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Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

Artificial intelligence in drug discovery and development.

Artificial intelligence-integrated drug discovery and development has accelerated the growth of the pharmaceutical sector, leading to a revolutionary change in the pharma industry. Here, we discuss areas of integration, tools, and techniques utilized in enforcing AI, ongoing challenges, and ways to overcome them.

Exploring the impact of a decision support algorithm to improve clinicians' chemotherapy-induced peripheral neuropathy assessment and management practices: a two-phase, longitudinal study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) negatively affects physical function and chemotherapy dosing, yet, clinicians infrequently document CIPN assessment and/or adhere to evidence-based CIPN management in practice. The primary aims of this two-phase, pre-posttest study were to explore the impact of a CIPN clinician decision support algorithm on clinicians' frequency of CIPN assessment documentation and adherence to evidence-based management. METHODS: One hundred sixty-two patients receiving neurotoxic chemotherapy (e.g., taxanes, platinums, or bortezomib) answered pati

Pain Management in Patients with Multiple Myeloma: An Update.

Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblasti

Rationale and design of platelet transfusions in haematopoietic stem cell transplantation: the PATH pilot study.

IntroductionIn patients with transient thrombocytopenia being treated with high-dose chemotherapy followed by stem cell rescue-haematopoietic stem cell transplantation (HSCT), prophylactic transfusions are standard therapy to prevent bleeding. However, a recent multicentre trial suggests that prophylactic platelet transfusions in HSCT may not be necessary. Additionally, the potential overuse of platelet products places a burden on a scarce healthcare resource. Moreover, the benefit of prophylactic platelet transfusions to prevent clinically relevant haemorrhage is debatable. Current randomised

Mixed-Methods to Define Meaningful Change using Exit Interviewand Clinical Trial Data in Patients with Tenosynovial Giant Cell Tumor (TGCT).

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm associated with limited range of motion (ROM), stiffness, joint damage, pain, and reduced physical functioning (PF). The MOTION Phase 3 trial (NCT05059262) was a randomized, placebo-controlled, double-blind study of vimseltinib among patients with TGCT. The objective of the current study was to define meaningful changes in clinical outcome assessments (COAs) measuring active ROM, PF, and stiffness using qualitative and quantitative data from patients in the MOTION trial. METHODS: Embedded exit interviews with pa

Measurable Residual Disease Testing During Treatment with Bispecific Antibodies for Lymphoma.

The introduction of bispecific antibodies (BsAbs) has led to significant improvements in survival for patients with relapsed and refractory B-cell lymphomas. Despite these advances, there remains a significant number of patients who experience disease progression after these novel therapies. Predicting which patients may respond to certain treatments and the durability of their responses remains challenging. Measurable residual disease (MRD) has become easier to detect and quantify through the use of genomic next-generation sequencing tools and has been studied as a possible biomarker to predi

Targeted synthesis of a trimethoxyphenyltetrahydropyrimidine analogue designed as a DNA intercalator: in silico, multi-spectroscopic, thermodynamic, and in vitro approaches.

Based on the rational design of DNA intercalators and Topo-II inhibitors and taking into consideration the main pharmacophoric features of doxorubicin (Dox) as a reference standard, we theoretically designed novel substituted tetrahydropyrimidine analogues (T1-35). The designed analogues (T1-35) were investigated for their inhibitory potential towards the hybrid DNA and Topo-II target receptor using molecular docking. Interestingly, the theoretically designed analogue T30 with a 3,4,5-trimethoxy phenyl side chain was found to be the superior candidate, achieving a binding score of -7.06 kcal m

Trajectory, interactions, and predictors of higher symptom burden during induction therapy for multiple myeloma.

BACKGROUND: Patients with multiple myeloma (MM) experience disabling symptoms that are difficult to manage and may persist after induction therapy. Monitoring disease-related and induction therapy-induced symptoms and identifying patients at greater risk for high symptom burden are unmet clinical needs. The objective of this study was to examine the trajectories of symptom severity over time and identify predictors of high symptom burden during MM induction therapy. METHODOLOGY: Eligible patients with MM rated their symptoms by completing the MD Anderson Symptom Inventory MM module repeatedly

MR and CT angiography in the diagnosis of vasculitides.

Vasculitides represent the wide-ranging series of complex inflammatory diseases that involve inflammation of blood vessel walls. These conditions are characterized according to the caliber of the predominantly involved vessels. The work-up of vasculitides often includes imaging to narrow a differential diagnosis and guide management. Findings from CT and MR angiography in conjunction with a thorough history and physical exam are of utmost importance in making an accurate diagnosis. Further, imaging can be used for follow-up, in order to monitor disease progression and response to treatment. Th

Tips and Tricks and Clinical Outcome of Cryopreserved Human Amniotic Membrane Application for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Pilot Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, antifibrotic, antimicrobial, antiviral, and analgesic effects. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with suitable mechanical properties (permeability, stability, elasticity, flex

"Is this the GVHD?" A qualitative exploration of quality of life issues in individuals with graft-versus-host disease following allogeneic stem cell transplant and their experiences of a specialist multidisciplinary bone marrow transplant service.

BackgroundGraft-versus-host disease (GVHD) is a significant cause of morbidity and mortality following allogeneic stem cell transplantation. These patients face unique challenges due to the complexity of GVHD which can affect multiple organ systems, and the toxicity of treatments. Despite the known impact on quality of life (QOL), qualitative data within the bone marrow transplantation (BMT) literature is rare, and there has been no qualitative work exploring patient experience of specialist healthcare provision for GVHD in the United Kingdom.MethodsWe conducted a primary explorative qualitati

Patient-Derived Tumor Organoids for Drug Repositioning in Cancer Care: A Promising Approach in the Era of Tailored Treatment.

Malignancies heterogeneity represents a critical issue in cancer care, as it often causes therapy resistance and tumor relapse. Organoids are three-dimensional (3D) miniaturized representations of selected tissues within a dish. Lately, organoid technology has been applied to oncology with growing success and Patients Derived Tumor Organoids (PDTOs) constitute a novel available tool which fastens cancer research. PDTOs are in vitro models of cancer, and importantly, they can be used as a platform to validate the efficacy of anti-cancer drugs. For that reason, they are currently utilized in cli

State-of-the-art imaging for diagnosis of metastatic bone disease.

Metastatic bone disease (MBD) is common-it is detected in up to 65-75% of patients with breast or prostate cancer, in over 35% of patients with lung cancer; and almost all patients with symptomatic multiple myeloma have focal lesions or a diffuse bone marrow infiltration. Metastatic bone disease can cause a variety of symptoms and is often associated with a poorer prognosis, with high social and health-care costs. Population-based cohort studies confirm significantly increased health-care utilization costs in patients presenting with cancer with MBD compared with those without MBD. The prolong

Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response.

Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on m

Targeting Oncoproteins for Molecular Cancer Therapy

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Навязчивое сексуальное поведение и проблематичное использование порнографии: всеобъемлющий, междисциплинарный и экспертный обзор описательной информации с указанием предлагаемых направлений будущей деятельности.

СПРАВОЧНАЯ ИНФОРМАЦИЯ И МАТЕРИАЛЫ: Характер и классификация дисрегулированного сексуального поведения по-прежнему широко обсуждаются. Сексуальные расстройства, связанные с сексуальным поведением, и проблематичное использование порнографии (PUP) two Наиболее часто изученные конструкции в этой области, каждая из которых имеет значительные последствия для психического здоровья, межличностного функционирования и более широкого благосостояния. Хотя научные результаты по этим темам за последнее десятилетие быстро расширились, в последних обзорах основное внимание, как правило, уделялось конкретным п

Immunoglobulin A Nephropathy: Molecular Pathogenesis and Targeted Therapy.

Immunoglobulin A nephropathy (IgAN), the most prevalent primary glomerulonephritis globally, is characterized by mesangial IgA deposition and heterogeneous clinical trajectories. Historically, management relied on renin-angiotensin system inhibition and empirical immunosuppression, yet high lifetime kidney failure risk persists despite optimized care. This review synthesizes advances in molecular pathogenesis, highlighting how the traditional multi-hit hypothesis-while foundational for targeted therapy development-fails to capture IgAN's recurrent, self-amplifying nature. We introduce the "spi

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… The antisense oligonucleotide RO7434656, which reduces hepatic factor B production, demonstrated 45% proteinuria reduction in phase 2 studies and is advancing to the IMAGINATION phase 3 trial. … reduction >10 months | Global Complement inhibitors Iptacopan (LNP023) | Factor B inhibition | Small molecule | Phase 3 | APPLAUSE‐IgAN | NCT04578834 | Active, not recruiting | 43.8% proteinuria reduction; US FDA approved | Global RO7434656 | Factor B inhibition | Antisense oligonucleotide | Phase 3 | IMAGINATION …

Development of an Active Chimeric IL13Rα2 ADC for Diffuse Intrinsic Pontine Glioma.

IntroductionDiffuse intrinsic pontine glioma (DIPG) is a rare pediatric brain tumor with a critical unmet need due to the lack of approved, curative interventions available. The interweaving of malignant cells with normal tissue makes surgical extraction essentially impossible, and radiation provides only transient benefit. The recent ONC201 FDA approval, however, suggests DIPG therapy is tractable. Having identified overexpression of IL13Rα2 in DIPG tumor tissue versus normal brain tissue, we investigated binding of commercially available IL13Rα2 monoclonal antibodies. The top candidate antib

BCMA-Targeting Therapy: Driving a New Era of Immunotherapy in Multiple Myeloma.

The treatment of multiple myeloma (MM) has entered into a new era of immunotherapy. Novel immunotherapies will significantly improve patient outcome via simultaneously targeting malignant plasma cell (PC) and reversing immunocompromised bone marrow (BM) microenvironment. B-cell maturation antigen (BCMA), selectively expressed in PCs and a key receptor for A proliferation-inducing ligand (APRIL), is highly expressed in MM cells from patients at all stages. The APRIL/BCMA signal cascades promote the survival and drug resistance of MM cells and further modulate immunosuppressive BM milieu. Impres