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This article discusses a study on double expressor lymphoma (DEL) subtypes and the therapeutic mechanism of epigenetic agents. The study identified three subtypes of DEL with unique characteristics and found that DEL had an inferior survival compared to double negative lymphoma (DNL). The subtypes of DEL were associated with different cell-of-origin and genetic classifications. The study also analyzed the effects of tucidinostat and doxorubicin treatment on different oncogenic transcriptional factors and signaling networks in these subtypes. The results showed distinct molecular heterogeneity and a complex tumor microenvironment in DEL, which contribute to resistance to standard treatment. However, tucidinostat plus doxorubicin demonstrated broad-spectrum sensitivity in vitro and in vivo. The study provides insights for optimizing current treatment paradigms in DEL. [Extracted from the article]

Gastric cancer (GC) is a gastric epithelium‐derived malignancy insensitive to post‐surgical radiotherapy. Paclitaxel, an anti‐microtubule drug, has been proven to induce apoptosis of GC cells; however, its exact mechanism of action is unclear. Therefore, the molecular mechanism by which paclitaxel inhibits the proliferation, migration and invasion of GC cells was investigated in this study. First off, SNU‐719 cells were co‐cultured with paclitaxel and/or Caspase1 inhibitor VX765. Then the proliferation ability of the cells was detected by MTT after paclitaxel treatment (0, 10, 20, 40, and 80 nM), the migration ability by scratch assay, and the invasion ability by Transwell assay. Next, the levels of interleukin (IL)‐1β and IL‐18 in cell culture supernatant were detected by the enzyme linked immunosorbent assay (ELISA). And the level of lactate dehydrogenase (LDH) in the supernatant was measured by a corresponding kit. Finally, western blot was performed to detect the concentrations of Gasdermin E (GSDME), GSDME‐N, nod‐like receptor family pyrin domain‐containing 3 (NLRP3), caspase‐1, cleaved caspase‐1 protein in GC cells. As a result, paclitaxel inhibited the proliferation, migration, and invasion of SNU‐719 cells in a concentration‐dependent manner. Moreover, it induced the pyroptosis of SNU‐719 cells. After cell co‐culture with VX765 paclitaxel showed decreased inhibitory effect on the migration and invasion of SNU‐719 cells. VX765, additionally, suppressed the NLRP3/caspase‐1/GSDME mediated pyroptosis pathway activated by paclitaxel. In a nutshell, paclitaxel may inhibit the migration and invasion of GC cells SNU‐719 through the NLRP3/caspase‐1/GSDME mediated pyroptosis pathway. [ABSTRACT FROM AUTHOR]

CD47 overexpression is associated with tumor-associated macrophage infiltration and the progression of diffuse large B-cell lymphoma (DLBCL). High CD47 expression is linked to elevated serum lactic dehydrogenase levels and an increased proportion of non-germinal center B-cell subtype. Patients with high CD47 expression have lower progression-free survival and overall survival rates compared to those with low CD47 expression. CD47 is also involved in genetic mutations and dysregulated pathways in DLBCL, and it promotes the polarization of M2-polarized macrophages and an immunosuppressive microenvironment. CD47 expression can be evaluated using immunohistochemistry, and it serves as a potential immunotherapeutic target for DLBCL treatment. [Extracted from the article]

Diffuse large B‐cell lymphoma (DLBCL) is a genetically heterogeneous disease with complex tumor microenvironment (TME) alterations. However, immune cell signatures of TME and their prognostic value remain unclear in DLBCL. We aimed to identify high‐risk DLBCL with specific immune cell signatures in TME. Clinical and gene expression data of DLBCL patients were obtained from previously reported retrospective datasets in Gene Expression Omnibus (GSE108466 and GSE5378616) and a multi‐center prospective clinical trial NHL001 (NCT01852435). Patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (n = 159) from GSE10846 were referred as training cohort for CHOP regimen, while patients treated with rituximab‐CHOP (R‐CHOP) regimen (n = 192) from GSE10846 as training cohort for R‐CHOP regimen. Patients from NHL001 (n = 68) and GSE53786 (n = 57) were referred as validation cohorts for R‐CHOP regimen. CIBERSORT was applied to estimate the relative proportions of 22 subtype of immune cells. We established a prognostic model for model for R‐CHOP regimen included Age, performance status, lactate dehydrogenase, T cells follicular helper and macrophages M0, defining a low‐risk group with 2‐years OS of 92.9% and a high‐risk group with 2‐years OS of 52.5% (HR 6.57 [3.27–13.18], p < 0.0001). Immune cell signatures could be used as prognostic markers and provided further insights for individualized immunotherapeutic strategies in DLBCL. [ABSTRACT FROM AUTHOR]

Gene mutations were first screened in 180 patients with WGS/WES/targeted sequencing data, including 40 cases of EBER-positive DLBCL and 140 cases of EBER-negative DLBCL. As serum EBV DNA is mostly derived from tumor cells,6 our findings emphasized the advantage of serum EBV DNA as noninvasive biomarker for predicting tumor EBER status and prognostic factor of DLBCL. Epstein-Barr virus (EBV) is an important human oncogenic virus and closely related to the pathogenesis of diffuse large B-cell lymphoma.1 This is, to our knowledge, the first study to systematically evaluate the clinical impact of EBV infection on DLBCL, based on a prospective clinical trial (NHL-001, NCT01852435). [Extracted from the article]

Two recent reports in the New England Journal of Medicine highlight the successful application of novel targeted therapies to improve the clinical outcomes of diffuse large B-cell lymphoma (DLBCL). These findings encourage us to pursue further mechanism-based therapeutic uses to make DLBCL curable in the era of precision medicine. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B‐cell lymphoma (DLBCL) is an aggressive subtype of lymphoma, and multiple extranodal involvement (ENI) indicates adverse clinical outcomes. The aim of this study was to investigate the influence of oncogenic mutations and tumor microenvironment alterations on ENI in DLBCL. Methods: The clinical features of 1960 patients with newly diagnosed DLBCL were analyzed, and DNA and RNA sequencing was performed on 670 and 349 patients, respectively. Oncogenic mutations and tumor microenvironment alterations were compared according to ENI and evaluated in zebrafish patient‐derived tumor xenograft models. Results: Multiple ENI was significantly associated with poor performance status, advanced stage, elevated serum lactate dehydrogenase, low response rate, and inferior prognosis. Lymphoma invasion of the bones, spleen, bone marrow, liver, and central nervous system were independent unfavorable prognostic factors. MYD88 was frequently mutated in patients with multiple ENI, co‐occurred with mutations in CD79B, PIM1, TBL1XR1, BTG1, MPEG1, and PRDM1, and correlated with invasion of the bones, kidney/adrenal glands, breasts, testes, skin, and uterus/ovaries. For tumor microenvironment alterations, patients with multiple ENI showed higher regulatory T‐cell (Treg)‐recruiting activity, but lower extracellular matrix‐encoding gene expression, than those without ENI and with single ENI. Elevated Treg‐recruiting activity was related to mutations in B2M, SGK1, FOXO1, HIST1H1E, and ARID1A, and correlated with invasion of the bone marrow and thyroid. Additionally, mutations in MYD88, PIM1, TBL1XR1, SGK1, FOXO1, HIST1H1E, and ARID1A were associated with decreased major histocompatibility complex class I expression. Zebrafish models further revealed relationships between MYD88 mutations and invasion of the kidneys and gonads, as well as B2M mutations and invasion of the bone marrow. Increased CXCR4 expression is linked to bone marrow invasion in an organotropic way. Conclusions: Our findings thus contribute to an improved understanding of the biological behavior of multiple ENI and provide a clinical rationale for targeting ENI in DLBCL. [ABSTRACT FROM AUTHOR]

Background: To determine the seroprevalence, latent infection rate and risk factors for severe fever with thrombocytopenia syndrome virus (SFTSV) infection, a cross-sectional study was conducted in the general population of the Western region of Anhui Province of China from 1 September to 31 December 2014. Methods: Twelve villages with the highest rates of endemic SFTS infection were selected from six towns in two counties in the western region of Anhui Province. Blood samples were collected and tested for the presence of SFTSV-IgG antibodies by ELISA. Each participant was interviewed using a structured questionnaire before blood collection. Participants with seropositive specimens were further investigated using another structured questionnaire. Results: Of 2126 blood specimens collected, 99 (4.66%) were seropositive for SFTSV. None of the participants had been diagnosed with SFTS before the blood collection or were accompanied by fever, thrombocytopenia and leukocytopenia after blood collection. Multivariate logistic regression model analysis revealed living in areas of uncontrolled vegetation growth, long-term residents of the locality and tick bites as high risk factors for SFTSV infection. Conclusions: The overall seroprevalence of SFTSV is higher in the western region of Anhui, possibly due to latent infection, with the main risk factors being living in areas of uncontrolled vegetation growth, long-term residents of the locality and tick bites. Further investigations are warranted to clarify the modes of SFTS virus transmission, while vector management, education on tick bite prevention and personal hygiene management should be implemented for high risk groups in endemic areas. [ABSTRACT FROM PUBLISHER]