Next-Generation Sequencing:Application in Liver Cancer-Past, Present and Future?

Hepatocellular Carcinoma (HCC) is the third most deadly malignancy worldwide characterized by phenotypic and molecular heterogeneity. In the past two decades, advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. More recently, improvements of sophisticated next-generation sequencing (NGS) technologies have enabled complete and cost-efficient analyses of cancer genomes at a single nucleotide resolution and advanced into valuable tools in translational medicine. Although the use of NGS in human liver cancer is still in its infancy, great promise rests in the systematic integration of different molecular analyses obtained by these methodologies, i.e., genomics, transcriptomics and epigenomics. This strategy is likely to be helpful in identifying relevant and recurrent pathophysiological hallmarks thereby elucidating our limited understanding of liver cancer. Beside tumor heterogeneity, progress in translational oncology is challenged by the amount of biological information and considerable “noise” in the data obtained from different NGS platforms. Nevertheless, the following review aims to provide an overview of the current status of next-generation approaches in liver cancer, and outline the prospects of these technologies in diagnosis, patient classification, and prediction of outcome. Further, the potential of NGS to identify novel applications for concept clinical trials and to accelerate the development of new cancer therapies will be summarized

In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression

April 1, 2010Mouse models have markedly improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic experimentation. Here, we report the adaptation of loss-of-function screening to mouse models of cancer. Specifically, we have been able to introduce a library of shRNAs into individual mice using transplantable Eμ-myc lymphoma cells. This approach has allowed us to screen nearly 1,000 genetic alterations in the context of a single tumor-bearing mouse. These experiments have identified a central role for regulators of actin dynamics and cell motility in lymphoma cell homeostasis in vivo. Validation experiments confirmed that these proteins represent bona fide lymphoma drug targets. Additionally, suppression of two of these targets, Rac2 and twinfilin, potentiated the action of the front-line chemotherapeutic vincristine, suggesting a critical relationship between cell motility and tumor relapse in hematopoietic malignancies.National Institutes of Health (U.S.) (RO1 CA128803-01)Massachusetts Institute of Technology. Dept. of Biology (Training Grant)Massachusetts Institute of Technology. Undergraduate Research Opportunities ProgramNational Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant 1-U54-CA112967

BepiColombo’s Cruise Phase: Unique Opportunity for Synergistic Observations

The investigation of multi-spacecraft coordinated observations during the cruise phase of BepiColombo (ESA/JAXA) are reported, with a particular emphasis on the recently launched missions, Solar Orbiter (ESA/NASA) and Parker Solar Probe (NASA). Despite some payload constraints, many instruments onboard BepiColombo are operating during its cruise phase simultaneously covering a wide range of heliocentric distances (0.28 AU–0.5 AU). Hence, the various spacecraft configurations and the combined in-situ and remote sensing measurements from the different spacecraft, offer unique opportunities for BepiColombo to be part of these unprecedented multipoint synergistic observations and for potential scientific studies in the inner heliosphere, even before its orbit insertion around Mercury in December 2025. The main goal of this report is to present the coordinated observation opportunities during the cruise phase of BepiColombo (excluding the planetary flybys). We summarize the identified science topics, the operational instruments, the method we have used to identify the windows of opportunity and discuss the planning of joint observations in the future

BepiColombo's Cruise Phase : Unique Opportunity for Synergistic Observations

The investigation of multi-spacecraft coordinated observations during the cruise phase of BepiColombo (ESA/JAXA) are reported, with a particular emphasis on the recently launched missions, Solar Orbiter (ESA/NASA) and Parker Solar Probe (NASA). Despite some payload constraints, many instruments onboard BepiColombo are operating during its cruise phase simultaneously covering a wide range of heliocentric distances (0.28 AU-0.5 AU). Hence, the various spacecraft configurations and the combined in-situ and remote sensing measurements from the different spacecraft, offer unique opportunities for BepiColombo to be part of these unprecedented multipoint synergistic observations and for potential scientific studies in the inner heliosphere, even before its orbit insertion around Mercury in December 2025. The main goal of this report is to present the coordinated observation opportunities during the cruise phase of BepiColombo (excluding the planetary flybys). We summarize the identified science topics, the operational instruments, the method we have used to identify the windows of opportunity and discuss the planning of joint observations in the future.Peer reviewe

Differential expression of Caveolin-1 in hepatocellular carcinoma: correlation with differentiation state, motility and invasion

WOS: 000264914000001PubMed ID: 19239691Turkish Scientific and Technological Research Council (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [SBAG-107S026]; Dokuz Eylul University Research FoundationDokuz Eylul University [05.KB.SAG.071]We thank Prof. Mehmet Ozturk for providing us HCC cell lines and for his critical reading of the manuscript; and Prof. Aykut Uren for his helpful discussions on the manuscript. We also thank to Evin Ozen for her technical assistance. This work was supported by grants to Nese ATABEY from the Turkish Scientific and Technological Research Council (TUBITAK, SBAG-107S026) and Dokuz Eylul University Research Foundation (05.KB.SAG.071)

Deleted in Liver Cancer 2 (DLC2) Was Dispensable for Development and Its Deficiency Did Not Aggravate Hepatocarcinogenesis

DLC2 (deleted in liver cancer 2), a Rho GTPase-activating protein, was previously shown to be underexpressed in human hepatocellular carcinoma and has tumor suppressor functions in cell culture models. We generated DLC2-deficient mice to investigate the tumor suppressor role of DLC2 in hepatocarcinogenesis and the function of DLC2 in vivo. In this study, we found that, unlike homologous DLC1, which is essential for embryonic development, DLC2 was dispensable for embryonic development and DLC2-deficient mice could survive to adulthood. We also did not observe a higher incidence of liver tumor formation or diethylnitrosamine (DEN)-induced hepatocarcinogenesis in DLC2-deficient mice. However, we observed that DLC2-deficient mice were smaller and had less adipose tissue than the wild type mice. These phenotypes were not due to reduction of cell size or defect in adipogenesis, as observed in the 190B RhoGAP-deficient mouse model. Together, these results suggest that deficiency in DLC2 alone does not enhance hepatocarcinogenesis

Investigating Mercury’s Environment with the Two-Spacecraft BepiColombo Mission

The ESA-JAXA BepiColombo mission will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric dynamics at Mercury as well as their interactions with the solar wind, radiation, and interplanetary dust. Many scientific instruments onboard the two spacecraft will be completely, or partially devoted to study the near-space environment of Mercury as well as the complex processes that govern it. Many issues remain unsolved even after the MESSENGER mission that ended in 2015. The specific orbits of the two spacecraft, MPO and Mio, and the comprehensive scientific payload allow a wider range of scientific questions to be addressed than those that could be achieved by the individual instruments acting alone, or by previous missions. These joint observations are of key importance because many phenomena in Mercury’s environment are highly temporally and spatially variable. Examples of possible coordinated observations are described in this article, analysing the required geometrical conditions, pointing, resolutions and operation timing of different BepiColombo instruments sensors

A novel potent tumour promoter aberrantly overexpressed in most human cancers

The complexity and heterogeneity of tumours have hindered efforts to identify commonalities among different cancers. Furthermore, because we have limited information on the prevalence and nature of ubiquitous molecular events that occur in neoplasms, it is unfeasible to implement molecular-targeted cancer screening and prevention. Here, we found that the FEAT protein is overexpressed in most human cancers, but weakly expressed in normal tissues including the testis, brain, and liver. Transgenic mice that ectopically expressed FEAT in the thymus, spleen, liver, and lung spontaneously developed invasive malignant lymphoma (48%, 19/40) and lung-metastasizing liver cancer (hepatocellular carcinoma) (35%, 14/40) that models human hepatocarcinogenesis, indicating the FEAT protein potently drives tumorigenesis in vivo. Gene expression profiling suggested that FEAT drives receptor tyrosine kinase and hedgehog signalling pathways. These findings demonstrate that integrated efforts to identify FEAT-like ubiquitous oncoproteins are useful and may provide promising approaches for cost-effective cancer screening and prevention