LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944.

Gemcitabine (GEM) is the gold-standard therapeutic regimen for patients with pancreatic cancer (PC); however, patients may receive limited benefits due to the drug resistance of GEM. LncRNA SNHG6 is reported to play key roles in drug resistance, but its role and molecular mechanism in PC remain incompletely understood. We found that LncRNA SNHG6 is drastically downregulated in GEM-resistant PC and is positively correlated with the survival of PC patients. With the help of bioinformatic analysis and molecular approaches, we show that LncRNA SNHG6 can sponge miR-944, therefore causing the upregulation of the target gene KPNA5. In vitro experiments showed that LncRNA SNHG6 and KPNA5 suppress PC cell proliferation and colony formation. The Upregulation of LncRNA SNHG6 and KPNA5 increases the response of GEM-resistant PANC-1 cells to GEM. We also show that the expression of KPNA5 is higher in patients without GEM resistance than in those who developed GEM resistance. In summary, our findings indicate that the LncRNA SNHG6/miR944/KPNA5 axis plays a pivotal role in overcoming GEM resistance, and targeting this axis may contribute to an increasing of the benefits of PC patients from GEM treatment.

Serum pepsinogen reference intervals in apparently healthy Chinese population with latex enhanced turbidimetric immunoassay.

AIM: Serum pepsinogen (sPG) has been used to help in diagnosing atrophic corpus gastritis and in screening for gastric cancer non-invasively. There are as yet no reports on sPG reference intervals (RIs) with latex enhanced turbidimetric immunoassay (LIA). In this study, we established the RIs for sPG in a healthy Chinese population using LIA. METHODS: Serum PGI and PGII levels in a healthy population (aged 17-80 years) were measured simultaneously using LIA. RIs were determined following Clinical Laboratory and Standards Institute C28-A3 guidelines using a non-parametric method. RESULTS: 95% RIs in men (ng/mL) were: ≤40 years old, 25.53-100.76 for PGI and ≤24.42 for PGII; 41-50 years old, 26.62-124.74 for PGI and ≤26.81 for PGII; and 51-80 years old, 30.40-153.25 for PGI and ≤32.62 for PGII. Corresponding RIs for women (ng/mL) were: ≤40 years old, 21.20-87.44 for PGI and ≤25.53 for PGII; and 41-80 years, 26.40-127.46 for PGI and ≤30.18 for PGII. 95% RI for PGI/PGII in both men and women at any age was ≥2.51. CONCLUSIONS: We established the RIs for sPG using LIA in a healthy Chinese population, which can provide a reference for clinical and laboratory studies.

Clinical significance of simultaneous determination of serum tryptophan and tyrosine in patients with lung cancer.

BACKGROUND: To explore the clinical significance of serum tyrosine (Tyr) and tryptophan (Trp) in patients with lung cancer, we used a simple and efficient method of high-performance liquid chromatography with fluorescence detection (HPLC-FD) that simultaneously measured serum Trp and Tyr contents. METHODS: The concentrations of Tyr and Trp were measured simultaneously by HPLC-FD in the sera of 80 patients with lung cancer and 120 healthy controls. RESULTS: Trp concentrations were significantly lower in patients with lung cancer than in healthy controls (39.26±5.44 vs. 49.93±5.43 µmol/l, respectively; P<0.01), whereas in Tyr concentrations there were no differences with healthy controls (65.38±7.94 vs.66.40±8.55 µmol/l, respectively; P>0.05). In addition, patients in the adenocarcinoma group had significantly lower Trp and Tyr concentrations than those in squamous cell carcinoma group. There was no difference between the early stage and advanced stage of lung cancer. CONCLUSIONS: Determination of serum Trp and Tyr concentrations can be employed to assist the diagnosis of the histotypes of lung cancer and tumor stage. Tyr and Trp as indexes on the lung cancer diagnostic sensitivity, specificity were 54.9, 62.9% and 82.4, 92.1%, Trp is an important and special index for lung cancer diagnosis of which the specificity of diagnosis of lung cancer is more than 92%.

Simultaneous determination of serum tryptophan metabolites in patients with systemic lupus erythematosus by high performance liquid chromatography with fluorescence detection.

BACKGROUND: To provide a more comprehensive clinic marker of tryptophan (TRP) catabolism in patients with systemic lupus erythematosus (SLE), we developed a simple and efficient method that simultaneously measured serum TRP, kynurenine (KYN), and kynurenic acid (KYNA) using high performance liquid chromatography with fluorescence detection (HPLC-FD). METHODS: A simple and specific high performance liquid chromatography (HPLC) method was developed for simultaneously quantitative determination of TRP, KYN and KYNA with fluorescence detection (FD) using programmed wavelength and on-column fluorescence derivatization. Thirty patients with SLE and 80 healthy control subjects were analyzed for serum TRP metabolites using the assay we developed. The tryptophan breakdown index (TBI) and neuroprotective ratio (NPR) were calculated. RESULTS: The retention time of KYN, KYNA and TRP were 8.5 min, 13.7 min and 17.6 min, respectively. The linear range for TRP was 0.245-196 micromol/L, the limit of detection (LOD) was 0.001 micromol/L and average recovery was 103.71%. The linear range for KYN was 0.049-98 v/L, the LOD was 0.0245 micromol/L, and average recovery was 97.45%. The linear range for KYNA was 1.05-2093 nmol/L, the LOD was 0.05 nmol/L, and average recovery was 100.60%. Inter-day and intra-day relative standard deviations (SDs) were <5%. Phenylalanine, tyrosine, 5-hydroxytryptamine and creatinine did not interfere with the method. The results showed great differences in TRP, KYN and KYNA contents and TBI between patients with SLE and healthy controls, but little difference in NPR. CONCLUSIONS: The method is simple, fast, accurate, and meets the requirements for simultaneous determination of TRP, KYN and KYNA in serum.