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A comparative analysis of transcriptomics of newly diagnosed multiple myeloma: exploring drug repurposing.

Multiple myeloma (MM) is an incurable malignant plasma cell disorder characterized by the infiltration of clonal plasma cells in the bone marrow compartment. Gene Expression Profiling (GEP) has emerged as a powerful investigation tool in modern myeloma research enabling the dissection of the molecular background of MM and allowing the identification of gene products that could potentially serve as targets for therapeutic intervention. In this study we investigated shared transcriptomic abnormalities across newly diagnosed multiple myeloma (NDMM) patient cohorts. In total, publicly available tr

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… Downregulation of metallothionein 1F, a putative oncosuppressor, by loss of heterozygosity in colon cancer tissue. Biochim Biophys Acta. (2012) 1822:918–26. doi: 10.1016/j.bbadis.2012.02.021 60. Lu DD, Chen YC, Zhang XR, Cao XR, Jiang HY, Yao L. …

Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy.

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. Although surgical resection is a potentially curative approach for localized cases of GC, most cases of GC are diagnosed in an advanced, non-curable stage and the response to traditional chemotherapy is limited. Fortunately, recent advances in our understanding of the molecular mechanisms that mediate GC hold great promise for the development of more effective treatment strategies. In this review, an overview of the morphological classification, current treatment approaches, and molecular alterations that have been c

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… MSI: microsatellite instability; GS: genomically stable; EBV: Epstein-Barr virus; CIN: chromosomally unstable; LOH: loss of heterozygosity. … These findings are also partly consistent with the observation that the highest frequency of loss of heterozygosity occurs at the APC (36%) and TP53 (33%) loci [ 4 ]. …

Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies.

Treatment of myelofibrosis (MF), a BCR-ABL-negative myeloproliferative neoplasm, is challenging. The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. The remaining patients are treated with palliative therapies to manage MF-related anemia and splenomegaly. Identification of a mutation in the Janus kinase 2 (JAK2) gene (JAK2 V617F) in more than half of all patients with MF has prompted the discovery and clinical development of inhibitors that target JAK2. Although treatment with JAK2 inhibitors has been shown to improve sy

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… This type of signaling has been observed in basal cell carcinoma ( PTCH and SMO mutations) [ 94 , 95 ], medulloblastoma ( PTCH and SUFU mutations) [ 96 ], and rhabdomyosarcoma ( PTCH and SUFU loss of heterozygosity) [ 97 ]. …

Novel Molecular Therapies and Genetic Landscape in Selected Rare Diseases with Hematologic Manifestations: A Review of the Literature.

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria (KIT, ADAMTS13, GBA1, and PIG-A genes, respectively). In Castleman disease, improper ETS1, PTPN6, TGFBR2, DNMT3A, and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF, MAP2K1, MAP3K1, ARAF, ERBB3, NRAS, KRAS, PICK1, PIK3R2, and PIK3CA. Genes like H

Multiple cystic lung disease.

Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main dise

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… Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis . Am J Hum Genet 1998 ; 62 : 810 – 815 . 9529362 10.1086/301804 PMC1377043 21 Vianna FG , Marchiori E , Zanetti G , et al. …

Резюме докладов 51st Конференция Европейского общества генетики человека: плакаты

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Advanced Lung Cancer Inflammation Index: A Novel Comprehensive Biomarker of Host Status for Patients with Metastatic Colorectal Cancer.

Numerous biomarkers that reflect host status have been identified for patients with metastatic colorectal cancer (mCRC). However, there has been a paucity of biomarker studies that comprehensively indicate body composition, nutritional assessment, and systemic inflammation status. The advanced lung cancer inflammation index (ALI), initially introduced as a screening tool for patients with non-small-cell lung cancer in 2013, emerges as a holistic marker encompassing all body composition, nutritional status, and systemic inflammation status. The index is calculated by the simple formula: body ma

Understanding Rare Anemias: Emerging Frontiers for Diagnosis and Treatment.

Background-This review provides a comprehensive overview of rare anemias, emphasizing their hereditary and acquired causes, diagnostic advancements, and evolving treatment strategies. It outlines the significance of rare anemias within public health, historical challenges in recognition and treatment, and the role of European initiatives like ENERCA and EuroBloodNet in advancing care. Content-This document discusses diagnostic technologies like next-generation sequencing and the impact of artificial intelligence, alongside the promising avenues of gene therapy, targeted drug treatments, and st

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… Accordingly, the detection of acquired 6p copy number-neutral loss of heterozygosity using bone marrow array for the diagnosis of aAA and the measure of telomere length by flow-FISH for short telomere syndromes and other inherited BMF are important advances in the diagnosis of BMF syndromes [ 5 ]. 5.6 …

Множественный вариант жесткости склероза в DYSF-ZNF638 связует с нейронной потерей и воспалением.

Был выявлен генетический вариант rs10191329AA, связанный с более быстрым накоплением инвалидности при множественном склерозе (MS). Мы изучили воздействие переносчика Rs10191329AA на MS патологию и флангающие гены дисферлин (DYSF) и белкового цинка 638 (ZNF638) в голландском банке мозга (n = 290) путем сопоставления rs10191329AA (n = 6) с совпадающими rs10191329CC носителями (n = 12). rs10191329A носителями, связанными с более острым аксоном стрессом, снижением нейронной плотности слоя 2 и более высокой долей повреждений пенистыми микроглией. В rs10191329AA спонсоры, обычно выделявшиеся белое в

Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia.

Despite considerable growth in our understanding of the heterogeneous biology and pathogenesis of acute myeloid leukemia (AML) in recent decades, for nearly forty years, little progress was gained in the realm of novel therapeutics. Since 2017, however, nine agents have been FDA-approved for patients with AML in both the upfront and relapsed/refractory (R/R) settings. Most of these compounds function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival. They have been approved both as single agents and in combination with conventional or reduce

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… Early investigation using single-nucleotide polymorphism arrays or conventional cytogenetic techniques has associated post-transplant AML relapse with the acquisition of chromosome duplications, deletions, or loss of heterozygosity in the relapse sample compared with the diagnostic counterpart [ 35 , …

Enhancement of Neuroblastoma NK-Cell-Mediated Lysis through NF-kB p65 Subunit-Induced Expression of FAS and PVR, the Loss of Which Is Associated with Poor Patient Outcome.

High-risk neuroblastoma (NB) is a rare childhood cancer whose aggressiveness is due to a variety of chromosomal genetic aberrations, including those conferring immune evasion. Indeed, NB cells adopt several molecular strategies to evade recognition by the immune system, including the downregulation of ligands for NK-cell-activating receptors. To date, while molecular strategies aimed at enhancing the expression of ligands for NKG2D- and DNAM-1-activating receptors have been explored, no evidence has been reported on the immunomodulatory mechanisms acting on the expression of death receptors su

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… Specifically, one patient showed loss of both FAS and PVR genes, 12 showed loss of only the FAS gene, including one with copy-neutral loss of heterozygosity (cnLOH), and 9 patients showed loss of only the PVR gene ( Table 2 ). …

Inborn Errors of Immunity and Cancer.

Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders characterized by a defect in the function of at least one, and often more, components of the immune system. The aim of this narrative review is to discuss the epidemiology, the pathogenesis and the correct management of tumours in patients with IEI. PubMed was used to search for all of the studies published over the last 20 years using the keywords: "inborn errors of immunity" or "primary immunodeficiency" and "cancer" or "tumour" or "malignancy". Literature analysis showed that the overall risk for cancer in children with

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… Furthermore, EBV expresses genes that inhibit cell-mediated immunity, making it immortal within B cells, which proliferate uncontrollably under the viral stimulus, acquiring mutations due to loss of heterozygosity and/or cytogenetic rearrangements [ 46 ]. …

Overcoming Oncogenic Mediated Tumor Immunity in Prostate Cancer.

Immunotherapy is being tested intensively in clinical trials for prostate cancer; it includes immune checkpoint inhibition, prostate specific antigen (PSA) vaccines and dendritic cell-based strategies. Despite increasing evidence for clinical responses, the consensus of multiple trials is that prostate cancers are poorly responsive to immunotherapy. Prostate cancer has a high degree of pathological and genetic heterogeneity compared to other cancer types, which may account for immunotherapeutic resistance. This hypothesis also implies that select types of prostate tumors may be differentially

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… Single allelic loss of the PTEN tumor suppressor through loss of heterozygosity (LOH) may serve as an important transition to invasive disease [ 32 , 112 ] and castration resistance. …

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

Drug Repurposing in Oncology: A Systematic Review of Randomized Controlled Clinical Trials.

Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of t

Integrated genomic and clinical modeling for prognostic assessment of radiotherapy response in rectal neoplasms.

The aim of this study is to develop a prognostic model for evaluating radiotherapy response in patients diagnosed with rectal neoplasms by integrating genomic and clinical data. Publicly accessible datasets from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed to identify differentially expressed genes associated with drug resistance and mitophagy. Functional enrichment analyses were conducted to investigate relevant biological pathways. A prognostic risk model was constructed using least absolute shrinkage and selection operator regression and validated via receiver operating

New insight into adiponectin role in obesity and obesity-related diseases.

Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined "adipocytokines," protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production tha

Lymphangioleiomyomatosis and Pregnancy-Do We Have All the Answers for a Woman Who Desires to Conceive?-Literature Review.

Lymphangioleiomyomatosis (LAM) is a rare, progressive, and poor-prognosis systemic disorder that primarily affects women of reproductive age, with a higher prevalence among individuals of Caucasian origin. However, there are limited reliable data on the prevalence of LAM during pregnancy. The fulminant respiratory clinical presentation that often includes progressive dyspnea on exertion, cough, or hemoptysis, frequently complicated by pneumothorax, and the increased risk of spontaneous abortion due to increased estrogen and progesterone production during gestation, are arguments that most ofte

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… Loss of heterozygosity in one of the TSC genes, particularly TSC2 (TSC2-LOH), has been identified in LAM cells present in blood, urine, or chylous fluid, suggesting its potential utility as a biomarker in clinical practice. …

European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when.

The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histopathological, and radiological markers of disease. Specific tests are needed both at presentation and during follow-up in order to reach the correct diagnosis and characterize the disease precisely. These tests can also serve

Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma.

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytome

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… Some early genetic alterations include 3p, 9p, and 17p loss of heterozygosity, as well as cyclin-dependent kinase inhibitor 2A (CDKN2A) and tumor protein 53 (TP53) inactivation seen already in dysplasia. …