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FOXM1 contributes to treatment failure in acute myeloid leukemia.

Acute myeloid leukemia (AML) patients with NPM1 mutations demonstrate a superior response to standard chemotherapy treatment. Our previous work has shown that these favorable outcomes are linked to the cytoplasmic relocalization and inactivation of FOXM1 driven by mutated NPM1. Here, we went on to confirm the important role of FOXM1 in increased chemoresistance in AML. A multiinstitution retrospective study was conducted to link FOXM1 expression to clinical outcomes in AML. We establish nuclear FOXM1 as an independent clinical predictor of chemotherapeutic resistance in intermediate-risk AML i

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… Current genomic predictors of resistance to induction chemotherapy in AML include mutations in RUNX1, ASXL1, and TP53; elevated SNP-A–based genomic complexity; and specific recurrent copy number aberrations/loss of heterozygosity ( 32 ). …

A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges.

Fibroblast growth factors (FGFs) orchestrate a variety of cellular functions by binding to their transmembrane tyrosine-kinase receptors (FGFRs) and activating downstream signalling pathways, including RAS/MAPK, PLCγ1, PI3K, and STATs. In the last ten years, it has become clear that FGF signalling is altered in a high proportion of bladder tumours. Activating mutations and/or overexpression of FGFR3 are common in urothelial tumours with low malignant potential and low-stage and -grade urothelial carcinomas (UCs) and are associated with a lower risk of progression and better survival in some su

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… Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma. Oncogene. 2001;20(6):686–691. doi: 10.1038/sj.onc.1204110. 27. van Rhijn BWG, Montironi R, Zwarthoff EC, Jöbsis AC, van der Kwast TH. Frequent FGFR3 mutations in urothelial papilloma. …

New Insights into the Pathogenesis of Systemic Mastocytosis.

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management o

T cells in gastric cancer: friends or foes.

Gastric cancer is the second cause of cancer-related deaths worldwide. Helicobacter pylori is the major risk factor for gastric cancer. As for any type of cancer, T cells are crucial for recognition and elimination of gastric tumor cells. Unfortunately T cells, instead of protecting from the onset of cancer, can contribute to oncogenesis. Herein we review the different types, "friend or foe", of T-cell response in gastric cancer.

Adoptive cell therapies in solid tumors: current clinical landscape, challenges, and future directions.

Adoptive cell therapy (ACT) has emerged as a transformative strategy in cancer immunotherapy, offering durable clinical benefit in hematologic malignancies and expanding therapeutic potential in solid tumors. However, the translation of ACT to solid malignancies remains constrained by biological, immunological, and logistical challenges. This narrative review provides an evidence based overview of the current clinical landscape of ACT in solid tumors, with a focus on chimeric antigen receptor T cell (CAR-T), tumor-infiltrating lymphocyte (TIL), and T cell receptor-engineered T cell (TCR-T) the

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… EVEREST-2: Initial data of the logic-gated Tmod chimeric antigen receptor T-cell (CAR T) therapy A2B694 for patients with solid tumors associated with mesothelin (MSLN) expression and with human leukocyte antigen (HLA) loss of heterozygosity (LOH) . … PMID: 41909186 28 Ward J Randolph Hecht J Kirtane K Spencer K Marar R Garon E . 535 EVEREST-2: a phase 1/2 study of A2B694, a logic-gated Tmod CAR T therapy to treat solid tumors expressing mesothelin (MSLN) with HLA-A*02 loss of heterozygosity: initial safety and efficacy results . …

Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios.

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis. Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cf

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… Additionally, Anna Rogers suggested the utility of detecting the loss of heterozygosity (LOH) in cfDNA for leukemia prognosis. However, considering resource limitations, comprehensive sequencing of cfDNA may not be feasible for all patients. …

Cancer evolution: mathematical models and computational inference.

Cancer is a somatic evolutionary process characterized by the accumulation of mutations, which contribute to tumor growth, clinical progression, immune escape, and drug resistance development. Evolutionary theory can be used to analyze the dynamics of tumor cell populations and to make inference about the evolutionary history of a tumor from molecular data. We review recent approaches to modeling the evolution of cancer, including population dynamics models of tumor initiation and progression, phylogenetic methods to model the evolutionary relationship between tumor subclones, and probabilisti

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… of heterozygosity; Loss of one parental allele with or without a copy number change. logR | Logarithmic intensity ratio of tumor and control DNA in an array CGH experiment. … The dynamics of TSG inactivation are more complex, because here two alleles need to be hit, either by two point mutations, or by one point mutation and loss of heterozygosity (LOH). For simplicity, we assume that the first hit does not confer any selective advantage. …

Role of microRNAs in hematological malignancies research: A bibliometric analysis.

ObjectivesMicroRNAs (miRNAs) are pivotal regulators of cancer biology, including hematological malignancies. Their roles include tumor suppression, oncogenic activities, modulation of immune responses, and treatment resistance. This study aimed to provide a quantitative analysis of research trends, thematic evolution, and key contributions to the field of miRNAs and hematological malignancies.MethodsUsing BIBLIO-Checklist and advanced visualization tools (VOSviewer and bibliometrix), data from key databases were analyzed for publication trends, author co-citations, thematic clusters, and emerg

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… According to Calin et al, human miRNA genes are often found in fragile sites and known cancer regions of the genome, such as loss of heterozygosity and amplification. …

Хроническое низкосортное воспаление, генетическая восприимчивость и риск множественных склерозов: перспективное когортное исследование.

КОЛИЧЕСТВО: Иммунное регулирование дискрипции имеет центральное значение для многочисленных патогенеза склероза (MS), однако потенциальные данные, связывающие периферийные низкосортные воспаления (LGI) с риском НР, остаются ограниченными и непоследовательными. Мы расследовали связь LGI с риском случившегося и связанными с MS структурными мерами мозга в большой потенциальной группе. Мы проанализировали данные, полученные от 377,487 Участники < < Биобанка > > Соединенного Королевства 40 в адрес 69 Годы. Комбинированный показатель воспаления (INFLA-score) был получен на основе C-реакт

Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia.

Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients w

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… The mechanisms involved in the regulation of SOCS1 expression include aberrant DNA methylation, gene mutation, loss of heterozygosity and others. …

Comprehensive understanding of the adverse effects associated with temozolomide: a disproportionate analysis based on the FAERS database.

BACKGROUND: Temozolomide, which is the standard drug for glioma treatment, has several Adverse events (AEs) in the treatment of gliomas and other tumors that are not yet fully understood. This is due to the pharmacological nature of the alkylating agent. A significant proportion of these effects have not been systematically documented or reported. METHODS: We selected data from the United States FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2023. Four algorithms were used for disproportionate analysis, with the objective of assessi

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… Acquired aplastic anemia may be linked to frequent loss of HLA alleles associated with copy number-neutral 6p arms loss of heterozygosity ( Katagiri et al., 2011 ). …

Recognition and management of persistent chylomicronemia: A Joint Expert Clinical Consensus by the National Lipid Association and the American Society for Preventive Cardiology.

Extreme hypertriglyceridemia, defined as triglyceride (TG) levels ≥1000 mg/dL, is almost always indicative of chylomicronemia. The current diagnostic approach categorizes individuals with chylomicronemia into familial chylomicronemia syndrome (FCS; prevalence 1-10 per million), caused by the biallelic combination of pathogenic variants that impair the lipolytic action of lipoprotein lipase (LPL), or multifactorial chylomicronemia syndrome (MCS, 1 in 500). A pragmatic framework should emphasize the severity of the phenotype and the risk of complications. Therefore, we endorse the term "persiste

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs-including spheroids, organo

Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.

Over the past two decades, Next-Generation Sequencing (NGS) has revolutionized the approach to cancer research. Applications of NGS include the identification of tumor specific alterations that can influence tumor pathobiology and also impact diagnosis, prognosis and therapeutic options. Pharmacogenomics (PGx) studies the role of inheritance of individual genetic patterns in drug response and has taken advantage of NGS technology as it provides access to high-throughput data that can, however, be difficult to manage. Machine learning (ML) has recently been used in the life sciences to discover

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… In addition, sequencing of paired tumor and normal tissues allows unambiguous identification of individual germline and somatic variants as well as loss of heterozygosity and the “second hit” mutations ( Mandelker and Ceyhan-Birsoy, 2020 ). … Targeted panels are often designed to provide information on known biomarkers such as genomic instability score (GIS), loss of heterozygosity (LOH), microsatellite instability (MSI), and tumor mutation burden (TMB). …

Malignancies in systemic rheumatic diseases: A mini review.

There is an increased risk of malignancies in patients with many systemic rheumatic diseases, which negatively impact on their quality of life. The risk and types of malignancies can differ by the type of rheumatic diseases. Possible mechanisms linking them are dynamic and complicated, including chronic inflammation and damage in rheumatic disease, inability to clear oncogenic infections, shared etiology and some anti-rheumatic therapies. Although certain disease-modifying anti-rheumatic drugs (DMARDs) have been proved to be potentially carcinogenic, the majority of them were not associated wi

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… Tumour TIF1 mutations and loss of heterozygosity related to cancer-associated myositis . Rheumatol (Oxford) ( 2018 ) 57 ( 2 ): 388–96 . doi: 10.1093/rheumatology/kex413 PMC5850766 29149307 34 Lafyatis R Valenzi E . Assessment of disease outcome measures in systemic sclerosis . …

The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.

Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in

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… Potential contributory factors of post-TIL failure include TµE alteration, immunosuppressive signaling or evolution of tumor molecular profiles over space and time. 94 This could be associated with defects in the antigen processing and presentation machinery, including HLA-I/II loss of heterozygosity … This could be detected imperfectly through the finding of loss of heterozygosity (LOH) at the Chromosome 6p MHC locus because large chromosomal deletions were the most common mediating event. 223 This has been found as the cause of primary immune resistance to T cell therapy with class I reactivity and …

The role of interleukin-17 in inflammation-related cancers.

Emerging evidence indicates a correlation between inflammation and the development and progression of cancer. Among the various inflammatory signals, interleukin-17 (IL-17) family cytokines serve as a critical link between inflammation and cancer. IL-17 is a highly versatile pro-inflammatory cytokine that plays a pivotal role in host defense, tissue repair, the pathogenesis of inflammatory diseases, and cancer progression. During the early stages of tumorigenesis, IL-17 signaling directly promotes the proliferation of tumor cells. Conversely, IL-17 has been shown to exhibit antitumor immunity

NTP toxicology and carcinogensis studies of vanadium pentoxide (CAS No. 1314-62-1) in F344/N rats and B6C3F1 mice (inhalation).

UNLABELLED: Vanadium pentoxide, commercially the most important compound of vanadium, presents a potential occupational hazard during the cl … lasia was present in many exposed females. MOLECULAR ONCOLOGY STUDIES: K-ras codon 12 mutation and loss of heterozygosity on chromosome 6 were detected in vanadium pentoxide-induced alveolar/bronchiolar carcinomas from mice. GENETIC TOXICOLOGY: Vanadium pentoxide was not mutagenic in Salmonella typhimurium strain TA97, TA98, TA100, TA102, or TA1535, with or without in …

Spontaneous genomic alterations in a chimeric model of colorectal cancer enable metastasis and guide effective combinatorial therapy.

Colon cancer is the second most common cause of cancer mortality in the Western world with metastasis commonly present at the time of diagnosis. Screening for propagation and metastatic behavior in a novel chimeric-mouse colon cancer model, driven by mutant p53 and β-Catenin, led to the identification of a unique, invasive adenocarcinoma. Comparison of the genome of this tumor, CB42, with genomes from non-propagating tumors by array CGH and sequencing revealed an amplicon on chromosome five containing CDK6 and CDK14, and a KRAS mutation, respectively. Single agent small molecule inhibition of

ProTarget: a Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on genomic profiling - a national, phase 2, prospective, multi-drug, non-randomized, open-label basket trial.

BackgroundAn increasing number of trials indicate that treatment outcomes in cancer patients with metastatic disease are improved when targeted treatments are matched with druggable genomic alterations in individual patients (pts). An estimated 30-80% of advanced solid tumors harbor actionable genomic alterations. However, the efficacy of personalized cancer treatment is still scarcely investigated in larger, controlled trials due to the low frequency and heterogenous distribution of druggable alterations among different histologic tumor types. Therefore, the overall effect of targeted cancer