Huaping Yang

Decreased expression of microRNA-375 in nonsmall cell lung cancer and its clinical significance.

Objective: Emerging evidence has shown the association of aberrant microRNA-375 (miR-375) expression with tumourigenesis in many types of human malignancy. This prospective study characterized the contribution of miR-375 to the initiation and progression of nonsmall cell lung cancer (NSCLC). Methods: The real-time reverse transcription-polymerase chain reaction was used to examine miR-375 levels prospectively in 96 pairs of samples of NSCLC tissue and adjacent noncancerous tissue (> 2 cm from cancer tissue). The relationship between miR-375 levels and clinico pathological features was also explored. Results: MiR-375 was downregulated in 89% (85/96) of NSCLC samples compared with matched noncancerous tissue samples. Decreased miR-375 correlated significantly with advanced disease stage and lymphatic metastasis. Univariate and multivariate Cox proportional hazard regression analyses revealed that underexpression of miR-375 was an unfavourable prognostic factor for overall survival in NSCLC. Conclusions: This study suggested that miR-375 is a novel prognostic indicator in NSCLC and might be a potential target for diagnosis and gene therapy.

Rnd3 regulates lung cancer cell proliferation through notch signaling.

Rnd3/RhoE is a small Rho GTPase involved in the regulation of different cell behaviors. Dysregulation of Rnd3 has been linked to tumorigenesis and metastasis. Lung cancers are the leading cause of cancer-related death in the West and around the world. The expression of Rnd3 and its ectopic role in non-small cell lung cancer (NSCLC) remain to be explored. Here, we reported that Rnd3 was down-regulated in three NSCLC cell lines: H358, H520 and A549. The down-regulation of Rnd3 led to hyper-activation of Rho Kinase and Notch signaling. The reintroduction of Rnd3 or selective inhibition of Notch signaling, but not Rho Kinase signaling, blocked the proliferation of H358 and H520 cells. Mechanistically, Notch intracellular domain (NICD) protein abundance in H358 cells was regulated by Rnd3-mediated NICD proteasome degradation. Rnd3 regulated H358 and H520 cell proliferation through a Notch1/NICD/Hes1 signaling axis independent of Rho Kinase.

EGCG induces lung cancer A549 cell apoptosis by regulating Ku70 acetylation

Lung cancer is the leading cause of cancer-related death worldwide. (-)-Epigallocatechin-3-gallate (EGCG) is a potential chemopreventive and therapeutic agent for lung cancer. Induction of apoptosis was examined using Annexin V/PI double staining flow cytometry. Western blot analysis detected the protein expression of cleaved caspase-3, Bax and Bcl-xL. Co-immunoprecipitation was used to detect the interaction of Ku70-Bax and the acetylation status of Ku70. Treatment of A549 cells with EGCG-induced apoptosis via increased expression of cleaved caspase-3 and Bax, but decreased expression of Bcl-xL. EGCG upregulated the K70 acetylation status of A549 cells and downregulated the interaction of Bax-Ku70 in a concentration- and time-dependent manner. The apoptosis-promoting effect of EGCG on A549 cells was obviously weakened, along with strengthening of the Bax-Ku70 interaction, after pCDNA3.1(+)-Ku70 plasmid and pCDNA3.1(+)-Ku70539/542R plasmid transfection. Our results established a role of EGCG in inducing cell apoptosis by suppressing Bax activity. Regulating Ku70 acetylation by EGCG, that block the interaction between Ku70 and Bax, will result in lung cancer cell apoptosis.

Transforming growth factor-β-induced miR‑143 expression in regulation of non-small cell lung cancer cell viability and invasion capacity in vitro and in vivo

Altered expression of miRNAs contributes to development and progression of non-small cell lung cancer (NSCLC), while transforming growth factor-β (TGF-β) promotes NSCLC cell epithelial-mesenchymal transition. This study aimed to investigate the effects of TGF-β-induced miR‑143 expression in regulation of NSCLC cell viability, invasion capacity in vitro, and xenograft formation and growth in nude mice. NSCLC A549 cells treated with TGF-β were subjected to miRNA microarray analysis and miR‑143 was selected for further study of tumor cell viability, wound healing, invasion capacity in vitro, and tumor growth in nude mice. TGF-β treatment upregulated expression of 16 miRNAs and downregulated expression of 42 miRNAs in A549 cells. qRT-PCR and in situ hybridization data showed that miR‑143 was significantly downregulated in 24 NSCLC and lymph node metastatic tumor tissues, but upregulated by TGF-β treatment in A549 cells. In vitro experiments showed that miR‑143 expression could significantly suppress NSCLC cell viability and invasion capacity, and nude mouse experiments confirmed the in vitro data. Bioinformatic data predicted that Smad3, CD44 and K-Ras were the targeting genes of miR‑143. TGF-β-induced miR‑143 expression was associated with suppressed expression of Smad3, CD44, and K-Ras. This study sheds light on the role of TGF-β in upregulation of miR‑143 and the role of miR‑143 in NSCLC progression, indicating that the target of miR‑143 expression could be further studied as a novel therapeutic strategy for future control of NSCLC.

Snail1-expressing cancer-associated fibroblasts induce lung cancer cell epithelial-mesenchymal transition through miR-33b

Lung cancer has a high propensity for metastasis. Cancer-associated fibroblasts (CAFs) are the main type of stromal cells in cancer tissue, are activated by tumor cells, and play a significant role in tumor development. However, whether CAFs induce lung cancer cell metastasis, as well as pathway involved in CAF-induced lung cancer cell metastasis, is uncertain. Snail1 is a transcriptional factor whose expression in the stroma is associated with lower survival rates in patients with cancer. However, how Snail1 regulates the crosstalk between stromal cells and tumor cells when it is expressed in the stroma has not been determined. Altered microRNA (miRNA) expression is correlated with lung cancer metastasis. Our previous study of microRNAs showed that miR-33b levels were clearly reduced in lung cancer cell lines and lung cancer tissues, and miR-33b suppressed tumor cell epithelial-mesenchymal transition (EMT) when its expression was elevated. In this study, we found that co-culturing CAFs with lung cancer cells induced miR-33b downregulation and promoted epithelial cells EMT. Moreover, we found that miR-33b overexpression in lung cancer cells counteracted CAF-induced EMT. Interestingly, Snail1 expression in fibroblasts activate the inductive effects of CAFs on lung cancer cell EMT. Hence, understanding the molecular mechanism underlying the communication between stromal cells and tumor cells mediated by miR-33b may lead to the identification of novel targets for the treatment of lung cancer. Additionally, understanding the role of Snail1 driving CAFs to induce lung cancer cell EMT may provide with a new perspective on the treatment of lung cancer.

Metastatic hepatic clear cell carcinoma presenting as lump in the hilum of the lung: a case report and review of the literature.

We report a case of a 52-year-old Chinese woman with a history of primary hepatic cell carcinoma who presented with chest pain, cough, expectoration and bloody phlegm. Chest computer tomography (CT) revealed a 6.2 cm × 6.8 cm shallow lobulated irregular shaped mass in the hilum of the right lung. Bronchoscopy and CT guided lung biopsy was performed. Histopathological and immunohistochemical examinations of biopsies revealed the diagnosis of lung metastatic hepatic clear cell carcinoma. This case is thought to be extremely rare.

The utilization of next-generation sequencing to detect somatic mutations and predict clinical prognosis of Chinese non-small cell lung cancer patients

Purpose The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients. Materials and methods We performed NGS on either liquid or tissue tumor biopsies obtained from 53 NSCLC patients. The sequences were analyzed for oncogenic mutations, which were then correlated to clinical prognosis and smoking history. Results NGS of tumor biopsies detected both well-known driver mutations as well as rare or novel mutations. EGFR was the most frequently mutated gene, accounting for 32.4% (33/102) of the somatic mutations in this study. The EGFR mutations detected included rare variants such as EGFR exon 19 insertion (K745_E746insIPVAIK) and in cis H835L+L833V. Additionally, novel RET fusion mutations PCM1–RET and ADD3-RET were detected in two adenocarcinoma patients. To demonstrate the functional applications of NGS, we correlated mutations with patient characteristics, outcomes of matched targeted therapy, and outcomes based on allelic frequency of the EGFR-T790M mutation. Finally, we demonstrated that circulating tumor DNA can be used both to measure response to targeted therapy and as a predictor of clinical outcome, by presenting a case study of a single patient. Conclusion We demonstrated that NGS can be used in multiple applications to effectively identify potential oncogenic driver mutations, guide mutation-targeted therapy decisions, and predict clinical outcomes in Chinese NSCLC patients.

Report of 12 cases with tracheobronchial mucormycosis and a review

Tracheobronchial mucormycosis is a rare and invasive pulmonary mucormycosis involving the tracheobronchial tree.

Diagnosis and Management of Solitary Laryngeal Neurofibromas

Abstract: Solitary laryngeal neurofibromas are exceedingly rare with only 14 cases reported in the previous literature. Herein, we reported a case of solitary laryngeal neurofibroma and reviewed all the published cases of this disease on the clinical manifestations and management options. Patients with solitary laryngeal neurofibromas can present with a variety of respiratory symptoms. Immunohistochemical examination of tumor specimen is critical for pathologic diagnosis and complete surgical resection is the optimal therapy. Endoscopic microsurgeries followed by CO2 laser management of the surgical border may be effective on preventing recurrence. Depending on the location, size and invasiveness of the lesions, the management and prognosis vary among patients. Long‐term follow‐up is highlighted owing to the possibility of recurrence during a long period of time after surgery.

Multinodule abnormalities of the tracheobronchus: bronchoscopy findings and clinical diagnosis.

Bronchoscopy is an important method for diagnosing respiratory disease. Multiple tracheobronchial nodules are rarely reported and their causes remain unclear.