Efficacy of capillary pattern type IIIA/IIIB by magnifying narrow band imaging for estimating depth of invasion of early colorectal neoplasms

<p>Abstract</p> <p>Background</p> <p>Capillary patterns (CP) observed by magnifying Narrow Band Imaging (NBI) are useful for differentiating non-adenomatous from adenomatous colorectal polyps. However, there are few studies concerning the effectiveness of magnifying NBI for determining the depth of invasion in early colorectal neoplasms. We aimed to determine whether CP type IIIA/IIIB identified by magnifying NBI is effective for estimating the depth of invasion in early colorectal neoplasms.</p> <p>Methods</p> <p>A series of 127 consecutive patients with 130 colorectal lesions were evaluated from October 2005 to October 2007 at the National Cancer Center Hospital East, Chiba, Japan. Lesions were classified as CP type IIIA or type IIIB according to the NBI CP classification. Lesions were histopathologically evaluated. Inter and intraobserver variabilities were assessed by three colonoscopists experienced in NBI.</p> <p>Results</p> <p>There were 15 adenomas, 66 intramucosal cancers (pM) and 49 submucosal cancers (pSM): 16 pSM superficial (pSM1) and 33 pSM deep cancers (pSM2-3). Among lesions diagnosed as CP IIIA 86 out of 91 (94.5%) were adenomas, pM-ca, or pSM1; among lesions diagnosed as CP IIIB 28 out of 39 (72%) were pSM2-3. Sensitivity, specificity and diagnostic accuracy of the CP type III for differentiating pM-ca or pSM1 (<1000 μm) from pSM2-3 (≥1000 μm) were 84.8%, 88.7 % and 87.7%, respectively. Interobserver variability: κ = 0.68, 0.67, 0.72. Intraobserver agreement: κ = 0.79, 0.76, 0.75</p> <p>Conclusion</p> <p>Identification of CP type IIIA/IIIB by magnifying NBI is useful for estimating the depth of invasion of early colorectal neoplasms.</p

Investigation of the Exclusive 3He(e,e'pp)n Reaction

Cross sections for the 3He(e,e'pp)n reaction were measured over a wide range of energy and three- momentum transfer. At a momentum transfer q=375 MeV/c, data were taken at transferred energies omega ranging from 170 to 290 MeV. At omega=220 MeV, measurements were performed at three q values (305, 375, and 445 MeV/c). The results are presented as a function of the neutron momentum in the final-state, as a function of the energy and momentum transfer, and as a function of the relative momentum of the two-proton system. The data at neutron momenta below 100 MeV/c, obtained for two values of the momentum transfer at omega=220 MeV, are well described by the results of continuum-Faddeev calculations. These calculations indicate that the cross section in this domain is dominated by direct two-proton emission induced by a one-body hadronic current. Cross section distributions determined as a function of the relative momentum of the two protons are fairly well reproduced by continuum-Faddeev calculations based on various realistic nucleon-nucleon potential models. At higher neutron momentum and at higher energy transfer, deviations between data and calculations are observed that may be due to contributions of isobar currents.Comment: 14 pages, 1 table, 17 figure

Probing the DeltaNN component of 3He

The 3He(gamma,pi^+/- p) reactions were measured simultaneously over a tagged photon energy range of 800<E_gamma<1120 MeV, well above the Delta resonance region. An analysis was performed to kinematically isolate Delta knockout events from conventional Delta photoproduction events, and a statistically significant excess of pi+p events was identified, consistent with Delta++ knockout. Two methods were used to estimate the DeltaNN probability in the 3He ground state, corresponding to the observed knockout cross section. The first gave a lower probability limit of 1.5+/-0.6+/-0.5%; the second yielded an upper limit of about 2.6%.Comment: 14 page

Decentralizing Inner-Product Functional Encryption

International audienceMulti-client functional encryption (MCFE) is a more flexible variant of functional encryption whose functional decryption involves multiple ciphertexts from different parties. Each party holds a different secret key and can independently and adaptively be corrupted by the adversary. We present two compilers for MCFE schemes for the inner-product functionality, both of which support encryption labels. Our first compiler transforms any scheme with a special key-derivation property into a decentralized scheme, as defined by Chotard et al. (ASIACRYPT 2018), thus allowing for a simple distributed way of generating functional decryption keys without a trusted party. Our second compiler allows to lift an unnatural restriction present in existing (decentralized) MCFE schemes, which requires the adversary to ask for a ciphertext from each party. We apply our compilers to the works of Abdalla et al. (CRYPTO 2018) and Chotard et al. (ASIACRYPT 2018) to obtain schemes with hitherto unachieved properties. From Abdalla et al., we obtain instantiations of DMCFE schemes in the standard model (from DDH, Paillier, or LWE) but without labels. From Chotard et al., we obtain a DMCFE scheme with labels still in the random oracle model, but without pairings

Subthreshold rho^0 photoproduction on 3He

A large reduction of the rho^0 mass in the nuclear medium is reported, inferred from dipion photoproduction spectra in the 1 GeV region, for the reaction 3He(gamma,pi+ pi-)X with a 10% duty factor tagged-photon beam and the TAGX multi-particle spectrometer. The energy range covered (800 < E(gamma) < 1120 MeV) lies mostly below the free rho^0 production threshold, a region which is believed sensitive to modifications of light vector-meson properties at nuclear-matter densities. The rho^0 masses extracted from the MC fitting of the data, m*(rho^0) = 642 +/- 40, 669 +/- 32, and 682 +/- 56 MeV/c^2 for E(gamma) in the 800-880, 880-960, and 960-1040 MeV regions respectively, are independently corroborated by a measured, assumption-free, kinematical observable. This mass shift, far exceeding current mean-field driven theoretical predictions, may be suggestive of rho^0 decay within the range of the nucleonic field.Comment: 40 pages, 13 figures, submitted to Phys. Rev.

Mechanism of trifluorothymidine potentiation of oxaliplatin-induced cytotoxicity to colorectal cancer cells

Oxaliplatin (OHP) is an anticancer agent that acts by formation of Platinum-DNA (Pt-DNA) adducts resulting in DNA-strand breaks and is used for the treatment of colorectal cancer. The pyrimidine analog trifluorothymidine (TFT) forms together with a thymidine phosphorylase inhibitor (TPI) the anticancer drug formulation TAS-102, in which TPI enhances the bioavailability of TFT in vivo. In this in vitro study the combined cytotoxic effects of OHP with TFT were investigated in human colorectal cancer cells as a model for TAS-102 combinations. In a panel of five colon cancer cell lines (WiDr, H630, Colo320, SNU-C4 and SW1116) we evaluated the OHP-TFT drug combinations using the multiple drug–effect analysis with CalcuSyn software, in which the combination index (CI) indicates synergism (CI<0.9), additivity (CI=0.9–1.1) or antagonism (CI>1.1). Drug target analysis was used for WiDr, H630 and SW1116 to investigate whether there was an increase in Pt-DNA adduct formation, DNA damage induction, cell cycle delay and apoptosis. Trifluorothymidine combined with OHP resulted in synergism for all cell lines (all CI<0.9). This was irrespective of schedule in which either one of the drugs was kept at a constant concentration (using variable drug ratio) or when the two drugs were added in a 1 : 1 IC50-based molar ratio. Synergism could be increased for WiDr using sequential drug treatment schedules. Trifluorothymidine increased Pt-DNA adduct formation significantly in H630 and SW1116 (14.4 and 99.1%, respectively; P<0.05). Platinum-DNA adducts were retained best in SW1116 in the presence of TFT. More DNA-strand breaks were induced in SW1116 and the combination increased DNA damage induction (>20%) compared with OHP alone. Exposure to the drugs induced a clear cell-cycle S-phase arrest, but was dose schedule and cell line dependent. Trifluorothymidine (TFT) and OHP both induced apoptosis, which increased significantly for WiDr and SW1116 after TFT–OHP exposure (18.8 and 20.6% respectively; P<0.05). The basal protein levels of ERCC1 DNA repair enzyme were not related to the DNA damage that was induced in the cell lines. In conclusion, the combination of TFT with the DNA synthesis inhibitor OHP induces synergism in colorectal cancer cells, but is dependent on the dose and treatment schedule used

VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer

Inflammation drives expression of VEGFR2, which is expressed on and drives growth of tumor cells in colitis-associated cancer

Sequential morphological characteristics of murine fetal liver hematopoietic microenvironment in Swiss Webster mice

Embryonic hematopoiesis occurs via dynamic development with cells migrating into various organs. Fetal liver is the main hematopoietic organ responsible for hematopoietic cell expansion during embryologic development. We describe the morphological sequential characteristics of murine fetal liver niches that favor the settlement and migration of hematopoietic cells from 12 days post-coitum (dpc) to 0 day post-partum. Liver sections were stained with hematoxylin and eosin, Lennert’s Giemsa, Sirius Red pH 10.2, Gomori’s Reticulin, and Periodic Acid Schiff/Alcian Blue pH 1.0 and pH 2.5 and were analyzed by bright-field microscopy. Indirect imunohistochemistry for fibronectin, matrix metalloproteinase-1 (MMP-1), and MMP-9 and histochemistry for naphthol AS-D chloroacetate esterase (NCAE) were analyzed by confocal microscopy. The results showed that fibronectin was related to the promotion of hepatocyte and trabecular differentiation; reticular fibers did not appear to participate in fetal hematopoiesis but contributed to the physical support of the liver after 18 dpc. During the immature phase, hepatocytes acted as the fundamental stroma for the erythroid lineage. The appearance of myeloid cells in the liver was related to perivascular and subcapsular collagen, and NCAE preceded MMP-1 expression in neutrophils, an occurrence that appeared to contribute to their liver evasion. Thus, the murine fetal liver during ontogenesis shows two different phases: one immature and mainly endodermic (<14 dpc) and the other more developed (endodermic-mesenchymal; >15 dpc) with the maturation of hepatocytes, a better definition of trabecular pattern, and an increase in the connective tissue in the capsule, portal spaces, and liver parenchyma. The decrease of hepatic hematopoiesis (migration) coincides with hepatic maturation

Mesenchymal Stem Cell Transition to Tumor-Associated Fibroblasts Contributes to Fibrovascular Network Expansion and Tumor Progression

Tumor associated fibroblasts (TAF), are essential for tumor progression providing both a functional and structural supportive environment. TAF, known as activated fibroblasts, have an established biological impact on tumorigenesis as matrix synthesizing or matrix degrading cells, contractile cells, and even blood vessel associated cells. The production of growth factors, cytokines, chemokines, matrix-degrading enzymes, and immunomodulatory mechanisms by these cells augment tumor progression by providing a suitable environment. There are several suggested origins of the TAF including tissue-resident, circulating, and epithelial-to-mesenchymal-transitioned cells.We provide evidence that TAF are derived from mesenchymal stem cells (MSC) that acquire a TAF phenotype following exposure to or systemic recruitment into adenocarcinoma xenograft models including breast, pancreatic, and ovarian. We define the MSC derived TAF in a xenograft ovarian carcinoma model by the immunohistochemical presence of 1) fibroblast specific protein and fibroblast activated protein; 2) markers phenotypically associated with aggressiveness, including tenascin-c, thrombospondin-1, and stromelysin-1; 3) production of pro-tumorigenic growth factors including hepatocyte growth factor, epidermal growth factor, and interleukin-6; and 4) factors indicative of vascularization, including alpha-smooth muscle actin, desmin, and vascular endothelial growth factor. We demonstrate that under long-term tumor conditioning in vitro, MSC express TAF-like proteins. Additionally, human MSC but not murine MSC stimulated tumor growth primarily through the paracrine production of secreted IL6.Our results suggest the dependence of in vitro Skov-3 tumor cell proliferation is due to the presence of tumor-stimulated MSC secreted IL6. The subsequent TAF phenotype arises from the MSC which ultimately promotes tumor growth through the contribution of microvascularization, stromal networks, and the production of tumor-stimulating paracrine factors