Search

Abstract Background Ovarian cancer (OC) is one of the most malignant gynecological tumors, associated with excess death rate (50–60%) in ovarian cancer patients. Particularly, among newly occurred ovarian cancer patients, 70% of clinical cases are diagnosed at the advanced stage, which definitely delay the timely treatment and lead to high mortality rate within 5 years post diagnosis. Therefore, identification of sensitive gene markers, as well as development of reliable genetic diagnosis, are important for the early detection and precise therapy for OC patients. This study aims to identify novel genetic mutations and develop a feasible clinical approach for early OC diagnosis. Methods The OC tissue-derived DNA sample was acquired from 31 OC patients, and the somatic gene mutations will be identified after comparison with normal samples, using Genome-wide analysis and next-generation sequencing. Results A total of 463 somatic mutations, which were considered as potential pathogenic sites, were assigned to 473 genes. Among them, 15 genes (TP53, TTN, MUC16, OR4N2, BRCA1, CAD, CCDC129, INSR, NAV3, NELL2, NRAS, OBSCN, PGLYRP4, RBM15B and TRPC7) were mutated on at least two sites. These genes were mapped to RNA sequencing (RNAseq) data, and a total of 117 genes had an absolute fold- change ≥ 2 and p ≤ 0.01. Five genes were mutated in at least two OC patients. Gene ontology (GO) classification indicated that a majority of genes participated in biological processes. Kyoto Enrichment of Genes and Genomes (KEGG) enrichment pathway analysis revealed that the genes were mainly involved in the regulation of metabolic signaling pathways. Conclusions Taken together, this study identified several novel genetic alterations pathway for early clinical diagnosis and provided abundant information for understanding molecular mechanisms of the OC occurrence and development.

A low-power, high-sensitive current converter for implantable electrochemical glucose sensor tags based on radio frequency identification is presented. The current converter can work in the incremental sigma delta (ΣΔ) converter mode or the dual-slope converter mode. The two modes can be switched automatically according to the input current value for the target measuring range from 10 fA to 1 nA. The dual-mode converter offers a 10 fA-input current sensitivity, 100 dB dynamic range and consumes 4.26 µW of power from a 1.5 V supply. [ABSTRACT FROM AUTHOR]

Background Epithelial-to mesenchymal transition (EMT) involves in metastasis, causing loss of epithelial polarity. Metastasis is the major cause of carcinoma-induced death, but mechanisms are poorly understood. Here we identify differentially expressed in adenocarcinoma of the lung-1 (DAL-1), a protein belongs to the membrane-associated cytoskeleton protein 4.1 family, as an efficient suppressor of EMT in lung cancer. Methods The relationship between DAL-1 and EMT markers were analyzed by using immunohistochemistry in the clinical lung cancer tissues. Quantitative real-time PCR and western blot were used to characterize the expression of the EMT indicator mRNAs and proteins in DAL-1 overexpressed or knockdown cells. DAL-1 combined proteins were assessed by co-immunoprecipitation. Results DAL-1 levels were strongly reduced even lost in lymph node metastasis and advanced pathological stage of human lung carcinomas. Overexpression of DAL-1 altered the expression of numerous EMT markers, such as E-cadherin, β-catenin Vimentin and Ncadherin expression, meanwhile changed the morphological shape of lung cancer cells, and whereas silencing DAL-1 had an opposite effect. DAL-1 directly combined with E-cadherin promoter and regulated its expression that could be the reason for impairing EMT and decreasing cell migration and invasion. Strikingly, HSPA5 was found as DAL-1 direct binding protein. Conclusions These results suggest that tumor suppressor DAL-1 could also attenuate EMT and be important for tumor metastasis in the early transformation process in lung cancer. [ABSTRACT FROM AUTHOR]

Abstract Limited understanding of ovarian cancer (OC) genome portrait has hindered the therapeutic advances. The serial monitoring of tumor genotypes is becoming increasingly attainable with circulating cell-free DNA (cf-DNA) and circulating tumor cells (CTCs) emerging as “liquid biopsies”. They represent non-invasive biomarkers and are viable, as they can be isolated from human plasma, serum and other body fluids. Molecular characterization of circulating tumor DNA (ct-DNA) and CTCs offer unique potentials to better understand the biology of metastasis and resistance to therapies. The liquid biopsies may also give innovative insights into the process of rapid and accurate identification, resistant genetic alterations and a real time monitoring of treatment responses. In addition, liquid biopsies are shedding light on elucidating signal pathways involved in invasiveness and metastasis competence; but the detection and molecular characterization of ct-DNA and CTCs are still challenging, since they are rare, and the amount of available samples are very limited. This review will focus on the clinical potential of ct-DNA and CTCs in both the early and advanced diagnosis, prognosis, and in the identification of resistance mutations in OC.

Peak-shaving is a very efficient and practical strategy for a day-ahead hydropower scheduling in power systems, usually aiming to appropriately schedule hourly (or in less time interval) power generations of individual plants so as to smooth the load curve while enforcing the energy production target of each plant. Nowadays, the power marketization and booming development of renewable energy resources are complicating the constraints and diversifying the objectives, bringing challenges for the peak-shaving method to be more flexible and efficient. Without a pre-set or fixed peak-shaving order of plants, this paper formulates a new peak-shaving model based on the mixed integer linear programming (MILP) to solve the scheduling problem in an optimization way. Compared with the traditional peak-shaving methods that need to determine the order of plants to peak-shave the load curve one by one, the present model has better flexibility as it can handle the plant-based operating zones and prioritize the constraints and objectives more easily. With application to six cascaded hydropower reservoirs on the Lancang River in China, the model is tested efficient and practical in engineering perspective.

Pancreatic ductal adenocarcinoma is a lethal malignant disease with a very low medium survival. Currently, metastatic pancreatic cancer poorly responds to conventional treatments and exhibits an acute resistance to most chemotherapy. Few approaches have been shown to be effective for metastatic pancreatic cancer treatment. Novel therapeutic approaches to treat patients with pancreatic adenocarcinoma are in great demand. Last decades, immunotherapies have been evaluated in clinical trials and received great success in many types of cancers. However, it has very limited success in treating pancreatic cancer. As pancreatic cancer poorly responds to many single immunotherapeutic agents, combination immunotherapy was introduced to improve efficacy. The combination therapies hold great promise for enhancing immune responses to achieve better therapeutic effects. This review summarizes the existing and potential combination immunotherapies for the treatment of pancreatic cancer.