non-Hodgkin Research Articles

Translational History and Hope of Immunotherapy of Canine Tumors.

Companion dogs have served an important role in cancer immunotherapy research. Sharing similar environments and diets with humans, dogs naturally develop many of the same cancers. These shared exposures, coupled with dogs' diverse genetic makeup, make them ideal subjects for studying cancer therapies. Tumors like osteosarcoma, hemangiosarcoma, soft-tissue sarcoma, and non-Hodgkin lymphoma occur with greater frequency than their counterpart disease in humans. Canine brain tumors allow the study of therapy strategies with imaging, surgery, and radiotherapy equipment in veterinary patients with near-human geometry. Nonspecific immunostimulants, autologous and allogeneic vaccines, immune checkpoint inhibitors, and cellular therapies used in treating canine cancers have been tested in veterinary clinical trials. These treatments have not only improved outcomes for dogs but have also provided valuable insights for human cancer treatment. Advancements in radiation technology and the development of tools to characterize canine immune responses have further facilitated the ability to translate veterinary clinical trial results to human applications. Advancements in immunotherapy of canine tumors have directly supported translation to human clinical trials leading to approved therapies for patients with cancer around the world. The study of immunotherapy in dogs has been and will continue to be a promising avenue for advancing human cancer treatment.

Outcomes of patients with R/R B-cell NHL and limited (

AbstractUnirradiated patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who undergo anti-CD19 chimeric antigen receptor T-cell therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized disease before CART. This study reports on the outcomes of patients with R/R NHL and limited (<5 involved sites) disease bridged with or without radiotherapy. A multicenter retrospective review of 150 patients with R/R NHL who received CART with <5 disease sites before leukapheresis was performed. Bridging treatment, if any, was administered between leukapheresis and CART infusion. Study end points included relapse-free survival (RFS), event-free survival (EFS), and overall survival. Before CART infusion, 48 patients (32%) received bridging radiotherapy (BRT), and 102 (68%) did not. The median follow-up was 21 months. After CART infusion, BRT patients had higher objective response (92% vs 78%; P = .046) and sustained complete response rates (54% vs 33%; P = .015). Local relapse in sites present before CART was lower in the BRT group (21% vs 46%; P = .003). BRT patients had improved 2-year RFS (53% vs 44%; P = .023) and 2-year EFS (37% vs 34%; P = .039) compared with patients who did not receive BRT. The impact of BRT was most prominent in patients who had ≤2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared with 42% in those who did not (P = .002). BRT before CART for patients with limited (<5 involved disease sites) R/R NHL improves response rate, local control, RFS, and EFS without causing significant toxicities.

Mitigating infection risks: The promise and challenge of bispecific antibodies in haematological malignancies.

Bispecific antibodies have shown significant clinical efficacy in patients with relapsed/refractory B-cell non-Hodgkin lymphomas and multiple myeloma, expanding treatment options for these patients. While these advancements are promising, it is important to be aware of associated side effects, such as cytokine release syndrome, neutropenia and infections. Gonugunta etal. provide valuable insights into the infection risks linked to the use of bispecific antibodies in haematological malignancies, drawing on both clinical trial data and real-world experiences. Commentary on: Gonugunta etal. Risk of infections with bispecific antibodies in B-cell non-Hodgkin lymphomas and multiple myeloma-The current state. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19633.

Proteomic signatures improve risk prediction for common and rare diseases

For many diseases there are delays in diagnosis due to a lack of objective biomarkers for disease onset. Here, in 41,931 individuals from the United Kingdom Biobank Pharma Proteomics Project, we integrated measurements of ~3,000 plasma proteins with clinical information to derive sparse prediction models for the 10-year incidence of 218 common and rare diseases (81–6,038 cases). We then compared prediction models developed using proteomic data with models developed using either basic clinical information alone or clinical information combined with data from 37 clinical assays. The predictive performance of sparse models including as few as 5 to 20 proteins was superior to the performance of models developed using basic clinical information for 67 pathologically diverse diseases (median delta C-index = 0.07; range = 0.02–0.31). Sparse protein models further outperformed models developed using basic information combined with clinical assay data for 52 diseases, including multiple myeloma, non-Hodgkin lymphoma, motor neuron disease, pulmonary fibrosis and dilated cardiomyopathy. For multiple myeloma, single-cell RNA sequencing from bone marrow in newly diagnosed patients showed that four of the five predictor proteins were expressed specifically in plasma cells, consistent with the strong predictive power of these proteins. External replication of sparse protein models in the EPIC-Norfolk study showed good generalizability for prediction of the six diseases tested. These findings show that sparse plasma protein signatures, including both disease-specific proteins and protein predictors shared across several diseases, offer clinically useful prediction of common and rare diseases.

Immunohistochemistry-based investigation of MYC, BCL2, and Ki-67 protein expression and their clinical impact in diffuse large B-cell lymphoma in upper Northern Thailand.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that accounts for approximately 25-40% of all NHL cases. The objective of this study was to investigate the protein expression, clinical impact, and prognostic role of MYC, BCL2, and Ki-67 in Thai DLBCL patients. A retrospective analysis was conducted on 100 DLBCL patients diagnosed between January 2018 and December 2019. Immunohistochemistry was used to assess the expression of MYC, BCL2, and Ki-67. The study revealed a significant association between extranodal involvement and positive cases of MYC and BCL2. MYC expressions were associated with Ki-67 expression, while BCL2 positivity was associated with the non-germinal center B-cell (non-GCB) subtype. However, there were no significant differences in the three-year overall survival (OS) and three-year progression-free survival (PFS) rates when using cut-off points of ≥ 40% for MYC, ≥ 50% for BCL2, and ≥ 70% for Ki-67. Notably, DLBCL cases with co-expression of MYC and BCL2 exhibited significantly inferior three-year OS compared to other cases (0% vs. 53%; p = 0.020). Multivariate analysis identified age ≥ 60 years and Eastern Cooperative Oncology Group (ECOG) performance status as independent prognostic factors. In conclusion, MYC, BCL2, and Ki-67 expression can serve as prognostic biomarkers; however, their prognostic value may vary based on the specific cut-off values used. Therefore, determining the appropriate threshold for each biomarker based on individual laboratory analyses and clinical outcomes is crucial.

Correlation Between the Hepatitis C Virus NS3 Protein and CD30 Expression in Diffuse Large B-cell Lymphoma.

One of the etiologies of non-Hodgkinlymphoma (NHL) is chronic infection related to lymphoma pathogenesis, with a high prevalence ofhepatitis C virus (HCV) infection seen. In determining the treatment and prognosis of NHL, cluster of differentiation 30 (CD30) immunohistochemical staining plays an important role. High levels of CD30are found in patients with HCV infection. This study aimed to determine the prevalence of CD30 and HCV expression and its correlation with clinicopathological characteristics of Indonesian diffuse large B-cell lymphoma (DLBCL) patients. A total of 86 formalin-fixed paraffin-embedded (FFPE) samples of DLBCL cases were collected over the course of two years from the Anatomical Pathology department at Dr. Sardjito General Hospital in the special region of Yogyakarta, Indonesia. Immunohistochemistry was performed to detect the two markers (CD30 and HCV). Chi-square tests were used to investigate the correlations between CD30 expression and clinicopathological features in DLBCL patients. The positivity rate of CD30 expression in 86 DLBCL samples was 25.6% (22/86) when using a 0% cut-off, and 7.0% (6/86) while using a 20% cutoff. The positivity rate of HCV expression in DLBCL samples was 34.9% (30/86). Positive CD30 expression, HCV expression and clinicopathological features (age, sex, Ann Arbor stage, extranodal involvement, and morphological variations) did not have statistically significant relationships (p>0.05). There was no statistically significant correlation between CD30 immunoreactivity (cut-off >0% or >20%) and HCV NS3 expression and clinicopathological features (age, sex, Ann Arbor stage, extranodal involvement, lactate dehydrogenase, Eastern Cooperative Oncology Group status and morphological variants) in DLBCL.

Intraocular manifestation of a diffuse large B-cell non-Hodgkin lymphoma of the pancreas.

Intraocular manifestation of a diffuse large B-cell non-Hodgkin lymphoma of the pancreas.

Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma.

Chemotherapy for malignant tumors can cause brain changes and cognitive impairment, leading to chemotherapy-induced cognitive impairment (CICI). Current research on CICI has focused on breast cancer and Hodgkin's lymphoma. Whether patients with non-Hodgkin's lymphoma (NHL) undergoing chemotherapy have cognitive impairment has not been fully investigated. To investigate whether NHL patients undergoing chemotherapy had cognitive impairments. The study included 100 NHL patients who were required to complete a comprehensive psychological scale including the Brief Psychiatric Examination Scale (MMSE) at two time points: before chemotherapy and within 2 wk of two chemotherapy courses. A language proficiency test (VFT), Symbol Number Pattern Test (SDMT), Clock Drawing Test (CDT), Abbreviated Daily Cognition Scale (ECog-12), Prospective and Retrospective Memory Questionnaire, and Karnofsky Performance Status were used to assess cognitive changes before and after chemotherapy. The VFT scores for before treatment (BT) and after treatment (AT) groups were 45.20 ± 15.62, and 42.30 ± 17.53, respectively (t -2.16, P < 0.05). The CDT scores were 8 (3.5-9.25) for BT and 7 (2.5-9) for AT groups (Z -2.1, P < 0.05). Retrospective memory scores were 13.5 (9-17) for BT and 15 (13-18) for AT (Z -3.7, P < 0.01). The prospective memory scores were 12.63 ± 3.61 for BT and 14.43 ± 4.32 for AT groups (t -4.97, P < 0.01). The ECog-12 scores were 1.71 (1.25-2.08) for BT and 1.79 (1.42-2.08) for AT groups (Z -2.84, P < 0.01). The SDMT and MMSE values did not show a significant difference between BT and AT groups. Compared to the AT group, the BT group showed impaired language, memory, and subjective cognition, but objective cognition and execution were not significantly affected.

Safety of TNF-α inhibitors: A real-world study based on the US FDA Adverse Event Reporting System Database.

As a common treatment for rheumatoid arthritis (RA), the adverse reactions of TNF-α inhibitors (TNFis) in practical application have garnered attention. This study aims to investigate the adverse drug events (ADEs) associated with TNFi in RA patients as reported in the FDA Adverse Event Reporting System, to offer insights for clinical use. Cases related to RA and primarily involving TNFi were extracted from the FDA Adverse Event Reporting System database and compared by gender stratification. Screening was conducted based on reporting odds ratio and information component to identify positive ADEs for different TNFis and evaluate common and unique ADEs among various TNFis. There are 4 common ADEs among TNFis, including pulmonary tuberculosis, infection, hypersensitivity, and herpes zoster, as described in the package inserts. However, each TNFi has unique positive ADEs. Adalimumab has 63 unique positive ADEs, including lower respiratory tract inflammation, systemic lupus erythematosus rash, vascular dementia, ovarian neoplasm, adhesion, sarcoma, coccidioidomycosis, etc. Golimumab has 6 unique positive ADEs, including pneumonia cryptococcal, device deployment issue, pneumonia bacterial, polyneuropathy, device malfunction, device issue, etc; certolizumab has 24 unique positive ADEs, including maternal exposure before pregnancy, premature rupture of membranes, exposure via breast milk, staphylococcal sepsis, erysipelas, low birth weight baby, herpes virus infection, premature delivery, etc; etanercept has 180 unique positive ADEs, including joint destruction, chondrolysis, finger deformity, ankle deformity, joint warmth, etc; infliximab has 60 unique positive ADEs, including Hodgkin's disease, metastatic neoplasm, non-Hodgkin's Lymphoma, etc. Although the aforementioned 5 TNFis share common ADEs such as herpes zoster, clinicians must exercise caution when selecting specific medications, especially for RA patients concurrently suffering from malignancies. The analysis indicates that infliximab is associated with 60 unique positive ADEs, including Hodgkin's disease, metastatic neoplasm, and non-Hodgkin's lymphoma; therefore, these patients should use infliximab with greater caution. Similarly, certolizumab should be used with increased caution in pregnant and postpartum women.

Optimization and characterization of Rituximab targeted multidrug loaded cyclodextrin nanoparticles against Non-Hodgkin Lymphoma

Currently, Non-Hodgkin Lymphoma (NHL) constitutes 85–90 % of all lymphomas. Clinical treatment of NHL is based on the “4-drug regimen” known as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Rituximab (RTX) is added to increase the effectiveness and selectivity of the treatment and is the first-line standard treatment for NHL patients. However, success is often prevented by the development of drug resistance. In this study, it was aimed to overcome drug resistance by using two novel tumor-targeted derivatives: guanidine-amphiphilic cyclodextrin (ACD) and guanidine-cyclodextrin polymer (PCD) nanoparticles (NP). These constructs display promise in overcoming drug resistance and enhancing the effectiveness of R-CHOP treatment while potentially eliminating the need for corticosteroid. NP were found to be smaller than 200 nm by dynamic light scattering (DLS). Hemolytic activity and cytotoxicity data on L929 cells demonstrated the safety of the newly synthesized CD derivatives. Additional in vitro characterization studies, including surface charge, physical stability, drug loading capacity, drug release profile, and imaging, as well as conventional and 3D cell culture studies were carried out. Compared to drug solutions, the viability of Daudi human lymphoma cells was statistically significantly decreased in both drug-loaded ACD and PCD NP formulations (p < 0.05). Additionally, RTX-conjugated and drug-loaded ACD NPs exhibited the lowest cell viability due to RTX dependent cytotoxicity.

HBx integration in diffuse large B-cell lymphoma inhibits Caspase-3-PARP related apoptosis

Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma, and is closely associated with hepatitis B virus (HBV) infection status and hepatitis B X (HBx) gene integration. This project investigated the cellular biological effects and molecular mechanisms responsible for lymphomagenesis and the progression of HBx integration in DLBCL. The data showed that clinical DLBCL cells demonstrated HBx integration, and the sequencing analysis of integrated sites validated HBx integration in the constructed HBx-transfected cells. Compared with control cells, HBx-transfected cells had a significantly reduced proportion of mitochondrial membrane potential, signals of chromosomal DNA breaks, and proportion of apoptotic cells. Further studies found that this decreased apoptosis level was associated with a significant reduction of cleaved Caspase-3 and downstream poly ADP-ribose polymerase (PARP) proteins, revealing the molecular mechanisms of HBx-associated apoptosis in DLBCL. Animal experiments also demonstrated that the protein expression of cleaved Caspase-3 and PARP was prominently reduced in HBx-transfected cells from subcutaneous tumors in mice. Furthermore, the HBx-integrated cells in clinical tissues had significantly lower cleaved PARP levels than the HBx-negative samples. Therefore, HBx integration inhibits cell apoptosis through the Caspase-3-PARP pathway in DLBCL indicating a potential biomarker and therapeutic target in HBV related DLBCL.

Bringing optimised COVID-19 vaccine schedules to immunocompromised populations (BOOST-IC): study protocol for an adaptive randomised controlled clinical trial

BackgroundImmunocompromised hosts (ICH) experience more breakthrough infections and worse clinical outcomes following infection with COVID-19 than immunocompetent people. Prophylactic monoclonal antibody therapies can be challenging to access, and escape variants emerge rapidly. Immunity conferred through vaccination remains a central prevention strategy for COVID-19. COVID-19 vaccines do not elicit optimal immunity in ICH but boosting, through additional doses of vaccine improves humoral and cellular immune responses. This trial aims to assess the immunogenicity and safety of different COVID-19 vaccine booster strategies against SARS-CoV-2 for ICH in Australia.MethodsBringing optimised COVID-19 vaccine schedules to immunocompromised populations (BOOST-IC) is an adaptive randomised trial of one or two additional doses of COVID-19 vaccines 3 months apart in people living with HIV, solid organ transplant (SOT) recipients, or those who have haematological malignancies (chronic lymphocytic leukaemia, non-Hodgkin lymphoma or multiple myeloma). Key eligibility criteria include having received 3 to 7 doses of Australian Therapeutic Goods Administration (TGA)-approved COVID-19 vaccines at least 3 months earlier, and having not received SARS-CoV-2-specific monoclonal antibodies in the 3 months prior to receiving the study vaccine. The primary outcome is the geometric mean concentration of anti-spike SARS-CoV-2 immunoglobulin G (IgG) 28 days after the final dose of the study vaccine. Key secondary outcomes include anti-spike SARS-CoV-2 IgG titres and the proportion of people seroconverting 6 and 12 months after study vaccines, local and systemic reactions in the 7 days after vaccination, adverse events of special interest, COVID-19 infection, mortality and quality of life.DiscussionThis study will enhance the understanding of COVID-19 vaccine responses in ICH, and enable the development of safe, and optimised vaccine schedules in people with HIV, SOT, or haematological malignancy.Trial registrationClinicalTrials.gov NCT05556720. Registered on 23rd August 2022.

Routine Histopathology of Tonsillectomy Specimens, Is It Necessary? A Prospective Observational Study

Routine histopathology of tonsillectomy specimens is not standard practice due to cost and resource constraints. This study aimed to evaluate the prevalence of abnormal histopathologies in tonsillectomy specimens to determine the necessity of routine histopathology. A prospective observational study was conducted from January 2014 to August 2016 at a general tertiary care center after approval of Institutional Ethics Committee (IEC). Patients scheduled for tonsillectomy surgery as per the AAOHNS 2011 criteria were included in the study. All tonsillectomy specimens were sent for histopathology, and abnormal findings were documented. Statistical analysis was performed. A total of 111 patients were enrolled in this study, and 222 tonsillectomy specimens were analyzed. The most common finding was chronic tonsillitis, which justified the selection criteria in 91.89% of patients. Two patients with chronic tonsillitis were also found to have actinomycosis present on the surface without parenchymal tissue reaction. Abnormal histopathological findings were observed in 9 (8.10%) of patients, leading to further investigations or treatment in 8 cases. These abnormalities included chronic granuloma, non-Hodgkin's lymphoma, early squamous cell carcinoma, and one choristoma. Tonsillar asymmetry, recent onset of symptoms and older age were found to be significantly correlated with abnormal histopathology and malignancy. Routine histopathology in tonsillectomy specimens helps to identify important findings that may require additional treatment. Based on the study we strongly recommend routine histopathology of tonsillectomy specimen. When significant cost constraints exist, risk-based approach can be adopted. Factors such as older age, asymmetry of tonsils, referred otalgia, duration of symptoms (recent onset) and a history of addiction should be considered for proceeding with histopathology.

Diffuse large B-cell lymphoma in the uterus with unexpected manifestations: a case report

BackgroundLymphoid neoplasm is a common disease, arising from lymphoid cells. It is divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be intranodular or extranodular, which happens in 25% of primary cases. The most common locations of extranodular non-Hodgkin lymphoma are the skin and gastrointestinal tract. The genital tract is a rare location; most lymphomas arise from the cervix and vagina, while the uterine corpus is an extremely rare location. In our case, the patient was diagnosed with primary extranodular non-Hodgkin lymphoma in different locations of her genital tract.Case presentationA 48-year-old nonparous Syrian woman complained of diffuse abdominal pain, fatigue, debility, high fever, vomiting, and urinary retention for a week. The last menstrual period of the patient was 5 years previously. The physical examination showed periodic abdominal pain with severe fatigue and increased abdominal size. The laboratory investigations were within normal limits except for a low level of hemoglobin and a high level of cancer antigen 125. The radiological investigations showed a uterine sizable lobulated mass with irregular borders and high and heterogeneous density, extending to the right and left ovaries, enlargement lymph nodes around the abdominal aortic and right iliac vessels, and severe right pleural effusion with right inferior lobe atelectasis. A total hysterectomy and oophorectomy were done. The histopathological examination showed that the patient had non-Hodgkin lymphoma (primary tumor).ConclusionPrimary non-Hodgkin lymphoma in the female genital tract is an extremely rare disease. Fast diagnosis and treatment can improve the outcomes, so this differential diagnosis should be in our minds even in the absence of systematic manifestations of lymphoma. More studies are needed to explain the pathology of this disease and to put guidelines that determine the perfect methods for diagnosis and treatment.

Predictive Factors for Early Immune Recovery in NHL Patients after Autologous Transplantation: A Multicenter Prospective Study.

Early lymphocyte recovery as manifested by an absolute lymphocyte count at d+15 (ALC-15) ≥ 0.5 × 109/L after autologous hematopoietic stem cell transplantation (AHCT) has been associated with a better outcome. This prospective multicenter study aimed to clarify factors associated with ALC-15 ≥ 0.5 × 109/L after AHCT among 178 patients with non-Hodgkin lymphoma. The mobilization capacity, as manifested by peak blood CD34+ cell numbers > 45 × 106/L correlated with higher ALC-15 levels (p = 0.020). In addition, the amount of CD3+CD4+ T cells > 31.8 × 106/kg in the infused graft predicted ALC-15 ≥ 0.5 × 109/L (p < 0.001). Also, the number of infused graft CD3+CD8+ T cells > 28.8 × 106/kg (p = 0.017) and NK cells > 4.4 × 106/kg was linked with higher ALC-15 (p < 0.001). The two-year progression-free survival after AHCT was significantly better in patients with ALC-15 ≥ 0.5 × 109/L (74 vs. 57%, p = 0.027). The five-year OS in patients with higher ALC-15 was 78% vs. 60% in those with lower ALC-15 (p = 0.136). To conclude, the mobilization capacity of CD34+ cells and detailed measures of graft cellular content mark prognostic tools that predict ALC-15 ≥ 0.5 × 109/L, which is associated with a better outcome in NHL patients after AHCT.

Clinical features and outcomes of digestive tract perforation in pediatric mature B-cell non-Hodgkin lymphoma

To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage Ⅲ to Ⅳ. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.

Cuproptosis-related gene &lt;i&gt;ATOX1&lt;/i&gt; promotes MAPK signaling and diffuse large B-cell lymphoma proliferation via modulating copper transport

Diffuse Large B-cell lymphoma (DLBCL) is a common subtype of non-Hodgkin lymphoma, highlighting the importance of studying susceptibility genes to develop personalized treatment strategies. While cuproptosis, caused by high levels of copper ions induced by ionophores, has been shown to affect cancer survival, its specific role in lymphoma is not yet clear. To investigate the involvement of upregulation-related genes in DLBCL, we employed bioinformatics techniques. Specifically, we analyzed the differentially expressed genes (DEGs) in the GSE25638 dataset using Weighted Gene Co-expression Network Analysis (WGCNA) and performed functional enrichment analysis. By building a Protein-Protein Interaction (PPI) network, candidate genes were identified. Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curve analysis were used to confirm the clinical diagnostic use of these genes. The effects of Antioxidant 1 (ATOX1) knockdown, CuCl2, and DCAC50 treatments on DLBCL cells and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway were investigated by conducting in vitro experiments. Bioinformatics and in vitro experiments confirmed elevated expression of ATOX1 in DLBCL cells and tumor samples. ATOX1 knockdown led to decreased cell proliferation and G2 cell cycle arrest in vitro. Additionally, Phosphorylated Extracellular Signal-Regulated Kinases 1 and 2 (P-ERK1/2) protein levels within the MAPK pathway were reduced as a result of ATOX1 knockdown, but these levels were recovered by CuCl2. Treatment with DCAC50 showed a dose-dependent antiproliferative effect in DLBCL cells, which was strengthened by ATOX1 knockdown. Our study demonstrated that ATOX1 may be important in DLBCL via controlling the MAPK pathway through copper transport, providing new insights into potential therapeutic strategies for DLBCL.

Advancements in Personalized CAR-T Therapy: Comprehensive Overview of Biomarkers and Therapeutic Targets in Hematological Malignancies.

Chimeric antigen receptor T-cell (CAR-T) therapy is a novel anticancer therapy using autologous or allogeneic T-cells. To date, six CAR-T therapies for specific B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphomas (NHL), and multiple myeloma (MM) have been approved by the Food and Drug Administration (FDA). Significant barriers to the effectiveness of CAR-T therapy include cytokine release syndrome (CRS), neurotoxicity in the case of Allogeneic Stem Cell Transplantation (Allo-SCT) graft-versus-host-disease (GVHD), antigen escape, modest antitumor activity, restricted trafficking, limited persistence, the immunosuppressive microenvironment, and senescence and exhaustion of CAR-Ts. Furthermore, cancer drug resistance remains a major problem in clinical practice. CAR-T therapy, in combination with checkpoint blockades and bispecific T-cell engagers (BiTEs) or other drugs, appears to be an appealing anticancer strategy. Many of these agents have shown impressive results, combining efficacy with tolerability. Biomarkers like extracellular vesicles (EVs), cell-free DNA (cfDNA), circulating tumor (ctDNA) and miRNAs may play an important role in toxicity, relapse assessment, and efficacy prediction, and can be implicated in clinical applications of CAR-T therapy and in establishing safe and efficacious personalized medicine. However, further research is required to fully comprehend the particular side effects of immunomodulation, to ascertain the best order and combination of this medication with conventional chemotherapy and targeted therapies, and to find reliable predictive biomarkers.

Causal association of circulating immune cells and lymphoma: A Mendelian randomization study.

Malignant lymphoma (ML) is a group of malignant tumors originating from the lymphatic hematopoietic system. Previous studies have found a correlation between circulating immune cells and ML. Nonetheless, the precise influence of circulating immune cells on ML remains uncertain. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and ML risk. A total of four types of immune signatures, median fluorescence intensities, relative cell, absolute cell, and morphological parameters were included. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between circulating immune cells and the risk of ML. Sensitivity analysis was conducted using Cochran's Q test, the Mendelian randomization Egger regression intercept test, and leave-one-out analysis. ML had a statistically significant effect on immunophenotypes. Twenty-three immunophenotypes were identified to be significantly associated with Hodgkin lymphoma risk through the IVW approach, and the odds ratio values of CD64 on CD14- CD16+ monocyte [2.31, 95% confidence interval (CI) = 1.41-3.79, P1 = 0.001], IgD+ CD24+ B-cell %lymphocyte (2.06, 95% CI = 1.13-3.79, P1 = 0.018), B-cell %lymphocyte (1.94, 95% CI = 1.08-3.50, P1 = 0.027), CD24+ CD27+ B-cell %lymphocyte (1.68, 95% CI = 1.03-2.74, P1 = 0.039), and CD14+ CD16- monocyte %monocyte (1.60, 95% CI = 1.15-2.24, P1 = 0.006) ranked in the top five. Eleven immunophenotypes were identified to be significantly associated with non-Hodgkin lymphoma risk, CD86 on granulocyte (2.35, 95% CI = 1.18-4.69, P1 = 0.015), CD28-CD8+ T-cell absolute count (1.76, 95% CI = 1.03-2.99, P1 = 0.036), CCR2 on myeloid dendritic cell (CD24+ CD27+ B cell, 95% CI = 1.02-1.66, P1 = 0.034), CD3 on effector memory CD8+ T cell (1.29, 95% CI = 1.02-1.64, P1 = 0.012), and natural killer T %lymphocyte (1.28, 95% CI = 1.01-1.62, P1 = 0.046) were ranked in the top five. This study presents compelling evidence indicating the correlation between circulating immune cells and lymphoma, thus providing guidance for future clinical research.

Exploring the Health Benefits of Boletus aereus Polysaccharides: Extraction, Structural Characterization, and Antiproliferative Properties against Non-Hodgkin's Lymphomas (NHLs).

Boletus aereus Fr. ex Bull. stands out as a delectable edible mushroom with high nutritional and medicinal values, featuring polysaccharides as its primary nutrient composition. In our continuous exploration of its beneficial substances, a novel polysaccharide (BAPN-1) with a molecular weight of 2279 kDa was prepared. It was identified as a glucan with a backbone composed of the residues →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1→ connected in a proportion of 5:1 and a β-Glcp-(1→ side residue attached at C6 of the →4,6)-α-Glcp-(1→ residue. Biologically, BAPN-1 exhibited broad-spectrum antiproliferative activities against various NHL cells, including HuT-78, OCI-LY1, OCI-LY18, Jurkat, RL, and Karpas-299, with IC50 values of 0.73, 1.21, 3.18, 1.52, 3.34, and 4.25 mg/mL, respectively. Additionally, BAPN-1 significantly induced cell cycle arrest in the G2/M phase and caused apoptosis of NHL cells. Mechanistically, bulk RNA sequencing and Western blot analysis revealed that BAPN-1 could upregulate cyclin B1 and enhance cleaved caspase-9 expression through the inhibition of FGFR3 and RAF-MEK-ERK signaling pathways. This work supports the improved utilization of B. aereus in high-value health products.