Epigenetics: Dissecting Gene Expression Alteration in PDAC

Pancreatic cancer is the fourth leading cause of cancer deaths, with a low 5-year survival rate of about 7% due to its highly invasive nature. Pancreatic ductal adenocarcinoma (PDAC) comprises more than 90% of all pancreatic cancer cases. At the time of detection, around 80% of cases harbor metastases due to the lack of early diagnosis. For decades, scientists have primarily focused on dissecting the origin of pancreatic cancer through genetic alterations and their contribution to diagnosis. Recently, PDAC research has turned into epigenetics to revolutionize our understanding about the silencing of critical regulatory genes. Epigenetic events can be divided mechanistically into various components, including DNA methylation, histone posttranslational modification, nucleosome remodeling, and regulation of transcription or translation by microRNA. The identified epigenetic processes in PDAC contribute to its specific epigenotype and are correlated phenotypic features. Strikingly, some of them have been suggested to have potential as cancer biomarkers, for disease monitoring, prognosis, and risk validation. As epigenetic aberrations are reversible, their correction will become as a promising therapeutic target

Autophagy-Related Gene Expression Changes Are Found in Pancreatic Cancer and Neurodegenerative Diseases

Genetic alterations can cause cancer, including pancreatic cancer (PC) as well as certain neurodegenerative diseases. Our lab has recently identified genes that are modulated during pancreatic cancer liver metastasis, and some are known to have a role in neurobiology or neurodegenerative diseases. Autophagy or self-eating portrays the lysosomal-dependent degradation and recycling of protein aggregates and defective organisms in eukaryotic cells. Deregulation of autophagy as a cellular mechanism is common in neurodegenerative diseases as well as cancer and may represent a platform by which some genes can affect both disorders. This is exemplified for optineurin, which is an autophagy receptor that was found among genes with intensive modulation of expression in PC liver metastasis. Our results on this autophagy receptor draw the attention to the expression status of this and other autophagy genes in pancreatic cancer progression

New limits on "odderon" amplitudes from analyticity constraints

In studies of high energy $pp$ and $\bar pp$ scattering, the odd (under crossing) forward scattering amplitude accounts for the difference between the $pp$ and $\bar pp$ cross sections. Typically, it is taken as $f_-=-\frac{p}{4\pi}Ds^{\alpha-1}e^{i\pi(1-\alpha)/2}$ ($\alpha\sim 0.5$), which has $\Delta\sigma, \Delta\rho\to0$ as $s\to\infty$, where $\rho$ is the ratio of the real to the imaginary portion of the forward scattering amplitude. However, the odd-signatured amplitude can have in principle a strikingly different behavior, ranging from having $\Delta\sigma\to$non-zero constant to having $\Delta\sigma \to \ln s/s_0$ as $s\to\infty$, the maximal behavior allowed by analyticity and the Froissart bound. We reanalyze high energy $pp$ and $\bar pp$ scattering data, using new analyticity constraints, in order to put new and precise limits on the magnitude of ``odderon'' amplitudes.Comment: 13 pages LaTex, 6 figure

Experimental Results Help Shape the Development of Personalized Medicine in Colorectal Cancer

With estimated 700,000 deaths each year, colorectal carcinoma (CRC) continues to be the fourth leading cause of cancer-related deaths worldwide. Fortunately, the mortality of CRC is considered to be most avertable; hence, it is essential to develop new approaches for more accurate and early diagnosis of primary as well as metastatic CRC, including genetic and biomarker tests. In this regard, the intercellular junctions and the insulin-like growth factor (IGF) axis attract increasing attention, since they are involved in several stages of cancer and for their vital role in regulating cell survival and growth; furthermore, constituents of intercellular junctions and of the IGF axis could be used as tumor and/or metastasis markers, which are becoming the focus of increasing research activities. Our experimental results highlight the importance of gene expression changes in the tight junction proteins claudins, and in the IGF-binding proteins IGFBP3 and IGFBP7. They show additionally that claudins and IGFBPs cannot be simply defined in terms of favoring or antagonizing cancer progression but have additional properties and activities, which become apparent only in the context of liver colonization. Furthermore, their intensive modulation during the initial phase of liver colonization may suggest them as early metastasis-related markers

Treatment of the Intrinsic Hamiltonian in Particle-Number Nonconserving Theories

We discuss the implications of using an intrinsic Hamiltonian in theories without particle-number conservation, e.g., the Hartree-Fock-Bogoliubov approximation, where the Hamiltonian's particle-number dependence leads to discrepancies if one naively replaces the particle-number operator by its expectation value. We develop a systematic expansion that fixes this problem and leads to an a posteriori justification of the widely-used one- plus two-body form of the intrinsic kinetic energy in nuclear self-consistent field methods. The expansion's convergence properties as well as its practical applications are discussed for several sample nuclei.Comment: 6 pages, 5 figure

Modulation of Gene Expression During Stages of Liver Colonization by Pancreatic Cancer in a Rat Model

Pancreatic ductal adenocarcinoma (PDAC) is known for its early spreading of tumor cells into the liver. The aim of this study was to investigate the modulated gene expression of PDAC cells during liver colonization. To that purpose, ASML rat pancreatic cancer cells marked with enhanced green fluorescent protein were inoculated into the portal vein of isogenic BDX rats and reisolated from livers by fluorescence-activated cell sorting sorting at early (1, 3 days), intermediate (9 days), advanced (15 days), and terminal (21 days) stages of liver colonization. Reisolated ASML cells were used for total RNA isolation and subsequently their gene expression was investigated by Illumina chip array for mRNA and miRNA species, followed by Ingenuity Pathway Analysis (IPA). Following reisolation, 7–20% of genes and 10% of miRNA species were modulated significantly in expression during the early stage of liver colonization and continuously thereafter. These overall changes led to distinguish certain categories and processes participating in cancer progression. The knowledge of these alterations in gene expression will suggest targets, which could be used for new diagnostic procedures as well as for combating liver metastasis successfully

Evolution of helicity in NOAA 10923 over three consecutive solar rotations

We have studied the evolution of magnetic helicity and chirality in an active region over three consecutive solar rotations. The region when it first appeared was named NOAA10923 and in subsequent rotations it was numbered NOAA 10930, 10935 and 10941. We compare the chirality of these regions at photospheric, chromospheric and coronal heights. The observations used for photospheric and chromospheric heights are taken from Solar Vector Magnetograph (SVM) and H_alpha imaging telescope of Udaipur Solar Observatory (USO), respectively. We discuss the chirality of the sunspots and associated H_alpha filaments in these regions. We find that the twistedness of superpenumbral filaments is maintained in the photospheric transverse field vectors also. We also compare the chirality at photospheric and chromospheric heights with the chirality of the associated coronal loops, as observed from the HINODE X-Ray Telescope.Comment: 8 pages, 4 figure

Electrodelivery of Drugs into Cancer Cells in the Presence of Poloxamer 188

In the present study it is shown that poloxamer 188, added before or immediately after an electrical pulse used for electroporation, decreases the number of dead cells and at the same time does not reduce the number of reversible electropores through which small molecules (cisplatin, bleomycin, or propidium iodide) can pass/diffuse. It was suggested that hydrophobic sections of poloxamer 188 molecules are incorporated into the edges of pores and that their hydrophilic parts act as brushy pore structures. The formation of brushy pores may reduce the expansion of pores and delay the irreversible electropermeability. Tumors were implanted subcutaneously in both flanks of nude mice using HeLa cells, transfected with genes for red fluorescent protein and luciferase. The volume of tumors stopped to grow after electrochemotherapy and the use of poloxamer 188 reduced the edema near the electrode and around the subcutaneously growing tumors