Vaccines targeting the neovasculature of tumors

Angiogenesis has a critical role in physiologic and disease processes. For the growth of tumors, angiogenesis must occur to carry sufficient nutrients to the tumor. In addition to growth, development of new blood vessels is necessary for invasion and metastases of the tumor. A number of strategies have been developed to inhibit tumor angiogenesis and further understanding of the interplay between tumors and angiogenesis should allow new approaches and advances in angiogenic therapy. One such promising angiogenic approach is to target and inhibit angiogenesis with vaccines. This review will discuss recent advances and future prospects in vaccines targeting aberrant angiogenesis of tumors. The strategies utilized by investigators have included whole endothelial cell vaccines as well as vaccines with defined targets on endothelial cells and pericytes of the developing tumor endothelium. To date, several promising anti-angiogenic vaccine strategies have demonstrated marked inhibition of tumor growth in pre-clinical trials with some showing no observed interference with physiologic angiogenic processes such as wound healing and fertility

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A Motion Planning Method for Omnidirectional Mobile Robot Based on the Anisotropic Characteristics

A more suitable motion planning method for an omni-directional mobile robot (OMR), an improved APF method (iAPF), is proposed in this paper by introducing the revolving factor into the artificial potential field (APF). Accordingly, the motion direction derived from traditional artificial potential field (tAPF) is regulated. The maximum velocity, maximum acceleration and energy consumption of the OMR moving in different directions are analyzed, based on the kinematic and dynamic constraints of an OMR, and the anisotropy of OMR is presented in this paper. Then the novel concept of an Anisotropic-Function is proposed to indicate the quality of motion in different directions, which can make a very favorable trade-off between time-optimality, stability and efficacy-optimality. In order to obtain the optimal motion, the path that the robot can take in order to avoid the obstacle safely and reach the goal in a shorter path is deduced. Finally, simulations and experiments are carried out to demonstrate that the motion resulting from the iAPF is high-speed, highly stable and highly efficient when compared to the tAPF

A Direct Plasma miRNA Assay for Early Detection and Histological Classification of Lung Cancer

Cell-free microRNAs in plasma provide circulating biomarkers for lung cancer. Most techniques for analysis of miRNAs require a large plasma volume to purify a sufficient RNA yield followed by complicated downstream processing. Small differences in the multiple procedures often cause large analytical variations and poor diagnostic values of the plasma biomarkers. Here we investigate whether directly quantifying plasma miRNAs without RNA purification could diagnose lung cancer. FirePlex assay was directly applied to 20 μl plasma of 56 lung cancer patients and 28 cancer free controls for quantifying 11 lung tumor–associated miRNAs. FirePlex assay is easier, less expensive and time-consuming for quantification of plasma miRNAs compared with conventional reverse transcription PCR with an equivalent analytic performance. From the lung tumor–associated miRNAs, a prediction model based on two miRNAs (miRs-205-5p and -210-3p) was developed, producing 78.6% sensitivity and 89.3% specificity for identifying lung cancer. The diagnostic value was independent of stage of lung tumor, and patients’ age and sex (all P > 0.05). Furthermore, based on the same two miRNAs, additional prediction models were developed with 75.0% sensitivity and 89.3% specificity for diagnosis of lung squamous cell carcinoma, and 82.2% sensitivity and 89.3% specificity for lung adenocarcinoma. The direct plasma assay can improve the efficacy of miRNA assessment in a small plasma volume by reducing multiple procedure-associated analytical variables. The developed plasma miRNA biomarkers might be useful for the early detection and histological classification of lung cancer

A Plasma Long Noncoding RNA Signature for Early Detection of Lung Cancer

The early detection of lung cancer is a major clinical challenge. Long noncoding RNAs (lncRNAs) have important functions in tumorigenesis. Plasma lncRNAs directly released from primary tumors or the circulating cancer cells might provide cell-free cancer biomarkers. The objective of this study was to investigate whether the lncRNAs could be used as plasma biomarkers for early-stage lung cancer. By using droplet digital polymerase chain reaction, we determined the diagnostic performance of 26 lung cancer–associated lncRNAs in plasma of a development cohort of 63 lung cancer patients and 33 cancer-free individuals, and a validation cohort of 39 lung cancer patients and 28 controls. In the development cohort, 7 of the 26 lncRNAs were reliably measured in plasma. Two (SNHG1 and RMRP) displayed a considerably high plasma level in lung cancer patients vs. cancer-free controls (all P  .05). The diagnostic value of the plasma lncRNA signature for lung cancer early detection was confirmed in the validation cohort. The plasma lncRNA signature may provide a potential blood-based assay for diagnosing lung cancer at the early stage. Nevertheless, a prospective study is warranted to validate its clinical value

Sensitive Detection of KRAS Mutations by Clustered Regularly Interspaced Short Palindromic Repeats

Kirsten rat sarcoma viral oncogene (KRAS) is the isoform most frequently mutated in human tumors. Testing for activating KRAS mutations has important implications for diagnosis and the personalized medicine of cancers. The current techniques for detecting KRAS mutations have moderate sensitivity. The emerging clustered regularly interspaced short palindromic repeats (CRISPR) system shows great promise in the detection of nucleic acids and is revolutionizing medical diagnostics. This study aimed to develop CRISPR–Cas12a as a sensitive test to detect KRAS mutations. Serially diluted DNA samples containing KRAS mutations are subjected to CRISPR–Cas12a and polymerase chain reaction (PCR). CRISPR–Cas12a and PCR can specifically detect 0.01% and 0.1% mutant KRAS DNA in the presence of wild-type KRAS DNA, respectively. Twenty pairs of lung tumor and noncancerous lung tissues are tested by CRISPR–Cas12a, PCR, and direct sequencing. CRISPR–Cas12a could identify the G12C mutation in five of 20 tumor tissues, while both PCR and direct sequencing discovered the KRAS mutation in three of the five tumor tissues. Furthermore, the results of CRISPR–Cas12a for testing the mutation could be directly and immediately visualized by a UV light illuminator. Altogether, CRISPR–Cas12a has a higher sensitivity for the detection of KRAS mutations compared with PCR and sequencing analysis, and thus has diagnostic and therapeutic implications. Nevertheless, the technique needs to be validated for its clinical significance in a large and prospective study