Publications by authors named "Yaxi Du"

11 Publications

  • Page 1 of 1

A neutral polysaccharide from restrains cisplatin-induced nephrotoxicity.

Food Sci Nutr 2021 Jul 11;9(7):3602-3616. Epub 2021 May 11.

Yunnan Provincial Key Laboratory of Panax notoginseng Faculty of Life Science and Technology Kunming University of Science and Technology Kunming China.

is an edible mushroom distributed over the south-eastern part of the Tibet Plateau, which is also recognized as an effective ethnomedicine to alleviate diseases. This study explored the effects of a kind of neutral polysaccharide (ONP) on RAW264.7 macrophages and cisplatin-induced nephrotoxicity. The results showed that ONP relieved the inflammatory response of RAW264.7 macrophages by increasing the expression level of anti-inflammatory factor IL-10. Furthermore, ONP treatment significantly prolonged the survival of the mice treated by cisplatin through decelerating pathological progress and alleviating damaged functions of the kidneys. Compared with the cisplatin group, ONP reduced the oxidative stress of the renal cells and the expression levels of pro-inflammatory factors. Apoptosis of renal cells was also weakened in the ONP treatment group. These findings indicated that ONP alleviated cisplatin nephrotoxicity mainly by inhibiting oxidative stress, inflammation, and apoptosis in the kidneys, underscoring the potential of ONP supplementation to alleviate the side effects of cisplatin chemotherapy.
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http://dx.doi.org/10.1002/fsn3.2317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269674PMC
July 2021

Blood Tumor Mutational Burden as a Predictive Biomarker in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC).

Front Oncol 2021 14;11:640761. Epub 2021 May 14.

Yunnan Cancer Hospital and The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Center, Kunming, China.

This study was designed to investigate the impact of blood tumor mutational burden (bTMB) on advanced NSCLC in Southwest China. The relationship between the tTMB estimated by next-generation sequencing (NGS) and clinical outcome was retrospectively analyzed in tissue specimens from 21 patients with advanced NSCLC. Furthermore, the relationship between the bTMB estimated by NGS and clinical outcome was retrospectively assessed in blood specimens from 70 patients with advanced NSCLC. Finally, 13 advanced NSCLC patients were used to evaluate the utility of bTMB assessed by NGS in differentiating patients who would benefit from immunotherapy. In the tTMB group, tTMB ≥ 10 mutations/Mb was related to inferior progression-free survival (PFS) (hazard ratio [HR], 0.30; 95% CI, 0.08-1.17; log-rank = 0.03) and overall survival (OS) (HR, 0.30; 95% CI, 0.08-1.16; log-rank = 0.03). In the bTMB group, bTMB ≥ 6 mutations/Mb was associated with inferior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank < 0.01) and OS (HR, 0.31; 95% CI, 0.14-0.7; log-rank < 0.01). In the immunotherapy section, bTMB ≥ 6 mutations/Mb was related to superior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank < 0.01) and objective response rates (ORRs) (bTMB < 6: 14.2%; 95% CI, 0.03-1.19; bTMB ≥ 6: 83.3%; 95% CI, 0.91-37.08; = 0.02). These findings suggest that bTMB is a validated predictive biomarker for determining the clinical outcome of advanced NSCLC patients and may serve as a feasible predictor of the clinical benefit of immunotherapies (anti-PD-1 antibody) in the advanced NSCLC population in Yunnan Province.
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http://dx.doi.org/10.3389/fonc.2021.640761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160368PMC
May 2021

Unique Profile of Driver Gene Mutations in Patients With Non-Small-Cell Lung Cancer in Qujing City, Yunnan Province, Southwest China.

Front Oncol 2021 13;11:644895. Epub 2021 Apr 13.

Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, China.

Objective: Qujing City, Yunnan Province, China, has a high incidence of lung cancer and related mortality. The etiology of NSCLC in Qujing area and distribution of associated molecular aberrations has not been fully elucidated. This study aimed to reveal the profile of driver gene mutations in patients with non-small-cell lung cancer (NSCLC) in Qujing and explore their relationships with clinicopathological characteristics.

Methods: In this study, the mutation profiles of NSCLC driver genes, including , and , were investigated in patients with NSCLC from Qujing and compared with those from other regions in Yunnan Province. The associations between molecular mutations and clinicopathological characteristics were further analyzed.

Results: A distinct profile of driver gene mutations was discovered in patients with NSCLC from Qujing. Interestingly, a higher proportion of compound mutations, including G719X + S768I (19.65% vs 3.38%, P < 0.0001) and G719X + L861Q (21.10% vs 2.82%, P < 0.0001), was observed in patients with NSCLC in Qujing compared with patients in non-Qujing area, besides significantly different distributions of (46.01% vs. 51.07%, = 0.0125), (3.17% vs. 6.97%, = 0.0012), (0.5% vs. 2.02%, = 0.0113), and (23.02% vs. 7.85%, < 0.0001). Further, compound mutations were more likely associated with the occupation of patients (living/working in rural areas, e.g., farmers). Moreover, G12C was the dominant subtype (51.11% vs 25.00%, = 0.0275) among patients with NSCLC having mutations in Qujing.

Conclusions: Patients with NSCLC in Qujing displayed a unique profile of driver gene mutations, especially a higher prevalence of compound mutations and dominant G12C subtype, in this study, indicating a peculiar etiology of NSCLC in Qujing. Therefore, a different paradigm of therapeutic strategy might need to be considered for patients with NSCLC in Qujing.
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http://dx.doi.org/10.3389/fonc.2021.644895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076749PMC
April 2021

Oncogenic Genetic Alterations in Non-Small-Cell Lung Cancer (NSCLC) in Southwestern China.

Cancer Manag Res 2020 29;12:10861-10874. Epub 2020 Oct 29.

Yunnan Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People's Republic of China.

Purpose: To investigate the impact of oncogenic genetic alterations (GAs) on non-small-cell lung cancer (NSCLC) in southwestern China.

Patients And Methods: We first collected 579 pathologically confirmed NSCLC specimens and then used next-generation sequencing (NGS) to evaluate the DNA samples for GAs. Both the tissue and plasma samples were provided by 28 patients. Furthermore, subgroup analyses based on sample type, concordance, and GA type were carried out.

Results: GAs were detected by NGS in 61.8% (358/579) of patients. Two hundred and twenty-nine patients (39.6%) harbored EGFR mutations, 63 (10.9%) harbored KRAS mutations, 13 (2.2%) harbored BRAF mutations, 30 (5.18%) harbored ALK fusions, and 13 (2.2%) had ROS1 fusions. We found that females ( < 0.01), nonsmokers ( < 0.001), adenocarcinoma ( < 0.001), and tissue ( = 0.03) had a relatively high EGFR mutation rate. Notably, NSCLC patients from Xuanwei had a significantly different mutational pattern for EGFR in comparison with that of non-Xuanwei patients (higher G719X + S768I mutations and multiple gene alterations, but fewer exon 19 deletion mutations and single gene alterations). We found that adenocarcinoma ( = 0.02), family history of malignancy ( = 0.03), Xuanwei origin ( < 0.001), and tissue ( = 0.04) were associated with a higher number of KRAS mutations. Subgroup analysis showed that ALK ( < 0.001) and ROS1 ( < 0.05) fusions and rare EGFR mutations ( < 0.001) were associated with non-Han ethnic patients.

Conclusion: Yunnan NSCLC patients from Xuanwei and non-Han ethnic patients had an obviously unique prevalence of GAs.
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http://dx.doi.org/10.2147/CMAR.S266069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605593PMC
October 2020

Tumor Mutational Burden and PD-L1 Expression in Non-Small-Cell Lung Cancer (NSCLC) in Southwestern China.

Onco Targets Ther 2020 8;13:5191-5198. Epub 2020 Jun 8.

Yunnan Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, People's Republic of China.

Purpose: To explore the impact between the tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression on NSCLC in the Yunnan region of southwestern China.

Patients And Methods: Seventy-one NSCLC specimens that were pathologically confirmed were collected at first. The TMB and driver genetic alterations were evaluated accordingly by next-generation sequencing (NGS). Afterwards, clinical parameters and tumor PD-L1 expressions were collected. Finally, the relationship between TMB, PD-L1 expression and clinical outcome was evaluated.

Results: The median TMB was 5 (0.6-49) mutations/Mb by our NGS panel and the majority of patients (63/71, 88.7%) did not receive immunotherapy. The progression-free survival (PFS) was longer in TMB-low patients versus TMB-high ones (median 18.0 vs. 9.0 months, hazard ratio = 0.34, 95% confidence interval 0.14 to 0.84, = 0.02) and the cut-off value was 10 mutations/Mb. The overall survival (OS) was longer in TMB-low patients vs. TMB-high ones (median 21.0 vs. 10.0 months, HR = 0.32, 95% CI 0.12 to 0.82, = 0.02). Notably, our study also found that, excluding the eight patients with immunotherapy, the PFS was longer in patients with TMB-low vs. TMB-high (median 19.0 vs. 8.0 months, HR = 0.11, 95% CI 0.03 to 0.39, < 0.01) and the OS was longer in TMB-low patients vs. TMB-high (median 21.0 vs 10.0 months, HR = 0.12, 95% CI 0.03 to 0.42, < 0.01).

Conclusion: TMB was a valid and independent prognostic biomarker for NSCLC patients' clinical outcome and comprehensive screening of TMB based on NGS is recommended for individualized treatment strategies in Yunnan population.
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http://dx.doi.org/10.2147/OTT.S255947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292484PMC
June 2020

Ophiocordyceps lanpingensis polysaccharides attenuate pulmonary fibrosis in mice.

Biomed Pharmacother 2020 Jun 4;126:110058. Epub 2020 Mar 4.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, China. Electronic address:

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with growing prevalence. Currently available therapies for treating IPF are not desirable due to the limited efficacy and multiple side effects. Ophiocordyceps lanpingensis is one strain of entomogenous fungi, which has been collected from the eastern part of the Himalayas. This study revealed that O. lanpingensis polysaccharides (OLP) could attenuate bleomycin (BLM) induced lung fibrosis in mice. Results showed that OLP treatments significantly reduced BLM-induced collagen deposition and decreased the accumulation of macrophages. The oxidative stress of the lung was alleviated by OLP. The expression levels of pro-inflammatory and pro-fibrogenic factors in OLP groups were also decreased compared with those in the BLM group, which might explain the improved alveolar integrity and function in the OLP treated groups. Our findings indicated that OLP treatment could alleviate pulmonary fibrosis progression mainly through reducing the recruitment of macrophages to the lungs.
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http://dx.doi.org/10.1016/j.biopha.2020.110058DOI Listing
June 2020

MicroRNA-195 suppresses the progression of lung adenocarcinoma by directly targeting apelin.

Thorac Cancer 2019 06 9;10(6):1419-1430. Epub 2019 May 9.

The International Cooperation Key Laboratory of Regional Tumor in High Altitude Area, Molecular Diagnostic Center, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.

Background: Apelin plays an important role in many types of tumors. We aimed to identify the effects of miR-195 on inhibiting apelin and clarify the regulating mechanism of miR-195-apelin in lung adenocarcinoma cells.

Methods: We detected the expression levels of apelin and miR-195 in lung adenocarcinoma tissues and lung cancer cell lines using Western blotting and quantitative reverse transcription PCR assay, respectively. Luciferase reporter assay was used to confirm the target gene of miR-195. The effects of miR-195 and apelin on the proliferation and cell cycle of lung adenocarcinoma cells were assessed by methyl thiazolyl tetrazolium and colony formation assays, and flow cytometry. Wound-healing and transwell invasion experiments were employed to examine cellular migration and invasion. A tumor xenograft model was then used to investigate the role of miR-195 on tumor growth in vivo.

Results: The expression level of apelin and miR-195 showed an inverse correlation in lung adenocarcinoma tissues and cell lines. Luciferase reporter assay suggested that miR-195 directly targets apelin messenger RNA. Overexpression of miR-195 significantly inhibited the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and suppressed tumor growth in vivo. Further analysis revealed that apelin is one of the functional target genes of miR-195, and the overexpression of apelin efficiently inhibits the promotion of cell proliferation and invasion mediated by miR-195 mimics in lung adenocarcinoma cells.

Conclusions: Our data constitute evidence that miR-195 inhibits lung adenocarcinoma cell proliferation and invasion though targeting apelin and provides novel insight into the mechanism underlying the development of lung adenocarcinoma.
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http://dx.doi.org/10.1111/1759-7714.13087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558452PMC
June 2019

Epidermal growth factor receptor T790M mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China.

Sci Rep 2018 10 18;8(1):15426. Epub 2018 Oct 18.

Cancer Research Institute of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University (Yunnan cancer Hospital), Kunming, 650118, P.R. China.

To explore the effect of epidermal growth factor receptor (EGFR) T790M mutation status on non-small cell lung cancer (NSCLC) in Yunnan province of southwestern China. First, this study used the super amplification refractory mutation system (Super ARMS) polymerase chain reaction (PCR) and Droplet Digital PCR (dd PCR) to evaluate the T790M gene mutation, in plasmatic ctDNA samples from 212 cases of NSCLC. The association between T790M mutations and clinical parameters were further explored. Next, to investigate the mechanism of drug resistance that resulted from T790M mutation, subgroup analyses according to duration of medicine (EGFR-TKIs) were carried out. Finally, we also evaluate the effectiveness of blood-based circulating tumor DNA (ctDNA) on detecting the T790M mutation by calculating Super ARMS's detection efficiency. We found that the T790M mutation rate was 8.4% (18/212) in overall patients. The T790M mutation was more frequent in patients with brain metastasis 30.0% (12/40) (p < 0.01). We found that post-TKI samples 42.8% (15/35) were associated with a higher T790M mutation rate (p < 0.01). Subgroup analysis showed that the duration of TKI therapy for 6 to 10 months 66.6% (8/12) (p < 0.01) and >10 months 75.0% (9/12) (p < 0.01) were also associated with a higher T790M mutation rate. Super ARMS's sensitivity, specificity, PPV, NPV, and accuracy were 100.0%, 99.4%, 94.7%, 100.0%, and 99.5% respectively. Generally, the EGFR-T790M mutation was more common in NSCLC patients with brain metastasis and those who received TKI therapy for more than 6 months. Moreover, Super ARMS is a sensitive, efficient, and practical clinic method for dynamically monitoring T790M mutation status and effectively guiding clinic treatment.
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http://dx.doi.org/10.1038/s41598-018-33816-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194063PMC
October 2018

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report.

J Med Case Rep 2018 Apr 23;12(1):104. Epub 2018 Apr 23.

Bone and Soft Tissue Tumors Research Center of Yunnan Province, Department of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan, 650118, People's Republic of China.

Background: Pembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and good benefits in recent clinical trials. However, patients infected with human immunodeficiency virus were excluded from most trials because it was assumed that their anti-tumor immunity was compromised compared with immunocompetent patients.

Case Presentation: In June 2016, a 52-year-old Chinese man presented with human immunodeficiency virus and lung adenocarcinoma (T1bN3M1b). From November 2016 to December 2016, systemic chemotherapy and palliative radiotherapy for bone metastasis of femoral neck were carried out, but the tumor progressed. In January 2017, after immunochemistry detection of programmed death-1 and programmed death-ligand 1 expression (both > 50%), pembrolizumab was started. Three weeks after pembrolizumab, we combined stereotactic body radiotherapy for the primary lung tumor. He received no comfort and his CD4 lymphocyte count was stable. Human immunodeficiency virus-ribonucleic acid remained below the limits of detection. In March 2017, after three cycles of pembrolizumab and 5 weeks of stereotactic body radiotherapy therapy, he suddenly presented with palpitations. Emergency computed tomography scanning showed massive pericardial effusion and interstitial pneumonia. So we interrupted the pembrolizumab use and initiated treatment with prednisolone 1 mg/kg; however, the tumor progressed. Then, his CD4 lymphocyte count declined. Finally he died in June 2017 due to dyscrasia.

Conclusions: Pembrolizumab combined with SBRT therapy for patients with human immunodeficiency virus infection and non-small cell lung cancer may lead to serious immune-related adverse events and more clinical trials are needed.
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http://dx.doi.org/10.1186/s13256-018-1667-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911965PMC
April 2018

Protective Effects of on Glycerol-Induced Acute Renal Failure in Mice.

J Immunol Res 2017 12;2017:2012585. Epub 2017 Oct 12.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Objective: Oxidative stress and immune response are associated with acute renal failure (ARF). (OL) might be an antioxidant and immunopotentiator. In this study, we explored the protective effects of OL on glycerol-induced ARF.

Methods: Male mice were randomly divided into four groups, specifically, glycerol-induced ARF model group, low-dose OL-treated group (1.0 g/kg/d), high-dose OL-treated group (2.0 g/kg/d), and control group. Renal conditions were evaluated using kidney index, serum creatinine (Cr), blood urea nitrogen (BUN), and histological analysis. Rhabdomyolysis was monitored using creatine kinase (CK) level. Oxidative stress was determined using kidney tissue glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Immune status was evaluated using immune organ indices and immunoglobulin G (IgG) level.

Results: OL could relieve renal pathological injury and decrease the abnormal levels of kidney index, serum Cr, CK, BUN, and MDA, as well as increase the immune organ indices and the levels of IgG, GSH, and SOD. Treatment with a high dose of OL had more positive therapeutic effects on ARF than using a low dose of OL.

Conclusion: OL could ameliorate renal dysfunction in glycerol-induced ARF in mice by inhibiting oxidative stress and enhancing immune response.
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http://dx.doi.org/10.1155/2017/2012585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660786PMC
June 2018

Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China.

Oncotarget 2017 Feb;8(9):15023-15033

Tumor Research Institute of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, 650118, PR China.

To investigate the Epidermal Growth Factor Receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) in Yunnan province in southwestern China, we detected EGFR mutation by Amplification Refractory Mutation System (ARMS) polymerase chain reaction (PCR) using DNA samples from 447 pathologically confirmed NSCLC specimens (175 tissue, 256 plasma and 16 cytologic samples). The relationship between EGFR mutations and demographic and clinical factors were further explored. Subgroup analyses according to sample type (tissue and plasma) and histological type (adenocarcinoma) were done. We found the mutation rate was 34.9% in overall patients (42.3%, 29.7%, and 37.5% for tissue, plasma, and cytologic samples respectively). We found female (p < 0.0001), no smoking (p = 0.001), adenocarcinoma (p < 0.0001), and tissue specimen (p = 0.026) were associated with higher EGFR mutation rate. The most common mutations were exon 19 deletions (40%) and L858R point (30%) mutation. Interestingly, NSCLC patients from Xuanwei harbored a strikingly divergent mutational pattern for EGFR when compared with non-Xuanwei patients (higher G719X, G719X+S768I mutations, but lower 19 deletion and L858R mutations). Generally, EGFR mutation rate and pattern in Yunnan province was in accord with other Asian populations. However, Xuanwei subgroup showed strikingly divergent EGFR mutation spectrum from other general population. Our analysis also indicated that cftDNA analysis for EGFR mutations detection was feasibility for the patients lacking sufficient tissue for molecular analyses.
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http://dx.doi.org/10.18632/oncotarget.14706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362464PMC
February 2017
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