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1.
J Biochem Mol Toxicol ; 37(10): e23438, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37421170

ABSTRACT

To explore the effects of anti-programmed death-1 (PD-1) therapy on advanced colorectal cancer (CRC) based on the intestinal microecology. Ninety-two patients with advanced CRC were selected. Patients were treated with Apatinib alone or anti PD-1 treatment combined with Apatinib. The lactulose/mannitol (L/M) value of the urine was detected by high performance liquid chromatography. The changes of intestinal microflora were determined by real-time fluorescence quantitative PCR. The risk factors were analyzed through multivariate logistic regression analysis. The curative effect of anti PD-1 treatment combined with the Apatinib treatment (82.61%) was much higher than that of the Apatinib treatment alone (63.04%, p < 0.05). After treatment, the contents of Bifidobacterium, Lactobacillus, and Enterococcus faecalis were higher with lower levels of Escherichia coli in the observation group than the control (p < 0.05). The level of D-lactic acid and urinary L/M value of the urine in the observation group was lower than that in control after treatment (p < 0.001). The patients had a 3-year survival rate of 91.30%. Age >60 years old, histological types of mucinous adenocarcinoma and signet ring cell carcinoma, vascular tumor thrombus, nerve invasion, TNM stage of Ⅲ-Ⅳ were independent risk factors, and anti PD-1 treatment was the protective factor (p < 0.05). In advanced CRC patients receiving anti PD-1 treatment combined with the Apatinib treatment, the progression of advanced CRC was effectively controlled by maintaining the intestinal microflora balance. Anti PD-1 therapy can improve the living quality of CRC patients.


Subject(s)
Colorectal Neoplasms , Humans , Middle Aged , Colorectal Neoplasms/pathology
2.
Cancer Biomark ; 28(4): 529-535, 2020.
Article in English | MEDLINE | ID: mdl-32568184

ABSTRACT

OBJECTIVE: To explore the effects of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway on the intestinal flora in patients with colorectal cancer (CRC). METHODS: A total of 30 CRC patients treated with PD-1 monoclonal antibody therapy in the Oncology Department of our hospital from January 2018 to January 2019, and another 30 patients treated with routine non-immune therapy were enrolled. The feces specimens were collected for sequencing, the CRC model was established, and the 16S rRNA gene sequences in intestinal flora in feces specimens of mice were analyzed. RESULTS: The 3-month progression-free survival could not be predicted through the gene count or abundance of metagenomic species (MGS) in intestinal microflora of patients. The gene count or MGS abundance was related to the clinical progression-free response. There were abundant unclassified Escherichia coli, s_lactobacillus and s_unclassified parasutterella in patients treated with PD-1. The reflection curve of microbiota had an obvious difference in richness (Chao1), but had no apparent difference in diversity (Shannon). CONCLUSION: The PD-1/PD-L1 signaling pathway can regulate the metabolic activity of intestinal flora, thereby promoting immune surveillance of tumors.


Subject(s)
Colorectal Neoplasms/drug therapy , Gastrointestinal Microbiome/immunology , Immune Checkpoint Inhibitors/pharmacology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Aged , Animals , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , Cell Line, Tumor , Colorectal Neoplasms/immunology , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/mortality , DNA, Bacterial/isolation & purification , Disease Models, Animal , Feces/microbiology , Female , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/genetics , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunologic Surveillance/drug effects , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Male , Metagenomics , Mice , Middle Aged , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Receptor/metabolism , Progression-Free Survival , RNA, Ribosomal, 16S/genetics , Signal Transduction/drug effects , Signal Transduction/immunology
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