Search

Colorectal cancer (CRC) metastasis plays a crucial role in disease progression, yet the regulatory mechanisms underlying metastasis remain incompletely understood. Isobutyric acid (IBA), a short‐chain fatty acid found at high levels in serum of CRC patients, has been shown to be a critical metabolite influencing CRC proliferation. However, its role in tumor metastasis remains unknown. Here, utilizing liquid chromatography tandem mass spectrometry (LC‐MS/MS) analysis, we found that levels of IBA were significantly higher in patients with distant organ metastasis of CRC than in those without. Furthermore, IBA promoted CRC metastasis both in vitro and in vivo. Mass spectrometry, immunofluorescence, and cellular thermal shift assay revealed that IBA interacts with RACK1. Mechanistically, IBA binding to and activating RACK1 promotes regulation of downstream Akt and FAK signaling and CRC metastasis. Collectively, our study highlights the critical interplay between IBA and RACK1 and its impact on tumor metastasis. This study suggests that targeting the IBA–RACK1 signaling axis may be an effective therapeutic strategy for controlling CRC metastasis. [ABSTRACT FROM AUTHOR]

Abnormal epigenetic regulation is identified to correlate with cancer progression and renders tumor refractory and resistant to reactive oxygen species (ROS)‐based anti‐tumor actions. To address it, a sequential ubiquitination and phosphorylation epigenetics modulation strategy is developed and exemplified by the well‐established Fe‐metal‐organic framework (Fe‐MOF)‐based chemodynamic therapy (CDT) nanoplatforms that load the 26S proteasome inhibitor (i.e., MG132). The encapsulated MG132 can blockade 26S proteasome, terminate ubiquitination, and further inhibit transcription factor phosphorylation (e.g., NF‐κB p65), which can boost pro‐apoptotic or misfolded protein accumulations, disrupt tumor homeostasis, and down‐regulate driving genes expression of metastatic colorectal cancer (mCRC). Contributed by them, Fe‐MOF‐unlocked CDT is magnified to considerably elevate ROS content for repulsing mCRC, especially after combining with macrophage membrane coating‐enabled tropism accumulation. Systematic experiments reveal the mechanism and signaling pathway of such a sequential ubiquitination and phosphorylation epigenetics modulation and explain how it could blockade ubiquitination and phosphorylation to liberate the therapy resistance to ROS and activate NF‐κB‐related acute immune responses. This unprecedented sequential epigenetics modulation lays a solid foundation to magnify oxidative stress and can serve as a general method to enhance other ROS‐based anti‐tumor methods. [ABSTRACT FROM AUTHOR]

A T4B hepatic flexure of colon cancer that had invaded the liver, gall bladder, and pancreas/duodenum was removed through a D3 expanded right hemicolectomy + pancreaticoduodenectomy +sectional VI and VII hepatic segmentectomy. [ABSTRACT FROM AUTHOR]

Purpose: The overall survival (OS) of patients diagnosed with stage II‐III colorectal cancer (CRC) can vary greatly, even between patients with the same tumor stage. We aimed to design a nomogram to predict OS in resected, stage II‐III CRC and stratify patients with CRC into different risk groups. Patients and Methods: Based on data from 873 patients with CRC, we used univariate Cox regression analysis to select the significant prognostic features, which were subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for feature selection. Cross‐validation was used to confirm suitable tuning parameters (λ) for LASSO logistic regression. Then, the nomogram was used to estimate 3‐ and 5‐year OS based on the multivariable Cox regression model. The survival curves of the two groups were produced using the Kaplan‐Meier method. Risk group stratification was performed to assess the predictive capacity of the nomogram. Results: Preoperative mean platelet volume, preoperative platelet distribution width, monocytes, and postoperative adjuvant chemotherapy were identified as independent prognostic factors by LASSO regression and integrated for the construction of the nomogram. The nomogram provided good discrimination, with C‐indices of 0.67 and 0.69 for the training and validation sets, respectively. Calibration plots illustrated excellent agreement between the nomogram predictions and actual observations for 3‐ and 5‐year OS. Moreover, a significant difference in OS was shown between patients stratified into different risk groups (P <.001). Conclusion: We constructed and validated an original predictive nomogram for OS in patients with CRC after surgery, facilitating physicians to appraise the individual survival of postoperative patients accurately and identify high‐risk patients who need more aggressive treatment and follow‐up strategies. [ABSTRACT FROM AUTHOR]