Metabolic landscape of disseminated cancer dormancy.

Cancer dormancy is a phenomenon defined by the entry of cancer cells into a reversible quiescent, nonproliferative state, and represents an essential part of the metastatic cascade responsible for cancer recurrence and mortality. Emerging evidence suggests that metabolic reprogramming plays a pivotal role in enabling entry, maintenance, and exit from dormancy in the face of the different environments of the metastatic cascade. Here, we review the current literature to understand the dynamics of metabolism during dormancy, highlighting its fine-tuning by the host micro- and macroenvironment, and put forward the importance of identifying metabolic vulnerabilities of the dormant state as therapeutic targets to eradicate recurrent disease.

Gastric-like (pseudopyloric and pseudofoveolar) metaplasia and Paneth cell hyperplasia-neglected histological features of chronic ileal inflammation.

Architectural distortion and basal plasmacytosis are the most widely recognized histologic features of chronic ileal inflammation. However, these features might be difficult to assess in small, poorly oriented, or superficial biopsies. Additional features of chronic mucosal damage, including pseudopyloric or pseudofoveolar metaplasia and Paneth cell hyperplasia, have been less commonly reported, and their broader appreciation could facilitate the diagnosis of chronic ileal inflammatory conditions.

Management of Recurrent Vancomycin-resistant Bacteremia With Oritavancin: A Case Report.

Background/aim: Vancomycin-resistant Enterococcus causes significant morbidity, mortality, and excess healthcare costs when compared to vancomycin-susceptible isolates. Patients with hematological malignancies, especially those who undergo hematopoietic stem cell transplantation, are at a particularly high risk for infections with vancomycin-resistant Enterococcus, with mortality ranging from 40-100%. Linezolid and daptomycin are the two most commonly used antibiotics for treatment of vancomycin-resistant enterococcal infections, however, there has been recent emergence of resistance to these drugs as well.

The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma.

Several therapeutic agents have been approved for treating multiple myeloma (MM), a cancer of bone marrow resident plasma cells. Predictive biomarkers for drug response could help guide clinical strategies to optimize outcomes. Here, we present an integrated functional genomic analysis of tumor samples from MM patients that were assessed for their ex vivo drug sensitivity to 37 drugs, clinical variables, cytogenetics, mutational profiles, and transcriptomes.

EGFR-mediated HSP70 phosphorylation facilitates PCNA association with chromatin and DNA replication.

Efficient DNA replication requires highly coordinated programs for the timely recruitment of protein complexes to DNA replication forks. Defects in this process result in replication stress, which in turn activates cell cycle checkpoints, suppresses cell proliferation and induces apoptosis. In response to persistent cell growth signals that speed up DNA replication processes, cells accelerate the recruitment of DNA replication proteins to avoid DNA replication stress.

Targeted degradation of the HPV oncoprotein E6 reduces tumor burden in cervical cancer.

Human Papilloma Virus (HPV)-related cancers are a global health burden, yet there are no targeted therapies available for chronically infected patients. The HPV protein E6 is essential for HPV-mediated tumorigenesis and immune evasion, making it an attractive target for antiviral drug development. In this study, we developed an E6-targeting Proteolysis Targeting Chimera (PROTAC) that inhibits the growth of HPV(+) tumors.

Ibrutinib for therapy of steroid-refractory chronic graft vs. host disease: A multicenter real-world analysis.

To examine activity of ibrutinib in steroid-refractory chronic GVHD (SR-cGVHD) after FDA approval, we conducted a multicenter retrospective study. Data were standardly collected (N=270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), GI (26%), lung (27%), liver (19%), genital (7%), other (4.

Discrepancy Between Liquid Biopsy and Tumor Next-Generation Sequencing Due to Low Tumor Fraction in a Patient With Lung Adenocarcinoma.

Tumor next-generation sequencing (NGS) is the gold standard molecular testing for driver genomic alterations in patients with advanced non-small cell lung cancer (NSCLC). However, it requires a biopsy, which is an invasive procedure. In contrast, a liquid biopsy is a minimally invasive test that measures circulating tumor DNA (ctDNA) in the plasma and can be also used for molecular profiling.

Direct catalytic photodecarboxylative amination of carboxylic acids with diazirines for divergent access to nitrogen-containing compounds.

Amines, hydrazines, and nitrogen-containing heterocycles are pivotal species in medicine, agriculture, fine chemicals, and materials. Diazirines have been recently reported to serve as versatile electrophilic amination reagents for the synthesis of building blocks or late-stage C-N bond formation. Here, we report the catalytic photodecarboxylative amination of carboxylic acids with diazirines under mild conditions.

Transgelin 2 guards T cell lipid metabolism and antitumour function.

Mounting effective immunity against pathogens and tumours relies on the successful metabolic programming of T cells by extracellular fatty acids. Fatty-acid-binding protein 5 (FABP5) has a key role in this process by coordinating the efficient import and trafficking of lipids that fuel mitochondrial respiration to sustain the bioenergetic requirements of protective CD8 T cells. However, the mechanisms that govern this immunometabolic axis remain unexplored.

Stratification of Wilms tumor patients using physicochemical properties of the adaptive immune receptor polypeptides, IGL and TRG.

Introduction: Wilms tumor (WT) is the most common pediatric renal malignancy. Current guidelines that stratify WT risk and determine treatment courses are inadequate, as over 60 % of WT survivors develop treatment-related complications. Recently, numerous advances in establishing patient sub-groups with different clinical features have been realized by evaluating the adaptive immune receptor (IR) complementarity determining region-3 (CDR3) amino acid (AA) sequences, a reasonable series of successes, given the prominent role of the CDR3 in antigen binding, including tumor antigen binding.

Histone deacetylase upregulation of neuropilin-1 in osteosarcoma is essential for pulmonary metastasis.

The lungs represent the most common site of metastasis for osteosarcoma (OS). Despite our advances in developing targeted therapies for treating solid malignancies, broad acting chemotherapies remain the first line treatment for OS. In assaying the efficacy of approved therapeutics for non-OS malignancies, we previously identified the histone deacetylase 1 and 2 (HDAC1 and 2) inhibitor, romidepsin, as effective for the treatment of established lung metastatic OS.

Diet and Survival in Black Women With Epithelial Ovarian Cancer.

Importance: Ovarian cancer survival among Black women is the lowest across all racial and ethnic groups. Poor dietary quality also disproportionately affects Black populations, but its association with ovarian cancer survival in this population remains largely unknown.

Objective: To examine associations between dietary patterns and survival among Black women diagnosed with epithelial ovarian cancer (EOC).

A ten-year overview of cancer genetic family history screening in Georgia's Latina population.

Background: Population-based cancer genetic family history (FH) screening to identify families at high risk for BRCA-associated cancers has been endorsed by national public health policies. This report aimed to describe the utilization of FH screening services from 2013 to 2022 according to rurality and socioeconomic deprivation among Latinas in Georgia.

Methods: Women who attended a medical appointment at participating Georgia Public Health Clinics were invited to complete FH screening.

Systemic Therapy Options for Peritoneal Mesothelioma.

Peritoneal mesothelioma is an uncommon malignancy affecting approximately 300 new patients annually in the United States. Due to its low incidence, prospective clinical trials specific to this disease are scant. Recommendations regarding systemic therapy are mostly extrapolated from clinical trials conducted among patients with pleural mesothelioma.

Outcomes of Haploidentical Stem Cell Transplant Recipients With HHV-6B Reactivation.

Background: Human herpesvirus 6B (HHV-6B) frequently reactivates following allogeneic stem cell transplant (alloHCT). Consensus guidelines note that haploidentical alloHCT may represent a high-risk population for which there is little evidence; this warrants further investigation.

Methods: In this single-center retrospective study, we evaluated 188 consecutive adult patients receiving haploidentical alloHCT between 11/2014 and 11/2020 and compared outcomes between patients with HHV-6B reactivation receiving targeted antiviral therapy and those who were clinically observed.

Fascial Manual Medicine: A Continuous Evolution.

From the perspective of fascial manual medicine (FMM), the body should not be considered as a set of compartments, but as a functional continuum, where most of the tissues (considering embryology) are fascia. The cells that make up the fascia can use multiple strategies to communicate, with neighboring cells, with the tissue to which they belong, and with the entire body, thanks to biochemical (microscopy) and electromagnetic (nanoscopy) possibilities. These multiple capacities to send and receive information make the border or layer of the different tissues seem absent.