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Comparison of oral chronic graft-versus-host disease characteristics between patients with malignant and non-malignant hematopoietic disorders.

ObjectivesTo characterize and compare the clinical manifestations of oral chronic graft-versus-host disease (cGVHD) in patients with malignant hematopoietic disorders versus those with non-malignant hematopoietic disorders, and to analyze associated risk factors.Materials and methodsDetailed examinations of the oral cavity were conducted in patients with malignant hematopoietic disorders (n = 52) and non-malignant hematopoietic disorders (n = 56) who developed oral cGVHD following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The severity of oral cGVHD was scored, and logisti

Surrogate Biomarkers in Gene Therapy for Orphan Diseases: Validation, Application, and Regulatory Aspects.

The development of gene therapies for rare hereditary disorders is hindered by small patient cohorts, incomplete characterization of natural disease history, and the impracticality of conducting long-term clinical trials. Surrogate biomarkers-quantifiable indicators predictive of clinical outcomes-represent a promising strategy to accelerate the evaluation of therapeutic efficacy. This review examines the role of surrogate endpoints in gene therapy, outlining essential validation criteria, including biological plausibility, analytical reproducibility, and clinical predictive value. Regulatory

Practical management of disease-related manifestations and drug toxicities in patients with multiple myeloma.

Multiple myeloma (MM) is a very heterogeneous disease with multiple symptoms and clinical manifestations. MM affects mainly elderly patients and is difficult to manage in the presence of comorbidities, polypharmacy, frailty and adverse events of disease-targeted drugs. The rapid changes in MM treatment resulting from constant innovations in this area, together with the introduction of numerous new drugs with distinct mechanisms of action and toxicity profiles, have led to an increased complexity in the therapeutic decision-making and patient management processes. The prolonged exposure to nove

PROTAC Technology as a New Tool for Modern Pharmacotherapy.

The publication focuses on the innovative applications of PROTAC (proteolysis-targeting chimera) technology in modern pharmacotherapy, with particular emphasis on cancer treatment. PROTACs represent an advanced therapeutic strategy that enables selective protein degradation, opening new possibilities in drug design. This technology shows potential in the treatment of cancers, viral infections (such as HIV and COVID-19), and chronic diseases including atherosclerosis, Alzheimer's disease, atopic dermatitis, and Huntington's disease. Promising results from clinical studies on the compound ARV-47

Guideline "diagnosis and non interventional therapy of neuropathic pain" of the German Society of Neurology (deutsche Gesellschaft für Neurologie).

2019 the DGN (Deutsche Gesellschaft für Neurology) published a new guideline on the diagnosis and non-interventional therapy of neuropathic pain of any etiology excluding trigeminal neuralgia and CRPS (complex regional pain syndrome). Neuropathic pain occurs after lesion or damage of the somatosensory system. Besides clinical examination several diagnostic procedures are recommended to assess the function of nociceptive A-delta and C-Fibers (skin biopsy, quantitative sensory testing, Laser-evoked potentials, Pain-evoked potentials, corneal confocal microscopy, axon reflex testing). First line

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… In addition to physiotherapy and occupational therapy, psychological support is also important. However, the data regarding multimodal pain therapy for neuropathic pain is very limited. …

Decoding chemotherapy-induced peripheral neuropathy: ion channels, disease models, and future directions.

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatments like paclitaxel and oxaliplatin, impacting patient quality of life (QoL). Despite much research, its underlying mechanisms remain unclear and effective therapies are lacking. This review evaluates whether current experimental models accurately reflect CIPN, emphasizing recent molecular and cellular findings, especially the role of sensory ion channels. We outline limitations of existing models and propose more translational preclinical approaches to better capture disease complexity and patient

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… Further research into multidisciplinary management - including physical therapy, occupational therapy, and emotional support - is warranted to better address quality of life for those affected. …

Geriatric assessment for the practicing clinician: The why, what, and how.

Older adults with cancer heterogeneously experience health care, treatment, and symptoms. Geriatric assessment (GA) offers a comprehensive evaluation of an older individual's health status and can predict cancer-related outcomes in individuals with solid tumors and those with hematologic malignancies. In the last decade, randomized controlled trials have demonstrated the benefits of GA and GA management (GAM), which uses GA information to provide tailored intervention strategies to address GA impairments (e.g., implementing physical therapy for impaired physical function). Multiple phase 3 cli

Polyphenols bind G4-Quadruplex structures and act as epigenetic modifiers with anti-cancer effects.

G4-quadruplexes (G4s) are non-canonical structures of nucleic acids that develop in guanine rich regions of DNA and RNA. Due to their presence in oncogenic promoters and telomeres, G4s represent attractive targets in anticancer drug designs. G4s have also been the subject of recent research regarding their role as epigenetic modulators, supporting their participation in epigenetic processes that control gene expression. The development of small compounds that preferentially target G4s have led to a better understanding of how G4s control these mechanisms. Natural products have greatly contribu

Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features.

The indiscriminate consumption of antimalarials against coronavirus disease-2019 emphasizes the longstanding clinical weapons of medicines. In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines th

Curcumin as a Multi-Target Bioactive Molecule: Mechanistic Insights and Translational Perspectives.

Curcumin, a natural polyphenolic compound derived from the curcuma genus, has attracted considerable attention due to its simple chemical structure, favorable safety profile, and broad-spectrum pharmacological activities. This review provides a comprehensive summary of recent advances in curcumin research, with a specific focus on its therapeutic potential in cancer, inflammation, depression, and metabolic disorders, including non-alcoholic fatty liver disease, hypertension, and osteoporosis. It highlights curcumin's modulation of critical signaling pathways, such as PI3K/Akt, NF-κB, JAK/STAT,

HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.

The hypoxic microenvironment is an essential characteristic of most malignant tumors. Notably, hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulatory factor of cellular adaptation to hypoxia, and many critical pathways are correlated with the biological activity of organisms via HIF-1α. In the intra-tumoral hypoxic environment, HIF-1α is highly expressed and contributes to the malignant progression of tumors, which in turn results in a poor prognosis in patients. Recently, it has been indicated that HIF-1α involves in various critical processes of life events and tumor development via r

Perturbing Enhancer Activity in Cancer Therapy.

Tight regulation of gene transcription is essential for normal development, tissue homeostasis, and disease-free survival. Enhancers are distal regulatory elements in the genome that provide specificity to gene expression programs and are frequently misregulated in cancer. Recent studies examined various enhancer-driven malignant dependencies and identified different approaches to specifically target these programs. In this review, we describe numerous features that make enhancers good transcriptional targets in cancer therapy and discuss different approaches to overcome enhancer perturbation.

Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008.

BackgroundHealth-related quality of life and survival are two important outcome measures in cancer research and practice. The aim of this paper is to examine the relationship between quality of life data and survival time in cancer patients.MethodsA review was undertaken of all the full publications in the English language biomedical journals between 1982 and 2008. The search was limited to cancer, and included the combination of keywords 'quality of life', 'patient reported-outcomes' 'prognostic', 'predictor', 'predictive' and 'survival' that appeared in the titles of the publications. In add

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss

Is Systemic Immunosuppression a Risk Factor for Oral Cancer? A Systematic Review and Meta-Analysis.

Even if the relationship between immunosuppression and increased incidence of systemic cancers is well known, there is less awareness about the risk of developing oral cancer in immunosuppressed patients. The aim of this review was to evaluate the association between immunosuppression and the development of oral cancer. Two authors independently and, in duplicate, conducted a systematic literature review of international journals and electronic databases (MEDLINE via OVID, Scopus, and Web of Science) from their inception to 28 April 2023. The assessment of risk of bias and overall quality of e

Aptamers and Antisense Oligonucleotides for Diagnosis and Treatment of Hematological Diseases.

Aptamers or chemical antibodies are single-stranded DNA or RNA oligonucleotides that bind proteins and small molecules with high affinity and specificity by recognizing tertiary or quaternary structures as antibodies. Aptamers can be easily produced in vitro through a process known as systemic evolution of ligands by exponential enrichment (SELEX) or a cell-based SELEX procedure. Aptamers and modified aptamers, such as slow, off-rate, modified aptamers (SOMAmers), can bind to target molecules with less polar and more hydrophobic interactions showing slower dissociation rates, higher stability,

The role of abnormal epigenetic regulation of small GTPases in glioma (Review).

Brain tumors are one of the most severe types of malignant tumors and glioma accounts for ~80% of malignant brain tumors. The current treatment methods for glioma are limited and patients with glioma often experience relapse following treatment, which leads to a poor prognosis for these patients. Therefore, novel therapeutic targets and methods urgently need to be explored. The present review screened studies that mainly focused on the epigenetic regulation of small guanosine triphosphate (GTP)ase in glioma. These small GTPases participate in most cellular biological processes, including diffe

Abstracts of the ICARE 2024 78th SIAARTI National Congress

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Unpacking adiposity: a narrative critical appraisal of diverse obesity definitions.

BACKGROUND: Obesity is a complex, multifaceted chronic disease that poses a major global health challenge. Traditionally, population-level screening and follow-up have relied heavily on body mass index (BMI). Although BMI provides a simple, standardized measure for epidemiological studies, it does not account for individual variations in muscle mass, fat distribution, or metabolic health. Consequently, relying solely on weight-to-height ratios-even when supplemented with waist circumference, waist-to-hip ratio, or waist-to-height ratio-limits precise individual diagnosis and comprehensive heal

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… Palliative measures, including pain management, occupational therapy, and psychosocial support The EOSS was able to predict mortality in a nationally representative US sample of adults with overweight or obesity (data from the National Health and Nutrition Examination Surveys III 1988–1994 and 1999– …

The DNA methylation landscape of multiple myeloma shows extensive inter- and intrapatient heterogeneity that fuels transcriptomic variability.

BackgroundCancer evolution depends on epigenetic and genetic diversity. Historically, in multiple myeloma (MM), subclonal diversity and tumor evolution have been investigated mostly from a genetic perspective.MethodsHere, we performed an analysis of 42 MM samples from 21 patients by using enhanced reduced representation bisulfite sequencing (eRRBS). We combined several metrics of epigenetic heterogeneity to analyze DNA methylation heterogeneity in MM patients.ResultsWe show that MM is characterized by the continuous accumulation of stochastic methylation at the promoters of development-related