Pengbo Deng

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.

MicroRNA-223 Promotes Tumor Progression in Lung Cancer A549 Cells via Activation of the NF-κB Signaling Pathway

Our study aimed to investigate the role of microRNA-223 (miR-223) in lung cancer A549 cells and to further elucidate its possible regulatory mechanism. The expression levels of normal human lung epithelial cell line BEAS-2B and human lung cancer cell line A549 were investigated by quantitative real-time PCR. The A549 cells were transfected with miR-223 inhibitor and miR-223 scramble. Afterward, the effects of miR-223 inhibition on cell viability, invasion, and apoptosis, as well as the expression levels of nuclear factor-κB (NF-κB) and its downstream proteins, were detected. In addition, the NF-κB inhibitor JSH-23 was used to detect the relationship between NF-κB and miR-223. miR-223 was upregulated in human lung cancer A549 cells when compared with BEAS-2B cells. In addition, miR-223 expression was successfully inhibited by the miR-223 inhibitor. Suppression of miR-223 significantly decreased cell viability, inhibited invasion, and induced apoptosis of lung cancer A549 cells. Suppression of miR-223 resulted in a significant decrease in the expression levels of NF-κB and its downstream proteins P-IKBα and P-IKKα/β. After treatment with the NF-κB inhibitor, the inhibitory effects of miR-233 inhibitor on cell invasion, as well as the expression levels of NF-κB and p-p65, were enhanced. Our findings indicate that miR-223 may increase proliferation, promote invasion, and inhibit apoptosis of lung cancer A549 cells via activation of the NF-κB signaling pathway. miR-223 may serve as a potential therapeutic target in lung cancer.

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.

Mutational landscape and clonal diversity of pulmonary adenoid cystic carcinoma

ABSTRACT Pulmonary adenoid cystic carcinoma is a rare and indolent lung malignancy, characterized by a protracted but unpredictable growth behavior. Currently, the treatment of PACC relies on surgery and local radiotherapy. However, treatment options for advanced PACC patients are limited. A larger number of studies demonstrated that advanced PACC patients obtained limited benefit from chemotherapy. Moreover, only a few case reports revealed PACC patients were candidates for target therapy. Therefore, there is an urgent need to develop novel therapies. Due to its rareness, its mutational landscape remains largely elusive. In this study, we performed capture-based ultra-deep sequencing on multiregional surgical specimens obtained from 8 PACC patients using a panel consisting of 295 cancer-related genes. Our data revealed distinctive mutational spectrum of PACC, which differed from non-small cell lung cancer and adenoid cystic carcinomas originated from other anatomical sites. PACC, lacking mutations in a majority of non-small cell lung cancer driver genes, has frequent mutations in genes participating in chromatin remodeling and NOTCH signaling pathway. We also elucidated spatial intra-tumoral heterogeneity, which varied among cases. Most mutations in chromatin remodelers were subclonal. Collectively, our findings elucidated molecular signature associated with PACC and highlighted the potential for epigenetic therapy in this disease.

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.

Primary pleural intermediate hemangioendothelioma with pleural effusion as the only manifestation

Intermediate hemangioendothelioma is a group of rare tumors of vascular origin that show a borderline biological behavior and commonly arise in extremities, trunk, head or neck. Intermediate hemangioendothelioma originating in pleura is extremely rare. Herein we describe a case of primary pleural intermediate hemangioendothelioma in a 48-year-old man presenting with pleural effusion only. The patient was diagnosed by pleura biopsy and immunohistochemistry in our hospital. Even though neither systemic chemotherapy nor surgery was applied, he got relieved gradually and sustained asymptomatic during follow-up for 10 months.

Clinical characteristics and prognostic significance of 92 cases of patients with primary mixed-histology lung cancer.

Mixed-histology primary lung cancer is a rare type of lung cancer, where data regarding epidemiology, clinical features and prognosis of survival are limited. The aim of this study was to analyze the clinical characteristics of patients with mixed-histology lung tumors, and to investigate the association between clinical characteristics, treatment and prognosis. Between January, 1999 and September, 2008, 1,842 patients were diagnosed with primary lung tumors. Of these, 92 presented a mixed histological pattern. Patient clinical characteristics, clinical tumor-node-metastasis (TNM) staging, diagnostic methods, treatment and survival data were collected in order to be retrospectively analyzed. Differences between the frequencies were examined using the χ2 test and survival rates using the Kaplan-Meier method. The log-rank test was used to compare the survival curves and a probability value <5% (P<0.05) was considered to indicate a statistically significant difference. Of the 92 lung cancer patients (4.99%) with a mixed histological pattern, most were adenosquamous carcinomas. Patients included 75 men and 17 women with a mean age of 56 years. Most cases were in late stage and 64 patients had metastasis. The 1-, 2- and 3-year survival of 52 mixed-histology and 54 non-small cell lung cancer (NSCLC) patients with resection who were successfully followed up, was 63.5, 23.1, 9.6 and 81.5, 48.1, 27.7% (P=0.013). The median survival time of mixed-histology lung cancer patients treated with surgery plus adjuvant therapy and surgery alone was 22 and 12 months, respectively (P=0.002). Mixed-histology lung cancer is characterized by higher malignancy and poor prognosis. However, surgery plus adjuvant therapy is able to prolong survival, compared to surgery alone.