J Med Chem
January 2025
Chemical Biology Section, Molecular Targets Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.
Autophagy, a recycling process in eukaryotes, contributes to tumor growth and metastasis by alleviating cellular stress and facilitating survival and chemoresistance. The development of small molecules that selectively inhibit this pathway has proven challenging and is required to determine if autophagy inhibition can be harnessed as an effective therapeutic strategy in cancer. Compound 19 was previously identified as a selective autophagy inhibitor that targets the ATG14L-Beclin1 protein-protein interaction, which regulates the formation, localization, and function of VPS34 Complex I to initiate autophagy.
View Article and Find Full Text PDFJ Natl Cancer Inst
January 2025
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Background: Adolescents and young adults (AYA) with germline CDH1 variants are at risk of overtreatment when precancer lesions are detected with endoscopic screening. We characterize diffuse-type gastric cancer prevalence and survival in AYA managed with prophylactic total gastrectomy (PTG) or endoscopic surveillance.
Methods: Prospective cohort study of 188 individuals aged 39 and younger enrolled from January 27, 2017, to May 1, 2023.
Cancer
January 2025
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Background: Testicular germ cell tumors (TGCTs) are the most common cancers among young men in the United States. Incidence rates among non-Hispanic White (NHW) men historically have been much higher than the rates among other men. To study whether this pattern had changed, the authors examined trends in TGCT incidence for the years 1992-2021.
View Article and Find Full Text PDFACS Omega
December 2024
Faculty of Health Science, University of Ss. Cyril and Methodius, 91701 Trnava, Slovakia.
A hybrid B3LYP version of the Density Functional Theory was applied in full geometry optimization followed by vibrational analysis of mustard-type molecules acting as antiblood cancer agents: melphalan and bendamustine. All calculations were performed with water as a solvent. In addition to the ground-state properties (dipole moment, quadrupole moment, dipole polarizability, solvated surface and volume, zero-point vibration energy, total entropic term), properties that characterize adiabatic redox processes (ionization energy, electron affinity, molecular electronegativity, chemical hardness, electrophilicity index) together with the absolute oxidation and reduction potentials were evaluated.
View Article and Find Full Text PDFFront Psychiatry
December 2024
Epidemiology Unit, National Institute for Health, Migration and Poverty, Istituto Nazionale per la promozione della salute delle popolazioni Migranti e per il contrasto delle malattie della Povertà (INMP), Rome, Italy.
Objective: Comprehensive evidence on the impact of the Coronavirus Disease 2019 (COVID-19) pandemic on the use of mental health services is scarce. The aim of this study was to evaluate the impact of the COVID-19 pandemic on the access to mental health services in Italy and to assess the socioeconomic and citizenship inequalities for the same outcome.
Methods: A population-based longitudinal open cohort of residents aged ≥ 10 years was established in three large centers covering about 6 million beneficiaries (nearly 10% of the entire population) of the Italian National Health Service (NHS) from 01 January 2018 to 31 December 2021.
JCO Oncol Adv
December 2024
Biometric Research Program, National Cancer Institute, Bethesda, MD.
Purpose: A phase II/III trial is a type of phase III trial that has embedded in it an intermediate phase II go/no-go decision as to whether to continue the accrual to the phase III sample size. We examine the design characteristics and experience of a well-defined set of National Cancer Institute phase II/III trials, with special emphasis on designed accrual suspensions while awaiting the data to become mature enough for the phase II analysis. This experience is used to highlight the potential of using a calendar backstop to avoid an inordinately long accrual suspension.
View Article and Find Full Text PDFMol Cell Biol
January 2025
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
RNA modifications are highly conserved across all domains of life, suggesting an early emergence and a fundamental role in cellular processes. The modification 3-(3-amino-3-carboxypropyl)uridine (acp³U) is found in tRNAs of eukaryotes and prokaryotes, and in the 16S rRNA of archaea. In eukaryotic rRNA, a complex modification containing the acp group, macpΨ is present at the analogous position.
View Article and Find Full Text PDFJ Anesth
January 2025
Department of Anesthesia and Critical Care Medicine, Cairo University, Cairo, Egypt.
Background: This study evaluated the ability of diaphragmatic excursion (DE), measured 2 h after extubation, to predict the need for resumption of ventilatory support within 48 h in surgical critically ill patients.
Methods: This prospective observational study included adult surgical critically ill patients intubated for > 24 h and extubated after a successful spontaneous breathing trial. Sonographic measurement of the DE was performed 2 h after extubation.
Eur J Pharm Biopharm
January 2025
Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Complete eradication of aggressive head and neck squamous cell carcinoma (HNSCC) still remains a major challenging problem due to numerous resistance properties of cancer stem cells (CSC) which is crucially responsible for tumor recurrence and metastasis. This challenge causes a high demand for the emergence of novel targeted treatment modalities for improved therapeutic efficacies. Phytochemicals derived from plants proves to be a wide reservoir of important drug candidates which have the potential to impede multiple aspects of malignant growth and progression.
View Article and Find Full Text PDFInt J Pharm
January 2025
General Surgery 3, Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128 Padua, Italy; NanoInspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy.
Macrophages are a pivotal immune cell population in the tumor microenvironment of colorectal cancer (CRC). Differently-polarized macrophages could be exploited to yield naturally-tailored biomimetic nanoparticles for CRC targeting. Here, membrane proteins were isolated from the THP-1 cell line, and anti-tumor macrophages (M1) were obtained from differentiation of THP-1.
View Article and Find Full Text PDFLancet Oncol
January 2025
Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA.
Transplant Cell Ther
January 2025
Dana-Farber Cancer Institute, Division of Transplantation and Cellular Therapy, Boston, MA. Electronic address:
Background: Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12-20% in haplo-HCT recipients using PTCy. The objective of this study was to determine if donor type influenced the risk of late graft failure following RIC HCT using PTCy-based GVHD prophylaxis.
View Article and Find Full Text PDFFluids Barriers CNS
January 2025
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 2108, Bethesda, MD, 20892, USA.
Nat Med
January 2025
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
The clinical management of people with multidrug-resistant (MDR) human immunodeficiency virus (HIV) remains challenging despite continued development of antiretroviral agents. A 58-year-old male individual with MDR HIV and Kaposi sarcoma (KS) was treated with a new antiretroviral regimen consisting of anti-CD4 domain 1 antibody UB-421 and capsid inhibitor lenacapavir. The individual experienced delayed but sustained suppression of plasma viremia and a substantial increase in the CD4 T cell count.
View Article and Find Full Text PDFNat Genet
January 2025
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.
View Article and Find Full Text PDFCancer Cell
December 2024
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA. Electronic address:
Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.
View Article and Find Full Text PDFJCO Glob Oncol
January 2025
Division of Medical Senology, European Institute of Oncology IRCCS, Milan, Italy.
Purpose: The use of social media is transforming physician-patient communication, mainly in the field of medical oncology. The pattern of social media use by medical oncologists is poorly studied. Therefore, we developed a survey to understand the preferences, experiences, opinions, and expectations of Italian medical oncologists and oncology fellows regarding the use of social media in cancer medicine to identify the different profiles of social media users.
View Article and Find Full Text PDFJ Clin Oncol
January 2025
Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Sci Immunol
January 2025
Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2.
View Article and Find Full Text PDFCell Rep
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) molecules retains the class II-associated invariant chain peptide (CLIP) fragment of the invariant chain bound to the MHC-II peptide binding groove due to reduced expression of the peptide editor H2-M and enhanced activity of the CLIP-generating proteinase cathepsin S. The net effect of this is that MHC-II molecules are unable to efficiently bind antigenic peptides.
View Article and Find Full Text PDFJAMA Netw Open
January 2025
Men's Health Inequities Research Lab, Milwaukee, Wisconsin.
Importance: Research indicates that social drivers of health are associated with cancer screening adherence, although the exact magnitude of these associations remains unclear.
Objective: To investigate the associations between individual-level social risks and nonadherence to guideline-recommended cancer screenings.
Design, Setting, And Participants: This cross-sectional study used 2022 Behavioral Risk Factor Surveillance System data from 39 US states and Washington, DC.
Neurochem Res
January 2025
Diagnostic Radiology Department, National Cancer Institute, Misrata, Libya.
Huntington's disease (HD) is a progressive neurodegenerative disease resulting from a mutation in the huntingtin (HTT) gene and characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Currently, no disease-modifying treatments are available. Recent research has developed therapeutic agents that may have the potential to directly target the disease pathology, such as gene silencing or clearing the mutant protein.
View Article and Find Full Text PDFInt J Colorectal Dis
January 2025
Medical Oncology Department, National Cancer Institute, Cairo University, Giza, Egypt.
Purpose: The role of adjuvant chemotherapy in rectal cancer patients downstaged to ypT0-2 N0 after neoadjuvant chemoradiotherapy (CRT), and surgery is still debated. This study investigates the impact of adjuvant chemotherapy on survival outcomes in this patient population.
Methods: This retrospective study analyzed hospital records of rectal cancer cases from Shefa Al Orman Cancer Hospital between January 2016 and December 2020, focusing on patients downstaged to ypT0-2 N0 after neoadjuvant CRT and surgery.
Cancer Immunol Immunother
January 2025
Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Tissue factor (TF) is a cell surface protein that plays a role in blood clotting but is also commonly expressed in many cancers. Recent research implicated TF in cancer proliferation, metastasis, angiogenesis, and immune escape. Therefore, TF can be considered a viable therapeutic target against cancer.
View Article and Find Full Text PDFClin Chem
January 2025
Prenatal Genomics and Therapy Section, Center for Precision Health Research, National Human Genome Institute, National Institutes of Health, Bethesda, MD, United States.
Background: Prenatal cell-free DNA (cfDNA) screening is a success story of clinical genomics that has translated to and transformed obstetric care. It is a highly sensitive and specific method of screening for the most common fetal aneuploidies, including trisomies 13, 18, and 21. While primarily designed to detect fetal chromosomal abnormalities, the test also analyzes maternal cfDNA, which can complicate interpretation of results.
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