Результаты поиска

Covalent targeting of PSMD14 by Eupalinolide B induces oncoprotein degradation and apoptosis in acute promyelocytic leukemia cells.

Treatment of acute promyelocytic leukemia (APL) remains challenged by toxicities associated with current regimens, highlighting the need for novel and safer therapeutic agents. Here, we identify Eupalinolide B (EB), a natural sesquiterpene lactone isolated from Eupatorium lindleyanum DC., as a potent anti-leukemic compound targeting the human APL-derived HL-60 cell line. Through integrated chemoproteomic profiling and functional validation, we demonstrate that EB covalently binds and inhibits 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a deubiquitinase enzyme (DUB) within the 19S

Patients admitted in the intensive care unit after solid organ or bone marrow transplantation: Retrospective cohort study.

BACKGROUND: Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) revolutionized the survival and quality of life of patients with malignant diseases, various immunologic, and metabolic disorders or those associated with a significant impairment in a patient's quality of life. AIM: To investigate admission causes and treatment outcomes of patients after SOT or HSCT treated in a medical intensive care unit (ICU). METHODS: We conducted a single-center, retrospective epidemiological study in the medical ICU at the University Hospital Centre Zagreb, Croatia coverin

From Symptom to Outcome: Defining Clinically Meaningful Patient-Reported Appetite Loss in Non-Small-Cell Lung Cancer.

BACKGROUND: Appetite loss is a common and distressing symptom in non-small-cell lung cancer (NSCLC), driven by both treatment side effects and disease progression. It often leads to unintended weight loss and cancer cachexia, significantly impairing patients' quality of life and survival. Yet, appetite loss remains under-recognized in oncology care, with no standard assessment tools or universal management guidelines. In this study, we developed a predictive model to identify clinically meaningful thresholds of appetite loss that were associated with significant weight reduction and decreased

Новые оценки издержек, связанных с неблагоприятными явлениями у больных раком.

Стоимость неблагоприятных явлений (ОЭ) является одним из важнейших компонентов экономических моделей здравоохранения для лечения раковых заболеваний; однако в настоящее время имеется мало всеобъемлющих оценок этих расходов. В предыдущих исследованиях основное внимание уделялось затратам, связанным с конкретными ПВ, типами рака или режимами лечения. В настоящем исследовании дается оценка дополнительных издержек, связанных с ЭВ, в различных областях 13 (Международная статистическая классификация болезней и связанных с ними проблем в области здравоохранения]ICD-10]) пациентам с диагнозом: 2016 и

Safety and toxicity of Iopofosine I 131 (CLR 131) with external beam radiation therapy in recurrent or metastatic head and neck cancer: results of a phase 1 single-centre, open-label, single-arm, dose escalation and dose expansion study.

BACKGROUND: Re-irradiation of recurrent head and neck cancer (HNC) is often limited by tumour adherence to critical structures and/or radiation tolerance of critical normal tissues. Iopofosine I 131 (CLR 131) is a targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to tumour cells. We conducted a phase 1, single-centre, open-label study to determine whether CLR 131 given with reduced dose of external beam radiation therapy (EBRT) would be tolerable and feasible. METHODS: All participants received previous curative intent treatment with radioth

Продольный анализ сетчатки и хориокастина у пациентов с множественным склерозом: a 3-year Учёба.

ЦЕЛИ: В рамках этого исследования изучалось продольное развитие структуры сетчатки и микроваскулатуры по сравнению с ней. 3 - годы у пациентов с множественным склерозом (RRMS) с релапсирующим излучением с использованием оптической томографии (OCT) и ангиографии OCT (OCTA). Она также изучила корреляцию между этими изменениями и оценками Расширенной шкалы взносов для инвалидов. МЕТОДЫ: В этом перспективном, продольном исследовании мы зачислялись 66 пациентов с RRMS, не имеющих зрительного неврита и 124 здоровый контроль. Все участники прошли полный офтальмологический осмотр, сканирование OCT/OCT

Симптомы расстройства питания при множественном склерозе: взаимосвязь между нейротикой, дисфункцией тела и самоэстеемом.

Предыстория/цели: Исследования нарушений питания (РУ) у лиц с множественным склерозом (МС) являются ограниченными. В популяциях эпидемиологов нейротицизм связан с симптомами эдактики из-за более низкой самооценки и большего недовольства телом, но эти отношения остаются неизученными в MS. Цель этого исследования заключалась в изучении вопроса о том, являются ли самоуважение и неудовлетворенность тела посредником в установлении связи между нейротикализмом и симптомами ЭД у отдельных лиц, имеющих MS. Методы: Нынешняя выборка состояла из 275 участников, которые сообщили о подтвержденном неврологом

Optimisation of anti-interleukin-6 therapy: Precision medicine through mathematical modelling.

BackgroundDysregulated interleukin (IL)-6 production can be characterised by the levels present, the kinetics of its rise and its inappropriate location. Rapid, excessive IL-6 production can exacerbate tissue damage in vital organs. In this situation, therapy with an anti-IL-6 or anti-IL-6 receptor (IL-6R) monoclonal antibody, if inappropriately dosed, may be insufficient to fully block IL-6 signalling and normalise the immune response.MethodsWe analysed inhibition of C-reactive protein (CRP) - a biomarker for IL-6 activity - in patients with COVID-19 or idiopathic multicentric Castleman disea

Burden of non-communicable diseases in Tunisia, 1990-2017: results from the global burden of disease study.

Introductionnon-communicable diseases (NCDs) are the leading cause of mortality and disability worldwide especially in developing countries such as Tunisia. We aimed to describe the national burden of non-communicable diseases in 2017 and to analyze disability-adjusted life year trends from 1990 to 2017 in Tunisia by cause and gender.Methodswe used Joinpoint regression analysis to assess trends of the age standardized disability-adjusted life year rate from 1990 to 2017 and to determine average annual percentage change.Resultsnon-communicable diseases accounted for 87.7% of total disability-ad

Assessment of the Diagnostic Potential of miR-29a-3p and miR-92a-3p as Circulatory Biomarkers in Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a set of Myeloproliferative neoplasms that are identified by excessive growth of myeloid blasts and production of abnormal blood cells. AML is the most common type of acute leukemia that occurs in adults. In addition, AML progresses rapidly and is considered a fatal disease. Thus, there is an urgent need to find new targets for molecularly designed therapies. In This study, we evaluated the circulatory levels of microRNA-29a-3p (miR-29a-3p) and miR-92a-3p beside exploring the expression pattern of their target gene myeloid cell leukemia sequence1 (MC

Psychometric properties of two physical activity questionnaires, the AQuAA and the PASE, in cancer patients.

BackgroundThis study aimed to evaluate the reliability and validity of two self-report physical activity (PA) questionnaires - the AQuAA (Activity Questionnaire for Adults and Adolescents) and PASE (Physical Activity Scale for the Elderly) - in cancer patients.MethodsTest-retest reliability was determined by administering the questionnaires twice within 5 days. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and smallest detectable difference (SDD) were calculated. Construct validity was determined by comparing the questionnaire results with ActiGraph acceleromete

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… Five main outcomes can be calculated: a total PA score (the AQuAA score in Metabolic Equivalent of Tasks (MET)*min/week, including all activities ≥ 2 METs), and the total time (in min/week) spent on sedentary (< 2 MET), light (2-4 METs), moderate (4-6.5 METs) and vigorous (> 6.5 METs) intensity activities …

Why pharmacogenomic biomarkers for chemotherapy-induced peripheral neuropathy fail: a systematic review of genetic associations, replication, and clinical translation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting toxicity of cancer treatment, yet reliable biomarkers to predict individual susceptibility remain lacking. Germline genetic variation has been widely investigated as a potential contributor to CIPN risk; however, the consistency and clinical utility of these associations remain unclear. We performed a systematic review of genetic association studies evaluating CIPN across neurotoxic chemotherapies. PubMed, Embase, Web of Science, and the Cochrane Library were searched (April 2025) for human studies assessing germline

Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies.

Multiple myeloma is a hematological cancer type. For its treatment, Bortezomib has been widely used. However, drug resistance to this effective chemotherapeutic has been developed for various reasons. 2D cell cultures and animal models have failed to understand the MM disease and Bortezomib resistance. It is therefore essential to utilize new technologies to reveal a complete molecular profile of the disease. In this review, we in-depth examined the possible molecular mechanisms that cause Bortezomib resistance and specifically addressed MM and Bortezomib resistance. Moreover, we also included

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the b

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma.

The proteasome is crucial for the degradation of intracellular proteins and plays an important role in mediating a number of cell survival and progression events by controlling the levels of key regulatory proteins such as cyclins and caspases in both normal and tumor cells. However, compared to normal cells, cancer cells are more dependent on the ubiquitin proteasome pathway (UPP) due to the accumulation of proteins in response to uncontrolled gene transcription, allowing proteasome to become a potent therapeutic target for human cancers such as multiple myeloma (MM). Up to date, three protea

Pre-clinical Research on Bladder Toxicity After Radiotherapy for Pelvic Cancers: State-of-the Art and Challenges.

Despite the dramatic advancements in pelvic radiotherapy, urinary toxicity remains a significant side-effect. The assessment of clinico-dosimetric predictors of radiation cystitis (RC) based on clinical data has improved substantially over the last decade; however, a thorough understanding of the physiopathogenetic mechanisms underlying the onset of RC, with its variegated acute and late urinary symptoms, is still largely lacking, and data from pre-clinical research is still limited. The aim of this review is to provide an overview of the main open issues and, ideally, to help investigators in

Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy.

Lymphocyte collection by apheresis for CAR-T production usually does not include blood mobilized using granulocyte colony stimulating factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinics, makes it necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent works

From Innate Immunity to Cancer Therapy: Antimicrobial Peptides as Emerging Anticancer Agents.

The potential for the use of antimicrobial peptides (AMPs) as anticancer agents has garnered much interest because of their selective cytotoxicity to tumor cells and ability to evade multidrug resistance mechanisms. AMPs are shorter cationic amphiphilic molecules, part of our innate immune system, with direct membrane-disruptive activity and immunomodulatory effects. Anticancer peptides (ACPs) can be derived from natural biophysical sources or synthetically engineered, taking advantage of the unique biophysical properties of cancer cell membranes to exert their anti-tumor activities rapidly an

Emerging strategies and therapies for treatment of Paget's disease of bone.

Paget's disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemi

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the