Circulating TP73-AS1 and CRNDE serve as diagnostic and prognostic biomarkers for non-small cell lung cancer.

BACKGROUND: Circulating long noncoding RNAs (lncRNAs) are considered a new class of biomarkers for the diagnosis and prognosis of various malignancies. We aimed to identify circulating lncRNAs as biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). METHODS: The expression of 14 candidate lncRNAs was measured in matched cancer and ipsilateral normal lung tissues of 20 patients with NSCLC using quantitative reverse-transcription PCR. In plasma samples from training and testing sets, significantly and aberrantly expressed lncRNAs, TA73-AS1 and CRNDE, were further analyzed. Receiver operating characteristic (ROC) curves were constructed, and the areas under the ROC curves (AUC) were obtained to assess diagnostic performance. The Kaplan-Meier survival analysis was used to assess the impact of plasma TA73-AS1 and CRNDE expression on tumor-free survival (TFS) of patients with NSCLC. The effect of TP73-AS1 expression on NSCLC cells was investigated in vitro. RESULTS: AUC values of plasma TA73-AS1 and CRNDE were 0.822 and 0.815 in the training set and 0.843 and 0.804 in the testing set, respectively, to distinguish NSCLC from healthy controls. The combination of plasma TP73-AS1, CRNDE, and two classical tumor markers, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1), showed excellent diagnostic performance for NSCLC (AUC =0.927 in the training set; AUC = 0.925 in the testing set). Furthermore, the high expression of the two plasma lncRNAs correlated with worse TFS in patients with NSCLC. In vitro cell model studies revealed that TP73-AS1 overexpression facilitated NSCLC cell survival, invasion, and migration. CONCLUSION: Circulating TP73-AS1 and CRNDE could be potential biomarkers for the diagnosis and prognostic prediction of NSCLC.

Assessment of a panel of miRNAs in serum and pleural fluid for the differential diagnosis of malignant and benign pleural effusion.

BACKGROUND: Differential diagnosis between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains a clinical challenge. OBJECTIVE: The aim of the study is to assess the efficacy of the serum and pleural fluid (PF) miRNA panels in distinguishing MPE from BPE. METHODS: Fourteen candidate miRNAs which were shown aberrant expression in lung cancer based on previous studies were tested by quantitative real-time PCR (qRT-PCR) in 20 MPE patients and 20 BPE patients. Significantly aberrantly expressed miRNAs were further assessed by qRT-PCR in all patients enrolled in this study. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to evaluated the diagnostic performance of the miRNAs. RESULTS: miR-21, miR-29c and miR-182 were found to be significantly aberrantly expressed in the serum and PF of MPE patients. The AUCs for the combination of miR-21, miR-29c and miR-182 in serum and PF were 0.832 and 0.89 respectively in distinguishing MPE from infection-associated PE including tuberculous pleurisy and parapneumonia PE, and 0.866 and 0.919 respectively for differentiating MPE from heart failure-associated PE, which were superior to AUC of each individual miRNAs. CONCLUSIONS: miR-21, miR-29c and miR-182 in serum and PF could be useful biomarkers for diagnosis of MPE.

YM155 sensitizes non-small cell lung cancer cells to EGFR-tyrosine kinase inhibitors through the mechanism of autophagy induction.

Resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib and gefitinib, is a major clinical problem in the treatment of patients with non-small cell lung cancer (NSCLC). YM155 is a survivin small molecule inhibitor and has been demonstrated to induce cancer cell apoptosis and autophagy. EGFR-TKIs have been known to induce cancer cell autophagy. In this study, we showed that YM155 markedly enhanced the sensitivity of erlotinib to EGFR-TKI resistant NSCLC cell lines H1650 (EGFR exon 19 deletion and PTEN loss) and A549 (EGFR wild type and KRAS mutation) through inducing autophagy-dependent apoptosis and autophagic cell death. The effects of YM155 combined with erlotinib on apoptosis and autophagy inductions were more obvious than those of YM155 in combination with survivin knockdown by siRNA transfection, suggesting that YM155 induced autophagy and apoptosis in the NSCLC cells partially depend on survivin downregulation. Meanwhile, we found that the AKT/mTOR pathway is involved in modulation of survivin downregulation and autophagy induction caused by YM155. In addition, YM155 can induce DNA damage in H1650 and A549 cell lines. Moreover, combining erlotinib further augmented DNA damage by YM155, which were retarded by autophagy inhibitor 3MA, or knockdown of autophagy-related protein Beclin 1, revealing that YM155 induced DNA damage is autophagy-dependent. Similar results were also observed in vivo xenograft experiments. Therefore, combination of YM155 and erlotinib offers a promising therapeutic strategy in NSCLC with EGFR-TKI resistant phenotype.

[Manipulative reduction and small splint fixation for treatment of three-part fractures of proximal humerus: a case-control study].

OBJECTIVE: To study Chinese medicine treatment in the three-part of the proximal humerus fractures. METHODS: From January 2009 to February 2012, 118 cases of proximal humerus three-part fractures were used two methods of operation and manipulation treatment,that were all acute and closed. In operation group: there were 22 males and 37 females,the mean age of the patients was (65.80 +/- 10.62) years (ranged from 45 to 83 years), and the interval from injury to hospital was (22.58 +/- 22.11) hours (ranged from 1 to 96 hours), used open reduction and locking plate fixation surgery. In manipulation group: there were 21 males and 38 females, the mean age of the patients was (65.98 +/- 11.10)years (ranged from 45 to 85 years), and the interval from injury to hospital was (20.85 +/- 22.63) hours (ranged from 1 to 107 hours), used manipulative reduction and small splinting external fixation. All patients were evaluated with shoulder pain, function, activity and anatomical indicators after treatment. RESULTS: All patients were followed up for 3 to 12 months with an average of 8.2 months. According to Neer Score, the total scores was 85.47 +/- 6.15 in operation group, 84.95 +/- 5.70 in manipulation group. The satisfaction rate of the operation group were 88.20%, and the manipulation group were 86.40%. The difference was not statistically significant between two groups (P > 0.05). CONCLUSION: The two treatment were able to achieve satisfactory results. The manipulative reduction and splinting treatment has the advantage of avoiding the risk of surgery, less blood damage, ensureing the efficacy, and reducing costs. It can effectively treat the proximal humerus three-part fracture.

[Case-control study on the manipulation reduction combined with small-splint fixation for the treatment of closed fracture of radius].

OBJECTIVE: To explore the clinical effects of the manipulation reduction combined with small splint fixation for the treatment of fresh closed fracture of radius for shorten hospital stays and reduce medical cost. METHODS: From July 2007 to December 2009, 200 patients (ranged the age from 40 to 80 years) with distal radius comminute fracture were treated and divided into CP group (including 21 males and 79 females, with a mean age of (62.98 +/- 0.85) years), and control group (including 20 males and 80 females, with a mean age of (63.19 +/- 0.88) years). All patients were treated manipulation reduction combined with small-splint fixation, control group removed small-splint 30 days after treatment, CP group removed 25 days after treatment. Two groups were checked by X-ray and took traditional chinese medicine (taking Yuanhu tablets, Chuangshangning tablets on the early stage; Guixiangzhenggu pill was taken on the middle stage; Shuanglongjie gu pill on the late stage), functional exercise was guided after removing of small splint. The condition of reduction and position of bone were evaluated and Gartland-Werlley scale was used to evaluate the function of wrist joint. RESULTS: Treatment time in CP group was decreased from (30.08 +/- 3.06) to (25.06 +/- 1.07) days; treatment cost in CP group was decreased from (2 100.00 +/- 332.12) to (1 644.00 +/- 125.20) Yuan. There was no significant difference in reduction and function recover of wrist joint between two groups. The results showed the effects of TCM clinic can be promised. CONCLUSION: Clinical pathway for outpatient can promote standardization of outpatient, short treatment time less medical economic burden, and worth widely used.