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Renal dysfunction, malignant neoplasms, atherosclerotic cardiovascular diseases, and sarcopenia as key outcomes observed in a three-year follow-up study using the Werner Syndrome Registry.

Werner syndrome is an adult-onset progeria syndrome that results in various complications. This study aimed to clarify the profile and secular variation of the disease. Fifty-one patients were enrolled and registered in the Werner Syndrome Registry. Their data were collected annually following registration. A cross-sectional analysis at registration and a longitudinal analysis between the baseline and each subsequent year was performed. Pearson's chi-squared and Wilcoxon signed-rank tests were used. Malignant neoplasms were observed from the fifth decade of life (mean onset: 49.7 years) and we

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… Using state-of-the-art technologies, such as genome, transcriptome, and epigenome analyses [ 67 ], study of the generation of iPS cells from patients with Werner syndrome and the correction of the WRN gene by the CRISPR/Cas9-mediated methods [ 68 ] will create new treatments for patients with Werner …

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brai

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… Epigenome-wide DNA methylation landscape of melanoma progression to brain metastasis reveals aberrations on homeobox d cluster associated with prognosis . …

Amino acid metabolism in primary bone sarcomas.

Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, bu

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… Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1. Cell Rep (2015) 10(7):1082–1095. 70. Boulay G, Sandoval GJ, Schimdl C, Riggi N, Iyer S, Buisson R, Naigles B, et al. …

Neuropsychiatric Disorders and Frailty in Older Adults over the Spectrum of Cancer: A Narrative Review.

BackgroundThe interplay between different neuropsychiatric conditions, beyond dementia, in the presence of a diagnosis of cancer in older adults may mediate patients' fitness and cancer-related outcomes. Here, we aimed to investigate the presence of depression, sleep disturbances, anxiety, attitude, motivation, and support in older adults receiving a diagnosis of cancer and the dimension of frailty in order to understand the magnitude of the problem.MethodsThis review provides an update of the state of the art based on references from searches of PubMed between 2000 and June 2021.ResultsThe ev

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… Sirt1 and Parp1 as epigenome safeguards and microRNAs as SASP-associated signals, in cellular senescence and aging. Ageing Res. Rev. 2017;40:120–141. doi: 10.1016/j.arr.2017.10.001. 72. Boreskie K.F., Oldfield C.J., Hay J.L., Moffatt T.L., Hiebert B.M., Arora R.C., Duhamel T.A. …

Novel diagnostic options for endometriosis - Based on the glycome and microbiome.

BackgroundEndometriosis is a chronic gynaecological disease whose aetiology is still unknown. Despite its prevalence among women of reproductive age, the pathology of the disease has not yet been elucidated and only symptomatic treatment is available. Endometriosis has high latency and diagnostic methods are both limited and invasive.Aim of reviewThe aim of this review is to summarise minimally invasive or non-invasive diagnostic methods for endometriosis and their diagnostic efficiencies. Furthermore, we discuss the identification and diagnostic potential of novel disease biomarkers of microb

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration.

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy-based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while othe

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… The epigenome in multiple myeloma: impact on tumor cell plasticity and drug response. Front Oncol 2018;8:566. 78. Lomas OC, Tahri S, Ghobrial IM. The microenvironment in myeloma. Curr Opin Oncol 2020;32:170–75. 79. Ryu D, Kim SJ, Hong Y, Jo A, Kim N, Kim HJ, et al. …

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.

AbstractThe treatment paradigm for lymphoma, a highly heterogeneous group of hematologic malignancies, has been revolutionized by the development of therapies targeting oncogenic signaling pathways. This shift from conventional chemotherapy to precision medicine is driven by a deep molecular understanding of the pathways that govern lymphoma cell survival and proliferation. This review comprehensively surveys the landscape of these targeted therapies, from fundamental molecular mechanisms to clinical breakthroughs. We first dissect the molecular architecture of key oncogenic drivers, covering

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… One major approach involves creating synergy within the epigenome itself. … In R/R PTCLs, therapies targeting the epigenome are particularly prominent. …

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications.

Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients' health and life. Systemic chemotherapy remains the first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with the potential to effectively extend patient survival. However, the development of drug resistance seriously limits the clinical efficiency of chemotherapy and ultimately results in treatment failure and patient death. A large number of studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RN

Exosomes liquid biopsy in Lymphoma precision medicine: applications and challenges.

Liquid biopsy is an emerging non-invasive detection technology that diagnoses tumors and provides prognostic value by analyzing samples such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Exosomes are nanoscale extracellular vesicles (EVs) secreted by cells, encapsulating a diverse array of biomolecules, including proteins, nucleic acids (e.g., mRNA and miRNA), and lipids. Lymphoma cells secrete various exosomes, whose contents carry abundant tumor-associated information and serve as messengers in the tumor microenvironment (TME). Consequently, tumor-derived ex

Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers.

Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase

Мы игнорируем сексуальные различия в гематологии? Призыв к совершенствованию отчетности.

Существуют явные различия по признаку пола в частотности, факторах риска и смертности от большинства гематологов (ГМ). Несмотря на известные различия в физиологии, гематопоисеях, молекулярных профилях, фармакокинетике наркотиков, токсичности, связанной с лечением, и опыте лечения, мужчины и женщины получают стандартизованное и одинаковое лечение большинства ТМ. Предыдущая опубликованная работа продемонстрировала различия в представленности женщин в клинических испытаниях на рак и выявила недостаток информации о результатах дифференцированного лечения и токсичности в разбивке по полу. Мы проана

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… Meta‐analysis of epigenome‐wide association studies in newborns and children show widespread sex differences in blood DNA methylation. Mutat Res. 2022;789:108415. 25. Hochstenbach K, van Leeuwen DM, Gmuender H, Gottschalk RW, Løvik M, Granum B, et al. …

Overcoming immunosuppression in cancer: how ketogenic diets boost immune checkpoint blockade.

Immune checkpoint blockade (ICB) is now part of the standard of care in the treatment of many forms of cancer, yet it lacks efficacy in some patients, necessitating adjunct therapies to support the anti-tumor immune response. Ketogenic diets (KDs), i.e., high-fat low-carbohydrate diets, have been shown to have antiproliferative and immunomodulatory effects in various preclinical cancer studies. Here, we review current knowledge of the complex interplay of KDs and the anti-tumor immune response in the context of ICB therapy, to update our understanding of diet-induced immunometabolic reprogramm

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… Rather other factors, for example alterations of the immune response, reduced insulin signaling, the levels of reactive oxygen species, the metabolic profile of the TME, the epigenome, and the microbiome, as well as KB-induced signaling pathways, could contribute to KD-mediated attenuation of tumor growth …

Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, V

Noncoding RNAs improve the predictive power of network medicine.

Network medicine has improved the mechanistic understanding of disease, offering quantitative insights into disease mechanisms, comorbidities, and novel diagnostic tools and therapeutic treatments. Yet, most network-based approaches rely on a comprehensive map of protein-protein interactions (PPI), ignoring interactions mediated by noncoding RNAs (ncRNAs). Here, we systematically combine experimentally confirmed binding interactions mediated by ncRNA with PPI, constructing a comprehensive network of all physical interactions in the human cell. We find that the inclusion of ncRNA expands the nu

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… Lee , Lessons from X-chromosome inactivation: Long ncRNA as guides and tethers to the epigenome . Genes. Dev. 23 , 1831 – 1842 ( 2009 ). 19684108 10.1101/gad.1811209 PMC2725936 34 R. Lyle , The imprinted antisense RNA at the lgf2r locus overlaps but does not imprint Mas1 . Nat. …

The Clinical Impact of Death Domain-Associated Protein and Holliday Junction Recognition Protein Expression in Cancer: Unmasking the Driving Forces of Neoplasia.

Death domain-associated protein (DAXX) and Holliday junction recognition protein (HJURP) act as chaperones of H3 histone variants H3.3 and centromere protein A (CENPA), respectively, and are implicated in many physiological processes, including aging and epigenetic regulation, by controlling various genes' transcription and subsequently protein expression. Research has highlighted both these biomolecules as participants in key procedures of tumorigenesis, including cell proliferation, chromosome instability, and oncogene expression. As cancer continues to exert a heavy impact on patients' well

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… The Art of War: Harnessing the epigenome against cancer F1000Research 2018 7 141 10.12688/f1000research.12833.1 29479426 PMC5801563 8. Pan W.-W. Zhou J.-J. Liu X.-M. Xu Y. Guo L.-J. Yu C. Shi Q.-H. Fan H.-Y. …

Pathogenesis and treatment of Sjogren's syndrome: Review and update.

Sjogren's syndrome (SS) is a chronic autoimmune disease accompanied by multiple lesions. The main manifestations include dryness of the mouth and eyes, along with systemic complications (e.g., pulmonary disease, kidney injury, and lymphoma). In this review, we highlight that IFNs, Th17 cell-related cytokines (IL-17 and IL-23), and B cell-related cytokines (TNF and BAFF) are crucial for the pathogenesis of SS. We also summarize the advances in experimental treatment strategies, including targeting Treg/Th17, mesenchymal stem cell treatment, targeting BAFF, inhibiting JAK pathway, et al. Similar

New insights into the activities and toxicities of the old anticancer drug doxorubicin.

The anthracycline drug doxorubicin is among the most used-and useful-chemotherapeutics. While doxorubicin is highly effective in the treatment of various hematopoietic malignancies and solid tumours, its application is limited by severe adverse effects, including irreversible cardiotoxicity, therapy-related malignancies and gonadotoxicity. This continues to motivate investigation into the mechanisms of anthracycline activities and toxicities, with the aim to overcome the latter without sacrificing the former. It has long been appreciated that doxorubicin causes DNA double-strand breaks due to

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms

Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes.

The discovery of JAK2 (V617F) a decade ago led to optimism for a rapidly developing treatment revolution in Ph(-) myeloproliferative neoplasms. Unlike BCR-ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF), post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) syndromes. JAK-STAT inhibitors have ch

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… 2013 27 9 1861 1869 23619563 10.1038/leu.2013.119 133 Chang TY Dvorak CC Loh ML Bedside to bench in juvenile myelomonocytic leukemia: insights into leukemogenesis from a rare pediatric leukemia Blood 2014 124 16 2487 2497 25163700 10.1182/blood-2014-03-300319 134 Kim E Abdel-Wahab O Focus on the epigenome …