Therapie

PURPOSE: For children with neurodevelopmental disabilities (CWNDs), early diagnosis that leads to early intervention with regular targeted therapies is critical. In Qatar, private therapy centres that address this demand often have highly exclusive prices restricting families from availing them. This paper examines the challenges faced by families with CWNDs, as well as various financial and systemic obstacles, from the vantage point of these centres, all of which culminate in an extraordinarily high disability price tag for disability families in Qatar...

The advancement of mRNA-based immunotherapies for cancer is highly dependent on the effective delivery of RNA payloads using ionizable lipid nanoparticles (LNPs). However, the clinical application of these therapies is hindered by variable mRNA expression among different cancer types and the risk of systemic toxicity. The transient expression profile of mRNA further complicates this issue, necessitating frequent dosing and thus increasing the potential for adverse effects. Addressing these challenges, we utilized a high-throughput combinatorial method to synthesize and screen LNPs that efficiently deliver circular RNA (circRNA) to lung tumors...

The intricate tumor microenvironment in triple-negative breast cancer (TNBC) hampers chemotherapy and immunotherapy efficacy due to dense extracellular matrix (ECM) by tumor-associated fibroblasts (TAFs). Nanoparticle-based therapies, especially "all in one" nanoparticles, have shown great potential in combined drug delivery strategies to reshape the tumor microenvironment and enhance therapeutic efficiency. However, these "all in one" nanoparticles suffer from limitations in targeting different target cells, uncontrollable dosing ratio, and disregarding the impact of delivery schedules...

BACKGROUND: Exagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis through ex vivo clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing of the erythroid-specific enhancer region of BCL11A in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs). METHODS: We conducted an open-label, single-group, phase 3 study of exa-cel in patients 12 to 35 years of age with transfusion-dependent β-thalassemia and a β0 /β0 , β0 /β0 -like, or non-β0 /β0 -like genotype...

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) represents a high-risk B-lineage ALL subtype characterized by adverse clinical features and poor relapse-free survival despite risk-adapted multi-agent chemotherapy regimens. The advent of next-generation sequencing has unraveled the diversity of kinase-activating genetic drivers in Ph-like ALL that are potentially amenable to 'personalized' molecularly-targeted therapies. Based upon robust preclinical data and promising case series of clinical activity of tyrosine kinase inhibitor (TKI)-based treatment in adults and children with relevant genetic Ph-like ALL subtypes, several clinical trials have investigated the efficacy of JAK- or ABL-directed TKIs in CRLF2/JAK pathway-mutant or ABL-class Ph-like ALL, respectively...

BACKGROUND: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear...

In this retrospective study, CAR T-cells remained effective in relapsed/refractory LBCL patients after prior exposure to bispecific antibodies (BsAbs) targeting different antigens. These results are relevant to clinical practice, particularly given the increasing use of BsAbs in earlier treatment lines.

BACKGROUND: Cancer is the leading cause of death in Canada, and living with cancer generates psychological demands, including depression and anxiety among cancer survivors and caregivers. Text4Hope-Cancer Care SMS text messaging-based service was provided to people with cancer and caregivers during the COVID-19 pandemic to support their mental health. OBJECTIVE: The aim of this study is to examine the clinical effectiveness of and satisfaction with Text4Hope-Cancer Care in addressing mental health conditions among people living with cancer and caregivers...

IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2...

BACKGROUND: Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking...

Disruption of DNA damage repair via impaired homologous recombination is characteristic of Ewing sarcoma (EWS) cells. We hypothesize that this disruption results in increased reliance on non-homologous end joining (NHEJ) to repair DNA damage. In this study, we investigated if pharmacological inhibition of the enzyme responsible for NHEJ, the DNA-PK holoenzyme, alters the response of EWS cells to genotoxic standard of care chemotherapy. We used analyses of cell viability and proliferation to investigate the effects of clinical DNA-PK inhibitors (DNA-PKi) in combination with six therapeutic or experimental agents for EWS...

BACKGROUND: Black adults who smoke and have HIV experience immense stressors (eg, racial discrimination and HIV stigma) that impede smoking cessation success and perpetuate smoking-related health disparities. These stressors also place Black adults who smoke and have HIV at an increased risk of elevated interoceptive stress (eg, anxiety and uncomfortable bodily sensations) and smoking to manage symptoms. In turn, this population is more likely to smoke to manage interoceptive stress, which contributes to worse HIV-related outcomes in this group...

Chemotherapeutics, radiation, targeted therapeutics and immunotherapeutics each demonstrate clinical benefits for a small subset of patients with solid malignancies. Immune cells infiltrating the tumor and the surrounding stroma play a critical role in shaping cancer progression and modulating therapy response. They do this by interacting with the other cellular and molecular components of the tumor microenvironment (TME). Spatial multi-OMICs technologies are rapidly evolving. Currently, such technologies allow high-throughput RNA and protein profiling and retain geographical information about the TME cellular architecture and the functional phenotype of tumor, immune and stromal cells...

BACKGROUND: Primary prevention patients with ischemic cardiomyopathy and chronic total occlusion of an infarct-related coronary artery (IRA-CTO) are at a particularly high risk of implantable cardioverter-defibrillator (ICD) therapy occurrence. AIM: To evaluate the efficacy of preventive CTO-related substrate ablation strategy in ischaemic cardiomyopathy patients undergoing primary prevention ICD implantation. METHODS: The PREVENTIVE VT study was a prospective, multicenter, randomized trial including ischaemic patients with ejection fraction ≤40%, no documented VAs, and evidence of scar related to the coronary CTO...

Teclistamab, an off-the-shelf B-cell maturation antigen (BCMA) × CD3 bispecific antibody that mediates T-cell activation and subsequent lysis of BCMA-expressing myeloma cells, is approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). As a T-cell redirection therapy, clinical outcomes with teclistamab may be influenced by patient immune fitness and tumor antigen expression. We correlated tumor characteristics and baseline immune profiles with clinical response and disease burden in patients with RRMM from the pivotal phase 1/2 MajesTEC-1 study, focusing on patients treated with 1...

PURPOSE: Use of artificial intelligence (AI) in cancer care is increasing. What remains unclear is how best to design patient-facing systems that communicate AI output. With oncologist input, we designed an interface that presents patient-specific, machine learning-based 6-month survival prognosis information designed to aid oncology providers in preparing for and discussing prognosis with patients with advanced solid tumors and their caregivers. The primary purpose of this study was to assess patient and caregiver perceptions and identify enhancements of the interface for communicating 6-month survival and other prognosis information when making treatment decisions concerning anticancer and supportive therapy...

BACKGROUND: Psoriasis was long regarded as an inflammatory disease limited to the skin. Data from dermatologic, rheumatologic and cardiologic research now show it to be a systemic disease, for which the term psoriatic disease is used. METHODS: This paper is based on a selective literature search with special attention to the findings of clinical trials and other current publications, as well as the recommendations of international guidelines. RESULTS: Immunologically mediated inflammation of the skin, arteries, bones, and joints is a central feature of psoriatic disease...

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, causing a substantive threat to the public, which receives global concern. However, there are limited drugs targeting the treatment of DN. Owing to this, it is highly crucial to investigate the pathogenesis and potential therapeutic targets of DN. The process of ferroptosis is a type of regulated cell death (RCD) involving the presence of iron, distinct from autophagy, apoptosis, and pyroptosis. A primary mechanism of ferroptosis is associated with iron metabolism, lipid metabolism, and the accumulation of ROS...

BACKGROUND: Reducing proton treatment time improves patient comfort and decreases the risk of error from intrafractional motion, but must be balanced against clinical goals and treatment plan quality. PURPOSE: To improve the delivery efficiency of spot scanning proton therapy by simultaneously reducing the number of spots and energy layers using the reweighted <mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mi>l</mml:mi> <mml:mn>1</mml:mn></mml:msub> <mml:annotation>$l_1$</mml:annotation></mml:semantics> </mml:math> regularization method...

Tumor mutation burden (TMB) has profound implications for personalized cancer therapy, particularly immunotherapy. However, the size of the panel and the cutoff values for an accurate determination of TMB are still controversial. In this study, a pan-cancer analysis was performed on 22 cancer types from The Cancer Genome Atlas. The efficiency of gene panels of different sizes and the effect of cutoff values in accurate TMB determination was assessed on a large cohort using Whole Exome Sequencing data ( n  = 9929 patients) as the gold standard...