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1.
Environ Toxicol ; 39(3): 1107-1118, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37823609

ABSTRACT

The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosin staining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-ß1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-ß1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Mice , Animals , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Transforming Growth Factor beta1 , Vascular Endothelial Growth Factor A/metabolism , Mice, Nude , Interleukin-10 , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Interleukin-6 , TOR Serine-Threonine Kinases/metabolism , Colorectal Neoplasms/metabolism , Cell Line, Tumor
2.
Int J Surg ; 56: 221-233, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29940259

ABSTRACT

BACKGROUND: Widespread adoption of minimally invasive surgery for colon cancer has achieved improved short-term benefits and better long-term oncological outcomes compared with open surgery. However, it is still controversial whether laparoscopic surgery is suitable for patients with stage T4 colon cancer. The aim of this meta-analysis was to compare short- and long-term oncological outcomes associated with laparoscopic and conventional open surgery for pT4 colon cancer. METHODS: Published studies from 2003 to 2018 comparing oncological outcomes following laparoscopic and open surgery for pT4 colon cancer were systematically searched. Data on conversion rate, R0 resection rate, number of harvested lymph nodes, morbidity and mortality, and overall survival (OS) and disease-free survival (DFS) were subjected to meta-analysis using fixed-effect and random-effect models. RESULTS: Twelve observational studies met the inclusion criteria with a total of 2396 cases (1250 laparoscopic and 1146 open). There was no significant difference in R0 resection rate [relative risk (RR) = 1.007; 95% confidence interval (CI) = 0.935-1.085; P = 0.850], number of harvested lymph nodes (MD = 0.004; 95% CI = -0.139 to 0.148; P = 0.951), mortality (RR = 0.509; 95% CI = 0.176-1.470; P = 0.212), and 3-year OS (RR = 1.056; 95% CI = 0.939-1.188; P = 0.360), 5-year OS (RR = 1.003; 95% CI = 0.883-1.139; P = 0.966), 3-year DFS (RR = 1.032; 95% CI = 0.903-1.179; P = 0.642), and 5-year DFS (RR = 0.995; 95% CI = 0.868-1.140; P = 0.973) between the groups. The rate of conversion from laparoscopic to open procedures was 10.7% (95% CI = 0.090-0.124). There was a significant difference in incidence of complications within 30 postoperative days between laparoscopic and open surgery (RR = 0.703; 95% CI = 0.564-0.876; P = 0.002). CONCLUSION: Laparoscopic surgery is safe and feasible in pT4 colon cancer, oncological outcomes are similar, and more importantly, there are fewer postoperative complications compared with open surgery.


Subject(s)
Colectomy/mortality , Colonic Neoplasms/surgery , Laparoscopy/mortality , Aged , Colectomy/methods , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Disease-Free Survival , Female , Humans , Laparoscopy/methods , Lymph Nodes/pathology , Lymph Nodes/surgery , Male , Middle Aged , Neoplasm Staging , Observational Studies as Topic , Treatment Outcome
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