Background Expression profiles of circular ribonucleic acids (circRNAs) have been recently reported in lung cancers including lung adenocarcinoma (LUAD). Hypoxia is a hallmark of lung cancers. However, the role of hsa_circ_0008193 (circ_0008193) in LUAD under hypoxia remains to be illuminated. Material/Methods Gene expression levels were detected using real-time quantitative polymerase chain reaction and western blotting. Cell proliferation, migration, invasion, and Warburg effect were detected using 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide assay, transwell assays, special kits, and xenograft experiments. The relationship among circ_0008193, micro (mi)RNA (miR)-1180-3p, and tripartite motif containing 62 (TRIM62) was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. Results Expression of circ_0008193 was downregulated in human LUAD tumor tissues and cell lines (A549 and H1975), accompanied by miR-1180-3p upregulation and TRIM62 downregulation. Moreover, circ_0008193 downregulation was correlated with tumor size and lymph node metastasis. Functionally, circ_0008193 overexpression inhibited cell viability, glucose uptake, lactate production, migration, and invasion, as well as expression of hexokinase II, lactate dehydrogenase A, matrix metalloproteinase 2 (MMP2), and MMP9 in hypoxic LUAD cells in vitro . Furthermore, tumor growth of A549 cells in vivo was also hindered by circ_0008193 overexpression. Mechanically, circ_0008193 regulated TRIM62 expression via sponging miR-1180-3p, and TRIM62 was targeted by miR-1180-3p. Both miR-1180-3p upregulation and TRIM62 downregulation could abolish the suppressive role of circ_0008193 in LUAD cells. Conclusions Upregulating circ_0008193 inhibited LUAD cell proliferation, migration, invasion, and Warburg effect under hypoxia in vitro and in vivo through regulation of the miR-1180-3p/TRIM62 axis.

No abstract

Bevacizumab (BV) has an inhibitory effect on tumor growth including lung adenocarcinoma. However, its efficacy is greatly affected by drug resistance. Astragaloside IV (AST‐IV) is effective in combination with other drugs is effective to treat cancer. This study aimed to investigate the effect of AST‐IV on enhancing the sensibility of lung adenocarcinoma cells to BV. A549 cells were treated by different concentrations of BV and AST‐IV. Cell viability, cell cycle, and apoptosis were detected by thiazolyl blue tetrazolium bromide (MTT) and flow cytometry, respectively. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blotting were performed to detect the expression levels of autophagy‐ and apoptosis‐related proteins, protein kinase B (AKT), and mammalian target of rapamycin (mTOR). The results showed that BV or AST‐IV could inhibit the viability and promote the apoptosis of A549 cells in a concentration‐dependent manner. Moreover, BV or AST‐IV inhibited Bcl‐2 expression and increased the expressions of Bax and Cleaved caspase‐3, and promoted apoptosis. BV and AST‐IV in combination acted synergistically on viability and apoptosis of A549 cells. However, BV alone down‐regulated P62 expression, LC3I/LC3II level, the number of cells arrested at S phase and the phosphorylation levels of AKT and mTOR, but upregulated the number of cells arrested at G0/G1 phase and Beclin1 expression, whereas AST‐IV alone could reverse the effect of BV on autophagy‐related proteins, the phosphorylation levels of AKT and mTOR. This paper demonstrates that AST‐IV enhances the effect of BV on inhibiting proliferation and promoting apoptosis of lung adenocarcinoma cells through inhibiting autophagy pathway.

In recent years, immune checkpoint inhibition (ICI) therapy has made a tremendous improvement in the treatment of malignant tumors of gastrointestinal tract, especially for those with metastatic or recurrent lesions. However, while some patients benefit from ICI, others do not. In fact, predictive biomarkers can play a crucial role in screening patients who may benefit from a selected or targeted treatment, including immunotherapies such as programmed death-1/programmed death-1 ligand 1 (PD-1/PD-L1) inhibitors. A variety of techniques can be used to detect and quantify tumor biomarkers, each of which has a specific clinical application scenario and limitations. Cancer biomarkers in the gastrointestinal system involve an extremely complex network that requires careful interpretation and analysis. Different prognostic or predictive biomarkers are playing important roles in various tumor types, stages, and pathology/molecular subgroups, sometimes overlapping. Expression levels of biomarkers vary between different tumor types and even between the different lesions in the same tumor, depending on the heterogeneity of the patient, the tumor types, and the techniques of detection. The present systematic review comprehensively summarizes the potential biomarkers of immunotherapy, such as PD-1/PD-L1, total mutation burden (TMB), and tumor-infiltrating lymphocytes (TILs) in various gastrointestinal tumors, including tumors of the colon, stomach, esophagus, liver, and pancreas, to assist future application of immunotherapy and patient selection in clinical practice.

Background The efficacy of pulmonary rehabilitation exercise training for patients after lung cancer resection has been controversial. We sought to evaluate the efficacy of pulmonary rehabilitation on the incidence of complications and mortality in patients after lung cancer resection. Methods Search English databases PubMed, EMBASE, Medline to obtain literature. The literature compared the effect of pulmonary rehabilitation exercise training intervention or not on the efficacy of patients after lung cancer resection, and the outcomes included postoperative complications and mortality. The quality of the included literature was assessed according to the Cochrane risk of bias assessment work. The chi-square test was used to test for heterogeneity. When there is heterogeneity, a random effect model is used; when there is no heterogeneity, a fixed effect model is used. Results A total of 9 prospective clinical studies (comprising 1,338 patients) were included in this meta-analysis. Among the patients, there were 571 cases in the rehabilitation group and 767 cases in the control group. The incidence of postoperative complications in the rehabilitation group was lower than that in the control group. The odds ratio (OR) value was 0.66 and 95% confidence interval (CI) was 0.47–0.94 (P=0.02). There was no heterogeneity among studies and no publication bias. The incidence of postoperative pulmonary complications in the rehabilitation group was lower than that in the control group, OR =0.33 (95% CI: 0.22–0.50) (P<0.00001). There was no heterogeneity among studies and no publication bias. There was no significant difference in postoperative mortality between the 2 groups (OR =0.77; 95% CI: 0.26–2.30; P=0.65). There was no heterogeneity among studies and no publication bias. Discussion Implementing pulmonary rehabilitation significantly reduced postoperative complications and the risk of pulmonary complications in lung cancer patients, but had no significant effect on mortality. Pulmonary rehabilitation exercise training is recommended for patients undergoing lung cancer resection.

No abstract

Inflammatory cells mount an immune response against in vitro engineered cartilage implanted into immunocompetent animals, consequently limiting the usage of tissue-engineered cartilage to repair cartilage defects. In this study, curcumin (Cur)—an anti-inflammatory agent—was mixed with poly(lactic-co-glycolic acid) (PLGA) to develop a Cur/PLGA nanofibrous membrane with nanoscale pore size and anti-inflammatory properties. Fourier-transform infrared spectroscopy and high-performance liquid chromatography analyses confirmed the successful loading of Cur into the Cur/PLGA nanofibrous membrane. The results of the in vitro assay demonstrated the sustained release kinetics and enhanced stability of Cur in the Cur/PLGA nanofibrous membrane. Western blotting and enzyme-linked immunosorbent assay analyses revealed that the Cur/PLGA nanofibrous membrane significantly downregulated the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α). A chondrocyte suspension was seeded into a porous PLGA scaffold, and the loaded scaffold was cultured for 3 weeks in vitro to engineer cartilage tissues. The cartilage was packed with the in vitro engineered Cur/PLGA nanofibrous membrane and subcutaneously implanted into rats to generate an immunosuppressive niche. Compared with those in the PLGA-implanted and pure cartilage (without nanofibrous membrane package)-implanted groups, the cartilage was well preserved and the inflammatory response was suppressed in the Cur/PLGA-implanted group at weeks 2 and 4 post-implantation. Thus, this study demonstrated that packaging the cartilage with the Cur/PLGA nanofibrous membrane effectively generated an immunosuppressive niche to protect the cartilage against inflammatory invasion. These findings enable the clinical translation of tissue-engineered cartilage to repair cartilage defects.

No abstract