The transmission of information between tumor cells and other cell types in the tumor microenvironment plays an important role in tumor metastasis and is critically modulated by exosomes and other mediators. Tumor-derived exosomes can promote epithelial-mesenchymal transition, angiogenesis, immune escape, formation of the pre-metastatic microenvironment, and transmission of drug-resistant molecules, thereby promoting tumor growth, invasion, and metastasis. Integrins are important regulatory molecules on exosomes that can locate metastatic cells at the initial stage of metastasis and show good organotropism. This fact suggests that a clear understanding of the roles of exosomal integrins will be beneficial for future clinical applications. Follow-up studies on exosomes using continuously updated purification techniques and identification methods are extremely important. In addition to their potential as cancer biomarkers, exosomes also provide new research directions for precision medicine. Currently, exosomes have potential value in disease treatment and provide clinicians with more meaningful judgment standards.

Aim: To evaluate the role of clinical features and blood markers in patients with malignant digestive tract tumors bone metastasis. Materials & methods: A total of 267 patients were included in thi...

Background: Five-fluorouracil, folinic acid, oxaliplatin and irinotecan (FOLFOXIRI) regimen is used as the first-line treatment for metastatic colorectal cancer (mCRC). The use of capecitabine, an oral fluoropyrimidine pro-drug, is feasible and safe; hence, it provides an interesting alternative to 5-fluorouracil in the abovementioned regimen. This study aimed to evaluate the efficacy and safety of capecitabine, oxaliplatin, and irinotecan (XELOXIRI) regimen use with or without targeted drugs in Chinese patients with mCRC. Methods: We conducted a retrospective, longitudinal cohort study of patients with mCRC who received XELOXIRI regimen with or without targeted drugs (bevacizumab or cetuximab) every 2 weeks between January 2017 and November 2019 at the National Cancer Center/Cancer Hospital, the Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment efficacy was assessed by investigators by evaluating the objective response rate (ORR) and disease control rate (DCR). Overall survival (OS) was assessed using Cox proportional hazards models. The adverse events were also analyzed. Results: Sixty-one consecutive patients were examined and followed up for survival. As of November 8, 2021, the median follow-up time was 35.4 months. Disease progression and death occurred in 50 (82%) and 38 (62%) patients, respectively. The median treatment duration of XELOXIRI with or without bevacizumab or cetuximab was 10 cycles (range, 1–12 cycles). The median OS and PFS were 32.2 months (95%CI [24.8–39.6]) and 9.3 months (95% CI [8.1–10.5]), respectively. The ORR of 48 patients with measurable lesions was 70.8%, and the DCR was 89.6%. RAS/BRAF wild-type (HR 0.39; 95% CI [0.16–0.96], p = 0.04) and metastatic organs > 2 (HR 3.25; 95% CI [1.34–7.87], p = 0.009) were independent prognostic factors for OS. The incidence of any grade of adverse events (AEs) was 96.7% (59/61). Grade ≥ 3 AEs included neutropenia (19.7%), leukopenia (9.8%), diarrhea (3.3%), vomiting (3.3%), febrile neutropenia (1.6%), and thrombocytopenia (1.6%). No treatment-related death occurred. Conclusion: The use of the XELOXIRI regimen with or without a targeted drug was effective, with a manageable toxicity profile in Chinese patients with mCRC.

Purpose: Treatment options for refractory metastatic colorectal cancer (CRC) are scarce. This retrospective study aimed to evaluate the efficacy and safety of raltitrexed combined with S-1 and bevacizumab in patients with heavily pretreated metastatic CRC in a clinical real-world setting. Patients and Methods: Records of patients with metastatic CRC refractory to standard therapies who initiated raltitrexed plus S-1 and bevacizumab from October 2017 to December 2021 were retrospectively reviewed at our institution. The study endpoints included median overall survival (OS), overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs). Results: Forty-four patients with metastatic CRC, who had previously undergone standard chemotherapy received the regimen comprising raltitrexed plus S-1 and bevacizumab. As of March 2022, the median follow-up was 23.2 months (95% confidence interval 15.8− 30.6). The median OS and median PFS were 13.5 (95% CI 9.9– 17.1) and 4.7 months (95% CI 3.6– 5.8), respectively, with a 16-week PFS rate of 60.9%. Among 43 patients with measurable lesions, the ORR and DCR were 7.0% (3/43) and 65.1% (28/43), respectively. Patients without peritoneal metastases (P = 0.003, hazard ratio 0.160, 95% CI 0.048− 0.531), lower carcinoembryonic antigen level (≤ 42.8 ng/mL) (P = 0.039, HR 0.382, 95% CI 0.153− 0.952), and no previous treatment with both vascular endothelial growth factor inhibitors (VEGF) and S-1 (P = 0.020, HR 0.215, 95% CI 0.059− 0.785) had better OS. The incidence of any grade of treatment-related AEs was 88.6%, most of which were mild to moderate, and no treatment-related deaths occurred. Conclusion: Raltitrexed combined with S-1 and bevacizumab shows promising antitumor activity and safety and could be an alternative for patients with metastatic CRC who are refractory or intolerant to standard therapy.

This study (TACTIC GC‐01) aimed to evaluate the efficacy and safety of fruquintinib combined with albumin‐bound paclitaxel as a second‐line treatment for advanced gastric cancer (GC) following progression on programmed cell death protein 1 (PD‐1) inhibitor‐based therapy. In this single‐center, single‐arm, prospective trial, patients with metastatic gastric adenocarcinoma who failed first‐line anti‐PD‐1 combined with chemotherapy treatment received six cycles of albumin‐bound paclitaxel combined with fruquintinib, followed by fruquintinib maintenance monotherapy. The primary endpoint was progression‐free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse event (AE) incidence. Between February 24, 2022, and March 26, 2024, 41 patients were enrolled, with three receiving only one treatment cycle. The safety analysis included all 41 patients, while the full analysis set comprised 38 patients. Median PFS and OS were 5 months and 14 months, respectively, with corresponding 6‐ and 12‐month PFS rates of 31.7% and 17.3%, and OS rates of 87.8% and 51.7%, respectively. Log‐rank analysis identified frontline immunotherapy duration (≥3 cycles) as a key risk factor for PFS, while metastasis to ≥2 organs significantly impacted OS. The ORR and DCR were 44.7% and 94.7%, respectively. Treatment‐related AEs occurred in 90.2% of patients, with grade 3–4 AEs (notably neutropenia and thrombocytopenia) observed in 41.5% of them. These findings suggest that fruquintinib plus albumin‐bound paclitaxel exhibits promising efficacy and manageable toxicity in anti‐PD‐1‐refractory GC, warranting further exploration in combination strategies targeting alternative pathways.

Background: To expore the possible effect and mechanism of Astragalus Polysaccharide (APS) on bone metastasis of lung adenocarcinoma.Methods: The culture media of osteoclast (OC) precursor cells, osteoblasts (OBs) and A549 cells were constructed respectively. TRAP staining was used to detect the effect of APS on OC differentiation. Alizarin red staining was used to detect the effect of APS on OB differentiation. The expressions of OC differentiation related proteins and OB specific proteins were detected by Western blotting. The effects of APS on the proliferation and migration of A549 cells were detected by CCK-8 and Transwell assay, respectively. The effect of APS on A549 induced apoptosis was analyzed by flow cytometry. The expression of calcium sensing receptor (CaSR) / parathyroid hormone-related protein (PTHrP) signal pathway related proteins was detected by Western blotting. The mouse model of bone metastasis of lung adenocarcinoma was established. The occurrence of bone metastasis of lung adenocarcinoma in mice was verified by micro CT. The inhibition of APS on bone metastasis and the promotion of tumor cell apoptosis were detected by HE staining and TUNEL assay.Results: APS inhibited the formation of receptor activator of nuclear factor-κB ligand (RANKL) induced OCs and promoted the differentiation of OBs in a concentration dependent manner. APS inhibited RANKL induced OC differentiation and the expression of related proteins, and promoted OB differentiation and the expression of related proteins. APS inhibited the proliferation and migration of A549 cells and promoted apoptosis in a concentration dependent manner. APS may inhibit the proliferation and invasion of A549 cells by inhibiting CaSR / PTHrP signaling pathway, and inhibit the expression of CaSR / PTHrP signaling pathway related proteins. In vivo experiments confirmed that APS inhibited bone metastasis of lung adenocarcinoma.Conclusions: APS can inhibit the proliferation and invasion of lung adenocarcinoma cells by inhibiting the CaSR / PTHrP pathway, and then affect the balance of OCs and OBs in the bone microenvironment, so as to protect the bone metastasis of lung adenocarcinoma.