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Sample records for intestinal tumor susceptibility

  1. Tumors of the small intestine

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    Alonso Gamboa, Tatiana

    2013-01-01

    Differential diagnoses are performed to establish the cause of chronic abdominal pain in patients. Histological types are considered in patients with primary tumors of unknown origin. Benign and malignant neoplasms are described, including methods of diagnosis and treatment. Clinical manifestations are cited. Early and accurate diagnoses are important for an acceptable outcome in patients with malignant small bowel tumors. Recurrence is provoked many deaths, suggesting the importance of adjuvant chemotherapy [es

  2. Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine

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    Kathryn S. Brown

    2014-01-01

    Full Text Available Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1 mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC.

  3. [Treatment of polyps and villous tumors of the large intestine].

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    Nazarov, L U; Agavelian, A M; Kazarian, G A; Bagdasarian, A A; Martirosian, V S

    1987-07-01

    Polyps and villous tumors were found in 1525 of 10624 patients (14.3%) aged from 40 to 60. In 82% of the cases they were in combination with ulcer disease of the stomach and duodenum, with inflammatory diseases of the gastro-intestinal tract, diverticulitis, tumors of the colon. 1519 polypectomies and dissection of villous tumors both via the fibroscope, rectoscope and by transanal access were made. Complications were obtained in 5 patients, recurrent disease was noted in 3 patients (0.9%).

  4. Constipação intestinal em pacientes com tumores intracranianos Obstipación intestinal en pacientes com tumores intracraneanos Intestinal constipation in patients with intracranial tumors

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    Analuiza Cândido Torres

    2006-06-01

    Full Text Available O esforço que ocorre durante a manobra de Valsalva gera aumento da pressão intracraniana e pode descompensar pacientes com hipertensão intracraniana. Os objetivos deste estudo foram avaliar a incidência de constipação intestinal no pré-operatório de pacientes com tumores intracranianos e relacionar a constipação intestinal com a descompensação da hipertensão intracraniana. O estudo foi realizado na unidade de neurocirurgia do Hospital São Paulo, de agosto a outubro de 2003, com a avaliação de 37 pacientes. O tempo médio de pré-operatório foi de 12 dias, variando de 2 a 34 dias. Durante esse período, 6 (16,2% pacientes apresentaram constipação, sendo que todos receberam dieta laxativa e lactulose, e destes, 2 (33,3% necessitaram de enema. Todos os pacientes realizaram manobra de Valsalva durante a evacuação, e não foi observada descompensação da hipertensão intracraniana nos pacientes que apresentaram ou não constipação intestinal.El esfuerzo empleado durante la maniobra de Valsalva produce aumento de la presión intracraneana, que podría llevar a descompensación de los pacientes con hipertensión intracraneana. Los objetivos del presente estudio fueron evaluar la incidencia de constipación intestinal en el preoperatorio de pacientes con tumores intracraneanos y relacionar la constipación intestinal con la descompensación de la hipertensión intracraneana. El estudio fue realizado en la unidad de neurocirugía del Hospital São Paulo, Brasil, de agosto a octubre de 2003, evaluando a 37 pacientes. El tiempo medio de preoperatorio fue 12 días, oscilando entre 2 y 34 días. Durante éste periodo 6 (16,2% pacientes presentaron constipación, considerando que todos recibieron dieta laxante y lactulosa; de estos, 2 (33,3% necesitaron de enema. Todos los pacientes hicieron maniobra de Valsalva durante la eliminación de heces; no se observó descompensación de la hipertensión intracraneana en los pacientes que

  5. Independent occurence of gastric tumor and intestinal metaplasia by x-irradiation

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    Watanabe, Hiromitsu; Ito, Akihiro

    1986-01-01

    The selective occurence of gastric tumors and intestinal metaplasias in the stomach by X-irradiation were described both in mice and rats. The appearance of both lesions was greatly influenced by animal's strains in both species and also by the sex in rats. A few gastric tumors were observed in the animals given a high does with spilt into low doses of X-irradiation. The adequate dose for gastric tumorigenesis may be around 20 Gy in mice and 15 Gy in rats. A good relationship between X-ray dose and incidence of gastric tumor was observed in ICR mice. Frequency of intestinal metaplasia by X-irradiation was much higher in rats compared to that in mice. X-ray dose requested for moderate and induction of intestinal metaplasia was decreased with a dose which was induced erosion and gastric tumor. It has been empirically clarified that an elevation of pH value in the gastric juice is one of the principal factors responsible for the development of intestinal metaplasia in the gastric mucosa among the conditions thus for introduced. In this article, we have introduced the relevant examples about intestinal metaplasia without carcinogenic insult, and the relationship between gastric tumor and intestinal metaplasia were described. The intestinal metaplasia was not always observed within or adjacent to neoplastic gastric glands. A combined treatment of X-ray and MNNG was not effective for gastric tumor and frequency of intestinal metaplasia was inversely related to the incidence of gastric tumors. In conclusion, occurrence of gastric tumor and intestinal metaplasia may be independent, and intestinal metaplasia might not be a prerequite for the occurrence of gastric tumor. (author)

  6. Bacterial overgrowth and inflammation of small intestine after carboxymethylcellulose ingestion in genetically susceptible mice.

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    Swidsinski, Alexander; Ung, Victoria; Sydora, Beate C; Loening-Baucke, Vera; Doerffel, Yvonne; Verstraelen, Hans; Fedorak, Richard N

    2009-03-01

    Detergents and emulsifiers added to food may destroy the mucus barrier, which normally isolates bacteria from the intestinal wall, and lead to chronic bowel inflammation in susceptible persons. We investigated the influence of 2% carboxymethylcellulose (CMC) on the biostructure of the intestinal microbiota in IL-10 gene-deficient mice. Twenty to 27-week-old IL-10 gene-deficient mice received either 2% CMC solution (n = 7) or water (n = 6) orally for 3 weeks. Intestinal bacteria were investigated using fluorescence in situ hybridization in paraffin-fixed sections of the intestine. CMC-treated IL-10 gene-deficient mice demonstrated a massive bacterial overgrowth, distention of spaces between villi, with bacteria filling these spaces, adherence of bacteria to the mucosa, and migration of bacteria to the bottom of the crypts of Lieberkuehn. Leukocytes migrated into the intestinal lumen in 4 of the 7 CMC mice. The changes were similar to those observed in Crohn's disease in humans and were absent in control animals. CMC induces bacterial overgrowth and small bowel inflammation in susceptible animals. Because of its ubiquity in products and its unrestricted use in food of the industrial world, CMC is an ideal suspect to account for the rise of IBD in the 20th century.

  7. Lead, genetic susceptibility, and risk of adult brain tumors.

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    Rajaraman, Preetha; Stewart, Patricia A; Samet, Jonathan M; Schwartz, Brian S; Linet, Martha S; Zahm, Shelia Hoar; Rothman, Nathaniel; Yeager, Meredith; Fine, Howard A; Black, Peter M; Loeffler, Jay; Shapiro, William R; Selker, Robert G; Inskip, Peter D

    2006-12-01

    Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure. We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports. Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 microg/m3-y, 50 to 99 microg/m3-y, and >or=100 microg/m3-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk. Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype.

  8. Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis

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    Meisel, Marlies; Mayassi, Toufic; Fehlner-Peach, Hannah; Koval, Jason C.; O' Brien, Sarah L.; Hinterleitner, Reinhard; Lesko, Kathryn; Kim, Sangman; Bouziat, Romain; Chen, Li; Weber, Christopher R.; Mazmanian, Sarkis K.; Jabri, Bana; Antonopoulos, Dionysios A.

    2016-09-20

    Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin 15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and play a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). While the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S rRNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (v-IL-15tg mice) shows distinct changes in the composition of the intestinal bacteria. While some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum, and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.

  9. Obscure Gastrointestinal Bleeding Due to a Small Intestinal Gastrointestinal Stromal Tumor in a Young Adult

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    Mami Yamamoto

    2016-11-01

    Full Text Available The source of most cases of gastrointestinal bleeding is the upper gastrointestinal tract. Since bleeding from the small intestine is very rare and difficult to diagnose, time is required to identify the source. Among small intestine bleeds, vascular abnormalities account for 70–80%, followed by small intestine tumors that account for 5–10%. The reported peak age of the onset of small intestinal tumors is about 50 years. Furthermore, rare small bowel tumors account for only 1–2% of all gastrointestinal tumors. We describe a 29-year-old man who presented with obscure anemia due to gastrointestinal bleeding and underwent laparotomy. Surgical findings revealed a well-circumscribed lesion measuring 45 × 40 mm in the jejunum that initially appeared similar to diverticulosis with an abscess. However, the postoperative pathological diagnosis was a gastrointestinal stromal tumor with extramural growth.

  10. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

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    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...

  11. Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility

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    Aw, Tak Yee

    2005-01-01

    The intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation of oxidants like peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as inflammation and cancer. Despite this recognition, we know little of the pathways of intestinal transport, metabolism, and luminal disposition of dietary peroxides in vivo or of the underlying mechanisms of lipid peroxide-induced genesis of intestinal disease processes. This chapter summarizes our current understanding of the determinants of intestinal absorption and metabolism of peroxidized lipids. I will review experimental evidence from our laboratory and others (Table 1) supporting the pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and how reductant availability can be compromised under chronic stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and redox contribution to genesis of gut disorders. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of luminal GSH in preserving the integrity of the intestinal epithelium

  12. Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors

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    Rehfeld, Anders Aagaard; Plass, Mireya; Døssing, Kristina

    2014-01-01

    The tumorigenesis of small intestinal neuroendocrine tumors (SI-NETs) is poorly understood. Recent studies have associated alternative polyadenylation (APA) with proliferation, cell transformation, and cancer. Polyadenylation is the process in which the pre-messenger RNA is cleaved at a polyA site...... and a polyA tail is added. Genes with two or more polyA sites can undergo APA. This produces two or more distinct mRNA isoforms with different 3' untranslated regions. Additionally, APA can also produce mRNAs containing different 3'-terminal coding regions. Therefore, APA alters both the repertoire...... and the expression level of proteins. Here, we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three SI-NETs and a reference sample. In the tumors, 16 genes showed significant changes of APA pattern, which lead to either the 3' truncation of mRNA coding regions...

  13. The Intrauterine and Nursing Period Is a Window of Susceptibility for Development of Obesity and Intestinal Tumorigenesis by a High Fat Diet in Min/+ Mice as Adults

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    Ha Thi Ngo

    2015-01-01

    Full Text Available We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia/+ mice. The mice were given a 10% fat diet throughout life (negative control or a 45% fat diet in utero, during nursing, during both in utero and nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+ or 23 weeks for obesogenic effect (wild-type. Body weight at 11 weeks was increased after a 45% fat diet during nursing, during both in utero and nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or during in utero and nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.

  14. Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

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    Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

    2013-10-15

    Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

  15. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility.

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    Joshua M Uronis

    2009-06-01

    Full Text Available It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD and ulcerative colitis (UC collectively referred to as inflammatory bowel disease (IBD. Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC. However, the impact of the microbiota on the development of colitis-associated cancer (CAC remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM-exposed, conventionalized-Il10(-/- mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62% of AOM-Il10(-/- mice developed colon tumors compared to only 3/15 (20% of AOM- wild-type (WT mice. Conventionalized AOM-Il10(-/- mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10(-/- mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10(-/- mice. Germ-free AOM-treated Il10(-/- mice showed normal colon histology and were devoid of tumors. Il10(-/-; Myd88(-/- mice treated with AOM displayed reduced expression of Il12p40 and Tnfalpha mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma.

  16. Tumor del estroma gastrointestinal del intestino delgado Gastrointestinal stromal tumor of small intestine

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    Magaly Marión Luna Gozá

    2011-12-01

    the low belly accompanied by vomiting, fatigue and weakness. She was operated on and is diagnosed with a stump acute appendicitis and of occlusive type en elderly without to rule out an adhesion occlusion. Carrying out the laparotomy it was found that this not-coagulating cavity was blood-free and also a stalked hemorrhagic tumor with movements towards the terminal ileum. Authors carried out its exeresis resecting approximately 5 cm of small intestine with a termino-terminal suture later. A significant cleaning of peritoneal cavity was carried out with the habitual closure achieving a satisfactory evolution with her discharge at 7 days. Patient remains asymptomatic at one a half year postoperative and biopsy yielded a 5 cm-small intestine tumor with a low grade of malignancy.

  17. Modification of the intestinal postirradiation proliferative response by intraabdominal H-4-II-E2 tumors

    International Nuclear Information System (INIS)

    Evans, M.J.; Kovacs, C.J.; Schenken, L.L.; Burholt, D.R.

    1981-01-01

    Intraperitoneal injection of H-4-II-E 2 tumor cells gave rise to a number of individually growing intraabdominal tumors concentrated at sites of high abdominal vascularization. During tumor growth, both tumor and intestinal crypt cell proliferative activity were progressively depressed. A linear reduction of [ 3 H]TdR incorporation occurred in individual tumors independent of tumor size, suggesting that total tumor burden determines the proliferative status of individual tumors. Cytokinetic jejunal crypt analyses indicated that both a reduction in crypt cellularity and an abbreviated cell cycle transit time were noted during the depression of proliferative activity in the jejunum. In tumor-bearing rats the migration rate of cells from the jejunal crypt through the villus was reduced in response to a reduction in total cell production in the crypt. The life span of the epithelial cell in both tumor-bearing and normal rats was similar due to a reduction in villus cellularity in the tumor-bearing animals. Following abdominal irradiation of the tumor, the magnitude, but not the time course of hyperproliferative intestinal recovery, was influenced by the tumor mass. For nontumor-bearing animals, maximal hyperproliferation (>200% of control) occurred 96 hr postradiation. With increasing tumor burden the compensatory proliferative response to radiation was progressively reduced

  18. Intestinal alkaline phosphatase prevents antibiotic-induced susceptibility to enteric pathogens.

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    Alam, Sayeda Nasrin; Yammine, Halim; Moaven, Omeed; Ahmed, Rizwan; Moss, Angela K; Biswas, Brishti; Muhammad, Nur; Biswas, Rakesh; Raychowdhury, Atri; Kaliannan, Kanakaraju; Ghosh, Sathi; Ray, Madhury; Hamarneh, Sulaiman R; Barua, Soumik; Malo, Nondita S; Bhan, Atul K; Malo, Madhu S; Hodin, Richard A

    2014-04-01

    To determine the efficacy of oral supplementation of the gut enzyme intestinal alkaline phosphatase (IAP) in preventing antibiotic-associated infections from Salmonella enterica serovar Typhimurium (S. Typhimurium) and Clostridium difficile. The intestinal microbiota plays a pivotal role in human health and well-being. Antibiotics inherently cause dysbiosis, an imbalance in the number and composition of intestinal commensal bacteria, which leads to susceptibility to opportunistic bacterial infections. Previously, we have shown that IAP preserves the normal homeostasis of intestinal microbiota and that oral supplementation with calf IAP (cIAP) rapidly restores the normal gut flora. We hypothesized that oral IAP supplementation would protect against antibiotic-associated bacterial infections. C57BL/6 mice were treated with antibiotic(s) ± cIAP in the drinking water, followed by oral gavage of S. Typhimurium or C. difficile. Mice were observed for clinical conditions and mortality. After a defined period of time, mice were killed and investigated for hematological, inflammatory, and histological changes. We observed that oral supplementation with cIAP during antibiotic treatment protects mice from infections with S. Typhimurium as well as with C. difficile. Animals given IAP maintained their weight, had reduced clinical severity and gut inflammation, and showed improved survival. Oral IAP supplementation protected mice from antibiotic-associated bacterial infections. We postulate that oral IAP supplementation could represent a novel therapy to protect against antibiotic-associated diarrhea (AAD), C. difficile-associated disease (CDAD), and other enteric infections in humans.

  19. Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

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    Ikuta, Togo; Kurosumi, Masafumi; Yatsuoka, Toshimasa; Nishimura, Yoji

    2016-01-01

    Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc Min/+ mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

  20. Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

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    Ikuta, Togo, E-mail: togo@cancer-c.pref.saitama.jp [Department of Cancer Prevention, Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Kurosumi, Masafumi, E-mail: mkurosumi@cancer-c.pref.saitama.jp [Division of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Yatsuoka, Toshimasa, E-mail: yatsuoka-gi@umin.ac.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Nishimura, Yoji, E-mail: yojinish@cancr-c.pref.saitama.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan)

    2016-05-01

    Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc{sup Min/+}mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

  1. Dietary feeding of freeze-dried whole cranberry inhibits intestinal tumor development in Apcmin/+ mice

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    Dong, Wenxiao; Zhang, Yujie; Wang, Sinan; Xie, Runxiang; Wang, Bangmao; Cao, Hailong

    2017-01-01

    It is increasingly perceived that dietary components have been linked with the prevention of intestinal cancer. Cranberry is a rich source of phenolic constituents and non-digestible fermentable dietary fiber, which shows anti-proliferation effect in colorectal cancer cells. Herein, we investigated the efficacy of long-term cranberry diet on intestinal adenoma formation in Apcmin/+ mice. Apcmin/+ mice were fed a basal diet or a diet containing 20% (w/w) freeze-dried whole cranberry powder for 12 weeks, and the number and size of tumors were recorded after sacrifice. Our results showed that cranberry strongly prevented the growth of intestinal tumors by 33.1%. Decreased cell proliferation and increased apoptosis were observed in tumors of cranberry-fed mice. Cranberry diet reduced the expression profile of colonic inflammatory cytokines (IFN-γ, IL-1β and TNF-α) accompanied with increased levels of anti-inflammatory cytokines (IL-4 and IL-10). Moreover, the number of colonic goblet cells and MUC2 production were increased, and the intestinal barrier function was also improved. In addition, cranberry diet increased caecal short chain fatty acids concentrations, and down-regulated epidermal growth factor receptor signaling pathway. These data firstly show the efficacy and associated mechanisms of cranberry diet on intestinal tumor growth in Apcmin/+ mice, suggesting its chemopreventive potential against intestinal cancer. PMID:29228651

  2. Detection of coding microsatellite frameshift mutations in DNA mismatch repair-deficient mouse intestinal tumors.

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    Woerner, Stefan M; Tosti, Elena; Yuan, Yan P; Kloor, Matthias; Bork, Peer; Edelmann, Winfried; Gebert, Johannes

    2015-11-01

    Different DNA mismatch repair (MMR)-deficient mouse strains have been developed as models for the inherited cancer predisposing Lynch syndrome. It is completely unresolved, whether coding mononucleotide repeat (cMNR) gene mutations in these mice can contribute to intestinal tumorigenesis and whether MMR-deficient mice are a suitable molecular model of human microsatellite instability (MSI)-associated intestinal tumorigenesis. A proof-of-principle study was performed to identify mouse cMNR-harboring genes affected by insertion/deletion mutations in MSI murine intestinal tumors. Bioinformatic algorithms were developed to establish a database of mouse cMNR-harboring genes. A panel of five mouse noncoding mononucleotide markers was used for MSI classification of intestinal matched normal/tumor tissues from MMR-deficient (Mlh1(-/-) , Msh2(-/-) , Msh2(LoxP/LoxP) ) mice. cMNR frameshift mutations of candidate genes were determined by DNA fragment analysis. Murine MSI intestinal tumors but not normal tissues from MMR-deficient mice showed cMNR frameshift mutations in six candidate genes (Elavl3, Tmem107, Glis2, Sdccag1, Senp6, Rfc3). cMNRs of mouse Rfc3 and Elavl3 are conserved in type and length in their human orthologs that are known to be mutated in human MSI colorectal, endometrial and gastric cancer. We provide evidence for the utility of a mononucleotide marker panel for detection of MSI in murine tumors, the existence of cMNR instability in MSI murine tumors, the utility of mouse subspecies DNA for identification of polymorphic repeats, and repeat conservation among some orthologous human/mouse genes, two of them showing instability in human and mouse MSI intestinal tumors. MMR-deficient mice hence are a useful molecular model system for analyzing MSI intestinal carcinogenesis. © 2014 Wiley Periodicals, Inc.

  3. A rare case of retroperitoneal malignant triton tumor invading renal vein and small intestine

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    Mijović Žaklina

    2013-01-01

    Full Text Available Introduction. Malignant Triton tumor is a very rare malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation. Most of those tumors occur in patients with von Recklinghausen’s disease or as a late complication of irradiation and commonly seen in the head, neck, extremities and trunk. Case report. We reported retroperitoneal malignant Triton tumor in a 57-year-old female patient. Skin lesions were not present, and there was no family history of neurofibromatosis or previous irradiation. The presented case is one of a few recorded in the specialized literature that occurs in the retroperitoneal space in sporadic form. In this case, tumor consisted of a multilobular mass was in close relation with the abdominal aorta and inferior vena cava and involved the renal vein with gross invasion of the small intestine. The patient underwent total resection of the tumor and left nefrectomy was performed. The small intestine 10 cm in length was also resected and end-to-end anastomosis was conducted. The postoperative course was uneventful and the patient was discharged from the hospital ten days after the surgery. Conclusion. Diagnostically, it is crucial to recognize this uncommon histological variant because malignant Triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does. The use of the immunohistochemistry is essential in making the correct diagnosis. Only appropriate pathological evaluation supported by immunostaining with S-100 protein and desmin confirmed the diagnosis. Aggressive surgical management treatment improves the prognosis of such cases with adjuvant radiotherapy.

  4. Wip1 abrogation decreases intestinal tumor frequency in APC(Min/+) mice irrespective of radiation quality.

    Science.gov (United States)

    Suman, Shubhankar; Moon, Bo-Hyun; Thakor, Hemang; Fornace, Albert J; Datta, Kamal

    2014-09-01

    Low-linear energy transfer (low-LET) γ-ray exposure is a risk factor for colorectal cancer (CRC). Due to their high-LET nature, energetic iron ions found in space are expected to pose greater CRC risks to astronauts undertaking long-duration space missions beyond low Earth orbit. Wild-type p53-induced phosphatase 1 (Wip1) is important for cellular DNA damage response and its abrogation has been shown to inhibit spontaneous intestinal tumorigenesis in APC(Min/+) mice, a well-studied mouse model of human CRC. However, the relationship of Wip1 to radiation-induced intestinal tumorigenesis, especially by energetic iron ions, has not been investigated in APC(Min/+) mice. We have previously reported that there is a greater intestinal tumorigenic potential of iron-ion radiation relative to (137)Cs γ rays, so the purpose of the current study was to investigate whether Wip1 abrogation could influence high-LET dependent intestinal tumorigenesis in APC(Min/+) mice. Intestinal tumor frequency and grade were assessed in APC(Min/+)/Wip1(-/-) mice and results were compared to those in APC(Min/+)/Wip1(+/+) mice after exposure to a mean absorbed dose of 2 Gy from (137)Cs γ rays or 1.6 Gy from 1 GeV/n iron ions. Cellular differentiation and proliferation were also assessed in the intestinal tumors of sham-irradiated and irradiated mice. Decreased tumor frequency and lower tumor grade were observed in APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. Notably, a similar decrease (∼6-fold in both groups) in tumor number was observed in sham-irradiated and γ-irradiated APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. However, tumorigenesis in the energetic iron-ion exposed group was reduced ∼8-fold in APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. A significantly lower proliferation/differentiation index in tumors of iron-ion exposed APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice suggests that reduced proliferation and enhanced

  5. Wip1 abrogation decreases intestinal tumor frequency in APCMin/+ mice irrespective of radiation quality

    Science.gov (United States)

    Suman, Shubhankar; Moon, Bo-Hyun; Thakor, Hemang; Fornace, Albert J; Datta, Kamal

    2017-01-01

    Low linear energy transfer (low-LET) γ-ray exposure is a risk factor for colorectal cancer (CRC). Due to high-LET nature, energetic iron ions are expected to pose greater CRC risks to astronauts undertaking long duration space missions beyond low earth orbit (LEO). Wild-type p53-induced phosphatase 1 (Wip1) is important for cellular DNA damage response and its abrogation is reported to inhibit spontaneous intestinal tumorigenesis in APCMin/+ mice, a well-studied mouse model of human CRC. However, Wip1 in relation to radiation-induced especially energetic iron ions-induced intestinal tumorigenesis has not been investigated in APCMin/+ mice. While we earlier demonstrated greater intestinal tumorigenic potential of energetic iron ions relative to 137Cs γ rays, the purpose of the current study was to investigate if Wip1 abrogation could influence radiation quality dependent intestinal tumorigenesis in APCMin/+ mice. Intestinal tumor frequency and grade was assessed in APCMin/+;Wip1−/− mice and results were compared to those in APCMin/+;Wip1+/+ mice after exposure to a mean absorbed dose of 2 Gy from 137Cs γ rays or 1.6 Gy from 1 GeV/n iron ions. Cellular differentiation and proliferation were also assessed in the intestinal tumors of irradiated and sham irradiated mice. Decreased tumor frequency and lower tumor grade was observed in APCMin/+;Wip1−/− relative to APCMin/+;Wip1+/+ mice. Notably, similar decrease (~6 fold in both groups) in tumor number was observed in sham-, and γ-irradiated APCMin/+;Wip1−/− relative to APCMin/+;Wip1+/+ mice. However, tumorigenesis in energetic iron ions group was reduced ~8 fold in APCMin/+;Wip1−/− relative to APCMin/+;Wip1+/+ mice. Significantly lower proliferation/differentiation index in tumors of energetic iron ions exposed APCMin/+;Wip1−/− relative to APCMin/+;Wip1+/+ mice suggests reduced proliferation and enhanced differentiation as a result of Wip1 abrogation. In conclusion, the current study demonstrates

  6. A targeted constitutive mutation in the APC tumor suppressor gene underlies mammary but not intestinal tumorigenesis.

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    Claudia Gaspar

    2009-07-01

    Full Text Available Germline mutations in the adenomatous polyposis coli (APC gene are responsible for familial adenomatous polyposis (FAP, an autosomal dominant hereditary predisposition to the development of multiple colorectal adenomas and of a broad spectrum of extra-intestinal tumors. Moreover, somatic APC mutations play a rate-limiting and initiating role in the majority of sporadic colorectal cancers. Notwithstanding its multifunctional nature, the main tumor suppressing activity of the APC gene resides in its ability to regulate Wnt/beta-catenin signaling. Notably, genotype-phenotype correlations have been established at the APC gene between the length and stability of the truncated proteins encoded by different mutant alleles, the corresponding levels of Wnt/beta-catenin signaling activity they encode for, and the incidence and distribution of intestinal and extra-intestinal tumors. Here, we report a novel mouse model, Apc1572T, obtained by targeting a truncated mutation at codon 1572 in the endogenous Apc gene. This hypomorphic mutant allele results in intermediate levels of Wnt/beta-catenin signaling activation when compared with other Apc mutations associated with multifocal intestinal tumors. Notwithstanding the constitutive nature of the mutation, Apc(+/1572T mice have no predisposition to intestinal cancer but develop multifocal mammary adenocarcinomas and subsequent pulmonary metastases in both genders. The histology of the Apc1572T primary mammary tumours is highly heterogeneous with luminal, myoepithelial, and squamous lineages and is reminiscent of metaplastic carcinoma of the breast in humans. The striking phenotype of Apc(+/1572T mice suggests that specific dosages of Wnt/beta-catenin signaling activity differentially affect tissue homeostasis and initiate tumorigenesis in an organ-specific fashion.

  7. Insights into a microwave susceptible agent for minimally invasive microwave tumor thermal therapy.

    Science.gov (United States)

    Shi, Haitang; Liu, Tianlong; Fu, Changhui; Li, Linlin; Tan, Longfei; Wang, Jingzhuo; Ren, Xiangling; Ren, Jun; Wang, Jianxin; Meng, Xianwei

    2015-03-01

    This work develops a kind of sodium alginate (SA) microcapsules as microwave susceptible agents for in vivo tumor microwave thermal therapy for the first time. Due to the excellent microwave susceptible properties and low bio-toxicity, excellent therapy efficiency can be achieved with the tumor inhibiting ratio of 97.85% after one-time microwave thermal therapy with ultralow power (1.8 W, 450 MHz). Meanwhile, the mechanism of high microwave heating efficiency was confirmed via computer-simulated model in theory, demonstrating that the spatial confinement efficiency of microcapsule walls endows the inside ions with high microwave susceptible properties. This strategy offers tremendous potential applications in clinical tumor treatment with the benefits of safety, reliability, effectiveness and minimally invasiveness. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Expressions of tight junction proteins Occludin and Claudin-1 are under the circadian control in the mouse large intestine: implications in intestinal permeability and susceptibility to colitis.

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    Oh-oka Kyoko

    Full Text Available BACKGROUND & AIMS: The circadian clock drives daily rhythms in behavior and physiology. A recent study suggests that intestinal permeability is also under control of the circadian clock. However, the precise mechanisms remain largely unknown. Because intestinal permeability depends on tight junction (TJ that regulates the epithelial paracellular pathway, this study investigated whether the circadian clock regulates the expression levels of TJ proteins in the intestine. METHODS: The expression levels of TJ proteins in the large intestinal epithelium and colonic permeability were analyzed every 4, 6, or 12 hours between wild-type mice and mice with a mutation of a key clock gene Period2 (Per2; mPer2(m/m. In addition, the susceptibility to dextran sodium sulfate (DSS-induced colitis was compared between wild-type mice and mPer2(m/m mice. RESULTS: The mRNA and protein expression levels of Occludin and Claudin-1 exhibited daily variations in the colonic epithelium in wild-type mice, whereas they were constitutively high in mPer2(m/m mice. Colonic permeability in wild-type mice exhibited daily variations, which was inversely associated with the expression levels of Occludin and Claudin-1 proteins, whereas it was constitutively low in mPer2(m/m mice. mPer2(m/m mice were more resistant to the colonic injury induced by DSS than wild-type mice. CONCLUSIONS: Occludin and Claudin-1 expressions in the large intestine are under the circadian control, which is associated with temporal regulation of colonic permeability and also susceptibility to colitis.

  9. Mouse Rad1 deletion enhances susceptibility for skin tumor development

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    Wang Xiangyuan

    2010-03-01

    Full Text Available Abstract Background Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. The Rad1 protein, evolutionarily conserved from yeast to humans, exists in cells as monomer as well as a component in the 9-1-1 protein complex. Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. Results To address this question, we constructed mice with a deletion of Mrad1. Matings between heterozygous Mrad1 mutant mice produced Mrad1+/+ and Mrad1+/- but no Mrad1-/- progeny, suggesting the Mrad1 null is embryonic lethal. Mrad1+/- mice demonstrated no overt abnormalities up to one and half years of age. DMBA-TPA combinational treatment was used to induce tumors on mouse skin. Tumors were larger, more numerous, and appeared earlier on the skin of Mrad1+/- mice compared to Mrad1+/+ animals. Keratinocytes isolated from Mrad1+/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1+/+ control cells. Conclusion These data suggest that Mrad1 is important for preventing tumor development, probably through maintaining genomic integrity. The effects of heterozygous deletion of Mrad1 on proliferation and apoptosis of keratinocytes is different from those resulted from Mrad9 heterozygous deletion (from our previous study, suggesting that Mrad1 also functions independent of Mrad9 besides its role in the Mrad9-Mrad1-Mhus1 complex in mouse cells.

  10. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment.

    Science.gov (United States)

    Kostic, Aleksandar D; Chun, Eunyoung; Robertson, Lauren; Glickman, Jonathan N; Gallini, Carey Ann; Michaud, Monia; Clancy, Thomas E; Chung, Daniel C; Lochhead, Paul; Hold, Georgina L; El-Omar, Emad M; Brenner, Dean; Fuchs, Charles S; Meyerson, Matthew; Garrett, Wendy S

    2013-08-14

    Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that symbiotic Fusobacterium spp. are associated with human colorectal carcinoma, but whether this is an indirect or causal link remains unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas relative to surrounding tissues and in stool samples from colorectal adenoma and carcinoma patients compared to healthy subjects. Additionally, in the Apc(Min/+) mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from Apc(Min/+) mice exposed to F. nucleatum exhibit a proinflammatory expression signature that is shared with human fusobacteria-positive colorectal carcinomas. However, unlike other bacteria linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor immune microenvironment

    Science.gov (United States)

    Kostic, Aleksandar D.; Chun, Eunyoung; Robertson, Lauren; Glickman, Jonathan N.; Gallini, Carey Ann; Michaud, Monia; Clancy, Thomas E.; Chung, Daniel C.; Lochhead, Paul; Hold, Georgina L.; El-Omar, Emad M.; Brenner, Dean; Fuchs, Charles S.; Meyerson, Matthew; Garrett, Wendy S.

    2013-01-01

    SUMMARY Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that commensal Fusobacterium spp. are associated with human colorectal carcinoma but whether this is an indirect or causal link remains unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas relative to surrounding tissues and in stool samples from colorectal adenoma and carcinoma patients compared to healthy subjects. Additionally, in the ApcMin/+ mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from ApcMin/+ mice exposed to F. nucleatum exhibit a pro-inflammatory expression signature that is shared with human fusobacteria-positive colorectal carcinomas. However, unlike other bacteria linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis, enteritis or inflammation-associated intestinal carcinogenesis. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria, generate a pro-inflammatory microenvironment that is conducive for colorectal neoplasia progression. PMID:23954159

  12. Profiling of metastatic small intestine neuroendocrine tumors reveals characteristic miRNAs detectable in plasma.

    Science.gov (United States)

    Bowden, Michaela; Zhou, Chensheng W; Zhang, Sui; Brais, Lauren; Rossi, Ashley; Naudin, Laurent; Thiagalingam, Arunthi; Sicinska, Ewa; Kulke, Matthew H

    2017-08-15

    Current diagnostic and prognostic blood-based biomarkers for neuroendocrine tumors are limited. MiRNAs have tumor-specific expression patterns, are relatively stable, and can be measured in patient blood specimens. We performed a multi-stage study to identify and validate characteristic circulating miRNAs in patients with metastatic small intestine neuroendocrine tumors, and to assess associations between miRNA levels and survival. Using a 742-miRNA panel, we identified candidate miRNAs similarly expressed in 19 small intestine neuroendocrine tumors and matched plasma samples. We refined our panel in an independent cohort of plasma samples from 40 patients with metastatic small intestine NET and 40 controls, and then validated this panel in a second, large cohort of 120 patients with metastatic small intestine NET and 120 independent controls. miRNA profiling of 19 matched small intestine neuroendocrine tumors and matched plasma samples revealed 31 candidate miRNAs similarly expressed in both tissue and plasma. We evaluated expression of these 31 candidate miRNAs in 40 independent cases and 40 normal controls, and identified 4 miRNAs (miR-21-5p, miR-22-3p, miR-29b-3p, and miR-150-5p) that were differently expressed in cases and controls (p<0.05). We validated these 4 miRNAs in a separate, larger panel of 120 cases and 120 controls. We confirmed that high circulating levels of miR-22-3p (p<0.0001), high levels of miR 21-5p, and low levels of miR-150-5p (p=0.027) were associated with the presence of metastatic small intestine NET. While levels of 29b-3p were lower in cases than in controls in both the initial cohort and the validation cohort, the difference in the validation cohort did not reach statistical significance. We further found that high levels of circulating miR-21-5p, high levels of circulating miR-22-3p and low levels of circulating miR-150-5p were each independently associated with shorter overall survival. A combined analysis using all three markers

  13. The Yin and Yang of Invariant Natural Killer T Cells in Tumor Immunity—Suppression of Tumor Immunity in the Intestine

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    Ying Wang

    2018-01-01

    Full Text Available CD1d-restricted invariant natural killer T (iNKT cells are known as early responding, potent regulatory cells of immune responses. Besides their established role in the regulation of inflammation and autoimmune disease, numerous studies have shown that iNKT cells have important functions in tumor immunosurveillance and control of tumor metastasis. Tumor-infiltrating T helper 1 (TH1/cytotoxic T lymphocytes have been associated with a positive prognosis. However, inflammation has a dual role in cancer and chronic inflammation is believed to be a driving force in many cancers as exemplified in patients with inflammatory bowel disease that have an increased risk of colorectal cancer. Indeed, NKT cells promote intestinal inflammation in human ulcerative colitis, and the associated animal model, indicating that NKT cells may favor tumor development in intestinal tissue. In contrast to other cancers, recent data from animal models suggest that iNKT cells promote tumor formation in the intestine by supporting an immunoregulatory tumor microenvironment and suppressing TH1 antitumor immunity. Here, we review the role of iNKT cells in suppression of tumor immunity in light of iNKT-cell regulation of intestinal inflammation. We also discuss suppression of immunity in other situations as well as factors that may influence whether iNKT cells have a protective or an immunosuppressive and tumor-promoting role in tumor immunity.

  14. Obstrucción intestinal por tumor neuroendocrino. Reporte de un caso

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    Shirley Andrea Ramírez Merlano

    2013-02-01

    Full Text Available Los tumores neuroendocrinos bien diferenciados (NET anteriormente denominado "tumores carcinoides" son tumores relativamente raros procedentes del sistema difuso neuroendocrino, se encuentran con mayor frecuencia en los sistemas bronquial y gastrointestinal y su presencia puede ser imperceptible por años, sin signos obvios o síntomas. Se presenta el caso de un paciente de 61 años sin comorbilidades, quien consulta en varias ocasiones a una IPS (Institución Prestadora de Salud de la ciudad de Bucaramanga por sintomatología compatible con obstrucción intestinal a quien se le da manejo con medicamentos, teniendo poca mejoría. El paciente llega a nuestra IPS por cuadro de dolor abdominal tipo cólico, náuseas, distensión abdominal y sin deposiciones de dos días de evolución. Al examen físico se encuentra rubicundez en la cara. La laparotomía exploratoria muestra obstrucción intestinal y la investigación histopatológica de las biopsias revela un tumor carcinoide mixto. En el postoperatorio el estado de salud empeora. La obstrucción intestinal por este tipo de tumor, es de difícil diagnóstico y manejo, por lo cual se requiere de personal muy bien entrenado, así como de alta sospecha clínica para hacer un diagnóstico oportuno. [Ramírez S, Prada M. MedUNAB 2013; 15:175-179].

  15. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice Roston de; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

  16. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    Directory of Open Access Journals (Sweden)

    de Mello Maria

    2002-04-01

    Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

  17. Aspects of surgical treatment for gastro-intestinal stromal tumors; Chirurgische Therapieaspekte gastrointestinaler Stromatumoren

    Energy Technology Data Exchange (ETDEWEB)

    Hohenberger, P. [Medizinische Fakultaet Mannheim, Universitaet Heidelberg, Sektion Chirurgische Onkologie und Thoraxchirurgie, Chirurgische Universitaetsklinik, Mannheim (Germany)

    2009-12-15

    Gastro-intestinal stromal tumors (GIST) form the commonest subgroup of soft tissue sarcomas. They arise in the muscular layer of the esophagus, stomach, small intestines and rectum. Characteristic and important for the assessment of the extent of tumors is the peripheral rim vascularization of primary tumors and metastases. Indications for resection are given for tumors larger than 2 cm in size. Locally advanced GISTs can be advantageously treated with imatinib/sunitinib as neoadjuvant and it is often possible to select a low level of resection for this size of tumor and when the rim area is not hypervascularized. Even in the metastizing stage surgical treatment can be used for elimination of resistant metastases or for removal of residual tumor tissue in an attempt to counteract secondary tumor progression. The effect of this treatment is currently being tested in a randomized phase III study. (orig.) [German] Gastrointestinale Stromatumoren (GIST) stellen die haeufigste Subgruppe von Weichgewebesarkomen dar. Sie entstehen in der Muskularisschicht von Oesophagus, Magen, Duenndarm und Rektum. Charakteristisch und wichtig fuer die Einschaetzung des Tumorausmasses ist die Randvaskularisation von Primaertumoren und Metastasen. Die Indikation zur Resektion gilt fuer Tumoren ab 2 cm Groesse. Lokal fortgeschrittene GIST koennen sehr vorteilhaft mit Imatinib/Sunitinib neoadjuvant vorbehandelt werden, und es ist oft moeglich, bei der Tumorgroesse und wenn keine hypervaskularisierten Randbereiche vorliegen, ein geringeres Resektionsausmass zu waehlen. Auch im metastasierten Stadium hat die chirurgische Therapie einen Platz zur Eliminierung resistenter Metastasen bzw. zur Entfernung von Residualtumorgewebe als Versuch, einer sekundaeren Tumorprogression zu begegnen. Dieser Behandlungseffekt wird derzeit in einer randomisierten Phase-III-Studie ueberprueft. (orig.)

  18. Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility

    DEFF Research Database (Denmark)

    Fahmideh, Maral Adel; Lavebratt, Catharina; Schüz, Joachim

    2016-01-01

    Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. The study...... cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways....... to PBTs, whereas ERCC1rs3212986 may increase risk of these tumors. Moreover, stratified analyses indicated CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma subtype associated with EGFRrs9642393...

  19. Innovative Disease Model: Zebrafish as an In Vivo Platform for Intestinal Disorder and Tumors

    Directory of Open Access Journals (Sweden)

    Jeng-Wei Lu

    2017-09-01

    Full Text Available Colorectal cancer (CRC is one of the world’s most common cancers and is the second leading cause of cancer deaths, causing more than 50,000 estimated deaths each year. Several risk factors are highly associated with CRC, including being overweight, eating a diet high in red meat and over-processed meat, having a history of inflammatory bowel disease, and smoking. Previous zebrafish studies have demonstrated that multiple oncogenes and tumor suppressor genes can be regulated through genetic or epigenetic alterations. Zebrafish research has also revealed that the activation of carcinogenesis-associated signal pathways plays an important role in CRC. The biology of cancer, intestinal disorders caused by carcinogens, and the morphological patterns of tumors have been found to be highly similar between zebrafish and humans. Therefore, the zebrafish has become an important animal model for translational medical research. Several zebrafish models have been developed to elucidate the characteristics of gastrointestinal diseases. This review article focuses on zebrafish models that have been used to study human intestinal disorders and tumors, including models involving mutant and transgenic fish. We also report on xenograft models and chemically-induced enterocolitis. This review demonstrates that excellent zebrafish models can provide novel insights into the pathogenesis of gastrointestinal diseases and help facilitate the evaluation of novel anti-tumor drugs.

  20. Brush border Myosin Ia has tumor suppressor activity in the intestine

    Science.gov (United States)

    Mazzolini, Rocco; Dopeso, Higinio; Mateo-Lozano, Silvia; Chang, Wakam; Rodrigues, Paulo; Bazzocco, Sarah; Alazzouzi, Hafid; Landolfi, Stefania; Hernández-Losa, Javier; Andretta, Elena; Alhopuro, Pia; Espín, Eloy; Armengol, Manel; Tabernero, Josep; Ramón y Cajal, Santiago; Kloor, Matthias; Gebert, Johannes; Mariadason, John M.; Schwartz, Simo; Aaltonen, Lauri A.; Mooseker, Mark S.; Arango, Diego

    2012-01-01

    The loss of the epithelial architecture and cell polarity/differentiation is known to be important during the tumorigenic process. Here we demonstrate that the brush border protein Myosin Ia (MYO1A) is important for polarization and differentiation of colon cancer cells and is frequently inactivated in colorectal tumors by genetic and epigenetic mechanisms. MYO1A frame-shift mutations were observed in 32% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of promoter methylation was observed in a significant proportion of colon cancer cell lines and primary colorectal tumors. The loss of polarization/differentiation resulting from MYO1A inactivation is associated with higher tumor growth in soft agar and in a xenograft model. In addition, the progression of genetically and carcinogen-initiated intestinal tumors was significantly accelerated in Myo1a knockout mice compared with Myo1a wild-type animals. Moreover, MYO1A tumor expression was found to be an independent prognostic factor for colorectal cancer patients. Patients with low MYO1A tumor protein levels had significantly shorter disease-free and overall survival compared with patients with high tumoral MYO1A (logrank test P = 0.004 and P = 0.009, respectively). The median time-to-disease recurrence in patients with low MYO1A was 1 y, compared with >9 y in the group of patients with high MYO1A. These results identify MYO1A as a unique tumor-suppressor gene in colorectal cancer and demonstrate that the loss of structural brush border proteins involved in cell polarity are important for tumor development. PMID:22307608

  1. Comparison of adhesin genes and antimicrobial susceptibilities between uropathogenic and intestinal commensal Escherichia coli strains.

    Science.gov (United States)

    Qin, Xiaohua; Hu, Fupin; Wu, Shi; Ye, Xinyu; Zhu, Demei; Zhang, Ying; Wang, Minggui

    2013-01-01

    The presence of adhesins is arguably an important determinant of pathogenicity for Uropathogenic Escherichia coli (UPEC). Antimicrobial susceptibilities were tested by agar dilution method, fifteen adhesin genes were detected by polymerase chain reaction, and multilocus sequence typing (MLST) was analyzed in 70 UPEC isolates and 41 commensal E. coli strains. Extended-spectrum β-lactamase (ESBL) was determined with confirmatory test. The prevalence of ESBL-producers in UPEC (53%, 37/70) was higher than the commensal intestinal isolates (7%, 3/41), and 97% (36/37) of the ESBL-producing UPEC harbored bla CTX-M genes. afa was present in 36% (10/28) UPEC isolates from recurrent lower urinary tract infection (UTI), and none in the acute pyelonephritis, acute uncomplicated cystitis or commensal strains (PUPEC isolates, while 5% (2/41) of the commensal strains were papG positive (P = 0.0025), and the prevalence of papG was significantly higher in acute pyelonephritis group (71%) than the other two UTI groups (PUPEC isolates than in the commensal strains. ESBL-producing UPEC showed a lower prevalence of adhesin genes compared with non-ESBL-producing strains. The MLST profiles were different between UPEC and commensal strains, with ST131 (19%, 13/70) and ST10 (20%, 8/41) being the most common MLSTs, respectively. This study demonstrated that several adhesin genes were more prevalent in UPEC isolates than in commensal E. coli, and afa may be associated with recurrent lower UTI whereas papG is more frequently associated with acute pyelonephritis.

  2. [A modified guaiac test for the early detection of tumors of the intestinal tract (author's transl)].

    Science.gov (United States)

    Warm, K; Blazek, Z; Weithofer, G; Bloch, R

    1977-03-04

    Of 1400 patients who were submitted to the Haemoccult test, 46 showed a postive result. Among other things there were 29 polyps, of which 3 already showed a focal carcinoma, and 5 carcinomata of the large intestine and 3 gastric carcinomata were also diagnosed. Over 70% of the tumor hosts had observed bleeding per anum at some time. In order to detect the number of false nagative results, patients were investigated in the same way even when the Haemoccult test had been negative three times. In this way 55 polyps were found as well as 7 partly advanced carcinomata of the large intestine. 35% of the Haemoccult-negative patients stated bleeding per anum in their history. The number of false negative findings must be considerably higher than previously estimated.

  3. Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice

    Directory of Open Access Journals (Sweden)

    Allison R. Rogala

    2018-02-01

    Full Text Available Crohn's disease (CD represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM is an established risk allele in CD. We have shown previously that conventionally raised (CV mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1−/− mice were rederived into specific pathogen-free (SPF and germ-free (GF conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1−/− mice. Remarkably, in contrast to CV mice, SPF Irgm1−/− mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1−/− mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1−/− mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1−/− mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1−/− mice as a model to elucidate host

  4. Diarrhea-like condition and intestinal muscosal responses in susceptible homozygous and heterozygous F4R+ pigs challenged with enterotoxigenic Escherichia coli

    DEFF Research Database (Denmark)

    Sugiharto, Sugiharto; Hedemann, Mette Skou; Jensen, Bent Borg

    2012-01-01

    Enterotoxigenic Escherichia coli (ETEC) F4 is a major cause of diarrhea in both neonatal and young pigs. Indeed, only pigs having F4 receptors are susceptible. Among the susceptible pigs, it is yet unknown if spontaneous E. coli postweaning diarrhea (PWD) occurrence and intestinal mucosal responses...... to ETEC differ between genotypes. This study investigated a diarrhea-like condition and intestinal mucosal responses in F4 homo- and heterozygous susceptible weaner pigs. Sixteen weaned pigs (28 d of age) were used in a 2 × 2 factorial study with genotype (homo- or heterozygous F4R+) and inoculation...

  5. Small intestinal gastrointestinal stromal tumor in a young adult woman: a case report and review of the literature.

    Science.gov (United States)

    Manxhuka-Kerliu, Suzana; Sahatciu-Meka, Vjollca; Kerliu, Irma; Juniku-Shkololli, Argjira; Kerliu, Lloreta; Kastrati, Mevlyde; Kotorri, Vesa

    2014-09-28

    Gastrointestinal stromal tumor is the most common sarcoma of the gastrointestinal tract. We report a case of gastrointestinal stromal tumor in a small intestine, initially suspected for leiomyosarcoma given that gastrointestinal stromal tumors in young adult patients are limited due to their rarity. A 30-year-old Caucasian ethnic Albanian woman from Kosovo presented with abdominal pain, nausea and vomiting. Subsequently, the tumor was detected in her small intestine, as an infiltrating mass approximately 10 cm in diameter. The tumor was resected en bloc and duodenojejunal terminal-terminal anastomosis was performed. The tumor was a large, bulky, intramural mass, with fish-flesh to tan-brown appearance, as well as with foci of hemorrhage and necrosis. On histological examination the tumor showed transmural growth, deep infiltrative pattern and malignant feature, with mitotic count >5 per 50 high-power field, dense cellularity with plump spindle cells, and with eosinophilic cytoplasm within variably hyalinized and edematous stroma, skeinoid fibers (extracellular collagen globules) and foci of hemorrhage. In addition, the tumor was composed of areas with epithelioid morphology. The immunohistochemistry results showed high expression of proto-oncogene c-kit, CD117, CD34 and vimentin, whereas α-smooth muscle actin was focally positive. Desmin and S-100 protein were negative. Gastrointestinal stromal tumor should be included in the differential diagnoses of intestinal mesenchymal tumors presenting as a single mass in young female adults. Given that gastrointestinal stromal tumors in young adults represent a more heterogeneous group than gastrointestinal stromal tumor in pediatric cases, more effort should be made to investigate its pathogenesis and potentially more specific treatment.

  6. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation.

    Science.gov (United States)

    Agus, Allison; Denizot, Jérémy; Thévenot, Jonathan; Martinez-Medina, Margarita; Massier, Sébastien; Sauvanet, Pierre; Bernalier-Donadille, Annick; Denis, Sylvain; Hofman, Paul; Bonnet, Richard; Billard, Elisabeth; Barnich, Nicolas

    2016-01-08

    Recent advances have shown that the abnormal inflammatory response observed in CD involves an interplay among intestinal microbiota, host genetics and environmental factors. The escalating consumption of fat and sugar in Western countries parallels an increased incidence of CD during the latter 20(th) century. The impact of a HF/HS diet in mice was evaluated for the gut micro-inflammation, intestinal microbiota composition, function and selection of an E. coli population. The HF/HS diet created a specific inflammatory environment in the gut, correlated with intestinal mucosa dysbiosis characterized by an overgrowth of pro-inflammatory Proteobacteria such as E. coli, a decrease in protective bacteria, and a significantly decreased of SCFA concentrations. The expression of GPR43, a SCFA receptor was reduced in mice treated with a HF/HS diet and reduced in CD patients compared with controls. Interestingly, mice treated with an agonist of GPR43 were protected against DSS-induced colitis. Finally, the transplantation of feces from HF/HS treated mice to GF mice increased susceptibility to AIEC infection. Together, our results demonstrate that a Western diet could aggravate the inflammatory process and that the activation of the GPR43 receptor pathway could be used as a new strategy to treat CD patients.

  7. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Junqiang; Doi, Hiroshi [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Saar, Matthias; Santos, Jennifer [Department of Urology, School of Medicine, Stanford University, Stanford, California (United States); Li, Xuejun; Peehl, Donna M. [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Knox, Susan J., E-mail: sknox@stanford.edu [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States)

    2013-12-01

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.

  8. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    International Nuclear Information System (INIS)

    Tian, Junqiang; Doi, Hiroshi; Saar, Matthias; Santos, Jennifer; Li, Xuejun; Peehl, Donna M.; Knox, Susan J.

    2013-01-01

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy

  9. [Studies on the biotransformation of escin Ia by human intestinal bacteria and the anti-tumor activities of desacylescin I].

    Science.gov (United States)

    Yang, Xiu-Wei; Zhao, Jing; Cui, Jing-Rong; Guo, Wei

    2004-02-01

    To study Biotransformation of escin Ia by the crude enzymes of human intestinal bacteria and Lactobacillus brevis, determine the structures of biotransformation products and assay the inhibitory effect of desacylescin I on the tumor cell growth. The escin Ia was incubated with crude enzymes of human intestinal bacteria and Lactobacillus brevis in vitro, respectively. The biotransformation products were isolated and purified by the chromatographic methods and the structures were determined by the spectroscopic techniques. Escin Ia was converted into isoescin Ia, desacylescin I, 21beta-O-tigloylprotoaescigenin and protoaescigenin by crude enzymes of human intestinal bacteria and Lactobacillus brevis. Desacylescin I showed potentially inhibitory effects on tumor cell growth of mouse sarcoma-180, hepatic carcinoma H(22) and lung carcinoma in vivo. The results suggest that Escin Ia was a prodrug and its structure can be converted by human intestinal bacteria and Lactobacillus brevis. Desacylescin I as a biotransformation product showed potentially inhibitory effects on mouse tumor, and a potential candidate for anti tumor agents.

  10. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis

    OpenAIRE

    Scher, Jose U; Sczesnak, Andrew; Longman, Randy S; Segata, Nicola; Ubeda, Carles; Bielski, Craig; Rostron, Tim; Cerundolo, Vincenzo; Pamer, Eric G; Abramson, Steven B; Huttenhower, Curtis; Littman, Dan R

    2013-01-01

    eLife digest We share our bodies with a diverse set of microorganisms, known collectively as the human microbiome. Indeed, estimates suggest that our bodies contain 10 times as many microbial cells as human cells. Our stomach and intestines alone are home to many hundreds and possibly thousands of microbial species that break down indigestible compounds and help to prevent the growth of harmful bacteria. The immune system must therefore learn to tolerate these microorganisms, while retaining ...

  11. A probiotic strain of L. acidophilus reduces DMH-induced large intestinal tumors in male Sprague-Dawley rats.

    Science.gov (United States)

    McIntosh, G H; Royle, P J; Playne, M J

    1999-01-01

    Probiotic bacteria strains were examined for their influence on 1,2-dimethylhydrazine (DMH)-induced intestinal tumors in 100 male Sprague-Dawley rats. Lactobacillus acidophilus (Delvo Pro LA-1), Lactobacillus rhamnosus (GG), Bifidobacterium animalis (CSCC1941), and Streptococcus thermophilus (DD145) strains were examined for their influence when added as freeze-dried bacteria to an experimental diet based on a high-fat semipurified (AIN-93) rodent diet. Four bacterial treatments were compared: L. acidophilus, L. acidophilus + B. animalis, L. rhamnosus, and S. thermophilus, the bacteria being added daily at 1% freeze-dried weight (10(10) colony-forming units/g) to the diet. Trends were observed in the incidence of rats with large intestinal tumors for three treatments: 25% lower than control for L. acidophilus, 20% lower for L. acidophilus + B. animalis and L. rhamnosus treatments, and 10% lower for S. thermophilus. Large intestinal tumor burden was significantly lower for treated rats with L. acidophilus than for the control group (10 and 3 tumors/treatment group, respectively, p = 0.05). Large intestinal tumor mass index was also lower for the L. acidophilus treatment than for control (1.70 and 0.10, respectively, p L. acidophilus, no adenocarcinomas were present in the colons. Pulsed-field gel electrophoresis of bacterial chromosomal DNA fragments was used to differentiate introduced (exogenous) bacterial strains from indigenous bacteria of the same genera present in the feces. Survival during gut passage and displacement of indigenous lactobacilli occurred with introduced L. acidophilus and L. rhamnosus GG during the probiotic treatment period. However, introduced strains of B. animalis and S. thermophilus were not able to be isolated from feces. It is concluded that this strain of L. acidophilus supplied as freeze-dried bacteria in the diet was protective, as seen by a small but significant inhibition of tumors within the rat colon.

  12. Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs of the small intestine: before the era of imatinib mesylate

    Directory of Open Access Journals (Sweden)

    Jan Yi-Yin

    2006-10-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GISTs, the most common type of mesenchymal tumors of the gastrointestinal (GI tract, demonstrate positive kit staining. We report our surgical experience with 100 small intestine GIST patients and identify predictors for long-term disease-free survival (DFS and overall survival (OS to clarify the difference between high- and low-risk patients. Methods The clinicopathologic and follow-up records of 100 small intestine GIST patients who were treated at Chung Gung Memorial Hospital between 1983 and 2002 were retrospectively reviewed. Clinical and pathological factors were assessed for long-term DFS and OS by using a univariate log-rank test and a multivariate Cox proportional hazard model. Results The patients included 52 men and 48 women. Their ages ranged from 27 to 82 years. Among the 85 patients who underwent curative resection, 44 (51.8% developed disease recurrence (liver metastasis was the most common form of recurrence. The follow-up period ranged from 5 to 202 months (median: 33.2 months. The 1-, 3-, and 5-year DFS and OS rates were 85.2%, 53.8%, and 43.7%, and 91.5%, 66.6%, and 50.5%, respectively. Using multivariate analysis, it was found that high tumor cellularity, mitotic count >5/50 high-power field, and a Ki-67 index ≧10% were three independent factors that were inversely associated with DFS. However, absence of tumor perforation, mitotic count Conclusion Tumors with low cellularity, low mitotic count, and low Ki-67 index, which indicate low risk, predict a more favorable DFS for small intestine GIST patients undergoing curative resection. Absence of tumor perforation with low mitotic count and low cellularity, which indicates low risk, can predict long-term OS for small intestine GIST patients who have undergone curative resection.

  13. Porcine small intestine submucosal grafts for post-tumor resection orbital reconstruction.

    Science.gov (United States)

    Phillips, James; Riley, Kristen O; Woodworth, Bradford A

    2014-06-01

    Removal of the medial orbital wall for sinonasal tumor involvement is required to obtain complete oncologic resection. However, orbital fat herniation can produce significant morbidity, including enophthalmos and diplopia. The purpose of the current study was to evaluate outcomes following use of porcine small intestine submucosa (SIS) grafts for orbital reconstruction following extirpation of sinonasal malignancies. Case series in a tertiary hospital setting. Review of prospectively collected data regarding orbital reconstruction using SIS was performed. Demographics, tumor histology, size of orbital defect, adjuvant treatment, clinical status, and complications were recorded. Seventeen patients (average age, 58 years; range, 27-82 years) had SIS grafting of the medial orbital wall over a 5-year period at our tertiary academic institution. The average orbital wall defect size was 4.6 cm(2) (range, 1 cm(2)-24 cm(2)). Tumor histopathology included esthesioneuroblastoma (n = 5), squamous cell carcinoma (n = 4), adenocarcinoma (n = 2), sinonasal undifferentiated carcinoma (n = 2), melanoma (n = 3), and neuroendocrine carcinoma (n = 1). Surgical goals were curative intent in all patients. Ten patients had postoperative radiation therapy, whereas five individuals had surgical extirpation following neoadjuvant chemotherapy and radiation. All patients had complete locoregional control at last clinical follow-up (average, 16 months; range, 2-54 months), although three patients developed distant metastases. The only orbital complications noted were enophthalmos (n = 1), periorbital cellulitis (n = 1), and orbital wall crusting (n = 1). SIS reconstruction of orbital wall defects was effective in the current series of patients, with only one patient developing noticeable enophthalmos and a low incidence of surgical complications. 4. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  14. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu Wei

    2011-05-01

    Full Text Available Abstract Background The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. Methods To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. Results The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR = 1.25, 95% confidence interval (CI = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17. We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively. In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively. However, no association was seen between MDM2 SNP309 and tumor susceptibility

  15. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

    International Nuclear Information System (INIS)

    Wan, Yan; Wu, Wei; Yin, Zhihua; Guan, Peng; Zhou, Baosen

    2011-01-01

    The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP) at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro) and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17). We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively). In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively). However, no association was seen between MDM2 SNP309 and tumor susceptibility in the stratified analysis by p53 mutation status

  16. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis.

    Science.gov (United States)

    Scher, Jose U; Sczesnak, Andrew; Longman, Randy S; Segata, Nicola; Ubeda, Carles; Bielski, Craig; Rostron, Tim; Cerundolo, Vincenzo; Pamer, Eric G; Abramson, Steven B; Huttenhower, Curtis; Littman, Dan R

    2013-11-05

    Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA. DOI: http://dx.doi.org/10.7554/eLife.01202.001.

  17. Loci controlling lymphocyte production of interferon gamma after alloantigen stimulation in vitro and their co-localization with genes controlling lymphocyte infiltration of tumors and tumor susceptibility

    Czech Academy of Sciences Publication Activity Database

    Lipoldová, Marie; Havelková, Helena; Badalová, Jana; Vojtíšková, Jarmila; Quan, L.; Krulová, Magdalena; Sohrabi, Yahya; Stassen, A. P. M.; Demant, P.

    2010-01-01

    Roč. 59, č. 2 (2010), s. 203-213 ISSN 0340-7004 R&D Projects: GA MŠk(CZ) LC06009; GA AV ČR IAA500520606; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50520514 Keywords : Tumor susceptibility * Genetic control of interferon gamma production * Lymphocyte infiltration of tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.293, year: 2010

  18. Fanconi anemia patients are more susceptible to infection with tumor virus SV40.

    Directory of Open Access Journals (Sweden)

    Manola Comar

    Full Text Available Fanconi anemia (FA is a recessive DNA repair disease characterized by a high predisposition to developing neoplasms. DNA tumor polyomavirus simian virus 40 (SV40 transforms FA fibroblasts at high efficiency suggesting that FA patients could be highly susceptible to SV40 infection. To test this hypothesis, the large tumor (LT antigen of SV40, BKV, JCV and Merkel Cell (MC polyomaviruses were tested in blood samples from 89 FA patients and from 82 of their parents. Two control groups consisting of 47 no-FA patients affected by other genetic bone marrow failure diseases and 91 healthy subjects were also evaluated. Although JCV, BKV and MC were not found in any of the FA samples, the prevalence and viral load of SV40 were higher in FA patients (25%; mean viral load: 1.1×10(2 copies/10(5cells as compared with healthy individuals (4.3%; mean viral load: 0.8×10(1 copies/10(5cells and genetic controls (0% (p<0.005. A marked age-dependent frequency of SV40 was found in FA with respect to healthy subjects suggesting that, although acquired early in life, the virus can widespread more easily in specific groups of population. From the analysis of family pedigrees, 60% of the parents of SV40-positive probands were positive for the virus compared to 2% of the parents of the SV40-negative probands (p<0.005. It is worthy of note that the relative frequency of SV40-positive relatives detected in this study was the highest ever reported, showing that asymptomatic FA carriers are also more susceptible to SV40. In conclusion, we favor the hypothesis that SV40 spread could be facilitated by individuals who are genetically more susceptible to infection, such as FA patients. The increased susceptibility to SV40 infection seems to be associated with a specific defect of the immune system which supports a potential interplay of SV40 with an underlying genetic alteration that increases the risk of malignancies.

  19. Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans

    Science.gov (United States)

    Proctor, Deborah M.; Suh, Mina; Haws, Laurie C.; Kirman, Christopher R.; Harris, Mark A.

    2013-01-01

    Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors. PMID:23445218

  20. Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells

    DEFF Research Database (Denmark)

    Olsen, Anders Krüger; Coskun, Mehmet; Bzorek, Michael

    2013-01-01

    Wnt signaling is often constitutively active in colorectal cancer cells. The expression of the intestinal specific transcription factor CDX2 is found to be transiently decreased in invasive cells at the tumor/stroma interface. A recent ChIP-Seq study has indicated that several Wnt signaling...... suggest that a low CDX2 level has influence on the Wnt signaling in invasive colon cancer cells possibly promoting cellular migration....

  1. Diagnosis and treatment of small intestinal stromal tumor: an analysis of 45 cases

    Directory of Open Access Journals (Sweden)

    Yan ZENG

    2014-08-01

    Full Text Available Objective To study the clinical features, diagnosis and treatment of small intestinal stromal tumor (SIST. Methods Clinical data of 45 SIST patients admitted to our hospital from July 2007 to December 2013 were analyzed retrospectively. The diagnosis was confirmed pathologically in all the patients. Results The clinical manifestations of SIST were non-specific, and the most common manifestations were as follows: gastrointestinal bleeding in 29 patients (64.4 %, abdominal pain in 15 (33.3% and abdominal mass in 4 (8.9%. The most common predilection sites of SIST were jejunum (n=21, 46.7%, duodenum (n=13, 28.9% and ileum (n=9, 20.0%. The tumor was located at the jejunoileal junction in 2 patients (4.4%. The diagnostic rate of SIST by spiral CT was 73.7% (28/38, and it was the most accurate among all the examinations. Surgical operation was the most effective therapeutic method for SIST. All the 45 patients received surgical treatment, and according to Fletcher's criteria, there were 6 patients (13.3% at very low-risk, 16 (35.6% at low-risk, 8 (17.8% at moderate-risk and 15 (33.3% at highrisk of SIST. The postoperative immunohistochemistry showed that the positive rate of CD117 was 100%, while the positive rate of CD34 was 67.0% (30/45. Imatinib mesylate was helpful for patients who had palliative operation and for preventing postoperative recurrence. Reoperation could prolong the survival of patients who had a local recurrence or distant metastasis. Conclusions  Clinical manifestations of SIST are non-specific, and its early diagnosis is difficult. However, spiral CT has a high diagnostic value for SIST. The surgical operation is the main method for treatment of SIST, and long-time oral imatinib mesylate medication after surgery can attain a better result for a long duration. DOI: 10.11855/j.issn.0577-7402.2014.07.11

  2. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device

    International Nuclear Information System (INIS)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri

    2016-01-01

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. - Highlights: • Microfluidic system switches rapidly between normoxia and hypoxia (5 min). • Observation of rapid adaptation of PC3 cells to hypoxia and normoxia (30 min). • Drug susceptibility in tumor cells restored after chip switched to normoxia for 30 min.

  3. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device

    Energy Technology Data Exchange (ETDEWEB)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri, E-mail: d.pappas@ttu.edu

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. - Highlights: • Microfluidic system switches rapidly between normoxia and hypoxia (5 min). • Observation of rapid adaptation of PC3 cells to hypoxia and normoxia (30 min). • Drug susceptibility in tumor cells restored after chip switched to normoxia for 30 min.

  4. Effects of selected non-digestible dietary carbohydrates on the composition of the large intestinal microbiota and susceptibility to salmonella infections

    DEFF Research Database (Denmark)

    Petersen, Anne

    carbohydrates, known as prebiotics, are food components aimed at selectively stimulating such beneficial bacteria already colonizing the intestinal tract. In this regard, prebiotics and other ND dietary carbohydrates may improve host resistance to intestinal infections by selectively modulating the composition...... shown conflicting results. Therefore the aim of the present thesis was to investigate the effect of selected ND dietary carbohydrates on the large intestinal microbiota and susceptibility to Salmonella enterica serovar Typhimurium SL1344 infection in mice. The thesis contains an introduction...... studies performed. Results presented in Manuscript I demonstrated no in vivo protective effect of the investigated carbohydrates against the Salmonella infection. In contrast, two of the investigated substrates (fructo-oligosaccharides and xylo-oligosaccharides) demonstrated an adverse rather than...

  5. Failure to induce tumors in the large intestine of Capuchin mokeys (Cebus apella) by using 1,2-dimethylhydrazine.

    Science.gov (United States)

    Sánchez Negrette, M; Borda, J T; Montenegro, M A; Lertora, W J; Gimeno, E J

    2000-10-01

    The purpose of this study was to produce tumors in the large intestine of Capuchin Monkeys (Cebus apella) by the administration of the colonotropic carcinogen 1,2-dimethylhydrazine (DMH). The subjects were 12 monkeys, all males, age 30 months, with a mean weight of 2.858 kg. The DMH was administered subcutaneously to six of the monkeys at a dosage of 25 mg/kg of body weight once a week for 16 weeks; control monkeys received an equivalent volume of the stock solution without DMH. Twenty months after administration of the first dose, the animals were sacrificed. None of the monkeys showed intestinal tumors. Samples of the gastrointestinal tract were removed, fixed, and stained according to standard histological techniques. Histological changes were seen in all of the DMH-treated animals; these consisted of glandular hyperplasia and hyperplasia of the epithelium overlying the lymphoid nodules. In addition, foci of dysplasia were found in three of the animals. Our results suggest that the DMH induced pre-neoplastic changes, characterized by hyperplasia and dysplasia, in the mucosa of the large intestine.

  6. Structural Stability of the Coiled-Coil Domain of Tumor Susceptibility Gene (TSG)-101.

    Science.gov (United States)

    White, Jordan T; Toptygin, Dmitri; Cohen, Randy; Murphy, Natalie; Hilser, Vincent J

    2017-09-05

    The tumor susceptibility gene-101 coiled coil domain (TSG101cc) is an integral component of the endosomal maturation machinery and cytokinesis, and also interacts with several transcription factors. The TSG101cc has been crystallized as a homotetramer but is known to interact with two of its binding partners as a heterotrimer. To investigate this apparent discrepancy, we examined the solution thermodynamics of the TSG101cc. Here, we use circular dichroism, differential scanning calorimetry, analytical ultracentrifugation, fluorescence, and structural thermodynamic analysis to investigate the structural stability and the unfolding of the TSG101cc. We demonstrate that TSG101cc exists in solution primarily as a tetramer, which unfolds in a two-state manner. Surprisingly, no homodimeric or homotrimeric species were detected. Structural thermodynamic analysis of the homotetrameric structure and comparison with known oligomeric coiled-coils suggests that the TSG101cc homotetramer is comparatively unstable on a per residue basis. Furthermore, the homotrimeric coiled-coil is predicted to be much less stable than the functional heterotrimeric coiled-coil in the endosomal sorting complex required for transport 1 (ESCRT1). These results support a model whereby the tetramer-monomer equilibrium of TSG101 serves as the cellular reservoir of TSG101, which is effectively outcompeted when its binding partners are present and the heteroternary complex can form.

  7. Genetic Susceptibility to Refractive Error: Association of Vasoactive Intestinal Peptide Receptor 2 (VIPR2) with High Myopia in Chinese

    Science.gov (United States)

    Yiu, Wai Chi; Yap, Maurice K. H.; Fung, Wai Yan; Ng, Po Wah; Yip, Shea Ping

    2013-01-01

    Myopia is the most common ocular disease worldwide. We investigated the association of high myopia with the common single nucleotide polymorphisms (SNPs) of five candidate genes – early growth response 1 (EGR1), v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS), jun oncogene (JUN), vasoactive intestinal peptide (VIP), and vasoactive intestinal peptide receptor 2 (VIPR2). We recruited 1200 unrelated Chinese subjects with 600 cases (spherical equivalent ≤−8.00 diopters) and 600 controls (spherical equivalent within ±1.00 diopter). A discovery sample set was formed from 300 cases and 300 controls, and a replication sample set from the remaining samples. Tag SNPs were genotyped for the discovery sample set, and the most significant haplotypes and their constituent SNPs were followed up with the replication sample set. The allele and haplotype frequencies in cases and controls were compared by logistic regression adjusted for sex and age to give Pa values, and multiple comparisons were corrected by permutation test to give Paemp values. Odd ratios (OR) were calculated accordingly. In the discovery phase, EGR1, JUN and VIP did not show any significant association while FOS and VIPR2 demonstrated significant haplotype association with high myopia. In the replication phase, the haplotype association for VIPR2 was successfully replicated, but not FOS. In analysis combining both sample sets, the most significant association signals of VIPR2 were the single marker rs2071625 (Pa = 0.0008, Paemp = 0.0046 and OR = 0.75) and the 4-SNP haplotype window rs2071623-rs2071625-rs2730220-rs885863 (omnibus test, Pa = 9.10e-10 and Paemp = 0.0001) with one protective haplotype (GGGG: Paemp = 0.0002 and OR = 0.52) and one high-risk haplotype (GAGA: Paemp = 0.0027 and OR = 4.68). This 4-SNP haplotype window was the most significant in all sample sets examined. This is the first study to suggest a role of VIPR2 in the genetic susceptibility

  8. The tumor necrosis factor family member TNFSF14 (LIGHT) is required for resolution of intestinal inflammation in mice.

    Science.gov (United States)

    Krause, Petra; Zahner, Sonja P; Kim, Gisen; Shaikh, Raziyah B; Steinberg, Marcos W; Kronenberg, Mitchell

    2014-06-01

    The pathogenesis of inflammatory bowel disease (IBD) is associated with a dysregulated mucosal immune response. Expression of the tumor necrosis factor (TNF) superfamily member 14 (TNFSF14, also known as LIGHT [homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes]) on T cells is involved in their activation; transgenic expression of LIGHT on T cells in mice promotes inflammation in multiple organs, including intestine. We investigated the roles for LIGHT in recovery from intestinal inflammation in mice. We studied the role of LIGHT in intestinal inflammation using Tnfsf14(-/-) and wild-type mice. Colitis was induced by transfer of CD4(+)CD45RB(high) T cells into Rag1(-/-) or Tnfsf14(-/-)Rag1(-/-) mice, or by administration of dextran sulfate sodium to Tnfsf14(-/-) or wild-type C57BL/6J mice. Mice were weighed, colon tissues were collected and measured, and histology analyses were performed. We measured infiltrating cell populations and expression of cytokines, chemokines, and LIGHT. After administration of dextran sulfate sodium, Tnfsf14(-/-) mice developed more severe colitis than controls, based on their reduced survival, accelerated loss of body weight, and histologic scores. LIGHT protected mice from colitis via the lymphotoxin β receptor and was expressed mainly by myeloid cells in the colon. Colons of Tnfsf14(-/-) mice also had increased accumulation of innate immune cells and higher levels of cytokines than colons from control mice. LIGHT, therefore, appears to regulate inflammation in the colon. Tnfsf14(-/-) mice develop more severe colitis than control mice. LIGHT signals through the lymphotoxin β receptor in the colon to regulate the innate immune response and mediate recovery from intestinal inflammation. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

    Energy Technology Data Exchange (ETDEWEB)

    Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Hop Paul Brousse, INSERM, Hepatobiliary Ctr, U785, F-94800 Villejuif (France); Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Univ Paris Sud, Fac Med, F-94800 Villejuif (France); Boisgard, R.; Tavitian, B. [INSERM, U803, F-91400 Orsay (France); Boisgard, R.; Tavitian, B. [CEA, Serv Hosp Frederic Joliot, Lab Imagerie Mol Expt, F-91400 Orsay (France); Roux, J.; Cales, P. [Univ Angers, UPRES EA 3859, Lab Hemodynam Interact Fibrose et Invas Tumorale H, Angers (France); Clerc, J. [Hop Cochin, AP HP, Dept Nucl Med, F-75014 Paris (France)

    2008-07-01

    The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III {alpha}, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of {sup 131}I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. {sup 131}I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  10. Intestinal duplicity in the young adult as cause of recurrent abdominal tumor

    International Nuclear Information System (INIS)

    Rivero, Armando; Nunez, Margis; Cordero, Claudio; Armas, Juan C; Hernandez, Jose A; Valdes, Filiberto

    2003-01-01

    A white mal patient is reported, of 21 years of age with an intestinal duplication clerk of transverse colon, uncommon digestive malformation never before reported in our hospital. The clinical study and the called out complementary exams those are shown that included, humorales, contrasted X -rays of colon, abdominal ultra-sonography, laparoscopy, and the laparotomy. We describe the opposing malformation, the surgical technique employed and the histopathological conclusions of the extracted piece, the clinical evolution, and the complications. After 43 days he was discharged with ambulatory treatment, evolving favorably. The histopathological conclusions were: Intestinal Duplication clerk of the transverse colon. At present he is completely cured. A revision of the literature is carried out and the approaches of more interest are exposed

  11. NKD1 marks intestinal and liver tumors linked to aberrant Wnt signaling

    Czech Academy of Sciences Publication Activity Database

    Stančíková, Jitka; Krausová, Michaela; Kolář, Michal; Fafílek, Bohumil; Švec, Jiří; Sedláček, Radislav; Neroldová, M.; Dobeš, Jan; Horázná, Monika; Janečková, Lucie; Vojtěchová, Martina; Oliverius, M.; Jirsa, M.; Kořínek, Vladimír

    2015-01-01

    Roč. 27, č. 2 (2015), s. 245-256 ISSN 1873-3913 R&D Projects: GA ČR GAP305/11/1780; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LM2011032 Institutional support: RVO:68378050 Keywords : Wnt signaling * NKD 1 * Intestine * Liver * Colorectal cancer * Hepatocellular carcinoma Subject RIV: EB - Gene tics ; Molecular Biology

  12. Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.

    Science.gov (United States)

    Litchfield, Kevin; Levy, Max; Orlando, Giulia; Loveday, Chey; Law, Philip J; Migliorini, Gabriele; Holroyd, Amy; Broderick, Peter; Karlsson, Robert; Haugen, Trine B; Kristiansen, Wenche; Nsengimana, Jérémie; Fenwick, Kerry; Assiotis, Ioannis; Kote-Jarai, ZSofia; Dunning, Alison M; Muir, Kenneth; Peto, Julian; Eeles, Rosalind; Easton, Douglas F; Dudakia, Darshna; Orr, Nick; Pashayan, Nora; Bishop, D Timothy; Reid, Alison; Huddart, Robert A; Shipley, Janet; Grotmol, Tom; Wiklund, Fredrik; Houlston, Richard S; Turnbull, Clare

    2017-07-01

    Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes. Our findings implicate widespread disruption of developmental transcriptional regulators as a basis of TGCT susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in oncogenesis. Defective microtubule assembly and dysregulation of KIT-MAPK signaling also feature as recurrently disrupted pathways. Our findings support a polygenic model of risk and provide insight into the biological basis of TGCT.

  13. Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways.

    Directory of Open Access Journals (Sweden)

    Victoria Ifeadi

    Full Text Available BACKGROUND: Death receptors (DR of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTβR was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTβR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not LTβR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L and c-FLIP protein expression, this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can overcome Fas and TRAIL

  14. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  15. UPPER GASTRO-INTESTINAL BLEEDING IN THE YOUNG - GASTRIC GIST TUMOR OR PEPTIC ULCER DISEASE?

    Directory of Open Access Journals (Sweden)

    Ayodele Atolagbe

    2015-09-01

    Full Text Available GIST tumors is very unusual in the young and middle aged and a high index of suspicion is needed for the diagnosis in young patients who present with upper gastrointestinal bleeding. Appropriate imaging such as a Computed tomographic scan (CT scan may identify this tumor which may easily be misdiagnosed as a bleeding Peptic Ulcer Disease in the young. We present a case of a healthy 38 year old man with no alcohol use who presented with epigastric pain and melena and subsequent torrential bleeding uncontrolled during endoscopy necessitating an emergency exploratory laparotomy by the general surgery team. The bleeding intraluminal component of the tumor with gross splenic and pancreatic involvement was identified and surgical management consisted of a wedge resection of the greater curvature of the stomach incorporating the tumor and the spleen with successful dissection of the tumor off the tail of the pancreas. Histology was positive for C-KIT and DOG-1 markers. Postoperative course was uneventful and he is presently on Imatinib Mesylate.

  16. Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

    Directory of Open Access Journals (Sweden)

    Venturini James

    2009-06-01

    Full Text Available Abstract Background In order to attain a better understanding of the interactions between opportunist fungi and their hosts, we investigated the cytokine profile associated with the inflammatory response to Candida albicans infection in mice with solid Ehrlich tumors of different degrees. Methods Groups of eight animals were inoculated intraperitoneally with 5 × 106 C. albicans 7, 14 or 21 days after tumor implantation. After 24 or 72 hours, the animals were euthanized and intraperitoneal lavage fluid was collected. Peritoneal macrophages were cultivated and the levels of IFN-γ, TNF-α, IL-12, IL-10 and IL-4 released into the supernatants were measured by ELISA. Kidney, liver and spleen samples were evaluated for fungal dissemination. Tumor-free animals and animals that had only been subjected to C. albicans infection were used as control groups. Results Our results demonstrated that the mice produced more IFN-γ and TNF-α and less IL-10, and also exhibited fungal clearance, at the beginning of tumor evolution. With the tumor progression, this picture changed: IL-10 production increased and IFN-γ and TNF-α release decreased; furthermore, there was extensive fungal dissemination. Conclusion Our results indicate that solid tumors can affect the production of macrophage cytokines and, in consequence, affect host resistance to opportunistic infections.

  17. Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus.

    Directory of Open Access Journals (Sweden)

    Yonatan Y Mahller

    Full Text Available Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

  18. Increased susceptibility of tumor cells and chicken erythrocytes to lysis by antibody and complement after treatment with aminoethylisothiouronium bromide hydrobromide (AET)

    Energy Technology Data Exchange (ETDEWEB)

    Langone, J.J.; Borsos, T. (National Cancer Institute, Bethesda, MD (USA))

    1979-01-01

    After treatment with aminoethylisothiouronium bromide hydrobromide (AET), the ascites forms of the diethylnitrosamine-induced guinea pig hepatomas, line-1 and line-10, were susceptible or more susceptible to killing in vitro by certain combinations of tumor-specific or IgM anti-Forssman antibody and either human or guinea pig complement. Since AET could be toxic to either cell line, conditions of pH, concentration of AET, and duration of exposure of the cells to the reagent were determined that resulted in enhanced susceptibility without significantly affecting cell viability. Chicken erythrocytes (CE) also were tested and AET-treated cells found to be more susceptible to lysis by IgM anti-Forssman antibody and guinea pig complement. The enhancement apparently was not due to increased ability of AET-treated CE to fix antibody. In contrast to CE, the lytic susceptibility of sheep cells was not affected by AET treatment. In addition to AET, several drugs and enzymes that also can affect the susceptibility of the tumor cells to antibody and complement were tested and found to be ineffective against CE. Since AET reputedly acts directly on the cell surface, it seems reasonable to assume that the increased susceptibility of the tumor cells and CE to antibody and complement may result from a modification of the cell surface.

  19. Evaluation of the WHO 2010 grading and AJCC/UICC staging systems in prognostic behavior of intestinal neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Paula B Araujo

    Full Text Available BACKGROUND: The increasing incidence and heterogeneous behavior of intestinal neuroendocrine tumors (iNETs pose a clinicopathological challenge. Our goal was to decribe the prognostic value of the new WHO 2010 grading and the AJCC/UICC TNM staging systems for iNETs. Moreover, outcomes of patients treated with somatostatin analogs were assessed. METHODS: We collected epidemiological and clinicopathological data from 93 patients with histologically proven iNETs including progression and survival outcomes. The WHO 2010 grading and the AJCC/UICC TNM staging systems were applied for all cases. RECIST criteria were used to define progression. Kaplan-Meier analyses for progression free survival (PFS and overall survival (OS were performed. RESULTS: Mean follow-up was 58.6 months (4-213 months. WHO 2010 grading yielded PFS and disease-specific OS of 125.0 and 165.8 months for grade 1 (G1, 100.0 and 144.2 months for G2 and 15.0 and 15.8 months for G3 tumors (p = 0.004 and p = 0.001. Using AJCC staging, patients with stage I and II tumors had no progression and no deaths. Stage III and IV patients demonstrated PFS of 138.4 and 84.7 months (p = 0.003 and disease-specific OS of 210.0 and 112.8 months (p = 0.017. AJCC staging also provided informative PFS (91.2 vs. 50.0 months, p = 0.004 and OS (112.3 vs. 80.0 months, p = 0.005 measures with somatostatin analog use in stage IV patients. CONCLUSION: Our findings underscore the complementarity of WHO 2010 and AJCC classifications in providing better estimates of iNETS disease outcomes and extend the evidence for somatostatin analog benefit in patients with metastatic disease.

  20. Second mitochondria-derived activator of caspase (SMAC) mimetic potentiates tumor susceptibility toward natural killer cell-mediated killing.

    Science.gov (United States)

    Brinkmann, Kerstin; Hombach, Andreas; Seeger, Jens Michael; Wagner-Stippich, Diana; Klubertz, Daniela; Krönke, Martin; Abken, Hinrich; Kashkar, Hamid

    2014-03-01

    Resistance to apoptosis is a hallmark of cancer, and represents an important mechanism of how tumor cells resist immune cell destruction. Mitochondria are the central regulators of the apoptotic machinery by releasing pro-apoptotic factors including cytochrome c and second mitochondria-derived activator of caspase (SMAC) upon mitochondrial outer membrane permeabilization (MOMP). Small molecules activating MOMP such as BH3 mimetics or antagonizers of the inhibitor of apoptosis proteins (IAPs) such as SMAC mimetics have recently engendered new optimism for a more individualized and effective cancer therapy. Here we show that a SMAC mimetic potentiates cancer cell killing by natural killer (NK) cells through reactivation of tumor cell apoptosis. Specifically, the SMAC mimetic enhances the susceptibility of tumor cells toward NK cell-mediated effector mechanisms involving death receptors and cytolytic granules containing perforin and granzymes by relieving caspase activity. Our data highlight for the first time the specific use of SMAC mimetics for boosting immune cell-mediated immunotherapy, representing a novel and promising approach in the treatment of cancer.

  1. Meat, smoking, alcohol, and colorectal tumors: the role of genetic susceptibility

    NARCIS (Netherlands)

    Tiemersma, E.W.

    2002-01-01

    Colorectal cancer is the second most common cancer in the Western world and is thought to arise mainly from colorectal adenomas. Red meat and alcohol intake and (long-term) cigarette smoking probably increase colorectal tumor risk. Although risk increase was found to be weak, certain

  2. Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.

    Science.gov (United States)

    Peters, Ulrike; Jiao, Shuo; Schumacher, Fredrick R; Hutter, Carolyn M; Aragaki, Aaron K; Baron, John A; Berndt, Sonja I; Bézieau, Stéphane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J; Campbell, Peter T; Carlson, Christopher S; Casey, Graham; Chan, Andrew T; Chang-Claude, Jenny; Chanock, Stephen J; Chen, Lin S; Coetzee, Gerhard A; Coetzee, Simon G; Conti, David V; Curtis, Keith R; Duggan, David; Edwards, Todd; Fuchs, Charles S; Gallinger, Steven; Giovannucci, Edward L; Gogarten, Stephanie M; Gruber, Stephen B; Haile, Robert W; Harrison, Tabitha A; Hayes, Richard B; Henderson, Brian E; Hoffmeister, Michael; Hopper, John L; Hudson, Thomas J; Hunter, David J; Jackson, Rebecca D; Jee, Sun Ha; Jenkins, Mark A; Jia, Wei-Hua; Kolonel, Laurence N; Kooperberg, Charles; Küry, Sébastien; Lacroix, Andrea Z; Laurie, Cathy C; Laurie, Cecelia A; Le Marchand, Loic; Lemire, Mathieu; Levine, David; Lindor, Noralane M; Liu, Yan; Ma, Jing; Makar, Karen W; Matsuo, Keitaro; Newcomb, Polly A; Potter, John D; Prentice, Ross L; Qu, Conghui; Rohan, Thomas; Rosse, Stephanie A; Schoen, Robert E; Seminara, Daniela; Shrubsole, Martha; Shu, Xiao-Ou; Slattery, Martha L; Taverna, Darin; Thibodeau, Stephen N; Ulrich, Cornelia M; White, Emily; Xiang, Yongbing; Zanke, Brent W; Zeng, Yi-Xin; Zhang, Ben; Zheng, Wei; Hsu, Li

    2013-04-01

    Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 × 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 × 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10(-7)). In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further

  3. Neural - levelset shape detection segmentation of brain tumors in dynamic susceptibility contrast enhanced and diffusion weighted magnetic resonance images

    International Nuclear Information System (INIS)

    Vijayakumar, C.; Bhargava, Sunil; Gharpure, Damayanti Chandrashekhar

    2008-01-01

    A novel Neuro - level set shape detection algorithm is proposed and evaluated for segmentation and grading of brain tumours. The algorithm evaluates vascular and cellular information provided by dynamic contrast susceptibility magnetic resonance images and apparent diffusion coefficient maps. The proposed neural shape detection algorithm is based on the levels at algorithm (shape detection algorithm) and utilizes a neural block to provide the speed image for the level set methods. In this study, two different architectures of level set method have been implemented and their results are compared. The results show that the proposed Neuro-shape detection performs better in differentiating the tumor, edema, necrosis in reconstructed images of perfusion and diffusion weighted magnetic resonance images. (author)

  4. Lack of anti-tumor activity with the β-catenin expression inhibitor EZN-3892 in the C57BL/6J Min/+ model of intestinal carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Hasson, Rian M.; Briggs, Alexandra; Rizvi, Hira; Carothers, Adelaide M.; Davids, Jennifer S.; Bertagnolli, Monica M.; Cho, Nancy L., E-mail: nlcho@partners.org

    2014-02-14

    Highlights: • Wnt/β-catenin signaling is aberrantly activated in most colorectal cancers. • Locked nucleic acid (LNA)-based antisense is a novel tool for cancer therapy. • β-Catenin inhibition was observed in mature intestinal tissue of LNA-treated mice. • Further investigation of Wnt/β-catenin targeted therapies is warranted. - Abstract: Background: Previously, we showed that short-term inhibition of β-catenin expression and reversal of aberrant β-catenin subcellular localization by the selective COX-2 inhibitor celecoxib is associated with adenoma regression in the C57BL/6J Min/+ mouse. Conversly, long-term administration resulted in tumor resistance, leading us to investigate alternative methods for selective β-catenin chemoprevention. In this study, we hypothesized that disruption of β-catenin expression by EZN-3892, a selective locked nucleic acid (LNA)-based β-catenin inhibitor, would counteract the tumorigenic effect of Apc loss in Min/+ adenomas while preserving normal intestinal function. Materials and methods: C57BL/6J Apc{sup +/+} wild-type (WT) and Min/+ mice were treated with the maximum tolerated dose (MTD) of EZN-3892 (30 mg/kg). Drug effect on tumor numbers, β-catenin protein expression, and nuclear β-catenin localization were determined. Results: Although the tumor phenotype and β-catenin nuclear localization in Min/+ mice did not change following drug administration, we observed a decrease in β-catenin expression levels in the mature intestinal tissue of treated Min/+ and WT mice, providing proof of principle regarding successful delivery of the LNA-based antisense vehicle. Higher doses of EZN-3892 resulted in fatal outcomes in Min/+ mice, likely due to β-catenin ablation in the intestinal tissue and loss of function. Conclusions: Our data support the critical role of Wnt/β-catenin signaling in maintaining intestinal homeostasis and highlight the challenges of effective drug delivery to target disease without permanent

  5. Tumor Necrosis Factor B (TNFB) Genetic Variants and Its Increased Expression Are Associated with Vitiligo Susceptibility

    Science.gov (United States)

    Laddha, Naresh C.; Dwivedi, Mitesh; Gani, Amina R.; Mansuri, Mohmmad Shoab; Begum, Rasheedunnisa

    2013-01-01

    Genetic polymorphisms in TNFB are involved in the regulation of its expression and are found to be associated with various autoimmune diseases. The aim of the present study was to determine whether TNFB +252A/G (rs909253) and exon 3 C/A (rs1041981) polymorphisms are associated with vitiligo susceptibility, and expression of TNFB and ICAM1 affects the disease onset and progression. We have earlier reported the role of TNFA in autoimmune pathogenesis of vitiligo, and we now show the involvement of TNFB in vitiligo pathogenesis. The two polymorphisms investigated in the TNFB were in strong linkage disequilibrium and significantly associated with vitiligo. TNFB and ICAM1 transcripts were significantly increased in patients compared to controls. Active vitiligo patients showed significant increase in TNFB transcripts compared to stable vitiligo. The genotype-phenotype analysis revealed that TNFB expression levels were higher in patients with GG and AA genotypes as compared to controls. Patients with the early age of onset and female patients showed higher TNFB and ICAM1 expression. Overall, our findings suggest that the increased TNFB transcript levels in vitiligo patients could result, at least in part, from variations at the genetic level which in turn leads to increased ICAM1 expression. For the first time, we show that TNFB +252A/G and exon 3 C/A polymorphisms are associated with vitiligo susceptibility and influence the TNFB and ICAM1 expression. Moreover, the study also emphasizes influence of TNFB and ICAM1 on the disease progression, onset and gender bias for developing vitiligo. PMID:24312346

  6. Intestinal bacteria in charge of radiation-induced inhibition of tumor metastases

    International Nuclear Information System (INIS)

    Ando, K.; Matsumoto, T.; Koike, S.

    1984-01-01

    The authors previously reported that caecal irradiation prior to an i.v. challenge of tumor cells inhibited lung metastases formation. The authors here identified bacteria in charge of the radiation effect and reported kinetics of bacterial flora after abdominal irradiation. C3Hf/He male mice in either SPF, germ-free or gnotobiotic condition received abdominal irradiation with /sup 137/Cs γ-ray of 12 Gy and received an i.v. challenge of 10 fibrosarcoma (NFSa) 7 days thereafter. Gnotobiotes which were mono-associated with Enterobacter cloacae(Ent. cloacae) showed significantly smaller number of lung metastases than germ-free mice while monoassociation with Bifidobacilli failed to exert any inhibition. In SPF mice, Ent. cloacae translocated to mesenteric lymph nodes at day 5 to 7 of irradiation while Bifidobacilli and Lactobacili were detectable only at day 14. Considering that Ent. cloacae possess endotoxin while Bifidobacilli and Lactobacilli do not, abdominal irradiation probably releases endotoxin from caecum to the rest of the body, resulting in stimulation of the host defence mechanism against metastases

  7. Tumor necrosis factor receptor 1-dependent depletion of mucus in immature small intestine: a potential role in neonatal necrotizing enterocolitis

    OpenAIRE

    McElroy, Steven J.; Prince, Lawrence S.; Weitkamp, Jörn-Hendrik; Reese, Jeff; Slaughter, James C.; Polk, D. Brent

    2011-01-01

    Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. NEC is believed to occur when intestinal bacteria invade the intestinal epithelial layer, causing subsequent inflammation and tissue necrosis. Mucins are produced and secreted by epithelial goblet cells as a key component of the innate immune system and barrier function of the intestinal tract that help protect against bacterial invasion. To better understand the role of mucins in NEC, we quant...

  8. The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure

    Directory of Open Access Journals (Sweden)

    Lv Sa

    2009-09-01

    Full Text Available Abstract Background Spontaneous bacterial peritonitis (SBP is a common clinical disease and one of the most severe complications of acute liver failure (ALF. Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-α on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1 protein in a mouse model of ALF. Methods We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS or GalN/TNF-α and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-α IgG antibody or anti-TNF-α R1 antibody before administration of GalN/LPS or GalN/TNF-α, respectively, on TNF-α were also assessed. Results Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-α level. Electron microscopic analysis revealed tight junction (TJ disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-α IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-α R1 antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression. Conclusion TNF-α affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.

  9. Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

    Science.gov (United States)

    Laddha, Naresh C.; Dwivedi, Mitesh; Begum, Rasheedunnisa

    2012-01-01

    Abstract Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with TNF-α transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-α transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-α transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates

  10. Antimicrobial susceptibility and antibiotic resistance profiles of cultivable lactic acid bacteria from intestinal tract of domestic chickens collected in Adjara

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    Lia L. Amiranashvili

    2016-09-01

    Full Text Available Elaboration and introduction of safe, effective probiotic preparations as alternatives to antibiotics are being actively conducted throughout the world. 66 LAB isolates were isolated from ileal, cecal and rectal samples collected from domestic chickens collected in different districts of Adjara, Georgia. Their resistance to 17 antibiotics and antibacterial activity were studied using the agar diffusion method. Among the isolates, widespread resistance was found to metronidazole and nystatin, sensitivity – to ampicillin, tylosin, rifampicin and bacitracin. Most of isolates have intermediate susceptibility to the majority of the antibiotics. 3 LAB isolates were selected by antibacterial action against the several bacterial indicator strains that makes them effective remedy to control antibiotic-independent pathogen through competitive exclusion and promotion of good protective microbiota and perspective probiotic additives for chicken food. Future investigations, proving the safety of the strains and their antimicrobial compounds will enable to apply in vivo probiotic properties on poultry production.

  11. Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring.

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    Julia A Sabet

    Full Text Available The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.Male Apc1638N mice (prone to intestinal tumor formation were fed diets containing replete (control, CTRL, mildly deficient (DEF, or supplemental (SUPP quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.In this animal model, modulation of paternal B vitamin intake prior to mating

  12. Tumor necrosis factor receptor 1-dependent depletion of mucus in immature small intestine: a potential role in neonatal necrotizing enterocolitis.

    Science.gov (United States)

    McElroy, Steven J; Prince, Lawrence S; Weitkamp, Jörn-Hendrik; Reese, Jeff; Slaughter, James C; Polk, D Brent

    2011-10-01

    Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. NEC is believed to occur when intestinal bacteria invade the intestinal epithelial layer, causing subsequent inflammation and tissue necrosis. Mucins are produced and secreted by epithelial goblet cells as a key component of the innate immune system and barrier function of the intestinal tract that help protect against bacterial invasion. To better understand the role of mucins in NEC, we quantified the number of mucus-containing small intestinal goblet cells present in infants with NEC and found they had significantly fewer goblet cells and Paneth cells compared with controls. To test whether inflammation has a developmentally dependent effect on intestinal goblet cells, TNF-α was injected into mice at various stages of intestinal development. TNF-α caused a loss of mucus-containing goblet cells only in immature mice and induced Muc2 and Muc3 mRNA upregulation only in mature ileum. Only minimal changes were seen in apoptosis and in expression of markers of goblet cell differentiation. TNF-α increased small intestinal mucus secretion and goblet cell hypersensitivity to prostaglandin E2 (PGE(2)), a known mucus secretagogue produced by macrophages. These TNF-α-induced changes in mucus mRNA levels required TNF receptor 2 (TNFR2), whereas TNF-α-induced loss of mucus-positive goblet cells required TNFR1. Our findings of developmentally dependent TNF-α-induced alterations on intestinal mucus may help explain why NEC is predominantly found in premature infants, and TNF-α-induced alterations of the intestinal innate immune system and barrier functions may play a role in the pathogenesis of NEC itself.

  13. Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors

    International Nuclear Information System (INIS)

    Voisin, Laure; Basik, Mark; Meloche, Sylvain; Julien, Catherine; Duhamel, Stéphanie; Gopalbhai, Kailesh; Claveau, Isabelle; Saba-El-Leil, Marc K; Rodrigue-Gervais, Ian Gaël; Gaboury, Louis; Lamarre, Daniel

    2008-01-01

    The Ras-dependent ERK1/2 MAP kinase signaling pathway plays a central role in cell proliferation control and is frequently activated in human colorectal cancer. Small-molecule inhibitors of MEK1/MEK2 are therefore viewed as attractive drug candidates for the targeted therapy of this malignancy. However, the exact contribution of MEK1 and MEK2 to the pathogenesis of colorectal cancer remains to be established. Wild type and constitutively active forms of MEK1 and MEK2 were ectopically expressed by retroviral gene transfer in the normal intestinal epithelial cell line IEC-6. We studied the impact of MEK1 and MEK2 activation on cellular morphology, cell proliferation, survival, migration, invasiveness, and tumorigenesis in mice. RNA interference was used to test the requirement for MEK1 and MEK2 function in maintaining the proliferation of human colorectal cancer cells. We found that expression of activated MEK1 or MEK2 is sufficient to morphologically transform intestinal epithelial cells, dysregulate cell proliferation and induce the formation of high-grade adenocarcinomas after orthotopic transplantation in mice. A large proportion of these intestinal tumors metastasize to the liver and lung. Mechanistically, activation of MEK1 or MEK2 up-regulates the expression of matrix metalloproteinases, promotes invasiveness and protects cells from undergoing anoikis. Importantly, we show that silencing of MEK2 expression completely suppresses the proliferation of human colon carcinoma cell lines, whereas inactivation of MEK1 has a much weaker effect. MEK1 and MEK2 isoforms have similar transforming properties and are able to induce the formation of metastatic intestinal tumors in mice. Our results suggest that MEK2 plays a more important role than MEK1 in sustaining the proliferation of human colorectal cancer cells

  14. Labeling of vasoactive intestinal peptide (VIP) and VIP 10-28 fragment with radioiodine by direct method. Comparative study of the kinetics biodistribution and affinity for neuroendocrine tumor cells

    International Nuclear Information System (INIS)

    Colturato, Maria Tereza

    2005-01-01

    In the progress of the Nuclear Medicine, many protein based radiopharmaceuticals have been developed in the last years using antibodies and, more recently, biologically active natural peptides or similar synthetic peptides. In the search for agents with specificity for the target tissue in tumors detection, it was verified that small sequences of amino acids may interact with selective sites, with homogenous distribution, fast accumulation in tissues and fast blood clearance when compared to the antibodies. Among the peptides used in the diagnosis of tumors, Vasoactive Intestinal Peptide (VIP) has been studied. VIP labeled with iodine-123 is applied in the images of intestinal adenocarcinoma and endocrine tumors. The molecule of VIP contains two tyrosine residues, in the positions 10 and 22 that are, theoretically, equally susceptible to radioiodination for direct method. The objective of this work was to produce VIP labeled with radioiodine (iodine-123), in order to introduce to the brazilian medical class this radiopharmaceutical of interest for the diagnosis and recurrence of tumors that express specific receptors. In an unpublished way, the work studied the labeling and the kinetic distribution of the VIP fragment (VIP 10-28) and verified its potential as radiopharmaceutical applied in the identification of tumors that express VIP receptors. After the choice of the appropriated technique for labeling VIP and VIP 10-28 with radioiodine, using Ceremonial T as oxidant agent and sodium metabisulfite as reducing agent, the quality control procedures were accomplished (electrophoresis and high performance liquid chromatography, HPLC) for radiochemical purity determination as well as the separation of the radiochemical species obtained. Labeling and quality control procedures applied were efficient and accurate. [ 131 I]VIP and [ 131 l]VIP 10-28 were obtained with high radiochemical purity (> 95%). The purification studies to remove free radioiodine in the labeling

  15. Intestinal morphological effect of brachytherapy of low rate of dose, administrated in therapeutic form and its clinical manifestations in uterine cervix tumors

    International Nuclear Information System (INIS)

    Mendoza, Carmen; Contreras, Manuel

    2005-01-01

    Brachytherapy is effective to eradicate cancer in the cervix, in order to obtain the control of disease we use high dose with vesical and rectum toxicity. The objective is to investigate if brachytherapy by itself is the cause of intestinal damage, to know in addition if the intensity of the clinic manifestations is in direct relation to the given radiation dose and this gets worse when it is received in several applications. Hypothesis: The intensity of the radiation with brachytherapy of low rate of dose is proportional to the degree of clinical manifestations and morphologic damage of the intestine. A prospective analysis was made inpatients with cancer of cervix from september 2000 to june 2004. Each patient who enters to the department of brachytherapy of the hospital must be done laboratory examination that includes plaque and coagulation test before being accepted. We use the clinical card and a table in order to register data concerning teletherapy, implants of brachytherapy of low rate of dose, symptoms of intestinal toxicity and details of colonoscopia. Subsequent to the hospitable discharge the patient is sent to gastroenterology for clinical evaluation and to realize colonoscopia. From september 2000 to june 2004, 540 patients entered, 80 patients (15%) displayed intestinal manifestations, all received teletherapy and brachytherapy, nobody else received brachytherapy in exclusive form and only one patient (0.1%) received the total of the dose in 2 applications. The equipment of teletherapy Primus with energy of 6 and 18 Mv and implants of brachytherapy Manchester were used (70/55 patients). 79 (98%) patients received dose between 85-75 Gy in one single application, 58 (72%) received the total of the dose to the tumor, 21 (26%) in vaginal mucosa. Discussion: Brachytherapy is the cause of the damages in the intestinal mucosa. (The author)

  16. Ethanol increases tumor necrosis factor-alpha receptor-1 (TNF-R1) levels in hepatic, intestinal, and cardiac cells.

    Science.gov (United States)

    Rodriguez, Diego A; Moncada, Claudio; Núñez, Marco T; Lavandero, Sergio; Ponnappa, Biddanda C; Israel, Yedy

    2004-05-01

    Chronic ethanol consumption leads to cell injury in virtually every tissue. Tumor necrosis factor-alpha (TNF-alpha) constitutes a major factor in the development of alcohol-induced liver injury. In alcohol-dependent subjects, elevated levels of plasma TNF-alpha are strongly predictive of mortality. Binding of TNF-alpha to TNF-alpha receptor-1 (TNF-R1) activates death domain pathways, leading to necrosis and apoptosis in most tissues, and it also increases the expression of intercellular adhesion molecules (i.e., ICAM-1), which promote inflammation. We determined whether ethanol exposure leads to increases in cellular TNF-R1. We incubated HepG2 human hepatoma cells and H4-II-E-C3 rat hepatoma cells with 25, 50, and 100 mM ethanol for various intervals of time up to 48 h. Human colonic adenocarcinoma cells (Caco-2 cells) and neonatal rat primary cardiomyocytes were also incubated with different concentrations of ethanol. Levels of TNF-R1 were measured either by a sandwich enzyme-linked immunosorbent assay (ELISA) method or by determining the extracellular transmembrane domain of TNF-R1 by an intact-cell ELISA method. Ethanol exposure for 48 h increased TNF-R1 levels in human hepatoma cells in a dose-dependent manner. Levels increased significantly by 164% at 50 mM and by 240% at 100 mM ethanol. Effects were time dependent and did not reach a plateau at 48 h. Similar increases in TNF-R1 were also observed in rat hepatoma cells (90% at 50 mM and 230% at 100 mM ethanol). Under similar conditions, Caco-2 cells showed a significant 80% increase in TNF-R1 levels at 200 mM ethanol, a concentration found in intestine. Neonatal rat primary cardiomyocytes showed TNF-R1 increases of 36% at 50 mM and 44% at 100 mM ethanol. These results indicate that exposure of different cell types to pharmacologic concentrations of ethanol increases TNF-R1 levels and may augment TNF-alpha-mediated cell injury in different tissues.

  17. Acute GI bleeding by multiple jejunal gastrointestinal autonomic nerve tumour associated with neurofibromatosis type I Urgencia quirúrgica por sangrado intestinal debido a tumor intestinal de nervios autónomos asociados a neurofibromatosis tipo I

    Directory of Open Access Journals (Sweden)

    M. Keese

    2007-10-01

    Full Text Available We describe a surgical emergency due to GI-bleeding caused by gastrointestinal autonomic nerve tumours (GANT's in a patient with von Recklinghausen's disease. A 72 year old female patient with von Recklinghausen's disease was admitted with maelena. Endoscopy showed no active bleeding in the stomach and the colon. Therefore an angio-CT-scan was performed which revealed masses of the proximal jejunum as source of bleeding. Laparotomy was indicated and a 20 cm segment of jejunum which carried multiple extraluminal tumours was resected. The source of the bleeding was a 2 cm tumour which had eroded the mucosal surface. Immunohistologically, evidence of neuronal differentiation could be shown in the spindle-formed cells with positive staining for C-Kit (CD 117, CD 34, and a locally positive staining for synaptophysine and S100. This case report illustrates the association between neurofibromatosis and stromal tumours and should alert surgeons and gastroenterologist about gastrointestinal manifestations in patients with von Recklinghausen's disease.Se describe una urgencia quirúrgica por sangrado intestinal debido a tumor gastrointestinal de nervios autónomos (GANT asociado a enfermedad de von Recklinghausen. Una mujer de 72 años con neurofibromatosis fue ingresada con signos de melena. La endoscopia digestiva alta y baja fue negativa. Se indicó TAC con contraste que advirtió tumores yeyunales como causa del sangrado. Se realizó laparotomía y resección de un segmento de 20 cm de yeyuno que incluía varios tumores. La causa del sangrado activo fue lesión en mucosa intestinal por erosión tumoral. El análisis por inmunohistoquímica de la pieza mostró diferenciación neuronal, con células fusiformes con tinción positiva para el C-Kit (CD 117, CD 34. Esta nota clínica pone de manifiesto la asociación entre la neurofibromatosis y los tumores estromales y debe alertar a gastroenterólogos y cirujanos sobre las posibles manifestaciones

  18. Effect of enteral immunonutrition after radical surgery for esophageal carcinoma on anti-tumor immune response and intestinal mucosal barrier function

    Directory of Open Access Journals (Sweden)

    Tong He

    2017-07-01

    Full Text Available Objective: To study the effect of enteral immunonutrition after radical surgery for esophageal carcinoma on anti-tumor immune response and intestinal mucosal barrier function. Methods: A total of 102 patients who received radical surgery for esophageal carcinoma in our hospital between May 2013 and December 2016 were selected and randomly divided into observation group and control group who received postoperative enteral immunonutrition and routine enteral nutrition respectively. 1 d before operation as well as 1 d and 7 d after operation, peripheral blood immune cell marker expression and serum intestinal mucosal barrier injury marker levels were detected. Results: 1 d after operation, peripheral blood T-bet, NKG2D, NKp30, NKp44 and NKp46 fluorescence intensity of both groups of patients were significantly lower than those 1d before operation while peripheral blood GATA-3 and Foxp3 fluorescence intensity as well as serum DAO, Occludin, ZO-1 and claudin-1 levels were significantly higher than those 1d before operation; peripheral blood T-bet, NKG2D, NKp30, NKp44 and NKp46 fluorescence intensity of observation group 7 d after operation were significantly higher than those 1 d after operation while peripheral blood GATA-3 and Foxp3 fluorescence intensity as well as serum DAO, Occludin, ZO-1 and claudin-1 levels were significantly lower than those 1 d after operation; peripheral blood T-bet, GATA-3, Foxp3, NKG2D, NKp30, NKp44 and NKp46 fluorescence intensity of control group 7 d after operation were not significant different from those 1 d after operation, and serum DAO, Occludin, ZO-1 and claudin-1 levels were significantly lower than those 1d after operation. Conclusion: Enteral immunonutrition after radical surgery for esophageal carcinoma can enhance the anti-tumor immune response and improve the intestinal mucosal barrier function.

  19. The Homeodomain Transcription Factor Cdx1 Does Not Behave as an Oncogene in Normal Mouse Intestine

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    Mary Ann S. Crissey

    2008-01-01

    Full Text Available The Caudal-related homeobox genes Cdx1 and Cdx2 are intestine-specific transcription factors that regulate differentiation of intestinal cell types. Previously, we have shown Cdx1 to be antiproliferative and to promote cell differentiation. However, other studies have suggested that Cdx1 may be an oncogene. To test for oncogenic behavior, we used the murine villin promoter to ectopically express Cdx1 in the small intestinal villi and colonic surface epithelium. No changes in intestinal architecture, cell differentiation, or lineage selection were observed with expression of the transgene. Classic oncogenes enhance proliferation and induce tumors when ectopically expressed. However, the Cdx1 transgene neither altered intestinal proliferation nor induced spontaneous intestinal tumors. In a murine model for colitis-associated cancer, the Cdx1 transgene decreased, rather than increased, the number of adenomas that developed. In the polyps, the expression of the endogenous and the transgenic Cdx1 proteins was largely absent, whereas endogenous Villin expression was retained. This suggests that transgene silencing was specific and not due to a general Villin inactivation. In conclusion, neither the ectopic expression of Cdx1 was associated with changes in intestinal cell proliferation or differentiation nor was there increased intestinal cancer susceptibility. Our results therefore suggest that Cdx1 is not an oncogene in normal intestinal epithelium.

  20. Chemotherapy modulates intestinal immune gene expression including surfactant Protein-D and deleted in malignant brain tumors 1 in piglets

    DEFF Research Database (Denmark)

    Rathe, Mathias; Thomassen, Mads; Shen, René L.

    2016-01-01

    the BUCY and DOX piglets. Selected genes of potential biological significance with a similar change in expression across the treatments were controlled by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D and deleted in malignant brain tumors 1, were among...

  1. Co-existence of acute appendicitis and inflammatory myofibroblastic tumor of the small intestine: A case report

    Directory of Open Access Journals (Sweden)

    Nurcan Unver

    2015-09-01

    Conclusion: Coexistence of inflammatory myofibroblastic tumor located in the gastrointestinal system with acute appendicitis is a rare event. Complete surgical excision should be regarded as the mainstay of the treatment. Long-term follow up with serial imaging techniques is recommended.

  2. Cholinesterase response in the rhabdomyosarcoma tumor and small intestine of the BALB/c mice and the radioprotective actions of exogenous ATP after lethal dose of neutron radiation

    International Nuclear Information System (INIS)

    Szeinfeld, D.; De Villiers, N.

    1993-01-01

    The rhabdomyosarcoma tumors were subjected to different doses of 2.0, 3.8 and 7.0 Gy from a neutron beam facility p(66 MeV)/Be. Elevated levels of cholinesterase activity are observed in which there is a correlation between the different doses of neutron radiation and the augmentation response of this enzyme. The increase of cholinesterase activity after 7 Gy neutron irradiation as a feature of involvement in the homeostatic mechanism maintaining the proper choline/acetylcholine ratio in the cell is also observed at 1 and 24 h in both tissues, rhabdomyosarcoma and small intestine. The activity of the enzyme after neutron irradiation with prior administration of ATP showed smaller increases when compared with increase observed after neutron irradiation alone. Moreover in the present work the protective mechanism of ATP in the response of cholinesterase activity is marked differential between both, normal and tumoral tissue and correlated inversely with the administered of the following concentrations of exogenous ATP (8, 25, 80, 250, and 700 mg/kg body weight) prior to exposure to 7 Gy neutron radiation. These results reflect the radioprotective ability of exogenous ATP to exert a number of metabolic adaptations as a defense mechanism in which the cell exposed to neutron radiation could remain viable because the injury is potentially repairable. (orig.) [de

  3. Exposure to chromium (VI) in the drinking water increases susceptibility to UV-induced skin tumors in hairless mice

    International Nuclear Information System (INIS)

    Davidson, Todd; Kluz, Thomas; Burns, Fredric; Rossman, Toby; Zhang, Qunwei; Uddin, Ahmed; Nadas, Arthur; Costa, Max

    2004-01-01

    Hexavalent chromium (Cr (VI)) is a well known-human carcinogen with exposures occurring in both occupational and environmental settings. Although lung carcinogenicity has been well documented for occupational exposure via inhalation, the carcinogenic hazard of drinking water exposure to Cr (VI) has yet to be established. We used a hairless mouse model to study the effects of K 2 CrO 4 in the drinking water on ultraviolet radiation (UVR)-induced skin tumors. Hairless mice were unexposed or exposed to UVR alone (1.2 kJ/m 2 ), K 2 CrO 4 alone at 2.5 and 5.0 ppm, or the combination of UVR and K 2 CrO 4 at 0.5, 2.5, and 5.0 ppm. Mice were observed on a weekly basis for the appearance of skin tumors larger than 2 mm. All the mice were euthanized on day 182. The skin tumors were excised and subsequently analyzed microscopically for malignancy by histopathology. There was a total absence of observable skin tumors in untreated mice and in mice exposed to chromate alone. However, there was a dose-dependent increase in the number of skin tumors greater than 2 mm in mice exposed to K 2 CrO 4 and UV compared with mice exposed to UV alone. The increase in tumors larger than 2 mm was statistically significant (P 2 CrO 4 at the two highest K 2 CrO 4 doses (2.5 and 5.0 ppm), and there was a statistically significant increase in the numbers of malignant tumors per mouse in the UVR plus K 2 CrO 4 (5 ppm) group compared with UV alone. The data presented here indicate that K 2 CrO 4 increases the number of UV-induced skin tumors in a dose-dependent manner, and these results support the concern that regulatory agencies have relative to the carcinogenic health hazards of widespread human exposure to Cr (VI) in drinking water

  4. Sex-dependent Differences in Intestinal Tumorigenesis Induced in Apc1638N/+ Mice by Exposure to {gamma} Rays

    Energy Technology Data Exchange (ETDEWEB)

    Trani, Daniela [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Maastricht Radiation Oncology (MaastRO) Lab, GROW-School for Oncology and Developmental Biology, University of Maastricht (Netherlands); Moon, Bo-Hyun [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Kallakury, Bhaskar; Hartmann, Dan P. [Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Datta, Kamal [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Fornace, Albert J., E-mail: af294@georgetown.edu [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia)

    2013-01-01

    Purpose: The purpose of the present study was to assess the effect of 1 and 5 Gy radiation doses and to investigate the interplay of gender and radiation with regard to intestinal tumorigenesis in an adenomatous polyposis coli (APC) mutant mouse model. Methods and Materials: Apc1638N/+ female and male mice were exposed whole body to either 1 Gy or 5 Gy of {gamma} rays and euthanized when most of the treated mice became moribund. Small and large intestines were processed to determine tumor burden, distribution, and grade. Expression of proliferation marker Ki-67 and estrogen receptor (ER)-{alpha} were also assessed by immunohistochemistry. Results: We observed that, with both 1 Gy and 5 Gy of {gamma} rays, females displayed reduced susceptibility to radiation-induced intestinal tumorigenesis compared with males. As for radiation effect on small intestinal tumor progression, although no substantial differences were found in the relative frequency and degree of dysplasia of adenomas in irradiated animals compared with controls, invasive carcinomas were found in 1-Gy- and 5-Gy-irradiated animals. Radiation exposure was also shown to induce an increase in protein levels of proliferation marker Ki-67 and sex-hormone receptor ER-{alpha} in both non tumor mucosa and intestinal tumors from irradiated male mice. Conclusions: We observed important sex-dependent differences in susceptibility to radiation-induced intestinal tumorigenesis in Apc1638N/+ mutants. Furthermore, our data provide evidence that exposure to radiation doses as low as 1 Gy can induce a significant increase in intestinal tumor multiplicity as well as enhance tumor progression in vivo.

  5. Comparison of time until elective intestinal resection regarding previous anti-tumor necrosis factor exposure: a Brazilian study on patients with Crohn's disease

    Directory of Open Access Journals (Sweden)

    Paulo Gustavo Kotze

    2018-01-01

    Full Text Available Background/Aims: The use of anti-tumor necrosis factor (anti-TNF agents seems to reduce surgical rates and delay surgical procedures in prospective trials and population-based studies in the management of Crohn's disease (CD. This study aimed to identify whether preoperative anti-TNF agents influence the time from diagnosis to surgery. Methods: An observational retrospective cohort study was conducted on patients with CD submitted to intestinal resections due to complications or medical therapy failure in a period of 7 years. The patients were allocated into 2 groups according to their previous exposure to anti-TNF agents in the preoperative period. Epidemiological aspects regarding age at diagnosis, smoking, perianal disease, and preoperative conventional therapy were considered. A Kaplan-Meier survival analysis was used to outline possible differences between the groups regarding the time to surgery. Results: A total of 123 patients were included (71 and 52 with and without previous exposure to biologics, respectively. The overall time to surgery was 108±6.9 months (maximum, 276 months. The survival estimation revealed no difference in the mean time to intestinal resection between the groups (99.78±10.62 months in the patients without and 114.01±9.07 months in those with previous anti-TNF use (log-rank P=0.35. There was no significant difference in the time to surgery regarding perianal CD (P=0.49, smoking (P=0.63, preoperative azathioprine (P=0.073 and steroid use (P=0.58. Conclusions: The time from diagnosis to surgery was not influenced by the preoperative use of anti-TNF therapy in this cohort of patients.

  6. Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice

    Directory of Open Access Journals (Sweden)

    Jessica L. Fleming

    2013-04-01

    Full Text Available Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3’ reporter luciferase assays containing wildtype and mutated Ets1 3’UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis.

  7. IDH mutant and 1p/19q co-deleted oligodendrogliomas: tumor grade stratification using diffusion-, susceptibility-, and perfusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yu; Xing, Zhen; She, Dejun; Yang, Xiefeng; Zheng, Yingyan; Xiao, Zebin; Cao, Dairong [First Affiliated Hospital of Fujian Medical University, Department of Radiology, Fuzhou, Fujian (China); Wang, Xingfu [First Affiliated Hospital of Fujian Medical University, Department of Pathology, Fuzhou (China)

    2017-06-15

    Currently, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion are proven diagnostic biomarkers for both grade II and III oligodendrogliomas (ODs). Non-invasive diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) are widely used to provide physiological information (cellularity, hemorrhage, calcifications, and angiogenesis) of neoplastic histology and tumor grade. However, it is unclear whether DWI, SWI, and DSC-PWI are able to stratify grades of IDH-mutant and 1p/19q co-deleted ODs. We retrospectively reviewed the conventional MRI (cMRI), DWI, SWI, and DSC-PWI obtained on 33 patients with IDH-mutated and 1p/19q co-deleted ODs. Features of cMRI, normalized ADC (nADC), intratumoral susceptibility signals (ITSSs), normalized maxim CBV (nCBV), and normalized maximum CBF (nCBF) were compared between low-grade ODs (LGOs) and high-grade ODs (HGOs). Receiver operating characteristic curve and logistic regression were applied to determine diagnostic performances. HGOs tended to present with prominent edema and enhancement. nADC, ITSSs, nCBV, and nCBF were significantly different between groups (all P < 0.05). The combination of SWI and DSC-PWI for grading resulted in sensitivity and specificity of 100.00 and 93.33%, respectively. IDH-mutant and 1p/19q co-deleted ODs can be stratified by grades using cMRI and advanced magnetic resonance imaging techniques including DWI, SWI, and DSC-PWI. Combined ITSSs with nCBV appear to be a promising option for grading molecularly defined ODs in clinical practice. (orig.)

  8. IDH mutant and 1p/19q co-deleted oligodendrogliomas: tumor grade stratification using diffusion-, susceptibility-, and perfusion-weighted MRI.

    Science.gov (United States)

    Lin, Yu; Xing, Zhen; She, Dejun; Yang, Xiefeng; Zheng, Yingyan; Xiao, Zebin; Wang, Xingfu; Cao, Dairong

    2017-06-01

    Currently, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion are proven diagnostic biomarkers for both grade II and III oligodendrogliomas (ODs). Non-invasive diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) are widely used to provide physiological information (cellularity, hemorrhage, calcifications, and angiogenesis) of neoplastic histology and tumor grade. However, it is unclear whether DWI, SWI, and DSC-PWI are able to stratify grades of IDH-mutant and 1p/19q co-deleted ODs. We retrospectively reviewed the conventional MRI (cMRI), DWI, SWI, and DSC-PWI obtained on 33 patients with IDH-mutated and 1p/19q co-deleted ODs. Features of cMRI, normalized ADC (nADC), intratumoral susceptibility signals (ITSSs), normalized maxim CBV (nCBV), and normalized maximum CBF (nCBF) were compared between low-grade ODs (LGOs) and high-grade ODs (HGOs). Receiver operating characteristic curve and logistic regression were applied to determine diagnostic performances. HGOs tended to present with prominent edema and enhancement. nADC, ITSSs, nCBV, and nCBF were significantly different between groups (all P IDH-mutant and 1p/19q co-deleted ODs can be stratified by grades using cMRI and advanced magnetic resonance imaging techniques including DWI, SWI, and DSC-PWI. Combined ITSSs with nCBV appear to be a promising option for grading molecularly defined ODs in clinical practice.

  9. PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: Evidence from meta-analysis.

    Science.gov (United States)

    Xu, Xin; Xie, Yanqi; Lin, Yiwei; Xu, Xianglai; Zhu, Yi; Mao, Yeqing; Hu, Zhenghui; Wu, Jian; Chen, Hong; Zheng, Xiangyi; Qin, Jie; Xie, Liping

    2012-12-01

    Plasminogen activator inhibitor-1 (PAI-1), belonging to the urokinase plasminogen activation (uPA) system, is involved in cancer development and progression. The PAI-1 promoter 4G/5G polymorphism was shown to contribute to genetic susceptibility to cancer, although the results were inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Scopus, Web of Science and Chinese National Knowledge Infrastructure (CNKI) were searched; data were extracted and analyzed independently by two reviewers. Ultimately, 21 eligible case-control studies with a total of 8,415 cancer cases and 9,208 controls were included. The overall odds ratio (OR) with its 95% confidence interval (CI) showed a statistically significant association between the PAI-1 promoter 4G/5G polymorphism and cancer risk (4G/4G vs. 5G/5G: OR=1.25, 95% CI=1.07-1.47, P(heterogeneity)=0.001; 4G/4G vs. 4G/5G+5G/5G: OR=1.10, 95% CI=1.03-1.17, P(heterogeneity)=0.194; 4G/4G+4G/5G vs. 5G/5G: OR=1.17, 95% CI=1.01-1.35, P(heterogeneity)=0.041). In further subgroup analyses, the increased risk of cancer was observed in a subgroup of Caucasians with regards to endometrial cancer. Our meta-analysis suggests that the PAI-1 4G/5G polymorphism most likely contributes to susceptibility to cancer, particularly in Caucasians. Furthermore, the 4G allele may be associated with an increased risk of endometrial cancer.

  10. Encapsulating Ionic Liquid and Fe₃O₄ Nanoparticles in Gelatin Microcapsules as Microwave Susceptible Agent for MR Imaging-guided Tumor Thermotherapy.

    Science.gov (United States)

    Du, Qijun; Ma, Tengchuang; Fu, Changhui; Liu, Tianlong; Huang, Zhongbing; Ren, Jun; Shao, Haibo; Xu, Ke; Tang, Fangqiong; Meng, Xianwei

    2015-06-24

    The combination of therapies and monitoring the treatment process has become a new concept in cancer therapy. Herein, gelatin-based microcapsules have been first reported to be used as microwave (MW) susceptible agent and magnetic resonance (MR) imaging contrast agent for cancer MW thermotherapy. Using the simple coacervation methods, ionic liquid (IL) and Fe3O4 nanoparticles (NPs) were wrapped in microcapsules, and these microcapsules showed good heating efficacy in vitro under MW irradiation. The results of cell tests indicated that gelatin/IL@Fe3O4 microcapsules possessed excellent compatibility in physiological environments, and they could effectively kill cancer cells with exposure to MW. The ICR mice bearing H22 tumors treated with gelatin/IL@Fe3O4 microcapsules were obtained an outstanding MW thermotherapy efficacy with 100% tumor elimination under ultralow density irradiation (1.8 W/cm(2), 450 MHz). In addition, the applicability of the microcapsules as an efficient contrast agent for MR imaging in vivo was evident. Therefore, these multifunctional microcapsules have a great potential for MR imaging-guided MW thermotherapy.

  11. Intestinal Cancer

    Science.gov (United States)

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  12. Lipo sarcoma in small intestine

    International Nuclear Information System (INIS)

    Rodriguez Iglesias, J.; Pineyro Gutierrez, A.; Taroco Medeiros, L.; Fein Kolodny, C.; Navarrete Pedocchi, H.

    1987-01-01

    A case is presented by primitive liposarcoma in small intestine , an extensive bibliographical review foreigner and national in this case. It detach the exceptional of the intestinal topography of the liposarcomas; and making stress in the relative value of the computerized tomography and ultrasonography in the diagnose of the small intestine tumors . As well as in the sarcomas of another topography, chemo and radiotherapy associated to the exeresis surgery, it can be of benefit [es

  13. T2*-based MR imaging (gradient echo or susceptibility-weighted imaging) in midline and off-midline intracranial germ cell tumors. A pilot study

    International Nuclear Information System (INIS)

    Morana, Giovanni; Tortora, Domenico; Severino, Mariasavina; Rossi, Andrea; Alves, Cesar Augusto; Finlay, Jonathan L.; Nozza, Paolo; Ravegnani, Marcello; Pavanello, Marco; Milanaccio, Claudia; Garre, Maria Luisa; Maghnie, Mohamad

    2018-01-01

    The role of T2*-based MR imaging in intracranial germ cell tumors (GCTs) has not been fully elucidated. The aim of this study was to evaluate the susceptibility-weighted imaging (SWI) or T2* gradient echo (GRE) features of germinomas and non-germinomatous germ cell tumors (NGGCTs) in midline and off-midline locations. We retrospectively evaluated all consecutive pediatric patients referred to our institution between 2005 and 2016, for newly diagnosed, treatment-naive intracranial GCT, who underwent MRI, including T2*-based MR imaging (T2* GRE sequences or SWI). Standard pre- and post-contrast T1- and T2-weighted imaging characteristics along with T2*-based MR imaging features of all lesions were evaluated. Diagnosis was performed in accordance with the SIOP CNS GCT protocol criteria. Twenty-four subjects met the inclusion criteria (17 males and 7 females). There were 17 patients with germinomas, including 5 basal ganglia primaries, and 7 patients with secreting NGGCT. All off-midline germinomas presented with SWI or GRE hypointensity; among midline GCT, all NGGCTs showed SWI or GRE hypointensity whereas all but one pure germinoma were isointense or hyperintense to normal parenchyma. A significant difference emerged on T2*-based MR imaging among midline germinomas, NGGCTs, and off-midline germinomas (p < 0.001). Assessment of the SWI or GRE characteristics of intracranial GCT may potentially assist in differentiating pure germinomas from NGGCT and in the characterization of basal ganglia involvement. T2*-based MR imaging is recommended in case of suspected intracranial GCT. (orig.)

  14. Polymorphism in the tumor necrosis factor-alpha gene (TNFA -308 G/A is not associated with susceptibility to chronic periodontitis in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Paula Cristina Trevilatto

    2016-02-01

    Full Text Available Objective: Tumor necrosis factor-alpha (TNF-α is a major mediator of the immune-inflammatory response and may play an important role in the pathogenesis and progression of chronic periodontitis. Polymorphisms in the promoter of the TNFA gene have been associated with some types of inflammatory diseases. The present study investigated the association between a single-nucleotide polymorphism (SNP of the TNFA (G-308A gene and chronic periodontitis in Brazilians. Methods: One hundred and thirteen (113 over 25 years were divided according to the severity level of periodontal disease: 44 healthy individuals (control group, 31 subjects with moderate and 38 patients with severe periodontitis. Genomic DNA was obtained from epithelial cells. The samples were analyzed for TNFA (G-308A polymorphism using polymerase chain reaction-restriction fragment length polymorphism techniques. The significance of the differences in the genotype frequencies of the polymorphism was assessed by Chi-square test (p<0.05. Results: No significant differences in the genotype distribution and allele frequency were found between control and groups with periodontitis. Conclusion: It was concluded that TNFA (-308 polymorphism was not associated with chronic periodontitis. Other polymorphisms in this or/and other genes of the host inflammatory response might be involved in determining susceptibility to periodontitis in the study population.

  15. Relationship between intestinal microflora imbalance and nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    MA Ruijuan

    2015-01-01

    Full Text Available The intestinal microecosystem is composed of natural microflora, intestinal epithelial cells, and intestinal mucosal immune system. Nonalcoholic fatty liver disease (NAFLD is a metabolic stress-induced liver injury associated with insulin resistance and genetic susceptibility. In recent years, there has been increasing evidence showing the involvement of imbalanced intestinal microflora in the pathogenesis of NAFLD. Overgrowth of intestinal microflora, increased permeability of intestinal mucosa, intestinal endotoxemia, and production of inflammatory cytokines play important roles in the development of NAFLD. Further studies on the relationship between intestinal microflora imbalance and the pathogenesis of NAFLD may shed light on the treatment and prevention of NAFLD.

  16. Intestinal Obstruction

    Science.gov (United States)

    ... the obstruction along the intestines. Treatment Suction via nasogastric tube Fluids given by vein Surgery for strangulation Sometimes ... nose and placed in the stomach (called a nasogastric tube) or into the intestine. Suction is applied to ...

  17. Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

    DEFF Research Database (Denmark)

    Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel

    2011-01-01

    ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes...... in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumor. METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumor......, to assess the associations of twelve loci with breast cancer tumor characteristics. Associations were evaluated using a retrospective cohort approach. RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for eleven loci in both BRCA1 and BRCA2 carriers. Among...

  18. Differentiated thyroid carcinoma and intestinal polyposis syndromes.

    Science.gov (United States)

    Triggiani, Vincenzo; Angelo Giagulli, Vito; Tafaro, Angela; Resta, Francesco; Sabba, Carlo; Licchelli, Brunella; Guastamacchia, Edoardo

    2012-12-01

    Familial Adenomatous Polyposis, Cowden's Syndrome, and Peutz-Jeghers Syndrome are well known as Intestinal Polyposis Syndromes, inherited conditions characterized by the development of polyps of the gastro-intestinal tract in association with extra-intestinal manifestations, in particular malignant tumors at different sites. Thyroid carcinoma is sometimes a part of the clinical picture of these syndromes. The aim of this paper is to review the literature dealing with the association between differentiated thyroid carcinomas and Intestinal Polyposis Syndromes in order to point out peculiar aspects, providing suggestions for the screening and the management of thyroid tumors in these patients.

  19. Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease

    Science.gov (United States)

    2016-09-01

    evaluating the effects of these changes on intestinal susceptibility to inflammatory disease. 15. SUBJECT TERMS Radiation, microbiome , mycobiome...immune cells associated with the intestine and their interactions with the normal microbial contents of the gut. 2. KEYWORDS Radiation, microbiome ... microbiome following TBI. At the end of the experiment, we also harvested the intestines and mesenteric lymph nodes for multiparametric flow cytometry and

  20. Intestine transplantation

    Directory of Open Access Journals (Sweden)

    Tadeja Pintar

    2011-02-01

    Conclusion: Intestine transplantation is reserved for patients with irreversible intestinal failure due to short gut syndrome requiring total paranteral nutrition with no possibility of discontinuation and loss of venous access for patient maintenance. In these patients complications of underlying disease and long-term total parenteral nutrition are present.

  1. Intestinal Ischemia

    Science.gov (United States)

    ... weight loss Intestinal ischemia Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  2. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors

    DEFF Research Database (Denmark)

    Melin, Beatrice S; Barnholtz-Sloan, Jill S; Wrensch, Margaret R.

    2017-01-01

    Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified fi...

  3. Genotype versus phenotype: conflicting results in mapping a lung tumor susceptibility locus to the G7c recombination interval in the mouse MHC class III region

    NARCIS (Netherlands)

    van Kooij, M.; de Groot, K.; van Vugt, H.; Aten, J.; Snoek, M.

    2001-01-01

    Susceptibility to chemically induced lung tumorigenesis has previously been mapped to a genomic interval of 27 kb in the MHC class III region of the mouse using two H2 (a/b) intra- H2 recombinants, B10.A(1R) and B10.A(2R). Three genes are located within this interval, G7e (encoding a viral envelope

  4. Intestinal Coccidia

    OpenAIRE

    MJ Ggaravi

    2007-01-01

    Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycl...

  5. Small Intestine Disorders

    Science.gov (United States)

    ... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.

  6. Novel loci controlling lymphocyte proliferative response to cytokines and their clustering with loci controlling autoimmune reactions, macrophage function and lung tumor susceptibility

    Czech Academy of Sciences Publication Activity Database

    Lipoldová, Marie; Havelková, Helena; Badalová, Jana; Demant, P.

    2005-01-01

    Roč. 114, č. 3 (2005), s. 394-399 ISSN 0020-7136 R&D Projects: GA ČR(CZ) GA310/03/1381 Grant - others:European Commission(XE) CIPA-CT940040; Howard Hughes Medical Institute(US) 55000323 Institutional research plan: CEZ:AV0Z5052915 Keywords : lymphocyte activation * interleukin * lung cancer susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.700, year: 2005

  7. Loss of HLTF function promotes intestinal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sandhu Sumit

    2012-03-01

    Full Text Available Abstract Background HLTF (Helicase-like Transcription Factor is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown. Results To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apcmin/+ mutant background, Hltf- deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf -/-/Apcmin/+ mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apcmin/+ mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased. Conclusion Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.

  8. Spectrum of Intestinal Neoplasms: A study of 400 cases

    Directory of Open Access Journals (Sweden)

    Aminder Singh

    2015-02-01

    Full Text Available Objective: The present study is a five-year analysis of all the tumors of small and large intestine received in the Pathology Department of Dayanand Medical College and Hospital, Ludhiana. Methods: All the cases were grossly and microscopically examined and were staged according to Astler Coller Staging and classified and subtyped according to WHO classification. The important differences between the small and large intestine tumors were also analyzed. Results: There were 400 cases out of which 356 were in large intestine while 44 were in the small intestine. There were only 56 benign neoplasms while 344 were malignant tumors. Adenomas were the most common benign tumors while majority of malignant tumors were adenocarcinomas. Lymphomas, mesenchymal tumors, and carcinoid tumors were much more common in a small intestine as compared to large intestine. Majority of adenocarcinomas were located in the large intestine with most of them being moderately differentiated having Astler Coller Stage B II. Mucinous carcinomas had the worst prognosis as compared to adenocarcinomas. Anal canal had mainly squamous cell carcinomas. Conclusions: Tumors of large intestine were much commoner than of small intestine. There was a higher incidence of tumor in males with M:F ratio of 2.2:1. Mean age of presentation of benign tumor was younger, i.e., 32.6 years when compared to 54.5 years for malignant tumors. Tubular adenoma was the most common benign tumor and adenocarcinoma the commonest malignant neoplasm. [J Interdiscipl Histopathol 2015; 3(1.000: 19-23

  9. Immediate postconditioning during reperfusion attenuates intestinal injury.

    Science.gov (United States)

    Liu, Ke-Xuan; Li, Yun-Sheng; Huang, Wen-Qi; Chen, Shu-Qing; Wang, Zhong-Xin; Liu, Jia-Xin; Xia, Zhengyuan

    2009-05-01

    To test the hypothesis that immediate but not delayed ischemic postconditioning (IPo) during reperfusion attenuates intestinal injury, and that ischemic preconditioning (IPC) and IPo may confer synergy in intestinal protection. Prospective laboratory animal study with concurrent control. Adult Sprague-Dawley rats. Intestinal ischemia/reperfusion (II/R) injury in rats was produced by clamping superior mesenteric artery for 60 min followed by 60 min reperfusion; IPC was elicited by 10 min ischemia and 10 min reperfusion before index ischemia; IPo was performed by three cycles of 30 s reperfusion and 30 s ischemia initiated either immediately at the onset of reperfusion (IPo) or after reperfusion for 3 min (delayed-IPo). Combination of IPC and IPo was performed by combining both protocols. Intestinal ischemia/reperfusion resulted in significant intestinal injury evidenced as significant increase in Chiu's scores and wet-to-dry intestine weight ratio accompanied with increases in plasma levels of tumor necrosis factor-alpha and interleukin-6, as well as increases in the intestinal tissue lipid peroxidation product malonediadehyde and myeloperoxidase activity as compared to control animals (all P IPo or their combination (P IPo (P > 0.05). IPC and IPo showed synergistic protection compared with either protocol alone. Ischemic postconditioning reduces intestinal injury, in part, by inhibiting oxidative injury, neutrophils filtration and proinflammatory response. The early period of reperfusion is critical to intestinal protection by IPo, and intestinal protection with IPo can be enhanced by IPC.

  10. Highly stable microwave susceptible agents via encapsulation of Ti-mineral superfine powders in urea-formaldehyde resin microcapsules for tumor hyperthermia therapy

    Science.gov (United States)

    Long, Dan; Mao, Jingsong; Liu, Tianlong; Fu, Changhui; Tan, Longfei; Ren, Xiangling; Shi, Haitang; Su, Hongying; Ren, Jun; Meng, Xianwei

    2016-05-01

    In this study, Ti-mineral superfine powders (Ti-MSP) encapsulated in urea-formaldehyde resin microcapsules (Ti-MSP@UF-MC) were successfully prepared via a one-step microemulsion method for the first time. Because of the strong confinement effects, the Ti-MSP@UF-MC possessed perfect microwave heating effects. The temperature was 9.3 °C higher than that of the saline solution, superior to UF-MC (no significant microwave heating effect, 0 °C) and Ti-MSP (5.1 °C). The Ti-MSP@UF-MC showed low toxicity and good biocompatibility via a series of studies, including a hemolysis study and the MTT assay in vitro and in vivo. When the concentration was below 1000 μg mL-1, the hemolysis rate was lower than 5% (hemolysis study). When the concentration was below 400 μg mL-1, the cell activity was higher than 80% (MTT assay). Moreover, the Ti-MSP@UF-MC exhibited an ideal CT imaging effect in vivo owing to the large molecular weight of Ti-MSP. The Ti-MSP@UF-MC showed a favorable microwave therapy effect in vivo. Using mice bearing H22 tumor cells as an animal model, the tumor suppression rate could reach 100%.

  11. Cytokines and intestinal inflammation.

    Science.gov (United States)

    Bamias, Giorgos; Cominelli, Fabio

    2016-11-01

    Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation. The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-α, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa-protective function in acute injury but proinflammatory effects during chronic inflammation. The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine-specific therapies.

  12. The mouse small eye mutant, Del(2)Sey3H, which deletes the putative tumor suppressor region of the radiation-induced acute myeloid leukemia is susceptible to radiation

    International Nuclear Information System (INIS)

    Nitta, Yumiko; Yoshida, Kazuko; Tanaka, Kimio; Peters, Jo; Cattanach, Bruce M.

    2003-01-01

    Radiation-induced murine acute myeloid leukemia (AML) is characterized by the chromosome 2 deletions. Standing on the hypothesis that an AML suppressor gene would locate on the chromosome 2, a deletion-wide screen was performed on radiation-induced AMLs by the fluorescence in situ hybridization (FISH) method. The hemizugous deletion of the D2Mit15, a marker DNA at the 49.0cM region from the centromere, associated with the AMLs in 97 out of the 105 cases (92.4%). As the deletion region was close to the region of human WAGR syndrome (MIM194072), the mouse small eye mutants could be the animal model for radiation-induced AMLs. The mutant, Del(2)Sey3H (Sey3H) was found to delete around the 49.0cM region by the allelic loss mapping. The Sey3H showed high susceptibility to radiation to develop tumors including the myeloid leukemia with shorter latency. These finding support the existence of a putative tumor suppressor gene responsible for the radiation-leukemogenesis near the D2Mit15 region. (author)

  13. Hereditary intestinal polyposis syndromes.

    Science.gov (United States)

    Dean, P A

    1996-01-01

    Colorectal cancer is one of the most common cancers in the world, with overall mortality exceeding 40% even with treatment. Effective efforts for screening and prevention are most likely to succeed in patient groups identified as high risk for colorectal cancer, most notably the hereditary intestinal polyposis syndromes. In these syndromes, benign polyps develop throughout the intestinal tract prior to the development of colorectal cancer, marking the patient and associated family for precancer diagnosis followed by either close surveillance or preventive treatment. This review article was undertaken to discuss the most recent developments in the knowledge of hereditary intestinal polyposis syndromes, emphasizing the clinical approach to diagnosis and treatment relative to preventing the development of cancer. The most common of the hereditary polyposis syndromes is familial adenomatous polyposis (FAP), which is characterized by the development of hundreds to thousands of adenomatous polyps in the colon followed at an early age by colorectal cancer. Colorectal cancer can be prevented in this autosomal dominant condition by prophylactic colectomy, though a risk for other tumors, including periampullary cancers, remains throughout life. Variant of FAP associated with fewer and smaller polyps (hereditary flat adenoma syndrome), or even CNS tumors (Turcot's syndrome) also carry this high risk of colorectal cancer. Hereditary hamartomatous polyposis syndromes such as juvenile polyposis and Peutz-Jeghers syndrome (also autosomal dominant) are characterized by less frequent polyps. Though these are generally benign polyps, they are also associated with a significant risk of colorectal and other cancers. Other polyposis syndromes, including neurofibromatosis and Cowden's disease, do not carry this increased risk of colorectal cancer, and therefore affect different treatment strategies. Analysis of genetic factors responsible for these and other hereditary syndromes with

  14. Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer.

    Directory of Open Access Journals (Sweden)

    Emily L Lowe

    2010-09-01

    Full Text Available Inflammatory bowel disease (IBD is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC integrity. However, the role of TLR2 in the development of colorectal cancer has not been studied. We utilized the AOM-DSS model for colitis-associated colorectal cancer (CAC in wild type (WT and TLR2(-/- mice. Colons harvested from WT and TLR2(-/- mice were used for histopathology, immunohistochemistry, immunofluorescence and cytokine analysis. Mice deficient in TLR2 developed significantly more and larger colorectal tumors than their WT controls. We provide evidence that colonic epithelium of TLR2(-/- mice have altered immune responses and dysregulated proliferation under steady-state conditions and during colitis, which lead to inflammatory growth signals and predisposition to accelerated neoplastic growth. At the earliest time-points assessed, TLR2(-/- colons exhibited a significant increase in aberrant crypt foci (ACF, resulting in tumors that developed earlier and grew larger. In addition, the intestinal microenvironment revealed significantly higher levels of IL-6 and IL-17A concomitant with increased phospho-STAT3 within ACF. These observations indicate that in colitis, TLR2 plays a protective role against the development of CAC.

  15. TTC7A mutations disrupt intestinal epithelial apicobasal polarity

    NARCIS (Netherlands)

    Bigorgne, Amélie E; Farin, Henner F; Lemoine, Roxane; Mahlaoui, Nizar; Lambert, Nathalie; Gil, Marine; Schulz, Ansgar; Philippet, Pierre; Schlesser, Patrick; Abrahamsen, Tore G; Oymar, Knut; Davies, E Graham; Ellingsen, Christian Lycke; Leteurtre, Emmanuelle; Moreau-Massart, Brigitte; Berrebi, Dominique; Bole-Feysot, Christine; Nischke, Patrick; Brousse, Nicole; Fischer, Alain; Clevers, Hans; de Saint Basile, Geneviève

    Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and

  16. Intestinal perforation secondary to metastasic lung carcinoma

    Directory of Open Access Journals (Sweden)

    M. C. Álvarez Sánchez

    2014-11-01

    Full Text Available Secondary symptomatic gastrointestinal metastases from lung primary tumor are rare. They can cause a variety of clinical conditions such as perforation, obstruction and bleeding. Intestinal perforations of intestinal metastases have a very poor prognosis. We present a case of a patient with metastatic lung cancer who presents with intestinal perforation and pneumoperitoneum. A 67 year old male, immunosuppressed and smoker is diagnosed with acute abdomen secondary to perforation of a tumor of the terminal ileum, as well as three other similar injuries. Resection and anastomosis. The patient died two months after surgery. The final pathological diagnosis supports epidermoidide poorly differentiated lung carcinoma. It was concluded that given an intestinal perforation in a patient diagnosed with lung carcinoma, it shouldn´t be excluded the metastases origen . Surgery is a purely palliative procedure.

  17. Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0300 TITLE: Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER Effects of Radiation on the Microbiota and Intestinal Inflammatory Disease 5b. GRANT NUMBER W81XWH-15-1-0300 5c...changes in the microbiota on intestinal susceptibility to inflammatory disease . 15. SUBJECT TERMS Radiation, microbiome, mycobiome, colitis, cancer 16

  18. Gene expression profiling of chicken intestinal host responses

    NARCIS (Netherlands)

    Hemert, van S.

    2007-01-01

    Chicken lines differ in genetic disease susceptibility. The scope of the research described in this thesis was to identify genes involved in genetic disease resistance in the chicken intestine. Therefore gene expression in the jejunum was investigated using a microarray approach. An intestine

  19. Brain tumors and syndromes in children

    NARCIS (Netherlands)

    Bleeker, Fonnet E.; Hopman, Saskia M. J.; Merks, Johannes H. M.; Aalfs, Cora M.; Hennekam, Raoul C. M.

    2014-01-01

    (Brain) tumors are usually a disorder of aged individuals. If a brain tumor occurs in a child, there is a possible genetic susceptibility for this. Such genetic susceptibilities often show other signs and symptoms. Therefore, every child with a brain tumor should be carefully evaluated for the

  20. Intestinal pseudo-obstruction

    Science.gov (United States)

    Primary intestinal pseudo-obstruction; Acute colonic ileus; Colonic pseudo-obstruction; Idiopathic intestinal pseudo-obstruction; Ogilvie syndrome; Chronic intestinal pseudo-obstruction; Paralytic ileus - pseudo-obstruction

  1. Intestinal myiasis

    Directory of Open Access Journals (Sweden)

    U S Udgaonkar

    2012-01-01

    Full Text Available Purpose: Intestinal myiasis is a condition when the fly larvae inhabit the gastrointestinal tract and are passed out in faeces. This type of infestation results when eggs or larvae of the fly, deposited on food are inadvertently taken by man. They survive the unfavourable conditions within the gastrointestinal tract and produce disturbances, which may vary from mild to severe. The condition is not uncommon and is often misdiagnosed as pinworm infestation. Correct diagnosis by the clinical microbiologist is important to avoid unnecessary treatment. Materials and Methods: We had 7 cases of intestinal myiasis. In 2 cases the larvae were reared to adult fly in modified meat and sand medium (developed by Udgaonkar. This medium is simple and can be easily prepared in the laboratory. Results: Of the 7 larvae, 5 were Sarcophaga haemorrhoidalis, 1 Megaselia species and 1 was identified as Muscina stabulans. Conclusions: S. haemorrhoidalis was the commonest maggot involved. A high index of suspicion is required for clinical diagnosis when the patient complains of passing wriggling worms in faeces for a long period without any response to antihelminthics. The reason for long duration of illness and recurrence of infestation is baffling. The nearest to cure was colonic wash. We feel prevention is of utmost importance, which is to avoid eating food articles with easy access to flies.

  2. Measures to minimize small intestine injury in the irradiated pelvis

    International Nuclear Information System (INIS)

    Green, N.; Iba, G.; Smith, W.R.

    1975-01-01

    Small intestine injury causes long-term suffering and high mortality. Five of 187 of our patients had developed serious small intestine injury. Four patients had corrective surgery. Three patients died. All were women. Subsequently, all patients who received definitive pelvic irradiation had small intestine roentgenograms to determine its location and mobility. Female patients, thin patients, and elderly patients had larger amounts of small intestine in the whole pelvis, a deeper cul de sac, and a greater incidence of relatively immobile small intestine. Patients with relatively immobile small intestine in the treatment field may be predisposed to injury. There was no relationship of the incidence of relatively immobile small intestine to prior pelvic surgery. We used the findings from the small intestine roentgenograms to modify individually the radiotherapy regimen so as to minimize the risk for small intestine injury. Patients were placed in the prone position to displace the small intestine out of the treatment fields used for booster dose irradiation. The treatment field was modified to exclude the small intestine. The total tumor dose delivered was determined by expectations for cure vs complications. To date, none of the patients in this study group has developed small intestine injury. Cadaver studies showed the feasibility of elective shortening of the pelvic cul de sac. The small intestine can be displaced away from the bladder, prostate, or cervix. (U.S.)

  3. Is tumor necrosis factor - 376a promoter polymorphism associated with susceptibility to multiple sclerosis? ¿El polimorfismo-376A del promotor del gen del factor de necrosis tumoral se asocia con una mayor susceptibilidad a padecer esclerosis múltiple?

    Directory of Open Access Journals (Sweden)

    Marcelo A. Kauffman

    2007-10-01

    Full Text Available A single nucleotide polymorphism (SNP at position -376 of the tumor necrosis factor á gene (TNFA has been associated with susceptibility to multiple sclerosis (MS in Spain. However, no association was found in populations from the USA and The Netherlands. Here we investigate the association between the TNFA - 376A SNP and MS susceptibility in Argentinean patients with MS. The A/G genotype was found in 4.4% of patients (n=90 and in 4.8% of healthy individuals (n=84; p=0.92; odds ratio=0.93; confidence interval: 0.23- 3.84. Thus, no significant differences in genotype and allele frequencies were found between healthy individuals and patients with MS in Argentina.Un polimorfismo de nucleótido único (SNP, por sus iniciales en inglés en la posición -376 del gen codificante del factor de necrosis tumoral á (TNFA ha sido asociado en España con un mayor riesgo a padecer esclerosis múltiple (EM. Sin embargo, esta asociación no fue encontrada en estudios hechos en poblaciones provenientes de los EE.UU. y Holanda. Aquí investigamos la asociación entre el SNP TNFA -376A y el desarrollo de EM en una población de pacientes argentinos con EM. El genotipo A/G fue encontrado en 4.4% de los pacientes (n=90 y en 4.8% de los controles sanos (n=84; p=0.92; odds ratio=0.93; intervalo de confianza: 0.23-3.84. En consecuencia, no encontramos diferencias en las frecuencias alélicas y genotípicas entre los sujetos enfermos y los controles sanos en Argentina.

  4. Intestinal Failure (Short Bowel Syndrome)

    Science.gov (United States)

    Intestinal Failure (Short Bowel Syndrome) What is intestinal failure? Intestinal failure occurs when a significant portion of the small ... intestine does. Who is at risk for intestinal failure? N Babies (usually premature) who have had surgery ...

  5. Degree of Tissue Differentiation Dictates Susceptibility to BRAF-Driven Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Kevin Tong

    2017-12-01

    Full Text Available Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2, stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.

  6. Angiographic diagnosis of hemorrhage tumours of the small intestine

    International Nuclear Information System (INIS)

    Vadon, G.; Ehngloner, L.; Petri, K.

    1980-01-01

    2 angiographic investigations in small intestine tumors, accompanied with hemorrhage are considered. Conclusion is made that the most suitable moment for estimation of small intestine hemorrhage, according to the proper and literature data, is selective angiography. Wide application of the technique for preoperative detection of gastro-inestinal hemorrhage is recommended

  7. Intestinal mucus accumulation in a child with acutemyeloblastic leukemia

    Directory of Open Access Journals (Sweden)

    Namık Özbek

    2009-12-01

    Full Text Available Intestinal mucus accumulation is a very rare situation observed in some solid tumors, intestinal inflammation, mucosal hyperplasia, elevated intestinal pressure, and various other diseases. However, it has never been described in acute myeloblastic leukemia. The pathogenesis of intestinal mucus accumulation is still not clear. Here, we report a 14-year-old girl with acute myeloblastic leukemia and febrile neutropenia in addition to typhlitis. She was also immobilized due to joint contractures of the lower extremities and had intestinal mucus accumulation, which was, at first, misdiagnosed as intestinal parasitosis. We speculate that typhlitis, immobilization and decreased intestinal motility due to usage of antiemetic drugs might have been the potential etiologic factors in this case. However, its impact on prognosis of the primary disease is unknown.

  8. Radiological manifestations of intestinal tuberculosis

    International Nuclear Information System (INIS)

    Im, Jae Hoon

    1974-01-01

    Radiological findings of 87 cases of intestinal tuberculosis are analyzed and presented. The diagnosis was based on histopathology in 29 cases, and on clinical ground and radiological findings in 58 cases. The radio of male and female patients was 4:6, and peak incidence is between 10 and 30. Abdominal pain, diarrhea, weight loss, fever and general weakness are frequent symptoms, and tenderness of abdomen, ascites with abdominal distension, malnutrition and emaciation are frequent signs of the patients. Laboratory investigation reveal anemia, raised ESR, hypoalbuminaemia and positive occult blood reaction in the stool in most of the patients. Chest film show activity pulmonary tuberculosis in only 1/3 patients. There is no pathognomonic radiological findings in intestinal tuberculosis and their manifestations are protean, and differentiation from other inflammatory diseases and malignant tumors in gastrointestinal tract is very difficult on radiological ground alone. However, in patients with complaining vague abdominal symptoms and signs, the radiological diagnosis is most certain means in the decision of existence of organic lesion and suggestion of tuberculosis in the gastrointestinal tract and its extent as yet. Multiplicity of the lesion, involvement of adjacent organ such as peritoneum or mesenteric lymph nodes, typical nodularity or irregularity of mesenteric border and existence of active pulmonary tuberculosis are the suggestive findings of intestinal tuberculosis. In the diagnosis of inflammatory disease or malignant tumor of gastrointestinal tract, the possibility of tuberculosis should be borne in mind, and vice versa

  9. Cftr Modulates Wnt/β-Catenin Signaling and Stem Cell Proliferation in Murine Intestine

    Directory of Open Access Journals (Sweden)

    Ashlee M. Strubberg

    2018-01-01

    Conclusions: CF intestine shows increased ISC proliferation and Wnt/β-catenin signaling. Loss of Cftr increases pHi in ISCs, which stabilizes the plasma membrane association of the Wnt transducer Dvl, likely facilitating Wnt/β-catenin signaling. Absence of Cftr-dependent suppression of ISC proliferation in the CF intestine may contribute to increased risk for intestinal tumors.

  10. Differentiation of brain abscesses from glioblastomas and metastatic brain tumors: comparisons of diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MR imaging before and after mathematic contrast leakage correction.

    Science.gov (United States)

    Toh, Cheng Hong; Wei, Kuo-Chen; Chang, Chen-Nen; Ng, Shu-Hang; Wong, Ho-Fai; Lin, Ching-Po

    2014-01-01

    To compare the diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MRI before and after mathematic contrast leakage correction in differentiating pyogenic brain abscesses from glioblastomas and/or metastatic brain tumors. Cerebral blood volume (CBV), leakage-corrected CBV and leakage coefficient K2 were measured in enhancing rims, perifocal edema and contralateral normal appearing white matter (NAWM) of 17 abscesses, 19 glioblastomas and 20 metastases, respectively. The CBV and corrected CBV were normalized by dividing the values in the enhancing rims or edema to those of contralateral NAWM. For each study group, a paired t test was used to compare the K2 of the enhancing rims or edema with those of NAWM, as well as between CBV and corrected CBV of the enhancing rims or edema. ANOVA was used to compare CBV, corrected CBV and K2 among three lesion types. The diagnostic performance of CBV and corrected CBV was assessed with receiver operating characteristic (ROC) curve analysis. The CBV and correction CBV of enhancing rim were 1.45±1.17 and 1.97±1.01 for abscesses, 3.85±2.19 and 4.39±2.33 for glioblastomas, and 2.39±0.90 and 2.97±0.78 for metastases, respectively. The CBV and corrected CBV in the enhancing rim of abscesses were significantly lower than those of glioblastomas and metastases (P = 0.001 and P = 0.007, respectively). In differentiating abscesses from glioblastomas and metastases, the AUC values of corrected CBV (0.822) were slightly higher than those of CBV (0.792). Mathematic leakage correction slightly increases the diagnostic performance of CBV in differentiating pyogenic abscesses from necrotic glioblastomas and cystic metastases. Clinically, DSC perfusion MRI may not need mathematic leakage correction in differentiating abscesses from glioblastomas and/or metastases.

  11. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  12. Intestinal microbiome landscaping

    NARCIS (Netherlands)

    Shetty, Sudarshan A.; Hugenholtz, Floor; Lahti, Leo; Smidt, Hauke; Vos, de Willem M.

    2017-01-01

    High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss

  13. Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

    Directory of Open Access Journals (Sweden)

    Eliane von Klitzing

    Full Text Available Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction.Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based methods. At day 7 post infection (p.i. with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney and systemic compartments including spleen and serum.With respect to the intestinal microbiota composition "humanized" mice display

  14. TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis

    Science.gov (United States)

    Noti, Mario; Corazza, Nadia; Mueller, Christoph; Berger, Barbara

    2010-01-01

    Although tumor necrosis factor (α) (TNF) exerts proinflammatory activities in a variety of diseases, including inflammatory bowel disease, there is increasing evidence for antiinflammatory actions of TNF. In contrast, glucocorticoids (GCs) are steroid hormones that suppress inflammation, at least in part by regulating the expression and action of TNF. We report that TNF induces extraadrenal production of immunoregulatory GCs in the intestinal mucosa during acute intestinal inflammation. The absence of TNF results in a lack of colonic GC synthesis and exacerbation of dextran sodium sulfate–induced colitis. TNF seems to promote local steroidogenesis by directly inducing steroidogenic enzymes in intestinal epithelial cells. Therapeutic administration of TNF induces GC synthesis in oxazolone-induced colitis and ameliorates intestinal inflammation, whereas inhibition of intestinal GC synthesis abrogates the therapeutic effect of TNF. These data show that TNF suppresses the pathogenesis of acute intestinal inflammation by promoting local steroidogenesis. PMID:20439544

  15. Small Intestine Cancer Treatment

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  16. Surgical treatment of colorectal cancer complicated with acute intestinal obstruction

    Directory of Open Access Journals (Sweden)

    S. N. Schaeva

    2016-01-01

    Full Text Available Background. The main reason for urgent complications of colon cancer is an acute intestinal obstruction (AIO. This is complex pathological condition in 90 % of cases caused by colorectal cancer (CRC.Objective – to evaluate radicality of the performed operations in complicated colorectal cancer in general surgical hospitals. Dependence of the severity of intestinal obstruction by tumor localization, its morphological characteristics, determine dependence of the type of the surgical operation performed on the severity of intestinal obstruction.Materials and methods. We have studied the data on 667 patients with colorectal cancer complicated by acute intestinal obstruction. These patients were treated in the period from 2001 to 2013 in general surgical hospital in the territory of Smolensk and Smolensk region. For the processing of the obtained results we have used software Statistica 6.1. Differences were considered statistically at p ≤ 0.05.Results. All the patients were divided into 3 groups by the expression of intestinal obstruction. Group 1 (n = 279 consisted of patients with the presence of decompensated intestinal obstruction (DIO, group 2 (n = 313 consisted of patients with subcompensated intestinal obstruction (SIO, group 3 (n = 75 included patients with compensated intestinal obstruction (CIO. In case of tumor localization in right halfof the colon we most commonly observed clinical picture of acute development of decompensated intestinal obstruction (p = 0.041. Subcompensated intestinal obstruction prevailed in case of tumor localization in left half of the colon and rectal localization. In general surgical hospitals it is not always possible to speak about radicality of surgical treatment, as in a large number of cases (62.5 % the number of examined lymph nodes was less than 4. When DIO patients are admitted in the clinic, the percentage of singlestage operations is equal to 7.5 % (n = 21. In case of DIO and SIO there was a high

  17. Mediastinal tumor

    Science.gov (United States)

    Thymoma - mediastinal; Lymphoma - mediastinal ... mediastinal tumors in adults occur in the anterior mediastinum. They are usually cancerous (malignant) lymphomas, germ cell tumors, or thymomas. These tumors are ...

  18. Radiologic diagnosis of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Lunderquist, A.

    1989-01-01

    The radiologic work-up of a patient with a pancreatic endocrine tumor should follow a strict course. Ultrasonography as the first procedure should be followed by angiography, if possible. Negative ultrasonography should be followed by computed tomography (CT), which, whether positive or negative, is supplemented by angiography. Negative CT and angiography is followed by transhepatic venous sampling. In patients with suspected liver metastases from intestinal and pancreatic endocrine tumors, angiography may reveal more metastases than CT and ultrasonography. (orig.)

  19. Research Progress of Intestinal Microbiota in Inflammatory Bowel Diseases

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    Shao-shun YE

    2017-06-01

    Full Text Available Inflammatory bowel disseases (IBD are chronic recurrent diseases occurring in the gastrointestinal tract, mainly including ulcerative colitis (UC and Crohn’s disease (CD. At present, the etiological factors and mechanism of IBD are still unclear yet. However, it is widely believed that IBD is caused by immune dysfunction, genetic factors, gut barrier dysfuction and dysbacteriosis, change of dietary structure, use of antibiotics, smoking, and environment. Studies suggest that breaking the accurate balance between host and intestinal microbiota in patients with IBD can trigger immuno-inflammatory responses in genetically susceptible individuals. Therefore, regulating intestinal microbiota disturbance and recovery of intestinal homeostasis between host and intestinal microbiota become a new treatment direction for IBD. This article mainly reviewed research progress of intestinal microbiota in pathogenetic mechanism and treatment of IBD.

  20. Regionalized Development and Maintenance of the Intestinal Adaptive Immune Landscape

    DEFF Research Database (Denmark)

    Agace, William Winston; McCoy, Kathy D.

    2017-01-01

    The intestinal immune system has the daunting task of protecting us from pathogenic insults while limiting inflammatory responses against the resident commensal microbiota and providing tolerance to food antigens. This role is particularly impressive when one considers the vast mucosal surface...... and changing landscape that the intestinal immune system must monitor. In this review, we highlight regional differences in the development and composition of the adaptive immune landscape of the intestine and the impact of local intrinsic and environmental factors that shape this process. To conclude, we...... review the evidence for a critical window of opportunity for early-life exposures that affect immune development and alter disease susceptibility later in life....

  1. Human milk oligosaccharide effects on intestinal function and inflammation after preterm birth in pigs

    DEFF Research Database (Denmark)

    Rasmussen, Stine O.; Martin, Lena; Østergaard, Mette V.

    2017-01-01

    Human milk oligosaccharides (HMOs) may mediate prebiotic and anti-inflammatory effects in newborns. This is particularly important for preterm infants who are highly susceptible to intestinal dysfunction and necrotizing enterocolitis (NEC). We hypothesized that HMO supplementation of infant formu...

  2. Coagulation of sheep intestinal and prefemoral lymph.

    Science.gov (United States)

    Hanley, C A; Johnston, M G; Nelson, W

    1988-06-01

    We have determined the most suitable method for the automated analysis of the clotting parameters in sheep intestinal and prefemoral lymph as defined by the Activated Partial Thromboplastin Times (APTT; measure of intrinsic coagulation pathway) and the Prothrombin Times (PT; measure of extrinsic coagulation pathway). As opposed to optical density systems, the use of a Fibro-System Fibrometer was found to provide the most consistent assessment of coagulation with the endpoint being the time to fibrin strand formation. We measured APTT in sheep intestinal and prefemoral lymph of 59.78 +/- 7.69 seconds and 51.03 +/- 10.49 seconds respectively. These values were more prolonged than those obtained from sheep blood plasma but only in the case of intestinal lymph were the differences significant (p less than 0.025). Human blood APTT values were significantly less than both sheep blood (p less than 0.05) and sheep intestinal (p less than 0.001) and prefemoral lymph (p less than 0.01). PT values were found to be 21.56 +/- 1.14 seconds in intestinal and 22.00 +/- 1.88 seconds in prefemoral lymph. These values were also significantly greater than those obtained from sheep blood (both p less than 0.001). Human blood PTs were significantly less than both sheep blood (p less than 0.001) and intestinal and prefemoral lymph (both p less than 0.001). Measurement of APTT and PT values in intestinal lymph and PT determinations in prefemoral lymph were not affected by storage in the refrigerator or freezer. There was some indication that APTT values in prefemoral samples were susceptible to storage artifacts; however, the differences in coagulation times were not significant.

  3. Gastric and intestinal surgery.

    Science.gov (United States)

    Fossum, Theresa W; Hedlund, Cheryl S

    2003-09-01

    Gastric surgery is commonly performed to remove foreign bodies and correct gastric dilatation-volvulus and is less commonly performed to treat gastric ulceration or erosion, neoplasia, and benign gastric outflow obstruction. Intestinal surgery, although commonly performed by veterinarians, should never be considered routine. The most common procedures of the small intestinal tract performed in dogs and cats include enterotomy and resection/anastomosis. Surgery of the large intestine is indicated for lesions causing obstruction, perforations, colonic inertia, or chronic inflammation.

  4. Radiation susceptibility of the mouse smalleye mutants, Del(2)Sey3Hpax6 and Del(2)Sey4Hpax6, which delete the chromosome 2 middle regions

    International Nuclear Information System (INIS)

    Nitta, Y.; Hoshi, M.; Yoshida, K.; Yamate, J.; Peters, J.; Cattanach, B.M.

    2003-01-01

    Full text: LOH at the chromosome 2 middle regions is common in the radiation-induced mouse acute myeloid leukemia (AML). To identify the suppressor or the modifier gene of AML at this region, the mouse deletion mutants, Del(2)Sey3H pax6 and Del(2)Sey3H pax6 could be the good models, as they deleted the chromosome 2 middle regions hemizygously. The allele of the partially deleted chromosome 2 was paternally generated and maintained hemizygously. The exact deleted regions of the two mutants were mapped by the PCR-based detection of polymorphism of the STS markers. The length of the deletions was 3.01Mb and 10.11MB for Del(2)Sey3H pax6 and Del(2)Sey3H pax6 , respectively. For the induction of tumors, a radiation, 3.0Gy of Co-60 and a chemical carcinogen, N-methyl-N-nitrosourea were applied to the mutants. Their tumorigenicity was compared with those of control as well as normal sibs by the Kaplan-Meier analysis. Both mutants were found to predispose to small intestinal tumors. Intestinal tumors developed spontaneously with the incidence of 30%. The radiation and the chemical accelerated the malignancy and increased the incidence of the intestinal tumors. Radiation shortened the latency of AML development in the Del(2)Sey3H pax6 mutant but not in the Del(2)Sey3H pax6 . Spontaneous AML has not been observed, nor any increase in the incidence of induced AMLs. The commonly deleted region of the two mutants, the 3.01Mb region, must be critical for the development of tumors and the high susceptibility to radiation. The role of Pax6 gene should be considered in the intestinal tumorigenesis, as the Pax6 gene plays an important role in the pancreas development during the embryogenesis. The Wt1, a tumor suppressor gene, which is deleted hemizygously in these mutants as well. The screening of homozygous deletion has been started using the induced as well as spontaneously developed tumors

  5. Intestinal parasites and tuberculosis

    Directory of Open Access Journals (Sweden)

    Anuar Alonso Cedeño-Burbano

    2017-10-01

    Conclusions: The available evidence was insufficient to affirm that intestinal parasites predispose to developing tuberculous. The studies carried out so far have found statistically insignificant results.

  6. A hypermorphic epithelial β-catenin mutation facilitates intestinal tumorigenesis in mice in response to compounding WNT-pathway mutations

    Directory of Open Access Journals (Sweden)

    Michael Buchert

    2015-11-01

    Full Text Available Activation of the Wnt/β-catenin pathway occurs in the vast majority of colorectal cancers. However, the outcome of the disease varies markedly from individual to individual, even within the same tumor stage. This heterogeneity is governed to a great extent by the genetic make-up of individual tumors and the combination of oncogenic mutations. In order to express throughout the intestinal epithelium a degradation-resistant β-catenin (Ctnnb1, which lacks the first 131 amino acids, we inserted an epitope-tagged ΔN(1-131-β-catenin-encoding cDNA as a knock-in transgene into the endogenous gpA33 gene locus in mice. The resulting gpA33ΔN-Bcat mice showed an increase in the constitutive Wnt/β-catenin pathway activation that shifts the cell fate towards the Paneth cell lineage in pre-malignant intestinal epithelium. Furthermore, 19% of all heterozygous and 37% of all homozygous gpA33ΔN-Bcat mice spontaneously developed aberrant crypt foci and adenomatous polyps, at frequencies and latencies akin to those observed in sporadic colon cancer in humans. Consistent with this, the Wnt target genes, MMP7  and Tenascin-C, which are most highly expressed in benign human adenomas and early tumor stages, were upregulated in pre-malignant tissue of gpA33ΔN-Bcat mice, but those Wnt target genes associated with excessive proliferation (i.e. Cdnn1, myc were not. We also detected diminished expression of membrane-associated α-catenin and increased intestinal permeability in gpA33ΔN-Bcat mice in challenge conditions, providing a potential explanation for the observed mild chronic intestinal inflammation and increased susceptibility to azoxymethane and mutant Apc-dependent tumorigenesis. Collectively, our data indicate that epithelial expression of ΔN(1-131-β-catenin in the intestine creates an inflammatory microenvironment and co-operates with other mutations in the Wnt/β-catenin pathway to facilitate and promote tumorigenesis.

  7. Usefulness of computed tomography enteroclysis in the intestinal tract

    International Nuclear Information System (INIS)

    Onoda, Hideko; Shimizu, Kensaku; Washida, Yasuo; Matsunaga, Naofumi; Higaki, Shingo; Hashimoto, Shinichi; Matsunaga, Takaharu; Sakaida, Isao

    2010-01-01

    The aim of this study was to evaluate computed tomography enteroclysis (CTE) of the small intestinal tract. A total of 36 patients underwent CTE for further examination of small intestinal disease. The indications were obscure gastrointestinal bleeding (OGIB) (n=16), suspected Crohn's disease (n=7), suspected and diagnosed by exclusion a small intestinal tumor (n=5), and others (n=8). Regarding OGIB, positive findings were observed in nine patients: angiodysplasia (n=2), suspected ileac tumor (n=2), colon cancer (n=1), colon diverticulosis and diverticulitis (n=2), Crohn's disease (n=1), and enteritis (n=1). As for Crohn's disease, hyperplasia of the small intestinal wall was shown in six patents. Positive findings of a small intestinal tumor were observed in two patients. In the 'others' category, colon diverticulitis was found in three patients and isolated dissection of the superior mesenteric artery in one of four patients with abdominal pain. Primary carcinoid was identified in the pancreas in one patient, with liver carcinoid metastasis in the remaining four patients. CT enteroclysis is a noninvasive method and useful approach in the diagnosis of small intestinal diseases. (author)

  8. Malignant Glomus Tumor of the Peritoneum: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Baleato-González, Sandra; García-Figueiras, Roberto; Trujillo-Ariza, Maria Virginia [Department of Radiology, Complexo Hospitalario Universitario de Santiago de Compostela, Choupana s/n, 15701 Santiago de Compostela (A Coruña) (Spain); Carrera-Álvarez, Juan Jose [Department of Pathology, Complexo Hospitalario Universitario de Santiago de Compostela, Choupana s/n, 15701 Santiago de Compostela (A Coruña) (Spain)

    2014-07-01

    Glomus tumors are usually benign tumors that occur in the skin and soft tissues of the extremities. Visceral locations, such as stomach, intestines or lung, are extremely rare because glomus bodies are rare or absent in these organs. This report describes our experience in a 47-year-old woman diagnosed with a peritoneal malignant glomus tumor. This finding has not been previously reported.

  9. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... ABSTRACT. Background: Adhesions after abdominal and pelvic surgery are a major cause of intestinal obstruction in the western world and the pathology is steadily gaining prominence in our practice. Objective: To determine the magnitude of adhesive intestinal obstruction; to determine the types.

  10. Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

    DEFF Research Database (Denmark)

    Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel

    2011-01-01

    ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtype...

  11. Intestinal Barrier and Behavior.

    Science.gov (United States)

    Julio-Pieper, M; Bravo, J A

    2016-01-01

    The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses. © 2016 Elsevier Inc. All rights reserved.

  12. Intestinal histoplasmosis in immunocompetent adults.

    Science.gov (United States)

    Zhu, Lin-Lin; Wang, Jin; Wang, Zi-Jing; Wang, Yi-Ping; Yang, Jin-Lin

    2016-04-21

    To present a retrospective analysis of clinical and endoscopic features of 4 cases of immunocompetent hosts with intestinal histoplasmosis (IH). Four immunocompetent adults were diagnosed with IH between October 2005 and March 2015 at West China Hospital of Sichuan University. Clinical and endoscopic characteristics were summarized and analyzed retrospectively. GMS (Gomori methenamine silver), PAS (periodic acid-Schiff) and Giemsa staining technique were used to confirm Histoplasma capsulatum(H. capsulatum). The symptoms, signs, endoscopic presentations, radiographic imaging, pathological stain results and follow-up are presented as tables and illustrations. The cases were male patients, ranging from 33 to 61 years old, and primarily presented with non-specific symptoms such as irregular fever, weight loss, abdominal pain and distention. Hepatosplenomegaly and lymphadenopathy were the most common signs. Endoscopic manifestations were localized or diffuse congestion, edema, ulcers, and polypoid nodules with central erosion involving the terminal ileum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum, similar to intestinal tuberculosis, tumor, and inflammatory bowel disease. Numerous yeast-like pathogens testing positive for PAS and GMS stains but negative for Giemsa were detected in the cytoplasm of the histiocytes, which were highly suggestive of H. capsulatum. Immunocompetent individuals suffering from histoplasmosis are rarely reported. It is necessary that gastroenterologists and endoscopists consider histoplasmosis as a differential diagnosis, even in immunocompetent patients.

  13. Contribution of genes polymorphism to susceptibility and outcome of ...

    African Journals Online (AJOL)

    Harapan Tumangger

    HMGB1, TLR, PAI-1, DEFB1, HSP and MMP-9 has contribution to susceptibility and outcome of sepsis in some research. .... inflammatory cytokine gene polymorphism to susceptibility and outcome of patients with systemic inflammation and sepsis. 2. Genes polymorphism and sepsis. 2.1. Tumor necrosis factor (TNF) a.

  14. Small intestinal diverticulum with bleeding: Case report and literature review.

    Science.gov (United States)

    Zhao, Lifang; Lu, Wei; Sun, Yinping; Liang, Junrong; Feng, Shanshan; Shi, Yongquan; Wu, Qiong; Wang, Jianhong; Wu, Kaichun

    2018-03-01

    Small intestinal diverticulum with bleeding is an important reason for obscure gastrointestinal bleeding (OGB) , in addition to tumor and vascular diseases. Small intestinal diverticulum with bleeding is difficult to detect by barium meal and angiographic methods and has been regarded as an important cause of obscure gastrointestinal tract bleeding in adolescents. Because of its complicated etiology and non-specific clinical manifestations, it is relatively difficult to detect small intestinal diverticulum with bleeding, especially in patients with a large amount of bleeding and hemodynamic instability. This retrospective study collects clinical statistics of 19 patients admitted to our hospital from January 2010 to December 2016. Patients who had small intestinal diverticulum patients with bleeding were included in this study. Patients who were taking anticoagulants were excluded DIAGNOSES:: Small intestinal diverticulum patients with bleeding. This retrospective study describes the clinical features of patients with small intestinal diverticulum whose main symptom was gastrointestinal bleeding and analyze the literature on this topic, with particular reference to the clinical characteristics, pathological features, and choice of examination methods. Small intestinal diverticulum with bleeding is a common cause of obscure gastrointestinal bleeding, but it is difficult to detect using normal examination methods. For patients with repeated gastrointestinal bleeding and no positive results found on gastroscopy and colonoscopy, endoscopy of the small intestine and CTE with contrast can be considered as a diagnostic modality.

  15. The morphological profile of small bowel tumors - our experience.

    Science.gov (United States)

    Mărgăritescu, Nicolae Dragoş; Ciobanu, Mircea Ovidiu; Nemeş, Răducu Nicolae; Ghelase, Ştefan Mugurel; Pleşea, Răzvan Mihail; Georgescu, Ion; Voinea, Bogdan; Pleşea, Iancu Emil; ChiuŢu, LuminiŢa Cristina

    2016-01-01

    The authors assessed the morphological profile of tumor masses belonging to the small bowel discovered in their daily practice. 31 tumor masses located in different segments of small intestine operated between 2002 and 2013 in the 1st Surgical Department, Emergency County Hospital of Craiova, Romania, were analyzed. The investigated parameters were: tumor location and number, tumor dimensions, gross assessment, tumor extension and histological assessment. Tumor masses belonging to small intestine were rare. They usually expressed by their complications. In many cases, they were placed at the extremities of the small intestine. They were usually small but sometimes large and developing outwards intestinal wall. Commonly they had a fungating and ulcerated appearance. They were rather of mesenchymal origin than epithelial. However, some of them were inflammatory pseudotumors. Almost all neoplastic proliferations had a malignant phenotype, most often with regional extension. Our series of tumors had a morphological profile somehow similar with the profile described in the literature but with some particularities: the polarization to the extremities of the intestinal segment, a significant number of large tumors, clinical expression through different complications, the balance inclined in favor of mesenchymal origin of tumors and the clear predominance of malignant aggressive phenotype.

  16. Mycotoxins and the intestine

    Directory of Open Access Journals (Sweden)

    Leon Broom

    2015-12-01

    Full Text Available Fungal biochemical pathways can yield various compounds that are not considered to be necessary for their growth and are thus referred to as secondary metabolites. These compounds have been found to have wide ranging biological effects and include potent poisons (mycotoxins. Mycotoxins invariably contaminate crops and (thus animal feeds. The intestine is the key link between ingested mycotoxins and their detrimental effects on the animal. Effects on the intestine, or intestinal environment, and immune system have been reported with various mycotoxins. These effects are almost certainly occurring across species. Most, if not all, of the reported effects of mycotoxins are negative in terms of intestinal health, for example, decreased intestinal cell viability, reductions in short chain fatty acid (SCFA concentrations and elimination of beneficial bacteria, increased expression of genes involved in promoting inflammation and counteracting oxidative stress. This challenge to intestinal health will predispose the animal to intestinal (and systemic infections and impair efficient digestion and absorption of nutrients, with the associated effect on animal productivity.

  17. Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

    DEFF Research Database (Denmark)

    Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel

    2011-01-01

    ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtype...... subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers....

  18. Intestinal Microbiota and the Innate Immune System - A Crosstalk in Crohn's Disease Pathogenesis.

    Science.gov (United States)

    Haag, Lea-Maxie; Siegmund, Britta

    2015-01-01

    Crohn's disease (CD) is a chronic, relapsing inflammatory disorder that can occur anywhere along the gastrointestinal tract. The precise etiology of CD is still unclear but it is widely accepted that a complex series of interactions between susceptibility genes, the immune system and environmental factors are implicated in the onset and perpetuation of the disease. Increasing evidence from experimental and clinical studies implies the intestinal microbiota in disease pathogenesis, thereby supporting the hypothesis that chronic intestinal inflammation arises from an abnormal immune response against the microorganisms of the intestinal flora in genetically susceptible individuals. Given that CD patients display changes in their gut microbiota composition, collectively termed "dysbiosis," the question raises whether the altered microbiota composition is a cause of disease or rather a consequence of the inflammatory state of the intestinal environment. This review will focus on the crosstalk between the gut microbiota and the innate immune system during intestinal inflammation, thereby unraveling the role of the microbiota in CD pathogenesis.

  19. Intestinal carcinogenesis of two food processing contaminants, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 5-hydroxymethylfurfural, in transgenic FVB min mice expressing human sulfotransferases.

    Science.gov (United States)

    Svendsen, Camilla; Meinl, Walter; Glatt, Hansruedi; Alexander, Jan; Knutsen, Helle K; Hjertholm, Hege; Rasmussen, Tone; Husøy, Trine

    2012-12-01

    Humans express sulfotransferases (SULTs) of the SULT1A subfamily in many tissues, whilst the single SULT1A gene present in rodents is mainly expressed in liver. The food processing contaminants, 5-hydroxymethylfurfural (HMF) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are bioactivated by human SULT1A1 and SULT1A2. FVB multiple intestinal neoplasia (Min) mice, which spontaneously develop tumors and flat aberrant crypt foci (ACF) in intestine, were crossed with transgenic FVB mice expressing human SULT1A1 and 1A2 (hSULT) in several tissues, giving rise to wild-type and Min mice with and without hSULT. One-week-old Min mice with or without hSULT were given HMF (375 or 750 mg/kg bw) or saline by gavage three times a week for 11 wk. In another experiment, the F1 generation received subcutaneous injections of 50 mg/kg bw PhIP or saline 1 wk before birth, and 1, 2, and 3 wk after birth. HMF did not affect the formation of tumors, but may have induced some flat ACF (incidence 15-20%) in Min mice with and without hSULT. No control mouse developed any flat ACF. With the limitation that these putative effects were weak, they were unaffected by hSULT expression. The carcinogenic effect of PhIP increased in the presence of hSULT, with a significant increase in both incidence (31-80%) and number of colonic tumors (0.4-1.3 per animal). Thus, intestinal expression of human SULT1A1 and 1A2 might increase the susceptibility to compounds bioactivated via this pathway implying that humans might be more susceptible than conventional rodent models. Copyright © 2011 Wiley Periodicals, Inc.

  20. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...... membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption...

  1. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption......A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...

  2. HIV-associated non-hodgkins lymphoma of the small intestines ...

    African Journals Online (AJOL)

    Malignant tumors of the small intestines are uncommon. In this paper, an unusual case of HIV-associated non-Hodgkin's lymphoma involving the small intestine, which atypically presented both clinically and by ultrasonographic examination as a mass suspected to be a slow-leaking ectopic pregnancy, is discussed.

  3. Intestinal Stem Cell Markers in the Intestinal Metaplasia of Stomach and Barrett's Esophagus.

    Directory of Open Access Journals (Sweden)

    Bo Gun Jang

    Full Text Available Gastric intestinal metaplasia (IM is a highly prevalent preneoplastic lesion; however, the molecular mechanisms regulating its development remain unclear. We have previously shown that a population of cells expressing the intestinal stem cell (ISC marker LGR5 increases remarkably in IM. In this study, we further investigated the molecular characteristics of these LGR5+ cells in IM by examining the expression profile of several ISC markers. Notably, we found that ISC markers-including OLFM4 and EPHB2-are positively associated with the CDX2 expression in non-tumorous gastric tissues. This finding was confirmed in stomach lesions with or without metaplasia, which demonstrated that OLFM4 and EPHB2 expression gradually increased with metaplastic progression. Moreover, RNA in situ hybridization revealed that LGR5+ cells coexpress several ISC markers and remained confined to the base of metaplastic glands, reminiscent to that of normal intestinal crypts, whereas those in normal antral glands expressed none of these markers. Furthermore, a large number of ISC marker-expressing cells were diffusely distributed in gastric adenomas, suggesting that these markers may facilitate gastric tumorigenesis. In addition, Barrett's esophagus (BE-which is histologically similar to intestinal metaplasia-exhibited a similar distribution of ISC markers, indicating the presence of a stem cell population with intestinal differentiation potential. In conclusion, we identified that LGR5+ cells in gastric IM and BE coexpress ISC markers, and exhibit the same expression profile as those found in normal intestinal crypts. Taken together, these results implicate an intestinal-like stem cell population in the pathogenesis of IM, and provide an important basis for understanding the development and maintenance of this disease.

  4. Culturing intestinal stem cells: applications for colorectal cancer research

    Directory of Open Access Journals (Sweden)

    Masayuki eFujii

    2014-06-01

    Full Text Available Recent advance of sequencing technology has revealed genetic alterations in colorectal cancer. The biological function of recurrently mutated genes has been intensively investigated through mouse genetic models and colorectal cancer cell lines. Although these experimental models may not fully reflect biological traits of human intestinal epithelium, they provided insights into the understanding of intestinal stem cell self-renewal, leading to the development of novel human intestinal organoid culture system. Intestinal organoid culture enabled to expand normal or tumor epithelial cells in vitro retaining their stem cell self-renewal and multiple differentiation. Gene manipulation of these cultured cells may provide an attractive tool for investigating genetic events involved in colorectal carcinogenesis.

  5. Tumor vaccines

    International Nuclear Information System (INIS)

    Frank, M.; Ihan, A.

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regiments. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tumor vaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which immune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system, what makes them poorly immunogenic or even tolerogenic. Novel immunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor- specific T-lymphocyte transfer and tumor specific monoclonal antibodies). (author)

  6. Diagnosis of intestinal and extra intestinal amoebiasis

    International Nuclear Information System (INIS)

    Lopez, Myriam Consuelo; Quiroz, Damian Arnoldo; Pinilla, Analida Elizabeth

    2007-01-01

    The objective is to carry out a review of the national and international literature as of the XXth century in order to update the advances for the diagnosis of complex odd Entamoeba histolytic / Entamoeba dispar and that of intestinal and extra intestinal amoebiasis that may be of use to the scientific community. As well as to unify the diagnostic criteria of this parasitosis known as a public health problem, and as a consequence of that, optimize the quality of population care. Data source: there was a systematic search for the scientific literature Publisher in Spanish and English since 1960 until today, this selection started on the first semester of 2006 until 2007, in the development of the line on intestinal and extra-intestinal amoebiasis of the Medical School of the National University of Colombia. A retrospective search process was carried out, systematically reviewing the most relevant articles as well as the products of this research line. In deciding how to make this article, there was a continuous search in different data bases such as Medline, SciELO and other bases in the library of the National University of Colombia, as well as other classical books related to the subject. For that purpose the terms amoebiasis, odd Entamoeba histolytic, Entamoeba, diagnosis, epidemiology, dysentery, amoebic liver abscess, were used. Studies selection: titles and abstracts were reviewed to select the original publications and the most representative ones related to this article's subject. Data extraction: the articles were classified according to the subject, the chronology and the authors according to the scientific contribution to solve the problem. Synthesis of the data: in the fi rst instance, a chronological critical analysis was carried out to order and synthesize the progress made in the diagnosis until confirmation of the experts' agreements in the field of amoebiasis was obtained throughout the world. Conclusion: this article summarizes what has taken place

  7. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  8. Mammary tumors

    International Nuclear Information System (INIS)

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported

  9. Computed tomography in gastrointestinal stromal tumors

    International Nuclear Information System (INIS)

    Ghanem, Nadir; Altehoefer, Carsten; Winterer, Jan; Schaefer, Oliver; Springer, Oliver; Kotter, Elmar; Langer, Mathias; Furtwaengler, Alex

    2003-01-01

    The aim of this study was to define the imaging characteristics of primary and recurrent gastrointestinal stromal tumors (GIST) in computed tomography with respect to the tumor size. Computed tomography was performed in 35 patients with histologically confirmed gastrointestinal stromal tumors and analyzed retrospectively by two experienced and independent radiologist. The following morphologic tumor characteristics of primary (n=20) and (n=16) recurrent tumors were evaluated according to tumor size, shape, homogeneity, density compared with liver, contrast enhancement, presence of calcifications, ulcerations, fistula or distant metastases and the anatomical relationship to the intestinal wall, and the infiltration of adjacent visceral organs. Small GIST ( 5-10 cm) demonstrated an irregular shape, inhomogeneous density on unenhanced and contrast-enhanced images, a combined intra- and extraluminal tumor growth with aggressive findings, and infiltration of adjacent organs in 9 primary diagnosed and 2 recurrent tumors. Large GIST (>10 cm), which were observed in 8 primary tumors and 11 recurrent tumors, showed an irregular margin with inhomogeneous density and aggressive findings, and were characterized by signs of malignancy such as distant and peritoneal metastases. Small recurrent tumors had a similar appearance as compared with large primary tumors. Computed tomography gives additional information with respect to the relationship of gastrointestinal stromal tumor to the gastrointestinal wall and surrounding organs, and it detects distant metastasis. Primary and recurrent GIST demonstrate characteristic CT imaging features which are related to tumor size. Aggressive findings and signs of malignancy are found in larger tumors and in recurrent disease. Computed tomography is useful in detection and characterization of primary and recurrent tumors with regard to tumor growth pattern, tumor size, and varied appearances of gastrointestinal stromal tumors, and indirectly

  10. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  11. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  12. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  13. Intestinal anisakidosis (anisakiosis).

    Science.gov (United States)

    Takei, Hidehiro; Powell, Suzanne Z

    2007-10-01

    A case of intestinal anisakidosis in a 42-year-old man in Japan is presented. His chief complaint was an acute onset of severe abdominal pain. Approximately 12 hours before the onset of this symptom, he had eaten sliced raw mackerel ("sashimi"). Upper endoscopy was unremarkable. At exploratory laparotomy, an edematous, diffusely thickened segment of jejunum was observed, which was resected. The postoperative course was uneventful. The segment of small intestine showed a granular indurated area on the mucosal surface, and microscopically, a helminthic larva penetrating the intestinal wall, which was surrounded by a cuff of numerous neutrophils and eosinophils, as well as diffuse acute serositis. A cross section of the larva revealed the internal structures, pathognomonic of Anisakis simplex. Although anisakidosis is rare in the United States, with the increasing popularity of Japanese cuisine, the incidence is expected to increase, and pathologists should be familiar with this disease.

  14. Intestinal failure: a review

    Science.gov (United States)

    Allan, Philip; Lal, Simon

    2018-01-01

    Intestinal failure (IF) is the inability of the gut to absorb necessary water, macronutrients (carbohydrate, protein, and fat), micronutrients, and electrolytes sufficient to sustain life and requiring intravenous supplementation or replacement. Acute IF (types 1 and 2) is the initial phase of the illness and may last for weeks to a few months, and chronic IF (type 3) from months to years. The challenge of caring for patients with IF is not merely the management of the underlying condition leading to IF or the correct provision of appropriate nutrition or both but also the prevention of complications, whether thromboembolic phenomenon (for example, venous occlusion), central venous catheter-related bloodstream infection, IF-associated liver disease, or metabolic bone disease. This review looks at recent questions regarding chronic IF (type 3), its diagnosis and management, the role of the multidisciplinary team, and novel therapies, including hormonal treatment for short bowel syndrome but also surgical options for intestinal lengthening and intestinal transplant. PMID:29399329

  15. Small intestine diverticuli

    International Nuclear Information System (INIS)

    Pomakov, P.; Risov, A.

    1991-01-01

    The routine method of contrast matter passage applied to 850 patients with different gastrointestinal diseases proved inefficient to detect any small-intestinal diverticuli. The following modiffications of the method have been tested in order to improve the diagnostic possibilities of the X-ray: study at short intervals, assisted passage, enteroclysm, pharmacodynamic impact, retrograde filling of the ileum by irrigoscopy. Twelve diverticuli of the small-intestinal loops were identified: 5 Meckel's diverticuli, 2 solitary of which one of the therminal ileum, 2 double diverticuli and 1 multiple diverticulosis of the jejunum. The results show that the short interval X-ray examination of the small intestines is the method of choice for identifying local changes in them. The solitary diverticuli are not casuistic scarcity, its occurrence is about 0.5% at purposeful X-ray investigation. The assisted passage method is proposed as a method of choice for detection of the Meckel's diverticulum. 5 figs., 3 tabs. 18 refs

  16. Chronic intestinal pseudoobstruction syndrome

    International Nuclear Information System (INIS)

    Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok

    1992-01-01

    Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome

  17. Small Intestinal Infections.

    Science.gov (United States)

    Munot, Khushboo; Kotler, Donald P

    2016-06-01

    Small intestinal infections are extremely common worldwide. They may be bacterial, viral, or parasitic in etiology. Most are foodborne or waterborne, with specific etiologies differing by region and with diverse pathophysiologies. Very young, very old, and immune-deficient individuals are the most vulnerable to morbidity or mortality from small intestinal infections. There have been significant advances in diagnostic sophistication with the development and early application of molecular diagnostic assays, though these tests have not become mainstream. The lack of rapid diagnoses combined with the self-limited nature of small intestinal infections has hampered the development of specific and effective treatments other than oral rehydration. Antibiotics are not indicated in the absence of an etiologic diagnosis, and not at all in the case of some infections.

  18. Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation

    Directory of Open Access Journals (Sweden)

    Andrea C. Lei-Leston

    2017-09-01

    Full Text Available Pattern recognition receptors (PRR, such as NOD-like receptors (NLRs, sense conserved microbial signatures, and host danger signals leading to the coordination of appropriate immune responses. Upon activation, a subset of NLR initiate the assembly of a multimeric protein complex known as the inflammasome, which processes pro-inflammatory cytokines and mediates a specialized form of cell death known as pyroptosis. The identification of inflammasome-associated genes as inflammatory bowel disease susceptibility genes implicates a role for the inflammasome in intestinal inflammation. Despite the fact that the functional importance of inflammasomes within immune cells has been well established, the contribution of inflammasome expression in non-hematopoietic cells remains comparatively understudied. Given that intestinal epithelial cells (IEC act as a barrier between the host and the intestinal microbiota, inflammasome expression by these cells is likely important for intestinal immune homeostasis. Accumulating evidence suggests that the inflammasome plays a key role in shaping epithelial responses at the host–lumen interface with many inflammasome components highly expressed by IEC. Recent studies have exposed functional roles of IEC inflammasomes in mucosal immune defense, inflammation, and tumorigenesis. In this review, we present the main features of the predominant inflammasomes and their effector mechanisms contributing to intestinal homeostasis and inflammation. We also discuss existing controversies in the field and open questions related to their implications in disease. A comprehensive understanding of the molecular basis of intestinal inflammasome signaling could hold therapeutic potential for clinical translation.

  19. The intestinal calcistat

    Directory of Open Access Journals (Sweden)

    M K Garg

    2013-01-01

    Full Text Available The main physiological function of vitamin D is maintenance of calcium homeostasis by its effect on calcium absorption, and bone health in association with parathyroid gland. Vitamin D deficiency (VDD is defined as serum 25-hydroxy vitamin D (25OHD levels <20 ng/ml. Do all subjects with VDD have clinical disease according to this definition? We hypothesize that there exist an intestinal calcistat, which controls the calcium absorption independent of PTH levels. It consists of calcium sensing receptor (CaSR on intestinal brush border, which senses calcium in intestinal cells and vitamin D system in intestinal cells. CaSR dampens the generation of active vitamin D metabolite in intestinal cells and decrease active transcellular calcium transport. It also facilitates passive paracellular diffusion of calcium in intestine. This local adaptation adjusts the fractional calcium absorption according the body requirement. Failure of local adaptation due to decreased calcium intake, decreased supply of 25OHD, mutation in CaSR or vitamin D system decreases systemic calcium levels and systemic adaptations comes into the play. Systemic adaptations consist of rise in PTH and increase in active vitamin D metabolites. These adaptations lead to bone resorption and maintenance of calcium homeostasis. Not all subjects with varying levels of VDD manifest with secondary hyperparathyroidism and decreased in bone mineral density. We suggest that rise in PTH is first indicator of VDD along with decrease in BMD depending on duration of VDD. Hence, subjects with any degree of VDD with normal PTH and BMD should not be labeled as vitamin D deficient. These subjects can be called subclinical VDD, and further studies are required to assess beneficial effect of vitamin D supplementation in this subset of population.

  20. Autophagy and tight junction proteins in the intestine and intestinal diseases

    Directory of Open Access Journals (Sweden)

    Chien-An A. Hu

    2015-09-01

    Full Text Available The intestinal epithelium (IE forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus and antigens. The apical intercellular tight junctions (TJ are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD, necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6

  1. Intestinal microbiota and ulcerative colitis.

    Science.gov (United States)

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Small intestine aspirate and culture

    Science.gov (United States)

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  3. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  4. Designing of peptides with desired half-life in intestine-like environment

    KAUST Repository

    Sharma, Arun

    2014-08-20

    Background: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life.Results: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides.Conclusion: In summary, this study describes a web server \\'HLP\\' that has been developed for assisting scientific

  5. Stages of Small Intestine Cancer

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  6. SRC activates TAZ for intestinal tumorigenesis and regeneration.

    Science.gov (United States)

    Byun, Mi Ran; Hwang, Jun-Ha; Kim, A Rum; Kim, Kyung Min; Park, Jung Il; Oh, Ho Taek; Hwang, Eun Sook; Hong, Jeong-Ho

    2017-12-01

    Proto-oncogene tyrosine-protein kinase Src (cSRC) is involved in colorectal cancer (CRC) development and damage-induced intestinal regeneration, although the cellular mechanisms involved are poorly understood. Here, we report that transcriptional coactivator with PDZ binding domain (TAZ) is activated by cSRC, regulating CRC cell proliferation and tumor formation, where cSRC overexpression increases TAZ expression in CRC cells. In contrast, knockdown of cSRC decreases TAZ expression. Additionally, direct phosphorylation of TAZ at Tyr316 by cSRC stimulates nuclear localization and facilitates transcriptional enhancer factor TEF-3 (TEAD4)-mediated transcription. However, a TAZ phosphorylation mutant significantly decreased cell proliferation, wound healing, colony forming, and tumor formation. In a CRC mouse model, Apc Min/+ , activated SRC expression was associated with increased TAZ expression in polyps and TAZ depletion decreased polyp formation. Moreover, intestinal TAZ knockout mice had intestinal regeneration defects following γ-irradiation. Finally, significant correspondence between SRC activation and TAZ overexpression was observed in CRC patients. These results suggest that TAZ is a critical factor for SRC-mediated intestinal tumor formation and regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Location and pathogenic potential of Blastocystis in the porcine intestine.

    Directory of Open Access Journals (Sweden)

    Wenqi Wang

    Full Text Available Blastocystis is an ubiquitous, enteric protozoan of humans and many other species. Human infection has been associated with gastrointestinal disease such as irritable bowel syndrome, however, this remains unproven. A relevant animal model is needed to investigate the pathogenesis/pathogenicity of Blastocystis. We concluded previously that pigs are likely natural hosts of Blastocystis with a potentially zoonotic, host-adapted subtype (ST, ST5, and may make suitable animal models. In this study, we aimed to characterise the host-agent interaction of Blastocystis and the pig, including localising Blastocystis in porcine intestine using microscopy, PCR and histopathological examination of tissues. Intestines from pigs in three different management systems, i.e., a commercial piggery, a small family farm and a research herd (where the animals were immunosuppressed were examined. This design was used to determine if environment or immune status influences intestinal colonisation of Blastocystis as immunocompromised individuals may potentially be more susceptible to blastocystosis and development of associated clinical signs. Intestines from all 28 pigs were positive for Blastocystis with all pigs harbouring ST5. In addition, the farm pigs had mixed infections with STs 1 and/or 3. Blastocystis organisms/DNA were predominantly found in the large intestine but were also detected in the small intestine of the immunosuppressed and some of the farm pigs, suggesting that immunosuppression and/or husbandry factors may influence Blastocystis colonisation of the small intestine. No obvious pathology was observed in the histological sections. Blastocystis was present as vacuolar/granular forms and these were found within luminal material or in close proximity to epithelial cells, with no evidence of attachment or invasion. These results concur with most human studies, in which Blastocystis is predominantly found in the large intestine in the absence of

  8. Intestinal inflammatory myofibroblastic tumour

    African Journals Online (AJOL)

    abdominal X-ray of patients 1, 3 and 4 demonstrated dilated small bowel loops with fluid levels in keeping with intestinal ... myxoid/vascular pattern characterised by a variable admixture of capillary-calibre blood vessels, .... in the present study had a past history of abdominal trauma or surgery. Ancillary histopathological ...

  9. Small intestine and microbiota.

    Science.gov (United States)

    Cotter, Paul D

    2011-03-01

    To highlight the recent studies which have enhanced our appreciation of the composition of the microbiota in the human small intestine and its relevance to the health of the host. In the past number of years, the composition of the microorganisms present in our small intestines has been the subject of greater scrutiny than ever before. These investigations have been possible as a consequence of the development and utilization of new molecular tools which have revolutionized the field of microbial ecology and have focused predominantly on the small intestinal microbiota associated with pediatric celiac disease, inflammatory bowel disease, irritable bowel syndrome and pouchitis. The impact of invasive procedures, such as small bowel transplant, ileostomy and ileal pouch anal anastomosis, on the ileal microbiota has also been investigated. The ever greater appreciation of the link between the small intestinal microbiota and the health status of the host has the potential to lead to the development of new strategies to alter this microbiota in a targeted way to prevent or treat specific disorders.

  10. Intestinal obstruction repair

    Science.gov (United States)

    ... Ileostomy and your diet Ileostomy - caring for your stoma Ileostomy - changing your pouch Ileostomy - discharge Ileostomy - what to ask your doctor Intestinal or bowel obstruction - discharge Low-fiber diet Surgical wound care - open Types of ileostomy When you have nausea ...

  11. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... obstruction. Brit. I. Surg. 1998; 85: 1071-1074. The acute abdomen: Intestinal obstruction. In: Primary surgery, Vol. 1. Edited by Maurice King et al. Oxford. Med. PubL, Oxford. 1990; 142-169. Fluids and electrolyte management. In: Essentials of pediatric surgery. Edited by Marc Rowe et al. Mosby,. St. Louis ...

  12. Intestinal Complications of IBD

    Science.gov (United States)

    ... localized pocket of pus caused by infection from bacteria. More common in Crohn’s than in colitis, an abscess may form in the intestinal wall—sometimes causing it to bulge out. Visible abscesses, such as those around the anus, look like boils and treatment often involves lancing. Symptoms of ...

  13. Intestinal failure in childhood

    African Journals Online (AJOL)

    Short bowel syndrome (SBS) was one of the first recognised conditions of protracted IF. With the increasing and successful use of long-term PN during the last three decades, several other causes of IF have emerged. Long-term PN and home-PN are the mainstay of therapy, independent of the nature of “Intestinal failure” ...

  14. Intestinal Obstruction due to Complete Transmural Migration of a Retained Surgical Sponge into the Intestine

    Directory of Open Access Journals (Sweden)

    Takashi Kato

    2012-12-01

    Full Text Available A 56-year-old woman with a history of gynecological surgery for cervical cancer 18 years previously was referred to our hospital for colicky abdominal pain, nausea and vomiting. Intestinal obstruction was diagnosed by contrast-enhanced computed tomography (CT which showed dilation of the small intestine and suggested obstruction in the terminal ileum. In addition, CT showed a thick-walled cavitary lesion communicating with the proximal jejunum. 18F-fluorodeoxyglucose positron emission tomography showed abnormal uptake at the same location as the cavitary lesion revealed by CT. The patient underwent laparotomy for the ileus and resection of the cavitary lesion. At laparotomy, we found a retained surgical sponge in the ileum 60 cm from the ileocecal valve. The cavitary tumor had two fistulae communicating with the proximal jejunum. The tumor was resected en bloc together with the transverse colon, part of the jejunum and the duodenum. Microscopic examination revealed fibrous encapsulation and foreign body giant cell reaction. Since a retained surgical sponge without radiopaque markers is extremely difficult to diagnose, retained surgical sponge should be considered in the differential diagnosis of intestinal obstruction in patients who have undergone previous abdominal surgery.

  15. Enteric Helminths Promote Salmonella Coinfection by Altering the Intestinal Metabolome.

    Science.gov (United States)

    Reynolds, Lisa A; Redpath, Stephen A; Yurist-Doutsch, Sophie; Gill, Navkiran; Brown, Eric M; van der Heijden, Joris; Brosschot, Tara P; Han, Jun; Marshall, Natalie C; Woodward, Sarah E; Valdez, Yanet; Borchers, Christoph H; Perona-Wright, Georgia; Finlay, B Brett

    2017-04-15

    Intestinal helminth infections occur predominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional 3-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial coinfection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  16. Immune and genetic gardening of the intestinal microbiome.

    Science.gov (United States)

    Jacobs, Jonathan P; Braun, Jonathan

    2014-11-17

    The mucosal immune system - consisting of adaptive and innate immune cells as well as the epithelium - is profoundly influenced by its microbial environment. There is now growing evidence that the converse is also true, that the immune system shapes the composition of the intestinal microbiome. During conditions of health, this bidirectional interaction achieves a homeostasis in which inappropriate immune responses to non-pathogenic microbes are averted and immune activity suppresses blooms of potentially pathogenic microbes (pathobionts). Genetic alteration in immune/epithelial function can affect host gardening of the intestinal microbiome, contributing to the diversity of intestinal microbiota within a population and in some cases allowing for unfavorable microbial ecologies (dysbiosis) that confer disease susceptibility. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Intestinal uptake of bone seeking radiotracer: possible mechanisms and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D. W.; Kim, C. G.; Park, S. A.; Chang, J. A. [WonKwang University Hospital, Iksan (Korea, Republic of)

    2007-07-01

    This study was undertaken to investigate the frequency of intestinal accumulation of Tc-99m 3, 3-diphosphono-1, 2-propanedicarboxylic acid (DPD) on bone scans, describe the patterns of intestinal Tc-99m DPD uptake and discuss the possible mechanisms of this unusual finding. Three thousand, one hundred and ninety-four consecutive patients have been evaluated for intestinal Tc-99m DPD uptake on bone scans. A whole-body bone scan and various spot views were obtained to evaluate the location and intensity of intestinal uptake. Delayed scan and SPECT study were performed to define characteristics of intestinal uptake in some of patients. Available reports of co-relative radiologic imaging, endoscopic studies and laboratory tests were also reviewed to explain the intestinal uptake. Eighteen (9 female, 9 male) patients out of 3194 with a mean age of 57 years showed intestinal Tc-99m DPD uptake. The locations of intestinal uptake were well dispersed throughout the abdomen. The majority of the cases showed lower intensity than iliac spine (12/18, 67%). Eight patients didn't show significant change of uptake characteristics on the delayed images, while intestinal uptake traveled distally in nine patients. Two cases were revealed uptake of peritoneal carcinomatosis with small amount ascites and three cases were revealed tumoral uptake of intestine. Four patients with gastritis showed similar characteristic of intestinal uptake. Six cases of distally traveled intestinal uptake suggested intraluminal Tc-99m DPD activity such as gastrointestinal bleeding. However, stool occult blood tests were negative in three patients, and there is no clinical evidence of gastrointestinal bleeding in other three patients. Intestinal Tc-99m DPD uptake can be observed in 0.5% of bone scans. The mechanism of intestinal uptake is still unclear in some of the patients. Delayed imaging additional spot views and SPECT studies help in the differentiation of this finding from possible

  18. Recent trends in feline intestinal neoplasia: an epidemiologic study of 1,129 cases in the veterinary medical database from 1964 to 2004.

    Science.gov (United States)

    Rissetto, Kerry; Villamil, J Armando; Selting, Kim A; Tyler, Jeff; Henry, Carolyn J

    2011-01-01

    A retrospective epidemiologic study evaluated 1,129 feline intestinal tumor patients via data entered into the Veterinary Medical Database (VMDB) from 1964 to 2004. Cases were analyzed by breed, age, yr of diagnosis, tumor type, and location. The VMDB incidence of all intestinal tumors reported during this 40 yr period was 0.4%, with small intestinal tumors predominating. The most common intestinal tumor was lymphoma, but the most common nonlymphoid tumor was adenocarcinoma. The Siamese breed and increasing age after 7 yr conferred an increased risk. Intact males and females appeared to have a decreased risk compared with neutered patients, but this may be explained by the age difference among these patients as older patients were more likely to be neutered. Prospective studies evaluating neuter status predilection and prognosis are warranted.

  19. Primary fibrosarcoma im small intestine of dog - Case report

    Directory of Open Access Journals (Sweden)

    Geórgia Modé Magalhães

    2015-06-01

    Full Text Available ABSTRACT. Magalhães G.M., Santilli J., Calazans S.G., Nishimura L.T., Cerejo S.A. & Dias F.G.G. [Primary fibrosarcoma im small intestine of dog - Case report.] Fibrossarcoma primário em intestino delgado de cão - Relato de caso. Revista Brasileira de Medicina Veterinária, 37(2:145-148, 2015. Programa de Pós-Graduação em Medicina Veterinária de Pequenos Animais, Universidade de Franca, Av. Dr. Armando Salles Oliveira, 201, Cx postal 82, Parque Universitá- rio, Franca, SP 14404-600, Brasil. E-mail: georgiamode@hotmail.com Intestinal neoplasms are uncommon in dogs, and among the most frequently diagnosed are smooth muscle, lymphomas and carcinomas. The fibrosarcoma is extremely rare in the intestine of animals of this species therefore, little is known about the macroscopic and behavior of this tumor. Given this unusual intestinal disease in dogs, the present study aimed to report a case of intestinal fibrosarcoma in a poodle breed dog, 15 years old, with no apparent clinical signs. The mass was pedunculated, whitish and firm consistency. The diagnosis was made by histopathology. After four months of surgical excision, there was no recurrence and metastasis. We conclude that the intestinal fibrosarcoma has low aggressiveness, are rare and can present macroscopic pediculated.

  20. Genetic Factors in Animal Models of Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    R Balfour Sartor

    1995-01-01

    Full Text Available The critical importance of host genetic susceptibility in determining chronicity, aggressiveness and complications of intestinal inflammation is clearly demonstrated by studies of inbred rodents, transgenic rats and spontaneous mutants. Inbred Lewis rats challenged by purified bacterial cell wall polymers, indomethacin or small bowel bacterial overgrowth develop chronic granulomatous intestinal inflammation with fibrosis and extraintestinal manifestations, whereas Fischer (major histocompatibility complex identical to Lewis and Buffalo rats identically stimulated demonstrate only self-limited enterocolitis with no chronic inflammation, fibrosis, granulomas or extraintestinal inflammation. Similar differential patterns of intestinal inflammation are apparent in inbred mouse strains challenged with trinitrobenzene-sulphonic acid, Citrobacter freundii or backcrossed with T cell receptor deficient (knockout mice. The dominant role of genetic background in induction of intestinal inflammation is further documented by spontaneous colitis which develops in spontaneously mutant mice, cotton-top tamarins, human leukocyte antigen-B27/ β2 microglobulin transgenic rats and mice with targeted deletions of certain immunoregulatory cytokine and T lymphocyte genes. Identification of the immunological mechanisms of host genetic susceptibility and the genetic basis of spontaneous colitis should provide new insights into the pathogenesis of human inflammatory bowel disease.

  1. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tol...

  2. Polymorphisms of transporter associated with antigen presentation, tumor necrosis factor-α and interleukin-10 and their implications for protection and susceptibility to severe forms of dengue fever in patients in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Anira N Fernando

    2015-01-01

    Full Text Available Context: To date, a clear understanding of dengue disease pathogenesis remains elusive. Some infected individuals display no symptoms while others develop severe life-threatening forms of the disease. It is widely believed that host genetic factors influence dengue severity. Aims: This study evaluates the relationship between certain polymorphisms and dengue severity in Sri Lankan patients. Settings and Design: Polymorphism studies are carried out on genes for; transporter associated with antigen presentation (TAP, promoter of tumor necrosis factor-α (TNF-α, and promoter of interleukin-10 (IL-10. In other populations, TAP1 (333, TAP2 (379, TNF-α (−308, and IL-10 (−1082, −819, −592 have been associated with dengue and a number of different diseases. Data have not been collected previously for these polymorphisms for dengue patients in Sri Lanka. Materials and Methods: The polymorphisms were typed by amplification refractory mutation system polymerase chain reaction in 107 dengue hemorrhagic fever (DHF patients together with 62 healthy controls. Statistical Analysis Used: Pearson′s Chi-square contingency table analysis with Yates′ correction. Results: Neither the TAP nor the IL-10 polymorphisms considered individually can define dengue disease outcome with regard to severity. However, the genotype combination, IL-10 (−592/−819/−1082 CCA/ATA was significantly associated with development of severe dengue in these patients, suggesting a risk factor to developing DHF. Also, identified is the genotype combination IL-10 (−592/−819/−1082 ATA/ATG which suggested a possibility for protection from DHF. The TNF-α (−308 GG genotype was also significantly associated with severe dengue, suggesting a significant risk factor. Conclusions: The results reported here are specific to the Sri Lankan population. Comparisons with previous reports imply that data may vary from population to population.

  3. Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Proinflammatory Responses in Intestinal Lymphoid Tissues

    Science.gov (United States)

    Siefker, David T.; Echeverry, Andrea; Brambilla, Roberta; Fukata, Masayuki; Schesser, Kurt

    2014-01-01

    Neonatal animals are generally very susceptible to infection with bacterial pathogens. However, we recently reported that neonatal mice are highly resistant to orogastric infection with Yersinia enterocolitica. Here, we show that proinflammatory responses greatly exceeding those in adults arise very rapidly in the mesenteric lymph nodes (MLN) of neonates. High-level induction of proinflammatory gene expression occurred in the neonatal MLN as early as 18 h postinfection. Marked innate phagocyte recruitment was subsequently detected at 24 h postinfection. Enzyme-linked immunosorbent spot assay (ELISPOT) analyses indicated that enhanced inflammation in neonatal MLN is contributed to, in part, by an increased frequency of proinflammatory cytokine-secreting cells. Moreover, both CD11b+ and CD11b− cell populations appeared to play a role in proinflammatory gene expression. The level of inflammation in neonatal MLN was also dependent on key bacterial components. Y. enterocolitica lacking the virulence plasmid failed to induce innate phagocyte recruitment. In contrast, tumor necrosis factor alpha (TNF-α) protein expression and neutrophil recruitment were strikingly higher in neonatal MLN after infection with a yopP-deficient strain than with wild-type Y. enterocolitica, whereas only modest increases occurred in adults. This hyperinflammatory response was associated with greater colonization of the spleen and higher mortality in neonates, while there was no difference in mortality among adults. This model highlights the dynamic levels of inflammation in the intestinal lymphoid tissues and reveals the protective (wild-type strain) versus harmful (yopP-deficient strain) consequences of inflammation in neonates. Moreover, these results reveal that the neonatal intestinal lymphoid tissues have great potential to rapidly mobilize innate components in response to infection with bacterial enteropathogens. PMID:24478090

  4. Small intestinal transplantation.

    LENUS (Irish Health Repository)

    Quigley, E M

    2012-02-03

    The past few years have witnessed a considerable shift in the clinical status of intestinal transplantation. A great deal of experience has been gained at the most active centers, and results comparable with those reported at a similar stage in the development of other solid-organ graft programs are now being achieved by these highly proficient transplant teams. Rejection and its inevitable associate, sepsis, remain ubiquitous, and new immunosuppressant regimes are urgently needed; some may already be on the near horizon. The recent success of isolated intestinal grafts, together with the mortality and morbidity attendant upon the development of advanced liver disease related to total parenteral nutrition, has prompted the bold proposal that patients at risk for this complication should be identified and should receive isolated small bowel grafts before the onset of end-stage hepatic failure. The very fact that such a suggestion has begun to emerge reflects real progress in this challenging field.

  5. The use of radionuclides for tumor therapy

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Wang, T.S.T.; Hardy, M.A.

    1986-01-01

    The successful use of radionuclides for tumor therapy depends to a major extent on the ability to achieve a high concentration of radioactivity in the tumor relative to other radiosensitive organs not involved by tumor, such as bone marrow, intestinal mucosa, liver, and kidneys. Techniques designed to achieve such differential localization of the radionuclides include the use of (1) radiopharmaceuticals that enter specific metabolic pathways unique to certain tumor types; (2) radiolabeled antibodies that attach to tumor-associated antigens present on tumor cell surfaces; (3) heterologous antibodies that attach to tumor-associated antigens present on tumor cell surfaces and which are then identified by radiolabeled antibodies directed against the species in which the original, unlabeled antibody was made; and (4) radiolabeled compounds injected regionally at the tumor site. Although both clinical and experimental evidence on the use of radionuclides for tumor therapy is encouraging in preliminary studies, extensive further research needs to be done in this area to insure the clinical efficacy of radionuclides for tumor therapy. (author)

  6. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  7. Carcinoid Tumors

    Science.gov (United States)

    ... spread to other parts of the body. Doctors don't know what causes the mutations that can lead to carcinoid tumors. But they know that carcinoid tumors develop in neuroendocrine cells. Neuroendocrine cells are found in various organs throughout the body. They perform some nerve cell ...

  8. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  9. Intestinal stromal cells in mucosal immunity and homeostasis.

    Science.gov (United States)

    Owens, B M J; Simmons, A

    2013-03-01

    A growing body of evidence suggests that non-hematopoietic stromal cells of the intestine have multiple roles in immune responses and inflammation at this mucosal site. Despite this, many still consider gut stromal cells as passive structural entities, with past research focused heavily on their roles in fibrosis, tumor progression, and wound healing, rather than their contributions to immune function. In this review, we discuss our current knowledge of stromal cells in intestinal immunity, highlighting the many immunological axes in which stromal cells have a functional role. We also consider emerging data that broaden the potential scope of their contribution to immunity in the gut and argue that these so-called "non-immune" cells are reclassified in light of their diverse contributions to intestinal innate immunity and the maintenance of mucosal homeostasis.

  10. Brush border myosin Ia inactivation in gastric but not endometrial tumors

    NARCIS (Netherlands)

    Mazzolini, Rocco; Rodrigues, Paulo; Bazzocco, Sarah; Dopeso, Higinio; Ferreira, Ana M.; Mateo-Lozano, Silvia; Andretta, Elena; Woerner, Stefan M.; Alazzouzi, Hafid; Landolfi, Stefania; Hernandez-Losa, Javier; Macaya, Irati; Suzuki, Hiromu; Ramon y Cajal, Santiago; Mooseker, Mark S.; Mariadason, John M.; Gebert, Johannes; Hofstra, Robert M. W.; Reventos, Jaume; Yamamoto, Hiroyuki; Schwartz, Simo; Arango, Diego

    2013-01-01

    Brush border Myosin Ia (MYO1A) has been shown to be frequently mutated in colorectal tumors with microsatellite instability (MSI) and to have tumor suppressor activity in intestinal tumors. Here, we investigated the frequency of frameshift mutations in the A8 microsatellite in exon 28 of MYO1A in

  11. Gastrointestinal estromal tumor: Presentation of a case

    International Nuclear Information System (INIS)

    Gil Gonzalez, Alexis; Hernandez Perez, Arnaldo; Gonzalez Rodriguez, Diana; Hernandez Fernandez, Diana M; Castanneda Munnoz, Angela

    2009-01-01

    Since the first descriptions made by Golden and Stout, this group of mesenchymal lesions is considered of muscular origin and they were named as leiomyoma, cellular leiomyoma, epithelioid leiomyoma, leiomyoblastoma, bizarre leiomyoma and leiomyosarcoma. But Mazur and Clark created the term estromal tumor only after they began to use the inmunohistochemistry and subsequently showed the absence of muscular markers, and the occasional presence of neural markers. Nowadays, gastrointestinal estromal tumors are called the primary mesenchymal CD117 positive, fusiform or epithelioid tumors of the gastrointestinal tract, epiplon, mesenterio, and retroperitoneum. The gastrointestinal estromal tumors appear at the wall of the digestive tube: stomach (50-60 %), small intestine (20-30 %), large intestine (10 %) and esophagus (5 %), and occasionally in epiplon, mesenterio, and retroperineum (5 %). In our work we present a 67 year-old patient, entered in our hospital for presenting high digestive bleeding. We studied the case, and found a 6 cm tumor of the gastric fundus. The tumor was operated and the definitive results of the pathologic anatomy showed a gastrointestinal estromal tumor

  12. Small intestinal cytochromes P450.

    Science.gov (United States)

    Kaminsky, L S; Fasco, M J

    1991-01-01

    Small intestinal cytochromes P450 (P450) provide the principal, initial source of biotransformation of ingested xenobiotics. The consequences of such biotransformation are detoxification by facilitating excretion, or toxification by bioactivation. P450s occur at highest concentrations in the duodenum, near the pylorus, and at decreasing concentrations distally--being lowest in the ileum. Highest concentrations occur from midvillus to villous tip, with little or none occurring in the crypts of Lieberkuehn. Microsomal P4503A, 2C8-10, and 2D6 forms have been identified in human small intestine, and P450s 2B1, possibly 2B2, 2A1, and 3A1/2 were located in endoplasmic reticulum of rodent small intestine, while P4502B4 has been purified to electrophoretic homogeneity from rabbit intestine. Some evidence indicates a differential distribution of P450 forms along the length of the small intestine and even along the villus. Rat intestinal P450s are inducible by xenobiotics--with phenobarbital (PB) inducing P4502B1, 3-methylcholanthrene (3-MC) inducing P4501A1, and dexamethasone inducing two forms of P4503A. Induction is most effectively achieved by oral administration of the agents, and is rapid--aryl hydrocarbon hydroxylase (AHH) was increased within 1 h of administration of, for example, 3-MC. AHH, 7-ethoxycoumarin O-deethylase (ECOD), and 7-ethoxyresorufin O-deethylase (EROD) have been used most frequently as substrates to characterize intestinal P450s. Dietary factors affect intestinal P450s markedly--iron restriction rapidly decreased intestinal P450 to beneath detectable values; selenium deficiency acted similarly but was less effective; Brussels sprouts increased intestinal AHH activity 9.8-fold, ECOD activity 3.2-fold, and P450 1.9-fold; fried meat and dietary fat significantly increased intestinal EROD activity; a vitamin A-deficient diet increased, and a vitamin A-rich diet decreased intestinal P450 activities; and excess cholesterol in the diet increased intestinal

  13. The value of digital subtraction angiography in diagnosing small intestinal hemorrhage with unknown reasons

    International Nuclear Information System (INIS)

    Luo Guanghua; Xiao Wenlian; Tang Deqiu; Chan Hong

    2006-01-01

    Objective: To discuss the diagnostic value of DSA for unknown reason hemorrhage of small intestine. Methods: 25 patients with hemorrhage of small intestine were performed angiography with Seldinger's technique through superior mesenteric artery. Results: Eleven cases demonstrated direct signs of hemorrhage, 12 cases of indirect signs of hemorrhage and 5 with both of the signs. The positive rate of hemorrhage was 72% including 10 cases of tumor (6 leiomyomas, 2 leiomyosarcomas, 1 interstitial tumor, 1 small intestinal cancer), 4 cases of Meckel's diverticulum, 3 cases of vascular malformation and 1 case of inflammation. The coincidence rate of positive cases with pathology was 75% and the diagnostic accuracy of localization was 100%. Conclusions: DSA angiography is very helpful for determining the location and character of unknown reason hemorrhage of small intestine. (authors)

  14. HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis

    Science.gov (United States)

    Antignano, Frann; Korinek, Vladimir; Underhill, T. Michael

    2018-01-01

    The intestinal immune system must be able to respond to a wide variety of infectious organisms while maintaining tolerance to non-pathogenic microbes and food antigens. The Vitamin A metabolite all-trans-retinoic acid (atRA) has been implicated in the regulation of this balance, partially by regulating innate lymphoid cell (ILC) responses in the intestine. However, the molecular mechanisms of atRA-dependent intestinal immunity and homeostasis remain elusive. Here we define a role for the transcriptional repressor Hypermethylated in cancer 1 (HIC1, ZBTB29) in the regulation of ILC responses in the intestine. Intestinal ILCs express HIC1 in a vitamin A-dependent manner. In the absence of HIC1, group 3 ILCs (ILC3s) that produce IL-22 are lost, resulting in increased susceptibility to infection with the bacterial pathogen Citrobacter rodentium. Thus, atRA-dependent expression of HIC1 in ILC3s regulates intestinal homeostasis and protective immunity. PMID:29470558

  15. The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants : A randomized controlled trial

    NARCIS (Netherlands)

    van den Berg, Anemone; Fetter, Willem P. F.; Westerbeek, Elisabeth A. M.; van der Vegt, Ina M.; van der Molen, Hilda R. A.; van Elburg, Ruurd M.

    2006-01-01

    Background: Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as

  16. The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants: A randomized controlled trial

    NARCIS (Netherlands)

    van den Berg, Anemone; Fetter, Willem P. F.; Westerbeek, Elisabeth A. M.; van der Vegt, Ina M.; van der Molen, Hilda R. A.; van Elburg, Ruurd M.

    2006-01-01

    Background: Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as

  17. Saireito (TJ-114, a Japanese traditional herbal medicine, reduces 5-fluorouracil-induced intestinal mucositis in mice by inhibiting cytokine-mediated apoptosis in intestinal crypt cells.

    Directory of Open Access Journals (Sweden)

    Shinichi Kato

    Full Text Available Clinical chemotherapy frequently causes intestinal mucositis as a side effect, which is accompanied by severe diarrhea. We recently showed that the cytokine-mediated apoptotic pathway might be important for the development of intestinal mucositis induced by 5-fluorouracil (5-FU. Saireito, the traditional Japanese herbal (Kampo medicine, is widely used to treat diarrhea and various inflammatory diseases in Japan. In the present study, we investigated the effect of saireito on 5-FU-induced intestinal mucositis in mice, especially in relation to apoptosis in the intestinal crypt. Male C57BL/6 mice were given 5-FU (50 mg/kg, i.p. once daily for 6 days. Intestinal mucositis was evaluated histochemically. Saireito (100-1000 mg/kg was administered p.o. twice daily for 6 days. Repeated 5-FU treatment caused severe intestinal mucositis including morphological damage, which was accompanied by body weight loss and diarrhea. Daily administration of saireito reduced the severity of intestinal mucositis in a dose-dependent manner. Body weight loss and diarrhea during 5-FU treatment were also significantly attenuated by saireito administration. The number of apoptotic and caspase-3-activated cells in the intestinal crypt was increased, and was accompanied by up-regulated tumor necrosis factor (TNF-α and interleukin (IL-1β mRNA within 24 h of the first 5-FU injection. However, all of these measures were significantly lower after saireito administration. These results suggest that saireito attenuates 5-FU-induced intestinal mucositis. This action may come from the reduction of apoptosis in the intestinal crypt via suppression of the up-regulation of inflammatory cytokines. Therefore, saireito may be clinically useful for the prevention of intestinal mucositis during cancer chemotherapy.

  18. Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae

    Science.gov (United States)

    Campagna, Shawn R.; Blanchard, Eugene E.; Ronis, Martin J. J.

    2017-01-01

    Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis). To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole) via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls) liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control) animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein. Collectively, these

  19. Obstrução intestinal no idoso Intestinal obstruction in the elderly

    Directory of Open Access Journals (Sweden)

    Maria Aparecida Coelho de Arruda Henry

    2007-12-01

    Full Text Available RACIONAL: O envelhecimento da população é realidade sentida na vivência diária, levando à necessidade associada de prover cuidados médicos eletivos e de emergência a um número cada vez maior de idosos. OBJETIVO: Avaliar os aspectos clínicos, terapêuticos e evolutivos de pacientes idosos com obstrução intestinal atendidos no Hospital das Clínicas da Faculdade de Medicina de Botucatu - UNESP. MÉTODOS: Análise retrospectiva de pacientes internados no período de janeiro de 2002 a dezembro de 2006. Foram estudados 50 pacientes, 24 homens e 26 mulheres, com idade média de 74,7 ± 7,4 anos, analisando-se a diferenciação entre obstrução funcional e orgânica; a freqüência das causas obstrutivas; a mortalidade; a incidência dos sinais e sintomas; e correlação laboratorial. RESULTADOS: O quadro obstrutivo intestinal teve as seguintes causas: brida (38%, câncer de colon (24%, hérnias (12%, impactacão fecal (12%, carcinomatose (10% e volvo da sigmóide (4%. A mortalidade foi de 18% associada à complicações infecciosas em todos os pacientes. CONCLUSÕES: a A distinção entre a obstrução intestinal funcional e orgânica oferece dificuldade no idoso; b o câncer do colon constitui-se em importante causa de obstrução intestinal com quadro obstrutivo já na primeira manifestação clínica desse tumor; c bridas e hérnias são igualmente importantes na etiologia da obstrução intestinal; d os sinais clínicos obstrutivos são poucos evidentes no idoso e a leucometria é mais fidedigna para este diagnóstico.BACKGROUND: Population aging is a reality that is experienced daily, leading to an associated need for providing elective and emergency medical care to an increasing number of elderly individuals. AIM: To evaluate clinical, therapeutic and developmental aspects of patients with intestinal obstruction assisted at the University Hospital of the Botucatu School of Medicine - UNESP. METHODS: Retrospective analysis of

  20. Role of c-Myc in Apc mutant intestinal phenotype: case closed or time for a new beginning?

    Science.gov (United States)

    Bommer, Guido T; Fearon, Eric R

    2007-05-01

    Inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene occurs in most colorectal cancers. The proto-oncogene c-MYC was one of the first genes linked to APC inactivation, but the in vivo significance of c-MYC's enhanced expression in intestinal cells with APC defects has been uncertain. Sansom et al. recently reported that targeted inactivation of c-Myc in murine intestinal epithelium potently inhibited phenotypical and transcriptional changes seen in Apc-deficient intestinal epithelium. While these findings are very interesting, some questions remain about the assignment of c-Myc as the pre-eminent beta-catenin-regulated gene in intestinal epithelium.

  1. IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Serkan I. Göktuna

    2014-06-01

    Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

  2. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide.

    OpenAIRE

    Viaud S; Saccheri F; Mignot G; Yamazaki T; Daill\\xere R; Hannani D; Enot DP; Pfirschke C; Engblom C; Pittet MJ; Schlitzer A; Ginhoux F; Apetoh L; Chachaty E; Woerther PL

    2013-01-01

    Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate anti-tumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram+ bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of “pathogenic” T helper 17 (pTh17) cel...

  3. Tumor Markers

    Science.gov (United States)

    ... only a small number of people will test positive for the disease who do not have it—in other words, it will result in very few false-positive results. Although tumor markers are extremely useful in ...

  4. Tumor Grade

    Science.gov (United States)

    ... Peer Review and Funding Outcomes Step 4: Award Negotiation & Issuance Manage Your Award Grants Management Contacts Monitoring ... may require immediate or more aggressive treatment. The importance of tumor grade in planning treatment and determining ...

  5. Enhanced gastrointestinal expression of cytosolic malic enzyme (ME1 induces intestinal and liver lipogenic gene expression and intestinal cell proliferation in mice.

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Dwairi

    Full Text Available The small intestine participates in lipid digestion, metabolism and transport. Cytosolic malic enzyme 1 (ME1 is an enzyme that generates NADPH used in fatty acid and cholesterol biosynthesis. Previous work has correlated liver and adipose ME1 expression with susceptibility to obesity and diabetes; however, the contributions of intestine-expressed ME1 to these conditions are unknown. We generated transgenic (Tg mice expressing rat ME1 in the gastrointestinal epithelium under the control of the murine villin1 promoter/enhancer. Levels of intestinal ME1 protein (endogenous plus transgene were greater in Tg than wildtype (WT littermates. Effects of elevated intestinal ME1 on body weight, circulating insulin, select adipocytokines, blood glucose, and metabolism-related genes were examined. Male Tg mice fed a high-fat (HF diet gained significantly more body weight than WT male littermates and had heavier livers. ME1-Tg mice had deeper intestinal and colon crypts, a greater intestinal 5-bromodeoxyuridine labeling index, and increased expression of intestinal lipogenic (Fasn, Srebf1 and cholesterol biosynthetic (Hmgcsr, Hmgcs1, genes. The livers from HF diet-fed Tg mice also exhibited an induction of cholesterol and lipogenic pathway genes and altered measures (Irs1, Irs2, Prkce of insulin sensitivity. Results indicate that gastrointestinal ME1 via its influence on intestinal epithelial proliferation, and lipogenic and cholesterologenic genes may concomitantly impact signaling in liver to modify this tissue's metabolic state. Our work highlights a new mouse model to address the role of intestine-expressed ME1 in whole body metabolism, hepatomegaly, and crypt cell proliferation. Intestinal ME1 may thus constitute a therapeutic target to reduce obesity-associated pathologies.

  6. Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection.

    Directory of Open Access Journals (Sweden)

    Philipp Rausch

    2015-07-01

    Full Text Available Glycans play important roles in host-microbe interactions. Tissue-specific expression patterns of the blood group glycosyltransferase β-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2 are variable in wild mouse populations, and loss of B4galnt2 expression is associated with altered intestinal microbiota. We hypothesized that variation in B4galnt2 expression alters susceptibility to intestinal pathogens. To test this, we challenged mice genetically engineered to express different B4galnt2 tissue-specific patterns with a Salmonella Typhimurium infection model. We found B4galnt2 intestinal expression was strongly associated with bacterial community composition and increased Salmonella susceptibility as evidenced by increased intestinal inflammatory cytokines and infiltrating immune cells. Fecal transfer experiments demonstrated a crucial role of the B4galnt2-dependent microbiota in conferring susceptibility to intestinal inflammation, while epithelial B4galnt2 expression facilitated epithelial invasion of S. Typhimurium. These data support a critical role for B4galnt2 in gastrointestinal infections. We speculate that B4galnt2-specific differences in host susceptibility to intestinal pathogens underlie the strong signatures of balancing selection observed at the B4galnt2 locus in wild mouse populations.

  7. The role of PGE2 in intestinal inflammation and tumorigenesis.

    Science.gov (United States)

    Montrose, David C; Nakanishi, Masako; Murphy, Robert C; Zarini, Simona; McAleer, Jeremy P; Vella, Anthony T; Rosenberg, Daniel W

    2015-01-01

    Release of the free fatty acid arachidonic acid (AA) by cytoplasmic phospholipase A2 (cPLA2) and its subsequent metabolism by the cyclooxygenase and lipoxygenase enzymes produces a broad panel of eicosanoids including prostaglandins (PGs). This study sought to investigate the roles of these mediators in experimental models of inflammation and inflammation-associated intestinal tumorigenesis. Using the dextran sodium sulfate (DSS) model of experimental colitis, we first investigated how a global reduction in eicosanoid production would impact intestinal injury by utilizing cPLA2 knockout mice. cPLA2 deletion enhanced colonic injury, reflected by increased mucosal ulceration and pro-inflammatory cytokine expression. Increased disease severity was associated with a significant reduction in the levels of several eicosanoid metabolites, including PGE2. We further assessed the precise role of PGE2 synthesis on mucosal injury and repair by utilizing mice with a genetic deletion of microsomal PGE synthase-1 (mPGES-1), the terminal synthase in the formation of inducible PGE2. DSS exposure caused more extensive acute injury as well as impaired recovery in knockout mice compared to wild-type littermates. Increased intestinal damage was associated with both reduced PGE2 levels as well as altered levels of other eicosanoids including PGD2. To determine whether this metabolic redirection impacted inflammation-associated intestinal tumorigenesis, Apc(Min/+) and Apc(Min/+):mPGES-1(-/-) mice were exposed to DSS. DSS administration caused a reduction in the number of intestinal polyps only in Apc(Min/+):mPGES-1(-/-) mice. These results demonstrate the importance of the balance of prostaglandins produced in the intestinal tract for maintaining intestinal homeostasis and impacting tumor development. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Intestinal adenocarcinoma in a herd of farmed Sika deer (Cervus nippon): a novel syndrome.

    Science.gov (United States)

    Kelly, P A; Toolan, D; Jahns, H

    2015-01-01

    Intestinal adenocarcinomas were identified in 76 adult deer from a closed herd of 193 breeding animals grazing pasture heavily infested with bracken fern (Pteridium aquilinum). Tumors were observed postmortem in 32 animals with rapid weight loss, and similar neoplasms were detected in a further 44 clinically normal deer at "cull." Tumors were located in distal ileum, cecum, and proximal colon and presented as single (26%) or multiple (74%), variably sized, pale-gray, firm, poorly circumscribed neoplasms with associated intestinal strictures. Histopathologically tumors were well-differentiated, locally infiltrative, low-grade adenocarcinomas of tubular (51%), mucinous (33.5%), or mixed (15.5%) types. Extraintestinal metastases were not observed. The high incidence of intestinal adenocarcinoma within this herd suggests a specific and novel syndrome, and genetic and/or environmental factors may be involved in the pathogenesis. © The Author(s) 2014.

  9. Intestinal parasites : associations with intestinal and systemic inflammation

    NARCIS (Netherlands)

    Zavala, Gerardo A; García, Olga P; Camacho, Mariela; Ronquillo, Dolores; Campos-Ponce, Maiza; Doak, Colleen; Polman, Katja; Rosado, Jorge L

    2018-01-01

    AIMS: Evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. METHODS AND RESULTS: Plasma concentrations of CRP, leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and

  10. Activation of intestinal epithelial Stat3 orchestrates tissue defense during gastrointestinal infection.

    Directory of Open Access Journals (Sweden)

    Nadine Wittkopf

    Full Text Available Gastrointestinal infections with EHEC and EPEC are responsible for outbreaks of diarrheal diseases and represent a global health problem. Innate first-line-defense mechanisms such as production of mucus and antimicrobial peptides by intestinal epithelial cells are of utmost importance for host control of gastrointestinal infections. For the first time, we directly demonstrate a critical role for Stat3 activation in intestinal epithelial cells upon infection of mice with Citrobacter rodentium - a murine pathogen that mimics human infections with attaching and effacing Escherichia coli. C. rodentium induced transcription of IL-6 and IL-22 in gut samples of mice and was associated with activation of the transcription factor Stat3 in intestinal epithelial cells. C. rodentium infection induced expression of several antimicrobial peptides such as RegIIIγ and Pla2g2a in the intestine which was critically dependent on Stat3 activation. Consequently, mice with specific deletion of Stat3 in intestinal epithelial cells showed increased susceptibility to C. rodentium infection as indicated by high bacterial load, severe gut inflammation, pronounced intestinal epithelial cell death and dissemination of bacteria to distant organs. Together, our data implicate an essential role for Stat3 activation in intestinal epithelial cells during C. rodentium infection. Stat3 concerts the host response to bacterial infection by controlling bacterial growth and suppression of apoptosis to maintain intestinal epithelial barrier function.

  11. [Primary non-polipoid intestinal folicular lymphoma: case report and review of the literature].

    Science.gov (United States)

    Beltran, Brady; Alva, José Carlos; Morales, Domingo; Portanova, Michel

    2015-01-01

    The primary intestinal follicular lymphoma is a rare disease described in the last classification of lymphomas from WHO. It is a localized disease with excellent prognosis. We describe in this article ,a 64 year-old Peruvian female with abdominal pain and delayed vomiting for the last two years, has undergone a partial intestinal resection due to bowel obstruction. There was a well-circumscribed annular tumor. A diagnosis of non-polypoid primary intestinal follicular lymphoma was made. We report the case and review the literature in this article.

  12. Pathology of Rodent Models of Intestinal Cancer: Progress Report and Recommendations

    Science.gov (United States)

    Washington, Mary Kay; Powell, Anne E.; Sullivan, Ruth; Sundberg, John; Wright, Nicholas; Coffey, Robert J.; Dove, William F.

    2013-01-01

    In October 2010, a pathology review of rodent models of intestinal neoplasia was held at The Jackson Laboratory. This review complemented 2 other concurrent events: a workshop on methods of modeling colon cancer in rodents and a conference on current issues in murine and human colon cancer. We summarize the results of the pathology review and the committee’s recommendations for tumor nomenclature. A virtual high-resolution image slide box of these models has been developed. This report discusses significant recent developments in rodent modeling of intestinal neoplasia, including the role of stem cells in cancer and the creation of models of metastatic intestinal cancer. PMID:23415801

  13. Effect of Inherited Breast Cancer Susceptibility on Treatment Outcomes After Conservative Surgery and Radiation Therapy

    National Research Council Canada - National Science Library

    Nixon, Asa

    1998-01-01

    ... cancer susceptibility genes. The presence of a mutation in a tumor suppressor gene, such as BRCA1, may have implications for patient management if patients with these mutations can be identified...

  14. Krüppel-like factor 4 regulates intestinal epithelial cell morphology and polarity.

    Directory of Open Access Journals (Sweden)

    Tianxin Yu

    Full Text Available Krüppel-like factor 4 (KLF4 is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which it regulates homeostasis and represses tumorigenesis in the intestine is not well understood. In our study, KLF4 was partially depleted in the differentiated intestinal epithelial cells by a tamoxifen-inducible Cre recombinase. We found a significant increase in the number of goblet cells in the KLF4-deleted small intestine, suggesting that KLF4 is not only required for goblet cell differentiation, but also required for maintaining goblet cell numbers through its function in inhibiting cell proliferation. The number and position of Paneth cells also changed. This is consistent with the KLF4 knockout study using villin-Cre [1]. Through immunohistochemistry (IHC staining and statistical analysis, we found that a stem cell and/or tuft cell marker, DCAMKL1, and a proliferation marker, Ki67, are affected by KLF4 depletion, while an enteroendocrine cell marker, neurotensin (NT, was not affected. In addition, we found KLF4 depletion altered the morphology and polarity of the intestinal epithelial cells. Using a three-dimensional (3D intestinal epithelial cyst formation assay, we found that KLF4 is essential for cell polarity and crypt-cyst formation in human colon cancer cells. These findings suggest that, as a tumor suppressor in colorectal cancer, KLF4 affects intestinal epithelial cell

  15. Positional mapping and candidate gene analysis of the mouse Ccs3 locus that regulates differential susceptibility to carcinogen-induced colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Charles Meunier

    Full Text Available The Ccs3 locus on mouse chromosome 3 regulates differential susceptibility of A/J (A, susceptible and C57BL/6J (B6, resistant mouse strains to chemically-induced colorectal cancer (CRC. Here, we report the high-resolution positional mapping of the gene underlying the Ccs3 effect. Using phenotype/genotype correlation in a series of 33 AcB/BcA recombinant congenic mouse strains, as well as in groups of backcross populations bearing unique recombinant chromosomes for the interval, and in subcongenic strains, we have delineated the maximum size of the Ccs3 physical interval to a ∼2.15 Mb segment. This interval contains 12 annotated transcripts. Sequencing of positional candidates in A and B6 identified many either low-priority coding changes or non-protein coding variants. We found a unique copy number variant (CNV in intron 15 of the Nfkb1 gene. The CNV consists of two copies of a 54 bp sequence immediately adjacent to the exon 15 splice site, while only one copy is found in CRC-susceptible A. The Nfkb1 protein (p105/p50 expression is much reduced in A tumors compared to normal A colonic epithelium as analyzed by immunohistochemistry. Studies in primary macrophages from A and B6 mice demonstrate a marked differential activation of the NfκB pathway by lipopolysaccharide (kinetics of stimulation and maximum levels of phosphorylated IκBα, with a more robust activation being associated with resistance to CRC. NfκB has been previously implicated in regulating homeostasis and inflammatory response in the intestinal mucosa. The interval contains another positional candidate Slc39a8 that is differentially expressed in A vs B6 colons, and that has recently been associated in CRC tumor aggressiveness in humans.

  16. Tumor of the gastrointestinal stroma

    International Nuclear Information System (INIS)

    Montero Leon, Jorge Felipe; Silveira Pablos, Juan Mario; Figueroa, Alejandro Joan; Fuente Pelaez, Alexis

    2012-01-01

    The tumors of the gastrointestinal stroma, known in English language as GIST (gastrointestinal stromal tumors) are mesenchymal tumors appearing in any place throughout the intestinal tract. The objective of present paper is to present the case of a female patient aged 60 came to Gynecology consultation of the National Institute of Oncology and Radiobiology due pain in epigastrium irradiating to right flank with increase of volume in the right iliac fossa and by ultrasonography it is a tumor of right ovary projecting to epigastrium and the right hypochondrium. The surgical intervention is described as well as the findings noted in macro- and microscopic studies, as well ass in latter studies by immunohistochemistry of lesion. We conclude with a diagnosis of tumor of gastrointestinal stroma and the results of performed surgical and drugs interventions. It is recommended to assess the significance of a close relationship among general surgeons and gynecologists in face of unexpected diseases due to its difficult preoperative diagnosis leading to a appropriate surgical treatment due to its complexity it is necessary the competence of both surgical specialties

  17. Transcriptional modulation of intestinal innate defense/inflammation genes by preterm infant microbiota in a humanized gnotobiotic mouse model.

    Science.gov (United States)

    Lu, Lei; Yu, Yueyue; Guo, Yuee; Wang, Yunwei; Chang, Eugene B; Claud, Erika C

    2015-01-01

    It is known that postnatal functional maturation of the small intestine is facilitated by microbial colonization of the gut. Preterm infants exhibit defects in gut maturation, weak innate immunity against intestinal infection and increased susceptibility to inflammatory disorders, all of which may be related to the inappropriate microbial colonization of their immature intestines. The earliest microbes to colonize the preterm infant gut encounter a naïve, immature intestine. Thus this earliest microbiota potentially has the greatest opportunity to fundamentally influence intestinal development and immune function. The aim of this study was to characterize the effect of early microbial colonization on global gene expression in the distal small intestine during postnatal gut development. Gnotobiotic mouse models with experimental colonization by early (prior to two weeks of life) intestinal microbiota from preterm human infants were utilized. Microarray analysis was used to assess global gene expression in the intestinal epithelium. Multiple intestinal genes involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication, and immune function are developmental- and intestinal microbiota- regulated. Using a humanized gnotobiotic mouse model, we demonstrate that certain early preterm infant microbiota from prior to 2 weeks of life specifically induce increased NF-κB activation and a phenotype of increased inflammation whereas other preterm microbiota specifically induce decreased NF-κB activation. These fundamental differences correlate with altered clinical outcomes and suggest the existence of optimal early microbial communities to improve health outcomes.

  18. Fourie susceptible.pmd

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    majority having adequate resistance. Teebus, Cerillos, Bonus and PAN 159 were most susceptible, with Mkuzi exhibiting highest levels of resistance. No correlation was obtained between disease rating and yield. Although a number of cultivars exhibited field resistance to halo blight and bacterial brown spot, all cultivars ...

  19. Dynamic susceptibility of nanopillars

    NARCIS (Netherlands)

    Dao, T.N.N.; Dao, N.; Donahue, M.J.; Dumitru, I.; Spinu, L.; Whittenburg, S.L.; Lodder, J.C.

    2004-01-01

    We have calculated the dynamic susceptibility of patterned cobalt and Permalloy pillars with a diameter of 50 nm and different pillar heights using micromagnetic simulations. The resonance modes obtained from these simulations are compared to the results obtained from an analytical solution of

  20. Genetic susceptibility of periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Crielaard, W.; Loos, B.G.

    2012-01-01

    In this systematic review, we explore and summarize the peer-reviewed literature on putative genetic risk factors for susceptibility to aggressive and chronic periodontitis. A comprehensive literature search on the PubMed database was performed using the keywords ‘periodontitis’ or ‘periodontal

  1. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    Search Menu Facebook Twitter YouTube Flickr Instagram LinkedIn Brain Tumor Information | News & Blog Our Mission Our History Mission Leadership & Staff Financials Careers News & Blog Contact Us Donate Now Our Impact Our Impact Recent News News & ...

  2. Hippo signalling directs intestinal fate

    DEFF Research Database (Denmark)

    le Bouteiller, Marie Catherine M; Jensen, Kim Bak

    2015-01-01

    Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal epit...

  3. MDCT in blunt intestinal trauma

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Stefania [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy)]. E-mail: stefromano@libero.it; Scaglione, Mariano [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Tortora, Giovanni [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Martino, Antonio [Trauma Center, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Di Pietto, Francesco [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Romano, Luigia [Department of Diagnostic Imaging, ' A.Cardarelli' Hospital, 80131 Naples (Italy); Grassi, Roberto [Department ' Magrassi-Lanzara' , Section of Radiology, Second University of Naples, 80138 Naples (Italy)

    2006-09-15

    Injuries to the small and large intestine from blunt trauma represent a defined clinical entity, often not easy to correctly diagnose in emergency but extremely important for the therapeutic assessment of patients. This article summarizes the MDCT spectrum of findings in intestinal blunt lesions, from functional disorders to hemorrhage and perforation.

  4. MDCT in blunt intestinal trauma

    International Nuclear Information System (INIS)

    Romano, Stefania; Scaglione, Mariano; Tortora, Giovanni; Martino, Antonio; Di Pietto, Francesco; Romano, Luigia; Grassi, Roberto

    2006-01-01

    Injuries to the small and large intestine from blunt trauma represent a defined clinical entity, often not easy to correctly diagnose in emergency but extremely important for the therapeutic assessment of patients. This article summarizes the MDCT spectrum of findings in intestinal blunt lesions, from functional disorders to hemorrhage and perforation

  5. Human intestinal P-glycoprotein activity estimated by the model substrate digoxin

    DEFF Research Database (Denmark)

    Larsen, U L; Hyldahl Olesen, L; Nyvold, Charlotte Guldborg

    2007-01-01

    P-glycoprotein (Pgp) plays a part in the intestinal uptake of xenobiotics and has been associated with susceptibility to ulcerative colitis. The aim of this study was to examine Pgp activity in relation to age, gender, medical treatment (rifampicin or ketoconazole) and the multidrug resistance (MDR...

  6. Obstructive mobile small intestinal tumor without radiographic stigmata of bezoar

    Directory of Open Access Journals (Sweden)

    Elif Onursal

    2017-01-01

    Conclusion: In the absence of clear clinical or radiographic etiology for obstruction, developing a heightened degree of suspicion for native tissue “bezoar” may allow quick and appropriate management of similar cases and limit complications associated with prolonged obstruction. To our knowledge, this is the first reported case of mobile intraluminal leiomyoma causing small bowel obstruction.

  7. Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin.

    Science.gov (United States)

    Nickerson, Kourtney P; Chanin, Rachael; McDonald, Christine

    2015-01-01

    Inflammatory bowel disease (IBD) is a complex, multi-factorial disease thought to arise from an inappropriate immune response to commensal bacteria in a genetically susceptible person that results in chronic, cyclical, intestinal inflammation. Dietary and environmental factors are implicated in the initiation and perpetuation of IBD; however, a singular causative agent has not been identified. As of now, the role of environmental priming or triggers in IBD onset and pathogenesis are not well understood, but these factors appear to synergize with other disease susceptibility factors. In previous work, we determined that the polysaccharide dietary additive, maltodextrin (MDX), impairs cellular anti-bacterial responses and suppresses intestinal anti-microbial defense mechanisms. In this addendum, we review potential mechanisms for dietary deregulation of intestinal homeostasis, postulate how dietary and genetic risk factors may combine to result in disease pathogenesis, and discuss these ideas in the context of recent findings related to dietary interventions for IBD.

  8. Mediastinal tumors

    International Nuclear Information System (INIS)

    Canizares, Claudio; Araujo, Ivan; Rodriguez, Amparo; Robles, Wilson; Simba, Catalina

    2005-01-01

    In our practice the mediastinal tumors are infrequent. The mediastinum is the portion of the thoracic cavity that contains numerous organs and structures which makes a crossroad for the diagnostic process. Within which congenital cysts, inflammatory and benign tumors, malignant neoplasms may develop. In the superior compartment are found: thymoma and thymic cysts, germ cell tumors, thyroid lesions, parathyroid adenomas, malignant lymphomas, paragangliomas, hemangiomas, lipomas, and inflammatory lesions such as fibrosing mediastinitis. In the middle portion: pericardial cysts, bronchial cysts, malignant lymphomas. In the posterior region: neurogenic tumors such as Shawnomas, neurofibromas, ganglioneuroblastomas, neuroblastomas, paragangliomas, and gastro enteric cysts. We describe two cases. One of a female patient with a prominent tumor in the anterior compartment of the mediastinum, detected by the x-ray films. Initially a cardiac lesion was excluded by echographic, angiographic studies. The biopsy exhibited a prominent fibrosis that suggested fibrosing mediastinitis (sclerosing). Whoever the immunohistochemical phenotype was positive for lambda chains, determining the diagnosis of lymphoma. The other case is of a young male with a thymoma associated to a pure red cell aplasia, which was the initial clinical symptom. Computerized tomography and thyroid scintigraphy was used. (The author)

  9. Small bowel Gastrointestinal Stromal Tumors can physiologically alter gut motility before causing mechanical obstruction

    OpenAIRE

    Kothari, Manish S; Kosmoliaptsis, Vasilis; Meyrick-Thomas, John

    2005-01-01

    Background Gastro Intestinal Stromal Tumors (GISTs) are rare stromal neoplasms that represent the most common mesenchymal tumor of the G.I. tract, accounting for 5% of all sarcomas [1,2]. Originating from interstitial cells of Cajal, which are regulators of gut peristalsis, they are preferentially located in the stomach and the small intestine [3] and clinical presentation is variable, ranging from vague complaints to major G.I. bleeding. Surgical resection is the mainstay of treatment for pa...

  10. [Aorto-intestinal fistulas. 4 case reports].

    Science.gov (United States)

    Bansky, G; Valli, C; Häcki, W H; Turina, M

    1984-09-15

    Four cases of aorto-enteric fistula are reported. The two primary types occurred after rupture of an aneurysm of the abdominal aorta into the duodenum and as a consequence of tumor infiltration of both the aorta and the intestinal wall in a woman with metastatic ovarian cancer. The two secondary types developed as a late complication of reconstructive surgery of the abdominal aorta. The condition was diagnosed or suspected on the basis of endoscopic findings in two cases. The pathogenetic role of graft infection in the development of secondary aorto-enteric fistula is emphasized. The generally poor prognosis can be considerably improved if prompt resection of the graft is combined with axillo-bifemoral anastomosis.

  11. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  12. Modulation of Intestinal Microbiome Prevents Intestinal Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Alessandra Bertacco

    2017-12-01

    Full Text Available Background: Butyrate protects against ischemic injury to the small intestine by reducing inflammation and maintaining the structure of the intestinal barrier, but is expensive, short-lived, and cannot be administered easily due to its odor. Lactate, both economical and more palatable, can be converted into butyrate by the intestinal microbiome. This study aimed to assess in a rat model whether lactate perfusion can also protect against intestinal ischemia.Materials and Methods: Rat intestinal segments were loaded in an in vitro bowel perfusion device, and water absorption or secretion was assessed based on fluorescence of FITC-inulin, a fluorescent marker bound to a biologically inert sugar. Change in FITC concentration was used as a measure of ischemic injury, given the tendency of ischemic cells to retain water. Hematoxylin and eosin-stained sections at light level microscopy were examined to evaluate intestinal epithelium morphology. Comparisons between the data sets were paired Student t-tests or ANOVA with p < 0.05 performed on GraphPad.Results: Lactate administration resulted in a protective effect against intestinal ischemia of similar magnitude to that observed with butyrate. Both exhibited approximately 1.5 times the secretion exhibited by control sections (p = 0.03. Perfusion with lactate and methoxyacetate, a specific inhibitor of lactate-butyrate conversion, abolished this effect (p = 0.09. Antibiotic treatment also eliminated this effect, rendering lactate-perfused sections similar to control sections (p = 0.72. Perfusion with butyrate and methoxyacetate did not eliminate the observed increased secretion, which indicates that ischemic protection was mediated by microbial conversion of lactate to butyrate (p = 0.71.Conclusions: Lactate's protective effect against intestinal ischemia due to microbial conversion to butyrate suggests possible applications in the transplant setting for reducing ischemic injury and ameliorating intestinal

  13. Retinoic acid suppresses intestinal mucus production and exacerbates experimental enterocolitis

    Directory of Open Access Journals (Sweden)

    Stefan H. Oehlers

    2012-07-01

    Exposure to retinoids for the treatment of acne has been linked to the etiology of inflammatory bowel disease (IBD. The intestinal mucus layer is an important structural barrier that is disrupted in IBD. Retinoid-induced alteration of mucus physiology has been postulated as a mechanism linking retinoid treatment to IBD; however, there is little direct evidence for this interaction. The zebrafish larva is an emerging model system for investigating the pathogenesis of IBD. Importantly, this system allows components of the innate immune system, including mucus physiology, to be studied in isolation from the adaptive immune system. This study reports the characterization of a novel zebrafish larval model of IBD-like enterocolitis induced by exposure to dextran sodium sulfate (DSS. The DSS-induced enterocolitis model was found to recapitulate several aspects of the zebrafish trinitrobenzene-sulfonic-acid (TNBS-induced enterocolitis model, including neutrophilic inflammation that was microbiota-dependent and responsive to pharmacological intervention. Furthermore, the DSS-induced enterocolitis model was found to be a tractable model of stress-induced mucus production and was subsequently used to identify a role for retinoic acid (RA in suppressing both physiological and pathological intestinal mucin production. Suppression of mucin production by RA increased the susceptibility of zebrafish larvae to enterocolitis when challenged with enterocolitic agents. This study illustrates a direct effect of retinoid administration on intestinal mucus physiology and, subsequently, on the progression of intestinal inflammation.

  14. Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice

    Science.gov (United States)

    Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activati...

  15. Invasive inflammatory myofibroblastic tumor of the spleen treated with partial splenectomy in a child.

    Science.gov (United States)

    Krl, Elif Altnay; Orhan, Diclehan; Haliloğlu, Mithat; Karnak, Ibrahim

    2012-05-01

    Inflammatory myofibroblastic tumor (IMT) is a rare benign tumor that can be found in intra-abdominal organs such as the liver, intestine, extrahepatic bile ducts, and mesentery. The spleen is an extremely unusual location for an IMT. The authors report the case of a 14-year-old boy with invasive splenic IMT, present a review on the current literature about childhood splenic IMT, and emphasize the necessity of total excision of the tumor together with tumor-invaded surrounding tissues.

  16. Genetic Susceptibility to Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sanja Kovacic

    2012-01-01

    Full Text Available Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic ground significantly influences susceptibility to atherosclerotic vascular diseases. Besides further investigations of monogenetic diseases, candidate genes, genetic polymorphisms, and susceptibility loci associated with atherosclerotic diseases have been identified in recent years, and their number is rapidly increasing. This paper discusses main genetic investigations fields associated with human atherosclerotic vascular diseases. The paper concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on prospective prediction from an early age of individuals who are predisposed to develop premature atherosclerosis as well as to facilitate the discovery of novel drug targets.

  17. Marijuana Usage and Hypnotic Susceptibility

    Science.gov (United States)

    Franzini, Louis R.; McDonald, Roy D.

    1973-01-01

    Anonymous self-reported drug usage data and hypnotic susceptibility scores were obtained from 282 college students. Frequent marijuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. (Author)

  18. Association between the porcine Escherichia coli F18 receptor genotype and phenotype and susceptibility to colonisation and postweaning diarrhoea caused by E-coli O138 : F18

    DEFF Research Database (Denmark)

    Frydendahl, K.; Jensen, Tim Kåre; Andersen, Jens Strodl

    2003-01-01

    and the porcine intestinal F18 receptor genotypes. Thirty-one pigs classified as either belonging to the susceptible or the resistant genotype were inoculated with cultures of an E. coli 0138:F18 isolated from a pig with postweaning diarrhoea. Susceptibility to colonisation and diarrhoea was assessed by clinical...

  19. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens.

    Science.gov (United States)

    Pamer, Eric G

    2016-04-29

    The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care-associated infections caused by highly antibiotic-resistant bacteria. Copyright © 2016, American Association for the Advancement of Science.

  20. Pituitary Tumors

    Science.gov (United States)

    ... nursing, or cause a man to lose his sex drive or lower his sperm count. Pituitary tumors often go undiagnosed because their symptoms resemble those of so many other more common diseases. × Definition The pituitary is a small, bean-sized gland ...

  1. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  2. Megacystis microcolon intestinal hypoperistalsis syndrome

    Science.gov (United States)

    Hiradfar, Mehran; Shojaeian, Reza; Dehghanian, Paria; Hajian, Sara

    2013-01-01

    Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a multisystemic disorder in which impaired intestinal motor activity causes recurrent symptoms of intestinal obstruction in the absence of mechanical occlusion, associated with bladder distention without distal obstruction of the urinary tract. MMIHS and prune belly syndrome may overlap in most of the clinical features and discrimination of these two entities is important because the prognosis, management and consulting with parents are completely different. MMIHS outcome is very poor and in this article we present two neonates with MMIHS that both died in a few days. PMID:23729700

  3. INFANTS’ INTESTINAL COLICS. MODERN DATA

    Directory of Open Access Journals (Sweden)

    N.I. Ursova

    2011-01-01

    Full Text Available The article analyzes modern data on infants’ intestinal colics. Peculiarities of nutrition, intestinal microbiocenose in healthy infants, methods of colcs’ correction are discussed. Author describes the principles of probiotics choice based on their clinical effectiveness in infants. Milk formula «Nan Comfort» can be useful in prophylaxis and treatment of functional disorders of gastrointestinal tract in children.Key words: infants, gastrointestinal tract, anatomy, physiology, intestinal colics, nutrition, probiotics.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 125–131

  4. Lychee (Litchi chinensis Sonn.) Pulp Phenolic Extract Provides Protection against Alcoholic Liver Injury in Mice by Alleviating Intestinal Microbiota Dysbiosis, Intestinal Barrier Dysfunction, and Liver Inflammation.

    Science.gov (United States)

    Xiao, Juan; Zhang, Ruifen; Zhou, Qiuyun; Liu, Lei; Huang, Fei; Deng, Yuanyuan; Ma, Yongxuan; Wei, Zhencheng; Tang, Xiaojun; Zhang, Mingwei

    2017-11-08

    Liver injury is the most common consequence of alcohol abuse, which is promoted by the inflammatory response triggered by gut-derived endotoxins produced as a consequence of intestinal microbiota dysbiosis and barrier dysfunction. The aim of this study was to investigate whether modulation of intestinal microbiota and barrier function, and liver inflammation contributes to the hepatoprotective effect of lychee pulp phenolic extract (LPPE) in alcohol-fed mice. Mice were treated with an ethanol-containing liquid diet alone or in combination with LPPE for 8 weeks. LPPE supplementation alleviated ethanol-induced liver injury and downregulated key markers of inflammation. Moreover, LPPE supplementation reversed the ethanol-induced alteration of intestinal microbiota composition and increased the expression of intestinal tight junction proteins, mucus protecting proteins, and antimicrobial proteins. Furthermore, in addition to decreasing serum endotoxin level, LPPE supplementation suppressed CD14 and toll-like receptor 4 expression, and repressed the activation of nuclear factor-κB p65 in the liver. These data suggest that intestinal microbiota dysbiosis, intestinal barrier dysfunction, and liver inflammation are improved by LPPE, and therefore, the intake of LPPE or Litchi pulp may be an effective strategy to alleviate the susceptibility to alcohol-induced hepatic diseases.

  5. Disorders of the Small Intestine

    Science.gov (United States)

    ... that move down the intestine in a peristaltic fashion (Phase III). Phase III represents a continuation of ... Activities, Legislative & Regulatory Research Leadership Contact us News Industry Treatment News Medical News Legislative & Regulatory News Press ...

  6. Defence Mechanisms during Intestinal Infection

    Directory of Open Access Journals (Sweden)

    André Buret

    1991-01-01

    Full Text Available This review examines and compares host defence mechanisms during intestinal infection with three types of organisms: a virus, a bacterium and a nematode parasite (ie, transmissible gastroenteritis virus [TGEV], Helicobacter jejuni and Trichinella spiralis. Diarrhea is commonly associated with all of these infections. It appears that T spiralis initiates the most elaborate defence system of the three organisms, involving full range humoral and cellular immunity, as well as mucus hypersecretion, epithelial alterations, altered gut motility and parasite impairment (morphological and physiological. In contrast, intestinal defence against H jejuni and TGEV involves fewer components. The latter seems to initiate the most rudimentary host response. Despite such differences, these mechanisms exhibit many similarities, thus further illustrating the relatively limited repertoire of defence systems that the intestine can mount. The mediators translating the insult of any intestinal pathogen into a common response deserve further investigation.

  7. INTESTINAL INTUSSUSCEPTION DUE TO CONCURRENT ...

    African Journals Online (AJOL)

    Administrator

    Hymenolepis nana and Dentostomella ... worms (H. nana and D. translucida) were observed in the lumen of the intestine with severe cellular infiltration .... helminthosis and Balantidosis in Red monkey (Erythrocebus patas) in Ibadan Nigeria Nigerian ...

  8. Treatment and outcomes: medical and surgical treatment for intestinal Behçet's disease

    Directory of Open Access Journals (Sweden)

    Tadakazu Hisamatsu

    2017-07-01

    Full Text Available Behçet's disease (BD is a chronic relapsing disease involving multiple organ systems. BD is characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. It is widely recognized that the presence of intestinal lesions may be a poor prognostic factor in intestinal BD, increasing the risk of surgery and decreasing the quality of life. Despite this, the management of intestinal BD has not been standardized. Empirical therapies including 5-aminosalicylic acid and corticosteroids have been used anecdotally to treat intestinal BD, but recent studies have provided evidence for the efficacy of anti-tumor necrosis factor α monoclonal antibodies. The development of agents targeting tumor necrosis factor α continues, it seems likely that they will change the therapeutic strategy and clinical outcomes of intestinal BD and inflammatory bowel disease. Monitoring disease activity such as endoscopic evaluation will become more important to obtain better outcomes. Here, we review current and future perspectives in the treatment and outcomes of intestinal BD.

  9. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

  10. Diversity in secreted PLA2-IIA activity among inbred mouse strains that are resistant or susceptible to Apc Min/+ tumorigenesis.

    Science.gov (United States)

    Markova, Marina; Koratkar, Revati A; Silverman, Karen A; Sollars, Vincent E; MacPhee-Pellini, Melina; Walters, Rhonda; Palazzo, Juan P; Buchberg, Arthur M; Siracusa, Linda D; Farber, Steven A

    2005-09-22

    The secreted phospholipase A2 type IIA (Pla2g2a) gene was previously identified as a modifier of intestinal adenoma multiplicity in Apc Min/+ mice. To determine if intestinal secreted phospholipase A2 (sPLA2) activity was also attenuated in susceptible strains, we developed a sensitive assay to directly quantitate sPLA2 activity in the murine intestinal tract utilizing a fluorescent BODIPY-labeled phospholipid substrate. Here, we report assay conditions that distinguish between secreted and cytosolic PLA2 enzyme activities in extracts of intestinal tissue. The small intestine exhibited higher activity levels than the large intestine. Consistent with predictions from the sPLA2-IIA gene sequence in inbred strains, we detected low levels of enzyme activity in inbred strains containing sPLA2-IIA mutations; these strains were also associated with greater numbers of intestinal polyps. Additionally, the assay was able to distinguish differences in levels of sPLA2 activity between neoplasia-resistant strains, which were then shown by sequencing to carry variant wild-type sPLA2-IIA alleles. Immunohistochemical analyses of intestinal tissues were consistent with sPLA2-IIA activity levels. This approach enables further studies of the mechanisms of sPLA2 action influencing the development and tumorigenesis of the small intestine and colon in both mice and humans.

  11. Parenteral Nutrition and Intestinal Failure.

    Science.gov (United States)

    Bielawska, Barbara; Allard, Johane P

    2017-05-06

    Severe short bowel syndrome (SBS) is a major cause of chronic (Type 3) intestinal failure (IF) where structural and functional changes contribute to malabsorption and risk of micronutrient deficiencies. Chronic IF may be reversible, depending on anatomy and intestinal adaptation, but most patients require long-term nutritional support, generally in the form of parenteral nutrition (PN). SBS management begins with dietary changes and pharmacologic therapies taking into account individual anatomy and physiology, but these are rarely sufficient to avoid PN. New hormonal therapies targeting intestinal adaptation hold promise. Surgical options for SBS including intestinal transplant are available, but have significant limitations. Home PN (HPN) is therefore the mainstay of treatment for severe SBS. HPN involves chronic administration of macronutrients, micronutrients, fluid, and electrolytes via central venous access in the patient's home. HPN requires careful clinical and biochemical monitoring. Main complications of HPN are related to venous access (infection, thrombosis) and metabolic complications including intestinal failure associated liver disease (IFALD). Although HPN significantly impacts quality of life, outcomes are generally good and survival is mostly determined by the underlying disease. As chronic intestinal failure is a rare disease, registries are a promising strategy for studying HPN patients to improve outcomes.

  12. Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing tumor angiogenesis.

    Science.gov (United States)

    Kitahara, Shuji; Suzuki, Yasuhiro; Morishima, Masae; Yoshii, Asuka; Kikuta, Sachiko; Shimizu, Kazuhiko; Morikawa, Shunichi; Sato, Yasufumi; Ezaki, Taichi

    2014-05-04

    Vasohibin-2 (VASH2) has been identified as an endogenous and vascular endothelial growth factor (VEGF)-independent angiogenic factor that is highly expressed in tumor cells. In the present study, we aimed to determine whether pre-existing vascular changes can be used to predict tumor transformation as benign or malignant. We sought to characterize microvascular changes and tumor development in the intestinal tract of ApcMin/+ mice and ApcMin/+/Vash2-/- mice. ApcMin/+ mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, a phenomenon termed the adenoma-carcinoma sequence. ApcMin/+ mice were mated with Vash2-/- mice with a mixed C57BL/6 background and the resulting pups were screened for the Min mutation and for the Vash2-/- gene by PCR. Intestinal tumors from ApcMin/+ mice and ApcMin/+/Vash2-/- mice were removed and either frozen or epon-embedded for subsequent analyses. For 3-dimensional imaging using confocal laser-scanning microscopy and transmission electron microscopy, cryosections were made, and immunofluorescent staining for various markers was performed. We found that structural abnormalities in tumor vessels from benign tumors resembled those in malignant tumors. In addition, a novel angiogenic factor, vasohibin-2 (VASH2) protein, was detected around tumor blood vessels in late-stage adenomas and adenocarcinomas, but was absent from early-stage adenomas in ApcMin/+ mice. Tumors used to examine endogenous VASH2 (derived from CMT93 colon carcinomas) were less vascularized in Vash2-/- mice and were more regular than those seen in wild-type (WT) mice. In addition, tumors in Vash2-/- mice were smaller than those in WT mice. Furthermore, cross-breeding of mice homozygous for a deletion of Vash2 with mice heterozygous for the APC mutation resulted in animals that showed a significant decrease in the number of polyps in the small intestine. We propose that VASH2 may modulate the onset of tumors in

  13. Haemorrhage and intestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Attilia M. Pizzini

    2013-04-01

    Full Text Available Background: The prevalence of coeliac disease is around 1% in general population but this is often unrecognised. The classical presentation of adult coeliac disease is characterized by diarrhoea and malabsorption syndrome, but atypical presentations are probably more common and are characterized by iron deficiency anaemia, weight loss, fatigue, infertility, arthralgia, peripheral neuropathy and osteoporosis. Unusual are the coagulation disorders (prevalence 20% and these are due to vitamin K malabsorption (prolonged prothrombin time. Clinical case: A 64-year-old man was admitted to our Department for an extensive spontaneous haematoma of the right leg. He had a history of a small bowel resection for T-cell lymphoma, with a negative follow-up and he didn’t report any personal or familiar history of bleeding. Laboratory tests showed markedly prolonged prothrombin (PT and partial-thromboplastin time (PTT, corrected by mixing studies, and whereas platelet count and liver tests was normal. A single dose (10 mg of intravenous vitamin K normalized the PT. Several days before the patient had been exposed to a superwarfarin pesticide, but diagnostic tests for brodifacoum, bromadiolone or difenacoum were negative. Diagnosis of multiple vitamin K-dependent coagulationfactor deficiencies (II, VII, IX, X due to intestinal malabsorption was made and coeliac disease was detected. Therefore the previous lymphoma diagnosis might be closely related to coeliac disease. Conclusions: A gluten free diet improves quality of life and restores normal nutritional and biochemical status and protects against these complications.

  14. [Malaria and intestinal protozoa].

    Science.gov (United States)

    Rojo-Marcos, Gerardo; Cuadros-González, Juan

    2016-03-01

    Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  15. Adult intestinal failure

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J., E-mail: Jdavidson@doctors.org.u [Salford Royal Hospital, Salford (United Kingdom); Plumb, A.; Burnett, H. [Salford Royal Hospital, Salford (United Kingdom)

    2010-05-15

    Intestinal failure (IF) is the inability of the alimentary tract to digest and absorb sufficient nutrition to maintain normal fluid balance, growth, and health. It commonly arises from disease affecting the mesenteric root. Although severe IF is usually managed in specialized units, it lies at the end of a spectrum with degrees of nutritional compromise being widely encountered, but commonly under-recognized. Furthermore, in the majority of cases, the initial enteric insult occurs in non-specialist IF centres. The aim of this article is to review the common causes of IF, general principles of its management, some commoner complications, and the role of radiology in the approach to a patient with severe IF. The radiologist has a crucial role in helping provide access for feeding solutions (both enteral and parenteral) and controlling sepsis (via drainage of collections) in an initial restorative phase of treatment, whilst simultaneously mapping bowel anatomy and quality, and searching for disease complications to assist the clinicians in planning a later, restorative phase of therapy.

  16. [Intestinal failure: from adaptation to transplantation].

    Science.gov (United States)

    Messing, B; Corcos, O; Amiot, A; Joly, F

    2009-01-01

    Optimised Home Parenteral Nutrition is still, after 35 years of progress, the of benign but chronic Intestinal Failure. A better recognition of chronic Intestinal Failure, in its multiple facets, is warranted for a better approach of associated treatment to Home Parenteral Nutrition, i.e., intestinal trophic factors (growth hormone, Glucagon Like Peptide-2), rehabilitative surgery (reestablishment of colonic continuity, reverse jejunal segment in severe short gut type II) and/or reconstructive surgery (intestinal transplantation for end stage intestinal failure patients). Boundaries of permanent, judged irreversible, intestinal failure will be certainly modified in the following years by combining the various and effective therapies which optimise management by ameliorating absorption of the remnant short gut. The work done on short bowel syndrome in the past 20 years should be done in the next years for chronic-intestinal - pseudo-obstruction patients presenting with intestinal failure on a large European scale because chronic-intestinal - pseudo-obstruction is a group of heterogeneous but rare intestinal diseases. Intestinal transplantation is now a mature therapy with formal indication especially in case of Home Parenteral Nutrition failure (mainly Home Parenteral Nutrition-associated severe liver disease) where combined Liver-intestine transplantation is indicated before end-stage liver failure occurs. For high-risk patients, "preemptive" indication for intestinal transplantation alone will be discussed before home parenteral nutrition complications occur. No doubt that, for improving overall outcome in intestinal failure patients, reference centres should have in expert hands the whole spectrum of medicosurgical therapies for intestinal failure.

  17. The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis.

    Science.gov (United States)

    Donaldson, David S; Else, Kathryn J; Mabbott, Neil A

    2015-09-01

    Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the small intestinal

  18. Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse.

    Science.gov (United States)

    Dawson, P A; Huxley, S; Gardiner, B; Tran, T; McAuley, J L; Grimmond, S; McGuckin, M A; Markovich, D

    2009-07-01

    Sulfate (SO(4)(2-)) is an abundant component of intestinal mucins and its content is decreased in certain gastrointestinal diseases, including inflammatory bowel disease. In this study, the hyposulfataemic NaS1 sulfate transporter null (Nas1(-/-)) mice were used to investigate the physiological consequences of disturbed sulfate homeostasis on (1) intestinal sulfomucin content and mRNA expression; (2) intestinal permeability and proliferation; (3) dextran sulfate sodium (DSS)-induced colitis; and (4) intestinal barrier function against the bacterial pathogen, Campylobacter jejuni. Intestinal sulfomucins and sialomucins were detected by high iron diamine staining, permeability was assessed by fluorescein isothiocyanate (FITC)-dextran uptake, and proliferation was assessed by 5-bromodeoxyuridine (BrdU) incorporation. Nas1(-/-) and wild-type (Nas1(+/+)) mice received DSS in drinking water, and intestinal damage was assessed by histological, clinical and haematological measurements. Mice were orally inoculated with C jejuni, and intestinal and systemic infection was assessed. Ileal mRNA expression profiles of Nas1(-/-) and Nas1(+/+) mice were determined by cDNA microarrays and validated by quantitative real-time PCR. Nas1(-/-) mice exhibited reduced intestinal sulfomucin content, enhanced intestinal permeability and DSS-induced colitis, and developed systemic infections when challenged orally with C jejuni. The transcriptional profile of 41 genes was altered in Nas1(-/-) mice, with the most upregulated gene being pancreatic lipase-related protein 2 and the most downregulated gene being carbonic anhydrase 1 (Car1). Sulfate homeostasis is essential for maintaining a normal intestinal metabolic state, and hyposulfataemia leads to reduced intestinal sulfomucin content, enhanced susceptibility to toxin-induced colitis and impaired intestinal barrier to bacterial infection.

  19. [Interaction between humans and intestinal bacteria as a determinant for intestinal health : intestinal microbiome and inflammatory bowel diseases].

    Science.gov (United States)

    Haller, Dirk; Hörmannsperger, G

    2015-02-01

    Recent scientific results underline the importance of the intestinal microbiome, the totality of all intestinal microbes and their genes, for the health of the host organism. The intestinal microbiome can therefore be considered as a kind of "external organ". It has been shown that the intestinal microbiota is a complex and dynamic ecosystem that influences host immunity and metabolism beyond the intestine. The composition and functionality of the intestinal microbiota is of major importance for the development and maintenance of intestinal functions. Inflammatory bowel diseases (IBD) are characterized by dysregulated interactions between the host and its microbiota.The present contribution summarizes current knowledge of the composition and development of the intestinal microbiome and gives an overview of the bidirectional interaction between host and microbiota. The contribution informs about insights regarding the role of the intestinal microbiota in IBD and finally discusses the protective potential of microbial therapies in the context of IBD.

  20. E. coli O124 K72 alters the intestinal barrier and the tight junctions proteins of guinea pig intestine.

    Science.gov (United States)

    Ren, Xiaomeng; Zhu, Yanyan; Gamallat, Yaser; Ma, Shenhao; Chiwala, Gift; Meyiah, Abdo; Xin, Yi

    2017-10-01

    Our research group previously isolated and identified a strain of pathogenic Escherichia coli from clinical samples called E. coli O124 K72. The present study was aimed at determining the potential effects of E. coli O124 K72 on intestinal barrier functions and structural proteins integrity in guinea pig. Guinea pigs were grouped into three groups; control (CG); E. coli O124 K72 (E. coli); and probiotics Lactobacillus rhamnosus (LGG). Initially, we create intestinal dysbiosis by giving all animals Levofloxacin for 10days, but the control group (CG) received the same volume of saline. Then, the animals received either E. coli O124 K72 (E. coli) or Lactobacillus rhamnosus (LGG) according to their assigned group. E. coli O124 K72 treatment significantly affected colon morphology and distorted intestinal barrier function by up-regulating Claudin2 and down-regulating Occludin. In addition, E. coli upregulated the mRNA expression of MUC1, MUC2, MUC13 and MUC15. Furthermore, suspected tumor was found in the E. coli treated animals. Our results suggested that E. coli O124 K72 strain has adverse effects on intestinal barrier functions and is capable of altering integrity of structural proteins in guinea pig model while at same time it may have a role in colon carcinogenesis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Effect of Polysaccharides from on Intestinal Mucosal Barrier of Lipopolysaccharide Challenged Mice

    Directory of Open Access Journals (Sweden)

    Jie Han

    2016-01-01

    Full Text Available To investigate the role of polysaccharide from Acanthopanax senticosus (ASPS in preventing lipopolysaccharide (LPS-induced intestinal injury, 18 mice (at 5 wk of age were assigned to three groups with 6 replicates of one mouse each. Mice were administrated by oral gavage with or without ASPS (300 mg/kg body weight for 14 days and were injected with saline or LPS at 15 days. Intestinal samples were collected at 4 h post-challenge. The results showed that ASPS ameliorated LPS-induced deterioration of digestive ability of LPS-challenged mice, indicated by an increase in intestinal lactase activity (45%, p<0.05, and the intestinal morphology, as proved by improved villus height (20.84%, p<0.05 and villus height:crypt depth ratio (42%, p<0.05, and lower crypt depth in jejunum (15.55%, p<0.05, as well as enhanced intestinal tight junction proteins expression involving occludin-1 (71.43%, p<0.05. ASPS also prevented intestinal inflammation response, supported by decrease in intestinal inflammatory mediators including tumor necrosis factor α (22.28%, p<0.05 and heat shock protein (HSP70 (77.42%, p<0.05. In addition, intestinal mucus layers were also improved by ASPS, as indicated by the increase in number of goblet cells (24.89%, p<0.05 and intestinal trefoil peptide (17.75%, p<0.05. Finally, ASPS facilitated mRNA expression of epidermal growth factor (100%, p<0.05 and its receptor (200%, p<0.05 gene. These results indicate that ASPS can prevent intestinal mucosal barrier injury under inflammatory conditions, which may be associated with up-regulating gene mRNA expression of epidermal growth factor and its receptor.

  2. Magnetic susceptibilities of minerals

    Science.gov (United States)

    Rosenblum, Sam; Brownfield, I.K.

    2000-01-01

    Magnetic separation of minerals is a topic that is seldom reported in the literature for two reasons. First, separation data generally are byproducts of other projects; and second, this study requires a large amount of patience and is unusually tedious. Indeed, we suspect that most minerals probably are never investigated for this property. These data are timesaving for mineralogists who concentrate mono-mineralic fractions for chemical analysis, age dating, and for other purposes. The data can certainly be used in the ore-beneficiation industries. In some instances, magnetic-susceptibility data may help in mineral identification, where other information is insufficient. In past studies of magnetic separation of minerals, (Gaudin and Spedden, 1943; Tille and Kirkpatrick, 1956; Rosenblum, 1958; Rubinstein and others, 1958; Flinter, 1959; Hess, 1959; Baker, 1962; Meric and Peyre, 1963; Rojas and others, 1965; and Duchesne, 1966), the emphasis has been on the ferromagnetic and paramagnetic ranges of extraction. For readers interested in the history of magnetic separation of minerals, Krumbein and Pettijohn (1938, p. 344-346) indicated nine references back to 1848. The primary purpose of this paper is to report the magnetic-susceptibility data on as many minerals as possible, similar to tables of hardness, specific gravity, refractive indices, and other basic physical properties of minerals. A secondary purpose is to demonstrate that the total and best extraction ranges are influenced by the chemistry of the minerals. The following notes are offered to help avoid problems in separating a desired mineral concentrate from mixtures of mineral grains.

  3. Intestinal Microbiota and the Innate Immune System – A Crosstalk in Crohn’s Disease Pathogenesis

    Science.gov (United States)

    Haag, Lea-Maxie; Siegmund, Britta

    2015-01-01

    Crohn’s disease (CD) is a chronic, relapsing inflammatory disorder that can occur anywhere along the gastrointestinal tract. The precise etiology of CD is still unclear but it is widely accepted that a complex series of interactions between susceptibility genes, the immune system and environmental factors are implicated in the onset and perpetuation of the disease. Increasing evidence from experimental and clinical studies implies the intestinal microbiota in disease pathogenesis, thereby supporting the hypothesis that chronic intestinal inflammation arises from an abnormal immune response against the microorganisms of the intestinal flora in genetically susceptible individuals. Given that CD patients display changes in their gut microbiota composition, collectively termed “dysbiosis,” the question raises whether the altered microbiota composition is a cause of disease or rather a consequence of the inflammatory state of the intestinal environment. This review will focus on the crosstalk between the gut microbiota and the innate immune system during intestinal inflammation, thereby unraveling the role of the microbiota in CD pathogenesis. PMID:26441993

  4. Associação timoma e estrongiloidíase intestinal grave

    Directory of Open Access Journals (Sweden)

    Godoy Pérsio

    1998-01-01

    Full Text Available Os autores relatam o caso de um homem de 59 anos de idade com timoma e estrongiloidíase intestinal grave. São revistos aspectos da resposta imunitária relacionados ao tumor e, possivelmente, implicados no desenvolvimento da hiperinfecção pelo Strongyloides stercoralis.

  5. Methods to assess Myc function in intestinal homeostasis, regeneration, and tumorigenesis

    NARCIS (Netherlands)

    Huels, David J.; Cammareri, Patrizia; Ridgway, Rachel A.; Medema, Jan P.; Sansom, Owen J.

    2013-01-01

    Within the intestinal epithelium, c-Myc has been characterized as a target of β-catenin-TCF signalling (He et al., Science 281:1509-1512, 1998). Given the most commonly mutated tumor suppressor gene within colorectal cancer (CRC) is the APC (Adenomatous Polyposis Coli) gene, a negative regulator of

  6. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  7. Brain Tumor Symptoms

    Science.gov (United States)

    ... Brain Anatomy Brain Tumor Symptoms Headaches Seizures Memory Depression Mood Swings & Cognitive Changes Fatigue Other Symptoms Diagnosis Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us ...

  8. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  9. Role of intestinal flora in colorectal cancer from the metabolite perspective: a systematic review

    Science.gov (United States)

    Han, Shuwen; Gao, Jianlan; Zhou, Qing; Liu, Shanshan; Wen, Caixia

    2018-01-01

    Colorectal cancer is one of the most common human malignant tumors. Recent research has shown that colorectal cancer is a dysbacteriosis-induced disease; however, the role of intestinal bacteria in colorectal cancer is unclear. This review explores the role of intestinal flora in colorectal cancer. In total, 57 articles were included after identification and screening. The pertinent literature on floral metabolites in colorectal cancer from three metabolic perspectives – including carbohydrate, lipid, and amino acid metabolism – was analyzed. An association network regarding the role of intestinal flora from a metabolic perspective was constructed by analyzing the previous literature to provide direction and insight for further research on intestinal flora in colorectal cancer. PMID:29440929

  10. Cytokine levels in the preterm infant with neonatal intestinal injury.

    Science.gov (United States)

    Bhatia, Amina M; Stoll, Barbara J; Cismowski, Mary J; Hamrick, Shannon E

    2014-06-01

    The purpose of this study is to characterize the cytokine response of preterm newborns with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) before surgical treatment and to relate these finding to intestinal disease (NEC vs. SIP). The study was a 14-month prospective, cohort study of neonates undergoing surgery or drainage for NEC or SIP or surgical ligation of patent ductus arteriosus (PDA). Multiplex cytokine detection technology was used to analyze six inflammatory markers: interleukin-2, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 β (IL-1β), interferon-gamma, and tumor necrosis factor-α (TNF-α). Patients with NEC had much higher median preoperative levels of IL-6 (NEC: 8,381 pg/mL; SIP: 36 pg/mL; PDA: 25 pg/mL, p neonate. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. The CT diagnosis and operative indication for panperitonitis carcinomatosa with intestinal obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Kitahara, Shinzo; Shirakura, Tatsuya; Kanemitsu, Hiroyuki; Shimada, Nagato; Nonaka, Kyoei; Hashimura, Chiaki; Shiba, Tadaaki; Tsugu, Yukio [Toho Univ., Tokyo (Japan). School of Medicine

    1997-05-01

    For the purpose of clarifying the discrimination points in the CT diagnosis of peritonitis carcinomatosa and operative indication for the disease, 52 patients with peritonitis carcinomatosa presenting with intestinal obstruction admitted to the hospital in a 5-year period (January 1990 to December 1994) were retrospectively studied, by comparing to another 22 cases of benign ileus in which CT was performed. As for the CT images, the following 10 items were evaluated: ascites, epiploic thickening, intestinal mass, intraperitoneal tumor, intestinal wall thickening, the mesenteric macule-shaped and funicular views, intestinal liquid being full, expansion intestinal tract gas, visualization of the Kerckring folds and mirror surface formation. Furthermore, the additional five items were examined as reference views: pleural effusion, liver metastasis, bile duct occlusion, hydronephrosis and paraaortic lymphnode swelling. The degree of each view was scored. When an average score in total was asked, it was 5.3{+-}2.9 S.D. in peritonitis carcinomatosa or -1.6{+-}2.9 S.D. in the benign ileus, with sensitivity of 95.7%, specificity of 76.7%, and accuracy of 90.0%. This score evaluation is useful to make a diagnosis of peritonitis carcinomatosa with intestinal obstruction. As to operative indication, possibilities are suggested that patients showing a mirror surface image can be candidates for excision of the intestine and anastomosis and that patients having hydronephrosis should not be candidates for operation. (author)

  12. All-trans-retinoic acid attenuates intestinal injury in a neonatal rat model of necrotizing enterocolitis.

    Science.gov (United States)

    Ozdemir, Ramazan; Yurttutan, Sadık; Sari, Fatma Nur; Oncel, Mehmet Yekta; Erdeve, Omer; Unverdi, Hatice Germen; Uysal, Bülent; Dilmen, Ugur

    2013-01-01

    Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators. This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC). Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4°C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis. Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-α levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p intestinal injury through its anti-inflammatory and antioxidant properties. Copyright © 2013 S. Karger AG, Basel.

  13. Anterior Abdominal Wall Desmoids Tumor in a Five Year Old Girl – A ...

    African Journals Online (AJOL)

    xp

    ABSTRACT: Desmoid tumors are rare, slow – growing, mesenchymal monoclinic proliferation. It may occur as intra-abdominal tumor usually affecting the mesentery of the intestine or it could be extra-abdominal in which they may affect the popliteal region, the chest wall or the anterior abdominal wall. Reports in children ...

  14. Anterior Abdominal Wall Desmoids Tumor in a Five Year Old Girl – A ...

    African Journals Online (AJOL)

    Desmoid tumors are rare, slow – growing, mesenchymal monoclinic proliferation. It may occur as intra-abdominal tumor usually affecting the mesentery of the intestine or it could be extra-abdominal in which they may affect the popliteal region, the chest wall or the anterior abdominal wall. Reports in children less than 10 ...

  15. Susceptibility to anchoring effects

    Directory of Open Access Journals (Sweden)

    Todd McElroy

    2007-02-01

    Full Text Available Previous research on anchoring has shown this heuristic to be a very robust psychological phenomenon ubiquitous across many domains of human judgment and decision-making. Despite the prevalence of anchoring effects, researchers have only recently begun to investigate the underlying factors responsible for how and in what ways a person is susceptible to them. This paper examines how one such factor, the Big-Five personality trait of openness-to-experience, influences the effect of previously presented anchors on participants' judgments. Our findings indicate that participants high in openness-to-experience were significantly more influenced by anchoring cues relative to participants low in this trait. These findings were consistent across two different types of anchoring tasks providing convergent evidence for our hypothesis.

  16. Topological susceptibility from slabs

    Energy Technology Data Exchange (ETDEWEB)

    Bietenholz, Wolfgang [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, A.P. 70-543, Distrito Federal, C.P. 04510 (Mexico); Forcrand, Philippe de [Institute for Theoretical Physics, ETH Zürich,CH-8093 Zürich (Switzerland); CERN, Physics Department, TH Unit, CH-1211 Geneva 23 (Switzerland); Gerber, Urs [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, A.P. 70-543, Distrito Federal, C.P. 04510 (Mexico); Instituto de Física y Matemáticas, Universidad Michoacana de San Nicolás de Hidalgo,Edificio C-3, Apdo. Postal 2-82, Morelia, Michoacán, C.P. 58040 (Mexico)

    2015-12-14

    In quantum field theories with topological sectors, a non-perturbative quantity of interest is the topological susceptibility χ{sub t}. In principle it seems straightforward to measure χ{sub t} by means of Monte Carlo simulations. However, for local update algorithms and fine lattice spacings, this tends to be difficult, since the Monte Carlo history rarely changes the topological sector. Here we test a method to measure χ{sub t} even if data from only one sector are available. It is based on the topological charges in sub-volumes, which we denote as slabs. Assuming a Gaussian distribution of these charges, this method enables the evaluation of χ{sub t}, as we demonstrate with numerical results for non-linear σ-models.

  17. Topological Susceptibility from Slabs

    CERN Document Server

    Bietenholz, Wolfgang; Gerber, Urs

    2015-01-01

    In quantum field theories with topological sectors, a non-perturbative quantity of interest is the topological susceptibility chi_t. In principle it seems straightforward to measure chi_t by means of Monte Carlo simulations. However, for local update algorithms and fine lattice spacings, this tends to be difficult, since the Monte Carlo history rarely changes the topological sector. Here we test a method to measure chi_t even if data from only one sector are available. It is based on the topological charges in sub-volumes, which we denote as slabs. Assuming a Gaussian distribution of these charges, this method enables the evaluation of chi_t, as we demonstrate with numerical results for non-linear sigma-models.

  18. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  19. Modeling intestinal disorders using zebrafish.

    Science.gov (United States)

    Zhao, X; Pack, M

    2017-01-01

    Although the zebrafish was initially developed as a model system to study embryonic development, it has gained increasing attention as an advantageous system to investigate human diseases, including intestinal disorders. Zebrafish embryos develop rapidly, and their digestive system is fully functional and visible by 5days post fertilization. There is a large degree of homology between the intestine of zebrafish and higher vertebrate organisms in terms of its cellular composition and function as both a digestive and immune organ. Furthermore, molecular pathways regulating injury and immune responses are highly conserved. In this chapter, we provide an overview of studies addressing developmental and physiological processes relevant to human intestinal disease. These studies include those related to congenital disorders, host-microbiota interactions, inflammatory diseases, motility disorders, and intestinal cancer. We also highlight the utility of zebrafish to functionally validate candidate genes identified through mutational analyses and genome-wide association studies, and discuss methodologies to investigate the intestinal biology that are unique to zebrafish. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Isotopic identification of intestinal strangulation

    International Nuclear Information System (INIS)

    Anderson, M.C.; Selby, J.B.

    1982-01-01

    A small series of eleven dogs prepared with a strangulating segment of jejunum demonstrated that a radionuclide, 99 mTc-labelled albumin, concentrates in the lumen and bowel wall of the affected intestinal segment. Modern scanning equipment accurately localized the strangulating loop. This technique has the potential of identifying patients with intestinal obstruction, in whom strangulation is a factor, prior to the development of impaired arterial inflow and frank gangrene. These findings confirmed earlier obstructions that were reported when nuclear scanning instrumentation was less sophisticated. Identification of patients at risk for intestinal strangulation requires a high index of suspicion. Excruciating cramping abdominal pain out of proportion to physical findings, roentgenogram evidence, and laboratory studies should alert the physician to the possibility of intestinal ischemia and closed loop obstruction. Radionuclide scanning in such cases may be of assistance in defining or excluding the diagnosis of a strangulating mechanism. The test is simple, relatively economical, and represents a low risk procedure to patients. It would have no place when the classic physical and laboratory findings of intestinal infarction are present

  1. Isotopic identification of intestinal strangulation

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, M.C.; Selby, J.B.

    1982-12-01

    A small series of eleven dogs prepared with a strangulating segment of jejunum demonstrated that a radionuclide, /sup 99/mTc-labelled albumin, concentrates in the lumen and bowel wall of the affected intestinal segment. Modern scanning equipment accurately localized the strangulating loop. This technique has the potential of identifying patients with intestinal obstruction, in whom strangulation is a factor, prior to the development of impaired arterial inflow and frank gangrene. These findings confirmed earlier obstructions that were reported when nuclear scanning instrumentation was less sophisticated. Identification of patients at risk for intestinal strangulation requires a high index of suspicion. Excruciating cramping abdominal pain out of proportion to physical findings, roentgenogram evidence, and laboratory studies should alert the physician to the possibility of intestinal ischemia and closed loop obstruction. Radionuclide scanning in such cases may be of assistance in defining or excluding the diagnosis of a strangulating mechanism. The test is simple, relatively economical, and represents a low risk procedure to patients. It would have no place when the classic physical and laboratory findings of intestinal infarction are present.

  2. The Li-Fraumeni syndrome: an inherited susceptibility to cancer.

    Science.gov (United States)

    Evans, S C; Lozano, G

    1997-09-01

    The Li-Fraumeni syndrome is a rare autosomal-dominant disease whose hallmark is a predisposition to a wide range of cancers among members of a family. Many of these families have a germline mutation within the tumor suppressor gene TP53, which encodes the p53 protein. The inheritance of a mutant TP53 allele results in a 25-fold increase in the chance of developing cancer by 50 years of age, compared with the general population. TP53 mutations are also very common in the development of somatic tumors. This article reviews the biological and biochemical role of p53 in the susceptibility to cancer in Li-Fraumeni syndrome.

  3. [Glomus jugulare tumor: perioperative management].

    Science.gov (United States)

    Ferrando, A; Fraile, J R; Bermejo, L; de Miguel, A; Aristegui, M; Hervías, M; Quirós, P

    1996-12-01

    Surgical treatment of glomus jugulare tumors yields high rates of perioperative morbidity and mortality for several reasons, among them neuroendocrine secretory activity, a high degree of vascularization, intracranial extension, duration of surgery and cranial nerve lesion. Secretory activity (e.g. catecholamines and serotonin) should be investigated before surgery and treated appropriately. Carotid arteriography (and ball occlusion) are useful to assess vascularization of the tumor and determine the need to clamp the carotid artery during the procedure. Potential complications such as hemodynamic alterations (bleeding or endocrine response), pulmonary embolism (air or thrombotic), hypothermia, facial nerve lesion, should be monitored for during surgery. After surgery cranial nerve involvement, which can lead to dysphagia and bronchoaspiration, must be looked for; the risk of cerebro-spinal fluid fistula is also high. We report the case of a woman who underwent surgery for a non secreting glomus jugulare tumor with extradural intracranial invasion. The main complications during surgery were bleeding with hemodynamic repercussions, pulmonary embolism, lesions in the VII, VIII and X cranial nerves, and opening of the dura mater (which required insertion of an intradural drain to prevent formation of a fistula). After surgery oral intake was delayed until intestinal function was established and glottic sphincter competence was verified by fiberoptic laryngoscopy. The only complication presenting at this time was cephalea, which disappeared upon removal of the drain on day 4. The patient was released on day 10.

  4. Antimicrobial Susceptibility of Enteric Gram Negative Facultative Anaerobe Bacilli in Aerobic versus Anaerobic Conditions

    Science.gov (United States)

    Amachawadi, Raghavendra G.; Renter, David G.; Volkova, Victoriya V.

    2016-01-01

    Antimicrobial treatments result in the host’s enteric bacteria being exposed to the antimicrobials. Pharmacodynamic models can describe how this exposure affects the enteric bacteria and their antimicrobial resistance. The models utilize measurements of bacterial antimicrobial susceptibility traditionally obtained in vitro in aerobic conditions. However, in vivo enteric bacteria are exposed to antimicrobials in anaerobic conditions of the lower intestine. Some of enteric bacteria of food animals are potential foodborne pathogens, e.g., Gram-negative bacilli Escherichia coli and Salmonella enterica. These are facultative anaerobes; their physiology and growth rates change in anaerobic conditions. We hypothesized that their antimicrobial susceptibility also changes, and evaluated differences in the susceptibility in aerobic vs. anaerobic conditions of generic E. coli and Salmonella enterica of diverse serovars isolated from cattle feces. Susceptibility of an isolate was evaluated as its minimum inhibitory concentration (MIC) measured by E-Test® following 24 hours of adaptation to the conditions on Mueller-Hinton agar, and on a more complex tryptic soy agar with 5% sheep blood (BAP) media. We considered all major antimicrobial drug classes used in the U.S. to treat cattle: β-lactams (specifically, ampicillin and ceftriaxone E-Test®), aminoglycosides (gentamicin and kanamycin), fluoroquinolones (enrofloxacin), classical macrolides (erythromycin), azalides (azithromycin), sulfanomides (sulfamethoxazole/trimethoprim), and tetracyclines (tetracycline). Statistical analyses were conducted for the isolates (n≥30) interpreted as susceptible to the antimicrobials based on the clinical breakpoint interpretation for human infection. Bacterial susceptibility to every antimicrobial tested was statistically significantly different in anaerobic vs. aerobic conditions on both media, except for no difference in susceptibility to ceftriaxone on BAP agar. A satellite experiment

  5. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

    Science.gov (United States)

    2018-04-23

    Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma

  6. Intestine immune homeostasis after alcohol and burn injury.

    Science.gov (United States)

    Li, Xiaoling; Hammer, Adam M; Rendon, Juan L; Choudhry, Mashkoor A

    2015-06-01

    Traumatic injury remains one of the most prevalent reasons for patients to be hospitalized. Burn injury accounts for 40,000 hospitalizations in the United States annually, resulting in a large burden on both the health and economic system and costing millions of dollars every year. The complications associated with postburn care can quickly cause life-threatening conditions including sepsis and multiple organ dysfunction and failure. In addition, alcohol intoxication at the time of burn injury has been shown to exacerbate these problems. One of the biggest reasons for the onset of these complications is the global suppression of the host immune system and increased susceptibility to infection. It has been hypothesized that infections after burn and other traumatic injury may stem from pathogenic bacteria from within the host's gastrointestinal tract. The intestine is the major reservoir of bacteria within the host, and many studies have demonstrated perturbations of the intestinal barrier after burn injury. This article reviews the findings of these studies as they pertain to changes in the intestinal immune system after alcohol and burn injury.

  7. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.

    Directory of Open Access Journals (Sweden)

    Amy M Becker

    Full Text Available Specific G protein coupled receptors (GPRs regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation.

  8. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.

    Science.gov (United States)

    Zhu, Shu; Ding, Siyuan; Wang, Penghua; Wei, Zheng; Pan, Wen; Palm, Noah W; Yang, Yi; Yu, Hua; Li, Hua-Bing; Wang, Geng; Lei, Xuqiu; de Zoete, Marcel R; Zhao, Jun; Zheng, Yunjiang; Chen, Haiwei; Zhao, Yujiao; Jurado, Kellie A; Feng, Ningguo; Shan, Liang; Kluger, Yuval; Lu, Jun; Abraham, Clara; Fikrig, Erol; Greenberg, Harry B; Flavell, Richard A

    2017-06-29

    Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens.

  9. Intestinal microflora as potential modifiers of sensitizer activity in vivo

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Clarke, C.; Dawson, K.B.; Simpson, W.; Simmons, D.J.C.

    1984-01-01

    Treatment of mice (some bearing Lewis lung tumors), with penicillin (PEN) at 500 mg/l drinking water for one week prior to treatment with misonidazole (MIS), resulted in: the elimination of their anaerobic cecal flora; a decrease in MIS-induced neurotoxicity; an increase in pharmacological exposure to MIS; a decrease in MIS chemopotentiation; a probable increase in MIS radiosensitization; an increase in MIS induced hypothermia. Assuming no chemical interaction between PEN and MIS, these observations indicate that the intestinal microflora can influence the activity of MIS in vivo. The observed reduction in the neurotoxic but not the radiosensitizing potential of MIS following PEN treatment indicates a therapeutic benefit

  10. Galanin and vasoactive intestinal polypeptide

    DEFF Research Database (Denmark)

    Harling, H; Messell, T; Poulsen, Steen Seier

    1991-01-01

    By immunohistochemistry and double staining technique, almost complete coexistence of galanin-like immunoreactivity (GAL-LI) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) was demonstrated in submucosal ganglionic cells and mucosal nerve fibers of the porcine ileum. The rele......By immunohistochemistry and double staining technique, almost complete coexistence of galanin-like immunoreactivity (GAL-LI) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) was demonstrated in submucosal ganglionic cells and mucosal nerve fibers of the porcine ileum...

  11. Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Maria C. Opazo

    2018-03-01

    Full Text Available The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases.

  12. Gintonin absorption in intestinal model systems

    Directory of Open Access Journals (Sweden)

    Byung-Hwan Lee

    2018-01-01

    Conclusion: The present study shows that gintonin could be absorbed in the intestine through transcellular and paracellular diffusion, and active transport. In addition, the lipid component of gintonin might play a key role in its intestinal absorption.

  13. Microbiota, intestinal immunity, and mouse bustle

    OpenAIRE

    Kruglov, A.; Nedospasov, S.

    2014-01-01

    The composition of the intestinal microbiota is regulated by the immune system. This paper discusses the role of cytokines and innate immunity lymphoid cells in the intestinal immune regulation by means of IgA.

  14. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility.

    Science.gov (United States)

    Xia, Lei-Zhou; Liu, Yi; Xu, Xiao-Zhou; Jiang, Peng-Cheng; Ma, Gui; Bu, Xue-Feng; Zhang, Yong-Jun; Yu, Feng; Xu, Ke-Sen; Li, Hua

    2014-08-28

    To identify the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and gastric cancer (GC) susceptibility. Systematic searches were performed on the electronic databases PubMed, ISI, Web of knowledge, CNKI and Wanfang, as well as manual searching of the references of the identified articles. A total of 26 papers were included in this meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95%CI were used to evaluate the associations between MTHFR polymorphisms and GC risk. The I (2) statistics were used to evaluate between-study heterogeneity. Sensitivity analysis was also performed. Increased risk was found for the MTHFR C677T polymorphism under four genetic models (TT + CT vs CC: OR = 1.23, P = 0.002; T vs C: OR = 1.15, P = 0.001; TT vs CC: OR = 1.37, P = 0.0005; TT vs CT + CC: OR = 1.17, P = 0.0008). Subgroup analysis by ethnicity suggested that C677T polymorphism conferred a risk of GC in eastern but not in western populations. Stratification by tumor site showed an association between the C677T polymorphism and gastric cardia cancer and non-cardia GC in the worldwide population and in eastern populations. Regardless of comparisons with controls or diffuse-type GC, a positive association was found for the C677T polymorphism and an increased risk of intestinal-type GC in the whole population and in western populations. With regard to the A1298C polymorphism, we found that genotype CC was significantly decreased and conferred protection against GC in eastern populations (CC vs AA: OR = 0.44, P = 0.03; CC vs AC + AA: OR = 0.46, P = 0.04). MTHFR C677T polymorphism is a risk factor for GC, and the A1298C polymorphism may be a protective factor against GC in eastern populations.

  15. Gastrointestinal stromal tumor: a case report and review of the literature

    International Nuclear Information System (INIS)

    Macedo, Leonardo Lopes de; Torres, Lucas Rios; Faucz, Rafael Artigas; Tornin, Olger de Souza; Souza, Ricardo Pires de; Fonseca, Carlos Alberto Marcovechio

    2006-01-01

    Gastrointestinal stromal tumors are the most common mesenchymal tumors and are characterized by expression of KIT (CD117), a tyrosine-kinase growth factor receptor. They occur in individuals over 50 years of age and commonly arise in stomach or in the small intestine. To emphasize our paper we report a case of gastrointestinal stromal tumor that showed the typical image and pathologic findings of the primary lesion and its metastases. (author)

  16. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Thomas Gress

    2012-02-01

    Full Text Available Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-a, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  17. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rinke, Anja, E-mail: sprengea@staff.uni-marburg.de; Michl, Patrick; Gress, Thomas [Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, Marburg D-35043 (Germany)

    2012-02-08

    Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN) should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-α, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET) has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  18. Short-term carcinogenicity testing of a potent murine intestinal mutagen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), in Apc1638N transgenic mice

    DEFF Research Database (Denmark)

    Sørensen, Ilona Kryspin; Kristiansen, E.; Mortensen, Alicja

    1997-01-01

    Transgenic Apc1638N mice, heterozygous for a targeted frameshift mutation at codon 1638 of the endogenous adenomatous polyposis coli (APC) gene, are predisposed to develop multiple adenomas and adenocarcinomas along the intestinal tract and to a number of extra-intestinal lesions including, among...... increased number of small intestinal tumors as well as an increased number of aberrant crypt foci (ACF) were observed in male Apc(+)/Apc1638N mice compared with untreated transgenic mice, No differences in intestinal and mammary tumor multiplicity were observed between treated and control Apc(+)/Apc1638N...... others, mammary tumors, We have studied these mice in a short-term carcinogenicity test with 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a potent murine small intestinal mutagen and lymphomagen. Upon dietary administration of 0.03% PhIP in a short-term (6 months) study, a significantly...

  19. Treatment Option Overview (Small Intestine Cancer)

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  20. General Information about Small Intestine Cancer

    Science.gov (United States)

    ... all of an organ that contains cancer. The resection may include the small intestine and nearby organs (if the cancer has spread). The doctor may remove the section of the small intestine that contains cancer and perform an anastomosis (joining the cut ends of the intestine together). ...

  1. Abdominal tuberculosis presenting as intestinal obstruction- Case ...

    African Journals Online (AJOL)

    One of the complications of abdominal tuberculosis is intestinal obstruction, which can be acute, chronic or acute on chronic. Other complications include intestinal haemorrhage, perforation of the intestine (rare), faecal fistula, cold abscess formation, mal-absorption syndrome and dissemination of the tuberculosis to other ...

  2. Exercise and the gastro-intestinal tract

    African Journals Online (AJOL)

    on perfonnance and me value of cardiovascular training in improving performance in aerobic sports is well recognised. The role of me gastro-intestinal tracr, bom as a limiting and sustaining facror in aerobic exercises, is less well appreciared. Gastro-intestinal symptoms. The spectrum of gastro-intestinal effecrs of exercise ...

  3. Childhood intestinal obstruction in Northwestern Nigeria

    African Journals Online (AJOL)

    of childhood intestinal obstruction in this study agrees with those reportedis'gi m3 from other parts of the coun- try. Mortality from childhood intestinal obstruction is still high in our environment. References. 1. Otu AA. Tropical surgical abdominal emergencies: acute intestinal obstruction. Postgrad. Doctor (Afr) 1992; 14: 51. 2.

  4. Protein malnutrition and metronidazole induced intestinal bacterial ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-09-17

    Sep 17, 2008 ... The gastrointestinal tract serves as a potent barrier that prevents luminal bacteria from entering the host. This barrier function is maintained by a well-balanced intestinal flora, an unaltered perme- ability of the intestinal mucosa, and a normal functioning immune system. Furthermore, the intestinal mucosa, in.

  5. Childhood intestinal obstruction in Northwestern Nigeria | Uba ...

    African Journals Online (AJOL)

    Background: Intestinal obstruction is a common cause of childhood surgical emergency in the tropics. The aim of this paper was to assess the pattern and the outcome of mangement of intestinal obstruction in Nigerian children. Study design: The clinical reccords of all the cases of childhood intestinal obstructions managed ...

  6. The TNO gastro-intestinal model (TIM)

    NARCIS (Netherlands)

    Minekus, M.

    2015-01-01

    The TNO Gastro–Intestinal Model (TIM) is a multi–compartmental model, designed to realistically simulate conditions in the lumen of the gastro–intestinal tract. TIM is successfully used to study the gastro–intestinal behavior of a wide variety of feed, food and pharmaceutical products. Experiments

  7. Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Yuxia Xiong

    2018-02-01

    Full Text Available Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP. Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg or normal saline (control immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET, interleukin 1β (IL-1β, tumor necrosis factor α (TNF-α, nitric oxide (NO, myeloperoxidase (MPO, capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3, apoptosis-associated speck-like protein containing a CARD domain (ASC, casepase-1, secretary immunoglobulin A (SIgA, regulatory T cells (Tregs, and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1β, TNF-α, and NO in the blood and TNF-α, IL-1β, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while

  8. Differences in Radiation Dose Response between Small and Large Intestinal Crypts.

    Science.gov (United States)

    Otsuka, Kensuke; Suzuki, Keiji

    2016-09-01

    The protection of intestinal epithelial cells from the lethal effects induced by high-dose radiation is an important issue in radiotherapy and in the treatment of acute radiation syndrome. However, the effects of middle- and low-dose radiation on intestinal epithelial cells remain unclear. Because the accumulation of DNA damage in intestinal stem cells may be crucial for the development of cancer-initiating cells, it is important to understand the kinetics of DNA repair and tissue response (which are involved in the elimination of damaged cells and tissue injury repair) to middle- to low-dose irradiation. In this study, mice were X-ray irradiated with 0.1, 1 or 4 Gy, after which the small intestine (duodenum and ileum) and colon were harvested from the animals. DNA damage repair and the elimination of damaged cells were quantified by measuring the number of foci of 53BP1, a surrogate marker for DNA double-strand breaks. Tissue-proliferative response was evaluated by determining the number of Ki-67(+) and mitotic cells. Intra-crypt response differed considerably between the small intestine and the colon. In the small intestine, 53BP1 foci were detected immediately after irradiation, but rapidly disappeared thereafter, especially noticeable in Lgr5(+) stem cells. Cellular growth was temporally arrested; however, cell numbers and mitotic cell numbers in the crypt did not change. The kinetics of DNA damage repair in Lgr5(+) stem cells were similar to those in the small intestines, while the colon was more susceptible to radiation-induced damage. Preferential cell loss in the lower crypt was clearly observed in the colon; and after low-dose X-ray irradiation, only the colon exhibited considerably reduced cell numbers and dramatic induction of mitosis. These results suggest that differences in radiation dose response between the small and the large intestine may depend on the growth activity of stem cells after DNA repair.

  9. Entomoftoromicose intestinal: relato de caso

    Directory of Open Access Journals (Sweden)

    Fábia Aparecida Carvalho

    1997-02-01

    Full Text Available Os autores relatam um caso de entomoftoromicose intestinal causada por Entomophthorales, em indivíduo de 19 anos, agricultor e sem doença associada. O paciente foi submetido a ressecção intestinal e o diagnóstico foi feito após análise da peça cirúrgica. Após revisão da literatura, são discutidos a evolução clínica, as características clinicopatológicas, as dificuldades no diagnóstico e o tratamento dessa entidade rara.A case of intestinal entomophthoramycosis caused by Entomophthorales in a man with 19 years-old, farmer and without associated disease. The patient was submitted to a intestinal ressection and diagnosis was carried through after analisys of the surgical specimen. After a review of the literature, the clinical evolution, clinico-pathologic features, difficulties in diagnosis and treatment are discussed.

  10. Diversity of insect intestinal microflora

    Czech Academy of Sciences Publication Activity Database

    Mrázek, Jakub; Štrosová, Lenka; Fliegerová, Kateřina; Kott, T.; Kopečný, Jan

    2008-01-01

    Roč. 53, č. 3 (2008), s. 229-233 ISSN 0015-5632 R&D Projects: GA ČR GA303/06/0974 Institutional research plan: CEZ:AV0Z50450515 Keywords : insect intestinal microflora Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008

  11. Circadian disorganization alters intestinal microbiota.

    Science.gov (United States)

    Voigt, Robin M; Forsyth, Christopher B; Green, Stefan J; Mutlu, Ece; Engen, Phillip; Vitaterna, Martha H; Turek, Fred W; Keshavarzian, Ali

    2014-01-01

    Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.

  12. Milk products and intestinal health

    NARCIS (Netherlands)

    Van der Meer, R; Bovee-Oudenhoven, IMJ; Sesink, ALA; Kleibeuker, JH

    Milk products may improve intestinal health by means of the cytoprotective effects of their high calcium phosphate (CaPi) content. We hypothesized that this cytoprotection may increase host defenses against bacterial infections as well as decrease colon cancer risk. This paper summarizes our studies

  13. [Chronic intestinal pseudo-obstruction].

    Science.gov (United States)

    Joly, Francisca; Amiot, Aurélien; Coffin, Benoît; Lavergne-Slove, Anne; Messing, Bernard; Bouhnik, Yoram

    2006-01-01

    Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.

  14. INTESTINAL PERMEABILITY IN PEDIATRIC GASTROENTEROLOGY

    NARCIS (Netherlands)

    VANELBURG, RM; UIL, JJ; DEMONCHY, JGR; HEYMANS, HSA

    1992-01-01

    The role of the physiologic barrier function of the small bowel and its possible role in health and disease has attracted much attention over the past decade. The intestinal mucosal barrier for luminal macromolecules and microorganism is the result of non-immunologic and immunologic defense

  15. Microcontainers for Intestinal Drug Delivery

    DEFF Research Database (Denmark)

    Tentor, Fabio; Mazzoni, Chiara; Keller, Stephan Sylvest

    Among all the drug administration routes, the oral one is the most preferred by the patients being less invasive, faster and easier. Oral drug delivery systems designed to target the intestine are produced by powder technology and capsule formulations. Those systems including micro- and nano...

  16. A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis

    Science.gov (United States)

    Yang, Lianjun; Wang, Liping; Wang, Xin; Xian, Cory J.; Lu, Hai

    2016-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, for which the pathogenesis is thought to be a result of the combination of host genetic factors and environmental triggers. However, the precise factors that determine one’s susceptibility to AS remain to be unraveled. With 100 trillion bacteria residing in the mammalian gut having established a symbiotic relation with their host influencing many aspects of host metabolism, physiology, and immunity, a growing body of evidence suggests that intestinal microbiota may play an important role in AS. Several mechanisms have been suggested to explain the potential role of the microbiome in the etiology of AS, such as alterations of intestinal permeability, stimulation of immune responses, and molecular mimicry. In this review, the existing evidence for the involvement of the microbiome in AS pathogenesis was discussed and the potential of intestinal microbiome-targeting strategies in the prevention and treatment of AS was evaluated. PMID:27999312

  17. A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis.

    Science.gov (United States)

    Yang, Lianjun; Wang, Liping; Wang, Xin; Xian, Cory J; Lu, Hai

    2016-12-17

    Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, for which the pathogenesis is thought to be a result of the combination of host genetic factors and environmental triggers. However, the precise factors that determine one's susceptibility to AS remain to be unraveled. With 100 trillion bacteria residing in the mammalian gut having established a symbiotic relation with their host influencing many aspects of host metabolism, physiology, and immunity, a growing body of evidence suggests that intestinal microbiota may play an important role in AS. Several mechanisms have been suggested to explain the potential role of the microbiome in the etiology of AS, such as alterations of intestinal permeability, stimulation of immune responses, and molecular mimicry. In this review, the existing evidence for the involvement of the microbiome in AS pathogenesis was discussed and the potential of intestinal microbiome-targeting strategies in the prevention and treatment of AS was evaluated.

  18. Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae.

    Directory of Open Access Journals (Sweden)

    Derrick R Samuelson

    2017-06-01

    Full Text Available Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis. To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein

  19. Phospholipid ether analogs for the detection of colorectal tumors.

    Directory of Open Access Journals (Sweden)

    Dustin A Deming

    Full Text Available The treatment of localized colorectal cancer (CRC depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer/therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum IVIS (Perkin Elmer and a Fluobeam (Fluoptics. The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76×10(10 vs 3.27×10(9 respectively, p = 0.006. Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131I-CLR1404 was performed as part of a clinical trial in patients with advanced solid tumors. 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease.

  20. Intestinal Microbiota and the Innate Immune System – A Crosstalk in Crohn’s Disease Pathogenesis

    OpenAIRE

    Haag, Lea-Maxie; Siegmund, Britta

    2015-01-01

    Crohn’s disease (CD) is a chronic, relapsing inflammatory disorder that can occur anywhere along the gastrointestinal tract. The precise etiology of CD is still unclear but it is widely accepted that a complex series of interactions between susceptibility genes, the immune system and environmental factors are implicated in the onset and perpetuation of the disease. Increasing evidence from experimental and clinical studies implies the intestinal microbiota in disease pathogenesis, thereby sup...

  1. The Starting Lineup: Key Microbial Players in Intestinal Immunity and Homeostasis

    OpenAIRE

    Nicola Catherine Reading; Nicola Catherine Reading; Dennis L. Kasper; Dennis L. Kasper

    2011-01-01

    The complexity of microbiota inhabiting the intestine is increasingly apparent. Delicate balance of numerous bacterial species can affect development of the immune system, how susceptible a host is to pathogenic organisms, and the auto-inflammatory state of the host. In the last decade, with the increased use of germ-free mice, gnotobiotic mice, and animal models in which a germ-free animal has been colonized with a foreign microbiota such as humanized mice, it has been possible to deline...

  2. Perforated small intestine in a patient with T-cell lymphoma; a rare cause of peritonitis

    Directory of Open Access Journals (Sweden)

    Petrişor Banu

    2016-04-01

    Full Text Available The nontraumatic perforations of the small intestine are pathological entities with particular aspects in respect to diagnosis and treatment. These peculiarities derive from the nonspecific clinical expression of the peritonitis syndrome, and from the multitude of causes that might be the primary sources of the perforation: foreign bodies, inflammatory diseases, tumors, infectious diseases, etc. Accordingly, in most cases intestinal perforation is discovered only by laparotomy and the definitive diagnosis is available only after histopathologic examination. Small bowel malignancies are rare; among them, lymphomas rank third in frequency, being mostly B-cell non Hodgkin lymphomas. Only 10% of non-Hodgkin lymphomas are with T-cell. We report the case of a 57 years’ old woman with intestinal T-cell lymphoma, whose first clinical symptomatology was related to a complication represented by perforation of the small intestine. Laparotomy performed in emergency identified an ulcerative lesion with perforation in the jejunum, which required segmental enterectomy with anastomosis. The nonspecific clinical manifestations of intestinal lymphomas make from diagnosis a difficult procedure. Due to the fact that surgery does not have a definite place in the treatment of the small intestinal lymphomas (for cases complicated with perforation, and beyond the morbidity associated with the surgery performed in emergency conditions, prognosis of these patients is finally given by the possibility to control the systemic disease through adjuvant therapy.

  3. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  4. Tumors and Pregnancy

    Science.gov (United States)

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  5. DCB - Tumor Metastasis Research

    Science.gov (United States)

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  6. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  7. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  8. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course......The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...

  9. [Antimicrobial susceptibility in Chile 2012].

    Science.gov (United States)

    Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

    2014-04-01

    Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

  10. WHO Grade 2 Neuroendocrine Tumor in a 15-Year-Old Male: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Eric Johannesen

    2014-01-01

    Full Text Available Neuroendocrine tumors, distinguished from adenocarcinomas by their neuroendocrine differentiation, are the most common pediatric epithelial malignancy that most often occurs in the appendix. In 2010, the WHO classified neuroendocrine neoplasms into three grades based on morphology, mitotic count, and Ki67 proliferation index. A 15-year-old male with a history of anemia and failure to thrive was diagnosed with a well-differentiated neuroendocrine tumor in the jejunum that invaded into the subserosal soft tissue and metastasized to four lymph nodes. Pediatric neuroendocrine tumors frequently arise within hereditary tumor syndromes with pancreatic neuroendocrine tumors being the most common. Several studies also indicate an elevated risk of small intestinal neuroendocrine tumors in which children born to a parent with a history of neuroendocrine tumors in the small intestine have a significant increased risk of developing one.

  11. A etiological factors in mechanical intestinal obstruction

    International Nuclear Information System (INIS)

    Asad, S.; Khan, H.; Khan, I.A.; Ghaffar, S.; Rehman, Z.U.

    2012-01-01

    Background: Intestinal obstruction occurs when the normal flow of intestinal contents is interrupted. The most frequent causes of intestinal obstruction are postoperative adhesions and hernias, which cause extrinsic compression of the intestine. Less frequently, tumours or strictures of the bowel can cause intrinsic blockage. Objective of the study was to find out the various a etiological factors of mechanical intestinal obstruction and to evaluate the morbidity and mortality in adult patients presenting to Surgical 'A' unit of Ayub teaching hospital with mechanical intestinal obstruction. Methods: This cross-sectional study was conducted from March 2009 to September, 2009. All patients presenting with intestinal obstruction and were above the age of 12 years were included in the study. Patients with non-mechanical obstruction were excluded from the study and those who responded to conservative measures were also excluded. Results: A total of 36 patients with age ranging from 12 to 80 years (Mean age 37.72+-19.74 years) and male to female ratio of 1.77:1, were treated for mechanical intestinal obstruction. The most common cause for mechanical intestinal obstruction was adhesions (36.1%). Intestinal tuberculosis was the second most common cause (19.4%), while hernias and sigmoid volvulus affected 13.9% patients each. Malignancies were found in 5.6% cases. Conclusion: Adhesions and Tuberculosis are the leading causes of mechanical intestinal obstruction in Pakistan. Although some patients can be treated conservatively, a substantial portion requires immediate surgical intervention. (author)

  12. Molecular Control of Innate Immune Response to Pseudomonas aeruginosa Infection by Intestinal let-7 in Caenorhabditis elegans

    Science.gov (United States)

    Wang, Daoyong; Wang, Dayong

    2017-01-01

    The microRNA (miRNA) let-7 is an important miRNA identified in Caenorhabditis elegans and has been shown to be involved in the control of innate immunity. The underlying molecular mechanisms for let-7 regulation of innate immunity remain largely unclear. In this study, we investigated the molecular basis for intestinal let-7 in the regulation of innate immunity. Infection with Pseudomonas aeruginosa PA14 decreased let-7::GFP expression. Intestine- or neuron-specific activity of let-7 was required for its function in the regulation of innate immunity. During the control of innate immune response to P. aeruginosa PA14 infection, SDZ-24 was identified as a direct target for intestinal let-7. SDZ-24 was found to be predominantly expressed in the intestine, and P. aeruginosa PA14 infection increased SDZ-24::GFP expression. Intestinal let-7 regulated innate immune response to P. aeruginosa PA14 infection by suppressing both the expression and the function of SDZ-24. Knockout or RNA interference knockdown of sdz-24 dampened the resistance of let-7 mutant to P. aeruginosa PA14 infection. Intestinal overexpression of sdz-24 lacking 3’-UTR inhibited the susceptibility of nematodes overexpressing intestinal let-7 to P. aeruginosa PA14 infection. In contrast, we could observed the effects of intestinal let-7 on innate immunity in P. aeruginosa PA14 infected transgenic strain overexpressing sdz-24 containing 3’-UTR. In the intestine, certain SDZ-24-mediated signaling cascades were formed for nematodes against the P. aeruginosa PA14 infection. Our results highlight the crucial role of intestinal miRNAs in the regulation of the innate immune response to pathogenic infection. PMID:28095464

  13. Intestinal Epithelial Sirtuin 1 Regulates Intestinal Inflammation During Aging in Mice by Altering the Intestinal Microbiota.

    Science.gov (United States)

    Wellman, Alicia S; Metukuri, Mallikarjuna R; Kazgan, Nevzat; Xu, Xiaojiang; Xu, Qing; Ren, Natalie S X; Czopik, Agnieszka; Shanahan, Michael T; Kang, Ashley; Chen, Willa; Azcarate-Peril, M Andrea; Gulati, Ajay S; Fargo, David C; Guarente, Leonard; Li, Xiaoling

    2017-09-01

    Intestinal epithelial homeostasis is maintained by complex interactions among epithelial cells, commensal gut microorganisms, and immune cells. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD), but the mechanisms of this process are not clear. We investigated how Sirtuin 1 (SIRT1), a conserved mammalian NAD + -dependent protein deacetylase, senses environmental stress to alter intestinal integrity. We performed studies of mice with disruption of Sirt1 specifically in the intestinal epithelium (SIRT1 iKO, villin-Cre+, Sirt1 flox/flox mice) and control mice (villin-Cre-, Sirt1 flox/flox ) on a C57BL/6 background. Acute colitis was induced in some mice by addition of 2.5% dextran sodium sulfate to drinking water for 5-9 consecutive days. Some mice were given antibiotics via their drinking water for 4 weeks to deplete their microbiota. Some mice were fed with a cholestyramine-containing diet for 7 days to sequester their bile acids. Feces were collected and proportions of microbiota were analyzed by 16S rRNA amplicon sequencing and quantitative PCR. Intestines were collected from mice and gene expression profiles were compared by microarray and quantitative PCR analyses. We compared levels of specific mRNAs between colon tissues from age-matched patients with ulcerative colitis (n=10) vs without IBD (n=8, controls). Mice with intestinal deletion of SIRT1 (SIRT1 iKO) had abnormal activation of Paneth cells starting at the age of 5-8 months, with increased activation of NF-κB, stress pathways, and spontaneous inflammation at 22-24 months of age, compared with control mice. SIRT1 iKO mice also had altered fecal microbiota starting at 4-6 months of age compared with control mice, in part because of altered bile acid metabolism. Moreover, SIRT1 iKO mice with defective gut microbiota developed more severe colitis than control mice. Intestinal tissues from patients with ulcerative colitis expressed significantly lower

  14. Intestinal perfusion in the study of intestinal absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Several techniques for studying absorption by means of intestinal perfusion have been developed. While the principle is simple, the practice is complicated by absorption of the solvent and by excretion of fluid into the lumen. To improve reliability a ''marker'' is incorporated into the system; it should behave as nearly as possible like the nutrient of interest, except that it should be unabsorbable. A great many markers, including several labelled with radionuclides, have been developed for use with numerous nutrients, and perfusion methods using double or triple tubes or occlusive balloons have been tested. The perfusion technique is too complicated for routine diagnostic use, but it offers at present the only possibility of studying the function of defined sections of the small intestine in the intact human. (author)

  15. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis.

    Science.gov (United States)

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-03-17

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia's gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus.

  16. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis

    Science.gov (United States)

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-01-01

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia’s gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

  17. X radiation up-regulates the occurrence and the multiplicity of invasive carcinomas in the intestinal tract of Apc(min/+) mice.

    Science.gov (United States)

    Nakayama, Toshiyuki; Yamazumi, Kazuyuki; Uemura, Takashi; Yoshizaki, Ayumi; Yakata, Yuichi; Matsuu-Matsuyama, Mutsumi; Shichijo, Kazuko; Sekine, Ichiro

    2007-10-01

    X rays are well known to cause genetic damage and to induce many types of carcinomas in humans. The Apc(min/+) mouse, an animal model for human familial adenomatous polyposis (FAP), contains a truncating mutation in the APC gene and spontaneously develops intestinal adenomas. To elucidate the role of X rays in the development of intestinal tumors, we examined the promotion of carcinogenesis in X-irradiated Apc(min/+) mice. Forty out of 77 (52%) X-irradiated Apc(min/+) mice developed adenocarcinomas that invaded the proprial muscle layer of the small intestine; 24 of 44 (55%) were in males, and 16 of 33 (49%) were in females. In contrast, invasive carcinomas were detected in the small intestines of only 13 of 64 (20%) nonirradiated Apc(min/+) mice; nine of 32 (28%) were in males and four of 32 (13%) were in females. These differences between X-irradiated and nonirradiated Apc(min/+) mice in the occurrence of invasive intestinal carcinomas were statistically significant (P polyps in the large intestine with or without X irradiation; there was no difference in the number of polyps between the two groups. Also, invasive carcinomas were not detected in the large intestine with or without irradiation. The occurrence of mammary tumors, which was observed in Apc(min/+) mice, was found to be increased in irradiated Apc(min/+) mice (P polyps in the small and large intestines with or without X irradiation. X-irradiated Apc(min/+) mice had highly invasive carcinomas in the small intestine with multiplicities associated with invasiveness. Our results suggest that X radiation may promote the invasive activity of intestinal tumors in Apc(min/+) mice.

  18. Chemopreventive Effects of RXR-Selective Rexinoid Bexarotene on Intestinal Neoplasia of ApcMin/+ Mice

    Directory of Open Access Journals (Sweden)

    Naveena B. Janakiram

    2012-02-01

    Full Text Available Retinoid X receptor (RXR has been implicated in several neoplastic diseases. Previously, we have shown that RXR-α is downregulated in human and rodent colonic tumors, suggesting a potential target for colon cancer prevention (http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/colorectal-cancer-key-statistics. Experiments were designed to assess the chemopreventive efficacy of the selective RXR agonist bexarotene for the suppression of intestinal tumorigenesis in ApcMin/+ mice. Before the efficacy studies, we determined that the maximal tolerated dose in C57BL/6J mice was less than 400 ppm. For the efficacy study, 6-week-old male and female C57BL/6J-ApcMin/+ mice (nine mice per group were fed diets containing 0, 30, and 60 ppm of bexarotene or 200 ppm of bexarotene for 80 days before intestinal tumors were evaluated. Dietary administration of 30 and 60 ppm of bexarotene suppressed the intestinal polyp formation by 38% (P < .015 and 60% (P < .0001 in males, respectively, and by 8.5% and 37% (P < .007 in females, respectively. Also, significant inhibition (50%–100% of colonic tumor formation was observed in both male and female mice with bexarotene treatment. Administration of 200 ppm of bexarotene showed significant suppression of tumor formation (66%, P < .0001; however, it had significant toxicity. Intestinal tumors of bexarotene-fed mice showed significantly reduced expression of proliferating cell nuclear antigen (60%, P < .0001, cyclin D1, and cyclooxygenase 2 and increased RXR-α messenger RNA and uptake of oleate (34%, P < .01. Also, bexarotene-fed mice showed dose-dependent suppression of serum triglycerides (25%–72%, P < .0001 and inflammatory cytokines.

  19. Hypnotic susceptibility and dream characteristics.

    Science.gov (United States)

    Zamore, N; Barrett, D

    1989-11-01

    This study examined the relationship of hypnotic susceptibility to a variety of dream characteristics and types of dream content. A Dream Questionnaire was constructed synthesizing Gibson's dream inventory and Hilgard's theoretical conceptions of hypnosis. Employing the Harvard Group Scale of Hypnotic Susceptibility and the Field Inventory for evaluating hypnotic response, several dream dimensions correlated significantly with hypnotizability. For subjects as a whole, the strongest correlates were the frequency of dreams which they believed to be precognitive and out-of-body dreams. Ability to dream on a chosen topic also correlated significantly with hypnotic susceptibility for both genders. For females only, there was a negative correlation of hypnotic susceptibility to flying dreams. Absorption correlated positively with dream recall, ability to dream on a chosen topic, reports of conflict resolution in dreams, creative ideas occurring in dreams, amount of color in dreams, pleasantness of dreams, bizarreness of dreams, flying dreams and precognitive dreams.

  20. Mechanism underlying methyl eugenol attenuation of intestinal ischemia/reperfusion injury.

    Science.gov (United States)

    Saleh, Hanan; El-Shorbagy, Haidan M

    2017-10-01

    Intestinal ischemia/reperfusion (I/R) injury is associated with a high risk of mortality in the clinical situation. Many factors are involved in I/R, including reactive oxygen species, cytokine release, and apoptosis. We aimed to determine whether a pure methyl eugenol (ME) given before intestinal ischemia, protects against intestinal I/R injury and the possible mechanism involved in this protection. Rat received ME (100 mg/kg) for 30 days then underwent intestinal I/R with 30 min ischemia and 60 min reperfusion. Serum lactate dehydrogenase (LDH) level, tissue malondialdehyde (MDA), as well as some antioxidant biomarkers were assessed, while the serum level of tumor necrosis factor alpha (TNF-α) was determined by ELISA. The change in TNF-α and interleukin 6 (IL-6) gene expressions were evaluated and confirmed by assessing protein level of TNF-α in the intestinal tissue by immunohistochemistry. Apoptosis was evaluated using DNA-laddering assay and by detecting caspase-3 immunohistochemically. Administration of ME prior to I/R injury resulted in a modulation of the production of MDA, LDH, and nitric oxide and restoration of the tested oxidative stress biomarkers. Pretreatment with ME downregulated messenger RNA of TNF-α and IL-6 inflammatory cytokines and their protein expressions in I/R rats. Marked inhibition of the apoptotic DNA and improvement of the architectures of small intestine were observed after pretreatment with ME. ME exhibits a protective effect against intestinal I/R via amelioration of the oxidative stress and inflammatory cytokines gene expression. Therefore, the supplementation of ME prior to intestinal I/R might be helpful in the attenuation of I/R complications.

  1. The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.

    Science.gov (United States)

    Yu, Huimin; Hasan, Nesrin M; In, Julie G; Estes, Mary K; Kovbasnjuk, Olga; Zachos, Nicholas C; Donowitz, Mark

    2017-02-10

    The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.

  2. Ancestral susceptibility to colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Huhn, S.; Pardini, Barbara; Naccarati, Alessio; Vodička, Pavel (ed.); Hemminki, K.; Försti, A.

    2012-01-01

    Roč. 27, č. 2 (2012), s. 197-204 ISSN 0267-8357 R&D Projects: GA ČR GA310/07/1430; GA ČR GAP304/10/1286 Grant - others:EU FP7(XE) HEALTH-F4-2007-200767 Institutional research plan: CEZ:AV0Z50390512 Keywords : cancer susceptibility * molecular epidemiology * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012

  3. Quantitative susceptibility mapping differentiates between blood depositions and calcifications in patients with glioblastoma.

    Directory of Open Access Journals (Sweden)

    Andreas Deistung

    Full Text Available OBJECTIVES: The application of susceptibility weighted imaging (SWI in brain tumor imaging is mainly used to assess tumor-related "susceptibility based signals" (SBS. The origin of SBS in glioblastoma is still unknown, potentially representing calcifications or blood depositions. Reliable differentiation between both entities may be important to evaluate treatment response and to identify glioblastoma with oligodendroglial components that are supposed to present calcifications. Since calcifications and blood deposits are difficult to differentiate using conventional MRI, we investigated whether a new post-processing approach, quantitative susceptibility mapping (QSM, is able to distinguish between both entities reliably. MATERIALS AND METHODS: SWI, FLAIR, and T1-w images were acquired from 46 patients with glioblastoma (14 newly diagnosed, 24 treated with radiochemotherapy, 8 treated with radiochemotherapy and additional anti-angiogenic medication. Susceptibility maps were calculated from SWI data. All glioblastoma were evaluated for the appearance of hypointense or hyperintense correlates of SBS on the susceptibility maps. RESULTS: 43 of 46 glioblastoma presented only hyperintense intratumoral SBS on susceptibility maps, indicating blood deposits. Additional hypointense correlates of tumor-related SBS on susceptibility maps, indicating calcification, were identified in 2 patients being treated with radiochemotherapy and in one patient being treated with additional anti-angiogenic medication. Histopathologic reports revealed an oligodendroglial component in one patient that presented calcifications on susceptibility maps. CONCLUSIONS: QSM provides a quantitative, local MRI contrast, which reliably differentiates between blood deposits and calcifications. Thus, quantitative susceptibility mapping appears promising to identify rare variants of glioblastoma with oligodendroglial components non-invasively and may allow monitoring the role of

  4. Diagnosis of local tumor recidivations after continence excision of rectal carcinoma by means of CAT scanning

    Energy Technology Data Exchange (ETDEWEB)

    Castrup, W.; Schlueter, B.; Wedell, J.; Banzhaf, G.

    1984-05-01

    On a patient collective of 19 with recurrent rectal carcinomas following previous resection and one patient with tumor recidivation after local excision of a villiferous adenoma, the demonstration of the different intra and extraluminal tumor infiltration paths by means of CAT scanning is investigated. After thorough cleaning of the intestine and additional application of a contrast enema using a watery contrast medium it is even possible to demonstrate tumor stenoses or a circumscribed thickening of the intestinal wall. With the majority of patients the tumor extends mainly outside the region of the anastomosis in the perirectal area. Early diagnosis of such perirectal infiltration therefore is decisive for the further treatment. As the possibilities of X-ray investigations of the colon and endoscopy for judging the extraluminal growth are limited, CAT scanning is an essential method in tumor aftercare.

  5. The intestinal microenvironment in sepsis.

    Science.gov (United States)

    Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

    2017-10-01

    The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

  6. Drug Transporters in the Intestine

    DEFF Research Database (Denmark)

    Steffansen, Bente

    2016-01-01

    that may impact drug absorption. Thus absorptive transporters may facilitate BA of APIs that are substrates/victims for the transporters and have permeability-limited absorption, i.e. those that are classified in the biopharmaceutics classification system (BCS) Class 3 and 4. On the other hand, exsorptive...... transporters may restrict BA of APIs that are victims for these efflux transporters, especially those APIs classified to have solubility-limited absorption, i.e. compounds in BCS Class 2 and 4. The aim of the present Chapter is to review drug transporters (DTs) present within the intestine and to discuss...... and exemplify their roles in drug absorption/exsorption and in drug-drug interactions (DDIs). Although focus in the present Chapter is on DTs that are mentioned in American and European regulatory guidances, the intestinal transporters for nutrients and endogens (endogenous compounds) are also briefly...

  7. Transcriptional-mediated effects of radiation on the expression of immune susceptibility markers in melanoma.

    Science.gov (United States)

    Werner, Lauryn R; Kler, Jasdeep S; Gressett, Monica M; Riegert, Maureen; Werner, Lindsey K; Heinze, Clinton M; Kern, Joseph G; Abbariki, Mahyar; Erbe, Amy K; Patel, Ravi B; Sriramaneni, Raghava N; Harari, Paul M; Morris, Zachary S

    2017-09-01

    We recently reported a time-sensitive, cooperative, anti-tumor effect elicited by radiation (RT) and intra-tumoral-immunocytokine injection in vivo. We hypothesized that RT triggers transcriptional-mediated changes in tumor expression of immune susceptibility markers at delayed time points, which may explain these previously observed time-dependent effects. We examined the time course of changes in expression of immune susceptibility markers following in vitro or in vivo RT in B78 murine melanoma and A375 human melanoma using flow cytometry, immunoblotting, and qPCR. Flow cytometry and immunoblot revealed time-dependent increases in expression of death receptors and T cell co-stimulatory/co-inhibitory ligands following RT in murine and human melanoma. Using high-throughput qPCR, we observed comparable time courses of RT-induced transcriptional upregulation for multiple immune susceptibility markers. We confirmed analogous changes in B78 tumors irradiated in vivo. We observed upregulated expression of DNA damage response markers days prior to changes in immune markers, whereas phosphorylation of the STAT1 transcription factor occurred concurrently with changes following RT. This study highlights time-dependent, transcription-mediated changes in tumor immune susceptibility marker expression following RT. These findings may help in the design of strategies to optimize sequencing of RT and immunotherapy in translational and clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Malignancy risk prediction for primary jejunum-ileal tumors

    Directory of Open Access Journals (Sweden)

    MARQUES Ruy Garcia

    2000-01-01

    Full Text Available This work is aimed at identifying factors associated with primary jejunum-ileal tumors malignancy, defining a prediction model with sensitivity, specificity and accuracy to distinguish malign from benign neoplasms. These tumors are rare, have highly unspecific presentation and, frequently, are diagnosed late. We reviewed the charts of 42 patients with primary jejunum-ileal tumors treated in the Department of General Surgery of Rio de Janeiro State University Hospital, Rio de Janeiro, RJ, Brazil, from 1969 to 1998. We performed bivariate analyses, based on chi² test, searching associations between tumors malignancy and demographic and clinical variables. Then logistic regression was employed to consider the independent effect of variables previously identified on malignancy risk. The malign tumors included 11 adenocarcinomas, 7 leiomyosarcomas, 5 carcinoids and 4 lymphomas; the benign tumors included 10 leiomyomas, 2 hamartomas, and single cases of adenoma, multiple neurilemoma and choristoma. The bivariate analyses indicated the association between malignancy and palpable abdominal mass (P = 0.003, period from signs and symptoms onset to diagnosis (P = 0.016, anemia (P = 0.020, anorexia (P = 0.003, abdominal pain (P = 0.031, weight loss (P = 0.001, nausea and vomit (P = 0.094, and intestinal obstruction (P = 0.066; no association with patients demographic characteristics were found. In the final logistic regression model, weight loss, anemia and intestinal obstruction were statistically associated with the dependent variable of interest. Based only on three variables -- weight loss, anemia and intestinal obstruction -- the model defined was able to predict primary jejunum-ileal tumors malignancy with sensitivity of 85.2%, specificity of 80.0%, and accuracy of 83.3%.

  9. Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila.

    Science.gov (United States)

    Narbonne-Reveau, Karine; Lanet, Elodie; Dillard, Caroline; Foppolo, Sophie; Chen, Ching-Huan; Parrinello, Hugues; Rialle, Stéphanie; Sokol, Nicholas S; Maurange, Cédric

    2016-06-14

    Pediatric neural tumors are often initiated during early development and can undergo very rapid transformation. However, the molecular basis of this early malignant susceptibility remains unknown. During Drosophila development, neural stem cells (NSCs) divide asymmetrically and generate intermediate progenitors that rapidly differentiate in neurons. Upon gene inactivation, these progeny can dedifferentiate and generate malignant tumors. Here, we find that intermediate progenitors are prone to malignancy only when born during an early window of development while expressing the transcription factor Chinmo, and the mRNA-binding proteins Imp/IGF2BP and Lin-28. These genes compose an oncogenic module that is coopted upon dedifferentiation of early-born intermediate progenitors to drive unlimited tumor growth. In late larvae, temporal transcription factor progression in NSCs silences the module, thereby limiting mitotic potential and terminating the window of malignant susceptibility. Thus, this study identifies the gene regulatory network that confers malignant potential to neural tumors with early developmental origins.

  10. [Chronic gastritis and intestinal metaplasia].

    Science.gov (United States)

    Castillo, T; Navarrete, J; Celestina, A

    1989-01-01

    Much has been written about gastric mucosae behavior and the occurrence of intestinal metaplasia. The aim of this paper is to learn something more about these matters in peruvian population. We selected 100 patients with endoscopically no localized lesions between 30 to 70 years of age. We took 8 samples of gastric mucosae in each patient which were carefully examined for the presence of inflammatory changes, settle the line type between antral and fundic mucosae and the frequency of intestinal metaplasia finding. The results showed disagreement between endoscopic and histological findings, so we conclude it is better to diagnose chronic gastritis on the basis of histological parameters. The line between antral and fundic mucosae was of the close type one found in 87% of all cases and it advanced proximally with increasing age. Intestinal metaplasia was present in 46% of the whole number of patients and the rate of occurrence increased in 50% over 50 years age. These findings will let us compare future investigations of gastric mucosae behavior with localized benign or malign lesions.

  11. [Intestinal parasitic diseases in children].

    Science.gov (United States)

    Mare, Anca; Man, A; Toma, Felicia; Székely, Edit; Lôrinczi, Lilla; Sipoş, Anca

    2007-01-01

    To compare the incidence of intestinal parasitosis between children with residence in urban and rural areas: to compare the efficacy of parasitologic diagnostic methods. In our study we included two lots of children. The first lot consisted in 74 children from rural areas from which we collected 44 samples of feces and 55 samples for the "Scotch tape" test. The second lot consisted in 214 children from urban areas from which we collected 44 samples of feces. We examined each sample of feces by three different methods. The study was performed between April to June 2006. The incidence of intestinal parasitosis increases in children from urban areas towards rural areas, and in children between 5 and 10 years. Ascariasis is the most frequent disease in both urban and rural areas. By examination of each fecal sample by three different methods, the number of positive cases increased. The residence in rural areas and age between 5 to 10 years are risk factors for intestinal parasitosis. The "Scotch tape" test was more efficient in Enterobius vermicularis infection than the methods performed from feces. We recommend using at the same time three diagnostic methods for feces examination to improve the diagnostic sensibility.

  12. Colon in acute intestinal infection.

    Science.gov (United States)

    Guarino, Alfredo; Buccigrossi, Vittoria; Armellino, Carla

    2009-04-01

    The colon is actively implicated in intestinal infections not only as a target of enteric pathogens and their products but also as a target organ for treatment. In the presence of diarrhea, both of osmotic and secretory nature, the colon reacts with homeostatic mechanisms to increase ion absorption. These mechanisms can be effectively exploited to decrease fluid discharge. A model of intestinal infections using rotavirus (RV) in colonic cells was set up and used to define a dual model of secretory and osmotic diarrhea in sequence. Using this model, antidiarrheal drugs were tested, namely zinc and the enkephalinase inhibitor racecadotril. Zinc was able to decrease the enterotoxic activity responsible for secretory diarrhea. It also inhibited the cytotoxic effect of RV. The mechanism of zinc was related at least in part to the activation of MAPK activity, but also a direct antiviral effect was observed. Racecadotril showed a potent and selective inhibition of active secretion, being particularly effective in the first phase of RV diarrhea. The use of drugs active at the colonic level, therefore, offers effective options to treat intestinal infections in childhood. In addition, the colon is the natural site of colonic microflora, a target of probiotic therapy, which is the first line of approach recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition to treat infectious diarrhea.

  13. Preclinical experiments for analysis of tumor regression due to negative pions

    International Nuclear Information System (INIS)

    Blattmann, H.; Cabeza, L.; Fritz-Niggli, H.

    To test the potential therapeutic value of negative pions in comparison with conventional x-rays, cobalt-60 γ rays, and high energy electrons and photons (Betatron), experimental analyses with induced tumors (transplant tumors) after irradiation are to be performed in vivo and in vitro (tumor cell suspensions, cell cultures, spontaneous tumors, carcinoma in ascites form); in addition to tumors primarily of mice, human cell tumors will be used; studies will also be made of cell kinetics with various cell types (normal cells, transformed (malignant) cells, beam-resistant, beam-sensitive types) using cell cultures from Chinese hamsters. An attempt will be made to compare slow- and fast-growing tumors. In a second phase, human tumors in conditioned animals will be tested in situ or as cell cultures. Skin, small intestine, regenerating liver and kidney, together with cell cultures, will serve as normal reaction systems

  14. Interactions between intestinal microbiota and innate immune system in pediatric inflammatory bowel disease.

    Science.gov (United States)

    Cucchiara, Salvatore; Stronati, Laura; Aloi, Marina

    2012-10-01

    Inflammatory bowel disease (IBD) is the result of an altered immune homeostasis within the intestinal mucosa against the gut microbiota, leading to chronic inflammation in genetically predisposed individuals. Under normal conditions, the immune system defends against pathogens and prevents the passage of excessive intestinal bacteria; regulatory pathways must maintain a low-grade, controlled inflammation in a healthy gut, but also induce a protective response against pathogens. The innate immune system is the first-line defense from microbes; dendritic cells, macrophages, and epithelial cells produce an initial, immediate response. The immune system constantly controls commensal bacteria and utilizes constitutive antimicrobial mechanisms to sustain immune homeostasis. The discovery that several genes linked to IBD modulate microbial recognition and innate immune pathways, such as nucleotide oligomerization domain 2 (Nod2), and genes that mediate autophagy (ie, ATG16L1, IRGM), has highlighted the critical role of host-microbe interactions in controlling intestinal immune homeostasis. Commensal microorganisms actively interact with the intestinal mucosa and influence the activity of the immune system as well as the amplitude of the immune response. In contrast, host factors can influence microbes, which in turn modulate disease susceptibility. In this paper, we focus on the mechanisms that mediate host-microbe interactions and how the disruption of this balance leads to chronic intestinal inflammation in IBD.

  15. Milk sialyllactose influences colitis in mice through selective intestinal bacterial colonization.

    Science.gov (United States)

    Fuhrer, Andrea; Sprenger, Norbert; Kurakevich, Ekaterina; Borsig, Lubor; Chassard, Christophe; Hennet, Thierry

    2010-12-20

    Milk oligosaccharides contribute to the development of the intestinal environment by acting as decoy receptors for pathogens and as prebiotics, which promote the colonization of commensal bacteria. Here, using α2,3- and α2,6-sialyltransferase-deficient mice, we investigated the role of the sialylated milk oligosaccharides sialyl(α2,3)lactose and sialyl(α2,6)lactose on mucosal immunity. The exposure of newborn mice to milk containing or deficient in sialyllactose had no impact on the development of mucosal leukocyte populations. However, when challenged by dextran sulfate sodium (DSS) in drinking water, adult mice that had been fostered on sialyl(α2,3)lactose-deficient milk were more resistant to colitis compared with mice fostered on normal milk or sialyl(α2,6)lactose-deficient milk. Analysis of intestinal microbiota showed different colonization patterns depending on the presence or absence of sialyl(α2,3)lactose in the milk. Germ-free mice reconstituted with intestinal microbiota isolated from mice fed on sialyl(α2,3)lactose-deficient milk were more resistant to DSS-induced colitis than germ-free mice reconstituted with standard intestinal microbiota. Thus, exposure to sialyllactose during infancy affects bacterial colonization of the intestine, which influences the susceptibility to DSS-induced colitis in adult mice.

  16. Three-dimensional reconstruction of colorectal tumors from serial tissue sections by computer graphics: a preliminary study.

    Science.gov (United States)

    Kikuchi, S; Matsuzaki, H; Kondo, K; Ohtani, Y; Ihara, A; Hiki, Y; Kakita, A; Kuwao, S

    2000-01-01

    We present herein the three-dimensional reconstruction of colorectal tumors, with particular reference to growth pattern into each layer of the colorectal wall, and measurement of tumor volume and surface area. Conventional tissue section images of colorectal tumors were analyzed using a computer graphics analysis program. The two-dimensional extent of invasion by each tumor into each layer of intestinal wall were determined from the images of each section. Based on data from multiple sections, tumor and surrounding normal tissue layers were reconstructed three-dimensionally, and volume and surface area of the tumors were determined. Using this technique, three-dimensional morphology of tumor and tumor progression into colorectal wall could be determined. Volume and surface area of the colon tumor were 4871 mm3 and 1741 mm2, respectively. Volume and surface area of the rectal tumor were 1090 mm3 and 877 mm2, respectively. This technique may provide a new approach for pathological analysis of colorectal carcinoma.

  17. Immunogenetic control of the intestinal microbiota.

    Science.gov (United States)

    Marietta, Eric; Rishi, Abdul; Taneja, Veena

    2015-07-01

    All vertebrates contain a diverse collection of commensal, symbiotic and pathogenic microorganisms, such as bacteria, viruses and fungi, on their various body surfaces, and the ecological community of these microorganisms is referred to as the microbiota. Mucosal sites, such as the intestine, harbour the majority of microorganisms, and the human intestine contains the largest community of commensal and symbiotic bacteria. This intestinal community of bacteria is diverse, and there is a significant variability among individuals with respect to the composition of the intestinal microbiome. Both genetic and environmental factors can influence the diversity and composition of the intestinal bacteria with the predominant environmental factor being diet. So far, studies have shown that diet-dependent differences in the composition of intestinal bacteria can be classified into three groups, called enterotypes. Other environmental factors that can influence the composition include antibiotics, probiotics, smoking and drugs. Studies of monozygotic and dizygotic twins have proven that genetics plays a role. Recently, MHC II genes have been associated with specific microbial compositions in human infants and transgenic mice that express different HLA alleles. There is a growing list of genes/molecules that are involved with the sensing and monitoring of the intestinal lumen by the intestinal immune system that, when genetically altered, will significantly alter the composition of the intestinal microflora. The focus of this review will be on the genetic factors that influence the composition of the intestinal microflora. © 2015 John Wiley & Sons Ltd.

  18. Intestinal microcirculatory dysfunction and neonatal necrotizing enterocolitis.

    Science.gov (United States)

    Zhang, Hong-yi; Wang, Fang; Feng, Jie-xiong

    2013-01-01

    Based on the observation that coagulation necrosis occurs in the majority of neonatal necrotizing enterocolitis (NEC) patients, it is clear that intestinal ischemia is a contributing factor to the pathogenesis of NEC. However, the published studies regarding the role of intestinal ischemia in NEC are controversial. The aim of this paper is to review the current studies regarding intestinal microcirculatory dysfunction and NEC, and try to elucidate the exact role of intestinal microcirculatory dysfunction in NEC. The studies cited in this review were mainly obtained from articles listed in Medline and PubMed. The search terms used were "intestinal microcirculatory dysfunction" and "neonatal necrotizing enterocolitis". Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected. Immature regulatory control of mesentery circulation makes the neonatal intestinal microvasculature vulnerable. When neonates are subjected to stress, endothelial cell dysfunction occurs and results in vasoconstriction of arterioles, inflammatory cell infiltration and activation in venules, and endothelial barrier disruption in capillaries. The compromised vasculature increases circulation resistance and therefore decreases intestinal perfusion, and may eventually progress to intestinal necrosis. Intestinal ischemia plays an important role through the whole course of NEC. New therapeutic agents targeting intestinal ischemia, like HB-EGF, are promising therapeutic agents for the treatment of NEC.

  19. Ketogenesis contributes to intestinal cell differentiation.

    Science.gov (United States)

    Wang, Qingding; Zhou, Yuning; Rychahou, Piotr; Fan, Teresa W-M; Lane, Andrew N; Weiss, Heidi L; Evers, B Mark

    2017-03-01

    The intestinal epithelium undergoes a continual process of proliferation, differentiation and apoptosis. Previously, we have shown that the PI3K/Akt/mTOR pathway has a critical role in intestinal homeostasis. However, the downstream targets mediating the effects of mTOR in intestinal cells are not known. Here, we show that the ketone body β-hydroxybutyrate (βHB), an endogenous inhibitor of histone deacetylases (HDACs) induces intestinal cell differentiation as noted by the increased expression of differentiation markers (Mucin2 (MUC2), lysozyme, IAP, sucrase-isomaltase, KRT20, villin, Caudal-related homeobox transcription factor 2 (CDX2) and p21 Waf1 ). Conversely, knockdown of the ketogenic mitochondrial enzyme hydroxymethylglutaryl CoA synthase 2 (HMGCS2) attenuated spontaneous differentiation in the human colon cancer cell line Caco-2. Overexpression of HMGCS2, which we found is localized specifically in the more differentiated portions of the intestinal mucosa, increased the expression of CDX2, thus further suggesting the contributory role of HMGCS2 in intestinal differentiation. In addition, mice fed a ketogenic diet demonstrated increased differentiation of intestinal cells as noted by an increase in the enterocyte, goblet and Paneth cell lineages. Moreover, we showed that either knockdown of mTOR or inhibition of mTORC1 with rapamycin increases the expression of HMGCS2 in intestinal cells in vitro and in vivo, suggesting a possible cross-talk between mTOR and HMGCS2/βHB signaling in intestinal cells. In contrast, treatment of intestinal cells with βHB or feeding mice with a ketogenic diet inhibits mTOR signaling in intestinal cells. Together, we provide evidence showing that HMGCS2/βHB contributes to intestinal cell differentiation. Our results suggest that mTOR acts cooperatively with HMGCS2/βHB to maintain intestinal homeostasis.

  20. Primitive neuroectodermal tumors of the central nervous system. Patterns of expression of neuroendocrine markers, and all classes of intermediate filament proteins.

    NARCIS (Netherlands)

    Gould, V E; Jansson, D S; Molenaar, W M; Rorke, L B; Trojanowski, J Q; Lee, V M; Packer, R J; Franke, W W

    1990-01-01

    Snap-frozen samples from 22 primitive neuroectodermal tumors (PNETs) primary in the central nervous system were studied with antibodies to synaptophysin, bombesin, somatostatin, substance P, vasoactive intestinal polypeptide, all classes of intermediate filaments, and desmoplakins I and II. Frozen

  1. Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities

    Science.gov (United States)

    Valentin-Vega, Yasmine A.; Box, Neil; Terzian, Tamara; Lozano, Guillermina

    2014-01-01

    Mdm4 is a critical inhibitor of the p53 tumor suppressor. Mdm4 null mice die early during embryogenesis due to increased p53 activity. In this study, we explore the role that Mdm4 plays in the intestinal epithelium by crossing mice carrying the Mdm4 floxed allele to mice with the Villin Cre transgene. Our data show that loss of Mdm4 (Mdm4intΔ) in this tissue resulted in viable animals with no obvious morphological abnormalities. However, these mutants displayed increased p53 levels and apoptosis exclusively in the proliferative compartment of the intestinal epithelium. This phenotype was completely rescued in a p53 null background. Notably, the observed compartmentalized apoptosis in proliferative intestinal epithelial cells was not due to restricted Mdm4 expression in this region. Thus, in this specific cellular context, p53 is negatively regulated by Mdm4 exclusively in highly proliferative cells. PMID:19371999

  2. Malignant phyllodes breast tumor

    OpenAIRE

    Lisa R. Shah-Patel, MD

    2017-01-01

    Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  3. Malignant phyllodes breast tumor

    Directory of Open Access Journals (Sweden)

    Lisa R. Shah-Patel, MD

    2017-12-01

    Full Text Available Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  4. Liver Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Liver Tumors KidsHealth / For Parents / Liver Tumors What's in this article? Types of Tumors ... Cancerous) Tumors Symptoms Diagnosis Treatment Coping Print The liver is the body's largest solid organ. Lying next ...

  5. Identification of genetic modifiers of susceptibility to radiation-induced lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Balmain, Allan [University of California, San Francisco, CA (United States)

    2007-03-28

    The specific aims of this project were as follows: Aim 1: Identify mouse genetic loci that affect the survival time of mice post radiation. Aim 2: Identify somatic genetic alterations that are indicative of tumor suppressor and oncogene loci involved in radiation-induced cancers. Aim 3: Identify candidate radiation susceptibility genes by gene expression microarray analysis of the radiation response in normal tissues or in tumors from the strains used for aims 1 and 2.

  6. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  7. Supratentorial tumors; Supratentorielle Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.; Dillmann, K.; Roth, C.; Backens, M.; Reith, W. [Universitaetsklinikum Saarland, Homburg (Germany). Klinik fuer Diagnostische und Interventionelle Neuroradiologie

    2007-06-15

    Magnetic resonance imaging is a routine diagnostic measure for a suspected intracerebral mass. Computed tomography is usually also indicated. Further diagnostic procedures as well as the interpretation of the findings vary depending on the tumor location. This contribution discusses the symptoms and diagnostics for supratentorial tumors separated in relation to their intra- or extracranial location. Supratentorial tumors include astrocytoma, differentiated by their circumscribed and diffuse growth, ganglioglioma, ependyoma, neurocytoma, primitive neuroectodermal tumors (PNET), oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNET), meningoangiomatosis, pineal tumors, hamartoma, lymphoma, craniopharyngeoma and metastases. The supratentorial extracranial tumors include the choroid plexus, colloid cysts, meningeoma, infantile myofibromatosis and lipoma. The most common subforms, especially of astrocytoma, will also be presented. (orig.)

  8. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

    Science.gov (United States)

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-11-01

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

  9. SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases.

    Science.gov (United States)

    Miettinen, Markku; Wang, Zengfeng; McCue, Peter A; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

    2014-03-01

    The SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non-germ cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10-week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, in which it was selectively expressed in intestinal-like and some squamous epithelia. In non-germ cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of the ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤ 5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4-positive carcinomas showed poorly differentiated patterns, and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of the kidney and extrarenal sites and in the Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of nonteratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem cell-like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful.

  10. SALL4 EXPRESSION IN GERM CELL AND NON GERM-CELL TUMORS – A SYSTEMATIC IMMUNOHISTOCHEMICAL STUDY OF 3215 CASES

    Science.gov (United States)

    Miettinen, Markku; Wang, Zengfeng; Mc. Cue, Peter A.; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

    2014-01-01

    SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non germ-cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10th week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, where it was selectively expressed in intestinal-like and some squamous epithelia. In non germ-cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4 positive carcinomas showed poorly differentiated patterns and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of kidney and extrarenal sites, and in Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of non-teratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem-cell like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful. PMID:24525512

  11. A noninvasive multimodal technique to monitor brain tumor vascularization

    Science.gov (United States)

    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E.

    2007-09-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.

  12. A noninvasive multimodal technique to monitor brain tumor vascularization

    International Nuclear Information System (INIS)

    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E

    2007-01-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present

  13. A tumor profile in Patau syndrome (trisomy 13).

    Science.gov (United States)

    Satgé, Daniel; Nishi, Motoi; Sirvent, Nicolas; Vekemans, Michel; Chenard, Marie-Pierre; Barnes, Ann

    2017-08-01

    Individuals with trisomic conditions like Down syndrome and Edwards syndrome are prone to certain types of malignancy. However, for Patau syndrome (constitutional trisomy 13), which occurs in 1/10,000-1/20,000 live births, the tumor profile has not been well characterized. An awareness of susceptibility to malignancies can improve care of affected individuals, as well as further our understanding of the contribution of trisomy to carcinogenesis. Therefore, we conducted an extensive review of the literature; we found 17 malignancies reported in individuals with Patau syndrome. These comprised eight embryonic tumors, three leukemias, two malignant germ cell tumors, two carcinomas, a malignant brain tumor, and a sarcoma. Benign tumors were mainly extragonadal teratomas. The small number of reported malignant tumors suggests that there is not an increased risk of cancer in the context of trisomy 13. The tumor profile in Patau syndrome differs from that observed in Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), suggesting that the supernumerary chromosome 13 could promote particular tumor formations as it does particular malformations. No general and direct relationships of tumor occurrence with organ weight, congenital malformations, histological changes, or presence of tumor suppressor genes on chromosome 13 were observed. However, some tumors were found in tissues whose growth and development are controlled by genes mapping to chromosome 13. Recent reports of successful outcomes following surgical treatment and adapted chemotherapy indicate that treatment of cancer is possible in Patau syndrome. © 2017 Wiley Periodicals, Inc.

  14. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...

  15. [Wilms tumor in hemihypertrophy].

    Science.gov (United States)

    Sauer, O; Wemmer, U

    1977-04-07

    The case of a 4-year-old boy with Wilms' tumor and hemihypertrophy is described. Wilms' tumors are frequently associated with congenital malformations of the urinary tract, with aniridia and hemihypertrophy. Hemihypertrophy is a relatively rare malformation (1:14000) in the common population, but in patients with Wilms' tumors its frequency is about 1:49. Besides Wilms' tumors tumors of the adrenal cortex and hepatoblastomas are frequently observed together with hemihypertrophy.

  16. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  17. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  18. Tumors and tumor-like lesions

    International Nuclear Information System (INIS)

    Koesling, S.; Stoevesandt, D.; Knipping, S.

    2007-01-01

    Tumors and tumor-like lesions are rare diseases in the paranasal sinuses. There is a great variety of histological types, but only a small number of morphological patterns on imaging. Histology is an important point in therapeutic planning. In most cases it is obtained by sampling, which is not as difficult in the sinonasal area as in other regions of the body. The main task of imaging is an exact estimation of the extent and spread of a lesion. This article discusses the possibilities and limitations of CT and MRI in the assessment of the dignity and spread of paranasal tumors and tumor-like lesions in consideration of necessary therapeutic information. Additionally, an overview of features on imaging of different paranasal tumors and tumor-like lesions is given. (orig.)

  19. Comparative transcriptomics of the nematode gut identifies global shifts in feeding mode and pathogen susceptibility.

    Science.gov (United States)

    Lightfoot, James W; Chauhan, Veeren M; Aylott, Jonathan W; Rödelsperger, Christian

    2016-03-05

    The nematode Pristionchus pacificus has been established as a model for comparative studies using the well known Caenorhabditis elegans as a reference. Despite their relatedness, previous studies have revealed highly divergent development and a number of morphological differences including the lack of a pharyngal structure, the grinder, used to physically lyse the ingested bacteria in C. elegans. To complement current knowledge about developmental and ecological differences with a better understanding of their feeding modes, we have sequenced the intestinal transcriptomes of both nematodes. In total, we found 464 intestine-enriched genes in P. pacificus and 724 in C. elegans, of which the majority (66%) has been identified by previous studies. Interestingly, only 15 genes could be identified with shared intestinal enrichment in both species, of which three genes are Hedgehog signaling molecules supporting a highly conserved role of this pathway for intestinal development across all metazoa. At the level of gene families, we find similar divergent trends with only five families displaying significant intestinal enrichment in both species. We compared our data with transcriptomic responses to various pathogens. Strikingly, C. elegans intestine-enriched genes showed highly significant overlaps with pathogen response genes whereas this was not the case for P. pacificus, indicating shifts in pathogen susceptibility that might be explained by altered feeding modes. Our study reveals first insights into the evolution of feeding systems and the associated changes in intestinal gene expression that might have facilitated nematodes of the P. pacificus lineage to colonize new environments. These findings deepen our understanding about how morphological and genomic diversity is created during the course of evolution.

  20. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    Science.gov (United States)

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  1. Identification of the intestinal type gastric adenocarcinoma transcriptomic markers using bioinformatic and gene expression analysis

    Directory of Open Access Journals (Sweden)

    V. V. Volkomorov

    2017-01-01

    Full Text Available Introduction. Searching for specific and sensitive molecular tumor markers is one of the important tasks of modern oncology. These markers can be used for early tumor diagnosis and prognosis as well as for prediction of therapeutic response, estimation of tumor volume or to assess disease recurrence through monitoring. Gene expression data base mining followed by experimental validation of results obtained is one of the promising approaches for searching of that kind.Objective: to identify several membrane proteins which can be used for serum diagnosis of intestinal type of gastric adenocarcinoma.Materials and methods. We used bioinformatic-driven search using Gene Ontology and The Cancer Genome Atlas (TCGA data to identify mRNA up-regulated in gastric cancer (GC. Then, the expression levels of the mRNAs in 55 pare clinical specimens were investigated using reverse transcription polymerase chain reaction.Results. Comparative analysis of the mRNA levels in normal and tumor tissues using a new bioinformatics algorithm allowed to identify 3 high-copy transcripts (SULF1, PMEPA1 and SPARC, intracellular content of which markedly increased in GC. Expression analysis of these genes in clinical specimens showed significantly higher mRNA levels of PMEPA1 and SPARC in tumor as compared to normal gastric tissue. Interestingly more than twofold increase in expression level of these genes was observed in 75 % of intestinal-type GC. The same results were found only in 25 and 38 % of diffuse-type GC respectively.Conclusions. As a result of original bioinforamtic analysis using TCGA data base two genes (PMEPA1 and SPARC were shown to be significantly upregulated in intestinal-type gastric adenocarcinoma. The findings show the importance of further investigation to clarify the clinical value of their expression level in stomach tumors as well as their role in carcinogenesis.

  2. A case of endometrioid adenocarcinoma originating from the serous surface of the small intestine

    Directory of Open Access Journals (Sweden)

    Natsuko Makihara

    2015-09-01

    Full Text Available Malignant transformation of endometriosis has been extensively described in the literature. However, extragonadal endometrioid adenocarcinoma, either de novo or arising from malignant transformation of endometriosis, is rare. The present case report describes a patient with endometrioid adenocarcinoma on the serous surface of the small intestine. A 25- year-old female with no history of endometriosis was referred to our hospital with an intrapelvic tumor. An internal examination, ultrasound, and magnetic resonance imaging revealed a round mass approximately 80 mm in diameter; however, identification of the affected organ was difficult. Because we could not rule out malignancy based on the non-specific radiologic findings, laparotomy was performed. A mass with ileal adhesions was detected intraoperatively. In addition, the uterus and bilateral adnexa appeared normal. The tumor was resected with part of the ileum. Histopathology confirmed a diagnosis of endometrioid adenocarcinoma originating from the serous surface of the small intestine.

  3. Benign Lesions in Mucosa Adjacent to Intestinal-Type Sinonasal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Blanca Vivanco

    2011-01-01

    Full Text Available Occupational exposure to wood dust is a strong risk factor for the development of intestinal-type sinonasal adenocarcinoma (ITAC; however, knowledge on possible precursor lesions or biomarkers is limited. Fifty-one samples of tumor-adjacent mucosa and 19 control samples of mucosa from the unaffected fossa of ITAC patients were evaluated for histological changes and p53 protein expression. Mild dysplasia was observed in 14%, cuboidal metaplasia in 57%, intestinal metaplasia in 8%, squamous metaplasia in 24%, and cylindrocellular hyperplasia in 53% of cases. P53 immunopositivity was generally weak occurring most frequently in squamous metaplasia. Wood dust etiology did not appear of influence on the histological changes, but p53 showed a tendency for higher positivity. Dysplasia adjacent to tumor was indicative of subsequent development of recurrence. In conclusion, precursor lesions do occur in mucosa adjacent to ITAC. This is clinically important, because it may justify the screening of high-risk individuals such as woodworkers.

  4. Effects of hemin and nitrite on intestinal tumorigenesis in the A/J Min/+ mouse model.

    Directory of Open Access Journals (Sweden)

    Marianne Sødring

    Full Text Available Red and processed meats are considered risk factors for colorectal cancer (CRC; however, the underlying mechanisms are still unclear. One cause for the potential link between CRC and meat is the heme iron in red meat. Two pathways by which heme and CRC promotion may be linked have been suggested: fat peroxidation and N-nitrosation. In the present work we have used the novel A/J Min/+ mouse model to test the effects of dietary hemin (a model of red meat, and hemin in combination with nitrite (a model of processed meat on intestinal tumorigenesis. Mice were fed a low Ca2+ and vitamin D semi-synthetic diet with added hemin and/or nitrite for 8 weeks post weaning, before termination followed by excision and examination of the intestinal tract. Our results indicate that dietary hemin decreased the number of colonic lesions in the A/J Min/+ mouse. However, our results also showed that the opposite occurred in the small intestine, where dietary hemin appeared to stimulate tumor growth. Furthermore, we find that nitrite, which did not have an effect in the colon, appeared to have a suppressive effect on tumor growth in the small intestine.

  5. Microbiota-Mediated Inflammation and Antimicrobial Defense in the Intestine

    Science.gov (United States)

    Caballero, Silvia; Pamer, Eric G.

    2015-01-01

    The diverse microbial populations constituting the intestinal microbiota promote immune development and differentiation, but because of their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized and mysterious. In the last decade, deep nucleic acid sequencing platforms, new computational and bioinformatics tools, and full-genome characterization of several hundred commensal bacterial species facilitated studies of the microbiota and revealed that differences in microbiota composition can be associated with inflammatory, metabolic, and infectious diseases, that each human is colonized by a distinct bacterial flora, and that the microbiota can be manipulated to reduce and even cure some diseases. Different bacterial species induce distinct immune cell populations that can play pro- and anti-inflammatory roles, and thus the composition of the microbiota determines, in part, the level of resistance to infection and susceptibility to inflammatory diseases. This review summarizes recent work characterizing commensal microbes that contribute to the antimicrobial defense/inflammation axis. PMID:25581310

  6. Effect of Dietary Fibers on Cecal Microbiota and Intestinal Tumorigenesis in Azoxymethane Treated A/J Min/+ Mice.

    Directory of Open Access Journals (Sweden)

    Birgitte Moen

    Full Text Available Foods naturally high in dietary fiber are generally considered to protect against development of colorectal cancer (CRC. However, the intrinsic effect of dietary fiber on intestinal carcinogenesis is unclear. We used azoxymethane (AOM treated A/J Min/+ mice, which developed a significantly higher tumor load in the colon than in the small intestine, to compare the effects of dietary inulin (IN, cellulose (CE or brewers spent grain (BSG on intestinal tumorigenesis and cecal microbiota. Each fiber was tested at two dose levels, 5% and 15% (w/w content of the AIN-93M diet. The microbiota was investigated by next-generation sequencing of the 16S rRNA gene (V4. We found that mice fed IN had approximately 50% lower colonic tumor load than mice fed CE or BSG (p<0.001. Surprisingly, all three types of fiber caused a dose dependent increase of colonic tumor load (p<0.001. The small intestinal tumor load was not affected by the dietary fiber interventions. Mice fed IN had a lower bacterial diversity than mice fed CE or BSG. The Bacteroidetes/Firmicutes ratio was significantly (p = 0.003 different between the three fiber diets with a higher mean value in IN fed mice compared with BSG and CE. We also found a relation between microbiota and the colonic tumor load, where many of the operational taxonomic units (OTUs related to low tumor load were significantly enriched in mice fed IN. Among the OTUs related to low tumor load were bacteria affiliated with the Bacteroides genus. These results suggest that type of dietary fiber may play a role in the development of CRC, and that the suppressive effect of IN on colonic tumorigenesis is associated with profound changes in the cecal microbiota profile.

  7. Colonisation of a phage susceptible Campylobacter jejuni population in two phage positive broiler flocks.

    Directory of Open Access Journals (Sweden)

    Sophie Kittler

    Full Text Available The pathogens Campylobacter jejuni and Campylobacter coli are commensals in the poultry intestine and campylobacteriosis is one of the most frequent foodborne diseases in developed and developing countries. Phages were identified to be effective in reducing intestinal Campylobacter load and this was evaluated, in the first field trials which were recently carried out. The aim of this study was to further investigate Campylobacter population dynamics during phage application on a commercial broiler farm. This study determines the superiority in colonisation of a Campylobacter type found in a field trial that was susceptible to phages in in vitro tests. The colonisation factors, i.e. motility and gamma glutamyl transferase activity, were increased in this type. The clustering in phylogenetic comparisons of MALDI-TOF spectra did not match the ST, biochemical phenotype and phage susceptibility. Occurrence of Campylobacter jejuni strains and phage susceptibility types with different colonisation potential seem to play a very important role in the success of phage therapy in commercial broiler houses. Thus, mechanisms of both, phage susceptibility and Campylobacter colonisation should be further investigated and considered when composing phage cocktails.

  8. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

  9. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    International Nuclear Information System (INIS)

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-01

    Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [ 14 C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [ 14 C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather

  10. Effects of Cortisol on the Intestinal Mucosal Immune Response during Cohabitant Challenge with IPNV in Atlantic Salmon (Salmo salar)

    DEFF Research Database (Denmark)

    Niklasson, Lars; Sundh, Henrik; Olsen, Rolf-Erik

    2014-01-01

    Infectious pancreatic necrosis virus (IPNV) causes high incidence of disease in salmonids during the first period after SW transfer. During this period as well as during periods of stress, cortisol levels increase and indications of a relationship between IPNV susceptibility and cortisol have been...... response differs from the systemic, but that both are modulated by the stress hormone cortisol....... suggested. The intestine is an entry route and a target tissue for IPNV displaying severe enteritis and sloughing of the mucosa in infected fish. The mechanisms behind effects of the virus on the intestinal tissue and the impact of cortisol on the effect remain unclear. In the present study, Atlantic salmon...

  11. Sonographic diagnosis of intestinal polyps in children.

    Science.gov (United States)

    Parra, Dimitri A; Navarro, Oscar M

    2008-06-01

    Although colonoscopy is the modality of choice for the diagnosis of intestinal polyps, sonography may be the first diagnostic modality in the evaluation of children with this pathology. Graded compression sonography of the small and large bowel may be useful in diagnosing intestinal polyps. A specific diagnosis is possible in many cases as most polyps have a characteristic appearance. Although sonography is not intended to replace endoscopy in the diagnostic work-up of intestinal polyps, it is important for radiologists to be aware of this appearance as they can be the first in making the diagnosis of intestinal polyps using sonography.

  12. Intestinal absorption of fluorescently labeled nanoparticles.

    Science.gov (United States)

    Simovic, Spomenka; Song, Yunmei; Nann, Thomas; Desai, Tejal A

    2015-07-01

    Characterization of intestinal absorption of nanoparticles is critical in the design of noninvasive anticancer, protein-based, and gene nanoparticle-based therapeutics. Here we demonstrate a general approach for the characterization of the intestinal absorption of nanoparticles and for understanding the mechanisms active in their processing within healthy intestinal cells. It is generally accepted that the cellular processing represents a major drawback of current nanoparticle-based therapeutic systems. In particular, endolysosomal trafficking causes degradation of therapeutic molecules such as proteins, lipids, acid-sensitive anticancer drugs, and genes. To date, investigations into nanoparticle processing within intestinal cells have studied mass transport through Caco-2 cells or everted rat intestinal sac models. We developed an approach to visualize directly the mechanisms of nanoparticle processing within intestinal tissue. These results clearly identify a mechanism by which healthy intestinal cells process nanoparticles and point to the possible use of this approach in the design of noninvasive nanoparticle-based therapies. Advances in nanomedicine have resulted in the development of new therapies for various diseases. Intestinal route of administration remains the easiest and most natural. The authors here designed experiments to explore and characterize the process of nanoparticle transport across the intestinal tissue. In so doing, further insights were gained for future drug design. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

  14. Intestinal myiasis caused by Muscina stabulans

    Directory of Open Access Journals (Sweden)

    Shivekar S

    2008-01-01

    Full Text Available Intestinal maggots were isolated from a patient, who had reported to the Department of General Medicine of Sri Manakula Vinayagar Medical College, Puducherry, in southern India with complaints of abdominal distress, bloating of abdomen and intestinal hurry following a meal. He was diagnosed as a case of intestinal myiasis. Maggots obtained from his stool were identified to be Muscina stabulans based on characteristic patterns of posterior spiracles. He was treated with purgatives and albendazole. This intestinal myiasis case caused by M. stabulans is reported here because of its rare occurrence and the need to establish a correct diagnosis.

  15. Ischemia-reperfusion and neonatal intestinal injury.

    Science.gov (United States)

    Young, Christopher M; Kingma, Sandra D K; Neu, Josef

    2011-02-01

    We review research relating ischemia/reperfusion to injury in the neonatal intestine. Epidemiologic evidence suggests that the most common form of necrotizing enterocolitis is not triggered by a primary hypoxic-ischemic event. Its late occurrence, lack of preceding ischemic events, and evidence for microbial and inflammatory processes preclude a major role for primary hypoxic ischemia as the sentinel pathogenic event. However, term infants, especially those with congenital heart disease who have development of intestinal necrosis, and those preterm infants with spontaneous intestinal perforations, are more likely to have intestinal ischemia as a primary component of their disease pathogenesis. Copyright © 2011 Mosby, Inc. All rights reserved.

  16. Antimicrobial resistances do not affect colonization parameters of intestinal E. coli in a small piglet group

    Directory of Open Access Journals (Sweden)

    Schierack Peter

    2009-10-01

    Full Text Available Abstract Background Although antimicrobial resistance and persistence of resistant bacteria in humans and animals are major health concerns worldwide, the impact of antimicrobial resistance on bacterial intestinal colonization in healthy domestic animals has only been rarely studied. We carried out a retrospective analysis of the antimicrobial susceptibility status and the presence of resistance genes in intestinal commensal E. coli clones from clinically healthy pigs from one production unit with particular focus on effects of pheno- and/or genotypic resistance on different nominal and numerical intestinal colonization parameters. In addition, we compared the occurrence of antimicrobial resistance phenotypes and genotypes with the occurrence of virulence associated genes typical for extraintestinal pathogenic E. coli. Results In general, up to 72.1% of all E. coli clones were resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, sulfamethoxazole or tetracycline with a variety of different resistance genes involved. There was no significant correlation between one of the nominal or numerical colonization parameters and the absence or presence of antimicrobial resistance properties or resistance genes. However, there were several statistically significant associations between the occurrence of single resistance genes and single virulence associated genes. Conclusion The demonstrated resistance to the tested antibiotics might not play a dominant role for an intestinal colonization success in pigs in the absence of antimicrobial drugs, or cross-selection of other colonization factors e.g. virulence associated genes might compensate "the cost of antibiotic resistance". Nevertheless, resistant strains are not outcompeted by susceptible bacteria in the porcine intestine. Trial Registration The study was approved by the local animal welfare committee of the "Landesamt für Arbeitsschutz, Gesundheitsschutz und technische Sicherheit" Berlin

  17. Inherited susceptibility and radiation exposure

    International Nuclear Information System (INIS)

    Little, J.B.

    1997-01-01

    There is continuing concern that some people in the general population may have genetic makeups that place them at particularly high risk for radiation-induced cancer. The existence of such a susceptible subpopulation would have obvious implications for the estimation of risks of radiation exposure. Although it has been long known that familial aggregations of cancer do sometimes occur, recent evidence suggests that a general genetic predisposition to cancer does not exist; most cancers occur sporadically. On the other hand, nearly 10% of the known Mendelian genetic disorders are associated with cancer. A number of these involve a familial predisposition to cancer, and some are characterized by an enhanced susceptibility to the induction of cancer by various physical and chemical carcinogens, including ionizing radiation. Such increased susceptibility will depend on several factors including the frequency of the susceptibility gene in the population and its penetrance, the strength of the predisposition, and the degree to which the cancer incidence in susceptible individuals may be increased by the carcinogen. It is now known that these cancer-predisposing genes may be responsible not only for rare familial cancer syndromes, but also for a proportion of the common cancers. Although the currently known disorders can account for only a small fraction of all cancers, they serve as models for genetic predisposition to carcinogen-induced cancer in the general population. In the present report, the author describes current knowledge of those specific disorders that are associated with an enhanced predisposition to radiation-induced cancer, and discusses how this knowledge may bear on the susceptibility to radiation-induced cancer in the general population and estimates of the risk of radiation exposure

  18. Effects of digested onion extracts on intestinal gene expression: an interspecies comparison using different intestine models

    NARCIS (Netherlands)

    Hulst, M.M.; Meulen, van der J.; Hoekman, A.J.W.; Smits, M.A.

    2016-01-01

    Applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as

  19. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure

    NARCIS (Netherlands)

    Korpela, K.; Mutanen, A.; Salonen, A.; Savilahti, E.; Vos, de W.M.; Pakarinen, M.P.

    2017-01-01

    BACKGROUND: Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. METHODS: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent

  20. pitting corrosion susceptibility pitting corrosion susceptibility of aisi ...

    African Journals Online (AJOL)

    eobe

    The susceptibility of austenitic (AISI 301) stainless steel to pitting corrosion was evaluated in sodium chloride ... halides, the most aggressive and thus, the most frequently investigated is the chloride ions, particularly its effect on pit formation in 18/8 stainless steel [1 - 3]. ... in sea water), and moderately high temperatures.

  1. Frequency of intestinal parasites in employees of a state hospital

    Directory of Open Access Journals (Sweden)

    Pınar Fırat

    2010-09-01

    Full Text Available Objectives: The prevalence of intestinal parasites isdifferent in our country and the world. Population move-ments, inadequate infrastructure, seasonal features, tra-ditional hygienic rules, the society’s socio-economic sta-tus and education level are factors that affect the distribu-tion of intestinal parasites. In the study, it was intendedto conduct porter analysis on Malatya State Hospital em-ployees. So, we aimed at determining the rate of intestinalparasites in the laboratory workers, kitchen staff, cleanersand nurses.Materials and Methods: From Malatya State hospitalstaff, perianal area materials and stool samples with cel-lophane tape method were collected. Examples wereexamined with native-Lugol, precipitation, and acid-fasttrichrome stains.Results: In 40.8% of 76 stools that were examined wasfound to positivity. The prevalences of parasites are 17.1Entamoeba coli, 6.6% Iodamoeba butschlii, 19.7% Blastocystishominis, 1.3% Chilomastix mesnilii, 5.3% Giardiaintestinalis and 1.3% Enterobius vermicularis.Conclusion: In the study, the studied staffs are healthworkers. Therefore, since the staffs working close contactwith patients were risk group in terms of infections, it wasrecommended that health staff susceptible to parasitesshould have a medical examination regularly and receivein-service training.

  2. Immune Development and Intestinal Microbiota in Celiac Disease

    Directory of Open Access Journals (Sweden)

    Tamara Pozo-Rubio

    2012-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. The etiology of this disorder is complex, involving both environmental and genetic factors. The major genetic risk factor for CD is represented by HLA-DQ genes, which account for approximately 40% of the genetic risk; however, only a small percentage of carriers develop the disease. Gluten is the main environmental factor responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Epidemiological and clinical data suggest that environmental factors other than gluten might play a role in disease development, including early feeding practices (e.g., breast milk versus formula and duration of breastfeeding, infections, and alterations in the intestinal microbiota composition. Herein, we review what is known about the influence of dietary factors, exposure to infectious agents, and intestinal microbiota composition, particularly in early life, on the risk of developing CD, as well as the possible dietary strategies to induce or increase gluten tolerance.

  3. A simple, quantitative method using alginate gel to determine rat colonic tumor volume in vivo.

    Science.gov (United States)

    Irving, Amy A; Young, Lindsay B; Pleiman, Jennifer K; Konrath, Michael J; Marzella, Blake; Nonte, Michael; Cacciatore, Justin; Ford, Madeline R; Clipson, Linda; Amos-Landgraf, James M; Dove, William F

    2014-04-01

    Many studies of the response of colonic tumors to therapeutics use tumor multiplicity as the endpoint to determine the effectiveness of the agent. These studies can be greatly enhanced by accurate measurements of tumor volume. Here we present a quantitative method to easily and accurately determine colonic tumor volume. This approach uses a biocompatible alginate to create a negative mold of a tumor-bearing colon; this mold is then used to make positive casts of dental stone that replicate the shape of each original tumor. The weight of the dental stone cast correlates highly with the weight of the dissected tumors. After refinement of the technique, overall error in tumor volume was 16.9% ± 7.9% and includes error from both the alginate and dental stone procedures. Because this technique is limited to molding of tumors in the colon, we utilized the Apc(Pirc/+) rat, which has a propensity for developing colonic tumors that reflect the location of the majority of human intestinal tumors. We have successfully used the described method to determine tumor volumes ranging from 4 to 196 mm³. Alginate molding combined with dental stone casting is a facile method for determining tumor volume in vivo without costly equipment or knowledge of analytic software. This broadly accessible method creates the opportunity to objectively study colonic tumors over time in living animals in conjunction with other experiments and without transferring animals from the facility where they are maintained.

  4. Intestinal bacteria condition dendritic cells to promote IgA production.

    Directory of Open Access Journals (Sweden)

    Joanna C Massacand

    Full Text Available Immunoglobulin (Ig A represents the predominant antibody isotype produced at the intestinal mucosa, where it plays an important role in limiting the penetration of commensal intestinal bacteria and opportunistic pathogens. We show in mice that Peyer's Patch-derived dendritic cells (PP-DC exhibit a specialized phenotype allowing the promotion of IgA production by B2 cells. This phenotype included increased expression of the retinaldehyde dehydrogenase 1 (RALDH1, inducible nitric oxide synthase (iNOS, B cell activating factor of the tumor necrosis family (BAFF, a proliferation-inducing ligand (APRIL, and receptors for the neuropeptide vasoactive intestinal peptide (VIP. The ability of PP-DC to promote anti-CD40 dependent IgA was partially dependent on retinoic acid (RA and transforming growth factor (TGF-beta, whilst BAFF and APRIL signaling were not required. Signals delivered by BAFF and APRIL were crucial for CD40 independent IgA production, although the contribution of B2 cells to this pathway was minimal. The unique ability of PP-DC to instruct naïve B cells to differentiate into IgA producing plasma cells was mainly imparted by the presence of intestinal commensal bacteria, and could be mimicked by the addition of LPS to the culture. These data indicate that exposure to pathogen-associated molecular patterns present on intestinal commensal bacteria condition DC to express a unique molecular footprint that in turn allows them to promote IgA production.

  5. IL-1β in eosinophil-mediated small intestinal homeostasis and IgA production

    Science.gov (United States)

    Jung, Y; Wen, T; Mingler, MK; Caldwell, JM; Wang, YH; Chaplin, DD; Lee, EH; Jang, MH; Woo, SY; Seoh, JY; Miyasaka, M; Rothenberg, ME

    2014-01-01

    Eosinophils are multifunctional leukocytes that reside in the gastrointestinal (GI) lamina propria, where their basal function remains largely unexplored. In this study, by examining mice with a selective deficiency of systemic eosinophils (by lineage ablation) or GI eosinophils (eotaxin-1/2 double–deficient or CC chemokine receptor 3–deficient), we show that eosinophils support immunoglobulin A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal microbial composition, and promote the development of Peyer’s patches. Eosinophil-deficient mice showed reduced expression of mediators of secretory IgA production, including intestinal interleukin 1β (IL-1β), inducible nitric oxide synthase, lymphotoxin (LT) α, and LT-β, and reduced levels of retinoic acid-related orphan receptor gamma t–positive (ROR-γt+) innate lymphoid cells (ILCs) while maintaining normal levels of APRIL (a proliferation-inducing ligand), BAFF (B cell–activating factor of the tumor necrosis factor family), and TGF-β (transforming growth factor β). GI eosinophils expressed a relatively high level of IL-1β, and IL-1β–deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA+ cells and ROR-γt+ ILCs. On the basis of these collective data, we propose that eosinophils are required for homeostatic intestinal immune responses including IgA production and that their affect is mediated via IL-1β in the small intestine. PMID:25563499

  6. High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids.

    Science.gov (United States)

    Stenman, Lotta K; Holma, Reetta; Korpela, Riitta

    2012-03-07

    To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism. Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF). Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon. High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.

  7. Morphological changes in the enteric nervous system caused by carcinoma of the human large intestine.

    Directory of Open Access Journals (Sweden)

    Janusz Godlewski

    2010-06-01

    Full Text Available The innervations of the large intestine is responsible for it peristalsis and contractibility. Investigations of the enteric nervous system in many colon diseases have revealed changes in this structure. No study has been carried out on morphological changes of the enteric nervous system in the human large intestine with carcinoma. The aim of this study was to investigate potential changes in the structure of the enteric neurons in patients with sigmoid and rectal cancer. Material for the study was obtained from patients undergoing operations due to carcinoma of the sigmoid colon and rectum. Microscopic observation of the cancerous tumor of the human large intestine revealed changes in the enteric nervous system innervating this part of the gastrointestinal tract. In the region of the enteric plexuses located close to the tumour, disruption of their correct placement and structure was observed. The changes also consisted of the disappearance of neurons and nerve fibers forming these plexuses. In the solid cancerous tumour, elements of the enteric nervous system were not present. Destruction of the enteric nervous system in the course of carcinoma of the large intestine may cause disruption of proper intestinal function and may be responsible for part of symptoms which the patients suffer.

  8. Inflammatory mediators and intestinal injury.

    Science.gov (United States)

    Caplan, M S; MacKendrick, W

    1994-06-01

    Although the causes of necrotizing enterocolitis (NEC) are not well understood, there is compelling evidence to suggest that the inflammatory mediators play an important role in the pathophysiology of the disease. This article examines the role of platelet-activating factor (PAF) and other mediators on the development of NEC, and attempts to explain the association of the putative NEC risk factors with altered mediator production and subsequent intestinal injury. The authors hypothesize that PAF is a key mediator in the final common pathway leading to NEC.

  9. Intestinal Lymphangiectasia Secondary to Neuroblastoma

    Directory of Open Access Journals (Sweden)

    RM Reifen

    1994-01-01

    Full Text Available An eight month-old infant presented with a 10-day history of vomiting and diarrhea, and a one-week history of swelling of the lower extremities. Laboratory evaluations revealed hypoproteinemia and lymphocytopenia due to protein-losing enteropathy. Peroral small bowel biopsy showed intestinal lymphangiectasia. Subsequent onset of unexplained ecchymosis and obstructive jaundice resulted in additional studies which revealed an omental neuroblastoma as the underlying etiology of the infant’s symptoms. This report emphasizes the importance of considering secondary, obstructive causes for lymphangiectasia and protein-losing enteropathy.

  10. Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-11-27

    Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

  11. Evaluation of intestinal perfusion by ICG fluorescence imaging in laparoscopic colorectal surgery with DST anastomosis.

    Science.gov (United States)

    Kawada, Kenji; Hasegawa, Suguru; Wada, Toshiaki; Takahashi, Ryo; Hisamori, Shigeo; Hida, Koya; Sakai, Yoshiharu

    2017-03-01

    Decreased blood perfusion is an important risk factor for postoperative anastomotic leakage (AL). Fluorescence imaging with indocyanine green (ICG) provides a real-time assessment of intestinal perfusion. This study evaluated the utility of ICG fluorescence imaging in determining the transection line of the proximal colon during laparoscopic colorectal surgery with double stapling technique (DST) anastomosis. This was a prospective single-institution study of 68 patients with left-sided colorectal cancers who underwent laparoscopic colorectal surgery between August 2013 and December 2014. After distal transection of the bowel, the specimen was extracted extracorporeally and then the mesentery was divided along the planned transection line determined by the surgeons' judgement under normal q. After ICG was injected intravenously, intestinal perfusion of the proximal colon was assessed in the fluorescent imaging mode. Intestinal perfusion was examined in relation to the patient-, tumor- and surgery-related variables using univariate and multivariate analyses. ICG fluorescence imaging showed that intestinal perfusion was present at 3 mm (median) distal to the initially planned transection line. ICG fluorescence imaging resulted in a proximal change of the transection line by more than 5 mm in 18 patients (26.5 %) and, particularly, by more than 50 mm in 3 patients (4.4 %), compared with the initially planned transection line. Univariate analysis revealed that diabetes mellitus, anticoagulation therapy, preoperative chemotherapy and operative time were significantly associated with poor intestinal perfusion. Multivariate analysis identified anticoagulation therapy (P = 0.021) and preoperative chemotherapy (P = 0.019) as independent risk factors for poor intestinal perfusion. Three patients (4.5 %) with a change of transection line developed AL. ICG fluorescence imaging is useful for determining the transection line in laparoscopic colorectal surgery with DST

  12. Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk

    DEFF Research Database (Denmark)

    Blackburn, Anneke C; Hill, Linda Z; Roberts, Amy L

    2007-01-01

    Low-penetrance breast cancer susceptibility alleles seem to play a significant role in breast cancer risk but are difficult to identify in human cohorts. A genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and C57BL/6, which differ in their susceptibility to mammary...... tumors, identified a modifier of mammary tumor susceptibility in an approximately 25-Mb interval on mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from 70.7 to 61.1 weeks and increased risk...

  13. A Rare Case Report: A Giant Angiomyolipoma Located in the Small Intestine

    Directory of Open Access Journals (Sweden)

    Sevilay Gürcan

    2015-04-01

    Full Text Available An angiomyolipoma is a mesenchymal neoplasm of the tumor and is composed of a varying heterogeneous mixture of blood vessels, smooth muscles, and adipose cells. Extra-renal angiomyolipomas are rarely seen and are most commonly found in the liver. Angiomyolipomas of the small intestine are extremely rare. We report the case of a 32-year-old man who had an ileal angiomyolipoma and who clinically presented with weakness and abdominal pain. A computed tomography scan of the abdomen showed a massive lesion, and segmental resection of the small intestine was performed. In the microscopic examination of the material that was sent for pathological evaluation, a tumor that included a cystic dilated vascular structure, adipose tissue, and muscular tissue extending from the serosa to the mucosa was seen. On immunohistochemical staining, various regions of the tumor were stained positive by actin, desmin, vimentin, CD31, CD34, and D2-40. With these histopathological findings, the patient was diagnosed with angiomyolipoma of the small intestinal mesentery.

  14. Tumors of the ampulla of vater: histopathologic classification and predictors of survival.

    Science.gov (United States)

    Carter, Jonathan T; Grenert, James P; Rubenstein, Laura; Stewart, Lygia; Way, Lawrence W

    2008-08-01

    The histology and clinical behavior of ampullary tumors vary substantially. We speculated that this might reflect the presence of two kinds of ampullary adenocarcinoma: pancreaticobiliary and intestinal. We analyzed patient demographics, presentation, survival (mean followup 44 months), and tumor histology for 157 consecutive ampullary tumors resected from 1989 to 2006. Histologic features were reviewed by a pathologist blinded to clinical outcomes. Survival was compared using Kaplan-Meier/Cox proportional hazards analysis. There were 33 benign (32 adenomas and 1 paraganglioma) and 124 malignant (118 adenocarcinomas and 6 neuroendocrine) tumors. One hundred fifteen (73%) patients underwent a Whipple procedure, 32 (20%) a local resection, and 10 (7%) a palliative operation. For adenocarcinomas, survival in univariate models was affected by jaundice, histologic grade, lymphovascular, or perineural invasion, T stage, nodal metastasis, and pancreaticobiliary subtype (p jaundice more often than those with the intestinal kind (p = 0.01) and had worse survival. In addition to other factors, tumor type (intestinal versus pancreaticobiliary) had a major effect on survival in patients with ampullary adenocarcinoma. The current concept of ampullary adenocarcinoma as a unique entity, distinct from duodenal and pancreatic adenocarcinoma, might be wrong. Intestinal ampullary adenocarcinomas behaved like their duodenal counterparts, but pancreaticobiliary ones were more aggressive and behaved like pancreatic adenocarcinomas.

  15. Hepatic tumors in children.

    Science.gov (United States)

    Stocker, J T

    2001-02-01

    Although they account for only 1% to 4% of solid tumors in children, hepatic tumors and pseudotumors offer a diagnostic challenge to the clinician seeing only an occasional case. Metastatic lesions such as neuroblastoma, Wilms' tumor, and lymphoma are the most common neoplasm seen in the liver, but 10 distinct primary tumors and pseudotumors of the liver occur with some regularity, and a few others may be seen rarely, including leiomyosarcoma, rhabdoid tumor, and endodermal sinus tumor. Five of these neoplasms--hepatoblastoma, infantile hemangio-endothelioma, mesenchymal hamartoma, undifferentiated embryonal sarcoma, and embryonal rhabdomyosarcoma of the biliary tree--occur only in children and are the major focus of the article.

  16. Gastrointestinal stromal tumor of the anal canal: An unusual presentation

    Directory of Open Access Journals (Sweden)

    Chhanda Das

    2017-01-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are the most common mesenchymal neoplasm of the gastrointestinal tract. The most common site is stomach, followed by small intestine, colon, and esophagus. However, GIST from the anal canal is an extremely rare tumor. Here, we report an extremely rare case of GIST of the anal canal in a 40-year-old female with a history of irregular bowel habits mixed with blood and constipation for 4 months. Diagnosis was made on the basis of histopathological and immunohistochemical examination.

  17. Prematurity reduces functional adaptation to intestinal resection in piglets

    DEFF Research Database (Denmark)

    Aunsholt, Lise; Thymann, Thomas; Qvist, Niels

    2015-01-01

    Background: Necrotizing enterocolitis and congenital gastrointestinal malformations in infants often require intestinal resection, with a subsequent risk of short bowel syndrome (SBS). We hypothesized that immediate intestinal adaptation following resection of the distal intestine with placement ...

  18. The Adaptive Response to Intestinal Oxidative Stress in Mammalian Hibernation

    National Research Council Canada - National Science Library

    Carey, Hannah V

    2006-01-01

    .... Specific Aim 2 examines consequences of intestinal oxidative stress during hibernation including seasonal changes in NF-kB activation in intestine, seasonal changes in the intestinal mucosal immune...

  19. Effect of Dietary Fibers on Cecal Microbiota and Intestinal Tumorigenesis in Azoxymethane Treated A/J Min/+ Mice

    Science.gov (United States)

    Måge, Ingrid; Knutsen, Svein Halvor; Rud, Ida; Hetland, Ragna Bogen; Paulsen, Jan Erik

    2016-01-01

    Foods naturally high in dietary fiber are generally considered to protect against development of colorectal cancer (CRC). However, the intrinsic effect of dietary fiber on intestinal carcinogenesis is unclear. We used azoxymethane (AOM) treated A/J Min/+ mice, which developed a significantly higher tumor load in the colon than in the small intestine, to compare the effects of dietary inulin (IN), cellulose (CE) or brewers spent grain (BSG) on intestinal tumorigenesis and cecal microbiota. Each fiber was tested at two dose levels, 5% and 15% (w/w) content of the AIN-93M diet. The microbiota was investigated by next-generation sequencing of the 16S rRNA gene (V4). We found that mice fed IN had approximately 50% lower colonic tumor load than mice fed CE or BSG (pBSG. The Bacteroidetes/Firmicutes ratio was significantly (p = 0.003) different between the three fiber diets with a higher mean value in IN fed mice compared with BSG and CE. We also found a relation between microbiota and the colonic tumor load, where many of the operational taxonomic units (OTUs) related to low tumor load were significantly enriched in mice fed IN. Among the OTUs related to low tumor load were bacteria affiliated with the Bacteroides genus. These results suggest that type of dietary fiber may play a role in the development of CRC, and that the suppressive effect of IN on colonic tumorigenesis is associated with profound changes in the cecal microbiota profile. PMID:27196124

  20. Breast carcinoma following radiotherapy of metastatic Wilms' tumor

    International Nuclear Information System (INIS)

    Reimer, R.R.; Fraumeni, J.F. Jr.; Reddick, R.; Moorhead, E.L. II.

    1977-01-01

    A 22-year-old woman developed breast cancer 15 years after radiotherapy to the lung for metastatic Wilms' tumor. Her 32-year-old mother died of bilateral breast cancer, suggesting a genetic predisposition to radiogenic cancer. Recent improvements in the survival of children with certain cancers necessitate long-term surveillance for iatrogenic neoplasia, particularly when familial susceptibility is evident

  1. Tumor-Initiating Cells and Methods of Use

    Science.gov (United States)

    Hlatky, Lynn (Inventor)

    2014-01-01

    Provided herein are an isolated or enriched population of tumor initiating cells derived from normal cells, cells susceptible to neoplasia, or neoplastic cells. Methods of use of the cells for screening for anti-hyperproliferative agents, and use of the cells for animal models of hyperproliferative disorders including metastatic cancer, diagnostic methods, and therapeutic methods are provided.

  2. Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation.

    Directory of Open Access Journals (Sweden)

    Keith C Summa

    Full Text Available The circadian clock orchestrates temporal patterns of physiology and behavior relative to the environmental light:dark cycle by generating and organizing transcriptional and biochemical rhythms in cells and tissues throughout the body. Circadian clock genes have been shown to regulate the physiology and function of the gastrointestinal tract. Disruption of the intestinal epithelial barrier enables the translocation of proinflammatory bacterial products, such as endotoxin, across the intestinal wall and into systemic circulation; a process that has been linked to pathologic inflammatory states associated with metabolic, hepatic, cardiovascular and neurodegenerative diseases - many of which are commonly reported in shift workers. Here we report, for the first time, that circadian disorganization, using independent genetic and environmental strategies, increases permeability of the intestinal epithelial barrier (i.e., gut leakiness in mice. Utilizing chronic alcohol consumption as a well-established model of induced intestinal hyperpermeability, we also found that both genetic and environmental circadian disruption promote alcohol-induced gut leakiness, endotoxemia and steatohepatitis, possibly through a mechanism involving the tight junction protein occludin. Circadian organization thus appears critical for the maintenance of intestinal barrier integrity, especially in the context of injurious agents, such as alcohol. Circadian disruption may therefore represent a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease, as well as other conditions associated with intestinal hyperpermeability and an endotoxin-triggered inflammatory state.

  3. How the Intricate Interaction among Toll-Like Receptors, Microbiota, and Intestinal Immunity Can Influence Gastrointestinal Pathology

    Directory of Open Access Journals (Sweden)

    Simona Frosali

    2015-01-01

    Full Text Available The gut is able to maintain tolerance to microbial and food antigens. The intestine minimizes the number of harmful bacteria by shaping the microbiota through a symbiotic relationship. In healthy human intestine, a constant homeostasis is maintained by the perfect regulation of microbial load and the immune response generated against it. Failure of this balance may result in various pathological conditions. Innate immune sensors, such as Toll-like receptors (TLRs, may be considered an interface among intestinal epithelial barrier, microbiota, and immune system. TLRs pathway, activated by pathogens, is involved in the pathogenesis of several infectious and inflammatory diseases. The alteration of the homeostasis between physiologic and pathogenic bacteria of intestinal flora causes a condition called dysbiosis. The breakdown of homeostasis by dysbiosis may increase susceptibility to inflammatory bowel diseases. It is evident that environment, genetics, and host immunity form a highly interactive regulatory triad that controls TLR function. Imbalanced relationships within this triad may promote aberrant TLR signaling, critically contributing to acute and chronic intestinal inflammatory processes, such as in IBD, colitis, and colorectal cancer. The study of interactions between different components of the immune systems and intestinal microbiota will open new horizons in the knowledge of gut inflammation.

  4. India, Genomic diversity & Disease susceptibility

    Indian Academy of Sciences (India)

    Table of contents. India, Genomic diversity & Disease susceptibility · India, a paradise for Genetic Studies · Involved in earlier stages of Immune response protecting us from Diseases, Responsible for kidney and other transplant rejections Inherited from our parents · PowerPoint Presentation · Slide 5 · Slide 6 · Slide 7.

  5. Prion protein and scrapie susceptibility

    NARCIS (Netherlands)

    Smits, M.A.; Bossers, A.; Schreuder, B.E.C.

    1997-01-01

    This article presents briefly current views on the role of prion protein (PrP) in Transmissible Spongiform Encephalopathies or prion diseases and the effect of PrP polymoryhisms on the susceptibility to these diseases, with special emphasis on sheep scrapie. The PrP genotype of sheep apears to be a

  6. Vulnerability of cultured canine lung tumor cells to NK cell-mediated cytolysis

    International Nuclear Information System (INIS)

    Haley, P.J.; Kohr, J.M.; Kelly, G.; Muggenburg, B.A.; Guilmette, B.A.

    1988-01-01

    Five cell lines, designated as canine lung epithelial cell (CLEP), derived from radiation induced canine lung tumors and canine thyroid adeno-carcinoma (CTAC) cells were compared for their susceptibility to NK cell-mediated cytolysis using peripheral blood lymphocytes from normal, healthy Beagle dogs as effector cells. Effector cells and chromium 51 radiolabeled target cells were incubated for 16 h at ratios of 12.5:1, 25:1, 50:1, and 100:1. Increasing cytolysis was observed for all cell lines as the effector-to-target-cell ratios increased from 12.5:1 to 100:1. The percent cytotoxicity was significantly less for all lung tumor cell lines as compared to CTAC at the 100:1 ratio. One lung tumor cell line, CLEP-9, had 85% of the lytic vulnerability of the CTAC cell line and significantly greater susceptibility to NK cell-mediated lysis than all of the other lung tumor cell lines. Susceptibility to NK cell cytolysis did not correlate with in vivo malignant behavior of the original tumor. These data suggest that cultured canine lung tumor cells are susceptible to NK cell cytolytic activity in vitro and that at least one of these cell lines (CLEP-9) is a candidate for substitution of the standard canine NK cell target, CTAC, in NK cell assays. The use of lung tumor cells in NK cell assays may provide greater insight into the control of lung tumors by immune mechanisms. (author)

  7. Mucin 1 Gene (MUC1 and Gastric-Cancer Susceptibility

    Directory of Open Access Journals (Sweden)

    Norihisa Saeki

    2014-05-01

    Full Text Available Gastric cancer (GC is one of the major malignant diseases worldwide, especially in Asia. It is classified into intestinal and diffuse types. While the intestinal-type GC (IGC is almost certainly caused by Helicobacter pylori (HP infection, its role in the diffuse-type GC (DGC appears limited. Recently, genome-wide association studies (GWAS on Japanese and Chinese populations identified chromosome 1q22 as a GC susceptibility locus which harbors mucin 1 gene (MUC1 encoding a cell membrane-bound mucin protein. MUC1 has been known as an oncogene with an anti-apoptotic function in cancer cells; however, in normal gastric mucosa, it is anticipated that the mucin 1 protein has a role in protecting gastric epithelial cells from a variety of external insults which cause inflammation and carcinogenesis. HP infection is the most definite insult leading to GC, and a protective function of mucin 1 protein has been suggested by studies on Muc1 knocked-out mice.

  8. Lymphoma Caused by Intestinal Microbiota

    Directory of Open Access Journals (Sweden)

    Mitsuko L. Yamamoto

    2014-09-01

    Full Text Available The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.

  9. Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice.

    Science.gov (United States)

    Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Fornace, Albert J; Datta, Kamal

    2017-05-01

    Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC 1638N/+ ) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC 1638N/+ mice after exposure to energetic heavy ions at high (50cGy/min) and relatively low (0.33cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50cGy of 28 Si (energy: 300MeV/n; LET: 70keV/μm) or 56 Fe (energy: 1000MeV/n; LET: 148keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n=20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56 Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28 Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor

  10. Butter feeding enhances TNF-alpha production from macrophages and lymphocyte adherence in murine small intestinal microvessels.

    Science.gov (United States)

    Fujiyama, Yoichi; Hokari, Ryota; Miura, Soichiro; Watanabe, Chikako; Komoto, Shunsuke; Oyama, Tokushige; Kurihara, Chie; Nagata, Hiroshi; Hibi, Toshifumi

    2007-11-01

    Dietary fat is known to modulate immune functions. Intake of an animal fat-rich diet has been linked to increased risk of inflammation; however, little is known about how animal fat ingestion directly affects intestinal immune function. The objective of this study was to assess the effect of butter feeding on lymphocyte migration in intestinal mucosa and the changes in adhesion molecules and cytokines involved in this effect. T-lymphocytes isolated from the spleen were fluorescence-labeled and injected into recipient mice. Butter was administered into the duodenum, and villus microvessels of the small intestinal mucosa were observed under an intravital microscope. mRNA expression of adhesion molecules and cytokines in the intestinal mucosa were determined by quantitative PCR. The effect of butter feeding on tumor necrosis factor (TNF)-alpha mRNA expression of intestinal macrophages was also determined. Intraluminal butter administration significantly increased lymphocyte adherence to intestinal microvessels accompanied by increases in expression levels of adhesion molecules ICAM-1, MAdCAM-1 and VCAM-1. This accumulation was significantly attenuated by anti-MAdCAM-1 and anti-ICAM-1 antibodies. Butter administration significantly increased TNF-alpha in the lamina proprial macrophages but not interleukin-6. Anti-TNF-alpha treatment attenuated the enhanced expression of adhesion molecules induced by butter administration. T-lymphocyte adherence to microvessels of the small intestinal mucosa was significantly enhanced after butter ingestion. This enhancement is due to increase in expression levels of adhesion molecules of the intestinal mucosa, which is mediated by TNF-alpha from macrophages in the intestinal lamina propria.

  11. Megacystis microcolon intestinal hypoperistalsis syndrome: a report ...

    African Journals Online (AJOL)

    The prognosis is poor and most patients die early because of sepsis or total parental nutrition-related complications. This report describes a new case of megacystis microcolon intestinal hypoperistalsis syndrome associated with meconium ileus, dilated stomach, and megaesophagus. Keywords: intestinal hypoperistalsis ...

  12. Intestinal cholesterol secretion: future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  13. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  14. Alkaline Phosphatases From Camel Small Intestine | Fahmy ...

    African Journals Online (AJOL)

    Camel intestinal alkaline phosphatase have been purified and characterized. The purification was carried out by chromatography on DEAE-cellulose. Five intestinal alkaline phosphatase isoenzymes (IAP1 to IAP5) were obtained. IAP2 and IAP5 with the highest activity levels were purified to homogeneity by Sephacryl ...

  15. Megacystis microcolon intestinal hypoperistalsis syndrome: a report ...

    African Journals Online (AJOL)

    intestinal peristalsis. The prognosis is poor and most patients die early because of sepsis or total parental nutrition-related complications. This report describes a new case of megacystis microcolon intestinal hypoperistalsis syndrome associated with meconium ileus, dilated stomach, and megaesophagus. Ann Pediatr Surg.

  16. Is nonoperative management of adhesive intestinal obstruction ...

    African Journals Online (AJOL)

    Background: Nonoperative management of adhesive intestinal obstruction gives good results in adults but there are scant studies on its outcome in children. This study reports outcomes and experiences with nonoperative and operative management of adhesive intestinal obstruction in children in a resource-poor country.

  17. Laparoscopic Treatment of Intestinal Malrotation in Children

    NARCIS (Netherlands)

    Ooms, N.; Matthyssens, L.E.; Draaisma, J.M.T.; Blaauw, I. de; Wijnen, M.H.

    2016-01-01

    Purpose Intestinal malrotation is a congenital intestinal rotation anomaly, which can be treated by either laparotomy or laparoscopy. Our hypothesis is that laparoscopic treatment leads to less small bowel obstruction because of the fewer adhesions in comparison to laparotomy, without increasing the

  18. Species and prevalence determination of Human Intestinal ...

    African Journals Online (AJOL)

    Intestinal parasitic infections constitute a global health burden causing clinical morbidity. Parasitic protozoa and helminthes are responsible for some of the most devastating and prevalent diseases of human. The study was conducted to determine the prevalence of intestinal parasites among patients attending Federal ...

  19. Ectoparasites and intestinal helminths of speckled pigeon ...

    African Journals Online (AJOL)

    Ectoparasites and intestinal helminths of speckled pigeon ( Columba guinea Hartlaub and Finsch 1870) in Zaria, Nigeria. ... Science World Journal ... A total of 30 (20 males and 10 females) Speckled Pigeons trapped from the wild in Zaria and its environs, Nigeria, were examined for ectoparasites and intestinal helminths, ...

  20. Species and prevalence determination of Human Intestinal ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: Intestinal parasitic infections constitute a global health burden causing clinical morbidity. Parasitic protozoa and helminthes are responsible for some of the most devastating and prevalent diseases of human. The study was conducted to determine the prevalence of intestinal parasites among patients attending ...

  1. Intestinal radiation syndrome: sepsis and endotoxin

    International Nuclear Information System (INIS)

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

    1985-01-01

    Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and 137 Cs γ rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and γ-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presence of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome

  2. Detection of Lawsonia intracellularis in formalinfixed Porcine Intestinal Tissue Samples: Comparison of Immunofluorescense and In-situ Hybridization, and Evaluation of the Effectf of Controlled Autolysis

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre; Boesen, H. T.; Vigre, Håkan

    2010-01-01

    methods had a specificity of 100%. Fifty normal porcine intestines were negative by both tests. IFA was much less susceptible than FISH to the effects of autolysis. Thus, three of nine samples from pigs with PE were FISH-negative after being kept at 20°C for 4 days, and seven were FISH negative after 2...

  3. Brain and Spinal Tumors

    Science.gov (United States)

    ... vessels. Also under investigation are ways to improve drug delivery to the tumor and to prevent the side- ... vessels. Also under investigation are ways to improve drug delivery to the tumor and to prevent the side- ...

  4. Regulation of intestinal calcium absorption by luminal calcium content: role of intestinal alkaline phosphatase.

    Science.gov (United States)

    Brun, Lucas R; Brance, María L; Lombarte, Mercedes; Lupo, Maela; Di Loreto, Verónica E; Rigalli, Alfredo

    2014-07-01

    Intestinal alkaline phosphatase is a brush border enzyme that is stimulated by calcium. Inhibition of intestinal alkaline phosphatase increases intestinal calcium absorption. We hypothesized that intestinal alkaline phosphatase acts as a minute-to-minute regulatory mechanism of calcium entry. The aim of this study was to evaluate the mechanism by which intestinal luminal calcium controls intestinal calcium absorption. We performed kinetic studies with purified intestinal alkaline phosphatase and everted duodenal sacs and showed that intestinal alkaline phosphatase modifies the luminal pH as a function of enzyme concentration and calcium luminal content. A decrease in pH occurred simultaneously with a decrease in calcium absorption. The inhibition of intestinal alkaline phosphatase by l-phenylalanine caused an increase in calcium absorption. This effect was also confirmed in calcium uptake experiments with isolated duodenal cells. Changes in luminal pH arising from intestinal alkaline phosphatase activity induced by luminal calcium concentration modulate intestinal calcium absorption. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Reporting tumor molecular heterogeneity in histopathological diagnosis.

    Directory of Open Access Journals (Sweden)

    Andrea Mafficini

    Full Text Available Detection of molecular tumor heterogeneity has become of paramount importance with the advent of targeted therapies. Analysis for detection should be comprehensive, timely and based on routinely available tumor samples.To evaluate the diagnostic potential of targeted multigene next-generation sequencing (TM-NGS in characterizing gastrointestinal cancer molecular heterogeneity.35 gastrointestinal tract tumors, five of each intestinal type gastric carcinomas, pancreatic ductal adenocarcinomas, pancreatic intraductal papillary mucinous neoplasms, ampulla of Vater carcinomas, hepatocellular carcinomas, cholangiocarcinomas, pancreatic solid pseudopapillary tumors were assessed for mutations in 46 cancer-associated genes, using Ion Torrent semiconductor-based TM-NGS. One ampulla of Vater carcinoma cell line and one hepatic carcinosarcoma served to assess assay sensitivity. TP53, PIK3CA, KRAS, and BRAF mutations were validated by conventional Sanger sequencing.TM-NGS yielded overlapping results on matched fresh-frozen and formalin-fixed paraffin-embedded (FFPE tissues, with a mutation detection limit of 1% for fresh-frozen high molecular weight DNA and 2% for FFPE partially degraded DNA. At least one somatic mutation was observed in all tumors tested; multiple alterations were detected in 20/35 (57% tumors. Seven cancers displayed significant differences in allelic frequencies for distinct mutations, indicating the presence of intratumor molecular heterogeneity; this was confirmed on selected samples by immunohistochemistry of p53 and Smad4, showing concordance with mutational analysis.TM-NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, moving one step closer to a next-generation histopathologic diagnosis that integrates morphologic, immunophenotypic, and multigene mutational analysis on routinely processed tissues, essential for personalized cancer therapy.

  6. Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier.

    Science.gov (United States)

    Zhai, Qixiao; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

    2016-07-15

    The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure. The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd contamination

  7. Aggressive malignant phyllodes tumor

    OpenAIRE

    Nathan Roberts; Dianne M. Runk

    2015-01-01

    Introduction: Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3–0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10–30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumo...

  8. Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon

    Directory of Open Access Journals (Sweden)

    Wu Xianli

    2009-09-01

    Full Text Available Abstract Background Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB on formation of aberrant crypt foci (ACF in colons of male Fisher F344 rats (inbred strain. However, effects of BB on colon tumors and in both genders are unknown. Methods We examined efficacy of BB in inhibition of azoxymethane (AOM-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain. Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults. Results Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (P P P > 0.05 to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (P > 0.1 by BB. There was a tendency (0.1 > P > 0.05 for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (P P Conclusion Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma by BB.

  9. Gallstone ileus resulting in strong intestinal obstruction

    Directory of Open Access Journals (Sweden)

    Israel Szajnbok

    Full Text Available Mechanic intestinal obstruction, caused by the passage of biliary calculus from vesicle to intestine, through fistulization, although not frequent, deserve study due to the morbi-mortality rates. Incidence in elder people explains the association with chronic degenerative diseases, increasing complexity in terms of therapy decision. Literature discusses the need and opportunity for the one or two-phase surgical attack of the cholecystenteric fistule, in front of the resolution on the obstructive urgency and makes reference to Gallstone Ileus as an exception for strong intestinal obstruction. The more frequent intestinal obstruction observed is when it occurs a Gallstone Ileus impacting in terms of ileocecal valve. The authors submit a Gallstone Ileus manifestation as causing strong intestinal obstruction, discussing aspects regarding diagnostic and treatment.

  10. Multispectral tissue characterization for intestinal anastomosis optimization

    Science.gov (United States)

    Cha, Jaepyeong; Shademan, Azad; Le, Hanh N. D.; Decker, Ryan; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel

    2015-10-01

    Intestinal anastomosis is a surgical procedure that restores bowel continuity after surgical resection to treat intestinal malignancy, inflammation, or obstruction. Despite the routine nature of intestinal anastomosis procedures, the rate of complications is high. Standard visual inspection cannot distinguish the tissue subsurface and small changes in spectral characteristics of the tissue, so existing tissue anastomosis techniques that rely on human vision to guide suturing could lead to problems such as bleeding and leakage from suturing sites. We present a proof-of-concept study using a portable multispectral imaging (MSI) platform for tissue characterization and preoperative surgical planning in intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI system coupled with polarizers and image analysis software. The system is tested on ex vivo porcine intestine tissue, and we demonstrate the feasibility of identifying optimal regions for suture placement.

  11. ACUTE INTESTINAL INFECTIONS: THERAPEUTICAL TACTICS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A.N. Surkov

    2011-01-01

    Full Text Available Acute intestinal infections are quite common among children. Their clinical presentations include intoxication syndrome (drowsiness, low appetite, fever etc, infectious toxic syndrome (toxicosis with exicosis, neurotoxicosi, hypovolemic or infectious-toxic shockand diarrhea syndrome. Sometimes intestinal infections can be quite severe and even lethal. However disease duration and outcome depend on timelines and adequacy of prescribed treatment. Main guidelines of intestinal infections treatment include probiotics. That is why the right choice of probiotics is important for a pediatrician. The article contains basic information upon etiopathogenesis, classification, diagnostic criteria and acute pediatric intestinal infections treatment guidelines.Key words: acute intestinal infections, etiopathogenesis, diagnostic criteria, treatment, probiotics, children. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (6: 141–147

  12. Regional specialization within the intestinal immune system

    DEFF Research Database (Denmark)

    Mowat, Allan M.; Agace, William Winston

    2014-01-01

    The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly...... implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout...... the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease...

  13. Complete Intestinal Obstruction and Necrosis as a Complication of a Ventriculoperitoneal Shunt in Children

    Science.gov (United States)

    Zhao, Rui; Shi, Wei; Yu, Jianzhong; Gao, Xiaofeng; Li, Hao

    2015-01-01

    Abstract Ventriculoperitoneal (VP) shunt complications are common, but abdominal complications are rare. The objective of this report is to present 2 cases of intestinal obstruction due to a VP shunt and review the literature for data on this rare occurrence. A 4-month-old boy received surgical resection of a medulloblastoma and a VP shunt was inserted to manage progressive hydrocephalus. Two months later, he was admitted with intermittent vomiting, and plain abdominal radiography showed complete intestinal obstruction. Emergency laparotomy revealed an adhesive intestinal obstruction around the catheter, and approximately 5 cm of necrotic ileum was resected. His recovery was uneventful. In the second case, a 6-year-old boy was diagnosed with a primary nongerminomatous malignant germ cell tumor and a VP shunt was place to treat hydrocephalus. Two weeks after the first course of chemotherapy, he went into a coma; computed tomography demonstrated enlargement of the tumor and gross total resection was performed. Two weeks later, he developed abdominal distention; plain radiography showed intestinal obstruction and laparotomy revealed adhesive intestinal obstruction around the catheter with 15 cm of necrotic ileum. The necrotic bowel was resected. Unfortunately, the patient developed sepsis and despite treatment remained in a vegetative state. Medline, Central, Embase, and Google Scholar databases were searched up to May 9, 2014, using the terms VP shunt, shunting, and/or intestinal obstruction. Only cases involving children or adolescents were included. Eleven reports involving patients with abdominal complications resulting from a VP shunt for hydrocephalus were identified. The dates of the reports spanned from 1971 to 2014. Volvulus was the most common cause of VP shunt-related obstruction, and mechanical obstruction due to twisting of the catheter the second most common. Only 1 case in the literature review was related to intestinal adhesions. Treatment in most

  14. Regional differences of physiological functions and cancer susceptibility in the human large intestine

    NARCIS (Netherlands)

    Cats, A; DeVries, EGE; Mulder, NH; Kleibeuker, JH

    1996-01-01

    Regional differences in function, metabolism and morphology between proximal colon, distal colon and rectum may be important in the pathogenesis and biologic behaviour of tumours originating from these segments. Thus, the effect of primary prevention of colorectal cancer may also differ from one

  15. Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine.

    Science.gov (United States)

    Maeda, Yuichi; Kurakawa, Takashi; Umemoto, Eiji; Motooka, Daisuke; Ito, Yoshinaga; Gotoh, Kazuyoshi; Hirota, Keiji; Matsushita, Masato; Furuta, Yoki; Narazaki, Masashi; Sakaguchi, Noriko; Kayama, Hisako; Nakamura, Shota; Iida, Tetsuya; Saeki, Yukihiko; Kumanogoh, Atsushi; Sakaguchi, Shimon; Takeda, Kiyoshi

    2016-11-01

    The intestinal microbiota is involved in the pathogenesis of arthritis. Altered microbiota composition has been demonstrated in patients with rheumatoid arthritis (RA). However, it remains unclear how dysbiosis contributes to the development of arthritis. The aim of this study was to investigate whether altered composition of human intestinal microbiota in RA patients contributes to the development of arthritis. We analyzed the fecal microbiota of patients with early RA and healthy controls, using 16S ribosomal RNA-based deep sequencing. We inoculated fecal samples from RA patients and healthy controls into germ-free arthritis-prone SKG mice and evaluated the immune responses. We also analyzed whether the lymphocytes of SKG mice harboring microbiota from RA patients react with the arthritis-related autoantigen 60S ribosomal protein L23a (RPL23A). A subpopulation of patients with early RA harbored intestinal microbiota dominated by Prevotella copri; SKG mice harboring microbiota from RA patients had an increased number of intestinal Th17 cells and developed severe arthritis when treated with zymosan. Lymphocytes in regional lymph nodes and the colon, but not the spleen, of these mice showed enhanced interleukin-17 (IL-17) responses to RPL23A. Naive SKG mouse T cells cocultured with P copri-stimulated dendritic cells produced IL-17 in response to RPL23A and rapidly induced arthritis. We demonstrated that dysbiosis increases sensitivity to arthritis via activation of autoreactive T cells in the intestine. Autoreactive SKG mouse T cells are activated by dysbiotic microbiota in the intestine, causing joint inflammation. Dysbiosis is an environmental factor that triggers arthritis development in genetically susceptible mice. © 2016, American College of Rheumatology.

  16. Susceptible-infected-recovered and susceptible-exposed-infected models

    Energy Technology Data Exchange (ETDEWEB)

    Tome, Tania; De Oliveira, Mario J, E-mail: oliveira@if.usp.br [Instituto de Fisica, Universidade de Sao Paulo, Caixa Postal 66318, 05315-970 Sao Paulo, Sao Paulo (Brazil)

    2011-03-04

    Two stochastic epidemic lattice models, the susceptible-infected-recovered and the susceptible-exposed-infected models, are studied on a Cayley tree of coordination number k. The spreading of the disease in the former is found to occur when the infection probability b is larger than b{sub c} = k/2(k - 1). In the latter, which is equivalent to a dynamic site percolation model, the spreading occurs when the infection probability p is greater than p{sub c} = 1/(k - 1). We set up and solve the time evolution equations for both models and determine the final and time-dependent properties, including the epidemic curve. We show that the two models are closely related by revealing that their relevant properties are exactly mapped into each other when p = b/[k - (k - 1)b]. These include the cluster size distribution and the density of individuals of each type, quantities that have been determined in closed forms.

  17. Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis in Mice via a Toll-Like Receptor 4/p21-Activated Kinase 1 Cascade.

    Science.gov (United States)

    Wu, Yaxin; Wu, Jiao; Chen, Ting; Li, Qing; Peng, Wei; Li, Huan; Tang, Xiaowei; Fu, Xiangsheng

    2018-03-05

    The underlying pathogenic mechanism of Fusobacterium nucleatum in the carcinogenesis of colorectal cancer has been poorly understood. Using C57BL/6-Apc Min/+ mice, we investigated gut microbial structures with F. nucleatum, antibiotics, and Toll-like receptor 4 (TLR4) antagonist TAK-242 treatment. In addition, we measured intestinal tumor formation and the expression of TLR4, p21-activated kinase 1 (PAK1), phosphorylated-PAK1 (p-PAK1), phosphorylated-β-catenin S675 (p-β-catenin S675), and cyclin D1 in mice with different treatments. Fusobacterium nucleatum and antibiotics treatment altered gut microbial structures in mice. In addition, F. nucleatum invaded into the intestinal mucosa in large amounts but were less abundant in the feces of F. nucleatum-fed mice. The average number and size of intestinal tumors in F. nucleatum groups was significantly increased compared to control groups in Apc Min/+ mice (P nucleatum groups compared to the control groups (P nucleatum groups (P nucleatum groups (P Fusobacterium nucleatum potentiates intestinal tumorigenesis in Apc Min/+ mice via a TLR4/p-PAK1/p-β-catenin S675 cascade. Fusobacterium nucleatum-induced intestinal tumorigenesis can be inhibited by TAK-242, implicating TLR4 as a potential target for the prevention and therapy of F. nucleatum-related colorectal cancer.

  18. Multiple Primary Tumors

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It ... KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous .... layer of the colon. The tumor cells are strongly positive to chromagranin and AE1/AE3. Features are those of carcinoid tumor of the colon. She was ...

  19. Granular Cell Tumor

    African Journals Online (AJOL)

    Necrosis within the tumor was absent, no mitosis was. Granular cell tumors are seldom diagnosed identified in the section and the edges of the accurately clinically. The lesion in this case was sample were tumor free (Figure 2). mistaken for a sebaceous cyst and following ulceration resembled carcinoma of the vulvar.

  20. Malignant tumors of childhood

    International Nuclear Information System (INIS)

    Brooks, B.J.

    1986-01-01

    This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children