A case of Li-Fraumeni syndrome caused by a 3.6 kb deletion in the TP53 gene suggested by additional data from the NCC Oncopanel.

A Japanese woman with Li-Fraumeni syndrome in her 40s underwent comprehensive genetic profiling accompanied by germline data using the Oncoguide NCC Oncopanel, but no germline pathogenic variants in the tumor suppressor gene TP53 were detected. However, careful examination of additional data in the report suggested the presence of a large TP53 deletion. Custom targeting next-generation sequencing and nanopore sequencing revealed a 3.

ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.

Factors Influencing Knowledge-Action Gap in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease: A Qualitative Study.

Objective: To explore the knowledge-action gap regarding health behaviors and their influencing factors among patients with metabolic dysfunction-associated fatty liver disease (MAFLD), using the Health Belief Model as a theoretical framework.

Design: A qualitative approach was adopted, involving semistructured interviews with individuals with MAFLD.

Setting: Participants were recruited from a community hospital and a tertiary hospital in Nanjing, China, between July and October 2022.

Experiences of patients who retest positive for SARS-CoV-2 Omicron variant after discharge: a qualitative study.

Introduction: In this study, we analyzed the psychological aspects of coronavirus disease 2019 (COVID-19) patients who were discharged from the hospitals in Shanghai, China, and later had positive nucleic acid retest results for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection (re-positive COVID-19). The purpose was to gain clarity on the patients' needs and to provide evidence for the medical staff to deliver scientific and targeted health care to the patients.

Methodology: We screened patients who tested positive for SARS-CoV-2 Omicron variant infection by nucleic acid testing after having previously recovered from a COVID-19 infection and being discharged from Shanghai shelter hospitals or COVID-19-designated hospitals from April 3, 2022, to May 10, 2022.

TRAF1 promotes osteoclastogenesis by enhancing metabolic adaptation to oxidative phosphorylation in an AKT-dependent manner.

Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a crucial signaling adaptor involved in multiple cellular events. However, its role in regulating osteoclastogenesis and energy metabolism remains unclear. Here, we report that TRAF1 promotes osteoclastogenesis and oxidative phosphorylation (OXPHOS).

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival.

One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems.

Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.

Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.

Lay views in Southern France of the acceptability of refusing to provide treatment because of alleged futility.

Aim: To carry out a detailed study of existing positions in the French public of the acceptability of refusing treatment because of alleged futility, and to try to link these to people's age, gender, and religious practice.

Method: 248 lay participants living in southern France were presented with 16 brief vignettes depicting a cancer patient at the end of life who asks his doctor to administer a new cancer treatment he has heard about. Considering that this treatment is futile in the patient's case, the doctor refuses to prescribe it.

Estimates and trends in death and disability from atrial fibrillation/atrial flutter due to high sodium intake, China, 1990 to 2019.

Objective: The effect of sodium intake on atrial fibrillation (AF)/atrial flutter (AFL), with respect to sex and age, has yet to be elucidated. This study aims to compare long-term trends in AF/AFL death and disability due to high sodium intake in China from 1990 to 2019.

Methods: We utilized data from the Global Burden of Disease study to assess the mortality and disability burden of AF/AFL attributable to high sodium intake (> 5 g/d) in China from 1990 to 2019.

Blood-based epigenome-wide association study and prediction of alcohol consumption.

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait.

The association between Chlamydia pneumoniae infection and prognosis in lung cancer patients: a prospective study.

Background: The prognostic value of Chlamydia pneumoniae (Cpn) infection in postoperative lung cancer patients remains unclear. This study aimed to evaluate the association between Cpn infection and survival in lung cancer patients.

Methods: This study included 309 newly diagnosed primary lung cancer patients from three hospitals in Fuzhou, China.

CSPG4 overexpression implicates higher risks of recurrence and tumorigenesis after surgical intervention of vocal fold Leukoplakia.

Background: Vocal fold leukoplakia (VFL), a precancerous lesion of the larynx, is characterized by white plaques on the vocal fold mucous membrane. Currently, there are no reliable biomarkers to predict the recurrence and malignant transformation of VFL. Considering chondroitin sulfate proteoglycan 4 (CSPG4) as a biomarker for malignant tumors such as laryngeal squamous cell carcinoma (LSCC), we conducted this cohort study to evaluate the prognostic influence of CSPG4 expression on VFL patients.

Circulating HPVDNA in patients undergoing transoral robotic surgery for oropharyngeal cancer: liquid biopsy could identify molecular residual disease.

Objectives: we evaluated the hypothesis that level of ctHPVDNA on the first postoperative day (POD-1); and at 15 days (POD-15) could be associated with the need for adjuvant therapy and the presence of recurrence.

Materials And Methods: this is a prospective observational study on biomarkers, focusing on the longitudinal monitoring of ctHPVDNA in a cohort of HPV-OPSCC patients undergoing TORS. Blood samples were collected according to the following schema: (1) pretreatment; (2) on first postoperative day (POD 1); and (3) at 15 days (POD 15).

A multicenter study of neurofibromatosis type 1 utilizing deep learning for whole body tumor identification.

Deep-learning models have shown promise in differentiating between benign and malignant lesions. Previous studies have primarily focused on specific anatomical regions, overlooking tumors occurring throughout the body with highly heterogeneous whole-body backgrounds. Using neurofibromatosis type 1 (NF1) as an example, this study developed highly accurate MRI-based deep-learning models for the early automated screening of malignant peripheral nerve sheath tumors (MPNSTs) against complex whole-body background.

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns.

Background: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Adding checkpoint inhibitors to first-line chemotherapy for NUT carcinoma patients.

Rare cancers present significant challenges in diagnosis, treatment, and research, accounting for up to 25% of global cancer cases. Due to their rarity and atypical presentations, they are often misdiagnosed, resulting in late-stage detection and poor outcomes. Here, we describe a patient case with advanced metastatic nasopharynx NUT carcinoma, one of the rarest and most aggressive cancers.

Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.

Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits a high frequency of neural invasion (NI). Schwann cells (SCs) have been shown to be reprogrammed to facilitate cancer cell migration and invasion into nerves. Since extracellular vesicles (EVs) affect the tumour microenvironment and promote metastasis, the present study analysed the involvement of EVs from pancreatic cancer cells and their microenvironment in altering SC phenotype as part of the early events in the process of NI.

A safe haven for cancer cells: tumor plus stroma control by DYRK1B.

The development of resistance remains one of the biggest challenges in clinical cancer patient care and it comprises all treatment modalities from chemotherapy to targeted or immune therapy. In solid malignancies, drug resistance is the result of adaptive processes occurring in cancer cells or the surrounding tumor microenvironment (TME). Future therapy attempts will therefore benefit from targeting both, tumor and stroma compartments and drug targets which affect both sides will be highly appreciated.

Basic Considerations for Data Pooling Strategy in Multi-Regional Clinical Trials (MRCTs).

The National Medical Products Administration of China has been implementing ICH E17, which describes the general principles for planning and designing of multi-regional clinical trials (MRCTs), yet there are several ambiguities in the execution and conduct remains in China or East Asia. In specific, pooling strategy, effect modifiers (EMs), statistical analysis, sample size allocation and their impact in alignment with global trial remains a challenge. In this paper, we explore on the criteria mentioned above under the context of China.

Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer.

Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and α-smooth muscle (α-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro.

Prognostic factors and outcomes of adjuvant and first-line metastatic treatments in melanoma a Turkish oncology group study.

Management of melanoma has changed significantly with the discovery of targeted therapies and immune checkpoint inhibitors (ICI). Our aim in the study is to determine which treatment alternatives, specifically dabrafenib plus trametinib and ICIs, are effective in adjuvant therapy and which treatment is effective as first-line metastatic therapy. This retrospective, multicenter study included 120 patients diagnosed with stage IIIB-IIID melanoma receiving both adjuvant and first-line metastatic treatment between 2007 and 2023.

Evaluation of transcriptomic changes after photobiomodulation in spinal cord injury.

Spinal cord injury (SCI) is a significant cause of lifelong disability, with no available disease-modifying treatments to promote neuroprotection and axon regeneration after injury. Photobiomodulation (PBM) is a promising therapy which has proven effective at restoring lost function after SCI in pre-clinical models. However, the precise mechanism of action is yet to be determined.