Zoledronic acid-associated osteonecro sis of the jaw in patients with EGFR-sensitive mutant lung cancer: two case reports.

Bone metastasis from lung cancer predicts a decrease in the quality of life and a shortening of survival for patients. While controlling the primary disease, active prevention and treatment of skeletal-related events (SREs) are crucial. The use of bisphosphonates as a basic drug for bone metastases from lung cancer has been increasing; also, the corresponding adverse effects have emerged. The case is here reported of two cases of osteonecrosis of the jaw associated with zoledronic acid treatment were reported in patients with epidermal growth factor receptor -sensitive mutation non-small-cell lung cancer(NSCLC) and discussed the clinical features, early recognition and interventions.

MiR-142-5p Suppresses Lung Cancer Cell Metastasis by Targeting Yin Yang 1 to Regulate Epithelial-Mesenchymal Transition.

This study aimed to investigate the mechanism of miR-142-5p and Yin Yang 1 (YY1) on regulating epithelial-mesenchymal transition (EMT) in lung cancer cell metastasis. The expressions of YY1 and miR-142-5p in different lung cancer cell lines were negatively correlated. The results of the dual-luciferase reporter assay further validated that miR-142-5p directly targeted YY1. Subsequently, transwell assays, wound-healing assay, and transplantation tumor model in nude mice proved that YY1 could promote the metastasis of lung cancer cells, whereas miR-142-5p impaired the stimulating effect of YY1 on the metastasis ability of lung cancer cells in vitro and in vivo. Western blot and quantitative real-time polymerase chain reaction analysis of the EMT-related proteins indicated that YY1 could enhance the metastasis ability of lung cancer cells by promoting EMT. On the contrary, miR-142-5p constrained the expression of mesenchymal markers by targeting YY1, reversed the differentiation of cells into mesenchymal cells, and weakened the metastasis ability of tumor cells in vitro and in vivo. In summary, miR-142-5p may regulate the expressions of EMT-related proteins by targeting YY1, thereby inhibiting lung cancer metastasis, which provides a promising therapeutic target for lung cancer.

Comparison of the characteristics of uncommon epidermal growth factor receptor (EGFR) mutations and EGFR-tyrosine kinase inhibitor treatment in patients with non-small cell lung cancer from different ethnic groups.

Patients with epidermal growth factor receptor (EGFR)-sensitive mutations generally have a significantly higher objective response rate (ORR) and longer progression-free survival (PFS) after EGFR-tyrosine kinase inhibitor (TKI) treatment. However, the efficacy of EGFR-TKIs in the case of uncommon EGFR mutations has remained elusive. In the present study, the characteristics of uncommon EGFR mutations and EGFR-TKI treatments were compared in patients with non-small cell lung cancer (NSCLC) from different ethnic groups. A total of 2,984 patients with pathologically confirmed NSCLC encountered between February 2012 to February 2017 at the Affiliated Tumor Hospital of Xinjiang Medical University (Urumqi, China) were enrolled in the present study. The Amplification Refractory Mutation System was adopted to determine EGFR gene expression, compare the ethnic differences in EGFR mutations between Xinjiang Uygur and Han people, analyze the distribution of uncommon mutation types and evaluate the link between clinicopathological features associated with uncommon mutations and the efficacy of EGFR-TKI treatment. There were significant differences in EGFR mutations in lung adenocarcinoma and lung squamous cell carcinoma between patients from the Xinjiang Uygur group and the Han group (P<0.001). The differences in the uncommon EGFR mutations were significant in patients with lung adenocarcinoma (P<0.05). The most common site of lymph node metastasis in patients with uncommon mutations was the hilar lymph node, supraclavicular/subclavian lymph node, cervical lymph node and mediastinal lymph node; the most common distant metastatic organs were the lung, bone, brain, liver and adrenal gland. Of the uncommon mutations, the most common single mutations were L861Q, G719X and 20ins mutations; the most common double mutation was the S768I and 20ins mutation. The incidence rate of EGFR gene mutations was significantly higher in Han people from Xinjiang than in Uygur people. There were marked differences between individuals regarding the efficacy of EGFR-TKI treatment and the survival time of patients with uncommon EGFR mutations, second-line EGFR-TKIs had a lower ORR and DCR while had a longer mPFS. All of these could provide a basis for the exploration of different regimens for patients with different types of uncommon mutations.

The Biological-Behavioral Effect Of Neuritin On Non-Small Cell Lung Cancer Vascular Endothelial Cells Via VEGFR And Notch1.

PURPOSE: This study aims to elucidate the biological behavior of Neuritin abnormal expression in pulmonary vascular endothelial cells (VECs) of non-small cell lung cancer (NSCLC), and explore its possible underlying mechanisms. PATIENTS AND METHODS: Primary NSCLC-VECs were isolated from 10 cancer tissues from NSCLC patients, purified and identified by CD34 and Factor VIII staining. Real-time PCR and Western-blot were adopted for detecting the expression levels of Neuritin, Notch1, and VEGFR in NSCLC-VECs and HPMECs. Neuritin-overexpression, Neuritin-knockdown NSCLC-VECs and HPMECs were constructed by transfection of pcDNA3, 1-Neuritin vector, and pBS/U6-Neuritin siRNA. Changes in cell proliferation, migration, cell cycle, and apoptosis were determined by using the MTT assay, scratch assay, transwell migration assay, and flow cytometry, respectively. Post-transfection changes in cell morphology were examined by scanning electron microscopy. RESULTS: The expression of Neuritin in NSCLC-VECs was significantly higher compared to that in HPMECs (p<0.01). Overexpression of Neuritin increased the expression of VEGFR while it reduced the expression of Notch1 (p<0.01); it also promoted cell proliferation, scratch healing, and in vitro migration (p<0.05) in HPMECs and NSCLC-VECs cells. Additionally, overexpression of Neuritin stimulated cell cycle progression and inhibited apoptosis in HPMECs and NSCLC-VECs (p<0.001). Under electron microscope, the pseudopodium of cell surface was obvious, indicating that the intercellular adhesion was upregulated. However, knockdown of Neuritin in HPMECs and NSCLC-VECs played exactly the opposite roles. CONCLUSION: Neuritin was key in the progression of NSCLC through its biological activities, including anti-apoptosis, promoting VEC proliferation, migration, and cell cycle progression. Neuritin may affect its biological activity by positively regulating VEGFR expression and negatively regulating Notch1 signaling. Neuritin may serve as a potential biomarker for NSCLC.

The oncogenic role of TRIP13 in regulating proliferation, invasion, and cell cycle checkpoint in NSCLC cells.

TRIP13 (thyroid hormone receptor interacting protein 13) AAA-ATPase has been reported to be involved in the metaphase checkpoint in human breast cancer, prostate cancer, and cervical cancer. However, the expression pattern and biologic role of TRIP13 in non-small cell lung cancer (NSCLC) remained unknown. In our present study, real-time PCR and western blot were used to detect the expression level of TRIP13 in NSCLC tissues and cell lines. We found that the expression levels of TRIP13 mRNA and protein were significantly upregulated in cell lines and lung tissues. Knockdown of TRIP13 by lentivirus inhibited cell proliferation and invasion in both A549 and H1299 cells. Furthermore, flow cytometry, western blot and immunoprecipitation showed that the MCC complex was disassembled and cells became arrested in metaphase, when TRIP13 was inhibited. In conclusion, here we first report that TRIP13 acts as a tumor promoter in regulating cell proliferation, invasion, and cell cycle checkpoint in NSCLC cells and may be a clinically useful marker for the diagnosis and treatment of lung cancer.

The clinicopathological significance of CDH1 in gastric cancer: a meta-analysis and systematic review.

BACKGROUND: CDH1 is a protein encoded by the CDH1 gene in humans. Loss of CDH1 function contributes to cancer progression by increasing proliferation, invasion, and/or metastasis. However, the association and clinicopathological significance between CDH1 hypermethylation and gastric cancer (GC) remains unclear. In this study, we systematically reviewed the studies of CDH1 hypermethylation and GC, and evaluated the association between CDH1 hypermethylation and GC using meta-analysis methods. METHODS: A comprehensive search of the PubMed and Embase databases was performed for publications up to July 2014. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analyses of pooled data were performed. Odds ratios (ORs) were calculated and summarized. RESULTS: A final analysis of 1,079 GC patients from 14 eligible studies was performed. CDH1 hypermethylation level in the cancer group was significantly higher compared to the normal gastric mucosa (OR =8.55, 95% confidence interval [CI]: 2.39-33.51, Z=5.47, P<0.00001). CDH1 hypermethylation was not significantly higher in GC than in adjacent gastric mucosa (OR =3.68, 95% CI: 0.96-14.18, Z=1.90, P=0.06). However, CDH1 hypermethylation was higher in adjacent gastric mucosa compared to that in normal gastric mucosa (OR =2.55, 95% CI: 1.22-5.32, Z=2.49, P<0.01). In addition, CDH1 hypermethylation was correlated with Helicobacter pylori (HP) status in GC. The pooled OR from six studies including 280 HP-positive GCs and 193 HP-negative GCs is 1.72 (95% CI: 1.13-2.61, Z=2.55, P=0.01). CONCLUSION: The results of this meta-analysis reveal that CDH1 hypermethylation levels in cancer and adjacent gastric mucosa are significantly higher compared to normal gastric mucosa. Thus, CDH1 hypermethylation is significantly correlated with GC risk. CDH1 hypermethylation is correlated with HP status, indicating that it plays a more important role in the pathogenesis of HP-positive GC and might be an interesting potential drug target for GC patients.