In humans, computed tomography (CT) is a widely performed technique for the diagnosis and staging of gastric tumors. The purpose of this retrospective case series study was to describe CT findings in a group of dogs with confirmed gastric tumors. For each included dog, the following CT parameters were recorded: gastric tumor location, tumor shape, gastric involvement pattern, tumor enhancement pattern in early and late phases, presence and location of lymphadenopathy, gastric tumor attenuation values, attenuation values of enlarged lymph nodes, maximum short-axis diameter (mm) of enlarged lymph node, maximum long-axis diameter (mm) of enlarged lymph node, and short-axis diameter to long-axis diameter ratio (short axis/long axis). A total of 16 dogs met inclusion criteria and had the following final diagnoses: five lymphoma, six adenocarcinoma, three inflammatory polyps, and two leiomyoma. In the early- and delayed-phase postcontrast images, the mean CT attenuation value for lymphoma was lower than that of other gastric tumors. Lymphadenopathy was widespread in lymphomas and regional in adenocarcinomas. Lymphadenopathy was not detected in leiomyomas. Lymph node measurements in lymphoma were larger than lymph node measurements in adenocarcinoma. Although there were overlapping findings for the different types of gastric tumors, contrast-enhanced CT provided helpful information for characterizing gastric tumors based on the following criteria: early and late enhancement patterns, the site of origin of the mass lesion, and extent of local invasion and distant metastases. Lymphoma should be considered for canine gastric tumors with low mean attenuation values during early- and delayed-phase postcontrast images, and widespread, bulky, and rounded lymphadenopathy.

This report presents a detailed description of hepatic architecture in 200 teleost livers by light microscopy and extensively discusses the phylogenetic viewpoint. The 200 teleost livers showed a great variety of histological images, but not the same image, as in mammalian livers. The hepatocyte-sinusoidal structures of the fish livers were classified into three different types: (a) cord-like form, (b) tubular form, (c) solid form. Biliary tract structures were classified into four types: (a) isolated type, (b) biliary-arteriolar tract (BAT) type, (c) biliary-venous tract (BVT) type, and (d) portal tract type. As phylogenic advancement is graded from low to high, the parenchymal arrangement progressed from solid or tubular form to cord-like form, but the biliary tract structures were not involved. We demonstrate that this study is the first to investigate teleost livers phylogenically, and their architectural differences are shown in the route of hepatic ontogenesis. In hepatic ontogenesis, the formation of the parenchymal arrangement is acquired phylogenically, but the biliary pathway may be adapted in the ecological and behavioral patterns.

DC-HIL/glycoprotein nmb (Gpnmb) expressed on antigen-presenting cells attenuates T-cell activation by binding to syndecan-4 (SD-4) on activated T cells. Because DC-HIL/Gpnmb is expressed abundantly by mouse and human melanoma lines, we posited that melanoma-associated DC-HIL/Gpnmb exerts similar inhibitory function on melanoma-reactive T cells. We generated small interfering RNA-transfected B16F10 melanoma cells to completely knock down DC-HIL/Gpnmb expression, with no alteration in cell morphology, melanin synthesis, or MHC class I expression. This knockdown had no effect on B16F10 proliferation in vitro or entry into the cell cycle following growth stimulation, but it markedly reduced the growth of these cells in vivo following their s.c. injection into syngeneic immunocompetent (but not immunodeficient) mice. This reduction in tumor growth was due most likely to an augmented capacity of DC-HIL-knocked down B16F10 cells (compared with controls) to activate melanoma-reactive T cells as documented in vitro and in mice. Whereas DC-HIL knockdown had no effect on susceptibility of melanoma to killing by cytotoxic T cells, blocking SD-4 function enhanced the reactivity of CD8 + T cells to melanoma-associated antigens on parental B16F10 cells.Using an assay examining the spread to the lung following i.v. injection, DC-HIL-knocked down cells produced lung foci at similar numbers compared with that produced by control cells, but the size of the former foci was significantly smaller than the latter. We conclude that DC-HIL/Gpnmb confers upon melanoma the ability to downregulate the activation of melanoma-reactive T cells, thereby allowing melanoma to evade immunologic recognition and destruction. As such, the DC-HIL/SD-4 pathway is a potentially useful target for antimelanoma immunotherapy. Cancer Res; 70(14); 5778-87. ©2010 AACR.

BackgroundThis report presents a detailed description of hepatic architecture in 46 amphibian livers by light microscopy, and extensively discusses the phylogenetic viewpoint.ResultsThe 46 amphibian livers showed a variety of histological features, but anurans were the same as in mammalian livers. The hepatocyte-sinusoidal structures of the amphibian livers were classified into three different types: (I) several-cell-thick plate type, (II) two-cell-thick plate type, and (III) one-cell-thick plate type, depending on the percentage extension of sinusoidal areas per unit area, measured by morphometry. Hematopoietic tissue structures were observed in the connective tissue of both the perihepatic subcapsular regions and portal triads in the order Caudata and Gymnophiona, but were not observed in the order Anura (except for the genus Bombina and Xenopus). As phylogenetic relationships are branched from urodeles to anurans, the parenchyma arrangement progressed from the combined several- and two-cell-thick plate type to one-cell-thick plate type as seen in the mammalian liver type. In contrast, hematopoietic tissue structures were exactly the opposite and did not involve anurans.ConclusionsThis study is the first to investigate amphibian livers phylogenically, and their architectural differences are shown in the route of hepatic ontogenesis. In this process, parenchymal arrangement formation is acquired phylogenically. The occurrence of hematopoietic cells may be related with the development of the systemic immune system in the spleen and bone marrow.

Background: Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery.Objectives: To investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumorinfiltrating regulatory T cells (Tregs), and intratumoral hypoxia.Animals: Ninety-two client-owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma.Methods: Retrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone.Differences were analyzed in the expression of vascular endothelial growth factor receptor-2 (VEGFR2) and the number of Foxp3 + Tregs and hypoxia-inducible factor (HIF)-1α + cells in tumor tissues sampled at the first and second (recurrence) surgeries.Results: Median TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65-0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF-1α + cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries.Conclusions and Clinical Importance: Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME. K E Y W O R D S adenocarcinoma, postoperative adjuvant treatment, toceranib phosphate, tumor microenvironment

: Aims/Background: The mammalian liver receives both sympathetic and parasympathetic nerves that contain aminergic, cholinergic and peptidergic components. The intrahepatic distribution of nerve fibers are highly species‐dependent; and also, even within one species, there are notable variations. To reveal the pattern and type of hepatic innervation in different species, we examined the distribution and density of these nerve fibers. Methods: The livers of rats, golden hamsters, guinea pigs, dogs and humans were used. Aminergic and peptidergic nerve fibers were identified by immunohistochemistry for tyrosine hydroxylase (TH), neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene‐related peptide (CGRP), and galanin (GAL), and cholinergic fibers were identified by the acetylcholinesterase (AChE) neurohistochemistry method. Results: AChE‐, TH‐, NPY‐, CGRP‐, VIP‐, and SP‐positive nerves were observed in the connective tissue of the portal region, and they were in close contact with hepatic arteries, portal veins and bile ducts in all five species. Within the parenchyma of guinea pig, dog and human livers, TH‐, NPY‐ and SP‐positive fibers were observed, but no AChE‐ and CGRP‐positive fibers were observed. In rat and hamster livers, no parenchymal nerve fibers could be demonstrated, but CGRP‐, NPY‐ and SP‐positive fibers were observed in the border of periportal areas. The density of CGRP‐positive nerve fibers were slightly higher around bile ducts than around hepatic arteries and portal veins. GAL‐positive fibers were not detected in any animal. Conclusions: These data indicate that there were differences in the patterns of hepatic innervation among rats, golden hamsters, guinea pigs, dogs and humans. The data also show that: 1) in rat and hamster livers, hepatic functions may be regulated by both sympathetic and parasympathetic nerves in the portal region; 2) in guinea pig, dog and human livers they may be regulated by these fibers both in the interlobular region (parasympathetic and sympathetic systems) and in the intraparenchymal region (sympathetic system); and thus, 3) in the latter three species, hepatocytes and sinusoidal cells may be innervated by sympathetic nerves.

APCs express receptors recognizing microbes and regulating immune responses by binding to corresponding ligands on immune cells. Having discovered a novel inhibitory pathway triggered by ligation of DC-HIL on APC to a heparin/heparan sulfate-like saccharide of syndecan-4 on activated T cells, we posited DC-HIL can recognize microbial pathogens in a similar manner. We showed soluble recombinant DC-HIL to bind the dermatophytes Trichophyton rubrum and Microsporum audouinii, but not several bacteria nor Candida albicans. Dermatophyte binding was inhibited completely by the addition of heparin. Because DC-HIL contains an ITAM-like intracellular sequence, we questioned whether its binding to dermatophytes can induce tyrosine phosphorylation in dendritic cells (DC). Culturing DC with T. rubrum (but not with C. albicans pseudohyphae) induced phosphorylation of DC-HIL, but not when the tyrosine residue of the ITAM-like sequence was mutated to phenylalanine. To examine the functional significance of such signaling on DC, we cross-linked DC-HIL with mAb (surrogate ligand), which not only induced tyrosine phosphorylation but also up-regulated expression of 23 genes among 662 genes analyzed by gene-array, including genes for profilin-1, myristoylated alanine rich protein kinase C substrate like-1, C/EBP, LOX-1, IL-1β, and TNF-α. This cross-linking also up-regulated expression of the activation markers CD80/CD86 and heightened APC capacity of DC to activate syngeneic T cells. Our findings support a dual role for DC-HIL: inhibition of adaptive immunity following ligation of syndecan-4 on activated T cells and induction of innate immunity against dermatophytic fungi.

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