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Search Results (427)

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Keywords = small-cell lymphoma

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17 pages, 1852 KiB  
Article
Overall Survival Associated with Real-World Treatment Sequences in Patients with CLL/SLL in the United States
by Joanna M. Rhodes, Naleen Raj Bhandari, Manoj Khanal, Dan He, Sarang Abhyankar, John M. Pagel, Lisa M. Hess and Alan Z. Skarbnik
Cancers 2025, 17(15), 2592; https://doi.org/10.3390/cancers17152592 - 7 Aug 2025
Abstract
Background/Objectives: This study compared overall survival (OS) associated with common real-world treatment sequences in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the United States. Methods: Utilizing the nationwide Flatiron Health electronic health record-derived de-identified database, adult CLL/SLL patients who initiated [...] Read more.
Background/Objectives: This study compared overall survival (OS) associated with common real-world treatment sequences in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the United States. Methods: Utilizing the nationwide Flatiron Health electronic health record-derived de-identified database, adult CLL/SLL patients who initiated systemic therapy (JAN2016-NOV2023) and received at least two lines of therapy (LoTs) were analyzed. Treatment regimens were categorized based on drug class, and most frequent (n ≥ 50) sequences (first LoT followed by [→] second LoT) were compared. OS from initiation of the first LoT was compared using multivariable Cox proportional hazard models, and adjusted hazard ratios with 95% CIs were reported. Results: Among 2354 eligible patients, n = 1711 (73%) received the 16 most frequent treatment sequences. Sequencing chemoimmunotherapy (CIT) → CIT (HR: 2.29 [1.23–4.28]), anti-CD20 monoclonal antibody (anti-CD20mab) monotherapy → CIT (1.95 [1.03–3.69]), and covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapy → anti-CD20mab monotherapy (2.00 [1.07–3.74]) were associated with worse OS compared to patients treated with cBTKi monotherapy → B-cell lymphoma 2 inhibitors (BCL2i) + anti-CD20mab (reference). Conclusions: OS associated with other sequences were not significantly different from the reference sequence in adjusted analyses, suggesting a lack of evidence for the optimal standard of care for sequencing the first two LoTs in real-world settings. Future research should reassess sequencing outcomes as novel treatments become adopted into clinical practice. Full article
(This article belongs to the Section Cancer Therapy)
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22 pages, 1241 KiB  
Systematic Review
Safety and Efficacy of Immune Checkpoint Inhibitors in Human Immunodeficiency Virus-Associated Cancer: A Systematic Scoping Review
by Ahmed D. Alatawi, Amirah B. Alaqyl, Reema J. Alalawi, Rahaf S. Alqarni, Razan A. Sufyani, Ghadi S. Alqarni, Raghad S. Alqarni, Jumana H. Albalawi, Raghad A. Alsharif, Ghada I. Alatawi, Elaf N. Albalawi, Danah A. Alanazi, Sultanah A. Naitah, Reem Sayad and Helal F. Hetta
Diseases 2025, 13(8), 230; https://doi.org/10.3390/diseases13080230 - 22 Jul 2025
Viewed by 377
Abstract
Background/Objective: People living with human immunodeficiency virus (PHIV) are at increased risk for malignancies, yet their access to immunotherapy remains limited due to concerns about safety and efficacy. This systematic scoping review evaluates the use of immune checkpoint inhibitors (ICIs) in HIV-associated cancers, [...] Read more.
Background/Objective: People living with human immunodeficiency virus (PHIV) are at increased risk for malignancies, yet their access to immunotherapy remains limited due to concerns about safety and efficacy. This systematic scoping review evaluates the use of immune checkpoint inhibitors (ICIs) in HIV-associated cancers, analyzing patient outcomes, safety profiles, and the impact on HIV status. Methods: A comprehensive literature search was conducted in databases including PubMed, Scopus, Web of Science (WoS), and Medline, up to January 2025. Studies included assessing the efficacy of ICIs in cancer patients with HIV. The primary outcomes were (a) the efficacy of immune ICIs on prognosis, progression-free survival (PFS), and overall survival (OS). Secondary outcomes were the immune-related adverse events (irAEs) and the survival rate of cancer patients receiving ICIs. Results: A total of 107 cases from 19 studies published between 2011 and 2024 were reviewed. Responses to programmed death 1 (PD-1) inhibitors varied, with 27.1% achieving partial response, 23.36% experiencing stable disease, and 6.54% achieving complete response, while 34.57% had disease progression. Adverse events, including hematologic and endocrine toxicities, were common but mostly manageable. HIV viral loads remained stable in most cases. Conclusions: PD-1 inhibitors demonstrated potential efficacy in HIV-associated malignancies with a safety profile comparable to the general population. However, disease progression remained a concern, highlighting the need for optimized patient selection. Further well-controlled trials are essential to establish treatment guidelines and ensure equitable access to immunotherapy for PHIV. Full article
(This article belongs to the Special Issue Cancer Inhibitory Receptors and Related Cancer Immunotherapy)
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20 pages, 3367 KiB  
Review
Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease
by Mario Della Mura, Joana Sorino, Filippo Emanuele Angiuli, Gerardo Cazzato, Francesco Gaudio and Giuseppe Ingravallo
Cancers 2025, 17(14), 2355; https://doi.org/10.3390/cancers17142355 - 15 Jul 2025
Viewed by 308
Abstract
Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence [...] Read more.
Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article
(This article belongs to the Special Issue Advances in Pathology of Lymphoma and Leukemia)
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18 pages, 1867 KiB  
Article
Blood Leukocyte Ratios as Predictive Markers of Chronic Enteropathy Phenotypes in Cats
by Alexandros O. Konstantinidis, Katerina K. Adamama-Moraitou, Ashley Griggs, Margaret L. Musser, Ariel S. Nenninger, Nektarios Soubasis, Dimitra Pardali, Mathios E. Mylonakis and Albert E. Jergens
Vet. Sci. 2025, 12(7), 613; https://doi.org/10.3390/vetsci12070613 - 24 Jun 2025
Viewed by 715
Abstract
This retrospective study assessed the potential of blood leukocyte ratios as diagnostic biomarkers in cats with chronic enteropathies (CE). Absolute neutrophil-to-lymphocyte (NLR), neutrophil-to-monocyte (NMR), and lymphocyte-to-monocyte (LMR) ratios were calculated from the hematological profiles of 221 cats, including healthy controls (n = [...] Read more.
This retrospective study assessed the potential of blood leukocyte ratios as diagnostic biomarkers in cats with chronic enteropathies (CE). Absolute neutrophil-to-lymphocyte (NLR), neutrophil-to-monocyte (NMR), and lymphocyte-to-monocyte (LMR) ratios were calculated from the hematological profiles of 221 cats, including healthy controls (n = 73), and those diagnosed with food-responsive enteropathy (FRE, n = 59), steroid-responsive enteropathy (SRE, n = 56), or small cell lymphoma (SCL, n = 33). SCL cats had higher NLRs than SRE (p = 0.002) and FRE (p = 0.028), and lower LMRs than SRE (p = 0.012) and FRE (p = 0.001). Healthy cats had lower NLRs compared to the FRE (p < 0.001), SRE (p < 0.001), and SCL (p < 0.001) cats and higher LMRs compared to the FRE (p < 0.001), SRE (p < 0.001), and SCL (p < 0.001) cats. Receiver operating characteristic (ROC) curve analysis demonstrated that NLR ≥ 11.6 differentiated SCL from SRE with 87.5% specificity but low sensitivity (39.4%). NMR ≥ 34.5 distinguished FRE from SRE with 52.5% sensitivity and 69.6% specificity. LMR ≥ 3.72 differentiated SRE from SCL with 67.9% sensitivity and 60.6% specificity. Although significant differences in leukocyte ratios were observed among groups, their diagnostic accuracy in differentiating CE phenotypes was suboptimal. These findings suggest that the utility of NLR, NMR, and LMR as standalone diagnostic tools is limited. Full article
(This article belongs to the Section Veterinary Internal Medicine)
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18 pages, 965 KiB  
Review
Refining Criteria for Choosing the First-Line Treatment for Real-World Patients with Advanced ALK-Rearranged NSCLC
by Edyta Maria Urbanska, Peter Rindom Koffeldt, Morten Grauslund, Linea Cecilie Melchior, Jens Benn Sørensen and Eric Santoni-Rugiu
Int. J. Mol. Sci. 2025, 26(13), 5969; https://doi.org/10.3390/ijms26135969 - 21 Jun 2025
Viewed by 731
Abstract
Choosing the optimal first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangements can be challenging in daily practice. Although clinical trials with next-generation ALK-tyrosine kinase inhibitors (TKIs) have played a key role in [...] Read more.
Choosing the optimal first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangements can be challenging in daily practice. Although clinical trials with next-generation ALK-tyrosine kinase inhibitors (TKIs) have played a key role in evaluating their efficacy and safety, which patients benefit from a specific ALK-TKI may still be questioned. The methodological inconsistencies in these trials, which led to the inclusion of different patient populations, appear to have been inadequately addressed. ALK-rearranged NSCLC is a heterogeneous disease, and co-existing molecular alterations may affect the outcome. The questions explored in these trials appear insufficient to support a personalized approach to the first-line treatment, while defining long-term responders and early progressors would be clinically useful. This narrative review presents several considerations from oncologists’ and pathologists’ perspectives. We propose defining favorable and unfavorable features, such as histology, type of ALK fusion, co-existing molecular alterations, plasma circulating tumor DNA (ctDNA, performance status, and brain metastases, to help identify patients with lower and higher risk of progression. Consequently, the most potent ALK-TKI to date, Lorlatinib, may be considered as the first-line treatment for high-risk patients with unfavorable features, while sequencing of ALK-TKIs may be appropriate for low-risk patients with favorable features. Although ALK signal inhibition is critical in this disease, it may not be sufficient for clinical control due to de novo co-alterations. A more personalized approach to first-line therapy requires consideration of risk factors for each patient. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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15 pages, 1458 KiB  
Article
Novel In Vitro Selection of Trans-Acting BCL-2 mRNA-Cleaving Deoxyribozymes for Cancer Therapy
by Veera Vijaya Basamshetty, Vijay Kumar Gangipangi, Uppulapu Shravan Kumar, Santhosh Shanthi Bhupathi, Sridhar Reddy Kaulagari, Prashant Giri, Swapnil Sinha, Utpal Mohan and Konstantinos Sdrimas
Cells 2025, 14(13), 945; https://doi.org/10.3390/cells14130945 - 20 Jun 2025
Viewed by 1555
Abstract
The B Cell Lymphoma-2 (BCL-2) family proteins are central regulators of apoptosis, and their dysregulation is frequently associated with cancer progression and resistance to therapy. While small molecules like venetoclax have shown promise, nucleic acid-based therapeutics targeting BCL-2 remain underexplored. Here, [...] Read more.
The B Cell Lymphoma-2 (BCL-2) family proteins are central regulators of apoptosis, and their dysregulation is frequently associated with cancer progression and resistance to therapy. While small molecules like venetoclax have shown promise, nucleic acid-based therapeutics targeting BCL-2 remain underexplored. Here, we report a novel in vitro evolution strategy to generate trans-acting RNA-cleaving DNAzymes targeting natural BCL-2 mRNA without requiring covalent substrate-linking. Using a 50-base region of BCL-2 mRNA as a selection target, we evolved several DNAzymes that demonstrate significant RNA cleavage activity. These DNAzymes downregulated BCL-2 expression, induced apoptosis, and reduced cell viability in HepG2 and MCF-7 cancer cells. In vivo, our novel DNAzymes significantly suppressed tumor growth in a syngeneic mouse breast cancer model, with efficacy comparable to 5-Fluorouracil. This study presents a proof of concept for a novel strategy to evolve functional DNAzymes against native mRNA sequences and highlights their potential as gene-silencing tools in cancer therapy. Future studies will explore the therapeutic potential of these findings in cancer patients. Additionally, investigating the underlying molecular mechanisms in more complex cancer models will further validate the observed effects. Full article
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25 pages, 540 KiB  
Review
Malignancies in Celiac Disease—A Hidden Threat with Diagnostic Pitfalls
by Aleksandra Kubas and Ewa Małecka-Wojciesko
Biomedicines 2025, 13(6), 1507; https://doi.org/10.3390/biomedicines13061507 - 19 Jun 2025
Viewed by 690
Abstract
Celiac disease (CeD) is an autoimmune disorder that is triggered by gluten ingestion in genetically predisposed individuals. Untreated or poorly controlled CeD leads to various disease complications, such as malnutrition, osteoporosis, autoimmune diseases, or refractory celiac disease (RCD). Accumulating recent research has highlighted [...] Read more.
Celiac disease (CeD) is an autoimmune disorder that is triggered by gluten ingestion in genetically predisposed individuals. Untreated or poorly controlled CeD leads to various disease complications, such as malnutrition, osteoporosis, autoimmune diseases, or refractory celiac disease (RCD). Accumulating recent research has highlighted the association between CeD and the development of malignancies, particularly enteropathy-associated T-cell lymphoma (EATL) and small bowel carcinoma (SBC), which are neoplasms with extremely poor prognoses. Genetic alterations in the JAK1–STAT3 pathway and the high prevalence of microsatellite instability may be the main drivers of CeD-associated lymphomagenesis and small bowel oncogenesis and therefore could be an attractive therapeutic target to block cancer transformation. However, to date, the risk factors and exact mechanisms underlying malignancy development in patients with CeD remain unclear, and prospective cohort studies that include molecular profiling are needed. Moreover, current guidelines on the management of CeD do not provide standardized protocols for cancer surveillance—particularly regarding screening intervals, risk stratification, and monitoring strategies for high-risk patients such as those with RCD. This paper reviews the existing knowledge on malignancies in CeD, highlights diagnostic challenges, and discusses future perspectives on the early detection, monitoring, and treatment of CeD-associated neoplasms. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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13 pages, 1648 KiB  
Article
KAT/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas
by Chiara Tarantelli, Filippo Spriano, Elisa Civanelli, Luca Aresu, Giorgia Risi, Eleonora Cannas, Omar Kayali, Luciano Cascione, Alberto J. Arribas, Anastasios Stathis, Young H. Ko and Francesco Bertoni
Cancers 2025, 17(12), 2034; https://doi.org/10.3390/cancers17122034 - 18 Jun 2025
Viewed by 602
Abstract
Background/Objectives: Reprogramming of the cellular metabolism is a hallmark of cancer, offering therapeutic opportunities to target cancer cell vulnerabilities for therapeutic purposes. 3-Bromopyruvate (3BP) is a small alkylating agent that functions as an anti-metabolite, targeting key substrates in cancer metabolism and demonstrating antitumor [...] Read more.
Background/Objectives: Reprogramming of the cellular metabolism is a hallmark of cancer, offering therapeutic opportunities to target cancer cell vulnerabilities for therapeutic purposes. 3-Bromopyruvate (3BP) is a small alkylating agent that functions as an anti-metabolite, targeting key substrates in cancer metabolism and demonstrating antitumor activity across multiple cancer types. However, unformulated 3BP is associated with significant toxicity. This study investigates the efficacy of KAT/3BP, a clinical derivative of 3BP currently in phase 1 trials for hepatocellular carcinoma, in preclinical lymphoma models. Results: In vitro, KAT/3BP exhibited cytotoxic activity across 12 lymphoma cell lines—including diffuse large B-cell lymphoma and mantle cell lymphoma—with a median IC50 of 3.7 μM. It also remained effective against lymphoma cell lines with acquired resistance to FDA-approved therapies. In vivo, treatment with KAT/3BP led to reduced tumor size in a syngeneic mouse model, with the combination of oral and intratumoral administration showing the greatest efficacy. Furthermore, KAT/3BP demonstrated synergistic activity when combined with standard lymphoma therapies such as bendamustine and R-CHOP. Conclusions: Our findings highlight the potential of KAT/3BP as a novel therapeutic option, either as a single agent or in combination regimens, for treating lymphomas. Full article
(This article belongs to the Special Issue Combination Therapy in Lymphoma)
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22 pages, 333 KiB  
Review
Diagnostic Challenges in Enteropathies: A Histopathological Review
by Iulia Enache, Ioan-Cristian Nedelcu, Marina Balaban, Daniel Vasile Balaban, Alina Popp and Mariana Jinga
Diagnostics 2025, 15(12), 1511; https://doi.org/10.3390/diagnostics15121511 - 13 Jun 2025
Viewed by 803
Abstract
Various enteropathies, including immune-mediated (IME) and infection-related conditions, can lead to small intestinal mucosal injury and malabsorption. While immune dysregulation plays a central role in diseases like celiac disease and autoimmune enteropathy, other conditions such as small intestinal bacterial overgrowth (SIBO) and tropical [...] Read more.
Various enteropathies, including immune-mediated (IME) and infection-related conditions, can lead to small intestinal mucosal injury and malabsorption. While immune dysregulation plays a central role in diseases like celiac disease and autoimmune enteropathy, other conditions such as small intestinal bacterial overgrowth (SIBO) and tropical sprue (TS) involve infectious or microbial pathogenesis. Common clinical manifestations include weight loss, chronic diarrhea, and nutritional deficiencies. While celiac disease (CD) remains the most prevalent IME in adults, an expanding spectrum of non-celiac enteropathies has been recognized, including autoimmune enteropathy (AIE), common variable immunodeficiency disease (CVID), olmesartan-induced enteropathy, tropical sprue, and small intestinal bacterial overgrowth. These conditions often present with overlapping clinical, serological, and histological features, complicating their differentiation from CD. Accurate diagnosis is critical for the timely initiation of effective treatment to prevent disease progression and associated complications such as severe malabsorption and enteropathy-associated T-cell lymphoma (EATL). The small intestine plays a dual role in nutrient absorption and immune regulation, making it uniquely vulnerable to immune dysregulation. In IMEs, hyperactive immune responses disrupt intestinal homeostasis, leading to mucosal damage and impaired nutrient absorption. Although CD is the prototypical IME, increasing the recognition of non-celiac IMEs, it highlights the need for a more nuanced approach to small bowel biopsy interpretation. This review explores the histopathological and clinical features of common IMEs, with a focus on distinguishing non-celiac disorders that mimic CD. By enhancing the understanding of these conditions, this review aims to improve diagnostic accuracy, facilitate appropriate therapeutic interventions, and mitigate complications associated with delayed or misdiagnosis. A multidisciplinary approach involving gastroenterologists and pathologists is emphasized to optimize outcomes for patients with IMEs. Immune-mediated enteropathies result from an abnormal immune response of the small intestinal mucosa to non-pathogenic molecules, often leading to malabsorption syndrome. The most common symptoms include weight loss, chronic diarrhea, and nutritional deficiencies. While celiac disease (CD) is the most well-known immune-mediated enteropathy (IME) in adults, other related disorders have been identified in recent years. These conditions share many clinical and histopathological features, therefore making differentiations between them challenging. This study aims to review the most common immune-mediated enteropathies, with a focus on non-celiac disorders that should be considered in the differential diagnosis of celiac disease in small bowel biopsies. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
14 pages, 631 KiB  
Article
Evaluation of Navify Mutation Profiler Tertiary Analysis Software Assessing for Hematologic Malignancies
by Ruby Singhrao, Michael J. Clark, Shikha Chugh, Lisha Capucion, Shuba Krishna, Ranga Yerram, Lili Niu, Adama Parham, Amy Harrell, John Duncan, Kristina Clark and Manana Javey
J. Mol. Pathol. 2025, 6(2), 9; https://doi.org/10.3390/jmp6020009 - 22 May 2025
Viewed by 753
Abstract
Background: Navify® Mutation Profiler (Navify MP) is a cloud-based, tertiary analysis software that provides curation, annotation, and reporting of somatic genomic alterations and biomarker signatures identified by next-generation sequencing. The Navify MP software leverages Association for Molecular Pathology/American Society of Clinical Oncology/College [...] Read more.
Background: Navify® Mutation Profiler (Navify MP) is a cloud-based, tertiary analysis software that provides curation, annotation, and reporting of somatic genomic alterations and biomarker signatures identified by next-generation sequencing. The Navify MP software leverages Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists (AMP/ASCO/CAP) Somatic Variant Classification Guidelines to provide information on detected somatic genomic variants and associated therapies according to region-specific approvals. Methods: This validation study assessed the accuracy of the Navify MP software and curation process for hematologic malignancies as compared to expert opinion. A total of 86 variants derived from hematologic malignancies (including myeloid and lymphoid leukemias, B cell lymphomas, and multiple myeloma) were used to contrive 12 VCF files. The VCFs were made up of the following classes of genomic alterations: single nucleotide variants, small insertions and deletions, fusions, and copy number alterations. Of the 86 variants, 42 were Tier IA, and 44 were non-Tier IA, based on AMP/ASCO/CAP classification. The study was performed at four sites with seven software users (molecular genetics experts). Results: Tier classification agreement between Navify MP and expert user assignment was 91.34% for Tier IA and 95.02% across all hematologic variants. The agreement on associated therapies for the Navify MP-classified Tier IA hematologic variants was 99.08%. Conclusions: Navify MP is a robust automated solution for genomic variant reporting of hematologic malignancies and remains up to date with evolving regional approvals and medical guidelines. Full article
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16 pages, 3204 KiB  
Article
Intestinal Ultrasonographic Measurements in Cats Diagnosed with Lymphoplasmacytic Enteritis and Low-Grade T-Cell Lymphoma Based on Either Histology/Immunohistochemistry or Clonality Testing—And Assessment of the Effects of Therapy on Wall Layering After 3 and 6 Months of Treatment
by Laura Beatrice, Junwei Föhr, Paula Grest, Maja Ruetten, Manfred Henrich, Simona Vincenti, Karolin Campbell and Peter Hendrik Kook
Animals 2025, 15(11), 1518; https://doi.org/10.3390/ani15111518 - 22 May 2025
Viewed by 1249
Abstract
It is unknown whether intestinal ultrasonographic measurements differ between lymphoplasmacytic enteritis (LPE) and low-grade intestinal T-cell lymphoma (LGITL) in cats if the diagnosis is based either on histology/immunohistochemistry (IHC) or on clonality assay results. The effects of treatment on intestinal ultrasonographic measurements are [...] Read more.
It is unknown whether intestinal ultrasonographic measurements differ between lymphoplasmacytic enteritis (LPE) and low-grade intestinal T-cell lymphoma (LGITL) in cats if the diagnosis is based either on histology/immunohistochemistry (IHC) or on clonality assay results. The effects of treatment on intestinal ultrasonographic measurements are also unknown. Therefore, we prospectively compared small intestinal wall layering between cats with LPE and LGITL and investigated whether there were differences between the groups when the diagnostic gold standard was either histology/IHC or clonality testing. We evaluated the effects of standardized treatment in a subset of cats. The thicknesses of the total wall, mucosa, muscularis, and submucosa were measured in the duodenum, jejunum, and ileum, and ratios (muscularis to submucosa, muscularis to total wall thickness) were calculated. The thickness of the largest mesenteric lymph nodes was also determined. Ultrasonographic measurements from duodenal and jejunal segments were grouped together, and ileal segments were assessed separately. Sixteen cats with standardized full-thickness biopsies from the stomach, duodenum, jejunum, and ileum were included. Samples for clonality testing were fresh-frozen and analyzed later, and the standardized treatment was based on histologic/IHC diagnoses. Ultrasonographic measurements were compared between LPE and LGITL when diagnoses were either based on histology/IHC or clonality testing using a linear mixed model. Repeated ultrasonographic measurements of segments were available for seven cats after 12 weeks (five LPE, two LGITL) and five cats after 24 weeks (three LPE, two LGITL) of standardized treatment. We found that none of the ultrasonographic measurements differed between LPE and LGITL regardless of the diagnostic gold standard used. During treatment, only the ratio of lamina muscularis thickness to total wall thickness decreased significantly in LPE cats after 12 and 24 weeks compared to baseline. In conclusion, the herein evaluated ultrasonographic variables did not differ between LPE and LGITL and the diagnostic gold standard used had no influence on the results. The detected change over time during treatment in LPE cats requires further study. Full article
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26 pages, 4181 KiB  
Article
Alleviating the Effect of Branched-Chain Fatty Acids on the Lipopolysaccharide-Induced Inflammatory Response in Calf Small Intestinal Epithelial Cells
by Siqi Zhang, Qingyuan Yu, Yukun Sun, Guangning Zhang, Yonggen Zhang and Hangshu Xin
Antioxidants 2025, 14(5), 608; https://doi.org/10.3390/antiox14050608 - 19 May 2025
Viewed by 830
Abstract
This study examined branched-chain fatty acids (BCFAs)’ effects on oxidative stress, energy metabolism, inflammation, tight junction disruption, apoptosis, and Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling in lipopolysaccharide (LPS)-induced calf small intestinal epithelial cells (CSIECs). Eight groups were used: a control [...] Read more.
This study examined branched-chain fatty acids (BCFAs)’ effects on oxidative stress, energy metabolism, inflammation, tight junction disruption, apoptosis, and Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling in lipopolysaccharide (LPS)-induced calf small intestinal epithelial cells (CSIECs). Eight groups were used: a control group, an LPS-induced group, and six BCFA treatment groups (12-methyltridecanoic acid (iso-C14:0), 13-methyltetradecanoic acid (iso-C15:0), 14-methylpentadecanoic acid (iso-C16:0), 15-methylhexadecanoic acid (iso-C17:0), 12-methyltetradecanoic acid (anteiso-C15:0), and 14-methylhexadecanoic acid (anteiso-C17:0)) with LPS. The BCFA pretreatments significantly increased CSIEC activity compared to the LPS-induced group, with iso-C14:0 showing the highest activity (89.73%). BCFA reduced Reactive Oxygen Species (ROS) generation and malondialdehyde (MDA) levels and improved the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities and glutathione (GSH) levels. Iso-C16:0 optimized total antioxidant capacity (T-AOC). BCFA enhanced the mitochondrial membrane potential, Adenosine Triphosphate (ATP) enzyme activity, and ATP content, with iso-C14:0 increasing ATP by 27.01%. BCFA downregulated interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, and interferon (INF)-γ gene expression, reduced IL-6 levels, and increased IL-10 expression. Myeloid differentiation factor 88 (MyD88) mRNA levels were reduced. BCFA alleviated Zonula Occludin (ZO-1), Claudin-1, and Claudin-4 decrease and increased Occludin levels. BCFA mitigated LPS-induced increases in Caspase-3 and BCL2-Associated X (BAX) mRNA levels, reduced Caspase-8 and Caspase-9 expression, and increased B-Cell Lymphoma-2 (BCL-2) mRNA levels. The Entropy Weight-TOPSIS method was adopted, and it was discovered that iso-C15:0 has the best effect. In summary, BCFA supplementation mitigated oxidative stress and enhanced mitochondrial function. BCFA inhibited TLR4/NF-κB signaling pathway overactivation, regulated inflammatory cytokine gene expression, reduced cellular apoptosis, preserved tight junction integrity, and supported barrier function. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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16 pages, 810 KiB  
Review
Bruton’s Tyrosine Kinase: A Double-Edged Sword in Cancer and Aging
by Zahraa Qusairy and Miran Rada
Kinases Phosphatases 2025, 3(2), 10; https://doi.org/10.3390/kinasesphosphatases3020010 - 7 May 2025
Viewed by 996
Abstract
Bruton’s tyrosine kinase (BTK) is a key signaling molecule involved in both hematological malignancies and solid tumors. In B-cell malignancies such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), BTK mediates B-cell receptor signaling, promoting tumor survival and proliferation, leading to the [...] Read more.
Bruton’s tyrosine kinase (BTK) is a key signaling molecule involved in both hematological malignancies and solid tumors. In B-cell malignancies such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), BTK mediates B-cell receptor signaling, promoting tumor survival and proliferation, leading to the development of BTK inhibitors like ibrutinib that improve patient outcomes. In solid tumors, BTK isoforms, particularly p65BTK, contribute to tumor growth and therapy resistance, with inhibition showing promise in cancers like colorectal, ovarian, and non-small cell lung cancer. BTK also influences the tumor microenvironment by modulating immune cells such as myeloid-derived suppressor cells and tumor-associated macrophages, aiding immune evasion. BTK inhibition can enhance anti-tumor immunity and reduce inflammation-driven tumor progression. Additionally, BTK contributes to tumor angiogenesis, with inhibitors like ibrutinib showing anti-angiogenic effects. Beyond cancer, BTK is linked to aging, where its modulation may reduce senescent cell accumulation and preserve cognitive function. This review explores BTK’s dual role, focusing on its oncogenic effects and potential impact on aging processes. We also discuss the use of BTK inhibitors in cancer treatment and their potential to address age-related concerns, providing a deeper understanding of BTK as a therapeutic target and mediator in the complex relationship between cancer and aging. Full article
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7 pages, 3451 KiB  
Case Report
Combination of Osimertinib and Brigatinib in the Treatment of EGFR Triple-Mutated Lung Adenocarcinoma: A Case Report
by Daphnée Demers and Marie Florescu
Curr. Oncol. 2025, 32(5), 270; https://doi.org/10.3390/curroncol32050270 - 7 May 2025
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Abstract
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in treating patients with EGFR-mutated non-small-cell lung cancers (NSCLCs), especially in cases with secondary resistance mutations. However, tertiary resistance mutations often arise, and there is currently no established [...] Read more.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in treating patients with EGFR-mutated non-small-cell lung cancers (NSCLCs), especially in cases with secondary resistance mutations. However, tertiary resistance mutations often arise, and there is currently no established standard of care for NSCLC harboring triple EGFR mutations. In recent years, brigatinib, an anaplastic lymphoma kinase (ALK) TKI, has shown effectiveness in treating EGFR triple-mutated NSCLC. Despite this, the combined use of osimertinib and brigatinib remains largely unstudied. This case report describes a 51-year-old woman with EGFR-mutated NSCLC who was initially treated with first- and second-generation EGFR TKIs, then switched to osimertinib upon development of an exon 20 T790M mutation. When an exon 20 C797S mutation emerged, the decision was made to add brigatinib to the osimertinib regimen. The combined treatment of osimertinib and brigatinib offers a promising new approach. Nonetheless, it is important to consider the potential risk of off-target toxicities. Full article
(This article belongs to the Section Thoracic Oncology)
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Case Report
Refractory/Relapsed Classic Hodgkin Lymphoma Mimicking Disseminated Tuberculosis
by Mohamed Nazem Alibrahim, Hussein Hammam, Antonino Carbone, Noor Alsaleh and Annunziata Gloghini
Hemato 2025, 6(2), 12; https://doi.org/10.3390/hemato6020012 - 3 May 2025
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Abstract
Background/Objectives: Classic Hodgkin lymphoma (cHL) is a predominantly curable B-cell malignancy. However, primary refractory and relapsed (R/R) cHL remain therapeutic challenges, especially in regions with high tuberculosis (TB) prevalence, where clinical and radiologic features overlap and can obscure the correct diagnosis. This article, [...] Read more.
Background/Objectives: Classic Hodgkin lymphoma (cHL) is a predominantly curable B-cell malignancy. However, primary refractory and relapsed (R/R) cHL remain therapeutic challenges, especially in regions with high tuberculosis (TB) prevalence, where clinical and radiologic features overlap and can obscure the correct diagnosis. This article, presenting a case of R/R cHL mimicking disseminated TB, reviews the evolving paradigm in R/R cHL management. Methods: A 30-year-old Middle Eastern male with advanced nodular sclerosis cHL initially achieved a complete remission (CR) with escalated BEACOPP chemotherapy. Shortly afterward, he developed respiratory symptoms and diffuse miliary pulmonary nodules, highly suggestive of disseminated TB. Despite extensive negative TB workup, including QuantiFERON-TB Gold testing, sputum acid-fast bacilli (AFB) staining, and PCR, his imaging raised concern for recurrent cHL. Due to the small size and diffuse distribution of nodules, biopsy was unfeasible, prompting empiric salvage therapy with DEHAP-Carbo, brentuximab vedotin (BV), and nivolumab. Results: The rapid and robust metabolic response on PET/CT supported lymphoma relapse rather than TB. Following four cycles of this combined regimen, he proceeded to autologous stem cell transplantation and achieved a second CR. Conclusions: This case highlights the diagnostic difficulties in differentiating cHL relapse from TB in endemic regions, emphasizes the critical role of PET/CT in guiding therapy when histopathological confirmation is impractical, and illustrates the impact of novel immunotherapies in improving outcomes. By underscoring the importance of early diagnostic suspicion and multimodal assessment, this article also reviews the evolving paradigm in R/R cHL management, where personalized approaches and targeted agents increasingly complement or replace traditional chemotherapy regimens. Full article
(This article belongs to the Section Lymphomas)
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