ABSTRACT
BACKGROUND: Pachymeningeal metastasis associated with gastric cancer, especially in its early stages, is extremely rare. OBSERVATIONS: The authors describe a 77-year-old man with a past medical history of lung cancer and previously treated chronic subdural hematoma who was admitted to their hospital because of hematemesis and newly diagnosed gastric cancer. He became unconscious during the hospitalization. The preoperative brain imaging studies had the appearance of recurrent subdural hematoma and extracranial tumor with skull invasion. Craniotomy revealed pachymeningeal carcinomatosis and en plaque metastasis of tumor. The histopathology of the tumors was consistent with metastatic gastric adenocarcinoma. LESSONS: This is the first reported case of metastatic gastric cancer as a pachymeninges-based en plaque entity. This report highlights the rare radiological presentation and operative findings in this case. The authors also summarize those case reports associated with dural metastasis arising from gastric cancer.
ABSTRACT
Three human nucleases, SNM1A, SNM1B/Apollo, and SNM1C/Artemis, belong to the SNM1 gene family. These nucleases are involved in various cellular functions, including homologous recombination, nonhomologous end-joining, cell cycle regulation, and telomere maintenance. These three proteins share a similar catalytic domain, which is characterized as a fused metallo-ß-lactamase and a CPSF-Artemis-SNM1-PSO2 domain. SNM1A and SNM1B/Apollo are exonucleases, whereas SNM1C/Artemis is an endonuclease. This review contains a summary of recent research on SNM1's cellular and biochemical functions, as well as structural biology studies. In addition, protein structure prediction by the artificial intelligence program AlphaFold provides a different view of the proteins' non-catalytic domain features, which may be used in combination with current results from X-ray crystallography and cryo-EM to understand their mechanism more clearly.
Subject(s)
DNA Repair Enzymes , DNA Repair , Humans , Artificial Intelligence , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , Endonucleases/genetics , Endonucleases/metabolism , Exodeoxyribonucleases/genetics , Exodeoxyribonucleases/metabolism , Nuclear Proteins/metabolism , Cell Cycle Proteins/metabolismABSTRACT
Ubiquitin has been recently identified as a chemokine receptor 4 (CXCR4) natural ligand, offering great potential for positron emission computed tomography (PET) imaging of CXCR4 expression. This study reports the preparation and evaluation of (64Cu)-radiolabeled ubiquitin for CXCR4 imaging. The ubiquitin was first fused with a C-terminal GGCGG sequence, and the resulting recombinant ubiquitin derivative UbCG4 was then functionalized with the trans-cyclooctene (TCO) moiety via thiol-maleimide click reaction, followed by 64Cu-radiolabeling through the TCO/Tz (tetrazine)-based Diels-Alder click reaction. In the prepared in vitro studies, the prepared (64Cu)-UbCG4 showed significantly higher specific uptakes in the 4T1 breast cancer cells compared with the uptakes in the CXCR4-knockdown 4T1 cells. In the in vivo evaluation in the 4T1-xenograft mouse model, (64Cu)-UbCG4 demonstrated a similar tumor uptake but much lower backgrounds compared with 64Cu-labeled AMD3465. These results suggested that (64Cu)-UbCG4 could serve as a potent PET tracer for the noninvasive imaging of CXCR4 expression in tumors.
ABSTRACT
Two hydrophilic spiroalkenes, azaspiro[2.3]hex-1-ene and azaspiro[2.4]hept-1-ene, were designed and synthesized. Compared to the previously reported spiro[2.3]hex-1-ene, the azaspiroalkenes exhibited greater water solubility and reactivity as dipolarophiles in the photoinduced tetrazole-alkene cycloaddition reaction. In addition, an azaspiro[2.3]hex-1-ene-containing amino acid, AsphK, was found to be charged by an engineered pyrrolysyl-tRNA synthetase into proteins via amber codon suppression in E. coli as well as in mammalian cells.