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Tumor markers are beneficial for the diagnosis and therapy monitoring of lung cancer. However, the value of tumor markers in lung cancer histological diagnosis is unknown. In this study, we analyzed the serum levels of six tumor markers (CEA, CYFRA21-1, SCC, NSE, ProGRP, and CA125) in 2097 suspected patients with lung cancer and determined whether the combination of the tumor markers was useful for histological diagnosis of lung cancer. We found that CYFRA21-1 was the most sensitive marker in NSCLC. ProGRP showed a better clinical performance than that of NSE in discriminating between SCLC and NSCLC. The serum level of CYFRA21-1 or SCC was significantly higher in squamous carcinoma (p < 0.05), and the levels of ProGRP and NSE were significantly higher in SCLC (p < 0.05). According to the criteria established, SCLC and NSCLC were discriminated with sensitivity of 87.12 and 62.63% and specificity of 64.61 and 99.5%, respectively. The sensitivity and specificity in the differentiation of adenocarcinoma and squamous carcinoma were 68.1 and 81.63% and 70.73 and 65.93%, with NPV of 46.03 and 68.97% and PPV of 85.82 and 79.47%, respectively. Our results suggested the combination of six tumor markers could discriminate the histological types of lung cancer.

BackgroundCytokine fusion protein that modulates the immune response holds great potential for cancer immunotherapy. IL-2 is an effective treatment against advanced cancers. However, the therapeutic efficacy of IL-2 is limited by severe systemic toxicity. Several mutants recombinant IL-2 can increase antitumor activity and minimize systemic toxicity. Melittin is an attractive anticancer candidate because of its wide-spectrum lytic properties. We previously generated a bifunctional fusion protein melittin-MIL-2, composed of melittin and a mutant IL-2. The melittin-MIL-2 inhibited the growth of human ovarian cancer SKOV3 cells in vitro and in vivo tumor growth. However, whether this antitumor effect could also be used in cancer immunotherapy was unknown. To assess its cancer immunotherapy potential, we further investigated its more effective antitumor immune response and antitumor effect against cancers of different tissue origins in vitro and in vivo.MethodsThe specific IL-2 activity of the melittin-MIL-2 fusion protein was tested on the cytokine growth dependent cell line CTLL-2. The cytolytic activity was detected by standard 4-h 51Cr-release assays. PBMC stimulation in response to the melittin-MIL-2 was determined by IFN-γ release assay. We observed the cancer cell proliferation of different tissue origins by MTT assay. The ability of melittin-MIL-2 to inhibit tumor growth in vivo was evaluated by using human liver (SMMC-7721 cancer cells), lung (A549 cancer cells) and ovarian (SKOV3 cancer cells) cancer xenograft models. To assess the immunity within the tumor microenvironment, the level of some cytokines including IFN-γ, TNF-α, IL-12 and IL-4 was analyzed by ELISA. We injected the MDA-MB-231 cells and the melittin-MIL-2 into mice, and the anti-metastatic effect was examined by counting nodules in the lung.ResultsThe melittin-MIL-2 was more effective in inducing T cell and NK-cell cytotoxicity. The fusion protein significantly increased IFN-γ production in PBMCs. In vitro, the melittin-MIL-2 mediated immune cells killing or directly killed the cancer cell lines of different tissue origins. In vivo, the fusion protein exhibited stronger inhibition on the growth of transplanted human tumors compared to rIL-2. The melittin-MIL-2 treatment promoted the IFN-γ secretion in tumor tissues and decreased the immunosuppressive cells in vivo. Furthermore, the fusion protein reduced lung metastasis of breast cancer.ConclusionsThis study provides the evidence that the melittin-MIL-2 can produce stronger immune stimulation and antitumor effects, and the fusion protein is a potent candidate for cancer immunotherapy.

BackgroundSerum uric acid (UA) has been reported as a risk factor for type 2 diabetes mellitus (T2DM). However, whether serum UA is associated with insulin resistance and insulin secretion, and the effect of gender on it in the case of the existed association, both remain undefined.MethodsA cross-sectional study was designed and performed, which enrolled a total of 403 newly diagnosed T2DM patients (mean age, 50.21 ± 13.34 years (62.5% males)). Clinical characteristics and islet function indexes of all participants were analyzed based on gender-specific tertiles of serum UA levels. In addition, multiple linear regression analysis was conducted to investigate covariates associated with islet function indexes.ResultsThe mean levels of serum UA were 331.05 μmol/L (interquartile range (IQR): 60.6, 400.9 μmol/L) and 267.9 μmol/L (IQR: 204.7, 331.9 μmol/L) in men and women, respectively. The values of insulin secretion indexes involving AUCins30/glu30, AUCins120/glu120 and total insulin disposition index (DI120) in females were significantly higher than those in males. Apart from the homeostasis model assessment insulin resistance of men, serum UA was positively associated with insulin secretion and insulin resistance indexes both in men and women. Multivariable linear regression analysis showed serum UA exerted an independent impact on insulin secretion in females, but not on insulin resistance. In males, islet function was simultaneously affected by serum UA age, body mass index (BMI), and serum lipids.ConclusionSerum UA harbored a positive correlation with insulin secretion and insulin resistance indexes in newly diagnosed T2DM patients, which was influenced by gender, BMI, serum lipids. Hence, serum UA may be considered as a predictor for islet function in clinical practice.

Based on micromagnetic simulation and analysis of Thiele's equation, in this work we demonstrate that ratchet motion of skyrmion can be induced by a biharmonic in-plane magnetic field hx(t) = h 1 sin(mt) + h 2 sin(nt + ), provided that integers m and n are coprime and that m + n is odd. Remarkably, the speed and direction of the ratchet motion can be readily adjusted by the field amplitude, frequency and phase, with the maximum speed being over 5 m/s and the direction rotatable over 360. The origin of the skyrmion ratchet motion is analyzed by tracing the excitation spectra of the dissipation parameter D and the skyrmion position R, and it shows that the dissipative force plays a key role in the appearance of ratchet motion. Such a ratchet motion of skyrmion is distinguished from those caused by single-frequency ac drives reported in the literature, and from that driven by pulsed magnetic fields as also predicted in this work. Our results show that skyrmion ratchet effect under biharmonic forces shares some common features of those found in many soliton systems, and the facile controllability of both the skyrmion speed and direction should be useful in practice.PACS number(s): 76.50.+g, 75.10.Hk, 75.78.−n *