Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.

Over the past several years, long non‐coding RNAs (lncRNAs) have attracted more and more attention due to their special functions. They are vital biomarkers in multiple diseases. LncRNA HOMEOBOX A11 (HOXA11) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the oncogenic role of it in promoting malignant progression and chemoresistance in lung adenocarcinoma (LUAD) cells. The expression of HOXA11‐AS was much stronger in cisplatin‐resistant LUAD cells. Based on The Cancer Genome Atlas database, patients with high expression of HOXA11‐AS had shorter survival time. Additionally, knockdown of HOXA11‐AS caused positive changes in cell activities of LUAD. For example, cell proliferation and migration were weakened, the epithelial mesenchymal transition process was reversed, and apoptosis was induced. These changes were more obvious in cells treated with cisplatin. Next, the HOXA11‐AS/miR‐454‐3p/Stat3 (signal transducer and activator of transcription 3) pathway was found to influence the cisplatin resistance of LUAD cells. HOXA11‐AS specifically acted as a competing endogenous RNA (ceRNA) in LUAD cells. The combinations among these three genes were demonstrated. Finally, rescue assays were applied to demonstrate the ceRNA pattern consisting of HOXA11‐AS, miR‐454‐3p and Stat3. In conclusion, lncRNA HOXA11‐AS acted as a ceRNA to promote cisplatin resistance of human LUAD cells via the miR‐454‐3p/Stat3 axis.

OBJECTIVES: To investigate the effect of transfer learning on computed tomography (CT) images for the benign and malignant classification on renal tumors and to attempt to improve the classification accuracy by building patient-level models. METHODS: One hundred ninety-two cases of renal tumors were collected and identified by pathologic diagnosis within 15 days after enhanced CT examination (66% male, 70% malignant renal tumors, average age of 62.27 ± 12.26 years). The InceptionV3 model pretrained by the ImageNet dataset was cross-trained to perform this classification. Five image-level models were established for each of the Slice, region of interest (ROI), and rectangular box region (RBR) datasets. Then, two patient-level models were built based on the optimal image-level models. The network's performance was evaluated through analysis of the receiver operating characteristic (ROC) and five-fold cross-validation. RESULTS: In the image-level models, the test results of model trained on the Slice dataset [accuracy (ACC) = 0.69 and Matthews correlation coefficient (MCC) = 0.45] were the worst. The corresponding results on the ROI dataset (ACC = 0.97 and MCC = 0.93) were slightly better than those on the RBR dataset (ACC = 0.93 and MCC = 0.85) when freezing the weights before the mixed6 layer. Compared with the image-level models, both patient-level models could discriminate better (ACC increased by 2%-5%) on the RBR and Slice datasets. CONCLUSIONS: Deep learning can be used to classify benign and malignant renal tumors from CT images. Our patient-level models could benefit from 3D data to improve the accuracy.

Ru species encapsulated in HCSs can effectively break the homogeneous electron distribution and generate abundant active sites for the HER.

Increasing studies showed that kinesin family member 20A (KIF20A) was overexpessed in several types of cancer, and its overexpression correlated with the oncogenesis and prognosis of cancers. However, little is known about the role of KIF20A in lung adenocarcinoma (LUAD). In this study, we employed the bioinformatics analysis to identify the upregulation of KIF20A in LUAD, then verified the results in human tumor specimens and LUAD cell lines. Compared with normal lung tissues, a ubiquitous upregulation of KIF20A was observed in LUAD tissues by immunohistochemistry (IHC) as well as TCGA analysis. Higher expression of KIF20A was significantly associated with more advanced clinicopathological features and shorter overall survival (OS). Moreover, multivariate Cox regression analysis revealed that KIF20A was an independent prognostic factor for OS. The expression of KIF20A was significantly elevated in LUAD cell lines. After silencing KIF20A, lung cancer cell cycle arrested in G1 phase and apoptosis increased. The same results were observed in vivo. Thus, our study demonstrated that KIF20A might confer malignant phenotype to LUAD by regulating cell proliferation and apoptosis, providing a new potential biomarker for clinical treatment of LUAD.

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The membrane-proximal external region (MPER) of the HIV-1 gp41 consists of epitopes for the broadly cross-neutralizing monoclonal antibodies 2F5 and 4E10. However, antigens containing the linear sequence of these epitopes are unable to elicit potent and broad neutralizing antibody responses in vaccinated hosts, possibly because of inappropriate conformation of these epitopes. Here we designed a recombinant antigen, designated NCM, which comprises the N- and C-terminal heptad repeats that can form a six-helix bundle (6HB) core and the MPER domain of gp41. Two mutations (T569A and I675V) previously reported to expose the neutralization epitopes were introduced into NCM to generate mutants named NCM(TA), NCM(IV), and NCM(TAIV). Our results showed that NCM and its mutants could react with antibodies specific for 6HB and MPER of gp41, suggesting that these antigens are in the form of a trimer of heterodimer (i.e., 6HB) with three exposed MPER tails. Antigen with double mutations, NCM(TAIV), elicited much stronger antibody response in rabbits than immunogens with single mutation, NCM(TA) and NCM(IV), or no mutation, NCM. The purified MPER-specific antibodies induced by NCM(TAIV) exhibited broad neutralizing activity, while the purified 6HB-specific antibodies showed no detectable neutralizing activity. Our recombinant antigen design supported by an investigation of its underlying molecular mechanisms provides a strong scientific platform for the discovery of a gp41 MPER-based AIDS vaccine.

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