Current Strategies for Cancer Cell-Derived Extracellular Vesicles for Cancer Therapy.

Cancer cell-derived extracellular vesicles (CEVs), a novel type of therapeutic agent in cancer treatment, can be prepared from the autocrine secretion of various cancer cells, the direct extraction of cancer cells and the combination of cancer cell-derived membranes with advanced materials. With various bioactive molecules, exosomes are produced by cells for intercellular communication. Although cancer cell-derived exosomes are known to inhibit tumor apoptosis and promote the progression of cancer, researchers have developed various innovative strategies to prepare anti-tumor vesicles from cancer cells. With current strategies for anti-tumor vesicles, four different kinds of CEVs are classified including irradiated CEVs, advanced materials combined CEVs, chemotherapeutic drugs loaded CEVs and genetically engineered CEVs. In this way, CEVs can not only be the carriers for anti-tumor drugs to the target tumor area but also act as immune-active agents. Problems raised in the strategies mainly concerned with the preparation, efficacy and application. In this review, we classified and summarized the current strategies for utilizing the anti-tumor potential of CEVs. Additionally, the challenges and the prospects of this novel agent have been discussed.

Identification of six hub genes and analysis of their correlation with drug sensitivity in acute myeloid leukemia through bioinformatics.

BACKGROUND: Acute myeloid leukemia (AML) is a common hematopoietic malignancy and have unsatisfactory prognosis. Our study aimed to identify hub genes in AML and explore potential biomarkers through integrated bioinformatics. METHODS: Microarray datasets were analyzed to screen the differentially expressed genes (DEGs). Functional enrichment analysis was performed, and protein-protein interaction (PPI) network was generated by the STRING (11.0) database and Cytoscape (3.7.2) software. Hub genes were screened and verified through GEPIA2 and GEO microarray database. Sensitivity of AML cell lines with high expression of hub genes to the small-molecule drugs were identified using GSCA Lite. RESULTS: A total of 456 DEGs were identified and top 100 genes were screened out, of which six genes (FLT3, PF4, CD163, MRC1, CSF2RB, PPBP) were upregulated in AML and individually had a worse prognosis by the overall survival (OS) analysis. AML cell lines with FLT3-overexpression and CSF2RB-overexpression were sensitive to most small-molecule drugs, while, AML cells with CD163-overexpression were only sensitive to a few drugs. However, sensitivity to Erlotinib was correlated with high expression of PF4 and PPBP. CONCLUSIONS: In summary, FLT3, PF4, CD163, MRC1, CSF2RB, PPBP may be potential biomarkers and potential sensitive small-molecule drugs were correlated with overexpression of the biomarkers in AML.

Decelerated tumor growth due to hypothyroidism with prolongation of survival in a patient with lung adenocarcinoma: a case report.

Lung adenocarcinoma is a form of non-small-cell lung cancer with high mortality in the advanced stages, and is one of the most common histological subtypes of lung cancer in most countries. Prognosis of lung adenocarcinoma is generally poor, with a median survival of 4-13 months. We report a case of unusually prolonged survival of a patient with advanced lung adenocarcinoma complicated by hypothyroidism. A 71-year-old man with stage IV lung adenocarcinoma presented with hypothyroidism. Surprisingly, without any anti-tumor and anti-hypothyroidism therapy, he survived this lung cancer for longer than 2.5 years before his last follow-up visit. Patients with advanced lung adenocarcinoma rarely survive for longer than 2 years, even after therapy. We hypothesize that hypothyroidism is the cause for this discrepancy. Thyroid hormones can promote growth of carcinoma. Therefore, hypothyroidism appears to be beneficial to anti-cancer therapy. We believe that hypothyroidism, as an adverse event commonly occurring in anti-tumor therapy (e.g., an immune checkpoint inhibitor), might not be able to be completely eliminated.

Logistic regression analysis of clinical and computed tomography features of pulmonary abscesses and risk factors for pulmonary abscess-related empyema

OBJECTIVES: This study was conducted to investigate the risk factors for pulmonary abscess-related empyema by investigating the clinical characteristics and chest computed tomography imaging features of patients with pulmonary abscesses. METHODS: We retrospectively analyzed the chest computed tomography findings and clinical features of 101 cases of pulmonary abscess, including 25 cases with empyema (the experimental group) and 76 cases with no empyema (the control group). The potential risk factors for pulmonary abscess-related empyema were compared between the groups by using univariate and multivariate logistic regression analyses. RESULTS: The incidence of pulmonary abscess-related empyema was 24.8% (25/101). Univariate analysis showed that male gender, diabetes, pleuritic symptoms, white blood cells >10×109/L, albumin level <25 g/L, and positive sputum cultures were potential clinical-related risk factors and that an abscess >5 cm in diameter and transpulmonary fissure abscesses were potential computed tomography imaging-related risk factors for pulmonary abscess-related empyema. Multivariate logistic regression analysis showed that transpulmonary fissure abscesses (odds ratio=9.102, p=0.003), diabetes (odds ratio=9.066, p=0.003), an abscess >5 cm in diameter (odds ratio=8.998, p=0.002), and pleuritic symptoms (odds ratio=5.395, p=0.015) were independent risk factors for pulmonary abscess-related empyema. CONCLUSIONS: Transpulmonary fissure abscesses, diabetes, giant pulmonary abscesses, and pleuritic symptoms increased the risk of empyema among patients with pulmonary abscesses.

Krüppel-like factor 17 inhibits urokinase plasminogen activator gene expression to suppress cell invasion through the Src/p38/ MAPK signaling pathway in human lung adenocarcionma.

Krüppel-like factor 17 (KLF17) has been reported to be involved in invasion and metastasis suppression in lung cancer, but the molecular mechanisms underlying the anti-invasion and anti-metastasis roles of KLF17 in lung cancer are not fully illustrated. Here, we showed that KLF17 inhibited the invasion of A549 and H322 cells; the anti-invasion effect of KLF17 was associated with the suppression of urokinase plasminogen activator (uPA/PLAU) expression. KLF17 can bind with the promoter of uPA and inhibit its expression. Enforced expression of uPA abrogated the anti-invasion effect of KLF17 in A549 and H322 cells. In addition, immunohistochemistry staining showed that the protein expression of KLF17 was negatively correlated with that of uPA in archived samples from patients with lymph node metastasis of lung adenocarcinoma (rho = -0.62, P = 0.01). The mutually exclusive expression of KLF17 with uPA could predict lymph node metastasis for lung adenocarcinoma (AUC = 0.758, P = 0.005). Enforced expression of KLF17 inhibited the expression of phosphorylated Src and phosphorylated p38/MAPK in A549 and H322 cells. The invasiveness of the cells were suppressed by treating with sb203580 (p38/MAPK inhibitor) or HY-13805 (PP2, Src inhibitor). furthermore, p38/MAPK inhibition could block the KLF17-induced reduction of p-p38/MAPK and uPA, and Src inhibition enhanced the KLF17-induced suppression of p-Src and uPA in A549 and H322 cells. In conclusion, our study indicated that KLF17 suppressed the uPA-mediated invasion of lung adenocarcinoma. The Src and p38/MAPK signaling pathways were suggested as mediators of KLF17-induced uPA inhibition, thus providing evidence that KLF17 might be a potential anti-invasion candidate for lung adenocarcinoma.

Reduced expression of Krüppel-like factor 17 is related to tumor growth and poor prognosis in lung adenocarcinoma.

Krüppel-like factor 17 (KLF17), a new member of the Krüppel-like factors (KLFs), has been reported to be a negative regulator of epithelial-mesenchymal transition (EMT) and metastasis in breast cancer. However, the biological role and clinical significance of KLF17 in lung adenocarcinoma has been less clear. In the present study, we showed that KLF17 expression was decreased in lung adenocarcinoma. Reduced expression of KLF17 was correlated significantly with a short survival time in patients with lung adenocarcinoma (P<0.0001). Moreover, KLF17 expression was an independent prognostic indicator for patients with lung adenocarcinoma. KLF17 expression level was correlated with the tumor stage (P=0.016) and tumor size (P=0.001) in lung adenocarcinoma. Overexpression of KLF17 inhibited cell growth in A549 and PC-9 cell lines. In conclusion, it is possible that KLF17 inhibits tumor growth in lung adenocarcinoma. The reduced expression of KLF17 is a valuable prognostic indicator for patients with lung adenocarcinoma, and KLF17 could be a novel target for treatment of lung adenocarcinoma.