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Shaping the Treatment Paradigm Based on the Current Understanding of the Pathobiology of Multiple Myeloma: An Overview.

Multiple myeloma is an incurable malignancy which despite progressive improvements in overall survival over the last decade remains characterised by recurrent relapse with progressively shorter duration of response and treatment-free intervals with each subsequent treatment. Efforts to unravel the complex and heterogeneous genomic alterations, the marked dysregulation of the immune system and the multifarious interplay between malignant plasma cells and those of the tumour microenvironment have not only led to improved understanding of myelomagenesis and disease progression but have facilitate

mTOR Cross-Talk in Cancer and Potential for Combination Therapy.

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understandi

Downregulation of SLC40A1 leads to iron accumulation in fibrotic lung fibroblasts.

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbe

Neoplastic Disorders and Cardiovascular Comorbidities in Geriatric Patients: A Simple Association?

Cardiovascular disease (CVD) and cancer frequently coexist in older patients, posing significant challenges in clinical management due to overlapping risk factors and treatment-related complications. This narrative review summarizes current knowledge on the epidemiology, shared pathophysiological mechanisms and clinical impact of neoplastic comorbidities in older adults with cardiovascular diseases. It highlights the increased mortality, morbidity and diminished quality of life resulting from the coexistence of these conditions. The review also discusses personalized management strategies, emp

Cognitive dysfunction associated with cellular immunotherapy for cancer.

Immunotherapies engage the individual's immune system to fight both hematologic and solid malignancies and have led to durable clinical responses for many patients. A subset of immunotherapies, including T cell engagers (TCEs) and chimeric antigen receptor T-cell therapies (CAR-T), use T cell mediated mechanisms to induce cancer cell death. These therapies can be very effective against the cancer while also causing significant systemic and neurologic toxicity, including cognitive dysfunction. Here, we provide a review on the existing and emerging literature describing the acute, subacute, and

Association of Physical Activity with Dementia Risk in Cancer Survivors: A Korean Nationwide Cohort Study.

PURPOSE: This study aimed to investigate the impact of physical activity on dementia risk among cancer survivors in South Korea. MATERIALS AND METHODS: This retrospective, population-based cohort study included 344,152 cancer survivors identified from the National Health Insurance Service database in South Korea. The mean follow-up time was 5.81 years. Different levels of physical activity post-cancer diagnosis, ranging from inactive to highly active, were assessed. The primary outcome was the incidence of overall dementia, Alzheimer's disease, and vascular dementia. Secondary outcomes includ

Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study.

AbstractThe phase 1 portion of SENTRY/XPORT-MF-034 (NCT04562389) evaluated the exportin 1 inhibitor selinexor (40 mg/60 mg once weekly) plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (n = 24). Primary end points were maximum tolerated selinexor dose, recommended clinical trial dose, and safety. No dose-limiting toxicities were reported. Common adverse events were nausea, fatigue, anemia, thrombocytopenia, constipation, vomiting, and headache. Nausea was transient, mainly grade 1, and managed by prophylactic antiemetics. Four deaths occurred, all unrelated to study treatmen

Therapeutic potential of cytokine-induced killer cell therapy for renal cell carcinoma and prostate cancer.

Renal cell carcinoma (RCC) and prostate cancer (PCa) are among the most prevalent and therapeutically challenging malignancies of the genitourinary system, particularly in advanced or metastatic stages. For advanced/metastatic RCC, targeted agents such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have improved progression-free and overall survival. For metastatic castration-sensitive PCa, androgen deprivation therapy (ADT) combined androgen receptor pathway inhibitors (ARPIs) with or without chemotherapy remains the standard of care. Despite these advances, ther

Corticosteroid-associated osteonecrosis in paediatric compared with adult patients: are they the same disease?

Osteonecrosis of the femoral head (ONFH) is a debilitating condition with a poorly characterized pathogenesis. Among the reported aetiologies, excessive alcohol consumption and corticosteroid administration are leading causes. Corticosteroids are often administered as a life-saving treatment for primary oncological or autoimmune conditions, but the subsequent development of ONFH can significantly impair the quality of life of both paediatric and adult patients. This review provides a comprehensive summary and critical analysis of recent advances in the understanding of corticosteroid-associate

Shaping the future of multiple myeloma with artificial intelligence and digital twins: from concept to clinic.

Multiple myeloma (MM) is an incurable hematological malignancy with significant clinical and biological heterogeneity. Despite development and refinement of numerous prognostic models for MM, challenges with accurate and reliable risk stratification remain, highlighted by unexpected, early relapse or progression of disease in patients termed functional high-risk (FHR). To improve decision-making and optimise outcome, there is an unmet need for precise identification of high-risk (HR) patients, to enable tailored therapeutic strategies. With a complex and rapidly evolving treatment landscape, a

European Recommendations for Transitioning the Care of Patients With Multiple Myeloma Treated With B-Cell Maturation Antigen Bispecific Antibodies From Academic Hospitals to Community-Based Centers and for Outpatient Step-Up Dosing.

INTRODUCTION: Safe outpatient delivery of B-cell maturation antigen-targeting bispecific antibodies (BCMA-BsAbs) in multiple myeloma (MM) is challenging, particularly during step-up dosing (SUD). Standardized guidance for European community practice is limited. METHODS: A modified Delphi methodology panel sought expert consensus on safe, effective outpatient SUD and transition of care from academic to community centers for patients receiving BCMA-BsAbs. A steering committee of 10 European specialists in MM and BCMA-BsAb delivery generated statements based on literature review and clinical exp

American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel.

OBJECTIVE: Vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality. METHODS: Given the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS. To address this gap, we formed an international multidisciplinary panel of VEXA

Premature hair graying: a multifaceted phenomenon.

Premature hair graying (PHG) is the early loss of natural hair color, influenced by genetic, biological, and environmental factors. This review discusses the significant psychological impacts of PHG and explores its underlying mechanisms, related health conditions, and available treatments. The review examines the roles of genetics, oxidative stress, and lifestyle factors such as smoking and diet in premature graying. It also considers associated medical conditions and current and emerging treatment options. This overview aims to improve understanding of PHG and its broader implications.

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… cutaneous synthesis, which requires exposure to sunlight, supplementation is often key in addressing a deficiency. 47 Additionally, while these interventions have not been formally evaluated, sun protection may also play a role in preventing UV rays exposure associated with premature graying. 28 Avoiding tanning …

Wisely frugal: ensuring sustainable funding for novel cancer therapeutics through a budget impact analysis in resource-limited settings.

IntroductionCancer care in Sri Lanka is predominantly provided through its state health system which is free at the point of delivery. We performed a budget impact analysis of novel cancer drugs with a view to enabling better prioritising of their procurement.MethodsMedian survival gain was obtained for each indication of a novel cancer drug by a review of the literature. The direct cost of drug procurement was obtained from the Ministry of Health of Sri Lanka and the cost per life year gained was computed for each indication. Two thresholds - per capita gross domestic product (GDP) per life y

Acute radiotoxicity studies and safety assessment of 166Ho-EDTMP and 166Ho-DOTMP for the palliative treatment of bone metastases.

Comprehensive studies on the acute toxicity and safety profiles of therapeutic doses of 166Ho-EDTMP and 166Ho-DOTMP in the bone tissue and bone marrow of animals are limited, particularly when 166Ho produced in low-power reactors is used. These bone-specific complexes were synthesized through the coordination of 166Ho3+ ions in a neutral buffer. Acute toxicity studies were conducted at a dose of 1850 MBq/kg over 14 days, whereas safety assessments were performed at therapeutic doses of 18.5, 37, and 74 MBq/kg over 30 days in ICR mice. Hematological, biochemical, and histopathological toxicitie

Patient-reported outcomes in patients with hematologic malignancies treated with CAR T-cell therapy in Europe.

AbstractPatient-reported outcomes (PROs) give direct insights into the treatment's impact on patient's life and complement clinical outcomes. However, since the advent of chimeric antigen receptor T-cell therapy (CAR-T), PROs have been underreported. Particularly, little is known about long-term health-related quality of life (HRQoL) and dimensions such as mental- and social well-being, working life, and financial burden. Therefore, we evaluated multidimensional PROs in a cross-sectional study among European patients who received CAR-T for hematologic malignancies. Patients completed validated

Rethinking corticosteroids use in oncology.

Corticosteroids (CSs), widely used in oncology for their anti-inflammatory and immunosuppressive properties, help manage cancer-related symptoms and side effects. However, their long-term use may negatively affect patient survival and exacerbate tumor progression. Elevated glucose and glutamine metabolism, disruption of vitamin D levels, and alterations in the microbiome are some of the key factors contributing to these adverse outcomes. Approaches such as ketogenic diets, fasting, sartans, and vitamin D supplementation have shown promise in providing similar benefits to CSs while mitigating t

Перспективы Талкетамаба и его полезности в лечении множественной миеломы: безопасность, эффективность и место в терапии.

Несмотря на недавние достижения, большинство пациентов с множественной миэломой в конечном итоге развивают сопротивление имеющимся методам лечения, подчеркивая необходимость новых терапевтических стратегий. G Класс рецептора с протеиновыми соединениями C 5 Член D (GPRC5D) стал жизнеспособной новой терапевтической целью для клеток миэломы, которая привела к клиническому развитию талькетамаба, первого GPRC5D-directed bi специфичный Т-активист (TCE). В августе Талкетамаб получил ускоренное утверждение 2023 Управление по контролю за продуктами питания и лекарствами. Помимо ожидаемой краткосрочной

Integrative Transcriptomic and Machine-Learning Analysis Reveals Immune-Inflammatory and Stress-Response Alterations in MRONJ.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies, yet its molecular mechanisms remain poorly defined. The present study employed an analysis of microarray data (GSE7116) from peripheral blood mononuclear cells of patients with multiple myeloma, myeloma patients with MRONJ, and healthy controls. Differentially expressed genes were identified using the limma package, followed by functional enrichment analysis, weighted gene co-expression network analysis, and LASSO regression and CytoHubba network ranking. The predicti

Диет с высоким содержанием жира с низким содержанием карбогидрата связан с защитой автономного иммунитета CNS.

Множественный склероз (MS) является воспалительным и нейродегенеративным заболеванием центральной нервной системы (КНС), которое, как считается, вызвано аутоиммунными механизмами. Генетические и экологические факторы связаны с развитием НР, и среди них диеты и питательные вещества становятся потенциальными важнейшими факторами. Вместе с тем отсутствует полное понимание их последствий и соответствующих механизмов. Применяя самые современные методы анализа геометрии питания, впервые становится очевидным, что увеличение предложения углеводов в глобальном масштабе связано с увеличением бремени бол