Shengjie Sun

Endobronchial ultrasound-guided transbronchial needle biopsy for the diagnosis of intrathoracic lymph node metastases from extrathoracic malignancies: A meta-analysis and systematic review

Intrathoracic lymph node metastases in patients with extrathoracic malignancies are a common clinical manifestation. Several studies evaluating intrathoracic lymph node metastases in patients with extrathoracic malignancy by using the endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) have been reported. The objective of this meta‐analysis is to investigate the diagnostic value of EBUS‐TBNA for diagnosing intrathoracic lymph node metastases in patients with extrathoracic malignancies. We systematically searched Cochrane Library, Medline and Embase for relevant studies published prior to May 2013. Studies specifically designed to evaluate the diagnostic accuracy of EBUS‐TBNA for intrathoracic lymph node metastases in patients with an extrathoracic malignancy were selected. Diagnostic accuracy meta‐analysis was conducted by pooling estimates of sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR) and diagnostic odds ratios (DOR) derived from a summary receiver operating characteristic (SROC) analysis of the original studies. Six studies were included, which provided a dataset of 533 patients. EBUS‐TBNA pooled estimates had 0.85 sensitivity (95% confidence interval (CI): 0.80–0.89), 0.99 specificity (95% CI: 0.95–1.00), PLR 28.63 (95% CI: 11.51–71.22) and NLR 0.16 (95% CI: 0.12–0.21). The overall DOR was 179.77 (95% CI: 66.29–487.50). The area under the SROC curve and the diagnostic accuracy were 0.9247 and 0.8588, respectively. Evidence gathered from studies of moderate quality reveals a high degree of diagnostic accuracy of EBUS‐TBNA for diagnosing intrathoracic lymph node metastases in patients with extrathoracic malignancies.

Specific growth inhibition of ErbB2‑expressing human breast cancer cells by genetically modified NK‑92 cells.

The natural killer cell line NK‑92 shows great cytotoxicity against various types of cancer. Several types of solid tumor cells, however, can effectively resist NK-mediated lysis by interaction of major histocompatibility complex (MHC) molecules with NK cell inhibitory receptors. To generate a eukaryotic expression vector encoding chimeric antigen receptor scFv anti-erbB2-CD28-ζ and to investigate the expression and action of this chimeric antigen receptor in cancer cells both in vitro and in vivo, NK‑92 cells were genetically modified with an scFv anti-erbB2-CD28-ζ chimeric recep-tor by optimized electro-poration using the Amaxa Nucleofector system. The expression of the chimeric receptor was evaluated by RT-PCR and immunofluorescence. The ability of the genetically modified NK‑92 cells to induce cell death in tumor targets was assessed in vitro and in vivo. The transduced NK‑92-anti-erbB2 scFv-CD28-ζ cells expressing high levels of the fusion protein on the cell surface were analyzed by fluorescence-activated cell-sorting (FACS) analysis. These cells specifically enhanced the cell death of the erbB2‑expressing human breast cancer cell lines MDA-MB-453 and SKBr3. Furthermore, adoptive transfer of genetically modified NK‑92 cells specifically reduced tumor size and lung metastasis of nude mice bearing established MDA-MB-453 cells, and significantly enhanced the survival period of these mice. The genetically modified NK‑92 cells significantly enhanced the killing of erbB2‑expressing cancer and may be a novel therapeutic strategy for erbB2‑expressing cancer cells.

Dysregulation of Circulating Follicular Helper T Cells in Nonsmall Cell Lung Cancer

Nonsmall cell lung cancer (NSCLC) is greatly affected by the dysregulation of the immune system. Circulating follicular helper T cells (Tfh) play critical roles in inducing B-cell activation and producing various cytokines. In the current study, we investigated levels of circulating Tfh in NSCLC. Circulating Tfh and it subtypes were determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 in 62 NSCLC patients and 66 healthy controls using flow cytometry. Data presented that percentage of circulating Tfh in the peripheral CD4(+) T cells was significantly increased in NSCLC (14.0%) than in controls (8.7%) (p<0.001). Further analysis revealed that the upregulation of Tfh was contributed by the Th2-Tfh subtype and the Th17-Tfh subtype, whereas the percentage of the Th1-Tfh subtype was significantly decreased in patients. Investigating the clinical stages of the patients demonstrated that prevalence of Tfh was significantly elevated in cases with advanced stages (III: 14.2%; IV: 16.4%) than those with primary stages (I: 10.9%; II: 10.8%). In addition, we analyzed Tfh in patients with different histological types. Results showed that the percentage of circulating Tfh was further upregulated in adenocarcima than squamous cell carcinoma or other types. This study suggests the involvement of circulating Tfh in the pathogenesis and progression of NSCLC, and provides a potential pathway for understanding this disease.

Adoptive Immunotherapy for Small Cell Lung Cancer by Expanded Activated Autologous Lymphocytes: a Retrospective Clinical Analysis

BACKGROUND To investigate the clinical efficacy of expanded activated autologous lymphocytes (EAAL) in patients with small cell lung cancer (SCLC). MATERIALS AND METHODS A total of 32 SCLC patients were selected and randomly divided into EAAL treatment and control groups, 16 cases in each. EAAL were obtained by proliferation of peripheral blood mononuclear cells (PBMCs) of patients followed by phenotype determination. Clinical data of all patients were recorded. Patients of both groups were followed up and the overall survival (OS) were compared retrospectively. RESULTS After culture and proliferation in vitro, the percentages of CD3+, CD3+CD8+, CD45RO+, CD28+, CD29+, CD8+CD28+ and CD3+CD16+/CD56+ cells increased markedly (p<0.05). The OS of the EAAL treatment group was longer than that of control group, but the difference was not statistically significant (p=0.060, HR=0.487, 95%CI 0.228~1.037). 1- to 3-year survival rates in EAAL treatment group were longer than those in control group, but there was still no significant difference (p>0.05). COX multivariate regression analysis showed that the number of chemotherapy cycles and the application of EAAL immunotherapy were independent prognostic factors for SCLC patients. The OS in females and chemotherapy≤6 cycles were obviously prolonged after EAAL immunotherapy. CONCLUSIONS In vitro induction and proliferation of EAAL is easy and biologically safe. Generally, EAAL adoptive immunotherapy can evidently prolong the OS of SCLC patients.

MicroRNA-302a Functions as a Putative Tumor Suppressor in Colon Cancer by Targeting Akt

Micro RNAs (miRNAs) are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in colon cancer. MiRNA-302a expression was detected in 44 colon cancer tissues and 10 normal colon tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on colon cancer cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal colon tissues, miRNA-302a expression was downregulated in colon cancer tissues. Overexpression of miRNA-302a induced G1/S cell cycle arrest in colon cancer cells, and suppressed colon cancer cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibited AKT expression by directly binding to its 3′ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 pathway. These results reveal miRNA-302a as a tumor suppressor in colon cancer, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in colon cancer.

High HER-2 protein levels correlate with clinicopathological features in colorectal cancer

AIM To obtain a correlation between HER-2 expression and the clinicopathological features incolorectal cancers. (CRCs) using a meta.analysis based approach. MATERIALS AND METHODS Electronic databases and reference lists were searched for relevant published studies. After inclusion and exclusion criteria were applied, case and control studies related to research topic were included in present meta-analysis. Data analysis was performed using Comprehensive Meta Analysis. (CMA) 2.0 software. RESULT A total of 30 studies comprising 4,942 CRC patients and 521 healthy controls met the inclusion criteria. Our major results implied that the expression level of HER-2 was significantly higher in CRC patients than healthy controls (odds ratio (OR) = 10.436, 95% confidence interval (CI) = 5.498-19.810, P < 0.001). Sample stratification based on Dukes stages suggested that increased expression level of HER-2 protein was found in CRC patients with Dukes C/D compared with CRC patients with Dukes A/B (OR = 0.335, 95% CI = 0.198-0.568, P < 0.001). The current meta-analysis also found that, in CRC patients with lymph node metastasis (LNM), the HER-2 expression was significantly higher than that in CRC patients without LNM (OR = 1.987, 95%CI = 1.209-3.265, P = 0.007). CONCLUSION Our meta-analysis study strongly suggests that HER-2 expression levels are clearly correlated with the clinicopathological features in CRC; therefore, HER-2 may be a potential biomarker for diagnosis and prognosis of CRC.

Insulin-induced gene 2 expression correlates with colorectal cancer metastasis and disease outcome.

Colorectal cancer (CRC) is one of the most common cancers worldwide accounting for ∼9% of cancer‐related deaths, 90% of which are due to metastasis resulting from resistance to chemotherapeutic agents. Hence, it is imperative to develop novel biomarkers of CRC. Insulin‐induced gene 2 (INSIG2) has been previously reported to be a negative regulator of cholesterol synthesis and was recently identified as a putative‐positive prognostic biomarker for colon and pancreatic cancer prognosis. Even though it has been suggested as a colon cancer biomarker and as an inhibitor of Bax‐mediated apoptosis, the role of INSIG2 in CRC is elusive. We initially validated that INSIG2 is a gene with univariate‐negative prognostic capacity to discriminate human colon cancer survivorship and that if present along with adenomatous polyposis coli (APC) gene mutations further decrease overall survival. Gain‐ and loss‐of‐function studies of INSIG2 showed that the gene product is responsible for inducing migration and invasion and maintenance of the mesenchymal phenotype in vitro and metastasis in vivo. Interestingly, loss of INSIG2 did not affect tumorigenic potential per se, but affected hepatic invasion in a xenograft assay. Our findings reinforce that INSIG2 is a novel colon cancer biomarker, and suggest, for the first time, an exclusive connection between INSIG2 and metastatic dissemination without any effect on tumorigenesis.