Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), western blotting, fluorescence microscopy, and reactive oxygen species (ROS) production were assayed. We found that chrysin exhibited similar inhibition of cell viability as the 5-FU combination in a panel of human CRC cells. Furthermore, the results showed that chrysin significantly increased the levels of LC3-II, an autophagy-related marker, in CRC cells, which was not observed with the 5-FU combination. More importantly, blockage of autophagy induction restored chrysin-attenuated CRC cell viability. Further mechanistic analysis revealed that chrysin, not the 5-FU combination, induced ROS generation, and in turn, inhibited the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Collectively, these results imply that chrysin may be a potential replacement for the 5-FU and oxaliplatin combination to achieve antitumor activity through autophagy for CRC treatment in the future.

CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino) phenyl]ethanone) is a major active agent of Camptotheca acuminata’s alkaloid derivative, and its anti-tumorigenic activity, a valuable biological property of the agent, has been reported in many types of cancer. In this study, we researched the novel CIL-102-induced protein for either the induction of cell apoptosis or the inhibition of cell migration/invasiveness in colorectal cancer cells (CRC) and their molecular mechanism. Firstly, our data showed that CIL-102 treatment not only increased the cytotoxicity of cells and the production of Reactive Oxygen Species (ROS), but it also decreased cell migration and invasiveness in DLD-1 cells. In addition, many cellular death-related proteins (cleavage caspase 9, cleavage caspase 3, Bcl-2, and TNFR1 and TRAIL) and JNK MAPK/p300 pathways were increased in a time-dependent manner. Using the proteomic approach with a MALDI-TOF-TOF analysis, CIL-102-regulated differentially expressed proteins were identified, including eight downregulated and 11 upregulated proteins. Among them, upregulated Endoplasmic Reticulum resident Protein 29 (ERP29) and Fumarate Hydratase (FUMH) by CIL-102 were blocked by the inhibition of ROS production, JNK activity, and p300/CBP (CREB binding protein) signaling pathways. Importantly, the knockdown of ERP29 and FUMH expression by shRNA abolished the inhibition of cell migration and invasion by CIL-102 in DLD-1 cells. Together, our findings demonstrate that ERP29 and FUMH were upregulated by CIL102 via ROS production, JNK activity, and p300/CBP pathways, and that they were involved in the inhibition of the aggressive status of colorectal cancer cells.

Purpose Stage III colorectal cancer (CRC) is typically treated with surgery; however, it has a high recurrence rate and inconsistent benefits from postoperative chemotherapy. Inflammatory markers like the neutrophil-to-lymphocyte ratio (NLR) have shown prognostic value in various cancers. However, the prognostic significance of NLR measured before and after CRC surgery is not clear. This study aims to clarify the prognostic value of the combination of pre- and post-surgery NLR in stage III CRC patients. Methods Patients with stage III CRC treated between 2001 and 2022 were retrospectively analyzed using data from the Chang Gung Medical Research Database. Patients were categorized into 4 groups based on their pre- and post-operative NLR levels. Kaplan–Meier survival analysis and Cox proportional hazard models were used to assess the associations between NLR levels and overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). Results Data from 2,742 patients, median age of 62 years and 54% male, were analyzed. After adjustment, patients in Group IV, with high NLR values both before and after surgery, had greater risks of worse DFS (adjusted hazard ratio [aHR] = 1.30, 95% confidence interval [CI]: 1.13–1.50), OS (aHR = 1.36, 95% CI: 1.14–1.63), and CSS (aHR = 1.27, 95% CI: 1.04–1.55) compared to Group I. Conclusions High NLR levels before and after surgery is a strong predictor of poor outcomes in stage III CRC patients. The findings suggest that monitoring NLR at both time points can be a valuable prognostic tool, guiding postoperative care and treatment strategies to improve patient outcomes.

Colopleural fistula is a rare condition, and only a limited number of cases have been reported. Here, we report a case of idiopathic colopleural fistula in an adult without any known predisposing factors. The patient presented with a lung abscess and refractory empyema and was successfully treated with surgical resection. A 47-year-old man with a history of lung tuberculosis, which had been completely cured 4 years ago, presented to our emergency department with a productive cough and fever for 3 d. Tracing his history, he had undergone left lower lobe segmentectomy of the left lung due to lung abscess one year ago at another hospital. However, he developed refractory empyema postoperatively despite surgical intervention including decortication and flap reconstruction. After admission, we reviewed his previous medical images and noted a fistula tract between the left pleural cavity and splenic flexure. In addition, according to his medical records, bacterial culture of the thoracic drainage showed growth of Escherichia coli and Bacteroides fragilis. Our lower gastrointestinal series and colonoscopy confirmed the diagnosis of colopleural fistula. The patient underwent a left hemicolectomy, splenectomy, and distal pancreatectomy, and the diaphragm was repaired under our care. No further empyema recurrence was noted during follow-up. Indicative signs of colopleural fistula include refractory empyema accompanied by the growth of colonic flora in the pleural fluid.