Mesenchymal-epithelial transition factor (MET) gene mutation is a large class of mutations commonly seen in non-small cell lung cancer (NSCLC). MET mutation includes subtypes such as MET exon 14 skipping mutation (METex14m) and MET amplification (METamp). For advanced NSCLC with METex14m, Savolitinib has a high sensitivity as a member of tyrosine kinase inhibitors (TKIs). METamp is a relatively rare genetic mutation type which can serve as a driver gene to mediate primary and later acquired drug resistance of epidermal growth factor receptor (EGFR)-TKIs. For advanced NSCLC with secondary METamp, EGFR-TKIs combined with MET-TKIs are usually used in clinical treatment, while the optimal treatment strategy for advanced NSCLC with primary METamp has not yet been determined. For locally advanced NSCLC patients with positive driver gene mutations such as EGFR, anaplastic lymphoma kinase (ALK) fusion and METex14m, there have been relevant cases reported that neoadjuvant targeted therapy could achieve a good prognosis, but there have been no cases of neoadjuvant targeted therapy for locally advanced NSCLC patients with METamp. This report describes a case of a locally advanced NSCLC patient with dual driver gene mutations (EGFR L858R combined with primary METamp), the tumor did not shrink after 1 month of Gefitinib monotherapy, but significantly subsided after 4 months of Savolitinib monotherapy. After radical surgery, the pathological results proved pathological complete response (pCR) of the tumor, and the patient had a good response to postoperative continual Savolitinib treatment, with no recurrence nor metastasis observed to date. This case reports the feasibility and effectiveness of neoadjuvant targeted therapy for locally advanced NSCLC with primary METamp, aiming to provide effective reference for perioperative treatment of locally advanced NSCLC with primary METamp.
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Humans ; Acrylamides/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Gene Amplification ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/genetics* ; Triazines

ObjectiveTo investigate the regulatory effect of Mankuining Formula （MKNF） on the gut microbiota and the NOD-like receptor （NLR）P3/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway-mediated inflammation in dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice. MethodSixty SPF C57BL/6 mice were randomly divided into a blank group， a model group， a MKNF group （20 g·kg^-1）， and a mesalazine group （0.266 g·kg^-1）， with 15 mice in each group. The UC model was induced in mice by freely drinking a 3% DSS solution for 7 days. After 12 hours of modeling， the treatment groups received daily oral administration， while the other groups received an equal volume of normal saline by gavage. Daily body weight and disease activity index （DAI） were recorded. On the 8th day， mice were euthanized after anesthesia， and the colon and feces were collected. The colon length was measured， and histopathological changes were observed after hematoxylin-eosin （HE） staining. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） levels in the colon were detected by enzyme-linked immunosorbent assay （ELISA）. The differences in gut microbiota among the groups were analyzed using 16S rRNA sequencing technology. The protein content of NLRP3/Caspase-1/GSDMD in colon tissues was detected by Western blot. ResultCompared with the blank group， mice in the model group showed increased DAI （P<0.01）， shortened colon length （P<0.01）， severe colon mucosal damage， elevated levels of TNF-α， IL-1β， and IL-18 （P<0.01）， increased protein content of NLRP3/Caspase-1/GSDMD in colon tissues （P<0.01）， altered gut microbiota structure with decreased abundance of Actinobacteria， Bacteroidetes， and Proteobacteria， and increased abundance of Firmicutes at the phylum level. At the genus level， there was a decrease in Lactobacillus， Alloprevotella， and Yersinia， and an increase in Bacteroides， Bacillus， and Lachnospiraceae_NK4A136. Compared with the model group， the MKNF group and the mesalazine group showed a significant reduction in DAI after the 3^rd day （P<0.01）， a significant increase in colon length （P<0.01）， alleviated colon inflammation and mucosal structural damage， and decreased TNF-α， IL-1β， and IL-18 levels in the colon （P<0.01）， reduced protein content of NLRP3/caspase-1/GSDMD in colon tissue （P<0.05， P<0.01），an increase in the abundance of Proteobacteria and Bacteroidetes， and a decrease in Firmicutes at the phylum level. ConclusionMKNF can alleviate UC-induced colonic inflammation， reduce colon damage， and improve dysbiosis of the gut microbiota by inhibiting the classical pyroptosis pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) have the highest incidence of lung cancer which treatment principles are diagnosis and treatment as early as possible. Because of its insidious onset and lack of specific markers for early screening, most patients are at an advanced stage when diagnosed which results in a low 5-year survival rate and poor prognosis. Therefore Exploring a sensitive biomarker is the focus of current diagnosis and treatment of lung cancer. The aim of this study is to investigate the biological markers in serum of patients with I-IIb stage NSCLC by differential peptidomics analysis. METHODS: The serum peptidome was compared and analyzed among the groups of normal health controls, benign lung diseases and early stage NSCLC patients using a nano ultra-performance liquid chromatography combined with a quadrupole-orbitrap mass spectrometer. The differentially expressed polypeptides were identified and analyzed quantitatively to screen the tumor biomarkers for the early diagnosis of NSCLC patients. RESULTS: According to the Swiss-Prot database, a total of 545 polypeptides originated from 118 proteins were identified. The spectral numbers of serum polypeptides in each group were compared and a total of 201 polypeptides differentially expressed were found. Following a quantitative analysis of the above peptides, we found that there were 7 peptides with the coefficient of variation (CV) less than 30% and among them the peptide of QGAKIPKPEASFSPR from ITIH4 was down-regulated and the peptide of CDDYRLC from MGP was up-regulated in NSCLC group. CONCLUSIONS The tumor biomarkers obtained by serum peptidome technology can provide a new clue for early diagnosis of NSCLC and the specific peptides hydrolyzed from ITIH4 and MGP may be the serum biological markers for early NSCLC patients.
Adult ; Aged ; Amino Acid Sequence ; Biomarkers, Tumor ; blood ; chemistry ; Carcinoma, Non-Small-Cell Lung ; blood ; diagnosis ; Early Detection of Cancer ; Female ; Humans ; Lung ; pathology ; Lung Neoplasms ; blood ; diagnosis ; Male ; Middle Aged ; Neoplasm Staging ; Peptides ; blood ; chemistry ; Proteomics ; methods ; Sensitivity and Specificity ; Young Adult