therapy resistance

OBJECTIVES: In recent years, adjunctive therapies for epilepsy management are being explored due to considerable side effects carried by antiepileptic drugs (AEDs) and widespread reports of drug-resistant epilepsy. One such approach is non-invasive musical neurostimulation. Within this context, Mozart's sonata K448 has received particular attention following reports of reduced seizure frequency and a decrease in epileptiform discharges during and after music exposure; often described as the 'Mozart effect'...

PURPOSE: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the one-sided significance level of 0.1 used for sample size calculation). METHODS: We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib...

Recurrent abnormalities in immune surveillance-related genes affect the progression of diffuse large B-cell lymphoma (DLBCL) and modulate the response to therapeutic interventions. CD58 interacts with the CD2 receptor on T cells and natural killer (NK) cells and is recurrently mutated and deleted in DLBCL, suggesting it may play a role in regulating antitumor immunity. Herein, we comprehensively analyzed the genomic characteristics of CD58 through targeted next-generation sequencing, RNA-sequencing, whole-exome sequencing, and single-cell RNA-sequencing in patients with newly diagnosed DLBCL...

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy...

New technologies regularly bring about profound changes in our daily lives. Romantic relationships are no exception to these transformations. Some philosophers expect the emergence in the near future of love drugs: a theoretically achievable biotechnological intervention that could be designed to strengthen and maintain love in romantic relationships. We investigated laypeople's resistance to the use of such technologies and its sources. Across two studies (Study 1, French and Peruvian university students, N after exclusion = 186; Study 2, Amazon Mechanical Turk sample, N after exclusion = 693, pre-registered), we found that the use of love drugs designed to strengthen and maintain love in romantic relationships are considered as more morally problematic than psychological therapy with the same aim...

To investigate the in vivo and in situ effect of different types of lasers in prevention of enamel demineralization in high caries risk cases (around orthodontic brackets, around restoration and in caries susceptible pits and fissures). PubMed was searched using the following keyword sequence; (Laser therapy OR laser irradiation OR laser application) AND (enamel caries prevention OR enamel demineralization OR enamel remineralization OR early enamel caries OR early-enamel caries OR enamel resistance OR enamel decalcification OR white spot lesions WSLs OR incipient lesion OR enamel decay OR enamel Dissolution OR enamel microhardness) AND (clinical trial OR Randomized clinical trial OR In situ study)...

RATIONALE: Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects...

PURPOSE: Lutetium-177 [177 Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177 Lu]Lu-PSMA-617...

PURPOSE: Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. METHODS: This was a retrospective monocentric study from 01/2019 to 12/2022...

BACKGROUND: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI). MATERIALS/METHODS: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW)...

UNLABELLED: Mycoplasma pneumoniae (MP) is an important cause of community-acquired pneumonia in children and young adolescents. Despite macrolide antibiotics effectiveness as a first-line therapy, persistence of fever and/or clinical deterioration sometimes may complicate treatment and may even lead to severe systemic disease. To date, there is no consensus on alternative treatment options, optimal dosage, and duration for treating severe, progressive, and systemic MP pneumonia after macrolide treatment failure...

BACKGROUND: Glioblastoma (GBM) is an extremely aggressive form of brain tumor with low survival rates. Current treatments such as chemotherapy, radiation, and surgery are problematic due to tumor growth, invasion, and tumor microenvironment. GBM cells are resistant to these standard treatments, and the heterogeneity of the tumor makes it difficult to find a universal approach. Progression of GBM and acquisition of resistance to therapy are due to the complex interplay between tumor cells and the TME...

Cancer immunotherapy, a burgeoning modality for cancer treatment, operates by activating the autoimmune system to impede the growth of malignant cells. Although numerous immunotherapy strategies have been employed in clinical cancer therapy, the resistance of cancer cells to immunotherapeutic medications and other apprehensions impede the attainment of sustained advantages for most patients. Recent advancements in nanotechnology for drug delivery hold promise in augmenting the efficacy of immunotherapy. However, the efficacy is currently constrained by the inadequate specificity of delivery, low rate of response, and the intricate immunosuppressive tumor microenvironment...

The rise of pyrazinamide (PZA)-resistant strains of Mycobacterium tuberculosis (MTB) poses a major challenge to conventional tuberculosis (TB) treatments. PZA, a cornerstone of TB therapy, must be activated by the mycobacterial enzyme pyrazinamidase (PZase) to convert its active form, pyrazinoic acid, which targets the ribosomal protein S1. Resistance, often associated with mutations in the RpsA protein, complicates treatment and highlights a critical gap in the understanding of structural dynamics and mechanisms of resistance, particularly in the context of the G97D mutation...

Sepsis is a serious disease characterized by an inappropriate host response to infection, resulting in widespread inflammation and systemic organ failure. The aim of this research is to investigate the possibility of pomegranate peel-derived silver nanoparticles (PGNP) as a potential alternative therapy for sepsis. Characterization using transmission electron microscopy revealed 10-30 nm spherical nanoparticles. In a rat model of sepsis, PGNP treatment improved spleen health, histology, and immune response as compared with septic rats...

Pathogenic microorganisms produce numerous metabolites, including volatile organic compounds (VOCs). Monitoring these metabolites in biological matrices (e.g., urine, blood, or breath) can reveal the presence of specific microorganisms, enabling the early diagnosis of infections and the timely implementation of targeted therapy. However, complex matrices only contain trace levels of VOCs, and their constituent components can hinder determination of these compounds. Therefore, modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed...

INTRODUCTION: Immunotherapy by blocking immune checkpoints programmed death/ligand (PD1/PDL1) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) has emerged as new therapeutic targets in cancer. However, their efficacy has been limited due to resistance. A new- checkpoint V-domain Ig-containing suppressor of T cell activation (VISTA) has appeared, but the use of its inhibition effect in combination with antibodies targeting PDL1/PD1and CTLA4 has not been reported in ovarian cancer...

OBJECTIVE: To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center. METHODS AND ANALYSIS: The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation...

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and one of the leading causes of cancer-related deaths worldwide. The Wnt/β-Catenin signaling pathway is a highly conserved pathway involved in several biological processes, including the improper regulation that leads to the tumorigenesis and progression of cancer. New studies have found that abnormal activation of the Wnt/β-Catenin signaling pathway is a major cause of HCC tumorigenesis, progression, and resistance to therapy...

BACKGROUND: Racial disparities in oncological outcomes resulting from differences in social determinants of health (SDOH) and tumour biology are well described in prostate cancer (PCa) but similar inequities exist in bladder (BCa) and renal cancers (RCCs). Precision medicine (PM) aims to provide personalized treatment based on individual patient characteristics and has the potential to reduce these inequities in GU cancers. OBJECTIVE: This article aims to review the current evidence outlining racial disparities in GU cancers and explore studies demonstrating improved oncological outcomes when PM is applied to racially diverse patient populations...