The worldwide incidence rate of cancer of unknown primary (CUP) reaches 5% (Kang et al, 2021; Lee, Sanoff, 2020; Yang et al, 2022). CUP has an alarmingly high mortality rate, with 84% of patients succumbing within the first year following diagnosis (Registration and Service, 2018). Under normal circumstances, tumor cell metastasis follows the «seed and soil» hypothesis, displaying a tissue-specific pattern of cancer cell homing behavior based on the microenvironment composition of secondary organs. In this study, we questioned whether seed and soil concept applies to CUP, and whether the pattern of tumor and metastasis manifestations for cancer of known primary (CKP) can be used to inform diagnostic strategies for CUP. We compared data from metastatic and primary CUP foci to the metastasis patterns observed in CKP. Furthermore, we evaluated several techniques for identifying the tissue-of-origin (TOO) in CUP profiling, including DNA, RNA, and epigenetic TOO techniques.
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http://dx.doi.org/10.1016/j.critrevonc.2024.104297 | DOI Listing |
Nat Commun
December 2024
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology.
View Article and Find Full Text PDFNat Commun
December 2024
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, China.
Although acute myeloid leukemia (AML) affects hematopoietic stem cell (HSC)-supportive microenvironment, it is largely unknown whether leukemia-modified bone marrow (BM) microenvironment can be remodeled to support normal hematopoiesis after complete remission (CR). As a key element of BM microenvironment, endothelial progenitor cells (EPCs) provide a feasible way to investigate BM microenvironment remodeling. Here, we find reduced and dysfunctional BM EPCs in AML patients, characterized by impaired angiogenesis and high ROS levels, could be partially remodeled after CR and improved by N-acetyl-L-cysteine (NAC).
View Article and Find Full Text PDFHere we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
View Article and Find Full Text PDFElife
December 2024
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands.
Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases.
View Article and Find Full Text PDFTher Adv Vaccines Immunother
December 2024
Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Background: Cannabis (CAN) use has risen significantly over the last few decades. CAN has potent immunosuppressive properties, which could antagonize the effect of immunotherapy (IO). The impact of CAN use on clinical cancer outcomes remains unclear.
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