Primary Pulmonary Lymphoepithelioma-like Carcinoma: A Case Report Utilizing Camrelizumab and Anlotinib for Prolonged Survival.

BACKGROUND: Primary Pulmonary Lymphoepithelioma-like Carcinoma (PPLELC) is a rare form of cancer for which no standard treatment has been established to date. Patients with advanced-stage PPLELC generally have a poor prognosis with overall survival of 22.7 months. CASE PRESENTATION: Here, we report a case of advanced primary pulmonary lymphoepithelioma-like carcinoma. Initially, the patient underwent a first-line (GP) and a second-line (DP) of chemotherapy, which provided temporary relief but resulted in varying degrees of myelosuppression. When the disease progressed again, we administered a third-line treatment consisting of camrelizumab combined with anlotinib. RESULT: This resulted in a progression-free survival of over 26 months without significant toxic side effects. CONCLUSION: Our findings suggest that combining camrelizumab and anlotinib could lead to a long progressionfree survival in patients with advanced PPLELC.

Ganodermasides E-H, four new ergosterol derivatives from the endophytic fungus Epicoccum poae DJ-F associated with Euphorbia royleana.

Ganodermasides E-H (1-4), four new ergosterol derivatives and two known ones (5 and 6) were isolated from the fermentation of the endophytic fungus Epicoccum poae DJ-F in the stems of Euphorbia royleana Boiss. Their structures were elucidated by spectroscopic analysis, including extensive 1D NMR, 2D NMR, and HRESIMS techniques. All the isolated compounds were tested for their vitro antibacterial activity. Compounds 1-6 showed weak inhibitory effects on Staphylococcus epidermidis, Pseudomonas syringae, and Ralstonia solanacearum with MIC values ranging from 0.4 to 3.6 mM.

HIF1α and HIF2α regulate non-small-cell lung cancer dedifferentiation via expression of Sox2 and Oct4 under hypoxic conditions.

OBJECTIVE: To explore HIF1α and HIF2α regulate the dedifferentiation of lung cancer cells under hypoxic conditions through Sox2 and Oct4. MATERIALS AND METHODS: HIF1α, HIF2α, Sox2 and Oct4 expression was analysed in lung cancer tissues. We analysed sphere formation by single-cell of differentiated lung cancer under hypoxia, and detected the expression of CD133, CD44, Sox2, Oct4, HIF1α and HIF2α. We knocked out HIF1α, HIF2α, Sox2 or Oct4 in cells, cultured the cells under hypoxic conditions and detected CD133 and CD44 using western blotting. We also detected the apoptosis rate of cells with HIF1α, HIF2α, Sox2 or Oct4 knockout. RESULTS: There was more sphere formation of differentiated lung cancer cells under hypoxic conditions than of control cells under normoxic conditions. These newly formed spheres highly expressed CD133 and CD44. TCGA database showed high expression of HIF1α and HIF2α in lung cancer tissues. After knocking out HIF1α and HIF2α, the expression of Sox2, Oct4, CD133 and CD44 decreased significantly, and after knocking out Sox2 or Oct4, the expression of CD133 and CD44 decreased. CONCLUSION: HIF1α and HIF2α regulate non-small-cell lung cancer dedifferentiation through Sox2 and Oct4 under hypoxic conditions.

A novel immune-related long non-coding RNAs risk model for prognosis assessment of lung adenocarcinoma.

BACKGROUND: The abundant immune-related long non-coding RNA (IRLNRs) in immune cells and immune microenvironment have the potential to forecast prognosis and evaluate the effect of immunotherapy. IRLNRs analysis will provide a new perspective for LUAC research. METHODS: We calculated the immune score of each sample according to the expression levels of immune-related genes (IRGs) and screened the survival-related IRLNRs (sIRLNRs) by Cox regression analysis. The expression levels of AC068338.3 and AL691432.2 in tissues and cell lines were confirmed by RT-qPCR. RESULTS: 36 IRLNRs were selected by Pearson correlation analysis. Ten sIRLNRs were significantly correlated with the clinical outcomes of LUAC patients. Five sIRLNRs were identified by multivariate COX regression analysis to establish the immune-related risk score model (IRRS). The overall survival (OS) in the high-risk group was shorter than that in the low-risk group. IRRS could be an independent prognostic factor with significant survival correlation The distributions of immune gene concentrations were different between high-risk group and low-risk group. Furthermore, we further verified that the expression levels of AC068338.3 and AL691432.2 in different LUAC cell lines and tumor tissues were lower than that in Human bronchial epithelial cell (HBE) and adjacent tissues respectively. The lower expression levels of AC068338.3 and AL691432.2 were detected with the more advance T-stages. CONCLUSIONS: Our results highlighted some sIRLNRs with significant clinical correlations and demonstrated their monitored and prognostic values for LUAC patients. The results of this study may provide a new perspective for immunological research and immunotherapy strategies.

Quaking I-5 protein inhibits invasion and migration of kidney renal clear cell carcinoma via inhibiting epithelial-mesenchymal transition suppression through the regulation of microRNA 200c.

BACKGROUND: It has been demonstrated that quaking I-5 protein (QKI-5) plays crucial roles in the metastasis of various kinds of cancers. However, the function and mechanism of QKI-5 in kidney renal clear cell carcinoma (KIRC) metastasis remains unclear. Therefore, this study aimed to explore the mechanism of QKI-5 in the metastasis of KIRC. METHODS: The expression of QKI-5 was detected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot in KIRC tissues and different cell lines. Immunohistochemical staining was used to detect the quantity of QKI-5 in primary and metastases of KIRC. Cell migration and invasion were measured using wound healing and transwell assays respectively. The quantity of epithelial mesenchymal transition marker proteins was detected using western blot and immunofluorescence staining. The interaction of QKI-5 via microRNA 200c (miR-200c) was confirmed using dual luciferase reporter assay. RESULTS: Although QKI-5 was significantly more likely to be downregulated in KIRC tissues than that in normal Kidney tissues, it was dramatically elevated in metastatic KIRC tumors. Upregulation of QKI-5 promoted cell migration and invasion and elevated the expression of epithelial-mesenchymal transition (EMT) marker proteins, including vimentin, snail and slug, while it was downregulated for E-cadherin. Furthermore, a dual luciferase reporter assay demonstrated that QKI-5 was a direct target of miR-200c, and that miR-200c could reverse the effect of QKI-5 on cell migration, invasion, and expression of EMT marker proteins. CONCLUSIONS: Our results revealed that downregulation of QKI-5 by miR-200c attenuated KIRC migration and invasion via the EMT process, indicating that QKI-5 may be a potential therapeutic target and a key indicator of KIRC progression.

Establishing a three-miRNA signature as a prognostic model for colorectal cancer through bioinformatics analysis.

BACKGROUND: Identification of more promising microRNAs (miRNAs) are being extensively studied with respect to colorectal cancer (CRC), since CRC is the leading cause of cancer deaths and most common malignant tumors worldwide. A series of colon cancer (CCa) samples from The Cancer Genome Atlas (TCGA) were analyzed to provide a new perspective into this field. METHODS: The expression of miRNAs, mRNAs and the clinical data of 437 CRC patients were downloaded from the TCGA database. The survival-related differentially expressed miRNAs (sDMIRs) and mRNAs were detected by COX regression analysis. The high-risk group and low-risk group were separated by the median risk score of the risk score model. The potential clinical characteristics of these sDMIRs were analyzed by R software. The potential molecular mechanisms of these sDMIRs were explored by computational biology. The expression levels of three sDMIRs were explored by qPCR in CRC samples. RESULTS: Three DMIRs (hsa-miR-21-3p, hsa-miR-194-3p and hsa-miR-891a-5p) correlated with the most remarkable prognostic values of CRC patients were selected to establish the risk score model (RSM) by univariate and multivariate COX regression analysis and the survival probability of the low-risk group was longer than that in the high-risk group. We detected the target genes of three sDMIRs and the potential molecular mechanisms of these sDMIRs. We further verified the high expression levels of hsa-miR-21-3p and hsa-miR-194-3p were associated with the early T-stages, while hsa-miR-891a-5p illustrated the reversed result. CONCLUSION: Our study demonstrated three sDMIRs with significantly clinical values illustrated the potential predicting values in the prognosis of CRC patients. Our results may provide a new perspective for the diagnostic methods and treatment strategies in CRC patients.

Efficacy and Safety of Apatinib in the Treatment of Postoperative Recurrence of Fibrosarcoma.

OBJECTIVE: To evaluate the efficacy and safety of apatinib in patients with relapse after surgery for fibrosarcoma. METHODS: We reviewed the clinical data of 56 patients who experienced recurrence after fibrosarcoma resection and who received chemotherapy from September 2015 to September 2017 (no significant difference in general data of patients) (p>0.05). Differences in drug use and adverse effects were observed between patients who received monotherapy and those who received regular chemotherapy (MAID/AI). RESULTS: Compared with the regular chemotherapy group, patients in the apatinib monotherapy group exhibited an improved overall response rate (ORR) and disease control rate (DCR). In patients treated with apatinib, the incidence of adverse reactions was improved, and the symptoms were mild (P<0.05). CONCLUSION: Apatinib is a single-drug regimen that can be used in cases of recurrence of fibrosarcoma with high expression of vascular endothelial growth factor receptor-2 (VEGFR-2); its short-term efficacy is excellent, and its side effects are minimal. This drug may be used as part of a regular chemotherapy program.

Hsa_circ_0101996 combined with hsa_circ_0101119 in peripheral whole blood can serve as the potential biomarkers for human cervical squamous cell carcinoma.

BACKGROUND: Previous study suggests changes in circRNAs in tumor tissues from cervical squamous cell carcinoma (CSCC) patients. However, little is known about the diagnostic value of circRNAs in CSCC. To assess the potential application of circRNAs as diagnostic tools in CSCC, the circulating circRNAs in peripheral whole blood were carried out. METHODS: Five up-regulated circRNAs in peripheral whole blood from 87 patients with CSCC and 55 healthy controls were first identified by real-time quantitative polymerase chain reaction (RT-qPCR). The diagnostic value was evaluated using receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC). RESULTS: Compared with healthy controls, hsa_circ_0101996, hsa_circ_0104649, hsa_circ_0104443 and hsa_circ_0101119 expression were significantly up-regulated in peripheral whole blood from CSCC patients. ROC analysis showed that hsa_circ_0101996 and hsa_circ_0101119 could distinguish CSCC patients from healthy controls with high AUC (0.906 and 0.887, respectively). Intriguingly, the combination of hsa_circ_0101996 and hsa_circ_0101119 markedly improved AUC (0.964). CONCLUSION: All of the findings suggest that hsa_circ_0101996 combined with hsa_circ_0101119 can serve as potential biomarkers for CSCC detection.

(-)-Epigallocatechin-3-gallate inhibits nasopharyngeal cancer stem cell self-renewal and migration and reverses the epithelial-mesenchymal transition via NF-κB p65 inactivation.

The cancer stem cell (CSC) theory states that many types of cancer, including nasopharyngeal cancer (NPC), are initiated from and maintained by CSCs, which may be responsible for tumor relapse and resistance to therapy. It is imperative that nasopharyngeal cancer stem cells (NPCSCs) be specifically targeted to eradicate NPC and prevent recurrence. Epigallocatechin-3-gallate (EGCG) inhibits cancer progression by attenuating NF-κB p65 activity, which is upregulated in CSCs and plays an important role in epithelial-mesenchymal transition (EMT). The purpose of this study is to confirm the self-renewal and migration inhibitory effects of EGCG toward NPCSCs and to clarify its mechanism of activity. We enriched and characterized NPCSCs by collecting spheroid-derived cells grown in serum-free medium (SFM) and examined the effects of EGCG on the characteristics of NPCSCs and studied the underlying mechanisms using soft agar colony assays, transwell migration assays, reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, immunofluorescence staining, and xenograft studies. NPC spheroids enriched from NPC cell lines acquired CSC traits and underwent EMT. EGCG inhibited the NPCSCs' self-renewal and migration and reversed EMT, and combined treatment with EGCG and cisplatin reduced the growth of CSC tumor xenografts. Moreover, EGCG inhibited NF-κB p65 activity by modulating the cellular localization of p65 and decreasing the transcriptional regulation of NF-κB p65 on Twist1 expression. NF-κB p65 is a novel therapeutic target in NPCSCs, and the inhibition of activated NF-κB p65 in CSCs by EGCG may offer an effective treatment for NPC.