MicroRNA-324-5p affects the radiotherapy response of cervical cancer via targeting ELAV-like RNA binding protein 1.

Cervical cancer (CC) seriously threatens the health of women. Radiation therapy (RT) is the major treatment for CC. However, the recurrent CC can acquire resistance to RT. Thus, it is necessary to find a new method for reversing RT resistance in CC. It has been reported that miR-324-5p can suppress the progression of multiple cancers. However, whether it can reverse resistance to RT in CC remains unclear. qRT-PCR and Western blotting were used to detect gene and protein expression in CC cells, respectively. Cell proliferation was tested by CCK-8 assay and colony formation assay. In addition, cell apoptosis was detected by flow cytometry. Transwell assays were performed to detect cell migration. Dual luciferase reporter assay and TargetScan were used to explore the targets of microRNA-324-5p (miR-324-5p). MiR-324-5p was downregulated in CC cells. Overexpression of miR-324-5p sensitized CC cells to RT. In addition, miR-324-5p mimics significantly induced apoptosis and inhibits the migration of CC cells in the presence of 137 Cs ionizing radiation. Furthermore, miR-324-5p sensitized CC cells to ionizing radiation by targeting ELAV-like RNA binding protein 1 (ELAVL1). MiR-324-5p overexpression affects the radiotherapy response of CC by targeting ELAVL1, which may serve as a new target for the treatment of CC.

Current progress and outcomes of clinical trials on using epidermal growth factor receptor-tyrosine kinase inhibitor therapy in non-small cell lung cancer patients with brain metastases.

Non-small cell lung cancer (NSCLC) continues to be one of the major causes of cancer-related deaths worldwide, and brain metastases are the major cause of death in NSCLC patients. With recent advances in understanding the underlying molecular mechanism of NSCLC development and progression, mutations in epidermal growth factor receptor (EGFR) have been recognized as a key predictor of therapeutic sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Using EGFR-TKI alone or in combination with standard treatments such as whole-brain radiotherapy and surgery has been an effective strategy for the management of brain metastasis. Particularly, a newer generation of EGFR-TKIs, including osimertinib and AZD3759, has been developed. These new EGFR-TKIs can cross the blood-brain barrier and potentially treat EGFR-TKI resistance and improve prognosis. In this article, current progress and outcomes of clinical trials on the use of EGFR-TKIs for treating NSCLC patients with brain metastasis will be reviewed.

Determining the Optimal Dose Prescription for the Planning Target Volume with Stereotactic Body Radiotherapy for Non- Small Cell Lung Cancer Patients.

OBJECTIVE: The aim of this study was to determine a method of dose prescription that minimizes normal tissue irradiation outside the planning target volume (PTV) during stereotactic body radiotherapy (SBRT) for patients with non-small cell lung cancer. METHODS: Previous research and patients with typical T1 lung tumors with peripheral lesions in the lung were selected for analysis. A PTV and several organs at risk (OARs) were constructed for the dose calculated; six treatment plans employing intensity modulated radiotherapy (IMRT) were produced, in which the dose was prescribed to encompass the PTV, with the prescription isodose level (PIL) set at 50, 60, 70, 80, 90 or 95% of the isocenter dose. Additionally, four OARs around the PTV were constructed to evaluate the dose received in adjacent tissues. RESULTS: The use of higher PILs for SBRT resulted in improved sparing of OARs, with the exception of the volume of lung treated with a lower dose. CONCLUSIONS: The use of lower PILs is likely to create significant inhomogeneity of the dose delivered to the target, which may be beneficial for the control of tumors with poor conformity indices.

Role of gross tumor volume in the prognosis of non-small cell lung cancer treated with 3D conformal radiotherapy: a meta-analysis.

PURPOSE: Three-dimensional conformal radiotherapy (3D-CRT) has become widely applied in patients with non-small cell lung cancer (NSCLC), and gross tumor volume (GTV) is a reliable index for predicting prognosis in patients with NSCLC. This meta-analysis investigated the association between GTV and prognosis in patients with NSCLC after 3D-CRT. METHODS: Electronic bibliographic databases were searched to identify articles related to NSCLC and 3D-CRT. The search results were carefully screened, using predetermined selection criteria, to select the most relevant studies. Newcastle-Ottawa Scale criteria were applied by 2 reviewers independently to evaluate the quality of the methodology of each included article., Based on GTV, each patient was assigned to either the study group (large GTV [≥112 cm(3)]) or the control group (small GTV [<112 cm(3)]), and the mean rates of overall survival (OS) and survival at 1, 3, and 5 years were calculated in each group. Summary hazard ratio (HR) with 95% CI was calculated. FINDINGS: The data from 10 cohort studies were incorporated into the current meta-analysis (1473 patients; study group, 773; control group, 700). The OS in the study group was significantly less than that in the control group (HR = 1.52; 95% CI, 1.10-1.94; P < 0.01). The study and control groups also had significantly different survival rates at 1 year (HR = 1.27; 95% CI, 1.10-1.46, P = 0.01), 3 years (HR = 2.06; 95% CI, 1.63-2.61; P < 0.01), and 5 years (HR = 2.25; 95% CI, 1.63-3.10; P < 0.01). Findings from funnel plots and Egger tests of the OS and 3-year survival rate suggested no publication bias. With respect to the 1- and 5-year survival rates, however, the funnel plots and Egger tests demonstrated publication bias among the included studies. IMPLICATIONS: The relatively small number of studies and small sample size, as well as the lack of a specific and standard method of defining small and large GTV, may have influenced the credibility and reliability of our results. The findings suggest that GTV influences prognosis in patients with NSCLC after 3D-CRT. However, further studies with larger sample sizes are needed to confirm our finding that a larger GTV is negatively associated with NSCLC prognosis after 3D-CRT.

Nano copper oxide-incorporated mesoporous carbon composite as multimode adsorbent for selective isolation of hemoglobin.

Assembly of nano-objects with tunable size, morphology and function into integrated nanostructures is critical for the development of a novel nanosystem in adsorption, sensing and drug/gene delivery. We demonstrate herein the fabrication of ordered mesoporous carbon by assembling uniform and highly dispersed copper-oxide (CuxOy) nanoparticles into the mesopores via evaporation of solvent from the mixture of triblock copolymer, carbon source and metal nitrate hydrate. The ordered 2D hexagonal mesoporous carbon composite possesses a large surface area of 580.8 cm(2)/g, a uniform pore size of 5.4 nm, a large pore volume of 0.64 cm(3)/g and a high metal content of 3.32 wt %. The mesoporous composite exhibits excellent adsorption selectivity and high adsorption capacity to hemoglobin (Hb) under the synergistic effect of hydrophobic and metal-affinity interactions as well as size exclusion. This facilitates multimode adsorption of hemoglobin fitting Langmuir adsorption model and offers an adsorption capacity of 1666.7 mg g(-1) for hemoglobin. The mesoporous composite is used for the isolation of hemoglobin from human whole blood with high purity. It demonstrates the potential of the copper-oxide nanoparticle-embedded mesoporous carbon composite in selective isolation/removal of specific protein species from biological sample matrixes.

Nuclear medical molecular imaging of tumor angiogenesis: current status and future prospects.

OBJECTIVE: To review the current status and progress on nuclear medical molecular imaging of angiogenesis. DATA SOURCES: A literature search was performed in Medline and PubMed published in English up to May 31, 2012. The search terms were molecular imaging, nuclear medicine and angiogenesis. STUDY SELECTION: Articles studying molecular imaging of angiogenesis using radionuclide were selected and reviewed. RESULTS: Molecular imaging has been used for studying angiogenesis by targeting integrin αVß3, VEGF/VEGFR, and matrix metalloproteinases (MMPs) with radionuclide-labeled tracers. The technology has been shown to be able to assess the angiogenesis status and/or predict the efficacy of anti-angiogenic therapy. Future directions of the research on the molecular imaging of angiogenesis include development of new tracers with better tumor targeting efficacy, desirable pharmacokinetics, and easy translation to clinical applications. CONCLUSION: Advances in molecular imaging of angiogenesis using radioculcide will make the technology a valuable tool for personalized anti-angiogenesis treatment.

Regulation of the chemokine receptor CXCR4 and metastasis by hypoxia-inducible factor in non small cell lung cancer cell lines.

Hypoxia promotes metastatic potential of tumor cells by largely unknown mechanisms. Hypoxia inducible factor (HIF) is a heterodimeric transcription factor consisting of alpha and beta (ARNT) subunits and plays an important role in tumor microenvironment. CXCR4 is a cell surface receptor that has been shown to mediate the metastasis of various tumors. CXCR4 induction by hypoxia is dependent on both activation of HIF and transcript stabilization. To investigate the mechanisms involved in hypoxia-induced metastasis and hypoxia-mediated chemokine receptor CXCR4 expression, we used lentiviral vector mediated RNA interfering (RNAi) to knock down expression of HIF-1alpha or HIF-2alpha in two NSCLC cell lines to investigate HIF-dependent invasion, migration and adhesion. Here we show that: (1) hypoxia is an important factor in regulating CXCR4 mediated metastasis and the cells exhibited reducing invasion, adhesion and migration in response to CXCL12 after knocking down HIF. (2) HIF-1alpha and HIF-2alpha are essential for hypoxic cellular response to cancer invasion and adhesion through upregulation of CXCR4. HIF-1alpha and HIF-2alpha are playing important roles in tumor metastasis, which may offer for future intervention strategies. We also show that the lentivirus mediated RNAi technology is very effective on knocking down gene expression.

[Clinical value of positron emission tomography-CT for the diagnosis of postoperative recurrence and metastasis in the patients with esophageal cancer].

OBJECTIVE: To evaluate the clinical value of the whole-body (18)F-fluoro-deoxy-D-glucose positron emission tomography with computerized tomography (PET-CT) for recurrence and distant metastasis after curative resection of the esophagus cancer. METHODS: From June 2003 to June 2004, thirty-one patients with clinical or radiologic suspicion of recurrent disease underwent conventional diagnostic work-up, including a spiral CT scan, and a dedicated whole-body PET-CT. All cases were examined by pathology or followed-up for 6 months. RESULTS: Among the 31 cases, recurrences were found in 23 patients, and 43 recurrent lesions were detected, including 14 perianastomotic lesions and 43 regional and distant lesions. For the diagnosis of recurrence, the accuracy, sensitivity and specificity of PET-CT were 97.7%, 100%, and 85.7%, while those of conventional CT were 77.3%, 61.7%, and 78.6% respectively. The sensitivity of PET-CT was significantly higher than that of conventional CT (100% vs 61.7%; chi (2)=4.161, P=0.041). CONCLUSIONS: The sensitivity of PET-CT is higher than that of conventional CT. PET-CT will play an important role in the diagnosis of postoperative recurrence and metastasis of esophageal cancer.

[Value of 18F-FDG PET in clinical staging of non-small-cell lung cancer].

OBJECTIVE: To evaluate the feasibility of 18F-deoxyglucose positron emission tomography (18F-FDG PET) in the staging of non-small-cell lung cancer (NSCLC). METHODS: 105 patients with NSCLC had been examined by 18F-FDG PET and staged by PET before radiotherapy. The results of 18F-FDG PET examination were compared with those of CT. RESULTS: The staging was changed in 38 patients because of 18F-FDG PET findings with PET upstaged in 31 patients and downstaged in 7 patients. Because of distant metastasis detected by PET, 21 patients received palliative treatment. Six of the 7 downstaged patients underwent radical surgery, among which the PET findings were concordant with the operative findings in 5 patients. Distant metastasis detected by PET increased with elevation of pre-PET stage: at stage I 10.0% (2/20), stage II 14.3% (3/21) and stage III 25.0% (16/64), respectively. CONCLUSION: 18F-FDG PET, by changing clinical staging in 36.2% (38/105) NSCLC patients has impact on treatment strategy in NSCLC patients.