Inhibitory Effect of Nano-targeted Micelle Administration Combined with in Vitro Radiotherapy on Glioma Based on Nuclear Magnetic Resonance Technology.

Glioma is a malignant tumor originating from the central nervous system. Glioma is the incidence rate of the central nervous system in adults. Nanotechnology has been widely used in drug delivery in vivo, achieving targeted drug delivery through surface modification. At the same time, the samples measured by NMR have no bias to all compounds, and there is no need for specific internal standards for quantification. Therefore, based on the use of nuclear magnetic resonance technology, this paper analyzed the inhibitory effect of nano-targeted micelles combined with in vitro radiotherapy on glioma. The results show that the coupling constants of ß - CH3 of Ala and ß - CH3 of Lac are close. It is difficult to distinguish the spectral lines of Ala and Lae by 1.5T NMR. DHA-PLys(s-s)P can efficiently deliver drugs across BBB and into brain parenchymal cells to release drugs. Due to its increased stability in the systemic circulation, DHA-PLys(s-s)P can help to improve drug delivery efficiency. The DNA damage of U87 and U251 cells was more serious than that of C6 cells. There was a positive correlation between DNA damage and Cho/Cr ratio, indicating that nano-targeted micelles combined with in vitro radiotherapy have an inhibitory effect on glioma.

Resistin effects on pancreatic cancer progression and chemoresistance are mediated through its receptors CAP1 and TLR4.

Resistin, secreted by macrophages in tumor microenvironment, has never been investigated in pancreatic cancer models, despite a vibrant tumor microenvironment around pancreatic tumors. We evaluated serum resistin levels in healthy individuals versus pancreatic cancer patients representing different tumor grades. In vitro mechanistic analysis involved MiaPaCa-2 and SW1990 cells. Resistin signaling depends on binding of resistin to its cognitive receptors. Therefore, we silenced adenylyl cyclase-associated protein 1 (CAP1) and toll-like receptor 4 (TLR4), its two known receptors, individually as well as in combination, by short hairpin RNA (shRNA). Effect of resistin on cell proliferation, migration, invasion, cell cycle, and sensitivity to gemcitabine was studied without or with silencing of resistin receptors CAP1 and/or TLR4. The results were also confirmed in vivo in mice xenografted with MiaPaCa-2 cells without or with receptor silencing. We report high resistin levels in pancreatic cancer patients which correlate positively with tumor grades. We observed a marked reduction in the resistin-induced proliferation, migration, invasion, and cell cycle of pancreatic cancer cells MiaPaCa-2 and SW1990 when the receptors were silenced. The results were confirmed in vivo wherein resistin effects were significantly attenuated in MiaPaCa-2 xenografts with silenced receptors. The combined silencing of CAP1 and TLR4 was found to be most effective in vitro and in vivo. We found activation of STAT3 by resistin in vivo and in vitro which was dependent on the presence of CAP1 and TLR4. Further, resistin was found to induce resistance to gemcitabine through its receptors. Our results describe novel functional roles of resistin with implications toward a better understanding of pancreatic tumor microenvironment.

USP4 expression independently predicts favorable survival in lung adenocarcinoma.

Ubiquitin specific protease 4 (USP4) is a member of the USPs family, which catalyzes the cleavage of ubiquitin from a series of protein substrates, thereby modulating a number of cellular signaling pathways. In this study, we aimed to explore the expression profile of USP4 in lung adenocarcinoma (LUAD) using large patient cohorts in the Cancer Genome Atlas and the International Cancer Genome Consortium and to investigate its prognostic value and the possible mechanisms of its dysregulation. Results showed that USP4 was significantly downregulated in LUAD tissues (N = 514) compared with the normal controls (N = 59). The high USP4 expression group had significantly better overall survival (OS) and recurrence-free survival (RFS). Multivariate analysis showed that preserved USP4 expression was an independent prognostic factor of favorable OS (HR: 0.574, 95%CI: 0.427-0.771, P < 0.001) and RFS (HR: 0.625, 95%CI: 0.444-0.880, P = 0.007) in LUAD. In comparison, although USP4 was downregulated in lung squamous cell carcinoma, its expression had no prognostic value in term of OS and RFS. By examining USP4 DNA copy number alterations (CNAs) (N = 511) and DNA methylation (N = 453) in LUAD, we found that DNA shallow deletion was frequent (-1, N = 239, 46.8%) and was associated with significantly decreased USP4 expression compared with the copy-neutral (0) cases. The methylation status of some CpG sites in USP4 DNA was negatively correlated with USP4 expression. Based on these findings, we infer that USP4 expression might be a favorable biomarker in terms of OS and RFS in LUAD patients. DNA shallow deletion and hypermethylation might be two important mechanisms of decreased USP4 in these patients. © 2018 IUBMB Life, 70(7):670-677, 2018.

Effect of Megestrol Acetate Combined With Oral Nutrition Supplement in Malnourished Lung Cancer Patients: A Single-Center Prospective Cohort Study.

Background: The optimal treatment of cancer-related malnutrition remains unknown. A single-center prospective cohort study was performed to compare the efficacy of megestrol acetate (MA) combined with oral nutrition supplement (ONS) and MA alone for the treatment of lung cancer-related malnutrition. Methods: 76 eligible patients were prospectively enrolled in two arms, Arm 1 patients (n = 40, 52.6%) received MA 160 mg/d, and Arm 2 patients (n = 36, 47.4%) received MA 160 mg/d combined with ONS 55.8 g/t.i.d, all orally. All patients received anticancer therapy. Treatment duration was 3 months. The primary endpoints were improvements in body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) score. Secondary endpoints were assessed by appetite, mid-upper arm circumference (MAC), serum pre-albumin levels, and serum albumin levels. Results: Baseline levels were comparable between Arm 1 and Arm 2 patients. Compared with Arm 1, primary endpoints (BMI, P = 0.018; ECOG, P = 0.022) and secondary endpoints (MAC, P = 0.025; serum pre-albumin, P = 0.043; and serum albumin, P = 0.034) were improved significantly after treatment in Arm 2. While toxicity was negligible and comparable between Arm 1 and Arm 2. Conclusion: MA combined with ONS may be an effective and safe treatment option for lung cancer-related malnutrition patients. Clinical Trial Registration:www.clinicaltrials.gov, identifier ChiCTR2100049007.