = 13), renal cell carcinoma (RCC, n = 19), and breast cancer (BC, n = 16) by dissociation of tumor tissue with collagenase/hyaluronidase. We investigated populations of naïve, effector, and memory T and TRM cells by flow cytometry.</p><p><strong>Results: </strong>Among CD8- cells, CC was associated with a significantly higher proportion of CD103+ T cells than other tumor types (p < 0.001). Among CD8+ cells, CC and SC were associated with higher CD103+ T-cell proportions than RCC and BC (p < 0.001). Significantly more CD8+ than CD8- cells expressed CD103 (p < 0.001). In association with SC, RCC, and BC, CD8+ T cells had a similar T-cell phenotype composition pattern: fewer effector T cells and more memory-type T cells among CD103+ cells compared with CD103- cells (p < 0.05). Tumors with higher proportion of CD103+ cells had no specific clinicopathologic characteristics than those with lower proportion of CD103+ cells.</p><p><strong>Conclusion: </strong>TRM cell abundance and phenotypes varied among CC, SC, RCC, and BC. Further studies regarding the functional differences of TRM associated with various tumors are warranted.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"116-126"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39474156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histological Prognostic Factors of Endometrial Cancer in Patients with Adenomyosis: A Systematic Review and Meta-Analysis.","authors":"Antonio Raffone,&nbsp;Antonio Travaglino,&nbsp;Diego Raimondo,&nbsp;Manuela Maletta,&nbsp;Paolo Salucci,&nbsp;Angela Santoro,&nbsp;Fulvio Zullo,&nbsp;Gian Franco Zannoni,&nbsp;Paolo Casadio,&nbsp;Renato Seracchioli,&nbsp;Antonio Mollo","doi":"10.1159/000521105","DOIUrl":"https://doi.org/10.1159/000521105","url":null,"abstract":"<p><strong>Background: </strong>A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been hypothesized based on a different prevalence of favorable EC histological prognostic factors. However, pooled risk of EC unfavorable histological prognostic factors in patients with adenomyosis has never been calculated.</p><p><strong>Objectives: </strong>We aimed to assess the risk of EC unfavorable histological prognostic factors in patients with adenomyosis.</p><p><strong>Methods: </strong>All studies with data about histological prognostic factors of EC in patients with and without adenomyosis were included. Relative risk for each unfavorable histological prognostic factor of EC, such as nonendometrioid histotype, FIGO grade 3, FIGO stage II-IV, lymphovascular space invasion (LVSI), and deep myometrial invasion, was calculated in patients with adenomyosis compared to patients without adenomyosis.</p><p><strong>Results: </strong>Seven studies with 4,439 patients were included in the quantitative analysis. EC patients with adenomyosis showed a pooled RR of 0.77 (p = 0.05) for nonendometrioid histotype, 0.55 (p < 0.00001) for FIGO grade 3, 0.60 (p = 0.005) for FIGO stage II-IV, 0.75 (p = 0.004) for LVSI, and 0.65 (p = 0.001) for deep myometrial invasion.</p><p><strong>Conclusion: </strong>EC patients with adenomyosis have a significantly decreased risk for unfavorable histological prognostic factors of EC compared to EC patients without adenomyosis. Such findings might explain the supposed better EC prognosis in patients with adenomyosis.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"127-134"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39837333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical and Transcriptional Analysis of SARS-CoV-2 Entry Factors and Renin-Angiotensin-Aldosterone System Components in Lethal COVID-19.","authors":"Jasmin Dionne Haslbauer,&nbsp;Anna Stalder,&nbsp;Carl Zinner,&nbsp;Stefano Bassetti,&nbsp;Kirsten Diana Mertz,&nbsp;Philip Went,&nbsp;Matthias Matter,&nbsp;Alexandar Tzankov","doi":"10.1159/000520221","DOIUrl":"https://doi.org/10.1159/000520221","url":null,"abstract":"<p><strong>Introduction: </strong>Since angiotensin converting enzyme-2 (ACE2) was discovered as an essential entry factor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), there has been conflicting evidence regarding the role of renin-angiotensin-aldosterone system (RAAS) in COVID-19. This study elucidates pulmonary expression patterns SARS-CoV-2 entry factors (ACE2 and transmembrane protease serine subtype 2, TMPRSS2) and RAAS components in lethal COVID-19.</p><p><strong>Methods: </strong>Lung tissue from COVID-19 autopsies (n = 27) and controls (n = 23) underwent immunohistochemical staining for RAAS components (angiotensin receptors 1 and 2, ACE2 and Mas-receptor) and bradykinin receptors 1 and 2. Staining of individual cellular populations (alveolar pneumocytes [ALV], desquamated cells [DES] and endothelium [END]) was measured by a binary scale (positive/negative). SARS-CoV-2 was detected using immunohistochemistry against nucleocapsid protein, in-situ hybridization and quantitative reverse transcriptase polymerase chain reaction. Gene expression profiling for ACE2, ACE and TMPRSS2 was performed.</p><p><strong>Results: </strong>Subtle differences were observed when comparing COVID-19 patients and controls not reaching statistical significance, such as a higher incidence of ACE2-positivity in END (52% vs. 39%) but lower positivity in ALVs (63% vs. 70%) and an overall downregulation of ACE2 gene expression (0.25 vs. 0.55). However, COVID-19 patients with RAAS inhibitor (RAASi) intake had significantly shorter hospitalization times (5 vs. 12 days), higher viral loads (57,517 vs. 15,980/106 RNase P-gene copies) and decreased ACE/ACE2-expression ratios (4.58 vs. 11.07) than patients without. TMPRSS2 expression was significantly (1.76-fold) higher in COVID-19 patients than controls.</p><p><strong>Conclusion: </strong>Our study delineates the heterogeneous expression patterns of RAAS components in the lungs, which vary amongst cellular populations, and implies that COVID-19 patients with RAASi-intake present with a more rapid disease progression, although this requires further investigation.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"166-177"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/a5/pat-0001.PMC8805061.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39593888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Expression of the RUVBL1 Component of the R2TP Complex Correlates with Poor Prognosis in DLBCL.","authors":"Moien Lone,&nbsp;Mahaiwon Shadang,&nbsp;Qulsum Akhter,&nbsp;Mithilesh Kumar,&nbsp;Saumyaranjan Mallick,&nbsp;Ajay Gogia,&nbsp;Nilima Nilima,&nbsp;Shyam S Chauhan,&nbsp;Riyaz A Mir","doi":"10.1159/000520723","DOIUrl":"https://doi.org/10.1159/000520723","url":null,"abstract":"<p><strong>Introduction: </strong>Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma (NHL) accounting for 30% of adult NHL worldwide and 50% in developing countries like India. DNA damage and Myc-induced transformation are well-known contributing factors towards development of DLBCL. A recently identified HSP90 co-chaperone complex R2TP has been shown to contribute towards DNA damage and Myc-induced transformation. This study aimed to analyse the immunohistochemical (IHC) expression of R2TP complex components RUVBL1, PIH1D1, and RPAP3 in DLBCL patients and correlate with prognosis.</p><p><strong>Methods: </strong>DLBCL (n = 54) histological slides were retrieved from archives, and detailed histomorphological and clinical features were noted. IHC staining of R2TP complex components RUVBL1, PIH1D1, and RPAP3 was performed on 54 cases (FFPE) of DLBCL. Expression data were correlated with survival and clinical features.</p><p><strong>Results: </strong>Out of the 54 DLBCL cases, 59.26% (n = 32) stained positive for RUVBL1. The RUVBL1 expression was associated with poor prognosis in both progression-free survival (PFS) (p = 0.0146) and overall survival (OS) (p = 0.0328). The expression was positively correlated with bone marrow involvement (p = 0.0525). The expression of PIH1D1 was observed in 68.51% (n = 32) of DLBCL cases, and positive correlation was observed with international prognostic index score (p = 0.0246); however, no correlation was observed with PFS or OS. Finally, RPAP3 was found immunopositive in only 1 case of DLBCL.</p><p><strong>Conclusions: </strong>Immunopositivity for RUVBL1 is associated with poor prognosis along with a higher relapse rate amongst the DLBCL patients. PIH1D1 immunopositivity correlated with a higher IPI score.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"146-156"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39948672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-31-5p/SOX4 Axis Affects Autophagy and Apoptosis of Chondrocytes by Regulating Extracellular Regulated Protein Kinase/Mechanical Target of Rapamycin Kinase Signalling.","authors":"Fei Xu,&nbsp;Yong-Ming Lv,&nbsp;Hai-Bin Wang,&nbsp;Ying-Chun Song","doi":"10.1159/000519006","DOIUrl":"https://doi.org/10.1159/000519006","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a common type of degenerative joint diseases that is regulated by a combination of complex intercellular signals and modulators, including non-coding RNAs. Mounting evidence suggests that miR-31-5p is physiologically involved in the regulation of chondrocytes, but the mechanism remains unclear.</p><p><strong>Methods: </strong>Expression levels of miR-31-5p and SOX4 in OA cartilage tissues and in IL-1β-stimulated chondrocytes were examined by quantification polymerase chain reaction (q-PCR) or immunohistochemistry assays. Cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Expression of LC3 was detected using immunofluorescence staining. Expressions of autophagy-related proteins and extracellular regulated protein kinase (ERK)/mechanical target of rapamycin kinase (mTORC1) signal-related proteins were measured by Western blot analysis. Molecular interaction was validated by dual luciferase reporter assay.</p><p><strong>Results: </strong>Downregulation of miR-31-5p and upregulation of SOX4 were observed in both OA patients and OA chondrocytes. Mechanistic experiments revealed that miR-31-5p negatively modulated SOX4 expression by directly targeting its 3'- untranslated region. Moreover, overexpression of miR-31-5p suppressed the activation of mTORC1 in an ERK-dependent manner by inhibiting SOX4. Further functional experiments demonstrated that overexpressing miR-31-5p in OA chondrocytes markedly promoted its proliferation and autophagy while inhibiting apoptosis. However, these effects were abolished by overexpression of SOX4 or treatment with 3BDO, an mTOR activator.</p><p><strong>Conclusion: </strong>These results demonstrated that miR-31-5p enhanced survival and autophagy of OA chondrocytes through inactivation of mTORC1 via directly targeting SOX4, suggesting that miR-31-5p may play a protective role in OA progression.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"63-73"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39603368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib.","authors":"Bruna Minniti Mançano,&nbsp;Mariana Bisarro Dos Reis,&nbsp;Daniel Antunes Moreno,&nbsp;Flávia Escremim de Paula,&nbsp;Carlos Roberto de Almeida Junior,&nbsp;Carlos Eduardo Bezerra Cavalcante,&nbsp;Maicon Fernando Zanon,&nbsp;Iara Viana Vidigal Santana,&nbsp;Marcus de Medeiros Matsushita,&nbsp;Rui Manuel Reis","doi":"10.1159/000521253","DOIUrl":"https://doi.org/10.1159/000521253","url":null,"abstract":"<p><p>Herein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor. A comprehensive molecular analysis on the tumor tissue showed a TPR-NTRK1 gene fusion. The patient was treated with a TRK inhibitor, larotrectinib, and exhibited a stable disease with residual lesion following 8 months of target therapy. The present study is the first report of an infantile gliosarcoma harboring NTRK1 rearrangement treated with larotrectinib.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"178-185"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39700938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}