Gastrointestinal stromal tumor of Meckel's diverticulum: a rare cause of intestinal volvulus.

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Cengız, Fevzi; Sun, Mehmet Ali; Esen, Özgür Sipahi; Erkan, Nazif

2012-08-01

Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract. Most cases are asymptomatic; however, when symptomatic, it is often misdiagnosed at presentation. Common complications presenting in adults include bleeding, obstruction, diverticulitis, and perforation. Tumors within a Meckel's diverticulum are rare. Herein, we present a gastrointestinal stromal tumor arising from the Meckel's diverticulum that led to intestinal obstruction by volvulus.

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...

The clinical pathological features, diagnosis, treatment and prognosis of small intestine primary malignant tumors.

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Guo, Xiaochuan; Mao, Zhiyuan; Su, Dan; Jiang, Zhaocai; Bai, Li

2014-04-01

The aim of the study was to describe and analyze the clinicopathological features and diagnosis of Chinese patients with small intestine primary malignant tumors and to explore the best therapy to small bowel adenocarcinoma (SBA). More than 26,000 patients with digestive tract malignant tumors received treatment in PLA hospital from 2000 to 2011, and among them, there were 887 patients who had small intestine primary malignant tumors, and 666 of 887 patients had the completed basic clinical documents. We retrospectively analyzed the correlation between clinical and pathological features of the 666 patients and analyzed the survival and prognosis of 173 SBA patients with follow-up data. Both the number of patients with primary malignant tumors of the small intestine and the number of patients who received chemotherapy showed an increasing trend. The ratio of male to female was 1.58:1. The male patients significantly exceed the female patients with tumors of non-ampullary duodenum, jejunum and duodenal ampulla; and most of the patients are over 60 years of age. For patients burdened with either of the pathological types of tumors, the males exceeded the females, but there was no significant difference. Abdominal pain was the main clinical manifestation for patients with tumors of non-ampullary duodenum, jejunum and ileum, and the most common clinical manifestations were jaundice and abdominal pain for patients with ampullary duodenal tumors, adenocarcinoma, neuroendocrine tumors and sarcoma. In addition, patients with stromal tumors were prone to gastrointestinal bleeding. Gastrointestinal endoscopy was the most common examinational procedure. Patients under 60 years of age were prone to surgery and chemotherapy after surgery, and patients over 60 years of age were prone to supportive treatment and chemotherapy without surgery. The medium overall survival of patients who received surgery without chemotherapy, chemotherapy after surgery, chemotherapy without surgery

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.

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.

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

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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.)

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

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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.

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.

Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after 177Lu[Lu]-octreotate therapy.

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Spetz, Johan; Rudqvist, Nils; Langen, Britta; Parris, Toshima Z; Dalmo, Johanna; Schüler, Emil; Wängberg, Bo; Nilsson, Ola; Helou, Khalil; Forssell-Aronsson, Eva

2018-05-01

Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with 177 Lu[Lu]-octreotate. Despite being highly effective in animal models, 177 Lu[Lu]-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for 177 Lu[Lu]-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq 177 Lu[Lu]-octreotate (non-curative amount) or mock-treated with saline solution. Animals were killed 1, 3, 7 or 41 d after injection. Total RNA was extracted from the tumor samples and profiled using Illumina microarray expression analysis. Differentially expressed genes were identified (treated vs. control) and pathway analysis was performed. Distribution of differentially expressed transcripts indicated a time-dependent treatment response in GOT1 tumors after 177 Lu[Lu]-octreotate administration. Regulation of CDKN1A, BCAT1 and PAM at 1 d after injection was compatible with growth arrest as the initial response to treatment. Upregulation of APOE and BAX at 3 d, and ADORA2A, BNIP3, BNIP3L and HSPB1 at 41 d after injection suggests first activation and then inhibition of the intrinsic apoptotic pathway during tumor regression and regrowth, respectively. Transcriptional analysis showed radiation-induced apoptosis as an early response after 177 Lu[Lu]-octreotate administration, followed by pro-survival transcriptional changes in the tumor during the regrowth phase. Time-dependent changes in cell cycle and apoptosis-related processes suggest different time points after radionuclide therapy when tumor cells may be more susceptible to additional treatment, highlighting the importance of timing when administering multiple therapeutic agents. Copyright © 2018 The Authors. Published by Elsevier Inc. All

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.

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

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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

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...... stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.......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. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations...

Comparison of the effects of an ornithine decarboxylase inhibitor on the intestinal epithelium and on intestinal tumors.

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Tutton, P J; Barkla, D H

1986-12-01

Ornithine decarboxylase (ODC) catalyzes the rate-limiting step in the synthesis of polyamines, it has a short half-life, and its synthesis is under hormonal control. Recently, insight into the role of ODC and thus into the physiology of polyamines has been gained by the use of an inhibitor of ODC, difluoromethylornithine (DFMO). In the present report cell proliferation was measured by a stathmokinetic method in the crypt epithelium of the jejunum and colon of normal rats and in dimethylhydrazine-induced colonic tumors. Growth of human colon tumor xenografts in immunosuppressed mice and mouse colon tumor isografts was also assessed. Cell proliferation in primary colonic tumors was substantially suppressed by a single dose of DFMO at 100 mg/kg whereas the normal crypt epithelium of the small and large intestine required two doses at 400 mg/kg to produce a similar magnitude of inhibition of cell proliferation. DFMO was also found to suppress cell proliferation in, and the growth of, the transplantable colon cancers. Because of the apparent selectivity of the antimitotic activity of DFMO towards tumors, ODC inhibitors may prove to be useful anticancer drugs.

Intestinal lesions induced by radiotherapy of malignant pelvic tumors. 2 cases

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Manigand, G; Pointud, P; Foulon, D; Montely, J M; Testas, P; Paillas, J; Deparis, M [Hopital de Bicetre, 94 - le Kremlin-Bicetre (France)

1976-11-16

Intestinal lesions after radiotherapy for pelvic malignant tumors are of two types: ulcerative colitis with stenosis and hemorrhage sometimes severe and repeated, and ileal involvement with focal ischemic lesions and malabsorption responsible for nutritional disorders. It is difficult to distinguish them from a recurrence of the tumor in spite of endoscopy, arteriography and biopsy. The course in 3 stages is of great value in diagnosis. A reduction in the frequency of such complications may be hoped for by assessment and exclusion of predisposing factors, by strict observance of therapeutic rules. They are serious owing to the marked irreversible conjunctivo-vascular changes and the fragility of the irradiated tissues during operation.

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

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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.

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

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

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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.

Enhanced Autoimmunity Associated with Induction of Tumor Immunity in Thyroiditis-Susceptible Mice

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Kari, Suresh; Flynn, Jeffrey C.; Zulfiqar, Muhammad; Snower, Daniel P.; Elliott, Bruce E.

2013-01-01

Background: Immunotherapeutic modalities to bolster tumor immunity by targeting specific sites of the immune network often result in immune dysregulation with adverse autoimmune sequelae. To understand the relative risk for opportunistic autoimmune disorders, we studied established breast cancer models in mice resistant to experimental autoimmune thyroiditis (EAT). EAT is a murine model of Hashimoto's thyroiditis, an autoimmune syndrome with established MHC class II control of susceptibility. The highly prevalent Hashimoto's thyroiditis is a prominent autoimmune sequela in immunotherapy, and its relative ease of diagnosis and treatment could serve as an early indicator of immune dysfunction. Here, we examined EAT-susceptible mice as a combined model for induction of tumor immunity and EAT under the umbrella of disrupted regulatory T cell (Treg) function. Methods: Tumor immunity was evaluated in female CBA/J mice after depleting Tregs by intravenous administration of CD25 monoclonal antibody and/or immunizing with irradiated mammary adenocarcinoma cell line A22E-j before challenge; the role of T cell subsets was determined by injecting CD4 and/or CD8 antibodies after tumor immunity induction. Tumor growth was monitored 3×/week by palpation. Subsequent EAT was induced by mouse thyroglobulin (mTg) injections (4 daily doses/week over 4 weeks). For some experiments, EAT was induced before establishing tumor immunity by injecting mTg+interleukin-1, 7 days apart. EAT was evaluated by mTg antibodies and thyroid infiltration. Results: Strong resistance to tumor challenge after Treg depletion and immunization with irradiated tumor cells required participation of both CD4+ and CD8+ T cells. This immunity was not altered by induction of mild thyroiditis with our protocol of Treg depletion and adjuvant-free, soluble mTg injections. However, the increased incidence of mild thyroiditis can be directly related to Treg depletion needed to achieve strong tumor immunity. Moreover

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

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Rehfeld, Anders; Plass, Mireya; Døssing, Kristina; Knigge, Ulrich; Kjær, Andreas; Krogh, Anders; Friis-Hansen, Lennart

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 or 3' untranslated regions. Among these, 11 genes had been previously associated with cancer, with 4 genes being known tumor suppressors: DCC, PDZD2, MAGI1, and DACT2. We validated the APA in three out of three cases with quantitative real-time-PCR. Our findings suggest that changes of APA pattern in these 16 genes could be involved in the tumorigenesis of SI-NETs. Furthermore, they also point to APA as a new target for both diagnostic and treatment of SI-NETs. The identified genes with APA specific to the SI-NETs could be further tested as diagnostic markers and drug targets for disease prevention and treatment.

Small Intestine Cancer—Health Professional Version

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Adenocarcinoma is the most common type of small intestine cancer. Other types of small intestine cancer are sarcomas, carcinoid tumors, gastrointestinal stromal tumors, and lymphomas. Find evidence-based information on small intestine cancer treatment, research, and statistics.

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.

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

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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.

The Homeodomain Transcription Factor Cdx1 Does Not Behave as an Oncogene in Normal Mouse Intestine1

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Crissey, Mary Ann S; Guo, Rong-Jun; Fogt, Franz; Li, Hong; Katz, Jonathan P; Silberg, Debra G; Suh, Eun Ran; Lynch, John P

2008-01-01

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. PMID:18231635

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 is...... 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....

Thymine DNA Glycosylase (TDG) is involved in the pathogenesis of intestinal tumors with reduced APC expression.

Science.gov (United States)

Xu, Jinfei; Cortellino, Salvatore; Tricarico, Rossella; Chang, Wen-Chi; Scher, Gabrielle; Devarajan, Karthik; Slifker, Michael; Moore, Robert; Bassi, Maria Rosaria; Caretti, Elena; Clapper, Margie; Cooper, Harry; Bellacosa, Alfonso

2017-10-27

Thymine DNA Glycosylase (TDG) is a base excision repair enzyme that acts as a thymine and uracil DNA N-glycosylase on G:T and G:U mismatches, thus protecting CpG sites in the genome from mutagenesis by deamination. In addition, TDG has an epigenomic function by removing the novel cytosine derivatives 5-formylcytosine and 5-carboxylcytosine (5caC) generated by Ten-Eleven Translocation (TET) enzymes during active DNA demethylation. We and others previously reported that TDG is essential for mammalian development. However, its involvement in tumor formation is unknown. To study the role of TDG in tumorigenesis, we analyzed the effects of its inactivation in a well-characterized model of tumor predisposition, the Apc Min mouse strain. Mice bearing a conditional Tdg flox allele were crossed with Fabpl ::Cre transgenic mice, in the context of the Apc Min mutation, in order to inactivate Tdg in the small intestinal and colonic epithelium. We observed an approximately 2-fold increase in the number of small intestinal adenomas in the test Tdg -mutant Apc Min mice in comparison to control genotypes (p=0.0001). This increase occurred in female mice, and is similar to the known increase in intestinal adenoma formation due to oophorectomy. In the human colorectal cancer (CRC) TCGA database, the subset of patients with TDG and APC expression in the lowest quartile exhibits an excess of female cases. We conclude that TDG inactivation plays a role in intestinal tumorigenesis initiated by mutation/underexpression of APC . Our results also indicate that TDG may be involved in sex-specific protection from CRC.

Intestinal Iron Homeostasis and Colon Tumorigenesis

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Yatrik M. Shah

2013-06-01

Full Text Available Colorectal cancer (CRC is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.

Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR

International Nuclear Information System (INIS)

Tippin, Brigette L; Kwong, Alan M; Inadomi, Michael J; Lee, Oliver J; Park, Jae Man; Materi, Alicia M; Buslon, Virgilio S; Lin, Amy M; Kudo, Lili C; Karsten, Stanislav L; French, Samuel W; Narumiya, Shuh; Urade, Yoshihiro; Salido, Eduardo; Lin, Henry J

2014-01-01

Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D 2 ) caused more adenomas in Apc Min/+ mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D 2 (PGD 2 ) binds to the prostaglandin D 2 receptor known as PTGDR (or DP1). PGD 2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD 2 . To assess, we produced Apc Min/+ mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced Apc Min/+ mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30–40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in Apc Min/+ mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. Apc Min/+ mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD 2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD 2 signals acting through PTGDR in suppression of intestinal tumors

Some regularities in the development of radiation tumors of the stomach and intestine

International Nuclear Information System (INIS)

Lebedeva, G.A.

1978-01-01

It was shown on dogs and rats that gastric and intestinal neoplasms arise under the influence of different kinds of radiation, these may be located in all portions of the stomach and bowel and are of a different histological origin. They are not infrequently primary multiple, mostly benign neoplasms which show multicentric growth. The frequency of tumors appearence, their localization, an average latent period, the degree of malignancy and multiplicity are conditioned by the amount of tissue dosage, the topography of their distribution in the alimentary tract and the level of whole-body irradiation. With the increased dosage of local irradiation the latent period and multiplicity are decreased, while the incidence of malignancy raises. The optimum levels of the tissue dosage and the time of maximum tumor appearance were determined for each type of radiation

Intestinal Ischaemia Associated with Carcinoid Tumor: A Case Report with Review of the Pathogenesis

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Oktay Yener

2013-01-01

Full Text Available Carcinoid tumors are rare, slow-growing neuroendocrine neoplasms that are often indolent and may not become clinically apparent until there is a metastatic spread or evidence of carcinoid syndrome.  A 44-year-old man presented to our clinic department with a history of previous left colon cancer operation, chronic crampy left lower quadrant pain, mass and severe anemia.  A MR scan was obtained which demonstrated a calcified mesenteric mass 12×8×10 cm diameter with surrounding left colon mesenteric infiltration. The liver was normal. A case of ischaemic ileal necrosis is reported. It was associated with elastic vascular sclerosis produced by mesenteric metastases of an ileal carcinoid tumor. It is postulated that intestinal ischaemia may be of more importance in the production of abdominal pain by carcinoid tumors than has been generally accepted, and that it is the result of functional and structural changes in and around the mesenteric blood vessels, caused by substances secreted by the carcinoid tumor.

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

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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.

Effects of intramuscularly administered enrofloxacin on the susceptibility of commensal intestinal Escherichia coli in pigs (sus scrofa domestica).

Science.gov (United States)

Römer, Antje; Scherz, Gesine; Reupke, Saskia; Meißner, Jessica; Wallmann, Jürgen; Kietzmann, Manfred; Kaspar, Heike

2017-12-04

In the European Union, various fluoroquinolones are authorised for the treatment of food producing animals. Each administration poses an increased risk of development and spread of antimicrobial resistance. The aim of this study was to investigate the impact of parenteral administration of enrofloxacin on the prevalence of enrofloxacin and ciprofloxacin susceptibilities in the commensal intestinal E. coli population. E. coli isolates from faeces of twelve healthy pigs were included. Six pigs were administered enrofloxacin on day 1 to 3 and after two weeks for further three days. The other pigs formed the control group. MIC values were determined. Virulence and resistance genes were detected by PCR. Phylogenetic grouping was performed by PCR. Enrofloxacin and ciprofloxacin were analysed in sedimentation samples by HPLC. Susceptibility shifts in commensal E. coli isolates were determined in both groups. Non-wildtype E. coli could be cultivated from two animals of the experimental group for the first time one week after the first administration and from one animal of the control group on day 28. The environmental load with enrofloxacin in sedimentation samples showed the highest amount between days one and five. The repeated parenteral administration of enrofloxacin to pigs resulted in rapidly increased MIC values (day 28: MIC up to 4 mg/L, day 35: MIC ≥ 32mg/L). E. coli populations of the control group in the same stable without direct contact to the experimental group were affected. The parenteral administration of enrofloxacin to piglets considerably reduced the number of the susceptible intestinal E. coli population which was replaced by E. coli strains with increased MIC values against enrofloxacin. Subsequently also pigs of the control were affected suggesting a transferability of strains from the experimental group through the environment to the control group especially as we could isolate the same PFGE strains from both pig groups and the environment.

Intestinal leiomyoma

Science.gov (United States)

... most often found when a person has an upper gastrointestinal (GI) endoscopy or colonoscopy for another reason. Rarely, these tumors can cause bleeding, blockage or rupture of the intestines If this ...

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

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

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

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

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

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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

Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.

Science.gov (United States)

Testa, Ugo; Pelosi, Elvira; Castelli, Germana

2018-04-13

Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

Molecular Diagnostics in the Neoplasms of Small Intestine and Appendix: 2018 Update.

Science.gov (United States)

Zhang, Yingtao; Zulfiqar, Muhammad; Bluth, Martin H; Bhalla, Amarpreet; Beydoun, Rafic

2018-06-01

Neoplasms of the small intestine are rare in comparison with colorectal tumors. The most common tumor types arising in the small intestine are adenocarcinomas, well-differentiated neuroendocrine tumors, gastrointestinal stromal tumors, and lymphoma. Primary appendiceal neoplasms are rare and found in less than 2% of appendectomy specimens with an incidence of approximately 1.2 cases per 100,000 people per year in the United States. This article explores molecular diagnostics in the neoplasms of small intestine and appendix. Copyright © 2018 Elsevier Inc. All rights reserved.

Surgical treatment of colorectal cancer complicated with acute intestinal obstruction

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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

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

[A Case of Small Intestinal Metastasis with Intussusception Due to Barium].

Science.gov (United States)

Tsujio, Gen; Nagahara, Hisashi; Nakao, Shigetomi; Fukuoka, Tatsunari; Shibutani, Masatsune; Maeda, Kiyoshi; Matsutani, Shinji; Kimura, Kenjiro; Toyokawa, Takahiro; Amano, Ryosuke; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Hirakawa, Kosei; Ohira, Masaichi

2017-11-01

A 48-year-old man noticed nausea and took health examination. After chest X-ray and gastrointestinal barium study was underwent, he was referred to our hospital because of abnormal shadow in the chest X-ray. CT scan revealed about 4 cm tumor in the hilum of left lung and target sign in the small intestine. He was diagnosed with intussusception and emergency operation was performed. During the laparotomy, we found 2 intussusceptions in the small intestine and we performed manual reduction using Hutchinson's maneuver. We confirmed the mass in oral side of the intussusception site but we did not confirmed any tumor in anal of the intussusception. This suggests the intussusception was caused by barium. Finally 3 small intestine tumor was observed and we resected and reconstructed each of the tumor. Histopathological examination showed small intestinal metastasis from pleomorphic carcinoma of the lung.

Susceptibility Imaging in Glial Tumor Grading; Using 3 Tesla Magnetic Resonance (MR) System and 32 Channel Head Coil.

Science.gov (United States)

Aydin, Omer; Buyukkaya, Ramazan; Hakyemez, Bahattin

2017-01-01

Susceptibility weighted imaging (SWI) is a velocity compensated, high-resolution three-dimensional (3D) spoiled gradient-echo sequence that uses magnitude and filtered-phase data. SWI seems to be a valuable tool for non-invasive evaluation of central nervous system gliomas. Relative cerebral blood volume (rCBV) ratio is one of the best noninvasive methods for glioma grading. Degree of intratumoral susceptibility signal (ITSS) on SWI correlates with rCBV ratio and histopathological grade. This study investigated the effectiveness of ITSS grading and rCBV ratio in preoperative assessment. Thirty-one patients (17 males and 14 females) with histopathogical diagnosis of glial tumor undergoing routine cranial MRI, SWI, and perfusion MRI examinations between October 2011 and July 2013 were retrospectively enrolled. All examinations were performed using 3T apparatus with 32-channel head coil. We used ITSS number for SWI grading. Correlations between SWI grade, rCBV ratio, and pathological grading were evaluated. ROC analysis was performed to determine the optimal rCBV ratio to distinguish between high-grade and low-grade glial tumors. There was a strong positive correlation between both pathological and SWI grading. We determined the optimal rCBV ratio to discriminate between high-grade and low-grade tumors to be 2.21. In conclusion, perfusion MRI and SWI using 3T MR and 32-channel head coil may provide useful information for preoperative glial tumor grading. SWI can be used as an accessory to perfusion MR technique in preoperative tumor grading.

Differences in Susceptibility to Heat Stress along the Chicken Intestine and the Protective Effects of Galacto-Oligosaccharides.

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Soheil Varasteh

Full Text Available High ambient temperatures negatively affect the human well-being as well as animal welfare and production. The gastrointestinal tract is predominantly responsive to heat stress. The currently available information about the multifaceted response to heat stress within different parts of the intestine is limited, especially in avian species. Hence, this study aims to evaluate the heat stress-induced sequence of events in the intestines of chickens. Furthermore, the gut health-promoting effect of dietary galacto-oligosaccharides (GOS was investigated in these heat stress-exposed chickens. Chickens were fed a control diet or diet supplemented with 1% or 2.5% GOS (6 days prior to and during a temperature challenge for 5 days (38-39°C, 8h per day. The parameters measured in different parts of the intestines included the genes (qPCR HSF1, HSF3, HSP70, HSP90, E-cadherin, claudin-1, claudin-5, ZO-1, occludin, TLR-2, TLR-4, IL-6, IL-8, HO-1, HIF-1α and their associated proteins HSP70, HSP90 and pan-cadherin (western blots. In addition, IL-6 and IL-8 plasma concentrations were measured by ELISA. In the jejunum, HSF3, HSP70, HSP90, E-cadherin, claudin-5, ZO-1, TLR-4, IL-6 and IL-8 mRNA expression and HSP70 protein expression were increased after heat stress exposure and a more pronounced increase in gene expression was observed in ileum after heat stress exposure, and in addition HSF1, claudin-1 and HIF-1α mRNA levels were upregulated. Furthermore, the IL-8 plasma levels were decreased in chickens exposed to heat stress. Interestingly, the heat stress-related effects in the jejunum were prevented in chickens fed a GOS diet, while dietary GOS did not alter these effects in ileum. In conclusion, our results demonstrate the differences in susceptibility to heat stress along the intestine, where the most obvious modification in gene expression is observed in ileum, while dietary GOS only prevent the heat stress-related changes in jejunum.

High-field, high-resolution, susceptibility-weighted magnetic resonance imaging: improved image quality by addition of contrast agent and higher field strength in patients with brain tumors

International Nuclear Information System (INIS)

Pinker, K.; Noebauer-Huhmann, I.M.; Szomolanyi, P.; Weber, M.; Grabner, G.; Trattnig, S.; Stavrou, I.; Knosp, E.; Hoeftberger, R.; Stadlbauer, A.

2008-01-01

To demonstrate intratumoral susceptibility effects in malignant brain tumors and to assess visualization of susceptibility effects before and after administration of the paramagnetic contrast agent MultiHance (gadobenate dimeglumine; Bracco Imaging), an agent known to have high relaxivity, with respect to susceptibility effects, image quality, and reduction of scan time. Included in the study were 19 patients with malignant brain tumors who underwent high-resolution, susceptibility-weighted (SW) MR imaging at 3 T before and after administration of contrast agent. In all patients, Multihance was administered intravenously as a bolus (0.1 mmol/kg body weight). MR images were individually evaluated by two radiologists with previous experience in the evaluation of pre- and postcontrast 3-T SW MR images with respect to susceptibility effects, image quality, and reduction of scan time. In the 19 patients 21 tumors were diagnosed, of which 18 demonstrated intralesional susceptibility effects both in pre- and postcontrast SW images, and 19 demonstrated contrast enhancement in both SW images and T1-weighted spin-echo MR images. Conspicuity of susceptibility effects and image quality were improved in postcontrast images compared with precontrast images and the scan time was also reduced due to decreased TE values from 9 min (precontrast) to 7 min (postcontrast). The intravenous administration of MultiHance, an agent with high relaxivity, allowed a reduction of scan time from 9 min to 7 min while preserving excellent susceptibility effects and image quality in SW images obtained at 3 T. Contrast enhancement and intralesional susceptibility effects can be assessed in one sequence. (orig.)

Congenital Infantile Fibrosarcoma Causing Intestinal Perforation in a Newborn

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Margarita Kaiser

2017-01-01

Full Text Available Congenital infantile fibrosarcoma (CIF is a rare malignant mesenchymal tumor and only 14 cases have been reported with gastrointestinal manifestation. We report about a female newborn delivered per emergency cesarean section at 34 weeks of gestation. Postnatally, she rapidly developed an acute abdomen and sonographic evidence of intestinal perforation requiring laparotomy on the first day of life. A perforated 2 × 3 cm sized spherical tumorous structure of the jejunum was identified. Due to unknown histopathology at this point and unclear resectional margins, she received a temporary ileostomy, which was closed two months later. Histopathology revealed a congenital intestinal fibrosarcoma without the characteristic ETV6-NTRK3 fusion transcript. In conclusion, this rare tumor must be considered as differential diagnosis of intestinal perforations in newborns.

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

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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.

Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria.

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Stecher, Bärbel; Chaffron, Samuel; Käppeli, Rina; Hapfelmeier, Siegfried; Freedrich, Susanne; Weber, Thomas C; Kirundi, Jorum; Suar, Mrutyunjay; McCoy, Kathy D; von Mering, Christian; Macpherson, Andrew J; Hardt, Wolf-Dietrich

2010-01-01

The intestinal ecosystem is formed by a complex, yet highly characteristic microbial community. The parameters defining whether this community permits invasion of a new bacterial species are unclear. In particular, inhibition of enteropathogen infection by the gut microbiota ( = colonization resistance) is poorly understood. To analyze the mechanisms of microbiota-mediated protection from Salmonella enterica induced enterocolitis, we used a mouse infection model and large scale high-throughput pyrosequencing. In contrast to conventional mice (CON), mice with a gut microbiota of low complexity (LCM) were highly susceptible to S. enterica induced colonization and enterocolitis. Colonization resistance was partially restored in LCM-animals by co-housing with conventional mice for 21 days (LCM(con21)). 16S rRNA sequence analysis comparing LCM, LCM(con21) and CON gut microbiota revealed that gut microbiota complexity increased upon conventionalization and correlated with increased resistance to S. enterica infection. Comparative microbiota analysis of mice with varying degrees of colonization resistance allowed us to identify intestinal ecosystem characteristics associated with susceptibility to S. enterica infection. Moreover, this system enabled us to gain further insights into the general principles of gut ecosystem invasion by non-pathogenic, commensal bacteria. Mice harboring high commensal E. coli densities were more susceptible to S. enterica induced gut inflammation. Similarly, mice with high titers of Lactobacilli were more efficiently colonized by a commensal Lactobacillus reuteri(RR) strain after oral inoculation. Upon examination of 16S rRNA sequence data from 9 CON mice we found that closely related phylotypes generally display significantly correlated abundances (co-occurrence), more so than distantly related phylotypes. Thus, in essence, the presence of closely related species can increase the chance of invasion of newly incoming species into the gut

Commensal-pathogen interactions in the intestinal tract

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Reynolds, Lisa A; Smith, Katherine A; Filbey, Kara J; Harcus, Yvonne; Hewitson, James P; Redpath, Stephen A; Valdez, Yanet; Yebra, María J; Finlay, B Brett; Maizels, Rick M

2016-01-01

The intestinal microbiota are pivotal in determining the developmental, metabolic and immunological status of the mammalian host. However, the intestinal tract may also accommodate pathogenic organisms, including helminth parasites which are highly prevalent in most tropical countries. Both microbes and helminths must evade or manipulate the host immune system to reside in the intestinal environment, yet whether they influence each other’s persistence in the host remains unknown. We now show that abundance of Lactobacillus bacteria correlates positively with infection with the mouse intestinal nematode, Heligmosomoides polygyrus, as well as with heightened regulatory T cell (Treg) and Th17 responses. Moreover, H. polygyrus raises Lactobacillus species abundance in the duodenum of C57BL/6 mice, which are highly susceptible to H. polygyrus infection, but not in BALB/c mice, which are relatively resistant. Sequencing of samples at the bacterial gyrB locus identified the principal Lactobacillus species as L. taiwanensis, a previously characterized rodent commensal. Experimental administration of L. taiwanensis to BALB/c mice elevates regulatory T cell frequencies and results in greater helminth establishment, demonstrating a causal relationship in which commensal bacteria promote infection with an intestinal parasite and implicating a bacterially-induced expansion of Tregs as a mechanism of greater helminth susceptibility. The discovery of this tripartite interaction between host, bacteria and parasite has important implications for both antibiotic and anthelmintic use in endemic human populations. PMID:25144609

Diaphragm disease of the small intestine: an interesting case report.

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Ullah, Sana; Ajab, Shereen; Rao, Rajashekhar; Raghunathan, Girish; DaCosta, Philip

2015-06-01

Diaphragm disease of small intestine usually presents with nonspecific clinical features. Radiological investigations often fail to differentiate it from small intestinal tumors and inflammatory bowel disease. It is therefore diagnosed on final histology after surgical resection. We hereby report an interesting case of a suspected small bowel tumor later diagnosed as diaphragm disease on histology. © The Author(s) 2014.

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

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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.

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

Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice.

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He, Zhengxiang; Chen, Lili; Souto, Fabricio O; Canasto-Chibuque, Claudia; Bongers, Gerold; Deshpande, Madhura; Harpaz, Noam; Ko, Huaibin M; Kelley, Kevin; Furtado, Glaucia C; Lira, Sergio A

2017-07-14

Increased expression of Interleukin (IL)-33 has been detected in intestinal samples of patients with ulcerative colitis, a condition associated with increased risk for colon cancer, but its role in the development of colorectal cancer has yet to be fully examined. Here, we investigated the role of epithelial expressed IL-33 during development of intestinal tumors. IL-33 expression was detected in epithelial cells in colorectal cancer specimens and in the Apc Min/+ mice. To better understand the role of epithelial-derived IL-33 in the intestinal tumorigenesis, we generated transgenic mice expressing IL-33 in intestinal epithelial cells (V33 mice). V33 Apc Min/+ mice, resulting from the cross of V33 with Apc Min/+ mice, had increased intestinal tumor burden compared with littermate Apc Min/+ mice. Consistently, Apc Min/+ mice deficient for IL-33 receptor (ST2), had reduced polyp burden. Mechanistically, overexpression of IL-33 promoted expansion of ST2 + regulatory T cells, increased Th2 cytokine milieu, and induced alternatively activated macrophages in the gut. IL-33 promoted marked changes in the expression of antimicrobial peptides, and antibiotic treatment of V33 Apc Min/+ mice abrogated the tumor promoting-effects of IL-33 in the colon. In conclusion, elevated IL-33 signaling increases tumor development in the Apc Min/+ mice.

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

[Circadian rhythm in susceptibility of mice to the anti-tumor drug carboplatin].

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Lu, X H; Yin, L J

1994-12-01

The platinum-containing compounds has become a major chemical agent in the treatment of cancer. A circadian rhythm in the susceptibility of rodents and human being to cisplatin has been demonstrated, the maximal tolerance being found in the animal's active phase. Carboplatin is a second generation analog. Two studies were performed on mice with carboplatin under 12:12 light dark cycle to study its chronotoxicity and chronoeffectiveness. In study I, single intraperitoneal injection of 192mg/kg (LD50) carboplatin was given to four groups of mice at four different circadian stage. It was found that at 50% the overall mortality of mice, there was a mortality difference of 28% for mice receiving the drug at 9 a.m. to 71% for mice receiving drug at 9 p.m. It demonstrated that carboplatin was better tolerated in the animal's early sleep phase. In study II, S180 tumor-bearing mice were treated with 50mg/kg of carboplatin. The longest mean survival time and the lowest marrow toxicity occurred in the group which received the drug at the beginning of the sleep phase. It showed that the susceptibility of mice to carboplatin is circadian stage dependent. These data clearly demonstrate that, by timing the administration of drugs according to body rhythms, such as the host susceptibility-resistance rhythm to a drug, one can gain a therapeutic advantage over an approach which ignores such rhythms.

Radiodiagnosis of diseases of the small intestine

International Nuclear Information System (INIS)

Anon.

1987-01-01

Roentgenological image of diseases, development anomalies, various diseases of the small intestine is presented. Roentgenological semiotics of chronic enterocolotis, absorption failure syndrome, Crohn's disease, tuberculosis, abdominal actinomycosis, carcenoid, benign tumors, small intestine cancer, is given. To state final correct diagnosis a complex investigation, comprising angiography, computer tomography and ultrasound diagnosis, is necessary

Copy number alterations in small intestinal neuroendocrine tumors determined by array comparative genomic hybridization

International Nuclear Information System (INIS)

Hashemi, Jamileh; Fotouhi, Omid; Sulaiman, Luqman; Kjellman, Magnus; Höög, Anders; Zedenius, Jan; Larsson, Catharina

2013-01-01

Small intestinal neuroendocrine tumors (SI-NETs) are typically slow-growing tumors that have metastasized already at the time of diagnosis. The purpose of the present study was to further refine and define regions of recurrent copy number (CN) alterations (CNA) in SI-NETs. Genome-wide CNAs was determined by applying array CGH (a-CGH) on SI-NETs including 18 primary tumors and 12 metastases. Quantitative PCR analysis (qPCR) was used to confirm CNAs detected by a-CGH as well as to detect CNAs in an extended panel of SI-NETs. Unsupervised hierarchical clustering was used to detect tumor groups with similar patterns of chromosomal alterations based on recurrent regions of CN loss or gain. The log rank test was used to calculate overall survival. Mann–Whitney U test or Fisher’s exact test were used to evaluate associations between tumor groups and recurrent CNAs or clinical parameters. The most frequent abnormality was loss of chromosome 18 observed in 70% of the cases. CN losses were also frequently found of chromosomes 11 (23%), 16 (20%), and 9 (20%), with regions of recurrent CN loss identified in 11q23.1-qter, 16q12.2-qter, 9pter-p13.2 and 9p13.1-11.2. Gains were most frequently detected in chromosomes 14 (43%), 20 (37%), 4 (27%), and 5 (23%) with recurrent regions of CN gain located to 14q11.2, 14q32.2-32.31, 20pter-p11.21, 20q11.1-11.21, 20q12-qter, 4 and 5. qPCR analysis confirmed most CNAs detected by a-CGH as well as revealed CNAs in an extended panel of SI-NETs. Unsupervised hierarchical clustering of recurrent regions of CNAs revealed two separate tumor groups and 5 chromosomal clusters. Loss of chromosomes 18, 16 and 11 and again of chromosome 20 were found in both tumor groups. Tumor group II was enriched for alterations in chromosome cluster-d, including gain of chromosomes 4, 5, 7, 14 and gain of 20 in chromosome cluster-b. Gain in 20pter-p11.21 was associated with short survival. Statistically significant differences were observed between primary

Lipo sarcoma in small intestine; Liposarcoma de intestino delgado

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

1987-12-01

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. [Spanish] Se presenta un caso de invaginacion yeyunal por liposarcoma primitivo de intestino delgado,realizandose una extensa revision bibliografica extranjera y nacional al respecto,destacando lo exepcional de la topografia intestinal de los piposarcomas; y haciendo hincapie en lo relativo valor de la tomografia computarizada y ultrasonografia en el diagnostico de los tumores de intestino delgado.Como en los sarcomas de otra topografia,la quimio y radioterapia asociadas a la cirugia de exeresis, puede ser de beneficio.

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

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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

Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors.

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Takehiro Mitsuishi

Full Text Available Epithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors.Among duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands.As for patient characteristics, there were 76 men (75.2% and 25 women (24.8%, with a median age of 65 years (range, 34 to 84. The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1% and gastric-type tumors (12 lesions, 10.9%. Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7% and tubulovillous-type tumors (7 lesions, 6.4%. Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7% and pyloric gland-type (PG tumors (9 lesions, 8.2%. The grade of atypia was significantly higher in gastric-type tumors (p<0.01. PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands.About 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.

A case of positive 68Ga-DOTATOC-PET/CT pancreatic heterotopia mimicking an intestinal neuroendocrine tumor.

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Zilli, Alessandra; Fanetti, Ilaria; Conte, Dario; Massironi, Sara

Gallium-68 DOTA-peptide positron emission tomography/computed tomography ( 68 Ga-PET/CT) has emerged as a promising tool for the diagnosis and staging of gastro-entero-pancreatic neoplasms, thanks to its high sensitivity and specificity. Heterotopic pancreas, which is relatively rare, has never been reported as a possible cause of false positives of 68 Ga-PET/CT. We report on the first case of a heterotopic pancreas showing pathological uptake at 68 Ga-PET/CT, thus mimicking an intestinal neuroendocrine tumor. The present case suggests that heterotopic pancreas should be included among the possible causes of false positives at 68 Ga PET. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain tumors and syndromes in children

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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

Imprint cytology of clear cell sarcoma-like tumor of the gastrointestinal tract in the small intestine: A case report.

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Kato, Takashi; Ichihara, Shin; Gotoda, Hiroko; Muraoka, Shunji; Kubo, Terufumi; Sugita, Shintaro; Hasegawa, Tadashi

2017-12-01

Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is an extremely rare malignant neoplasm in the digestive tract. Its cytomorphologic features have never previously been reported. Here, we describe a case of CCSLGT, including its cytologic examination findings. A 47-year-old woman presented with a mass in the small intestine, which was resected and sent for imprint cytology. Imprint smears revealed tumor cells with light eosinophilic or clear cytoplasm in a necrotic background. Many of the tumor cells were arranged in a perivascular growth with a pseudopapillary formation, and there were some non-neoplastic osteoclast-like giant cells. Histological examination revealed solid nests and a pseudopapillary pattern of the tumor cells with clear or pale eosinophilic cytoplasm and large nuclei with small nucleoli. Immunohistochemistry showed positive for vimentin, S-100, and SOX-10, and negative for SMA, c-KIT, cytokeratin, HMB-45, and MelanA. The EWSR1 gene split signal was detected by reverse transcriptase fluorescence in situ hybridization, and EWSR1-CREB1 gene fusion was indicated by reverse transcriptase polymerase chain reaction analysis. From these findings, we diagnosed the tumor as CCSLGT. To best of our knowledge, this is the first description of the imprint cytology features of CCSLGT. © 2017 Wiley Periodicals, Inc.

Loss of Chromosome 18 in Neuroendocrine Tumors of the Small Intestine: The Enigma Remains.

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Nieser, Maike; Henopp, Tobias; Brix, Joachim; Stoß, Laura; Sitek, Barbara; Naboulsi, Wael; Anlauf, Martin; Schlitter, Anna M; Klöppel, Günter; Gress, Thomas; Moll, Roland; Bartsch, Detlef K; Heverhagen, Anna E; Knoefel, Wolfram T; Kaemmerer, Daniel; Haybaeck, Johannes; Fend, Falko; Sperveslage, Jan; Sipos, Bence

2017-01-01

Neuroendocrine tumors of the small intestine (SI-NETs) exhibit an increasing incidence and high mortality rate. Until now, no fundamental molecular event has been linked to the tumorigenesis and progression of these tumors. Only the loss of chromosome 18 (Chr18) has been shown in up to two thirds of SI-NETs, whereby the significance of this alteration is still not understood. We therefore performed the first comprehensive study to identify Chr18-related events at the genetic, epigenetic and gene/protein expression levels. We did expression analysis of all seven putative Chr18-related tumor suppressors by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. Next-generation exome sequencing and SNP array analysis were performed with five SI-NETs with (partial) loss of Chr18. Finally, we analyzed all microRNAs (miRNAs) located on Chr18 by qRT-PCR, comparing Chr18+/- and Chr18+/+ SI-NETs. Only DCC (deleted in colorectal cancer) revealed loss of/greatly reduced expression in 6/21 cases (29%). No relevant loss of SMAD2, SMAD4, elongin A3 and CABLES was detected. PMAIP1 and maspin were absent at the protein level. Next-generation sequencing did not reveal relevant recurrent somatic mutations on Chr18 either in an exploratory cohort of five SI-NETs, or in a validation cohort (n = 30). SNP array analysis showed no additional losses. The quantitative analysis of all 27 Chr18-related miRNAs revealed no difference in expression between Chr18+/- and Chr18+/+ SI-NETs. DCC seems to be the only Chr18-related tumor suppressor affected by the monoallelic loss of Chr18 resulting in a loss of DCC protein expression in one third of SI-NETs. No additional genetic or epigenetic alterations were present on Chr18. © 2016 S. Karger AG, Basel.

Mesenteric lipoblastoma presenting as a small intestinal volvulus in an infant: A case report and literature review

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Yuka Nagano

2017-01-01

Full Text Available A 1-year-old boy with no underlying disorder presented with non-bilious vomiting since 4 days before admission. He was referred to our hospital and was diagnosed with a small bowel obstruction due to an intraabdominal tumor. Laparotomy revealed an intestinal volvulus with a soft and lobulated tumor arising from the mesentery. The resected tumor with a small part of the small bowel was diagnosed as lipoblastoma histologically. From a literature review, mesenteric lipoblastoma with an intestinal volvulus showed different characteristics such as greater frequency of vomiting and less frequency of abdominal mass as clinical symptoms, and the size of the tumor was smaller than that of the tumor without the intestinal volvulus.

Intestinal mucus accumulation in a child with acutemyeloblastic leukemia

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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.

The DNA Sensor AIM2 Maintains Intestinal Homeostasis via Regulation of Epithelial Antimicrobial Host Defense

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Shuiqing Hu

2015-12-01

Full Text Available Microbial pattern molecules in the intestine play immunoregulatory roles via diverse pattern recognition receptors. However, the role of the cytosolic DNA sensor AIM2 in the maintenance of intestinal homeostasis is unknown. Here, we show that Aim2−/− mice are highly susceptible to dextran sodium sulfate-induced colitis that is associated with microbial dysbiosis as represented by higher colonic burden of commensal Escherichia coli. Colonization of germ-free mice with Aim2−/− mouse microbiota leads to higher colitis susceptibility. In-depth investigation of AIM2-mediated host defense responses reveals that caspase-1 activation and IL-1β and IL-18 production are compromised in Aim2−/− mouse colons, consistent with defective inflammasome function. Moreover, IL-18 infusion reduces E. coli burden as well as colitis susceptibility in Aim2−/− mice. Altered microbiota in inflammasome-defective mice correlate with reduced expression of several antimicrobial peptides in intestinal epithelial cells. Together, these findings implicate DNA sensing by AIM2 as a regulatory mechanism for maintaining intestinal homeostasis.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

Science.gov (United States)

Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

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

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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.

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

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

Mesenteric lipoblastoma presenting as a small intestinal volvulus in an infant: A case report and literature review.

Science.gov (United States)

Nagano, Yuka; Uchida, Keiichi; Inoue, Mikihiro; Ide, Shozo; Shimura, Tadanobu; Hashimoto, Kiyoshi; Koike, Yuki; Kusunoki, Masato

2017-01-01

A 1-year-old boy with no underlying disorder presented with non-bilious vomiting since 4 days before admission. He was referred to our hospital and was diagnosed with a small bowel obstruction due to an intraabdominal tumor. Laparotomy revealed an intestinal volvulus with a soft and lobulated tumor arising from the mesentery. The resected tumor with a small part of the small bowel was diagnosed as lipoblastoma histologically. From a literature review, mesenteric lipoblastoma with an intestinal volvulus showed different characteristics such as greater frequency of vomiting and less frequency of abdominal mass as clinical symptoms, and the size of the tumor was smaller than that of the tumor without the intestinal volvulus. Copyright © 2013. Published by Elsevier Taiwan.

Primary intestinal hodgkin′s lymphoma: An uncommon presentation

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Shruti Sharma

2013-01-01

Full Text Available Primary intestinal lymphoma is a rare lymphoproliferative neoplasm of the small intestine. The primary nature is established on the basis of lack of evidence of lymphoma on chest X-ray, computerized tomographic scan, peripheral blood or bone marrow puncture. Tumor involvement is limited to the gastrointestinal tract, the criteria for inclusion are that the symptoms related to the small intestine are predominant or the only symptoms at the time of laparotomy. Hodgkin′s lymphoma (HL primarily in the small intestine is a rare entity and an uncommon presentation of the disease. Ileum is the more common site of infliction than the jejunum because of its abundant lymphoid follicles. Here, we present a case of primary intestinal HL, in a 30-year-old male.

Associação timoma e estrongiloidíase intestinal grave Thymoma and severe intestinal strongyloidiasis association

OpenAIRE

Pérsio Godoy; Christian Marcellus Camargos Campos; Guilherme Costa; Lúcia Porto Fonseca de Castro

1998-01-01

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.A 59-years-old man with thymoma and severe intestinal strongyloidiasis is reported. The authors pointed out a possible influence of immunological response related with thymoma in the development of hyperinfection by Strongyloide...

Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

Science.gov (United States)

Bevins, Charles L; Salzman, Nita H

2011-05-01

Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

Intestinal transplantation: The anesthesia perspective.

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Dalal, Aparna

2016-04-01

Intestinal transplantation is a complex and challenging surgery. It is very effective for treating intestinal failure, especially for those patients who cannot tolerate parenteral nutrition nor have extensive abdominal disease. Chronic parental nutrition can induce intestinal failure associated liver disease (IFALD). According to United Network for Organ Sharing (UNOS) data, children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list when compared with all candidates for solid organ transplantation. Intestinal transplant grafts can be isolated or combined with the liver/duodenum/pancreas. Organ Procurement and Transplantation Network (OPTN) has defined intestinal donor criteria. Living donor intestinal transplant (LDIT) has the advantages of optimal timing, short ischemia time and good human leukocyte antigen matching contributing to lower postoperative complications in the recipient. Thoracic epidurals provide excellent analgesia for the donors, as well as recipients. Recipient management can be challenging. Thrombosis and obstruction of venous access maybe common due to prolonged parenteral nutrition and/or hypercoaguability. Thromboelastography (TEG) is helpful for managing intraoperative product therapy or thrombosis. Large fluid shifts and electrolyte disturbances may occur due to massive blood loss, dehydration, third spacing etc. Intestinal grafts are susceptible to warm and cold ischemia and ischemia-reperfusion injury (IRI). Post-reperfusion syndrome is common. Cardiac or pulmonary clots can be monitored with transesophageal echocardiography (TEE) and treated with recombinant tissue plasminogen activator. Vasopressors maybe used to ensure stable hemodynamics. Post-intestinal transplant patients may need anesthesia for procedures such as biopsies for surveillance of rejection, bronchoscopy, endoscopy, postoperative hemorrhage, anastomotic leaks, thrombosis of grafts etc. Asepsis

Immune and genetic gardening of the intestinal microbiome

Science.gov (United States)

Jacobs, Jonathan P.; Braun, Jonathan

2014-01-01

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 nonpathogenic 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. PMID:24613921

Precision-cut intestinal slices as a culture system to analyze the infection of differentiated intestinal epithelial cells by avian influenza viruses.

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Punyadarsaniya, Darsaniya; Winter, Christine; Mork, Ann-Kathrin; Amiri, Mahdi; Naim, Hassan Y; Rautenschlein, Silke; Herrler, Georg

2015-02-01

Many viruses infect and replicate in their host via the intestinal tract, e.g. many picornaviruses, several coronaviruses and avian influenza viruses of waterfowl. To analyze infection of enterocytes is a challenging task as culture systems for differentiated intestinal epithelial cells are not readily available and often have a life span that is too short for infection studies. Precision-cut intestinal slices (PCIS) from chicken embryos were prepared and shown that the epithelial cells lining the lumen of the intestine are viable for up to 4 days. Using lectin staining, it was demonstrated that α2,3-linked sialic acids, the preferred receptor determinants of avian influenza viruses, are present on the apical side of the epithelial cells. Furthermore, the epithelial cells (at the tips) of the villi were shown to be susceptible to infection by an avian influenza virus of the H9N2 subtype. This culture system will be useful to analyze virus infection of intestinal epithelial cells and it should be applicable also to the intestine of other species. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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

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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

Expression of an Intestine-Specific Transcription Factor (CDX1) in Intestinal Metaplasia and in Subsequently Developed Intestinal Type of Cholangiocarcinoma in Rat Liver

Science.gov (United States)

Ren, Ping; Silberg, Debra G.; Sirica, Alphonse E.

2000-01-01

CDX1 is a caudal-type homeobox intestine-specific transcription factor that has been shown to be selectively expressed in epithelial cells in intestinal metaplasia of the human stomach and esophagus and variably expressed in human gastric and esophageal adenocarcinomas (Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, Traber PG: Gastroenterology 1997, 113: 478–486). Through the use of immunohistochemistry and Western blotting, we investigated whether CDX1 is also uniquely associated with the intestinal metaplasia associated with putative precancerous cholangiofibrosis induced in rat liver during furan cholangiocarcinogenesis, as well as expressed in neoplastic glands in a subsequently developed intestinal type of cholangiocarcinoma. In normal, control adult rat small intestine, specific nuclear immunoreactivity for CDX1 was most prominent in enterocytes lining the crypts. In comparison, epithelium from intestinal metaplastic glands within furan-induced hepatic cholangiofibrosis and neoplastic epithelium from later developed primary intestinal-type cholangiocarcinoma each demonstrated strong nuclear immunoreactivity for CDX1. CDX1-positive cells were detected in hepatic cholangiofibrotic tissue as early as 3 weeks after the start of chronic furan treatment. We further determined that the percentages of CDX1-positive neoplastic glands and glandular nuclei are significantly higher in primary tumors than in a derived, transplantable cholangiocarcinoma serially-propagated in vivo. Western blotting confirmed our immunohistochemical results, and no CDX1 immunoreactivity was detected in normal adult rat liver or in hyperplastic biliary epithelial cells. These findings indicate that CDX1 is specifically associated with early intestinal metaplasia and a later developed intestinal-type of cholangiocarcinoma induced in the liver of furan-treated rats. PMID:10666391

JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation

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Camilla A. Richmond

2018-01-01

Full Text Available The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs and slowly cycling, reserve ISCs (r-ISCs. Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response.

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

Autophagy and tight junction proteins in the intestine and intestinal diseases

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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

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

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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.

Nardilysin controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation.

Science.gov (United States)

Kanda, Keitaro; Sakamoto, Jiro; Matsumoto, Yoshihide; Ikuta, Kozo; Goto, Norihiro; Morita, Yusuke; Ohno, Mikiko; Nishi, Kiyoto; Eto, Koji; Kimura, Yuto; Nakanishi, Yuki; Ikegami, Kanako; Yoshikawa, Takaaki; Fukuda, Akihisa; Kawada, Kenji; Sakai, Yoshiharu; Ito, Akihiro; Yoshida, Minoru; Kimura, Takeshi; Chiba, Tsutomu; Nishi, Eiichiro; Seno, Hiroshi

2018-04-19

Colon cancer is a complex disease affected by a combination of genetic and epigenetic factors. Here we demonstrate that nardilysin (N-arginine dibasic convertase; NRDC), a metalloendopeptidase of the M16 family, regulates intestinal tumorigenesis via its nuclear functions. NRDC is highly expressed in human colorectal cancers. Deletion of the Nrdc gene in ApcMin mice crucially suppressed intestinal tumor development. In ApcMin mice, epithelial cell-specific deletion of Nrdc recapitulated the tumor suppression observed in Nrdc-null mice. Moreover, epithelial cell-specific overexpression of Nrdc significantly enhanced tumor formation in ApcMin mice. Notably, epithelial NRDC controlled cell apoptosis in a gene dosage-dependent manner. In human colon cancer cells, nuclear NRDC directly associated with HDAC1, and controlled both acetylation and stabilization of p53, with alterations of p53 target apoptotic factors. These findings demonstrate that NRDC is critically involved in intestinal tumorigenesis through its epigenetic regulatory function, and targeting NRDC may lead to a novel prevention or therapeutic strategy against colon cancer.

Studies on colon cancer prone rats. Spontaneous small intestinal carcinomas and tumor induction of small intestine by x-irradiation

Energy Technology Data Exchange (ETDEWEB)

Maeura, Y [Osaka Univ. (Japan). Faculty of Medicine

1979-12-01

Histological investigation was carried out for Wister-Furth (WF) rats, prone to cancers of the colon and small intestine. Gastric cancer was observed in about 1/4 of the rats with the cancers of the colon and the small intestine, indicating that these rats could be the model animals of the cancer family syndrome with multi-cancers in the gastrointestinal tracts. The small intestine of WF and SD (Sprague-Dowley) rats as exposed to 1000, 2 x 1000, 1500, and 2000 R of x-rays at a dose rate of 157 R/min. In each group the stomach, small intestine, cecum, and colon were histologically investigated, immediately and 15, 25, and 35 weeks after irradiation. The rates of cancer occurrence in 15, 25, and 35 weeks were 5/17, 9/19, and 9/14 for WF strain and 1/8, 2/7, and 2/8 for SD strain, respectively. The rate increased with the increment of the days after irradiation. It was suggested that the atypical epithelium of the gastrointestinal tracts induced the cancer in high rates when some trigger was added.

Polymorphisms in tumor necrosis factor genes and susceptibility to visceral leishmaniasis in Moroccan children

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Rajaa Ejghal

2015-05-01

Full Text Available Objective: To examine whether polymorphic alleles at these two loci are involved in the susceptibility to visceral leishmaniasis (VL in Moroccan children. Methods: We have genotyped polymorphisms by PCR-restricted fragment length polymorphisms in 102 patients with VL, 92 asymptomatic carriers [positive skin test delayedtype hypersensitivity (DTH+] and 40 healthy controls (negative skin test delayed-type hypersensitivity, with no history of Leishmania infection. Results: Regression analysis showed no significant association between polymorphisms of tumor necrosis factors-ααwhen comparing VL and DTH + group (P > 0.05. The associations were detected between VL and negative skin test delayed-type hypersensitivity for the heterozygote genotype (P = 0.021, the recessive model: 1/2 + 2/2 (P = 0.044 and the minor allele 2 (P = 0.019. The resistance to VL was found to be under the recessive model 1/2 + 2/2 of tumor necrosis factors-β, when comparing VL and DTH + group (odds ratios: 0.558, 95%; confidence interval: 0.316-0.987; P = 0.044. Conclusions: These results must be regarded to preliminary but suggestive that further study with larger populations is worthwhile.

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; Marcacao do peptideo intestinal vasoativo (VIP) e do fragmento VIP10-28 com radioiodo por metodo direto. Estudo comparativo da cinetica de biodistribuicao e da afinidade por celulas de tumor neuroendocrino

Energy Technology Data Exchange (ETDEWEB)

Colturato, Maria Tereza

2005-07-01

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. [{sup 131}I]VIP and [{sup 131}l]VIP 10-28 were obtained with high radiochemical purity (> 95%). The purification studies to remove free radioiodine in the

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....

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

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)

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

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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.

Double-balloon enteroscope for the diagnosis of small intestine diseases in children

International Nuclear Information System (INIS)

Hernandez Garces, Hector Ruben; Ruenes Domech, Caridad; Hano Garcia, Olga Marina

2010-01-01

A retrospective and descriptive study was conducted to assess the accuracy, effectiveness and extent of the double balloon enteroscope screening in the diagnosis of small intestine diseases in children. Eight patients were studied by means of physical examination and negative complementary ones of small intestine disease, seen between November, 2008 and October, 2009. In three patients there was the clinical and radiological suspicion of Crohn's disease; in other three the suspicion of small intestine tumor and remainder were seen due to hidden bleeding of intestinal origin

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.

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

Radiological manifestations of intestinal tuberculosis

Energy Technology Data Exchange (ETDEWEB)

Im, Jae Hoon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1974-10-15

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.

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)

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)

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

International Nuclear Information System (INIS)

Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Boisgard, R.; Tavitian, B.; Boisgard, R.; Tavitian, B.; Roux, J.; Cales, P.; Clerc, J.

2008-01-01

The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III α, 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 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. 131 I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

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

KAUST Repository

Sharma, Arun; Singla, Deepak; Rashid, Mamoon; Raghava, Gajendra Pal Singh

2014-01-01

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

Lignan precursors from flaxseed or rye bran do not protect against the development of intestinal neoplasia in Apc(Min) mice

DEFF Research Database (Denmark)

van Kranen, H.J.; Mortensen, Alicja; Sørensen, Ilona Kryspin

2003-01-01

lignan precursors, i.e., secoisolariciresinol and matairesinol. No statistically significant difference was observed in the incidence and multiplicity of small intestinal and colon tumors at terminal sacrifice between mice fed the control diet or the diet supplemented with 5% flaxseed. With the rye bran...... diet a statistically significant enhancement of the number of small intestinal tumors in female mice was observed. The number of colon tumors, however, was comparable between the control and rye bran-fed mice of either sex. Furthermore, no activating point mutations in the K-ras oncogene nor positive...... immunohistochemical staining for the p53 gene were observed in a set of 48 colon tumors. In conclusion, our results demonstrate that increased intake of lignan precursors from flaxseed or rye bran, administered in a Western-style diet, does not protect against intestinal tumor development in an appropriate animal...

Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice.

Science.gov (United States)

Samuels, S E; Knowles, A L; Tilignac, T; Debiton, E; Madelmont, J C; Attaix, D

2000-09-01

The impact of cancer cachexia and chemotherapy on small intestinal protein metabolism and its subsequent recovery was investigated. Cancer cachexia was induced in mice with colon 26 adenocarcinoma, which is a small and slow-growing tumor characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea, cystemustine (C6H12ClN3O4S). Both healthy mice and tumor-bearing mice were given a single i.p. injection of cystemustine (20 mg/kg) 3 days after the onset of cachexia. Cancer cachexia led to a reduced in vivo rate of protein synthesis in the small intestine relative to healthy mice (-13 to -34%; P synthesis compared with healthy mice (23-34%; P < 0.05). Northern hybridizations of mRNA encoding components of the major proteolytic systems suggested that proteolysis may not have mediated intestinal wasting or recovery. A major clinical goal should be to design methods to improve small intestinal protein metabolism before the initiation of chemotherapy.

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

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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.

Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer.

Directory of Open Access Journals (Sweden)

Eva Pastille

2017-09-01

Full Text Available Inflammatory bowel diseases (IBD are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs. This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.

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.

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.)

Selenium and sulindac are synergistic to inhibit intestinal tumorigenesis in Apc/p21 mice

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Bi Xiuli

2013-01-01

Full Text Available Abstract Background Both selenium and non-steroidal anti-inflammatory drug (NSAID sulindac are effective in cancer prevention, but their effects are affected by several factors including epigenetic alterations and gene expression. The current study was designed to determine the effects of the combination of selenium and sulindac on tumor inhibition and the underlying mechanisms. Results We fed the intestinal tumor model Apc/p21 mice with selenium- and sulindac-supplemented diet for 24 weeks, and found that the combination of selenium and sulindac significantly inhibited intestinal tumorigenesis, in terms of reducing tumor incidence by 52% and tumor multiplicities by 80% (p Conclusions The selenium is synergistic with sulindac to exert maximal effects on tumor inhibition. This finding provides an important chemopreventive strategy using combination of anti-cancer agents, which has a great impact on cancer prevention and has a promising translational potential.

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

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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.

CCDC26, CDKN2BAS, RTEL1 and TERT Polymorphisms in pediatric brain tumor susceptibility.

Science.gov (United States)

Adel Fahmideh, Maral; Lavebratt, Catharina; Schüz, Joachim; Röösli, Martin; Tynes, Tore; Grotzer, Michael A; Johansen, Christoffer; Kuehni, Claudia E; Lannering, Birgitta; Prochazka, Michaela; Schmidt, Lisbeth S; Feychting, Maria

2015-08-01

The role of genetic polymorphisms in pediatric brain tumor (PBT) etiology is poorly understood. We hypothesized that single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) on adult glioma would also be associated with PBT risk. The study is based on the Cefalo study, a population-based multicenter case-control study. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was extracted and genotyped for 29 SNPs reported by GWAS to be significantly associated with risk of adult glioma. Data were analyzed using unconditional logistic regression. Stratified analyses were performed for two histological subtypes: astrocytoma alone and the other tumor types combined. The results indicated that four SNPs, CDKN2BAS rs4977756 (p = 0.036), rs1412829 (p = 0.037), rs2157719 (p = 0.018) and rs1063192 (p = 0.021), were associated with an increased susceptibility to PBTs, whereas the TERT rs2736100 was associated with a decreased risk (p = 0.018). Moreover, the stratified analyses showed a decreased risk of astrocytoma associated with RTEL1 rs6089953, rs6010620 and rs2297440 (p trend = 0.022, p trend = 0.042, p trend = 0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (p trend = 0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (p trend = 0.009, p trend = 0.007, respectively). Our findings indicate that SNPs in CDKN2BAS, TERT, RTEL1 and CCDC26 may be associated with the risk of PBTs. Therefore, we suggest that pediatric and adult brain tumors might share common genetic risk factors and similar etiological pathways. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

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

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

Science.gov (United States)

2018-05-14

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

Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

International Nuclear Information System (INIS)

Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

2010-01-01

Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-α, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-α, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

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 (APC1638N/+) 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 APC1638N/+ mice after exposure to energetic heavy ions at high (50 cGy/min) and relatively low (0.33 cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50 cGy of 28Si (energy: 300 MeV/n; LET: 70 keV/μm) or 56Fe (energy: 1000 MeV/n; LET: 148 keV/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 150 days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe 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 28Si 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

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.

Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in Apc(Min/+) mice.

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Pierre, Christina C; Longo, Joseph; Mavor, Meaghan; Milosavljevic, Snezana B; Chaudhary, Roopali; Gilbreath, Ebony; Yates, Clayton; Daniel, Juliet M

2015-09-01

Constitutive Wnt/β-catenin signaling is a key contributor to colorectal cancer (CRC). Although inactivation of the tumor suppressor adenomatous polyposis coli (APC) is recognized as an early event in CRC development, it is the accumulation of multiple subsequent oncogenic insults facilitates malignant transformation. One potential contributor to colorectal carcinogenesis is the POZ-ZF transcription factor Kaiso, whose depletion extends lifespan and delays polyp onset in the widely used Apc(Min/+) mouse model of intestinal cancer. These findings suggested that Kaiso potentiates intestinal tumorigenesis, but this was paradoxical as Kaiso was previously implicated as a negative regulator of Wnt/β-catenin signaling. To resolve Kaiso's role in intestinal tumorigenesis and canonical Wnt signaling, we generated a transgenic mouse model (Kaiso(Tg/+)) expressing an intestinal-specific myc-tagged Kaiso transgene. We then mated Kaiso(Tg/+) and Apc(Min/+) mice to generate Kaiso(Tg/+):Apc(Min/+) mice for further characterization. Kaiso(Tg/+):Apc(Min/+) mice exhibited reduced lifespan and increased polyp multiplicity compared to Apc(Min/+) mice. Consistent with this murine phenotype, we found increased Kaiso expression in human CRC tissue, supporting a role for Kaiso in human CRC. Interestingly, Wnt target gene expression was increased in Kaiso(Tg/+):Apc(Min/+) mice, suggesting that Kaiso's function as a negative regulator of canonical Wnt signaling, as seen in Xenopus, is not maintained in this context. Notably, Kaiso(Tg/+):Apc(Min/+) mice exhibited increased inflammation and activation of NFκB signaling compared to their Apc(Min/+) counterparts. This phenotype was consistent with our previous report that Kaiso(Tg/+) mice exhibit chronic intestinal inflammation. Together our findings highlight a role for Kaiso in promoting Wnt signaling, inflammation and tumorigenesis in the mammalian intestine. Copyright © 2015 Elsevier B.V. All rights reserved.

Malignancy risk prediction for primary jejunum-ileal tumors

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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%.

Coagulation of sheep intestinal and prefemoral lymph.

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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.

Phospholipid ether analogs for the detection of colorectal tumors.

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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.

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.

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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.

Malignant Glomus Tumor of the Peritoneum: Case Report

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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.

Malignant Glomus Tumor of the Peritoneum: Case Report

International Nuclear Information System (INIS)

Baleato-González, Sandra; García-Figueiras, Roberto; Trujillo-Ariza, Maria Virginia; Carrera-Álvarez, Juan Jose

2014-01-01

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

Comparison of first-pass and second-bolus dynamic susceptibility perfusion MRI in brain tumors

International Nuclear Information System (INIS)

Spampinato, M.V.; Besenski, Nada; Rumboldt, Zoran; Wooten, Caroline; Dorlon, Margaret

2006-01-01

Our goal was to evaluate whether the T1 shortening effect caused by contrast leakage into brain tumors, a well-known confounding effect in the quantification of relative cerebral blood volume (rCBV) measurements, may be corrected by the administration of a predose of gadolinium-DTPA. As part of their presurgical imaging protocol, 25 patients with primary brain tumors underwent two consecutive dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MR studies. Intratumoral rCBV measurements and normalized rCBV values obtained during the first-pass and second-bolus studies were compared (Wilcoxon signed-ranks test). The frequency of relatively increased rCBV ratios on the second-bolus study was compared between enhancing and non-enhancing neoplasms (Fisher's exact test). Postprocessing perfusion studies were evaluated for image quality on a scale of 0-3 (Wilcoxon signed-ranks test). Four studies were excluded due to unacceptable image quality. Mean normalized rCBVs were 9.04 (SD 4.64) for the first-pass and 7.99 (SD 3.84) for the second-bolus study. There was no statistically significant difference between the two perfusion studies in either intratumoral rCBV (P=0.237) or rCBV ratio (P=0.181). Five enhancing and four non-enhancing tumors showed a relative increase in rCBV ratio on the second-bolus study, without a significant difference between the groups. Image quality was not significantly different between perfusion studies. Our results did not demonstrate a significant difference between first-pass and second-bolus rCBV measurements in DSC perfusion MR imaging. The administration of a predose of gadolinium-DTPA does not appear to be an efficient way of compensating for the underestimation of intratumoral rCBV values due to the T1 shortening effect. (orig.)

Apc inactivation, but not obesity, synergizes with Pten deficiency to drive intestinal stem cell-derived tumorigenesis.

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Tabrizian, Tahmineh; Wang, Donghai; Guan, Fangxia; Hu, Zunju; Beck, Amanda P; Delahaye, Fabien; Huffman, Derek M

2017-06-01

Obesity is a major risk factor for colorectal cancer and can accelerate Lgr5+ intestinal stem cell (ISC)-derived tumorigenesis after the inactivation of Apc However, whether non-canonical pathways involving PI3K-Akt signaling in ISCs can lead to tumor formation, and if this can be further exacerbated by obesity is unknown. Despite the synergy between Pten and Apc inactivation in epithelial cells on intestinal tumor formation, their combined role in Lgr5+-ISCs, which are the most rapidly dividing ISC population in the intestine, is unknown. Lgr5+-GFP mice were provided low-fat diet (LFD) or high-fat diet (HFD) for 8 months, and the transcriptome was evaluated in Lgr5+-ISCs. For tumor studies, Lgr5+-GFP and Lgr5+-GFP- Pten flox/flox mice were tamoxifen treated to inactivate Pten in ISCs and provided LFD or HFD until 14-15 months of age. Finally, various combinations of Lgr5+-ISC-specific, Apc- and Pten -deleted mice were generated and evaluated for histopathology and survival. HFD did not overtly alter Akt signaling in ISCs, but did increase other metabolic pathways. Pten deficiency, but not HFD, increased BrdU-positive cells in the small intestine ( P  Apc deficiency synergistically increased proliferative markers, tumor pathology and mortality, in a dose-dependent fashion ( P  Apc deficiency in ISCs synergistically increases proliferation, tumor formation and mortality. Thus, aberrant Wnt/β-catenin, rather than PI3K-Akt signaling, is requisite for obesity to drive Lgr5+ ISC-derived tumorigenesis. © 2017 Society for Endocrinology.

PAF-Myc-Controlled Cell Stemness Is Required for Intestinal Regeneration and Tumorigenesis.

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Kim, Moon Jong; Xia, Bo; Suh, Han Na; Lee, Sung Ho; Jun, Sohee; Lien, Esther M; Zhang, Jie; Chen, Kaifu; Park, Jae-Il

2018-03-12

The underlying mechanisms of how self-renewing cells are controlled in regenerating tissues and cancer remain ambiguous. PCNA-associated factor (PAF) modulates DNA repair via PCNA. Also, PAF hyperactivates Wnt/β-catenin signaling independently of PCNA interaction. We found that PAF is expressed in intestinal stem and progenitor cells (ISCs and IPCs) and markedly upregulated during intestinal regeneration and tumorigenesis. Whereas PAF is dispensable for intestinal homeostasis, upon radiation injury, genetic ablation of PAF impairs intestinal regeneration along with the severe loss of ISCs and Myc expression. Mechanistically, PAF conditionally occupies and transactivates the c-Myc promoter, which induces the expansion of ISCs/IPCs during intestinal regeneration. In mouse models, PAF knockout inhibits Apc inactivation-driven intestinal tumorigenesis with reduced tumor cell stemness and suppressed Wnt/β-catenin signaling activity, supported by transcriptome profiling. Collectively, our results unveil that the PAF-Myc signaling axis is indispensable for intestinal regeneration and tumorigenesis by positively regulating self-renewing cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Intestinal stromal cells in mucosal immunity and homeostasis.

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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.

Vasoactive intestinal peptide (VIP) labelling with iodine-131 by direct method; Marcacao do peptideo intestinal vasoativo (VIP) com iodo-131 por metodo direto

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Colturato, M.T.; Silva, C.P.G. da; Araujo, E.B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Centro de Radiofarmacia

2002-07-01

The Vasoactive Intestinal Peptide (VIP) is a 28-amino acid polypeptide with a great numbers of receptors in tumoral cells, including adenocarcinomas and pancreatic and colon carcinomas. The VIP molecule contains two tyrosine residues, in positions 10 and 22, that are theoretically equally susceptible to iodination, The VIP was labeled with 131-iodine by direct method using Iodogen as oxidant agent: 15.03 mmol VIP + 0.10 nmol KI + [{sup 131} I]NaI + 13.9 mmol Iodogen; the final volume was adjust to 100 {mu}L using 0.2 M phosphate buffer, pH 7.5 and the reaction proceed with stirring for 30 minutes at room temperature. The radiochemical purity was determined by electrophoresis (Whatman 1MM paper; 0.05 M barbital buffer; pH 8.6; 150 V; 40 minutes) that indicates low percent of free 131-iodine. The high performance liquid chromatography (HPLC) system using RPC{sup 18}, 10 {mu}m, 4 x 250mm column, was able to separate the different radiochemical species, only when an isocratic mixture of acetonitrile: 0.1% trifluoroacetic acid (27:73) was used, with 0.5 mL/min. flux. (author)

Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation

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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.

Colonisation of a phage susceptible Campylobacter jejuni population in two phage positive broiler flocks.

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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.

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

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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...

The usefulness of MDCT in acute intestinal bleeding

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Kim, Kum Rae; Park, Won Kyu; Kim, Jae Woon; Chang, Jay Chun; Jang, Han Won

2006-01-01

We wanted to evaluate the usefulness of MDCT for localizing a bleeding site and for helping make a decision on further management for acute intestinal bleeding. We conducted a retrospective review of 17 consecutive patients who presented with acute intestinal bleeding and who also underwent MDCT before angiography or surgery. The sensitivity of MDCT for detecting acute intestinal bleeding was assessed and compared with that of conventional angiography. The sensitivity of MDCT for the detection of acute intestinal bleeding was 77% (13 or 17), whereas that of angiography was 46% (6 or 13). All the bleeding points that were subsequently detected on angiography were visualized on MDCT. In three cases, the bleeding focus was detected on MDCT and not on angiography. In four cases, both MDCT and angiography did not detect the bleeding focus; for one of these cases, CT during SMA angiography was performed and this detected the active bleeding site. In patients with acute intestinal bleeding, MDCT is a useful image modality to detect the bleeding site and to help decide on further management before performing angiography or surgery. When tumorous lesions are detected, invasive angiography can be omitted

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

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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

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

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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

Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine.

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Pagel, René; Bär, Florian; Schröder, Torsten; Sünderhauf, Annika; Künstner, Axel; Ibrahim, Saleh M; Autenrieth, Stella E; Kalies, Kathrin; König, Peter; Tsang, Anthony H; Bettenworth, Dominik; Divanovic, Senad; Lehnert, Hendrik; Fellermann, Klaus; Oster, Henrik; Derer, Stefanie; Sina, Christian

2017-11-01

Endogenous circadian clocks regulate 24-h rhythms of physiology and behavior. Circadian rhythm disruption (CRD) is suggested as a risk factor for inflammatory bowel disease. However, the underlying molecular mechanisms remain unknown. Intestinal biopsies from Per1/2 mutant and wild-type (WT) mice were investigated by electron microscopy, immunohistochemistry, and bromodeoxyuridine pulse-chase experiments. TNF-α was injected intraperitoneally, with or without necrostatin-1, into Per1/2 mice or rhythmic and externally desynchronized WT mice to study intestinal epithelial cell death. Experimental chronic colitis was induced by oral administration of dextran sodium sulfate. In vitro , caspase activity was assayed in Per1/2-specific small interfering RNA-transfected cells. Wee1 was overexpressed to study antiapoptosis and the cell cycle. Genetic ablation of circadian clock function or environmental CRD in mice increased susceptibility to severe intestinal inflammation and epithelial dysregulation, accompanied by excessive necroptotic cell death and a reduced number of secretory epithelial cells. Receptor-interacting serine/threonine-protein kinase (RIP)-3-mediated intestinal necroptosis was linked to increased mitotic cell cycle arrest via Per1/2-controlled Wee1, resulting in increased antiapoptosis via cellular inhibitor of apoptosis-2. Together, our data suggest that circadian rhythm stability is pivotal for the maintenance of mucosal barrier function. CRD increases intestinal necroptosis, thus rendering the gut epithelium more susceptible to inflammatory processes.-Pagel, R., Bär, F., Schröder, T., Sünderhauf, A., Künstner, A., Ibrahim, S. M., Autenrieth, S. E., Kalies, K., König, P., Tsang, A. H., Bettenworth, D., Divanovic, S., Lehnert, H., Fellermann, K., Oster, H., Derer, S., Sina, C. Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine. © FASEB.

Polymorphism of the p53 tumor suppressor gene is associated with susceptibility to uterine leiomyoma.

Science.gov (United States)

Denschlag, Dominik; Bettendorf, Herta; Watermann, Dirk; Keck, Christoph; Tempfer, Clemens; Pietrowski, Detlef

2005-07-01

To evaluate the association between the presence of uterine leiomyoma and two single nuclear polymorphisms of the p53 tumor suppressor and the angiopoietin-2 (ANGPT2) genes. Prospective case control study. Academic research institution. One hundred thirty-two women with clinically and surgically diagnosed uterine leiomyomas and 280 controls. Peripheral venous puncture. Genotyping was performed by polymerase chain reaction-based amplification of the Arg and Pro variants at codon 72 of the p53 gene and by restriction fragment length polymorphism analysis of the G/G and G/A alleles in exon 4 of the ANGPT2 gene. Comparing women with uterine leiomyomas and controls, no statistically significant difference with respect to allele frequency and genotype distribution were ascertained for the ANGPT2 polymorphism (P=.2 and P=.5, respectively). However, for the p53 tumor suppressor gene polymorphism, statistically significant differences in terms of a higher Pro allele frequency and a higher prevalence of the Pro/Pro genotype among women with uterine leiomyoma (32.0% vs. 16.0%, respectively, and 21.3% vs. 4.7%, respectively) were ascertained (P=.001, OR 1.74; 95% CI 1.24-2.45, P=.001; OR 3.84, 95% CI 1.81-8.14; respectively). Carriage of the p53 polymorphism at codon 72 predicts the susceptibility to leiomyoma in a Caucasian population and may contribute to the pathogenesis of uterine leiomyoma.

Intestinal diffuse large B-cell lymphoma: an evaluation of different staging systems.

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Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Park, Chan-Sik; Huh, Jooryung

2014-01-01

The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.

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

was associated with endogenous downregulation of APC and AXIN2 expression in Caco-2 cells but did not affect GSK3β expression. Furthermore, elevated levels of nuclear β-catenin and reduced levels of cytoplasmic APC were correlated to a low CDX2 expression in migrating colon cancer cells in vivo. These results......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......-related genes are regulated by CDX2. The aim was to investigate the role of decreased CDX2 level on the expression of APC, AXIN2 and GSK3β in migrating colon cancer cells at the invasive front. CDX2-bound promoter and enhancer regions from APC, AXIN2 and GSK3β were analyzed for gene regulatory activity...

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.)

Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis.

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Catherine M Miller

Full Text Available Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis.Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice.Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation.

Identification of three QTLs with influence on susceptibility to helminth infections in pigs

DEFF Research Database (Denmark)

Nejsum, Peter; Thamsborg, Stig Milan; Göring, H. H.

  Intestinal helminth infections are causing health and welfare problems in both human and animal populations. A family, in which susceptibility towards Ascaris (large round worm) and Trichuris (whipworm) infections are segregating, was constructed. Our data demonstrate that genetic components...

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.

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.

2018-01-01

Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide1. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling2–5, 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. PMID:28636595

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

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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.

Intestinal Hedgehog signaling in tumors and inflammation

NARCIS (Netherlands)

Büller, N.V.J.A.

2015-01-01

In this thesis we investigated the role of Hedgehog signaling in tumors and inflammation. By using an inducible Indian Hedgehog (Ihh) knockout mouse we show that Ihh signals via the mesenchyme to the proliferating cells in the crypt to attenuate proliferation. Despite its anti-proliferative role in

Functional and morphological effects of diazepam and midazolam on tumor vasculature in the 9L gliosarcoma brain tumor model using dynamic susceptibility contrast MRI: a comparative study

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Yan N

2017-10-01

Full Text Available Nuo Yan,1 Yuzhen Zheng,2 Cheng Yang1 1Second Department of Anesthesiology, The Affiliated Hospital to Logistics University of PAP, Tianjin, 2Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin, China Abstract: Antiangiogenic therapy attenuates tumor growth by reducing vascularization. Diazepam (DZP and midazolam (MZL have antiangiogenic properties in human umbilical vein endothelial cells. Thus, we investigated the antiangiogenic activity of DZP and MZL in the rat 9L gliosarcoma brain tumor model. The effect on tumor vasculature was evaluated using dynamic susceptibility contrast magnetic resonance imaging with gradient-echo (GE and spin-echo (SE to assess perfusion parameters, including cerebral blood volume (CBV, cerebral blood flow (CBF, mean transit time (MTT, and mean vessel diameter. The GE-normalized CBF (nCBF in the tumors of untreated controls was significantly lower than that in normal brain tissue, whereas the CBV and MTT were higher. DZP- and MZL-treated rats had higher CBF and lower CBV and MTT values than did untreated controls. The tumor size decreased significantly to 33.5% in DZP-treated rats (P<0.001 and 22.5% in MZL-treated rats (P<0.01 relative to controls. The SE-normalized CBV was lower in DZP-treated (32.9% and MZL-treated (10.6% rats compared with controls. The mean vessel diameter decreased significantly by 32.5% in DPZ-treated and by 24.9% in MZL-treated rats compared with controls (P<0.01. The GE and SE nCBF values were higher in DZP-treated (49.9% and 40.1%, respectively and MZL-treated (41.2% and 32.1%, respectively rats than in controls. The GE- and SE-normalized MTTs were lower in DZP-treated (48.2% and 59.8%, respectively and MZL-treated (40.5% and 51.2%, respectively rats than in controls. Both DZP and MZL had antiangiogenic effects on tumor perfusion and vasculature; however, the antiangiogenic activity of DZP is more promising than that of MZL. Keywords: diazepam, midazolam, 9L gliosarcoma

Tumor del estroma gastrointestinal Tumor of the gastrointestinal stroma

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Jorge Felipe Montero León

2012-03-01

Full Text Available Los tumores del estroma gastrointestinal, conocidos según sus siglas en inglés como GIST (gastrointestinal stromal tumors, son tumores mesenquimales que aparecen en cualquier lugar a lo largo del tracto intestinal. Este trabajo tiene el propósito de presentar una paciente de 60 años de edad que asiste a la consulta de ginecología del Instituto Nacional de Oncología y Radiobiología, por presentar dolor en el epigastrio, que se irradia al flanco derecho, con un aumento de volumen en la fosa iliaca derecha, y por ultrasonografía se plantea un tumor de ovario derecho, que se proyecta hacia el epigastrio y a hipocondrio derecho. Se describe la intervención quirúrgica y los hallazgos encontrados en estudios macro y microscópicos, así como en estudios posteriores por inmunohistoquímica de la lesión. Se concluye con un diagnóstico de tumor del estroma gastrointestinal y los resultados de las intervenciones quirúrgicas y medicamentosas realizadas. Se recomienda valorar la importancia de una estrecha relación entre cirujanos generales y ginecólogos frente a enfermedades inesperadas, por su difícil diagnóstico preoperatorio, que conllevan a un tratamiento quirúrgico adecuado, y que por la complejidad que requieren, necesitan de la competencia de ambas especialidades quirúrgicas.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 Genecology 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 ovarium projecting to epigastrium and the right hypochondrium. The surgical intervention is described as well as the findings noted in macro- and microscopic studies

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.

Effects of dietary beef, pork, chicken and salmon on intestinal carcinogenesis in A/J Min/+ mice.

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Christina Steppeler

Full Text Available The International Agency for Research on Cancer has classified red meat as "probably carcinogenic to humans" (Group 2A. In mechanistic studies exploring the link between intake of red meat and CRC, heme iron, the pigment of red meat, is proposed to play a central role as a catalyzer of luminal lipid peroxidation and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle food (dry weight and 60% powder diet on Apc-driven intestinal carcinogenesis, from week 3-13 of age. Muscle food diets did not differentially affect carcinogenesis in the colon (flat ACF and tumors. In the small intestine, salmon intake resulted in a lower tumor size and load than did meat from terrestrial animals (beef, pork or chicken, while no differences were observed between the effects of white meat (chicken and red meat (pork and beef. Additional results indicated that intestinal carcinogenesis was not related to dietary n-6 polyunsaturated fatty acids, intestinal formation of lipid peroxidation products (thiobarbituric acid reactive substances, TBARS, or cytotoxic effects of fecal water on Apc-/+ cells. Notably, the amount of heme reaching the colon appeared to be relatively low in this study. The greatest tumor load was induced by the reference diet RM1, underlining the importance of the basic diets in experimental CRC. The present study in A/J Min/+ mice does not support the hypothesis of a role of red meat in intestinal carcinogenesis.

Defining new criteria for selection of cell-based intestinal models using publicly available databases

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Christensen Jon

2012-06-01

Full Text Available Abstract Background The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies. Results We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics. Conclusions This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models

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

Intestinal metaplasia induced by x-irradiation in different strains of rats

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Naito, Masashi; Kawashima, Kengo; Ito, Akihiro

1985-01-01

Attempts were made to examine strain differences in the susceptibility of rats to intestinal metaplasia induced by X-irradiation. The gastric regions of 4 inbred male rats (SHR, F344, WKY, and LEW strains) in 5-week-old and 2 random bred male rats (SD, and WIS strains) were irradiated with a total dose of 20 Gy X-ray given in two equal fractions separated by three days. Upon sacrifice at 6 months after the last irradiation, the number of intestinal metaplastic crypts with positive reaction to alkaline phosphatase (ALP) appeared highest in the SHR and lowest in the WIS rats. Morphologically, the number of crypts with intestinal metaplasia in whole glandular stomachs of SHR, WIS, F344, and SD rats were higher than those in WKY and LEW rats. In the pyloric gland, it was highest in WIS rats, while in the fundic gland it was highest in SHR rats. The results show that the appearance and location of intestinal metaplasia by X-irradiation are greatly influenced by the strain of the rat. (author)

Vasoactive intestinal peptide (VIP) labelling with iodine-131 by direct method

International Nuclear Information System (INIS)

Colturato, M.T.; Silva, C.P.G. da; Araujo, E.B.

2002-01-01

The Vasoactive Intestinal Peptide (VIP) is a 28-amino acid polypeptide with a great numbers of receptors in tumoral cells, including adenocarcinomas and pancreatic and colon carcinomas. The VIP molecule contains two tyrosine residues, in positions 10 and 22, that are theoretically equally susceptible to iodination, The VIP was labeled with 131-iodine by direct method using Iodogen as oxidant agent: 15.03 mmol VIP + 0.10 nmol KI + [ 131 I]NaI + 13.9 mmol Iodogen; the final volume was adjust to 100 μL using 0.2 M phosphate buffer, pH 7.5 and the reaction proceed with stirring for 30 minutes at room temperature. The radiochemical purity was determined by electrophoresis (Whatman 1MM paper; 0.05 M barbital buffer; pH 8.6; 150 V; 40 minutes) that indicates low percent of free 131-iodine. The high performance liquid chromatography (HPLC) system using RPC 18 , 10 μm, 4 x 250mm column, was able to separate the different radiochemical species, only when an isocratic mixture of acetonitrile: 0.1% trifluoroacetic acid (27:73) was used, with 0.5 mL/min. flux. (author)

Metagenomic Characterization of the Human Intestinal Microbiota in Fecal Samples from STEC-Infected Patients

NARCIS (Netherlands)

Gigliucci, Federica; von Meijenfeldt, F A Bastiaan; Knijn, Arnold; Michelacci, Valeria; Scavia, Gaia; Minelli, Fabio; Dutilh, Bas E|info:eu-repo/dai/nl/304546313; Ahmad, Hamideh M; Raangs, Gerwin C; Friedrich, Alex W; Rossen, John W A; Morabito, Stefano

2018-01-01

The human intestinal microbiota is a homeostatic ecosystem with a remarkable impact on human health and the disruption of this equilibrium leads to an increased susceptibility to infection by numerous pathogens. In this study, we used shotgun metagenomic sequencing and two different bioinformatic

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...

In-vitro activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota.

Science.gov (United States)

Weintraub, Andrej; Rashid, Mamun-Ur; Nord, Carl Erik

2016-12-01

Solithromycin is a novel fluoroketolide with high activity against bacteria associated with community-acquired respiratory tract infections as well as gonorrhea. However, data on the activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota are scarce. In this study, 1024 Gram-positive and Gram-negative anaerobic isolates from the normal intestinal microbiota were analyzed for in-vitro susceptibility against solithromycin and compared to azithromycin, amoxicillin/clavulanic acid, ceftriaxone, metronidazole and levofloxacin by determining the minimum inhibitory concentration (MIC). Solithromycin was active against Bifidobacteria (MIC 50 , 0.008 mg/L) and Lactobacilli (MIC 50 , 0.008 mg/L). The MIC 50 for Clostridia, Bacteroides, Prevotella and Veillonella were 0.5, 0.5, 0.125 and 0.016 mg/L, respectively. Gram-positive anaerobes were more susceptible to solithromycin as compared to the other antimicrobials tested. The activity of solithromycin against Gram-negative anaerobes was equal or higher as compared to other tested agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Virtual CT-colonoscopy resources in large intestine neoplasia

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Chalyk Yu.V.

2011-12-01

Full Text Available The research goal is to state possibility of virtual colonoscopy and to determine the localization and nature of neoplasms in the large intestine. Materials and methods: 38 patients have been examined by the method of virtual colonoscopy. The preceding stage of diagnosis by total fibrocolonoscopy has not been a success. Results: Virtual colonoscopy has been performed in 94.7% of patients. The same tumors have been identified in the proximal colon, direct examination of which has not been possible. Conclusion: Virtual colonoscopy is the method of choice for topical diagnosis of tumors of the colon

Disruption of estrogen receptor signaling enhances intestinal neoplasia in ApcMin/+ mice

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Cleveland, Alicia G.; Oikarinen, Seija I.; Bynoté, Kimberly K.; Marttinen, Maija; Rafter, Joseph J.; Gustafsson, Jan-Åke; Roy, Shyamal K.; Pitot, Henry C.; Korach, Kenneth S.; Lubahn, Dennis B.; Mutanen, Marja; Gould, Karen A.

2009-01-01

Estrogen receptors (ERs) [ERα (Esr1) and ERβ (Esr2)] are expressed in the human colon, but during the multistep process of colorectal carcinogenesis, expression of both ERα and ERβ is lost, suggesting that loss of ER function might promote colorectal carcinogenesis. Through crosses between an ERα knockout and ApcMin mouse strains, we demonstrate that ERα deficiency is associated with a significant increase in intestinal tumor multiplicity, size and burden in ApcMin/+ mice. Within the normal intestinal epithelium of ApcMin/+ mice, ERα deficiency is associated with an accumulation of nuclear β-catenin, an indicator of activation of the Wnt–β-catenin-signaling pathway, which is known to play a critical role in intestinal cancers. Consistent with the hypothesis that ERα deficiency is associated with activation of Wnt–β-catenin signaling, ERα deficiency in the intestinal epithelium of ApcMin/+ mice also correlated with increased expression of Wnt–β-catenin target genes. Through crosses between an ERβ knockout and ApcMin mouse strains, we observed some evidence that ERβ deficiency is associated with an increased incidence of colon tumors in ApcMin/+ mice. This effect of ERβ deficiency does not involve modulation of Wnt–β-catenin signaling. Our studies suggest that ERα and ERβ signaling modulate colorectal carcinogenesis, and ERα does so, at least in part, by regulating the activity of the Wnt–β-catenin pathway. PMID:19520794

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.

Primary fibrosarcoma im small intestine of dog - Case report

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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.

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

Porcine postweaning Escherichia coli enteritis is a cause of significant morbidity and mortality in pigs worldwide, and effective prevention remains an unsolved problem. This study examined the correlation between susceptibility of pigs to experimental infection with an E. coli F18 strain...... 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...... and heterozygotic susceptible pigs. Faecal shedding of the challenge strain correlated with the genetic receptor profile. Twenty pigs examined immunohistochemically revealed focal to extensive small intestinal mucosal colonisation by E. coli O138:F18 in nine of 10 susceptible and three of 10 resistant pigs. Results...

Benign Lesions in Mucosa Adjacent to Intestinal-Type Sinonasal Adenocarcinoma

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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.

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

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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.

Experimental research for tumor VIP receptor imaging

International Nuclear Information System (INIS)

Li Qianwei; Tan Tianzhi

1998-01-01

To study the possibility of radioactive labelled vasoactive intestinal peptide (VIP) for tumor VIP receptor imaging. 125 I-VIP was prepared by chloramine-T method, and purified by Sephadex G-50 column chromatography. The bioactivity and stability of 125 I-VIP were measured by silica 60 F 254 TLC and competition test to SGC7901 cell in vitro. The biodistribution of 125 I-VIP was studied in the nude mice bearing tumor. The results showed that labelled rate of 125 I was 73.8%, the specific activity was 18.2 PBq/mol, the radiochemical purity (RCP) was over 98% and remained 96.3% after 48 days stored at -80 degree C. The specific binding of 125 I-VIP to the SGC7901 cell was inhibited by VIP in dose dependence in the competition experiment. The radioactivity of tumor was higher than that of muscles in all phases (P<0.05-0.01), the peak activity of tumor occurred at 30 min (3.58 +- 0.48ID%/g) and the peak ratio of T/N occurred at 60 min after the injection. The activity of lungs was obviously higher than that of blood, the intestine was always in low level. Most of the activity in the body was mainly eliminated from kidney. The present study demonstrated that the radioactive labelled VIP is a promising agent for tumor VIP receptor scintigraphy

Studies into the transplantation biology of ultraviolet light-induced tumors

International Nuclear Information System (INIS)

Daynes, R.A.; Spellman, C.W.; Woodward, J.G.; Stewart, D.A.

1977-01-01

The majority of skin tumors induced in mice by ultraviolet (uv) light are rejected when implanted into normal syngeneic recipients. Subcarcinogenic levels of uv light exposure render the normally resistant mice susceptible to tumor challenge. The immunoregulatory effect of uv light appears to be additive, since the growth rate of a tumor transplant is dependent upon the length of uv exposure administered prior to implantation. This suppressive influence does not appear to be directly mediated by the uv light, because the amputation of uv-irradiated tail skin allows for a retention of tumor resistance in otherwise tumor-susceptible hosts. uv-irradiated mice could also be immunized against uv tumors, which suggests that immune recognition of tumor-specific transplantation antigens has not been inhibited. The ability of uv exposure to alter normal immunological reactivity to uv-induced tumors is possibly an integral factor in the mechanism underlying uv carcinogenesis

Effects of hemin and nitrite on intestinal tumorigenesis in the A/J Min/+ mouse model.

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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.

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

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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...

St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

International Nuclear Information System (INIS)

Hu Zeping; Yang Xiaoxia; Chan Suiyung; Xu Anlong; Duan Wei; Zhu Yizhun; Sheu, F.-S.; Boelsterli, Urs Alex; Chan, Eli; Zhang Qiang; Wang, J.-C.; Ee, Pui Lai Rachel; Koh, H.L.; Huang Min; Zhou Shufeng

2006-01-01

Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1β, IL-2, IL-6), interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1β, IL-2, IL-6, IFN-γ and TNF-α and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5-11. In particular, combination of SJW significantly inhibited the expression of TNF-α mRNA in the intestine over days 5-11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities

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

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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

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)

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

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Donaldson, David S.; Else, Kathryn J.

2015-01-01

ABSTRACT 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. IMPORTANCE 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

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

Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection

International Nuclear Information System (INIS)

Haydont, Valerie; Gilliot, Olivier; Rivera, Sofia; Bourgier, Celine; Francois, Agnes; Aigueperse, Jocelyne; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine

2007-01-01

Purpose: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Methods and Materials: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Results: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. Conclusion: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible

Glioblastomas vs. lymphomas. More diagnostic certainty by using susceptibility-weighted imaging (SWI)

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Peters, S.; Knoess, N.; Wodarg, F.; Cnyrim, C.; Jansen, O. [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Inst. fuer Neuroradiologie

2012-08-15

Purpose: It can be difficult to differentiate glioblastomas from lymphomas using only standard MR images. There are references suggesting that it might be possible to differentiate these tumors using susceptibility-weighted imaging (SWI). The purpose of this study is to prove the diagnostic benefit using susceptibility-weighted images. Material and Methods: Three neuroradiologists tried to differentiate 4 histologically verified lymphomas from 11 glioblastomas in retrospect. They first viewed the conventional MR images and declared a diagnosis with a grade of certainty. Afterwards they additionally reviewed the susceptibility-weighted images. Results: Glioblastomas have a clearly higher grade of susceptibility signals than lymphomas. By additionally using susceptibility-weighted images, the radiologists determined the correct diagnosis in 82.2 % of the cases. Without susceptibility-weighted images, the diagnosis was correct in 75.5 % of the cases. The subjective gain of certainty was 16.5 %. If there were no intratumoral susceptibility signals (ITSS) (grade 1), the sensitivity for diagnosing a lymphoma was 70 % and the specificity was 100 %. The sensitivity for diagnosing a glioblastoma was 90.5 % and the specificity was 100 % if there was a high rate of intratumoral susceptibility signals (grade 3). Conclusion: Susceptibility-weighted images are an additional tool in clinical practice for determining the correct diagnosis. The differentiation between glioblastomas and lymphomas and the certainty of the determined diagnosis are better. Therefore, we recommend adding susceptibility-weighted imaging to the clinical MR tumor protocol. (orig.)

Glioblastomas vs. lymphomas: more diagnostic certainty by using susceptibility-weighted imaging (SWI).

Science.gov (United States)

Peters, S; Knöß, N; Wodarg, F; Cnyrim, C; Jansen, O

2012-08-01

It can be difficult to differentiate glioblastomas from lymphomas using only standard MR images. There are references suggesting that it might be possible to differentiate these tumors using susceptibility-weighted imaging (SWI). The purpose of this study is to prove the diagnostic benefit using susceptibility-weighted images. Three neuroradiologists tried to differentiate 4 histologically verified lymphomas from 11 glioblastomas in retrospect. They first viewed the conventional MR images and declared a diagnosis with a grade of certainty. Afterwards they additionally reviewed the susceptibility-weighted images. Glioblastomas have a clearly higher grade of susceptibility signals than lymphomas. By additionally using susceptibility-weighted images, the radiologists determined the correct diagnosis in 82.2 % of the cases. Without susceptibility-weighted images, the diagnosis was correct in 75.5 % of the cases. The subjective gain of certainty was 16.5 %. If there were no intratumoral susceptibility signals (ITSS) (grade 1), the sensitivity for diagnosing a lymphoma was 70 % and the specificity was 100 %. The sensitivity for diagnosing a glioblastoma was 90.5 % and the specificity was 100 % if there was a high rate of intratumoral susceptibility signals (grade 3). Susceptibility-weighted images are an additional tool in clinical practice for determining the correct diagnosis. The differentiation between glioblastomas and lymphomas and the certainty of the determined diagnosis are better. Therefore, we recommend adding susceptibility-weighted imaging to the clinical MR tumor protocol. © Georg Thieme Verlag KG Stuttgart · New York.

Glioblastomas vs. lymphomas. More diagnostic certainty by using susceptibility-weighted imaging (SWI)

International Nuclear Information System (INIS)

Peters, S.; Knoess, N.; Wodarg, F.; Cnyrim, C.; Jansen, O.

2012-01-01

Purpose: It can be difficult to differentiate glioblastomas from lymphomas using only standard MR images. There are references suggesting that it might be possible to differentiate these tumors using susceptibility-weighted imaging (SWI). The purpose of this study is to prove the diagnostic benefit using susceptibility-weighted images. Material and Methods: Three neuroradiologists tried to differentiate 4 histologically verified lymphomas from 11 glioblastomas in retrospect. They first viewed the conventional MR images and declared a diagnosis with a grade of certainty. Afterwards they additionally reviewed the susceptibility-weighted images. Results: Glioblastomas have a clearly higher grade of susceptibility signals than lymphomas. By additionally using susceptibility-weighted images, the radiologists determined the correct diagnosis in 82.2 % of the cases. Without susceptibility-weighted images, the diagnosis was correct in 75.5 % of the cases. The subjective gain of certainty was 16.5 %. If there were no intratumoral susceptibility signals (ITSS) (grade 1), the sensitivity for diagnosing a lymphoma was 70 % and the specificity was 100 %. The sensitivity for diagnosing a glioblastoma was 90.5 % and the specificity was 100 % if there was a high rate of intratumoral susceptibility signals (grade 3). Conclusion: Susceptibility-weighted images are an additional tool in clinical practice for determining the correct diagnosis. The differentiation between glioblastomas and lymphomas and the certainty of the determined diagnosis are better. Therefore, we recommend adding susceptibility-weighted imaging to the clinical MR tumor protocol. (orig.)

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

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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.

Identification of the intestinal type gastric adenocarcinoma transcriptomic markers using bioinformatic and gene expression analysis

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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.

Malignant tumors of gastrointestinal tract

International Nuclear Information System (INIS)

Anon.

1989-01-01

International histological classification and classification according to TNM systems, domestic clinical classification according to stages of carcinoma of stomach, large intestine and rectum are presented. Diagnosis of tumoral processes of the given localizations should be based on complex application of diagnostic methods: clinical, ultrasonic, radiological and others. Surgical method and variants of surgical method with preoperative radiotherapy play a leading role in treatment of mentioned tumors. Combined method of treatment-surgical intervention with postoperation intravenous injection of colloid 198 Au - is applied for preventing propagation of stomach cancer metastases. Advisability of combining operations with radiological and antitumoral medicamentous therapy is shown. Reliable results of treatment of malignant tumors of gastrointestinal tract are presented

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)

[Adult intestinal malrotation associated with intestinal volvulus].

Science.gov (United States)

Hernando-Almudí, Ernesto; Cerdán-Pascual, Rafael; Vallejo-Bernad, Cristina; Martín-Cuartero, Joaquín; Sánchez-Rubio, María; Casamayor-Franco, Carmen

Intestinal malrotation is a congenital anomaly of the intestinal rotation and fixation, and usually occurs in the neonatal age. Description of a clinical case associated with acute occlusive symptoms. A case of intestinal malrotation is presented in a previously asymptomatic woman of 46 years old with an intestinal obstruction, with radiology and surgical findings showing an absence of intestinal rotation. Intestinal malrotation in adults is often asymptomatic, and is diagnosed as a casual finding during a radiological examination performed for other reasons. Infrequently, it can be diagnosed in adults, associated with an acute abdomen. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

A Patient with Advanced Gastric Cancer Presenting with Extremely Large Uterine Fibroid Tumor

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Kwang-Kuk Park

2014-01-01

Full Text Available Introduction. Uterine fibroid tumors (uterine leiomyomas are the most common benign uterine tumors. The incidence of uterine fibroid tumors increases in older women and may occur in more than 30% of women aged 40 to 60. Many uterine fibroid tumors are asymptomatic and are diagnosed incidentally. Case Presentation. A 44-year-old woman was admitted to our hospital with general weakness, dyspepsia, abdominal distension, and a palpable abdominal mass. An abdominal computed tomography scan showed a huge tumor mass in the abdomen which was compressing the intestine and urinary bladder. Gastroduodenal endoscopic and biopsy results showed a Borrmann type IV gastric adenocarcinoma. The patient was diagnosed with gastric cancer with disseminated peritoneal carcinomatosis. She underwent a hysterectomy with both salphingo-oophorectomy and bypass gastrojejunostomy. Simultaneous uterine fibroid tumor with other malignancies is generally observed without resection. But in this case, a surgical resection was required to resolve an intestinal obstruction and to exclude the possibility of a metastatic tumor. Conclusion. When a large pelvic or ovarian mass is detected in gastrointestinal malignancy patients, physicians try to exclude the presence of a Krukenberg tumor. If the tumors cause certain symptoms, surgical resection is recommended to resolve symptoms and to exclude a metastatic tumor.

Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

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Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

2012-01-01

SUMMARY The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588

Associação timoma e estrongiloidíase intestinal grave

OpenAIRE

Godoy,Pérsio; Campos,Christian Marcellus Camargos; Costa,Guilherme; Castro,Lúcia Porto Fonseca de

1998-01-01

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.

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

Salmonella enterica serovar Typhimurium exploits inflammation to modify swine intestinal microbiota.

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Rosanna eDrumo

2016-01-01

Full Text Available Salmonella enterica serovar Typhimurium is an important zoonotic gastrointestinal pathogen responsible for foodborne disease worldwide. It is a successful enteric pathogen because it has developed virulence strategies allowing it to survive in a highly inflamed intestinal environment exploiting inflammation to overcome colonization resistance provided by intestinal microbiota. In this study, we used piglets featuring an intact microbiota, which naturally develop gastroenteritis, as model for salmonellosis. We compared the effects on the intestinal microbiota induced by a wild type and an attenuated S. Typhimurium in order to evaluate whether the modifications are correlated with the virulence of the strain. This study showed that Salmonella alters microbiota in a virulence-dependent manner. We found that the wild type S. Typhimurium induced inflammation and a reduction of specific protecting microbiota species (SCFA-producing bacteria normally involved in providing a barrier against pathogens. Both these effects could contribute to impair colonization resistance, increasing the host susceptibility to wild type S. Typhimurium colonization. In contrast, the attenuated S. Typhimurium, which is characterized by a reduced ability to colonize the intestine, and by a very mild inflammatory response, was unable to successfully sustain competition with the microbiota.

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

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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.

Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

Science.gov (United States)

Jansen, Anne M L; Geilenkirchen, Marije A; van Wezel, Tom; Jagmohan-Changur, Shantie C; Ruano, Dina; van der Klift, Heleen M; van den Akker, Brendy E W M; Laros, Jeroen F J; van Galen, Michiel; Wagner, Anja; Letteboer, Tom G W; Gómez-García, Encarna B; Tops, Carli M J; Vasen, Hans F; Devilee, Peter; Hes, Frederik J; Morreau, Hans; Wijnen, Juul T

2016-01-01

Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

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)

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

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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.

Antimicrobial resistances do not affect colonization parameters of intestinal E. coli in a small piglet group

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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

Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development.

Science.gov (United States)

Fung, Camille M; White, Jessica R; Brown, Ashley S; Gong, Huiyu; Weitkamp, Jörn-Hendrik; Frey, Mark R; McElroy, Steven J

2016-01-01

Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.

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

Giant polypoid gastric heterotopia in the small intestine in a boy: A case report and literature review.

Science.gov (United States)

Cai, Jing; Yu, Haibo

2017-01-01

Heterotopic gastric mucosa has been described at various locations of the body; however, the polyp composed of heterotopic gastric mucosa in the small intestine is rare. A 15-year-old boy visited us for investigation of recurrent episodes of melena. Capsule endoscopy (CE) revealed a polypoid tumor in the ileum, with an active nearby hemorrhage. Contrast-enhanced computed tomography (CECT) showed a tumor in the right quadrant of the abdomen, with a diameter of about 18 × 14 mm. The patient was diagnosed with polypoid gastric heterotopia. We performed an operation to resect the lesion. The patient recovered smoothly after surgery and was discharged on postoperative day 7 and followed up for 3 months. He has not experienced gastrointestinal intestinal (GI) symptoms up to now. Giant polypoid gastric heterotopia in the small intestine is extremely rare, which can express as an occasional finding with or without symptoms. Surgical resection is the preferred therapy when symptoms appear.

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

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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)

A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

Science.gov (United States)

Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A

2017-04-11

Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .

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

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Lianjun Yang

2016-12-01

Full Text Available 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.

Steroid hormones as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

Science.gov (United States)

Tutton, P J; Barkla, D H

1988-01-01

Glucocorticoid and mineralocorticoid receptors are present in normal epithelial cells of both the small and large intestine and there have also been contentious reports of androgen, oestrogen and progesterone receptors in the epithelium of the normal large intestine. The majority of reports suggest that stimulation of the intestinal glucocorticoid receptors results in increased proliferation of epithelial cells in the small bowel, as does stimulation of androgen receptors and possibly mineralocorticoid receptors. The proliferative response of the normal intestine to oestrogens is difficult to evaluate and that to progestigens appears not to have been reported. Epidemiological studies reveal a higher incidence of bowel cancer in premenopausal women than in men of the same age and yet there is a lower incidence of these tumors in women of higher parity. These findings have been atributted to a variety of non-epithelial gender characteristic such as differences in bile metabolism, colonic bacterial and fecal transit times. In experimental animals, androgens have also been shown to influence carcinogenesis and this could well be attributed to changes in food intake etc. However, many studies have now revealed steroid hormone receptors on colorectal tumor cells and thus a direct effect of the steroid hormones on the epithelium during and after malignant transformation must now be considered.

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

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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.)

Location and pathogenic potential of Blastocystis in the porcine intestine.

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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

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

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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.

Pathogenicity of porcine intestinal spirochetes in gnotobiotic pigs.

Science.gov (United States)

Neef, N A; Lysons, R J; Trott, D J; Hampson, D J; Jones, P W; Morgan, J H

1994-06-01

Twelve intestinal spirochete strains of porcine origin were characterized on the basis of their phenotypic properties, by multilocus enzyme electrophoresis, and by pathogenicity testing in gnotobiotic pigs. The spirochetes used included two strains of Serpulina hyodysenteriae (B204 and P18A), two strains of Serpulina innocens (B256 and 4/71), one strain from the proposed new genus and species "Anguillina coli" (P43/6/78), and seven non-S. hyodysenteriae strains recently isolated from United Kingdom pig herds with a history of nonspecific diarrhea and typhlocolitis. By multilocus enzyme electrophoresis, five of these were identified as S. innocens, one was identified as an unspecified Serpulina sp., and one was identified as "A. coli." S. hyodysenteriae B204 and P18A, "A. coli" P43/6/78 and 2/7, and three (22/7, P280/1, and 14/5) of the five S. innocens field isolates induced mucoid feces and typhlocolitis in gnotobiotic pigs. None of the other spirochetes produced clinical signs or large intestinal pathology in this model. The "A. coli" strains induced a more watery diarrhea, with lesions present more proximally in the large intestine, than did the other pathogenic spirochetes. S. innocens 22/7 was also tested for pathogenicity in hysterotomy-derived pigs that had previously been artificially colonized with a spirochete-free intestinal flora and shown to be susceptible to swine dysentery. Despite effective colonization, strain 22/7 did not produce any disease, nor was there any exacerbation of large intestinal pathology or clinical signs when pigs with an experimentally induced existing colitis caused by Yersinia pseudotuberculosis were superinfected with strain 22/7. Certain non-S. hyodysenteriae spirochetes are therefore capable of inducing disease in gnotobiotic pigs, but their role as primary or opportunistic pathogens in conventional pigs remains equivocal.

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

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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

High Frequency of Interactions between Lung Cancer Susceptibility Genes in the Mouse : Mapping of Sluc5 to Sluc14

NARCIS (Netherlands)

Fijneman, Remond J.A.; Jansen, Ritsert C.; Valk, Martin A. van der; Demant, Peter

1998-01-01

Although several genes that cause monogenic familial cancer syndromes have been identified, susceptibility to sporadic cancer remains unresolved. Animal experiments have demonstrated multigenic control of tumor susceptibility. Recently, we described four mouse lung cancer susceptibility (Sluc) loci,

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 - Genetics ; Molecular Biology

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

African Journals Online (AJOL)

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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 ...

Analyses of susceptibility to radiation-induced tumors: Prkdc, a candidate modifier of lymphomas

International Nuclear Information System (INIS)

Mori, Nobuko; Okumoto, Masaaki; Nakao, Ren

2003-01-01

BALB/cHeA (BALB/c) mice are susceptible to radiation-induced lymphomas, while STS/A (STS) mice are resistant. To analyze the difference in susceptibility between these two strains of mice, we have performed 3 independent studies: 1) mapping of apoptosis susceptibility gene Rapopl (chromosome 16) and identification of Prkdc as a candidate modifier of apoptosis as well as lymphomas, 2) analysis of congenic lines for Lyr, a gene responsible for the lymphoma resistance of STS mice on chromosome 4, 3) genetic analyses of lymphoma susceptibility using a backcross [(BALB/c x STS)F 1 x STS]. Analysis of Rapopl congenic lines indicated a minor contribution of the STS allele at the Rapopl (Prkdc) locus to the lymphoma resistance of STS mice. On the other hand, homozygous STS alleles at Lyr had a substantial, but less potent, effect on radiation lymphomagenesis. Furthermore, there was no single marker where the potent resistance of the STS mice was achieved with the homozygous STS alleles. These results suggest potential involvement of another loci in the resistance of STS mice. (author)

Primary malignant small bowel tumor

Energy Technology Data Exchange (ETDEWEB)

Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk [Kosin College, Pusan (Korea, Republic of)

1990-07-15

Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings.

Primary malignant small bowel tumor

International Nuclear Information System (INIS)

Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

1990-01-01

Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings

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

International Nuclear Information System (INIS)

Kitahara, Shinzo; Shirakura, Tatsuya; Kanemitsu, Hiroyuki; Shimada, Nagato; Nonaka, Kyoei; Hashimura, Chiaki; Shiba, Tadaaki; Tsugu, Yukio

1997-01-01

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)

Analysis of the intestinal lumen microbiota in an animal model of colorectal cancer.

Directory of Open Access Journals (Sweden)

Qingchao Zhu

Full Text Available Recent reports have suggested that multiple factors such as host genetics, environment and diet can promote the progression of healthy mucosa towards sporadic colorectal carcinoma. Accumulating evidence has additionally associated intestinal bacteria with disease initiation and progression. In order to examine and analyze the composition of gut microbiota in the absence of confounding influences, we have established an animal model of 1, 2-dimethylhydrazine (DMH-induced colon cancer. Using this model, we have performed pyrosequencing of the V3 region of the 16S rRNA genes in this study to determine the diversity and breadth of the intestinal microbial species. Our findings indicate that the microbial composition of the intestinal lumen differs significantly between control and tumor groups. The abundance of Firmicutes was elevated whereas the abundance of Bacteroidetes and Spirochetes was reduced in the lumen of CRC rats. Fusobacteria was not detected in any of the healthy rats and there was no significant difference in observed Proteobacteria species when comparing the bacterial communities between our two groups. Interestingly, the abundance of Proteobacteria was higher in CRC rats. At the genus level, Bacteroides exhibited a relatively higher abundance in CRC rats compared to controls (14.92% vs. 9.22%, p<0.001. Meanwhile, Prevotella (55.22% vs. 26.19%, Lactobacillus (3.71% vs. 2.32% and Treponema (3.04% vs. 2.43%, were found to be significantly more abundant in healthy rats than CRC rats (p<0.001, respectively. We also demonstrate a significant reduction of butyrate-producing bacteria such as Roseburia and Eubacterium in the gut microbiota of CRC rats. Furthermore, a significant increase in Desulfovibrio, Erysipelotrichaceae and Fusobacterium was also observed in the tumor group. A decrease in probiotic species such as Ruminococcus and Lactobacillus was likewise observed in the tumor group. Collectively, we can conclude that a significant

Esophageal Gastrointestinal Stromal Tumors Presenting as Mediastinal Mass

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M. Kafeel

2013-11-01

Full Text Available Gastrointestinal stromal tumors (GISTs are the most common mesenchymal tumors of the gastrointestinal tract and are predominant in the stomach and intestine but rare in the esophagus. Here, we report a case of esophageal GIST which presented as a mediastinal mass on chest X-ray and dyspnea. The case was initially diagnosed as leiomyosarcoma, which could create a diagnostic dilemma. Therefore, recognizing this uncommon presentation as a mediastinal mass with esophageal GIST is important in the differential diagnosis.

The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.

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Ron Firestein

2008-04-01

Full Text Available Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD(+-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR, a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a beta-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates beta-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of beta-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of beta-catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in beta-catenin-driven malignancies.

A case of endometrioid adenocarcinoma originating from the serous surface of the small intestine

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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.

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 ...

Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

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Tao Cui

Full Text Available BACKGROUND: Small intestine neuroendocrine tumors (SI-NETs belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2 as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. METHODOLOGY/PRINCIPAL FINDINGS: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC, to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. CONCLUSION: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA for the risk of recurrence after radical operation of these tumors.

Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

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Cui, Tao; Hurtig, Monica; Elgue, Graciela; Li, Su-Chen; Veronesi, Giulia; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Pelosi, Giuseppe; Alimohammadi, Mohammad; Öberg, Kjell; Giandomenico, Valeria

2010-12-30

Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

Intestinal Cancer

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... 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 ...

Postmenopausal intestinal obstructive endometriosis: case report and review of the literature

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Pedro Popoutchi

Full Text Available CONTEXT: Endometriosis is characterized by the presence of endometrial tissue outside the uterine cavity, which is commonly detected in gynecological practice but rarely reported as a coloproctological disorder. The objective of the present report was to discuss a rare case of postmenopausal intestinal endometriosis simulating a malignant lesion, following a review of the literature. CASE REPORT: A 74-year-old woman with complaints of hematochezia and tenesmus of two months' duration accompanied by liquid feces and pelvic pain, but with no other gastrointestinal or gynecological complaints, was referred to our service. She had been menopausal for 22 years, with no hormone replacement treatment, and had undergone panhysterectomy three years before the referral to us, due to endometrial thickening and a right adnexal cyst. Five months before this referral, she had undergone laparotomy due to acute obstructive abdomen, which revealed a tumor mass involving the small bowel. Anatomopathological examination of the enterectomy suggested a hypothesis of intestinal endometriosis. A proctological examination was normal. Computed tomography of the pelvis revealed thickening of the rectosigmoid transition and colonoscopy revealed friable tumor formation in the rectum. A biopsy of the lesion revealed mucosal fragments of endometrial type, which led to a review of the previous anatomopathological examination. The patient underwent rectosigmoidectomy with protective transversotomy, with a good postoperative course, and anatomical examination confirmed the intestinal endometriosis. The patient subsequently suffered a stenosing recurrence of the lesion and has undergone colostomy since then.

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

Innate Lymphoid Cells in Intestinal Inflammation

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Geremia, Alessandra; Arancibia-Cárcamo, Carolina V.

2017-01-01

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an increased risk of

Innate Lymphoid Cells in Intestinal Inflammation

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Alessandra Geremia

2017-10-01

Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an

The food processing contaminant glyoxal promotes tumour growth in the multiple intestinal neoplasia (Min) mouse model.

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Svendsen, Camilla; Høie, Anja Hortemo; Alexander, Jan; Murkovic, Michael; Husøy, Trine

2016-08-01

Glyoxal is formed endogenously and at a higher rate in the case of hyperglycemia. Glyoxal is also a food processing contaminant and has been shown to be mutagenic and genotoxic in vitro. The tumourigenic potential of glyoxal was investigated using the multiple intestinal neoplasia (Min) mouse model, which spontaneously develops intestinal tumours and is susceptible to intestinal carcinogens. C57BL/6J females were mated with Min males. Four days after mating and throughout gestation and lactation, the pregnant dams were exposed to glyoxal through drinking water (0.0125%, 0.025%, 0.05%, 0.1%) or regular tap water. Female and male offspring were housed separately from PND21 and continued with the same treatment. One group were only exposed to 0.1% glyoxal from postnatal day (PND) 21. There was no difference in the number of intestinal tumours between control and treatment groups. However, exposure to 0.1% glyoxal starting in utero and at PND21 caused a significant increase in tumour size in the small intestine for male and female mice in comparison with respective control groups. This study suggests that glyoxal has tumour growth promoting properties in the small intestine in Min mice. Copyright © 2016 Norwegian Institute of Public Health. Published by Elsevier Ltd.. All rights reserved.

ROLE OF PARENTERAL NUTRITION IN ONCOLOGIC PATIENTS WITH INTESTINAL OCCLUSION AND PERITONEAL CARCINOMATOSIS.

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Aría Guerra, Eva; Cortés-Salgado, Alfonso; Mateo-Lobo, Raquel; Nattero, Lía; Riveiro, Javier; Vega-Piñero, Belén; Valbuena, Beatriz; Carabaña, Fátima; Carrero, Carmen; Grande, Enrique; Carrato, Alfredo; Botella-Carretero, José Ignacio

2015-09-01

the precise role of parenteral nutrition in the management of oncologic patients with intestinal occlusion is not well defined yet. We aimed to identify the effects of parenteral nutrition in these patients regarding prognosis. 55 patients with intestinal occlusion and peritoneal carcinomatosis were included. Parenteral nutrition aimed at 20-35 kcal/Kg/day, and 1.0 g/kg/day of amino-acids. Weight, body mass index, type of tumor, type of chemotherapy, and ECOG among others were recorded and analyzed. 69.1% of the patients had gastrointestinal tumors, 18.2% gynecologic and 12.7% others. Age was 60 ± 13y, baseline ECOG 1.5 ± 0.5 and body mass index 21.6 ± 4.3. Malnutrition was present in 85%. Survival from the start of parenteral nutrition was not significant when considering baseline ECOG (log rank = 0.593, p = 0.743), previous lines of chemotherapy (log rank = 2.117, p = 0.548), baseline BMI (log rank = 2.686, p = 0.261), or type of tumor (log rank = 2.066, p = 0.356). Survival in patients who received home parenteral nutrition after hospital discharge was higher than those who stayed in-hospital (log rank = 7.090, p = 0.008). Survival in patients who started chemotherapy during or after parenteral nutrition was higher than those who did not so (log rank = 17.316, p Parenteral nutrition in patients with advanced cancer and intestinal occlusion is safe, and in tho se who respond to chemotherapy, further administration of home parenteral nutrition together with chemotherapy may enhance prolonged survival. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

A small intestine volvulus caused by strangulation of a mesenteric lipoma: a case report.

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Kakiuchi, Yoshihiko; Mashima, Hiroaki; Hori, Naoto; Takashima, Hirotoshi

2017-03-13

An emergency department encounters a variety of cases, including rare cases of the strangulation of a mesenteric lipoma by the greater omentum band. A 67-year-old Japanese man presented with nausea, vomiting, and upper abdominal pain. There were no abnormalities detected by routine blood tests other than a slight rise in his white cell count. A contrast-enhanced computed tomography scan of his abdomen revealed a dilated intestine, a small intestine volvulus, and a well-capsulated homogeneous mass. He was suspected of having a small intestine volvulus that was affected by a mesenteric lipoma; therefore, single-port laparoscopic surgery was performed. Laparoscopy revealed a small intestine volvulus secondary to the strangulation of a mesenteric lipoma. The band and tumor were removed. He had no postoperative complications and was discharged on postoperative day 6. Although this case was an emergency, it showed that single-port laparoscopic surgery can be a safe, useful, and efficacious procedure.

Intestinal tract diseases

International Nuclear Information System (INIS)

Rozenshtraukh, L.S.

1985-01-01

Roentgenoanatomy and physiology of the small intestine are described. Indications for radiological examinations and their possibilities in the diagnosis of the small intestine diseases are considered.Congenital anomalies and failures in the small intestine development, clinical indications and diagnosis methods for the detection of different aetiology enteritis are described. Characteristics of primary malabsorption due to congenital or acquired inferiority of the small intestine, is provided. Radiological picture of intestinal allergies is described. Clinical, morphological, radiological pictures of Crohn's disease are considered in detail. Special attention is paid to the frequency of primary and secondary tuberculosis of intestinal tract. The description of clinical indications and frequency of benign and malignant tumours of the small intestine, methods for their diagnosis are given. Radiological pictures of parasitogenic and rare diseases of the small intestine are presented. Changes in the small intestine as a result of its reaction to pathological processes, developing in other organs and systems of the organism, are described

Poliovirus and other enteroviruses in children infected with intestinal parasites in Nigeria.

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Adekolujo, Daniel R; Olayinka, Suraj O; Adeniji, Johnson A; Oyeyemi, Oyetunde T; Odaibo, Alexander B

2015-10-29

Poliovirus, an enterovirus, still persists in Nigeria despite the global efforts tailored towards its eradication. This study aimed to assess the impacts of poliovirus and other enteroviruses on the susceptibility of individuals to intestinal parasite infections. A cross-sectional study on the prevalence of intestinal parasites was conducted on two-sample stool specimens of 717 Nigerian children (between 1 and 19 years of age) whose poliovirus/other enteroviruses infection status had been determined. The overall prevalence of Sabin poliovirus and other related enteroviruses infections were 6.6% and 13.8%, respectively. The prevalence of Ascaris lumbricoides was significantly higher than that of other intestinal parasites (p parasitic infection (OR = 11.7, CI = 9.2-15.0). While the prevalence of all species of parasites except S. mansoni showed no significant variations in children with Sabin poliovirus (p > 0.05), the prevalence of hookworms and Taenia spp. was significantly higher in children with other enteroviral infections (p parasites is an indication of possible association of the parasites in a more poliovirus-endemic population. A combined intervention approach for the two infections is advocated.

Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation

Science.gov (United States)

Fasano, Alessio

2008-01-01

The anatomical and functional arrangement of the gastrointestinal tract suggests that this organ, beside its digestive and absorptive functions, regulates the trafficking of macromolecules between the environment and the host through a barrier mechanism. Under physiological circumstances, this trafficking is safeguarded by the competency of intercellular tight junctions, structures whose physiological modulation is mediated by, among others, the recently described protein zonulin. To prevent harm and minimize inflammation, the same paracellular pathway, in concert with the gut-associated lymphoid tissue and the neuroendocrine network, controls the equilibrium between tolerance and immunity to nonself antigens. The zonulin pathway has been exploited to deliver drugs, macromolecules, or vaccines that normally would not be absorbed through the gastrointestinal mucosal barrier. However, if the tightly regulated trafficking of macromolecules is jeopardized secondary to prolonged zonulin up-regulation, the excessive flow of nonself antigens in the intestinal submucosa can cause both intestinal and extraintestinal autoimmune disorders in genetically susceptible individuals. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier competency. Understanding the role of zonulin-dependent intestinal barrier dysfunction in the pathogenesis of autoimmune diseases is an area of translational research that encompasses many fields. PMID:18832585

Immune Development and Intestinal Microbiota in Celiac Disease

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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.

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...

Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon

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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.

Coated metal stents installation for the treatment of malignant tumors complicated with colonic and rectal fistula

International Nuclear Information System (INIS)

Mao Aiwu; Fang Shiming; Liu Shiyi; Lin Qing; Jiang Haosheng; Jia Yiping; Gao Zhongdu

2007-01-01

Objective: To probe the clinical features of malignant colonic and rectal tumors together with coated metal stent placement. Methods: 24 cases of colonic fistula with late stage malignant tumors including 16 cases of intestinal cancer(66.7%), 2 cases of gastric and cervical cancers respectively(8.3%); 1 case of bladder, 1 case of prostate, 1 case of ovary and 1 case of gallbladder cancer(4.2%). The cause for the fistulas were direct invasion (37.5% )and radiotherapy (62.5%). The KPS was 30-60, and the median value was 40. CT were done preoperatively and followed by radiography of canulation contrast medium enema to ensure the location of the orifice of the fistula, the route of intestinal canal or complicated with obstruction and the condition with nearby tissues. Stents were finally implanted specifically according to the different situations of intestines. The sites of implanted stents and the occlusion of fistula should be strictly scrutinized; and then with careful follow up of patients complications and general condition. The procedure was carried out practically in 23 cases. Results: The successful rate of technique reached 96%(22/23), the failed one was due to the curve over sharpness of intestinal lock and resulting in non-expansion of the stent. The clinical successful rate was 91.3%. The two failed cased included the one with improper coherence to the intestinal wall leading to the stent migration and the other with a mild leakage after stent placement. The follow-up duration were 28-365 days, average 109 days, and the median value was 92 days. The average surviving period of 3 months and 6 months were 51% and 11% respectively. Conclusion: Intestinal fistula is the common complication after intestinal tumor operation and radiotherapy with poor prognosis. Metal covered stents provide a therapy of choice to improve the life quality and prolong the life span. (authors)

Granular cells Tumor in the gastrointestinal tract

International Nuclear Information System (INIS)

Castano LL, Rodrigo; Gaitan B, Maria H; Juliao E, Fabian

2005-01-01

Granular cells tumors are ubiquitous lesions in the gastrointestinal tract, are rare and asymptomatic and they are generally an incidental discovery at gastroduodenoscopy or colonoscopy. In the gastrointestinal tract they are more frequently located in the esophagus, right colon and rectum, stomach, appendix, small intestine or biliopancreatic tract. This article describes three patients with four tumors of granular cells in rectum, esophagus (2 lesions) and appendix. It becomes special emphasis in their neural origin, their benign behavior that justifies the endoscopic resections or limited surgical excisions and the necessity of a pursuit for the possibility, although little, of malignant transformation

Ageing sensitized by iPLA2β deficiency induces liver fibrosis and intestinal atrophy involving suppression of homeostatic genes and alteration of intestinal lipids and bile acids.

Science.gov (United States)

Jiao, Li; Gan-Schreier, Hongying; Zhu, Xingya; Wei, Wang; Tuma-Kellner, Sabine; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

2017-12-01

Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA 2 β is a homeostatic PLA 2 by playing a role in phospholipid metabolism and remodeling. Global iPLA 2 β -/- mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis. We hypothesize that iPLA 2 β deficiency may sensitize with ageing for an induction of GI injury. Male wild-type and iPLA 2 β -/- mice at 4 and 20-22months of age were studied. Aged, but not young, iPLA 2 β -/- mice showed increased hepatic fibrosis and biliary ductular expansion as well as severe intestinal atrophy associated with increased apoptosis, pro-inflammation, disrupted tight junction, and reduced number of mucin-containing globlet cells. This damage was associated with decreased expression of intestinal endoplasmic stress XBP1 and its regulator HNF1α, FATP4, ACSL5, bile-acid transport genes as well as nuclear receptors LXRα and FXR. By LC/MS-MS profiling, iPLA 2 β deficiency in aged mice caused an increase of intestinal arachidonate-containing phospholipids concomitant with a decrease in ceramides. By the suppression of intestinal FXR/FGF-15 signaling, hepatic bile-acid synthesis gene expression was increased leading to an elevation of secondary and hydrophobic bile acids in liver, bile, and intestine. In conclusions, ageing sensitized by iPLA 2 β deficiency caused a decline of key intestinal homeostatic genes resulting in the development of GI disease in a gut-to-liver manner. Copyright © 2017 Elsevier B.V. All rights reserved.

The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse

NARCIS (Netherlands)

Merlos-Suarez, A.; Barriga, F.M.; Jung, P.; Iglesias, M.; Cespedes, M.V.; Rossell, D.; Sevillano, M.; Hernando-Momblona, X.; da Silva-Diz, V.; Munoz, P.; Clevers, H.; Sancho, E.; Mangues, R.; Batlle, E.

2011-01-01

A frequent complication in colorectal cancer (CRC) is regeneration of the tumor after therapy. Here, we report that a gene signature specific for adult intestinal stem cells (ISCs) predicts disease relapse in CRC patients. ISCs are marked by high expression of the EphB2 receptor, which becomes

Intestinal Surgery.

Science.gov (United States)

Desrochers, André; Anderson, David E

2016-11-01

A wide variety of disorders affecting the intestinal tract in cattle may require surgery. Among those disorders the more common are: intestinal volvulus, jejunal hemorrhage syndrome and more recently the duodenal sigmoid flexure volvulus. Although general principles of intestinal surgery can be applied, cattle has anatomical and behavior particularities that must be known before invading the abdomen. This article focuses on surgical techniques used to optimize outcomes and discusses specific disorders of small intestine. Diagnoses and surgical techniques presented can be applied in field conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila.

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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.

Voluntary exercise inhibits intestinal tumorigenesis in ApcMin/+ mice and azoxymethane/dextran sulfate sodium-treated mice

International Nuclear Information System (INIS)

Ju, Jihyeung; Nolan, Bonnie; Cheh, Michelle; Bose, Mousumi; Lin, Yong; Wagner, George C; Yang, Chung S

2008-01-01

Epidemiological studies suggest that physical activity reduces the risk of colon cancer in humans. Results from animal studies, however, are inconclusive. The present study investigated the effects of voluntary exercise on intestinal tumor formation in two different animal models, Apc Min/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. In Experiments 1 and 2, five-week old female Apc Min/+ mice were either housed in regular cages or cages equipped with a running wheel for 6 weeks (for mice maintained on the AIN93G diet; Experiment 1) or 9 weeks (for mice on a high-fat diet; Experiment 2). In Experiment 3, male CF-1 mice at 6 weeks of age were given a dose of AOM (10 mg/kg body weight, i.p.) and, 12 days later, 1.5% DSS in drinking fluid for 1 week. The mice were then maintained on a high-fat diet and housed in regular cages or cages equipped with a running wheel for 16 weeks. In the Apc Min/+ mice maintained on either the AIN93G or the high-fat diet, voluntary exercise decreased the number of small intestinal tumors. In the AOM/DSS-treated mice maintained on a high-fat diet, voluntary exercise also decreased the number of colon tumors. In Apc Min/+ mice, voluntary exercise decreased the ratio of serum insulin like growth factor (IGF)-1 to IGF binding protein (BP)-3 levels. It also decreased prostaglandin E 2 and nuclear β-catenin levels, but increased E-cadherin levels in the tumors. These results indicate hat voluntary exercise inhibited intestinal tumorigenesis in Apc Min/+ mice and AOM/DSS-treated mice, and the inhibitory effect is associated with decreased IGF-1/IGFBP-3 ratio, aberrant β-catenin signaling, and arachidonic acid metabolism

Possibilities of Correction and Prophylaxis of Intestinal Microbiocenosis Disorders in Frequently Ill Children

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A. N. Surkov

2013-01-01

Full Text Available Frequently and protractedly ill children constitute a special for pediatricians group of patients. Acute respiratory infections with severe and frequently relapsing course badly affect children’s health and contribute to the decrease of the functional activity of the immune system. Risk factors of the high prevalence of acute respiratory infections are changes in the immune responses at the background of unfavorable ante- and perinatal conditions, numerous contacts with potential causative agents at the beginning of attendance of infant schools, widespread intra- and inter-family contacts as well as susceptibility to Th2 immune response (allergy and prolonged course of inflammatory process. Etiotropic treatment of acute respiratory infections often includes antibacterial drugs, which, however, have negative effects on intestinal microflora, such as dyspeptic syndrome and antibiotic-induced diarrhea. Intestinal dysbiosis affects homeostasis, leads to significant changes in functional activity of various organs and systems. That is why correction and prophylaxis of intestinal dysbacteriosis is very important in pediatric practice. In this article the main data on epidemiology, pathogenesis, forms, clinical manifestation, diagnostics and treatment of antibiotic-induced diarrhea in children.

Intermittent fasting promotes bacterial clearance and intestinal IgA production in Salmonella typhimurium-infected mice.

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Godínez-Victoria, M; Campos-Rodriguez, R; Rivera-Aguilar, V; Lara-Padilla, E; Pacheco-Yepez, J; Jarillo-Luna, R A; Drago-Serrano, M E

2014-05-01

The impact of intermittent fasting versus ad libitum feeding during Salmonella typhimurium infection was evaluated in terms of duodenum IgA levels, bacterial clearance and intestinal and extra-intestinal infection susceptibility. Mice that were intermittently fasted for 12 weeks or fed ad libitum were infected with S. typhimurium and assessed at 7 and 14 days post-infection. Next, we evaluated bacterial load in the faeces, Peyer's patches, spleen and liver by plate counting, as well as total and specific intestinal IgA and plasmatic corticosterone levels (by immunoenzymatic assay) and lamina propria IgA levels in plasma cells (by cytofluorometry). Polymeric immunoglobulin receptor, α- and J-chains, Pax-5 factor, pro-inflammatory cytokine (tumour necrosis factor-α and interferon-γ) and anti-inflammatory cytokine (transforming growth factor-β) mRNA levels were assessed in mucosal and liver samples (by real-time PCR). Compared with the infected ad libitum mice, the intermittently fasted infected animals had (1) lower intestinal and systemic bacterial loads; (2) higher SIgA and IgA plasma cell levels; (3) higher mRNA expression of most intestinal parameters; and (4) increased or decreased corticosterone levels on day 7 and 14 post-infection, respectively. No contribution of liver IgA was observed at the intestinal level. Apparently, the changes following metabolic stress induced by intermittent fasting during food deprivation days increased the resistance to S. typhimurium infection by triggering intestinal IgA production and presumably, pathogen elimination by phagocytic inflammatory cells. © 2014 John Wiley & Sons Ltd.

Fbxw7-associated drug resistance is reversed by induction of terminal differentiation in murine intestinal organoid culture

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Federica Lorenzi

2016-01-01

Full Text Available Colorectal cancer (CRC is one of the top three cancer-related causes of death worldwide. FBXW7 is a known tumor-suppressor gene, commonly mutated in CRC and in a variety of other epithelial tumors. Low expression of FBXW7 is also associated with poor prognosis. Loss of FBXW7 sensitizes cancer cells to certain drugs, while making them more resistant to other types of chemotherapies. However, is not fully understood how epithelial cells within normal gut and primary tumors respond to potential cancer therapeutics. We have studied genetically engineered mice in which the fbxw7 gene is conditionally knocked-out in the intestine (fbxw7ΔG. To further investigate the mechanism of Fbxw7-action, we grew intestinal crypts from floxed-fbxw7 (fbxw7fl/fl and fbxw7ΔG mice, in a Matrigel-based organoid (mini-gut culture. The fbxw7ΔG organoids exhibited rapid budding events in the crypt region. Furthermore, to test organoids for drug response, we exposed day 3 intestinal organoids from fbxw7fl/fl and fbxw7ΔG mice, to various concentrations of 5-fluorouracil (5-FU for 72 hours. 5-FU triggers phenotypic differences in organoids including changing shape, survival, resistance, and death. 5-FU however, rescues the drug-resistance phenotype of fbxw7ΔG through the induction of terminal differentiation. Our results support the hypothesis that a differentiating therapy successfully targets FBXW7-mutated CRC cells.

Impact of Intestinal Microbiota on Intestinal Luminal Metabolome

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Matsumoto, Mitsuharu; Kibe, Ryoko; Ooga, Takushi; Aiba, Yuji; Kurihara, Shin; Sawaki, Emiko; Koga, Yasuhiro; Benno, Yoshimi

2012-01-01

Low–molecular-weight metabolites produced by intestinal microbiota play a direct role in health and disease. In this study, we analyzed the colonic luminal metabolome using capillary electrophoresis mass spectrometry with time-of-flight (CE-TOFMS) —a novel technique for analyzing and differentially displaying metabolic profiles— in order to clarify the metabolite profiles in the intestinal lumen. CE-TOFMS identified 179 metabolites from the colonic luminal metabolome and 48 metabolites were present in significantly higher concentrations and/or incidence in the germ-free (GF) mice than in the Ex-GF mice (p metabolome and a comprehensive understanding of intestinal luminal metabolome is critical for clarifying host-intestinal bacterial interactions. PMID:22724057

Small Intestine Disorders

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... 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.

Paraneoplastic hypereosinophilia in a dog with intestinal T-cell lymphoma.

Science.gov (United States)

Marchetti, Veronica; Benetti, Cecilia; Citi, Simona; Taccini, Valentina

2005-09-01

A 9-year-old, intact male Doberman Pinscher was examined because of anorexia and weakness. Results of a CBC showed severe, microcytic, hypochromic anemia with mild eosinophilia (2944 cells/microL, reference interval 100-1250/microL) and thrombocytosis. Hypoferremia, hypoferritinemia, and a positive fecal occult blood test supported a diagnosis of iron deficiency anemia secondary to chronic intestinal hemorrhage. Abdominal ultrasound evaluation showed a thickened small intestinal loop, of which representative specimens were obtained during exploratory laparotomy. Histologically, the intestinal wall was infiltrated by a neoplastic population of large, round, lymphoid cells with vesicular chromatin, 1 or more prominent nucleoli, and a high number of mitotic figures. The cells were closely admixed with mature eosinophils, but were negative for metachromatic granules with toluidine blue. Immunohistochemically, tumor cells were positive for CD3, and negative for CD21, Pan B, and CD79a. A diagnosis of intestinal T-cell lymphoma was made. Chemotherapy was begun, with 30 mg/m;2 of doxorubicin administered intravenously every 3 weeks. Eosinophil concentration was 880/microL 2 weeks after surgery (on day 15 after presentation) but increased markedly to 62,914/microL on day 30, 62,400/microL on day 37, and 39,444/microL on day 58 after presentation. An association between hypereosinophilia and T-cell lymphoma is well established in human patients, in whom production of IL-5 by neoplastic T cells has been demonstrated. Hypereosinophilia has been reported only rarely with intestinal lymphoma in cats and horses, and with T-cell lymphoma in dogs.

Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

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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.

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

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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

The association between miR-499 polymorphism and cancer susceptibility: a meta-analysis

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Xu Z

2015-08-01

Full Text Available Zhongfei Xu, Enjiao Zhang, Weiyi Duan, Changfu Sun, Shuang Bai, Xuexin Tan Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, People’s Republic of China Background: MicroRNAs are a class of new noncoding RNA that play important roles in the pathogenesis of tumor. Rs3746444 in miR-499 is suggested to be associated with cancer susceptibility. In the present study, we assess the association between miR-499 rs3746444 polymorphism and cancer susceptibility through a meta-analysis. Methods: We searched relevant articles from the PubMed and Embase databases. We screened all the resulting articles for adherence to the inclusion and exclusion criteria. The associations between miR-499 polymorphism and cancer susceptibility were estimated by computing the odds ratios (ORs and 95% confidence intervals (CIs. All analyses were performed using Stata software. Results: There are 18 datasets included in the analysis. Statistically significant associations were found between the miR-499 rs3746444 polymorphism and susceptibility to cancer (GG versus AA: OR =1.24, 95% CI: 1.01–1.52; G versus A: OR =1.11, 95% CI: 1.01–1.23. A subsequent analysis, on the basis of ethnicity for the population characteristic, showed that Asians had increased susceptibility to cancer (GG versus AA: OR =1.32, 95% CI: 1.09–1.59; GG + AG versus AA: OR = 1.17, 95% CI: 1.01–1.37. In the subgroup analysis of tumor type, none of the genetic models had statistically significant results. The meta-regression suggested that race and cancer types are not the source of heterogeneity in the present meta-analysis. No publication bias was detected by either the inverted funnel plot or Egger’s test. Conclusion: Rs3746444 in miR-499 might be related to susceptibility to cancer. Keywords: microRNA, single-nucleotide polymorphism, tumor, risk factor

A case of chemotherapy-resistant intestinal-type sinonasal adenocarcinoma treated by gamma knife radiosurgery

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Andres M. Alvarez-Pinzon, M.D., Ph.D.

2017-12-01

Full Text Available Intestinal type sinonasal adenocarcinomas are a rare malignancy of the nasal cavity and paranasal sinuses ascending in the nasal cavity are particularly unusual. We report an infrequent case of an Intestinal sinonasal adenocarcinoma from the left lateral nasal wall. A 60-year-old Hispanic male complained of complete progressive nasal obstruction and epistaxis for 8 months. A nasal endoscopic exam displayed a prominent enlargement, which remained in connection with the anterior part of left inferior turbinate. Computed tomography revealed a medium-defined, soft tissue dense lesion in the left anterior nasal cavity. Mass biopsy histology confirmed a low grade differentiate Intestinal type sinonasal adenocarcinomas. The patient underwent 8 cycles of chemotherapy including paclitaxel, platinol and fluorouracil. According to the medical records, the patient responded well to the chemotherapy treatment until about six cycles. When a follow up CT scan showed tumor growth, the patient was placed on Doxorubicin but developed toxicity. The main treatment modality is surgical resection with histological clear margins but concerning the low differentiation, low response of chemotherapy, and surgical risk we offered an option with gamma knife radiosurgery. In our case, the patient demonstrated satisfactory relief of symptoms and reported the ability to breathe through the nose. 80% of tumor resolution was observed in 1 month following the CT scan.

Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response

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Asha Jayakumar

2017-08-01

Full Text Available Intestinal tumorigenesis in the ApcMin/+ model is initiated by aberrant activation of Wnt pathway. Increased IL-4 expression in human colorectal cancer tissue and growth of colon cancer cell lines implied that IL-4–induced Stat6-mediated tumorigenic signaling likely contributes to intestinal tumor progression in ApcMin/+ mice. Stat6 also appears to promote expansion of myeloid-derived suppressor cells (MDSCs cells. MDSCs promote polyp formation in the ApcMin/+ model. Hence, Stat6 could have a broad role in coordinating both polyp cell proliferation and MDSC expansion. We found that IL-4–induced Stat6-mediated proliferation of intestinal epithelial cells is augmented by platelet-derived growth factor–BB, a tumor-promoting growth factor. To determine whether polyp progression in ApcMin/+ mice is dependent on Stat6 signaling, we disrupted Stat6 in this model. Total polyps in the small intestine were fewer in ApcMin/+ mice lacking Stat6. Furthermore, proliferation of polyp epithelial cells was reduced, indicating that Stat6 in part controlled polyp formation. Stat6 also promoted expansion of MDSCs in the spleen and lamina propria of ApcMin/+ mice, implying regulation of antitumor T-cell response. More CD8 cells and reduced PD-1 expression on CD4 cells correlated with reduced polyps. In addition, a strong CD8-mediated cytotoxic response led to killing of tumor cells in Stat6-deficient ApcMin/+ mice. Therefore, these findings show that Stat6 has an oncogenic role in intestinal tumorigenesis by promoting polyp cell proliferation and immunosuppressive mediators, and preventing an active cytotoxic process.

Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response.

Science.gov (United States)

Jayakumar, Asha; Bothwell, Alfred L M

2017-08-01

Intestinal tumorigenesis in the ApcMin/+ model is initiated by aberrant activation of Wnt pathway. Increased IL-4 expression in human colorectal cancer tissue and growth of colon cancer cell lines implied that IL-4-induced Stat6-mediated tumorigenic signaling likely contributes to intestinal tumor progression in ApcMin/+ mice. Stat6 also appears to promote expansion of myeloid-derived suppressor cells (MDSCs) cells. MDSCs promote polyp formation in the ApcMin/+ model. Hence, Stat6 could have a broad role in coordinating both polyp cell proliferation and MDSC expansion. We found that IL-4-induced Stat6-mediated proliferation of intestinal epithelial cells is augmented by platelet-derived growth factor-BB, a tumor-promoting growth factor. To determine whether polyp progression in ApcMin/+ mice is dependent on Stat6 signaling, we disrupted Stat6 in this model. Total polyps in the small intestine were fewer in ApcMin/+ mice lacking Stat6. Furthermore, proliferation of polyp epithelial cells was reduced, indicating that Stat6 in part controlled polyp formation. Stat6 also promoted expansion of MDSCs in the spleen and lamina propria of ApcMin/+ mice, implying regulation of antitumor T-cell response. More CD8 cells and reduced PD-1 expression on CD4 cells correlated with reduced polyps. In addition, a strong CD8-mediated cytotoxic response led to killing of tumor cells in Stat6-deficient ApcMin/+ mice. Therefore, these findings show that Stat6 has an oncogenic role in intestinal tumorigenesis by promoting polyp cell proliferation and immunosuppressive mediators, and preventing an active cytotoxic process. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review

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Navid Kashaninejad

2016-07-01

Full Text Available With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1 Lung; (2 Bone marrow; (3 Brain; (4 Breast; (5 Urinary system (kidney, bladder and prostate; (6 Intestine; and (7 Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart–liver–intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET of

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

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

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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.

Tumor of small bowel

International Nuclear Information System (INIS)

Ruiz Lobo, Elmer Jair; Rubio Vargas, Romulo; Cecilia Hani, Albis

2009-01-01

Young woman who is having episodes of overt obscure gastrointestinal bleeding that requires transfusions. The endoscopic study consists of 2 endoscopies of the upper digestive system and two colonoscopies. The tests do not find the cause of the digestive hemorrhage. A double-balloon enteroscopy is performed and it is found that the Ileum has an ulcerate subepithelial lesion with neoplasia appearance which is marked with Chinese ink and biopsies are taken from the tissue which are not diagnosed. Studies of staging are performed ant the result is negative. A laparotomy is performed for diagnosis and treatment which includes the intestinal resection of ileum where the tumor is placed. The result of the test shows to be a neuroendocrine carcinoma of high degree of large cells undifferentiated. One appears in addition a revision to overt obscure gastrointestinal bleeding and neuroendocrine tumor of small

Combined IL-12 receptor and IgA deficiency in an adult man intestinally infested by an unknown, non-cultivable mycobacterium

DEFF Research Database (Denmark)

Schejbel, L; Rasmussen, E M; Kemp, Helle Bruunsgaard

2011-01-01

deficiencies could promote illness. Even though the IgA deficiency in itself does not predispose to mycobacterial disease, the lack of secreted IgA may have disturbed the intestinal homoeostasis and increased the susceptibility to the low-virulent mycobacterium that the patient was not able to clear because...

MR imaging of the gastro-intestinal tract in children

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Hoermann, Marcus [Medical University of Vienna/General Hospital, Department of General and Paediatric Radiology, Waehringerguertel 18-20, A-1090 Vienna (Austria)], E-mail: marcus.hoermann@meduniwien.ac.at

2008-11-15

MR imaging (MRI) is an established method for the evaluation of particularly inflammatory bowel disease in adults, as well as for acute abdominal pain in pregnant women. Despite the fact that MRI is ideally suited for the evaluation of children the method is still not established in these patients. The value of MRI in Crohn's disease, ulcerative colitis and appendicitis as well as intestinal tumors and malformations has been documented in children. There will be more indications in the future depending on the development of new imaging techniques, faster sequences, stronger gradients and increasing availability. Furthermore, the radiologist's attention must be drawn to decrease the radiation burden in children and to replace ionizing techniques especially in chronic disease with the need for repeated follow-up studies and in younger children. This review will discuss some general considerations for the use of MRI in evaluating the paediatric gastro-intestinal tract.

Human cerebral blood volume measurements using dynamic contrast enhancement in comparison to dynamic susceptibility contrast MRI

Energy Technology Data Exchange (ETDEWEB)

Artzi, Moran [Tel Aviv Sourasky Medical Center, Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Liberman, Gilad; Vitinshtein, Faina; Aizenstein, Orna [Tel Aviv Sourasky Medical Center, Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv (Israel); Nadav, Guy [Tel Aviv Sourasky Medical Center, Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv (Israel); Tel Aviv University, Faculty of Engineering, Tel Aviv (Israel); Blumenthal, Deborah T.; Bokstein, Felix [Tel Aviv Sourasky Medical Center, Neuro-Oncology Service, Tel Aviv (Israel); Bashat, Dafna Ben [Tel Aviv Sourasky Medical Center, Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv (Israel); Tel Aviv University, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv (Israel)

2015-07-15

Cerebral blood volume (CBV) is an important parameter for the assessment of brain tumors, usually obtained using dynamic susceptibility contrast (DSC) MRI. However, this method often suffers from low spatial resolution and high sensitivity to susceptibility artifacts and usually does not take into account the effect of tissue permeability. The plasma volume (v{sub p}) can also be extracted from dynamic contrast enhancement (DCE) MRI. The aim of this study was to investigate whether DCE can be used for the measurement of cerebral blood volume in place of DSC for the assessment of patients with brain tumors. Twenty-eight subjects (17 healthy subjects and 11 patients with glioblastoma) were scanned using DCE and DSC. v{sub p} and CBV values were measured and compared in different brain components in healthy subjects and in the tumor area in patients. Significant high correlations were detected between v{sub p} and CBV in healthy subjects in the different brain components; white matter, gray matter, and arteries, correlating with the known increased tissue vascularity, and within the tumor area in patients. This work proposes the use of DCE as an alternative method to DSC for the assessment of blood volume, given the advantages of its higher spatial resolution, its lower sensitivity to susceptibility artifacts, and its ability to provide additional information regarding tissue permeability. (orig.)

Intestinal Parasites in Children from a Day Care Centre in Matanzas City, Cuba

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Cañete, Roberto; Díaz, Mariuska Morales; Avalos García, Roxana; Laúd Martinez, Pedro Miguel; Manuel Ponce, Félix

2012-01-01

Background Intestinal parasitic infections are widely distributed throughout the world and children are the most affected population. Day care centres are environments where children have proven to be more susceptible to acquiring IP. Methods and Principal Findings A cross-sectional study was carried to determine the prevalence of intestinal parasites in stool samples among children who attend to a day care centre in an urban area of Matanzas city, Cuba, from March to June 2012. 104 children under five years old were included on the study after informed consent form was signed by parents or legal guardians. Three fresh faecal samples were collected from each child in different days and were examined by direct wet mount, formalin-ether, and Kato- Katz techniques. Data relating to demography, socioeconomic status, source of drinking water, and personal hygiene habits were also collected using a standardized questionnaire. In total, 71.1% of children harbored at least one type of intestinal parasite and 47 (45.2%) were infected by more than one species. Giardia duodenalis and Blastocystis sp. were the most common parasites found, with prevalence rates of 54.8% and 38.5% respectively. Conclusions Despite public health campaigns, improvement in the level of education, and the availability of and access to medical services in Cuba infections by intestinal protozoan is high in this centre. Almost nothing is published regarding intestinal parasites in Matanzas province during the last 40 years so this work could also be the initial point to carry out other studies to clarify the IP status in this region. PMID:23236493

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

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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.

Multi-level interactions between the nuclear receptor TRα1 and the WNT effectors β-catenin/Tcf4 in the intestinal epithelium.

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Maria Sirakov

Full Text Available Intestinal homeostasis results from complex cross-regulation of signaling pathways; their alteration induces intestinal tumorigenesis. Previously, we found that the thyroid hormone nuclear receptor TRα1 activates and synergizes with the WNT pathway, inducing crypt cell proliferation and promoting tumorigenesis. Here, we investigated the mechanisms and implications of the cross-regulation between these two pathways in gut tumorigenesis in vivo and in vitro. We analyzed TRα1 and WNT target gene expression in healthy mucosae and tumors from mice overexpressing TRα1 in the intestinal epithelium in a WNT-activated genetic background (vil-TRα1/Apc mice. Interestingly, increased levels of β-catenin/Tcf4 complex in tumors from vil-TRα1/Apc mice blocked TRα1 transcriptional activity. This observation was confirmed in Caco2 cells, in which TRα1 functionality on a luciferase reporter-assay was reduced by the overexpression of β-catenin/Tcf4. Moreover, TRα1 physically interacted with β-catenin/Tcf4 in the nuclei of these cells. Using molecular approaches, we demonstrated that the binding of TRα1 to its DNA target sequences within the tumors was impaired, while it was newly recruited to WNT target genes. In conclusion, our observations strongly suggest that increased β-catenin/Tcf4 levels i correlated with reduced TRα1 transcriptional activity on its target genes and, ii were likely responsible for the shift of TRα1 binding on WNT targets. Together, these data suggest a novel mechanism for the tumor-promoting activity of the TRα1 nuclear receptor.

Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated in Taiwan.

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Yeh, Jih-Ching; Lo, Dan-Yuan; Chang, Shao-Kuang; Kuo, Hung-Chih

2018-03-13

Some members of the Brachyspira genus cause diseases such as swine dysentery (SD) and porcine intestinal (or colonic) spirochetosis. Severe economic losses are caused by decreased feed intake and increased feed conversion ratio, as well as costs associated with treatment and death. A loss of clinical efficacy of some antimicrobial agents authorized for treating SD has been observed in many countries. The aim of this study was to analyze the antimicrobial susceptibility of Brachyspira isolated from Taiwan and to investigate the mechanism of decreased susceptibility to macrolides. A total of 55 Brachyspira isolates obtained from the grower-finisher period were evaluated in this study. These isolates included B. hyodysenteriae (n = 37), B. murdochii (n = 11), B. pilosicoli (n = 5), B. intermedia (n = 1), and B. innocens (n = 1). Antimicrobial susceptibility testing was performed to examine 12 selected antimicrobial agents. The results showed that the 50% and 90% minimum inhibitory concentration (MIC) values of the tested macrolides were all >256 μg/ml. The MIC 50 of lincomycin, tiamulin, carbadox, olaquindox, ampicillin, amoxicillin, doxycycline, oxytetracycline, and gentamicin were 32, 1, ≤0.125, ≤0.125, 0.5, 0.25, 2, 2, and 2 μg/ml. The genetic basis of the decreased susceptibility to tylosin and lincomycin in Brachyspira spp. was investigated and the results showed a possible connection to the mutations at position A2058 and G2032 of the 23S rRNA gene. These findings demonstrated that, in Taiwan, there may be a decrease in susceptibility of Brachyspira spp. to antimicrobials commonly used for the treatment of SD.

Comparative transcriptomics of the nematode gut identifies global shifts in feeding mode and pathogen susceptibility.

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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.

Transformation by Oncogenic Ras Expands the Early Genomic Response to Transforming Growth Factor β in Intestinal Epithelial Cells

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Carl E. Allen

2008-10-01

Full Text Available A substantial body of evidence implicates TGFβ as a tumor promoter in epithelial cells that have become resistant to its tumor suppressor activity. To better understand early, genome-wide TGFβ responses in cells resistant to growth inhibition by TGFβ, we used microarray analysis in a well-defined cell culture system of sensitive and resistant intestinal epithelial cells. TGFβ-regulated gene expression in TGFβ-growth-sensitive, nontransformed rat intestinal epithelial cells (RIE-1 was compared to expression in TGFβ-growth-resistant RIE cells stably transformed by oncogenic Ras(12V. Treatment of RIE-1 cells with 2 ng/ml TGFβ1 for 1 hour increased the expression of eight gene sequences by 2.6-fold or more, whereas eight were down regulated 2.6-fold. In RIE-Ras(12V cells, 42 gene sequences were upregulated and only 3 were down-regulated. Comparison of RIE and RIE-Ras(12V identified 37 gene sequences as unique, Ras-dependent genomic targets of TGFβ1. TGFβ-regulation of connective tissue growth factor and vascular endothelial growth factor, two genes up-regulated in RIE-Ras cells and previously implicated in tumor promotion, was independently confirmed and further characterized by Northern analysis. Our data indicate that overexpression of oncogenic Ras in intestinal epithelial cells confers a significantly expanded repertoire of robust, early transcriptional responses to TGFβ via signaling pathways yet to be fully elucidated but including the canonical Raf-1/MAPK/Erk pathway. Loss of sensitivity to growth inhibition by TGFβ does not abrogate TGFβ signaling and actually expands the early transcriptional response to TGFβ1. Expression of some of these genes may confer to Ras-transformed cells characteristics favorable for tumor promotion.

A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

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Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

2013-05-15

The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

Intestinal Lymphangiectasia

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... Overview of Crohn Disease Additional Content Medical News Intestinal Lymphangiectasia (Idiopathic Hypoproteinemia) By Atenodoro R. Ruiz, Jr., MD, ... Overview of Malabsorption Bacterial Overgrowth Syndrome Celiac Disease Intestinal ... Intolerance Short Bowel Syndrome Tropical Sprue Whipple ...

Interactions between intestinal pathogens, enteropathy and malnutrition in developing countries.

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Prendergast, Andrew J; Kelly, Paul

2016-06-01

This review focuses on recent data highlighting the interactions between intestinal pathogens, enteropathy and malnutrition in developing countries, which drive morbidity and mortality and hinder the long-term developmental potential of children. Diarrhoea remains the second commonest cause of death in children below 5 years, and malnutrition underlies 45% of all child deaths. Even in the absence of diarrhoea, subclinical pathogen carriage and enteropathy are almost universal in developing countries. Here, we review recent studies addressing the causes and consequences of diarrhoea; emerging data on environmental influences that govern postnatal development of the gut and microbiota; current concepts of environmental enteric dysfunction; and recent intervention trials in the field. We highlight the interactions between these processes, whereby intestinal pathogens drive a cycle of gut damage, malabsorption, chronic inflammation and failed mucosal regeneration, leading to malnutrition and susceptibility to further enteric infections. Efforts to improve child survival and long-term developmental potential need to address the overlapping and interacting effects of diarrhoea, enteropathy and malnutrition. Recent insights from human and animal studies suggest potential targets for intervention.

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

A Case of Advanced Descending Colon Cancer in an Adult Patient with Intestinal Malrotation

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Yoshifumi Nakayama

2016-01-01

Full Text Available This report presents an operative case of advanced descending colon cancer in an adult patient with intestinal malrotation. A 63-year-old Japanese male was suffering from left side abdominal pain, abdominal distension, and constipation. An endoscopic examination revealed an advanced tumor in the descending colon. Computed tomography (CT of the abdomen revealed the thickening of the descending colon wall and superior mesenteric vein rotation. An opaque enema detected severe stenosis of the descending colon. An abdominal X-ray examination revealed the dilation of the colon and small intestine with niveau. At the insertion of an ileus tube, the C-loop of the duodenum was observed to be absent and the small intestine was located on the right side of the abdomen. After the decompression of the bowel contents, laparotomy was performed. Descending colon cancer was observed to have directly invaded the left side of the transverse colon. Left hemicolectomy, lymph node dissection, and appendectomy were performed. The patient had an uneventful recovery and was discharged from the hospital on the 16th day after surgery. This report presents a rare operative case of descending colon cancer in an adult patient with intestinal malrotation.

Kampo medicine "Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats.

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Chikakiyo, Motoya; Shimada, Mitsuo; Nakao, Toshihiro; Higashijima, Jun; Yoshikawa, Kozo; Nishioka, Masanori; Iwata, Takashi; Kurita, Nobuhiro

2012-01-01

The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. Interleukin (IL)-1β, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1β and IFN-γ expression was improved significantly by DKT (P DKT (P DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity.

Intestinal Obstruction

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... Colostomy ) is required to relieve an obstruction. Understanding Colostomy In a colostomy, the large intestine (colon) is cut. The part ... 1 What Causes Intestinal Strangulation? Figure 2 Understanding Colostomy Gastrointestinal Emergencies Overview of Gastrointestinal Emergencies Abdominal Abscesses ...

The association between miR-499 polymorphism and cancer susceptibility: a meta-analysis.

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Xu, Zhongfei; Zhang, Enjiao; Duan, Weiyi; Sun, Changfu; Bai, Shuang; Tan, Xuexin

2015-01-01

MicroRNAs are a class of new noncoding RNA that play important roles in the pathogenesis of tumor. Rs3746444 in miR-499 is suggested to be associated with cancer susceptibility. In the present study, we assess the association between miR-499 rs3746444 polymorphism and cancer susceptibility through a meta-analysis. We searched relevant articles from the PubMed and Embase databases. We screened all the resulting articles for adherence to the inclusion and exclusion criteria. The associations between miR-499 polymorphism and cancer susceptibility were estimated by computing the odds ratios (ORs) and 95% confidence intervals (CIs). All analyses were performed using Stata software. There are 18 datasets included in the analysis. Statistically significant associations were found between the miR-499 rs3746444 polymorphism and susceptibility to cancer (GG versus AA: OR =1.24, 95% CI: 1.01-1.52; G versus A: OR =1.11, 95% CI: 1.01-1.23). A subsequent analysis, on the basis of ethnicity for the population characteristic, showed that Asians had increased susceptibility to cancer (GG versus AA: OR =1.32, 95% CI: 1.09-1.59; GG + AG versus AA: OR = 1.17, 95% CI: 1.01-1.37). In the subgroup analysis of tumor type, none of the genetic models had statistically significant results. The meta-regression suggested that race and cancer types are not the source of heterogeneity in the present meta-analysis. No publication bias was detected by either the inverted funnel plot or Egger's test. Rs3746444 in miR-499 might be related to susceptibility to cancer.

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

Background: Information about chemotherapy-induced intestinal gene expression may provide insight into the mechanisms underlying gut toxicity and help identify biomarkers and targets for intervention. Methods: We analyzed jejunal tissue from piglets subjected to two different, clinically relevant...... the upregulated genes for both treatments. Conclusion: In the developing intestine, chemotherapy increases the expression of genes related to innate immune functions involved in surveillance, protection, and homeostasis of mucosal surfaces....

75 FR 16490 - Prospective Grant of Exclusive License: Development of PANVAC and Tumor Associated Antigens as...

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2010-04-01

... exclusive license should be directed to: Sabarni K. Chatterjee, Ph.D. Licensing and Patenting Associate... indicates that Brachyury is aberrantly expressed on tumors of the lung, intestine, stomach, kidney, bladder...

Expression of the Na+/l- symporter (NIS is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus

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Wapnir Irene L

2007-01-01

Full Text Available Abstract Background The sodium/iodide symporter (NIS is a plasma membrane glycoprotein that mediates iodide (I- transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. Methods Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. Results Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. Conclusion That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.

Amebiasis intestinal Intestinal amebiasis

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JULIO CÉSAR GÓMEZ

2007-03-01

Full Text Available Entamoeba histolytica es el patógeno intestinal más frecuente en nuestro medio -después de Giardia lamblia-, una de las principales causas de diarrea en menores de cinco años y la cuarta causa de muerte en el mundo debida a infección por protozoarios. Posee mecanismos patogénicos complejos que le permiten invadir la mucosa intestinal y causar colitis amebiana. El examen microscópico es el método más usado para su identificación pero la existencia de dos especies morfológicamente iguales, una patógena ( E. histolytica y una no patógena ( Entamoeba dispar, ha llevado al desarrollo de otros métodos de diagnóstico. El acceso al agua potable y los servicios sanitarios adecuados, un tratamiento médico oportuno y el desarrollo de una vacuna, son los ejes para disminuir la incidencia y mortalidad de esta entidad.Entamoeba histolytica is the most frequent intestinal pathogen seen in our country, after Giardia lamblia, being one of the main causes of diarrhea in children younger than five years of age, and the fourth leading cause of death due to infection for protozoa in the world. It possesses complex pathogenic mechanisms that allow it to invade the intestinal mucosa, causing amoebic colitis. Microscopy is the most used method for its identification, but the existence of two species morphologically identical, the pathogen one ( E. histolytica, and the non pathogen one ( E. dispar, have taken to the development of other methods of diagnosis. The access to drinkable water and appropriate sanitary services, an opportune medical treatment, and the development of a vaccine are the axes to diminish the incidence and mortality of this entity.

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

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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.

Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.

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Zacuto, A C; Pesavento, P A; Hill, S; McAlister, A; Rosenthal, K; Cherbinsky, O; Marks, S L

2016-01-01

Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

The intestinal complement system in inflammatory bowel disease: Shaping intestinal barrier function.

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Sina, Christian; Kemper, Claudia; Derer, Stefanie

2018-06-01

The complement system is part of innate sensor and effector systems such as the Toll-like receptors (TLRs). It recognizes and quickly systemically and/or locally respond to microbial-associated molecular patterns (MAMPs) with a tailored defense reaction. MAMP recognition by intestinal epithelial cells (IECs) and appropriate immune responses are of major importance for the maintenance of intestinal barrier function. Enterocytes highly express various complement components that are suggested to be pivotal for proper IEC function. Appropriate activation of the intestinal complement system seems to play an important role in the resolution of chronic intestinal inflammation, while over-activation and/or dysregulation may worsen intestinal inflammation. Mice deficient for single complement components suffer from enhanced intestinal inflammation mimicking the phenotype of patients with chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD) or ulcerative colitis (UC). However, the mechanisms leading to complement expression in IECs seem to differ markedly between UC and CD patients. Hence, how IECs, intestinal bacteria and epithelial cell expressed complement components interact in the course of IBD still remains to be mostly elucidated to define potential unique patterns contributing to the distinct subtypes of intestinal inflammation observed in CD and UC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Function and expression of cystic fibrosis transmembrane conductance regulator after small intestinal transplantation in mice.

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Penghong Song

Full Text Available The secretion function of intestinal graft is one of the most important factors for successful intestinal transplantation. Cystic fibrosis transmembrane conductance regulator (CFTR mediates HCO3(- and Cl(- secretions in intestinal epithelial cells. In this study, we made investigation on the expression and function of CFTR in an experimental model of murine small intestinal transplantation. Heterotopic intestinal transplantations were performed in syngeneic mice. The mRNA and protein expressions of CFTR were analyzed by real time PCR and western blot. Murine intestinal mucosal HCO3(- and Cl(- secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (I(sc techniques. The results showed that forskolin, an activator of CFTR, stimulated jejunal mucosal epithelial HCO3(- and Cl(- secretions in mice, but forskolin-stimulated HCO3(- and Cl(- secretions in donor and recipient jejunal mucosae of mice after heterotopic jejunal transplantation were markedly decreased, compared with controls (P<0.001. The mRNA and protein expression levels of CFTR in donor and recipient jejunal mucosae of mice were also markedly lower than those in controls (P<0.001, and the mRNA and protein expression levels of tumor necrosis factor α (TNFα were markedly increased in donor jejunal mucosae of mice (P<0.001, compared with controls. Further experiments showed that TNFα down-regulated the expression of CFTR mRNA in murine jejunal mucosa. In conclusion, after intestinal transplantation, the function of CFTR was impaired, and its mRNA and protein expressions were down-regulated, which may be induced by TNFα.

Cancer stemness in Apc- vs. Apc/KRAS-driven intestinal tumorigenesis.

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Mehrnaz Ghazvini

Full Text Available Constitutive activation of the Wnt pathway leads to adenoma formation, an obligatory step towards intestinal cancer. In view of the established role of Wnt in regulating stemness, we attempted the isolation of cancer stem cells (CSCs from Apc- and Apc/KRAS-mutant intestinal tumours. Whereas CSCs are present in Apc/KRAS tumours, they appear to be very rare (<10(-6 in the Apc-mutant adenomas. In contrast, the Lin(-CD24(hiCD29(+ subpopulation of adenocarcinoma cells appear to be enriched in CSCs with increased levels of active β-catenin. Expression profiling analysis of the CSC-enriched subpopulation confirmed their enhanced Wnt activity and revealed additional differential expression of other signalling pathways, growth factor binding proteins, and extracellular matrix components. As expected, genes characteristic of the Paneth cell lineage (e.g. defensins are co-expressed together with stem cell genes (e.g. Lgr5 within the CSC-enriched subpopulation. This is of interest as it may indicate a cancer stem cell niche role for tumor-derived Paneth-like cells, similar to their role in supporting Lgr5(+ stem cells in the normal intestinal crypt. Overall, our results indicate that oncogenic KRAS activation in Apc-driven tumours results in the expansion of the CSCs compartment by increasing ®-catenin intracellular stabilization.

Maslinic acid-enriched diet decreases intestinal tumorigenesis in Apc(Min/+ mice through transcriptomic and metabolomic reprogramming.

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Susana Sánchez-Tena

Full Text Available Chemoprevention is a pragmatic approach to reduce the risk of colorectal cancer, one of the leading causes of cancer-related death in western countries. In this regard, maslinic acid (MA, a pentacyclic triterpene extracted from wax-like coatings of olives, is known to inhibit proliferation and induce apoptosis in colon cancer cell lines without affecting normal intestinal cells. The present study evaluated the chemopreventive efficacy and associated mechanisms of maslinic acid treatment on spontaneous intestinal tumorigenesis in Apc(Min/+ mice. Twenty-two mice were randomized into 2 groups: control group and MA group, fed with a maslinic acid-supplemented diet for six weeks. MA treatment reduced total intestinal polyp formation by 45% (P<0.01. Putative molecular mechanisms associated with suppressing intestinal polyposis in Apc(Min/+ mice were investigated by comparing microarray expression profiles of MA-treated and control mice and by analyzing the serum metabolic profile using NMR techniques. The different expression phenotype induced by MA suggested that it exerts its chemopreventive action mainly by inhibiting cell-survival signaling and inflammation. These changes eventually induce G1-phase cell cycle arrest and apoptosis. Moreover, the metabolic changes induced by MA treatment were associated with a protective profile against intestinal tumorigenesis. These results show the efficacy and underlying mechanisms of MA against intestinal tumor development in the Apc(Min/+ mice model, suggesting its chemopreventive potential against colorectal cancer.

Prevalence of intestinal parasite, Shigella and Salmonella species among diarrheal children in Jimma health center, Jimma southwest Ethiopia: a cross sectional study.

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Beyene, Getenet; Tasew, Haimanot

2014-02-05

Diarrheal disease continues to be an important cause of morbidity and mortality among young children in developing countries including Ethiopia. Globally, intestinal parasite, Shigella and Salmonella species remain major contributors to acute enteric infections. The study was aimed at determining the frequency of intestinal parasite, Shigella and Salmonella species identified from diarrheic children at Jimma Health Centre, Jimma south west Ethiopia. A health institution based cross sectional study was conducted from March to November 2012. A structured questionnaire was used for collection of data on socio- demographic characteristics. Parasite and bacteria identification as well as susceptibility testing was done using standard parasitological and bacteriological procedures. A total of 260 diarrheal children were included in the study. A total of 129 (49.6%) samples were positive for intestinal parasite, Shigella and Salmonella species. Of these, 107 (41.1%), 6 (2.3%) and 16 (6.2%) samples were positive for intestinal parasite, Shigella and Salmonella species respectively. The dominant isolated parasite was G. lamblia with prevalence of 13.5% followed by A. lumbricoides (11.5%). The least identified parasites were Schistosoma mansoni and Taenia species accounting 0.4% each. Multiple parasitic infections were observed in 19 (7.3%) patients. Shigella species showed hundred percent resistances to ampicillin, amoxacillin, and cotrimoxazole. All Salmonella isolates were resistant against amoxicillin. All Shigella and Salmonella species were susceptible to ceftriaxone, ciprofloxacin and gentamycin. The presence of reasonably high amount of intestinal parasite and Salmonella and Shigella species that are drug resistance to the commonly prescribed drugs is a treat to the children and community at large. Therefore, measures including health education, improvement of safe water supply, sanitation facilities and continuous monitoring of microbiological and antimicrobial

[Treatment of children with intestinal failure: intestinal rehabilitation, home parenteral nutrition or small intestine transplantation?

NARCIS (Netherlands)

Neelis, E.G.; Oers, H.A. van; Escher, J.C.; Damen, G.M.; Rings, E.H.; Tabbers, M.M.

2014-01-01

Intestinal failure is characterised by inadequate absorption of food or fluids, which is caused by insufficient bowel surface area or functioning. Children with chronic intestinal failure are dependent on parenteral nutrition (PN), which can be provided at home (HPN). In the Netherlands, HPN for

Lactobacillus casei Zhang and vitamin K2 prevent intestinal tumorigenesis in mice via adiponectin-elevated different signaling pathways.

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Zhang, Yong; Ma, Chen; Zhao, Jie; Xu, Haiyan; Hou, Qiangchuan; Zhang, Heping

2017-04-11

The incidence of colon cancer has increased considerably and the intestinal microbiota participate in the development of colon cancer. We showed that the L. casei Zhang or vitamin K2 (Menaquinone-7) intervention significantly alleviated intestinal tumor burden in mice. This was associated with increased serum adiponectin levels in both treatments. But osteocalcin level was only increased by L. casei Zhang. Furthermore, the anti-carcinogenic actions of L. casei Zhang were mediated by hepatic Chloride channel-3(CLCN3)/Nuclear Factor Kappa B(NF-κB) and intestinal Claudin15/Chloride intracellular channel 4(CLIC4)/Transforming Growth Factor Beta(TGF-β) signaling, while the vitamin K2 effect involved a hepatic Vitamin D Receptor(VDR)-phosphorylated AMPK signaling pathway. Fecal DNA sequencing by the Pacbio RSII method revealed there was significantly lower Helicobacter apodemus, Helicobacter mesocricetorum, Allobaculum stercoricanis and Adlercreutzia equolifaciens following both interventions compared to the model group. Moreover, different caecum acetic acid and butyric acid levels and enrichment of other specific microbes also determined the activity of the different regulatory pathways. Together these data show that L. casei Zhang and Vitamin K2 can suppress gut risk microbes and promote beneficial microbial metabolites to reduce colonic tumor development in mice.

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

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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

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

Current opinion on PET for gastrointestinal tumors

International Nuclear Information System (INIS)

Diederichs, C.G.; Schirrmeister, H.; Staib, L.

2000-01-01

The benefit of FDG-PET for restaging of colorectal carcinoma and for the differentiation of indeterminate hepatic lesions is well-documented. Accuracies of FDG-PET for recurrence, lymph node status and the detection of distant metastases are higher compared with computed tomography, for example. For other epithelial gastrointestinal tumors similar results have also been demonstrated in smaller trials or case presentations. The differentiation of recurrent rectal carcinoma from scar and PET for endocrine tumors are described elsewhere (Der Nuklearmediziner PET II, in preparation). Almost no data exist for rare tumors like anal carcinoma or tumors of the small intestines. For hepatocellular carcinoma, FDG-PET has a high positive predictive value, and the intensity of the uptake correlates well with grading. However, FDG-PET is not suitable for the exclusion of hepatocellular carcinoma due to insufficient sensitivity. The differentiation of benign and malignant pancreatic masses works well for selected patients. FDG-PET for lymph node staging is at least as accurate as conventional staging, and for the detection of distant metastases FDG-PET is superior compared with conventional staging. Few data exist on therapy control of gastrointestinal tumors. (orig.) [de

Epidemiology and antimicrobial resistance of B. fragilis group organisms isolated from clinical specimen and human intestinal microbiota Epidemiologia e resistência a antimicrobianos de microorganismos do grupo B. fragilis isolados de espécime clínico e microbiota intestinal humana

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Cibele Barreto Mano de Carvalho

1996-10-01

Full Text Available Epidemiological aspects and the antimicrobial susceptibility profile of the Bacteroides fragilis group isolated from clinical and human intestinal specimens were examined in this study. B. fragilis group strains were isolated from 46 (37% of 124 clinical specimens and the source of the samples was: Blood culture (3, intraabdominal infection (27, brain abscess (2, soft tissue infection (17, respiratory sinus (3, pleural aspirate (9, breast abscess (3, surgical infected wound (22, pelvic inflammatory disease (22, chronic otitis media (9 and miscellaneous (7. Intraabdominal and soft tissue infections were responsible for more than half of the clinical isolates. Susceptibility to penicillin, cefoxitin, tetracycline, metronidazole, chloramphenicol and clindamycin was examined. All isolates were susceptible to metronidazole and chloramphenicol. For clindamycin and cefoxitin the resistance rates observed were 21.7% and 10.9% respectively. Susceptibility profiles varied among the different species tested. A total of 37 species of B. fragilis group isolated from intestinal microbiota of individuals who had no antimicrobial therapy for at least 1 month before the sampling was also examined. All strains were also susceptible to chloramphenicol and motronidazole and the resistance rates to clindamycin and cefoxitin were 19.4% and 5.4% respectively. A few institutions, in Brazil, have monitored the antimicrobial susceptibility of B. fragilis group strains isolated from anaerobic infections. The resistance rates to cefoxitin and clindamycin and the variation in susceptibility patterns among the species isolated in this study emphasize the need for monitoring of susceptibility patterns of B. fragilis group organisms isolated, especially at our University Hospitals.Alguns aspectos epidemiológicos e o perfil de sensibilidade a antimicrobianos de amostras do grupo B. fragilis isoladas de espécime clínico e microbiota intestinal humana foram delineados neste

Fusion between Intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming.

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Powell, Anne E; Anderson, Eric C; Davies, Paige S; Silk, Alain D; Pelz, Carl; Impey, Soren; Wong, Melissa H

2011-02-15

The most deadly phase in cancer progression is attributed to the inappropriate acquisition of molecular machinery leading to metastatic transformation and spread of disease to distant organs. Although it is appreciated that metastasis involves epithelial-mesenchymal interplay, the underlying mechanism defining this process is poorly understood. Specifically, how cancer cells evade immune surveillance and gain the ability to navigate the circulatory system remains a focus. One possible mechanism underlying metastatic conversion is fusion between blood-derived immune cells and cancer cells. While this notion is a century old, in vivo evidence that cell fusion occurs within tumors and imparts genetic or physiologic changes remains controversial. We have previously demonstrated in vivo cell fusion between blood cells and intestinal epithelial cells in an injury setting. Here, we hypothesize that immune cells, such as macrophages, fuse with tumor cells imparting metastatic capabilities by transferring their cellular identity. We used parabiosis to introduce fluorescent-labeled bone marrow-derived cells to mice with intestinal tumors, finding that fusion between circulating blood-derived cells and tumor epithelium occurs during the natural course of tumorigenesis. Moreover, we identify the macrophage as a key cellular partner for this process. Interestingly, cell fusion hybrids retain a transcriptome identity characteristic of both parental derivatives, while also expressing a unique subset of transcripts. Our data supports the novel possibility that tumorigenic cell fusion may impart physical behavior attributed to migratory macrophages, including navigation of circulation and immune evasion. As such, cell fusion may represent a promising novel mechanism underlying the metastatic conversion of cancer cells. ©2011 AACR.

Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium.

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Nicholas Lahar

Full Text Available The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.

Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease.

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Schwiertz, Andreas; Spiegel, Jörg; Dillmann, Ulrich; Grundmann, David; Bürmann, Jan; Faßbender, Klaus; Schäfer, Karl-Herbert; Unger, Marcus M

2018-02-12

Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD. In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay. The study design controlled for potential confounding factors. Calprotectin, a fecal marker of intestinal inflammation, and two fecal markers of increased intestinal permeability (alpha-1-antitrypsin and zonulin) were significantly elevated in PD patients compared to age-matched controls. Lactoferrin, as a second fecal marker of intestinal inflammation, showed a non-significant trend towards elevated concentrations in PD patients. None of the four fecal markers correlated with disease severity, PD subtype, dopaminergic therapy, or presence of constipation. Fecal markers reflecting intestinal inflammation and increased intestinal permeability have been primarily investigated in inflammatory bowel disease so far. Our data indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non-invasive markers in PD as well. Even though these markers are not disease-specific, they corroborate the hypothesis of an intestinal inflammation as contributing factor in the pathogenesis of PD. Further investigations are needed to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to define PD subgroups and to monitor the effect of interventions in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intestinal cytochromes P450 regulating the intestinal microbiota and its probiotic profile

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Eugenia Elefterios Venizelos Bezirtzoglou

2012-09-01

Full Text Available Cytochromes P450 (CYPs enzymes metabolize a large variety of xenobiotic substances. In this vein, a plethora of studies were conducted to investigate their role, as cytochromes are located in both liver and intestinal tissues. The P450 profile of the human intestine has not been fully characterized. Human intestine serves primarily as an absorptive organ for nutrients, although it has also the ability to metabolize drugs. CYPs are responsible for the majority of phase I drug metabolism reactions. CYP3A represents the major intestinal CYP (80% followed by CYP2C9. CYP1A is expressed at high level in the duodenum, together with less abundant levels of CYP2C8-10 and CYP2D6. Cytochromes present a genetic polymorphism intra- or interindividual and intra- or interethnic. Changes in the pharmacokinetic profile of the drug are associated with increased toxicity due to reduced metabolism, altered efficacy of the drug, increased production of toxic metabolites, and adverse drug interaction. The high metabolic capacity of the intestinal flora is due to its enormous pool of enzymes, which catalyzes reactions in phase I and phase II drug metabolism. Compromised intestinal barrier conditions, when rupture of the intestinal integrity occurs, could increase passive paracellular absorption. It is clear that high microbial intestinal charge following intestinal disturbances, ageing, environment, or food-associated ailments leads to the microbial metabolism of a drug before absorption. The effect of certain bacteria having a benefic action on the intestinal ecosystem has been largely discussed during the past few years by many authors. The aim of the probiotic approach is to repair the deficiencies in the gut flora and establish a protective effect. There is a tentative multifactorial association of the CYP (P450 cytochrome role in the different diseases states, environmental toxic effects or chemical exposures and nutritional status.

Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

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Peris Mumbi Munyaka

Full Text Available Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota.Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted.ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels.The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

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Munyaka, Peris Mumbi; Eissa, N; Bernstein, Charles Noah; Khafipour, Ehsan; Ghia, Jean-Eric

2015-01-01

Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

78 FR 50425 - Prospective Grant of Exclusive License: Development of Brachyury Tumor Associated Antigens as...

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2013-08-19

... relating to the contemplated exclusive license should be directed to: Sabarni K. Chatterjee, Ph.D., M.B.A... target for human T-cell mediated cancer immunotherapy, such as for tumors of the lung, intestine, stomach...

Epidemiological Features of Clostridium difficile Colonizing the Intestine of Jordanian Infants

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Eman N. Abu-Khader

2017-01-01

Full Text Available Clostridium difficile is commonly found in the intestine of infants without causing any disease. This study investigated the most important epidemiological features of C. difficile strains colonizing intestine of Jordanian infants. A total of 287 fecal samples were collected from infants admitted to the Jordan University Hospital (JUH over the period of 2015. Samples were cultured for C. difficile and their growth was identified using microbiological culture and PCR. The overall C. difficile colonization rate among hospitalized and nonhospitalized infants was 37/287 (12.9%. Neonates were less colonized than other infants (8.7% verses 19.5%. Colonization of the infants with C. difficile toxigenic strains (TcdA and TcdB was observed in 54% of the isolates, whereas those colonized with nontoxigenic strains were 46% and only one isolate was positive for binary toxin. Breast feeding of infants is a significant factor associated with decreased colonization with C. difficile. All C. difficile strains were susceptible to vancomycin and metronidazole, while high resistance rate to ciprofloxacin (78.4% and less resistance rate to erythromycin (29.7% were detected among the isolates. The results showed that 40.5% of the isolates carried mutated gyrA and gyrB genes which have cross-resistance to ciprofloxacin and moxifloxacin. This study represents useful epidemiological features about C. difficile colonizing intestine of infants living in a developing country.

Primary Ewing's sarcoma/primitive neuroectodermal tumor of the ileum: case report of a 16-year-old Chinese female and literature review.

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Li, Teng; Zhang, Fang; Cao, Yarui; Ning, Shoubin; Bi, Yongmin; Xue, Weicheng; Ren, Li

2017-05-04

Ewing's sarcoma (ES) and primitive neuroectodermal tumors (PNET) are closely related tumors. Although soft tissue ES/PNET are common in clinical practice, they are rare in the small intestine. Because of the absence of characteristic clinical symptoms, they are easily misdiagnosed as other benign or malignant diseases. Here, we present the case of a 16-year-old female who complained of anemia and interval hematochezia. Her serum test results showed only a slight elevation of CA-125 and a low level of hemoglobin. Computer tomography and magnetic resonance imaging revealed a cystic and solid mass in the lower abdominal quadrant and pelvic region, which prompted suspicion of a malignant gastrointestinal stromal tumor of the small intestine. After resection, the tumor's histology and immunohistochemistry (positive for CD99, vimentin and synaptophysin) results suggested ES/PNET. Fluorescent in situ hybridization tests proved the breakpoint rearrangement of the EWSR1 gene in chr 22.Ultrastructural analysis revealed neurosecretory and glycogen granules in the tumor cell cytoplasm. Together, these data supported the diagnosis of a rare case of localized ES/PNET in the small intestine without adjuvant chemo- or radiotherapy. To our knowledge, this is the first report from China of a primary small bowel ES/PNET in the English-language literature. In addition, on the basis of findings from previous publications and the current case, the optimal treatment for localized gastrointestinal ES/PNET is discussed.

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

International Nuclear Information System (INIS)

Kamiya, Kenji; Nitta, Yumiko; Gould, M.N.

2000-01-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of 60 Co gamma rays at a dose rate of 26.58±1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

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Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Gould, M.N.

2000-07-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of {sup 60} Co gamma rays at a dose rate of 26.58{+-}1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Molecular biology of testicular germ cell tumors.

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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.

[Myosin B ATPase activity of the intestinal smooth muscle in intestinal obstruction].

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Takamatsu, H

1983-06-01

Intestinal smooth myosin B was prepared from muscle layers around the lesion in dogs with experimental colonic stenosis and in patients with congenital intestinal obstruction. Mg2+-ATPase activity of the myosin B was compared between the proximal dilated segment and distal segment to obstruction. Experimental colonic stenosis: In early period after surgery, proximal colons showed higher activity of myosin B ATPase than distal colons, decreasing to less than distal colon as time passed. Congenital intestinal obstruction: In three cases, whose atresia might have occurred at earlier period of gestation, proximal bowels showed less activity of myosin B ATPase than distal bowels. However, in two cases, whose atresia might have occurred at later period of gestation, and two cases with intestinal stenosis, proximal bowels indicated higher activity of myosin B ATPase than distal bowels. These data suggested that the contractibility of the proximal intestine was depending on the duration of obstruction, and it was depressed in the former patients and was accelerated in the latter patients. These results suggested that the extensive resection of dilated proximal bowel in the congenital atresia is not always necessary to obtain good postoperative intestinal dynamics at the operation of the atresial lesions which may be induced at later period of gestation. They also suggested that surgery for intestinal obstruction should be performed before the depression of intestinal contractibility to get good bowel function.

Ability of TEP1 in intestinal flora to modulate natural resistance of Anopheles dirus.

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Wang, Yanyan; Wang, Ying; Zhang, Jingru; Xu, Wenyue; Zhang, Jian; Huang, Fu Sheng

2013-08-01

Blocking transmission of malaria is a reliable way to control and eliminate infection. However, in-depth knowledge of the interaction between Plasmodium and mosquito is needed. Studies suggest that innate immunity is the main mechanism inhibiting development of malaria parasites in the mosquito. Recent studies have found that use of antibiotics that inhibit the mosquito gut flora can reduce the immune response of Anopheles gambiae, thereby contributing to the development of malaria parasites. In our study, we used the non susceptible model of Anopheles dirus-Plasmodium yoelii to explore the effect of Anopheles intestinal flora on the natural resistance of A. dirus to P. yoelii. We found that in mosquitoes infected with Plasmodium, the intestinal flora can regulate expression of thioester-containing protein (TEP1) via an RNAi gene-silencing approach. Our results suggest that in the absence of TEP1, the natural microbiota cannot suppress the development of P. yoelii in A. dirus. This suggests that AdTEP1 plays an important role in the resistance of A. dirus to P. yoelii. The intestinal flora may modulate the development of P. yoelii in A. dirus by regulating TEP1 expression. Copyright © 2013 Elsevier Inc. All rights reserved.

[Congenital intestinal lymphangiectasia].

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Popović, Dugan D j; Spuran, Milan; Alempijević, Tamara; Krstić, Miodrag; Djuranović, Srdjan; Kovacević, Nada; Damnjanović, Svetozar; Micev, Marjan

2011-03-01

Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortuous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and supportive therapy. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.

Monoclonal antibodies reactive with common tumor antigens on UV-induced tumors also react with hyperplastic UV-irradiated skin

International Nuclear Information System (INIS)

Spellman, C.W.; Beauchamp, D.A.

1986-01-01

Most murine skin tumors induced by ultraviolet light (UVB, 280-340 nm) can be successfully transplanted only into syngeneic hosts that have received subcarcinogenic doses of UVB. The tumor susceptible state is long-lived and mediated by T suppressor cells that control effector responses against common antigens on UV-induced tumors. Because antigen specific suppression arises prior to the appearance of a tumor, questions arise about the source of the original antigen. They have previously reported transplantation studies indicating that UV-irradiated skin is antigenically cross-reactive with UV-induced tumors. They now report on flow cytometry analyses showing that a series of MoAb reactive with common antigens expressed by UV-induced tumors are also reactive on cells from UV-irradiated skin. Various antigens appear at different times in the UV irradiation scheme, and some persist while others are transient. They speculate that the common antigens detected may be the ones to which functional suppression is directed. If true, these results suggest that successful tumors need not escape host defenses to emerge. Rather, tumors may arise and grow progressively if they express antigens that cross-react with specificities to which the host has previously mounted a suppressive response

Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

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Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-01-01

INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

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?

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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.

Modeling the growth dynamics of multiple Escherichia coli strains in the pig intestine following intramuscular ampicillin treatment.

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Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo; Græsbøll, Kaare; Toft, Nils; Matthews, Louise; Nielsen, Søren Saxmose; Olsen, John Elmerdahl

2016-09-06

This study evaluated how dosing regimen for intramuscularly-administered ampicillin, composition of Escherichia coli strains with regard to ampicillin susceptibility, and excretion of bacteria from the intestine affected the level of resistance among Escherichia coli strains in the intestine of nursery pigs. It also examined the dynamics of the composition of bacterial strains during and after the treatment. The growth responses of strains to ampicillin concentrations were determined using in vitro growth curves. Using these results as input data, growth predictions were generated using a mathematical model to simulate the competitive growth of E. coli strains in a pig intestine under specified plasma concentration profiles of ampicillin. In vitro growth results demonstrated that the resistant strains did not carry a fitness cost for their resistance, and that the most susceptible strains were more affected by increasing concentrations of antibiotics that the rest of the strains. The modeling revealed that short treatment duration resulted in lower levels of resistance and that dosing frequency did not substantially influence the growth of resistant strains. Resistance levels were found to be sensitive to the number of competing strains, and this effect was enhanced by longer duration of treatment. High excretion of bacteria from the intestine favored resistant strains over sensitive strains, but at the same time it resulted in a faster return to pre-treatment levels after the treatment ended. When the duration of high excretion was set to be limited to the treatment time (i.e. the treatment was assumed to result in a cure of diarrhea) resistant strains required longer time to reach the previous level. No fitness cost was found to be associated with ampicillin resistance in E. coli. Besides dosing factors, epidemiological factors (such as number of competing strains and bacterial excretion) influenced resistance development and need to be considered further in

Stem-cell-specific endocytic degradation defects lead to intestinal dysplasia in Drosophila

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Péter Nagy

2016-05-01

Full Text Available UV radiation resistance-associated gene (UVRAG is a tumor suppressor involved in autophagy, endocytosis and DNA damage repair, but how its loss contributes to colorectal cancer is poorly understood. Here, we show that UVRAG deficiency in Drosophila intestinal stem cells leads to uncontrolled proliferation and impaired differentiation without preventing autophagy. As a result, affected animals suffer from gut dysfunction and short lifespan. Dysplasia upon loss of UVRAG is characterized by the accumulation of endocytosed ligands and sustained activation of STAT and JNK signaling, and attenuation of these pathways suppresses stem cell hyperproliferation. Importantly, the inhibition of early (dynamin-dependent or late (Rab7-dependent steps of endocytosis in intestinal stem cells also induces hyperproliferation and dysplasia. Our data raise the possibility that endocytic, but not autophagic, defects contribute to UVRAG-deficient colorectal cancer development in humans.

Regulation of apoptosis by low serum in cells of different stages of neoplastic progression: enhanced susceptibility after loss of a senescence gene and decreased susceptibility after loss of a tumor suppressor gene.

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Preston, G A; Lang, J E; Maronpot, R R; Barrett, J C

1994-08-01

A cell culture model system has been used to study the susceptibility of cells to apoptotic cell death during different stages of neoplastic progression. This system consists of normal diploid Syrian hamster embryo (SHE) cells, two preneoplastic cell lines [tumor suppressor stage I (sup +I) and non-tumor suppressor stage II (sup -II)], and hamster tumor cell lines. Stage I preneoplastic cells are nontumorigenic immortal clones that suppress tumorigenicity when hybridized to tumor cells, whereas stage II cells have lost the ability to suppress tumorigenicity in cell hybrids. We refer to these two types of preneoplastic cells as sup +I and sup -II, respectively. Neoplastic progression is generally associated with cellular alterations in growth factor responsiveness. Therefore, to study the regulation of apoptosis in the system described above, cells were cultured in low serum (0.2%) as a means of withdrawing growth factors. In low serum, normal SHE cells were quiescent (labeling index of 0.2%), with little cell death. The sup +I cells showed a relatively low labeling index (1.6%) but, in contrast to the normal cells, died at a high rate (55% cell loss after 48 h) by apoptosis, as evidenced by morphology, DNA fragmentation, and in situ end-labeling of fragmented DNA. The apoptotic cells did not go through a replicative cycle while in low serum, implying that apoptosis was initiated in the G0/G1 phase of the cell cycle. The sup -II cell line showed a high labeling index (40%) after 48 h, but cell growth was balanced by cell death that occurred at approximately the same rate. The cells died, however, predominantly by necrosis. The tumor cell lines continued to proliferate in low serum, with high labeling indices (ranging from 27% to 43%) and a low level of apoptotic or necrotic cell death. To determine the relative ability of these cells to survive in vivo, normal SHE cells, sup +I cells, and sup -II cells were injected s.c. into nude mice. At 5 or 21 days after

Effect of ochratoxin A on the intestinal mucosa and mucosa-associated lymphoid tissues in broiler chickens.

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Solcan, Carmen; Pavel, Geta; Floristean, Viorel Cezar; Chiriac, Ioan Sorin Beschea; Şlencu, Bogdan Gabriel; Solcan, Gheorghe

2015-03-01

The immunotoxic effect of ochratoxin A (OTA) on the intestinal mucosa-associated lymphoid tissue and its cytotoxic action on the intestinal epithelium were studied in broiler chickens experimentally treated with the toxin. From the 7th day of life, 80 male broiler chickens (Ross 308) were randomly divided into four groups of 20 birds each. The three experimental groups (E1-3) were treated with OTA for 28 days (E1: 50 μg/kg body weight [bw]/day; E2: 20 μg/kg bw/day; E3: 1 μg/kg bw/day) and the fourth group served as control. Histological examination of the intestinal mucosa and immunohistochemical staining for identification of CD4+, CD8+, TCR1 and TCR2 lymphocytes in the duodenum, jejunum and ileocaecal junction were performed, and CD4+/CD8+ and TCR1/TCR2 ratios were calculated. OTA toxicity resulted in decreased body weight gain, poorer feed conversion ratio, lower leukocyte and lymphocyte count, and altered intestinal mucosa architecture. After 14 days of exposure to OTA, immunohistochemistry showed a significant reduction of the lymphocyte population in the intestinal epithelium and the lamina propria. After 28 days of exposure, an increase in the CD4+ and CD8+ values in both the duodenum and jejunum of chickens in Groups E1 and E2 was observed, but the TCR1 and TCR2 lymphocyte counts showed a significant reduction. No significant changes were observed in Group E3. The results indicate that OTA induced a decrease in leukocyte and lymphocyte counts and was cytotoxic to the intestinal epithelium and the mucosa-associated lymphoid tissue, altering the intestinal barrier and increasing susceptibility to various associated diseases.

Congenital intestinal lymphangiectasia

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Popović Dušan Đ.

2011-01-01

Full Text Available Background. Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortous, dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and medication are required for disease control. Case report. A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue. Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm. Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-protein diet containing medium-chain fatty acids, somatotropin and suportive therapy. Conclusion. Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of the disease and adequate treatment can prevent development of various complications.

Susceptibility and pathological consequences of catla, Catla catla (Hamilton experimentally infected with Edwardsiella tarda

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Devi Thongam Bidya

2016-12-01

Full Text Available The present study tested the susceptibility and pathological changes of catla, Catla catla (Hamilton infected with Edwardsiella tarda (ET-PG-29. The bacterium was isolated from the kidney of a diseased pangas catfish. To determine the median lethal dose (LD50, C. catla were challenged with this bacterium (108-103 CFU ml-1, and the LD50 was calculated as 105.5 CFU ml-1. Another set of healthy C. catla were injected intraperitoneally with the LD50 dose to induce edwardsiellosis. The clinical signs of the infected C. catla were observed and recorded. Tissues such as kidney, liver, intestine, heart, and gill from the infected fish with clinical signs of edwardsiellosis were used for histopathology. The clinical and gross signs were first visible at 1 d post-injection, and the infected fish showed typical signs of hemorrhagic septicemia. The most striking histopathological features were found in the kidney which showed multi-focal necrosis with the formation of granuloma indicating an inflammatory response against the pathogen. The intestine displayed goblet cell hyperplasia, the liver showed hydropic degeneration with hyperemic central veins, and there was inflammation of gill lamellae and cardiac myositis associated with leucocyte infiltration. Collectively, the results confirmed the susceptibility of C. catla to E. tarda infection and that this bacterium is a threat to C. catla in aquaculture practices.

Intestine transplantation

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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.

Determination of carcinoembryonic antigen in patients with tumors of the large intestine

International Nuclear Information System (INIS)

Lamerz, R.; Ruider, H.

1976-01-01

Specimens from 93 patients with histologically confirmed tumors of the large bowel (53 single, 40 sequential determinations) were investigated by a new CEA radioimmunoassay (double antibody method, direct serum determination). Of the single and preoperative sequential determinations 37-40% were normal (below 2.5 ng/ml), one third was intermediately elevated (2.6 ng/ml) and 26-28% were highly pathological leveled (over 15 ng/ml). Following operation, cases with local or regionally confined tumor showed significantly more normal or normalizing CEA levels within 1-6 weeks (17/27), whereas patients with overt metastases developed more pathological or increasingly pathological levels (8/11). (orig.) [de

Advance MRI for pediatric brain tumors with emphasis on clinical benefits

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Goo, Hyun Woo; Ra, Young Shin [Asan Medical Center, University of Ulsan College of Medicine, Seoul(Korea, Republic of)

2017-01-15

Conventional anatomic brain MRI is often limited in evaluating pediatric brain tumors, the most common solid tumors and a leading cause of death in children. Advanced brain MRI techniques have great potential to improve diagnostic performance in children with brain tumors and overcome diagnostic pitfalls resulting from diverse tumor pathologies as well as nonspecific or overlapped imaging findings. Advanced MRI techniques used for evaluating pediatric brain tumors include diffusion-weighted imaging, diffusion tensor imaging, functional MRI, perfusion imaging, spectroscopy, susceptibility-weighted imaging, and chemical exchange saturation transfer imaging. Because pediatric brain tumors differ from adult counterparts in various aspects, MRI protocols should be designed to achieve maximal clinical benefits in pediatric brain tumors. In this study, we review advanced MRI techniques and interpretation algorithms for pediatric brain tumors.

Influence of intestinal early enteral nutrition therapy on intestinal barrier function and immune response of patients with radiation enteritis

International Nuclear Information System (INIS)

Liu Guohui; Kang Xin; Chen Gong; Wang Guangyi

2012-01-01

Objective: To investigate the influence of early enteral nutrition therapy on the intestinal barrier function and immune response of the patients with radiation enteritis (ER) so as to find a relatively simple and effective method to treat RE. Methods: Fifty-six patients with radiation enteritis (RE) diagnosed by colonoscopy, X-rays, and pathology were randomly divided into 2 equal groups: experimental group undergoing enteral nutrition therapy, and control group undergoing conventional therapy only. Peripheral blood samples were collected 1, 11, and 21 days after admission. Plasma diamine oxidase (DAO), D-lactic acid, endotoxin, and lactulose/mannitol (L/M) ratio, and levels of IgG, IgM, and IgA, and CD4/CD8 ratio were examined. Five cases from the experimental group and 5 cases from the control group underwent second-time operation because of incomplete intestinal obstruction, intestinal stenosis, or recurrent tumor respectively. The biopsy specimens of the terminal ileum or distal descending colon taken during the first and second operations underwent pathological examination. Peripheral blood samples were collected 1, 11, and 21 days after admission. Plasma diamine oxidase (DAO), D-lactic acid, endotoxin, and lactulose/mannitol (L/M) ratio, and levels of IgG, IgM, and IgA, and CD4/CD8 ratio were examined. Results: There were no significant differences in the intestinal function and blood immunological indices between these 2 groups. The levels of DAO, D-lactic acid, and endotoxin,and the L/M ratio 11 days after admission of the experiment group were all significantly lower than those of the control group (t=2.568, 2.427, 2.143, 2.443, P<0.05), and all those indices 21 days after admission of the experiment group were all much more significantly lower in comparison with the control group (t=6.019, 12.834, 7.837, 7.997, P<0.01). The levels of IgG, IgM, and IgA, and CD4/CD8 ratio 11 days after admission of the experimental group were all significantly higher than

Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

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2010-01-01

Background Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD) in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'). To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. Results C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase). Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. Conclusion These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients. PMID:21040540

Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

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Kalischuk Lisa D

2010-11-01

Full Text Available Abstract Background Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'. To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. Results C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase. Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. Conclusion These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients.

Intestinal malrotation with suspected cow’s milk allergy: a case report

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Matsuki Takuma

2012-09-01

Full Text Available Abstract Background Intestinal malrotation is an incomplete rotation of the intestine. Failure to rotate leads to abnormalities in intestinal positioning and attachment that leave obstructing bands across the duodenum and a narrow pedicle for the midgut loop, thus making it susceptible to volvulus. One of the important differential diagnoses for malrotation is an allergy to cow’s milk. Several studies have described infants with surgical gastrointestinal diseases and cow’s milk allergy. However, to our knowledge, no study has reported infants with intestinal malrotation who have been symptomatic before surgery was performed and have been examined by allergen-specific lymphocyte stimulation test and food challenge tests with long-term follow-up. Case presentation The patient was a Japanese male born at 39 weeks of gestation. He was breast-fed and received commercial cow’s milk supplementation starting the day of birth and was admitted to our hospital at 6 days of age due to bilious vomiting. Plain abdominal radiography showed a paucity of gas in the distal bowel. Because we demonstrated malpositioning of the intestine by barium enema, we repositioned the bowel in a normal position by laparotomy. The patient was re-started on only breast milk 2 days post surgery because we suspected the presence of a cow’s milk allergy, and the results of an allergen-specific lymphocyte stimulation test showed a marked increase in lymphocyte response to kappa-casein. At 5 months of age, the patient was subjected to a cow’s milk challenge test. After the patient began feeding on cow’s milk, he had no symptoms and his laboratory investigations showed no abnormality. In addition, because the patient showed good weight gain and no symptoms with increased cow’s milk intake after discharge, we concluded that the present case was not the result of a cow’s milk allergy. At 1 year, the patient showed favorable growth and development, and serum allergy

Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

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Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-11-01

The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas

Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.

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Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha; Lionakis, Michail S; Ding, Li; Hsu, Amy P; Zelazny, Adrian M; Moutsopoulos, Niki M; Kuhns, Douglas B; Deming, Clay; Quiñones, Mariam; Segre, Julia A; Bryant, Clare E; Holland, Steven M

2016-04-05

Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium. Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.

Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

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Opazo, Maria C.; Ortega-Rocha, Elizabeth M.; Coronado-Arrázola, Irenice; Bonifaz, Laura C.; Boudin, Helene; Neunlist, Michel; Bueno, Susan M.; Kalergis, Alexis M.; Riedel, Claudia A.

2018-01-01

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. PMID:29593681

Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

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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.

Predominant modifier of extreme liver cancer susceptibility in C57BR/cdJ female mice localized to 6 Mb on chromosome 17

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Peychal, Stephanie E.-M.; Bilger, Andrea; Pitot, Henry C.; Drinkwater, Norman R.

2009-01-01

Sex hormones influence the susceptibility of inbred mice to liver cancer. C57BR/cdJ (BR) females are extremely susceptible to spontaneous and chemically induced liver tumors, in part due to a lack of protection against hepatocarcinogenesis normally offered by ovarian hormones. BR males are also moderately susceptible, and the susceptibility of both sexes of BR mice to liver tumors induced with N,N-diethylnitrosamine relative to the resistant C57BL/6J (B6) strain is caused by two loci designated Hcf1 and Hcf2 (hepatocarcinogenesis in females) located on chromosomes 17 and 1, respectively. The Hcf1 locus on chromosome 17 is the predominant modifier of liver cancer in BR mice. To validate the existence of this locus and investigate its potential interaction with Hcf2, congenic mice for each region were generated. Homozygosity for the B6.BR(D17Mit164-D17Mit2) region resulted in a 4-fold increase in liver tumor multiplicity in females and a 4.5-fold increase in males compared with B6 controls. A series of 16 recombinants covering the entire congenic region was developed to further narrow the area containing Hcf1. Susceptible heterozygous recombinants demonstrated a 3- to 7-fold effect in females and a 1.5- to 2-fold effect in males compared with B6 siblings. The effect in susceptible lines completely recapitulated the susceptibility of heterozygous full-length chromosome 17 congenics and furthermore narrowed the location of the Hcf1 locus to a single region of the chromosome from 30.05 to 35.83 Mb. PMID:19255062

Intestinal Permeability: The Basics

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Ingvar Bjarnason

1995-01-01

Full Text Available The authors review some of the more fundamental principles underlying the noninvasive assessment of intestinal permeability in humans, the choice of test markers and their analyses, and the practical aspects of test dose composition and how these can be changed to allow the specific assessment of regional permeability changes and other intestinal functions. The implications of increased intestinal permeability in the pathogenesis of human disease is discussed in relation to findings in patients with Crohn’s disease. A common feature of increased intestinal permeability is the development of a low grade enteropathy, and while quantitatively similar changes may be found in Crohn’s disease these seem to predict relapse of disease. Moreover, factors associated with relapse of Crohn’s disease have in common an action to increase intestinal permeability. While increased intestinal permeability does not seem to be important in the etiology of Crohn’s disease it may be a central mechanism in the clinical relapse of disease.

The Germline MLH1 K618A Variant and Susceptibility to Lynch Syndrome-Associated Tumors

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Medeiros, Fabiola; Lindor, Noralane M.; Couch, Fergus J.; Highsmith, W. Edward

2013-01-01

Missense variants discovered during sequencing of cancer susceptibility genes can be problematic for clinical interpretation. MLH1 K618A, which results from a 2-bp alteration (AAG→GCG) leading to a substitution of lysine to alanine in codon 618, has variously been interpreted as a pathogenic mutation, a variant of unknown significance, and a benign polymorphism. We evaluated the role of MLH1 K618A in predisposition to cancer by genotyping 1512 control subjects to assess its frequency in the general population. We also reviewed the literature concerning MLH1 K618A in families with colorectal cancer. The measured allele frequency of the K618A variant was 0.40%, which is remarkably close to the 0.44% summarized from 2491 control subjects in the literature. K618A was over-represented in families with suspected Lynch syndrome. In 1366 families, the allele frequency was 0.88% (OR = 2.1, 95% CI = 1.3 to 3.5; P = 0.006). In studies of sporadic cancers of the type associated with Lynch syndrome, K618A was over-represented in 1742 cases (allele frequency of 0.83) (OR = 2.0, 95% CI = 1.2 to 3.2; P = 0.008). We conclude that MLH1 K618A is not a fully penetrant Lynch syndrome mutation, although it is not without effect, appearing to increase the risk of Lynch syndrome-associated tumors approximately twofold. Our systematic assessment approach may be useful for variants in other genes. PMID:22426235

Frequency of intestinal parasites in employees of a state hospital

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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.

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

Intestinal ischemia-reperfusion injury augments intestinal mucosal injury and bacterial translocation in jaundiced rats.

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Yüksek, Yunus Nadi; Kologlu, Murat; Daglar, Gül; Doganay, Mutlu; Dolapci, Istar; Bilgihan, Ayse; Dolapçi, Mete; Kama, Nuri Aydin

2004-01-01

The aim of this study was to evaluate local effects and degree of bacterial translocation related with intestinal ischemia-reperfusion injury in a rat obstructive jaundice model. Thirty adult Sprague-Dawley rats (200-250 g) were divided into three groups; including Group 1 (jaundice group), Group 2 (jaundice-ischemia group) and Group 3 (ischemia group). All rats had 2 laparotomies. After experimental interventions, tissue samples for translocation; liver and ileum samples for histopathological examination, 25 cm of small intestine for mucosal myeloperoxidase and malondialdehyde levels and blood samples for biochemical analysis were obtained. Jaundiced rats had increased liver enzyme levels and total and direct bilirubin levels (p<0.05). Intestinal mucosal myeloperoxidase and malondialdehyde levels were found to be high in intestinal ischemia-reperfusion groups (p<0.05). Intestinal mucosal damage was more severe in rats with intestinal ischemia-reperfusion after bile duct ligation (p<0.05). Degree of bacterial translocation was also found to be significantly high in these rats (p<0.05). Intestinal mucosa is disturbed more severely in obstructive jaundice with the development of ischemia and reperfusion. Development of intestinal ischemia-reperfusion in obstructive jaundice increases bacterial translocation.

Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

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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.

Intestinal lymphangiectasia in children

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Isa, Hasan M.; Al-Arayedh, Ghadeer G.; Mohamed, Afaf M.

2016-01-01

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification. PMID:26837404

Differential Susceptibility of Bacteria to Mouse Paneth Cell a-Defensins under Anaerobic Conditions

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Jennifer R. Mastroianni

2014-10-01

Full Text Available Small intestinal Paneth cells secrete a-defensin peptides, termed cryptdins (Crps in mice, into the intestinal lumen, where they confer immunity to oral infections and define the composition of the ileal microbiota. In these studies, facultative bacteria maintained under aerobic or anaerobic conditions displayed differential sensitivities to mouse a-defensins under in vitro assay conditions. Regardless of oxygenation, Crps 2 and 3 had robust and similar bactericidal activities against S. typhimurium and S. flexneri, but Crp4 activity against S. flexneri was attenuated in the absence of oxygen. Anaerobic bacteria varied in their susceptibility to Crps 2-4, with Crp4 showing less activity than Crps 2 and 3 against Enterococcus faecalis, and Bacteroides fragilis in anaerobic assays, but Fusobacterium necrophorum was killed only by Crp4 and not by Crps 2 and 3. The influence of anaerobiosis in modulating Crp bactericidal activities in vitro suggests that a-defensin effects on the enteric microbiota may be subject to regulation by local oxygen tension.

Modeling the growth dynamics of multiple Escherichia coli strains in the pig intestine following intramuscular ampicillin treatment

DEFF Research Database (Denmark)

Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

2016-01-01

using a mathematical model to simulate the competitive growth of E. coli strains in a pig intestine under specified plasma concentration profiles of ampicillin. Results : In vitro growth results demonstrated that the resistant strains did not carry a fitness cost for their resistance, and that the most...... with ampicillin resistance in E. coli. Besides dosing factors, epidemiological factors (such as number of competing strains and bacterial excretion) influenced resistance development and need to be considered further in relation to optimal treatment strategies. The modeling approach used in the study is generic......Background : This study evaluated how dosing regimen for intramuscularly-administered ampicillin, composition of Escherichia coli strains with regard to ampicillin susceptibility, and excretion of bacteria from the intestine affected the level of resistance among Escherichia coli strains...

New insights into susceptibility to glioma.

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Liu, Yanhong; Shete, Sanjay; Hosking, Fay J; Robertson, Lindsay B; Bondy, Melissa L; Houlston, Richard S

2010-03-01

The study of inherited susceptibility to cancer has been one of the most informative areas of research in the past decade. Most of the cancer genetics studies have been focused on the common tumors such as breast and colorectal cancers. As the allelic architecture of these tumors is unraveled, research attention is turning to other rare cancers such as glioma, which are also likely to have a major genetic component as the basis of their development. In this brief review we discuss emerging data on glioma whole genome-association searches to identify risk loci. Two glioma genome-wide association studies have so far been reported. Our group identified 5 risk loci for glioma susceptibility (TERT rs2736100, CCDC26 rs4295627, CDKN2A/CDKN2B rs4977756, RTEL1 rs6010620, and PHLDB1 rs498872). Wrensch and colleagues provided further evidence to 2 risk loci (CDKN2B rs1412829 and RTEL1 rs6010620) for GBM and anaplastic astrocytoma. Although these data provide the strongest evidence to date for the role of common low-risk variants in the etiology of glioma, the single-nucleotide polymorphisms identified alone are unlikely to be candidates for causality. Identifying the causal variant at each specific locus and its biological impact now poses a significant challenge, contingent on a combination of fine mapping and functional analyses. Finally, we hope that a greater understanding of the biological basis of the disease will lead to the development of novel therapeutic interventions.

Intestinal pseudo-obstruction

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... Staying in bed for long periods of time (bedridden). Taking drugs that slow intestinal movements. These include ... be tried: Colonoscopy may be used to remove air from the large intestine. Fluids can be given ...

Identification of Aging-Associated Gene Expression Signatures That Precede Intestinal Tumorigenesis.

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Yoshihisa Okuchi

Full Text Available Aging-associated alterations of cellular functions have been implicated in various disorders including cancers. Due to difficulties in identifying aging cells in living tissues, most studies have focused on aging-associated changes in whole tissues or certain cell pools. Thus, it remains unclear what kinds of alterations accumulate in each cell during aging. While analyzing several mouse lines expressing fluorescent proteins (FPs, we found that expression of FPs is gradually silenced in the intestinal epithelium during aging in units of single crypt composed of clonal stem cell progeny. The cells with low FP expression retained the wild-type Apc allele and the tissues composed of them did not exhibit any histological abnormality. Notably, the silencing of FPs was also observed in intestinal adenomas and the surrounding normal mucosae of Apc-mutant mice, and mediated by DNA methylation of the upstream promoter. Our genome-wide analysis then showed that the silencing of FPs reflects specific gene expression alterations during aging, and that these alterations occur in not only mouse adenomas but also human sporadic and hereditary (familial adenomatous polyposis adenomas. Importantly, pharmacological inhibition of DNA methylation, which suppresses adenoma development in Apc-mutant mice, reverted the aging-associated silencing of FPs and gene expression alterations. These results identify aging-associated gene expression signatures that are heterogeneously induced by DNA methylation and precede intestinal tumorigenesis triggered by Apc inactivation, and suggest that pharmacological inhibition of the signature genes could be a novel strategy for the prevention and treatment of intestinal tumors.

Synergistic effect of aluminum and ionizing radiation upon ultrastructure, oxidative stress and apoptotic alterations in Paneth cells of rat intestine.

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Eltahawy, N A; Elsonbaty, S M; Abunour, S; Zahran, W E

2017-03-01

Environmental and occupational exposure to aluminum along with ionizing radiation results in serious health problems. This study was planned to investigate the impact of oxidative stress provoked by exposure to ionizing radiation with aluminum administration upon cellular ultra structure and apoptotic changes in Paneth cells of rat small intestine . Animals received daily aluminum chloride by gastric gavage at a dose 0.5 mg/Kg BW for 4 weeks. Whole body gamma irradiation was applied at a dose 2 Gy/week up to 8 Gy. Ileum malondialdehyde, advanced oxidative protein products, protein carbonyl and tumor necrosis factor-alpha were assessed as biomarkers of lipid peroxidation, protein oxidation and inflammation respectively along with superoxide dismutase, catalase, and glutathione peroxidase activities as enzymatic antioxidants. Moreover, analyses of cell cycle division and apoptotic changes were evaluated by flow cytometry. Intestinal cellular ultra structure was investigated using transmission electron microscope.Oxidative and inflammatory stresses assessment in the ileum of rats revealed that aluminum and ionizing radiation exposures exhibited a significant effect upon the increase in oxidative stress biomarkers along with the inflammatory marker tumor necrosis factor-α accompanied by a significant decreases in the antioxidant enzyme activities. Flow cytometric analyses showed significant alterations in the percentage of cells during cell cycle division phases along with significant increase in apoptotic cells. Ultra structurally, intestinal cellular alterations with marked injury in Paneth cells at the sites of bacterial translocation in the crypt of lumens were recorded. The results of this study have clearly showed that aluminum and ionizing radiation exposures induced apoptosis with oxidative and inflammatory disturbance in the Paneth cells of rat intestine, which appeared to play a major role in the pathogenesis of cellular damage. Furthermore, the

FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

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Leandra Fiori Lopes

2014-01-01

Full Text Available Triple negative breast cancer (TNBC is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2. FOXP3 (forkhead transcription factor 3 is a marker of regulatory T cells (Tregs, whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548 and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction. Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06 in relation to TNBC susceptibility. Most of the patients (83% showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026. In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.

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Fasano, Alessio

2011-01-01

The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a "leaky gut" in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis

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Jung-Soo Pyo

2015-05-01

Full Text Available Background: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC. Methods: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. Results: MUC2 expression was found in 58 of 167 GCs (34.7%. MUC2-expressing GC showed lower primary tumor (T, regional lymph node (N, and tumor node metastasis (TNM stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively. However, MUC2 expression was not correlated with Lauren’s classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively but not with Lauren’s classification, pN stage, or pTNM stage. Conclusions: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

Creatine maintains intestinal homeostasis and protects against colitis.

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Turer, Emre; McAlpine, William; Wang, Kuan-Wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R; Beutler, Bruce

2017-02-14

Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N -ethyl- N -nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted ( Gatm c/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatm c/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatm c/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease

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Deanna L. Gibson

2012-08-01

Full Text Available The gastrointestinal (GI microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn’s disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed.

Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo?Obstruction in 6 Dogs

OpenAIRE

Zacuto, A.C.; Pesavento, P.A.; Hill, S.; McAlister, A.; Rosenthal, K.; Cherbinsky, O.; Marks, S.L.

2015-01-01

Background Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo?obstruction in humans and animals. Objective To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Animals Six client?owned dogs. Methods Retrospective case series. Medical records were reviewed to de...

A Mimicker of Gallbladder Carcinoma: Cystic Gastric Heterotopia with Intestinal Metaplasia

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Gonca ÖZGÜN

2017-01-01

Full Text Available Heterotopic gastric mucosa in the gallbladder is an unusual entity and is usually clinically silent. We report a 75-year-old female patient who presented with intermittent upper abdomial pain radiating to the back. Abdominal imaging studies showed a sessile polypoid lesion and a gallstone in the gallbladder. Gallbladder carcinoma was suspected and cholecystectomy performed. Intraoperative frozen section examination suggested mucinous tumor, suspicious for malignancy. However, the permanent sections revealed aberrant gastric tissue consisted of gastric pyloric and fundic glands of heterotopic gastric mucosa with intestinal metaplasia in the gallbladder.

A Mimicker of Gallbladder Carcinoma: Cystic Gastric Heterotopia with Intestinal Metaplasia.

Science.gov (United States)

Özgün, Gonca; Adim, Şaduman Balaban; Uğraş, Nesrin; Kiliçturgay, Sadık

2017-01-01

Heterotopic gastric mucosa in the gallbladder is an unusual entity and is usually clinically silent. We report a 75-year-old female patient who presented with intermittent upper abdomial pain radiating to the back. Abdominal imaging studies showed a sessile polypoid lesion and a gallstone in the gallbladder. Gallbladder carcinoma was suspected and cholecystectomy performed. Intraoperative frozen section examination suggested mucinous tumor, suspicious for malignancy. However, the permanent sections revealed aberrant gastric tissue consisted of gastric pyloric and fundic glands of heterotopic gastric mucosa with intestinal metaplasia in the gallbladder.

Diffused and sustained inhibitory effects of intestinal electrical stimulation on intestinal motility mediated via sympathetic pathway.

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Zhao, Xiaotuan; Yin, Jieyun; Wang, Lijie; Chen, Jiande D Z

2014-06-01

The aims were to investigate the energy-dose response effect of intestinal electrical stimulation (IES) on small bowel motility, to compare the effect of forward and backward IES, and to explore the possibility of using intermittent IES and mechanism of IES on intestinal motility. Five dogs implanted with a duodenal cannula and one pair of intestinal serosal electrodes were studied in five sessions: 1) energy-dose response study; 2) forward IES; 3) backward IES; 4) intermittent IES vs. continuous IES; 5) administration of guanethidine. The contractile activity and tonic pressure of the small intestine were recorded. The duration of sustained effect after turning off IES was manually calculated. 1) IES with long pulse energy dose dependently inhibited contractile activity and tonic pressure of the small intestine (p intestine depended on the energy of IES delivered (p intestine. 5) Guanethidine blocked the inhibitory effect of IES on intestinal motility. IES with long pulses inhibits small intestinal motility; the effect is energy-dose dependent, diffused, and sustained. Intermittent IES has the same efficacy as the continuous IES in inhibiting small intestinal motility. Forward and backward IES have similar inhibitory effects on small bowel motility. This IES-induced inhibitory effect is mediated via the sympathetic pathway. © 2013 International Neuromodulation Society.

Application of small intestine decompression combined with oral feeding in middle and late period of malignant small bowel obstruction.

Science.gov (United States)

Li, Dechun; Du, Hongtao; Shao, Guoqing; Guo, Yongtuan; Lu, Wan; Li, Ruihong

2017-07-01

The application value of small intestine decompression combined with oral feeding in the middle and late period of malignant small bowel obstruction was examined. A total of 22 patients with advanced malignant small bowel obstruction were included in the present study. An ileus tube was inserted via the nose under fluoroscopy into the obstructed small intestine of each patient. At the same time, the insertion depth the of the catheter was adjusted. When the catheter was blocked, small bowel selective angiography was performed to determine the location and cause of the obstruction and the extent of the obstruction, and to determine the length of the small intestine in the site of obstruction, and to select the variety and tolerance of enteral nutrition. We observed the decompression tube flow and ease of intestinal obstruction. In total, 20 patients were treated with oral enteral nutrition after abdominal distension, and 22 cases were treated by the nose to observe the drainage and the relief of intestinal obstruction. The distal end of the catheter was placed in a predetermined position. The symptoms of intestinal obstruction were relieved 1-4 days after decompression. The 22 patients with selective angiography of the small intestine showed positive X-ray signs: 18 patients with oral enteral nutrition therapy had improved the nutritional situation 2 weeks later. In 12 cases, where there was anal defecation exhaust, 2 had transient removal of intestinal obstruction catheter. In conclusion, this comprehensive treatment based on small intestine decompression combined with enteral nutrition is expected to become a new therapeutic approach and method for the treatment of patients with advanced tumor small bowel obstruction.

Prognostic significance of microsatellite instability in curatively resected adenocarcinoma of the small intestine.

Science.gov (United States)

Brueckl, Wolfgang M; Heinze, Elvira; Milsmann, Catrin; Wein, Axel; Koebnick, Corinna; Jung, Andreas; Croner, Roland S; Brabletz, Thomas; Günther, Klaus; Kirchner, Thomas; Hahn, Eckhart G; Hohenberger, Werner; Becker, Heinz; Reingruber, Bertram

2004-01-20

Adenocarcinoma of the small intestine (ACSI) is a rare condition with few studies addressing follow-up and prognosis. Tumors of 35 patients with curative resection of an ACSI were retrospectively analyzed by immunohistochemistry: p53, hMLH1, hMSH2 and hMSH6 and microsatellite instability (MSI): BAT-26, BAX, TGF-beta RII. With a median follow up of 6.1 years, the median cancer-specific survival (CSS) was 36.2 months. Patients who were highly instable (MSI-H) (n=10) had a CSS of 49.6 months in contrast to patients with stable tumors (23.2 months) (P=0.010). Additionally, a low tumor stage according to UICC and MSI-H were shown to be independent factors (P=0.005 and P<0.001) for an increased survival in multivariate analysis. Therefore, it is suggested that analysis of the MSI status might prove useful in discerning prognosis within cancers of the same stage.

Clinical applications of susceptibility weighted MR imaging of the brain - a pictorial review

International Nuclear Information System (INIS)

Thomas, Bejoy; Somasundaram, Sivaraman; Thamburaj, Krishnamoorthy; Kesavadas, Chandrasekharan; Kumar Gupta, Arun; Bodhey, Narendra K.; Raman Kapilamoorthy, Tirur

2008-01-01

Susceptibility-weighted imaging (SWI) is a novel magnetic resonance (MR) technique that exploits the magnetic susceptibility differences of various tissues, such as blood, iron and calcification. This pictorial review covers many clinical conditions illustrating its usefulness. SWI consists of using both magnitude and phase images from a high-resolution, three-dimensional fully velocity-compensated gradient echo sequence. Phase mask is created from the MR phase images, and multiplying these with the magnitude images increase the conspicuity of the smaller veins and other sources of susceptibility effects, which is depicted using minimal intensity projection (minIP). The phase images are useful in differentiating between diamagnetic and paramagnetic susceptibility effects of calcium and blood, respectively. This unique MR sequence will help in detecting occult low flow vascular lesions, calcification and cerebral microbleed in various pathologic conditions and aids in characterizing tumors and degenerative diseases of the brain. This sequence also can be used to visualize normal brain structures with conspicuity. Susceptibility-weighted imaging is useful in differentiating and characterizing diverse brain pathologies. (orig.)

Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells

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Yu Takahashi

2017-09-01

Full Text Available Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs and adipocytes have not been investigated, in part because IEC physiology is difficult to replicate in culture. In this study, we originally prepared intact, polarized, and cytokine responsive IEC monolayers from primary or induced pluripotent stem cell-derived intestinal organoids by simple and repeatable methods. When these physiological IECs were co-cultured with differentiated adipocytes in Transwell, pro-inflammatory genes were induced in both cell types, suggesting reciprocal inflammatory activation in the absence of immunocompetent cells. These inflammatory responses were blocked by nuclear factor-κB or signal transducer and activator of transcription 3 inhibition and by anti-tumor necrosis factor- or anti-interleukin-6-neutralizing antibodies. Our results highlight the utility of these monolayers for investigating IEC biology. Furthermore, this system recapitulates the intestinal epithelium–mesenteric fat signals that potentially trigger or worsen inflammatory disorders such as Crohn's disease and obesity-related enterocolitis.

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

The inflammatory bowel disease (IBD susceptibility genes NOD1 and NOD2 have conserved anti-bacterial roles in zebrafish

Directory of Open Access Journals (Sweden)

Stefan H. Oehlers

2011-11-01

Inflammatory bowel disease (IBD, in the form of Crohn’s disease (CD or ulcerative colitis (UC, is a debilitating chronic immune disorder of the intestine. A complex etiology resulting from dysfunctional interactions between the intestinal immune system and its microflora, influenced by host genetic susceptibility, makes disease modeling challenging. Mutations in NOD2 have the highest disease-specific risk association for CD, and a related gene, NOD1, is associated with UC. NOD1 and NOD2 encode intracellular bacterial sensor proteins acting as innate immune triggers, and represent promising therapeutic targets. The zebrafish has the potential to aid in modeling genetic and environmental aspects of IBD pathogenesis. Here, we report the characterization of the Nod signaling components in the zebrafish larval intestine. The nod1 and nod2 genes are expressed in intestinal epithelial cells and neutrophils together with the Nod signaling pathway genes ripk2, a20, aamp, cd147, centaurin b1, erbin and grim-19. Using a zebrafish embryo Salmonella infection model, morpholino-mediated depletion of Nod1 or Nod2 reduced the ability of embryos to control systemic infection. Depletion of Nod1 or Nod2 decreased expression of dual oxidase in the intestinal epithelium and impaired the ability of larvae to reduce intracellular bacterial burden. This work highlights the potential use of zebrafish larvae in the study of components of IBD pathogenesis.

Three-dimensional reconstruction of colorectal tumors from serial tissue sections by computer graphics: a preliminary study.

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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.

The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors

Science.gov (United States)

Vercherat, Cécile; Blanc, Martine; Lepinasse, Florian; Gadot, Nicolas; Couderc, Christophe; Poncet, Gilles; Walter, Thomas; Joly, Marie-Odile; Hervieu, Valérie; Scoazec, Jean-Yves; Roche, Colette

2015-01-01

Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs. SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways. This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy. PMID:26447612

Intestinal lymphangiectasia in adults.

Science.gov (United States)

Freeman, Hugh James; Nimmo, Michael

2011-02-15

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial

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

The mammalian intestinal tract is a complex ecosystem colonised by a high and diverse number of commensal bacterial. Bacteria colonising the intestinal tract have a profound impact on host health e.g. by acting as a barrier against colonisation by pathogens and by contributing to digestion...... of complex food components. In this regard there is a considerable interest in dietary components that can modulate the gut microbiota and potentially improve gut health. Some gut bacteria, known as probiotics, are belived to improve gut health upond ingestion, whereas non-digestible (ND) dietary...... of the gut microbiota or by stimulating the immune response. Salmonella is a genus of Gram-negative bacteria that are a major cause of food-borne illness globally. Several studies with probiotics have demonstrated protective effects against murine Salmonella infections, while studies with prebiotics have...

The CT signs of intestinal volvulus

International Nuclear Information System (INIS)

Ji Jiansong; Wang Zufei; Xu Zhaolong; Lv Guijian; Xu Min; Zhao Zhongwei; Su Jinliang; Zhou Limin

2005-01-01

Objective: To improve the accuracy rate of spiral CT diagnosing intestinal volvulus. Methods: To analysis the CT findings of 9 cases of intestinal volvulus proved by operation, the main reconstruction techniques were multiplanar reformation (MPR) and sliding thin-slab maximum intensity projection (STS-MIP). Results: All the 9 cases were diagnosed accurately, the main signs were 'whirlpool' of intestine (6 cases) and vessels (9 cases),'target loop' (2 cases),'beak'(6 cases). Conclusion: 'Whirlpool' of vessels is a specific sign to diagnose intestinal volvulus, 'target loop', reduced enhancement of intestinal wall and ascites are the reliable signs to strangulated intestinal obstruction. Spiral CT and reconstructions have important value to diagnose the intestinal volvulus. (authors)

Recurrent small intestine intussusception in a patient with Peutz-Jeghers syndrome Invaginación recurrente del intestino delgado en un paciente con síndrome de Pentz-Jeghers

OpenAIRE

Orestis Ioannidis; Styliani Papaemmanouil; George Paraskevas; Anastasios Kotronis; Stavros Chatzopoulos; Athina Konstantara; Nikolaos Papadimitriou; Apostolos Makrantonakis; Emmanouil Kakoutis

2012-01-01

Peutz-Jeghers syndrome is a rare hereditary autosomal dominant disease caused by a mutation of the tumor suppressor gene serine/threonine kinase 11 located in chromosome 19p13.3. It is characterized by the presence of extensive mucocutaneous pigmentation, especially of the lips and the occurrence of hamartomatous polyps throughout the gastrointestinal tract. Gastrointestinal hamartomas occur predominantly in the small intestine and can become symptomatic leading usually to intestinal obstruct...

The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

Science.gov (United States)

Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

2016-05-23

DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Inherited susceptibility to cancer and other factors influencing occurrence of cancer

International Nuclear Information System (INIS)

Pawlak, A.L.

1994-01-01

The types of defects and polymorphisms leading to hereditary susceptibility to cancer include proneness to increased DNA damage, recessive syndromes of faulty DNA repair and differentiation, as well as dominant mutations of cell cycle and control proliferation. The cancer susceptibility syndromes inherited in a dominant fashion are caused by mutations in tumor suppressor genes. These genes are recessive in relation to wild type alleles. In two syndromes of hereditary mutations in tumor suppressor genes (Rb and WT2), their expression 'in vivo' may be influenced by the sex of the transmitting parent, what points to modulation by imprinting. Genetic heterogeneity of the population in susceptibility to genotoxic agents is related to the individual variation in acceptable levels of exposure to agents and factors, such as products of incomplete combustion (PIC), UV ('xeroderma pigmentosum') and ionizing radiation ('ataxia telangiectasia'). DNA damage and adducts are considered to be indicative of genotoxic exposure and its effect as well as modulation of carcinogenic damage by genetic polymorphisms. Gene and protein polymorphisms are considered as markers of increased individual risk. Since environmental factors are considered to be able to control, the individual susceptibility to enhanced DNA damage and environmentally induced cancers could be counteracted by decreasing the levels of contamination or exposure. This explains the wide interest in markers of this individual sensitivity. Most of the postulated markers of sensitivity to PIV do not, however, prove to be generally applicable in that sense. Their prognostic value is limited either by low amplitude of the effect, or by their character specific either to the population or to the cancer type. The polymorphisms most relevant to cancers induced by PIC exposures may be those of inductibility of benzopyrene hydroxylase, and some other DNA polymorphisms concerning the CYP1A1 gene. (author). 24 refs, 1 fig., 3 tabs

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)

Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract

Energy Technology Data Exchange (ETDEWEB)

Hayes, S L; Lye, D J; McKinstry, Craig A.; Vesper, Sephen J.

2010-01-01

Aeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small intestinal extracts, 24 hours after oral infection with an A. caviae strain, provides evidence of a Th1 type immune response. A large number of gamma-interferon (γ-IFN) induced genes are up-regulated as well as several tumor necrosis factor-alpha (TNF-α) transcripts. A. caviae has always been considered as opportunistic pathogen because it lacks obvious virulence factors. This current effort suggests that an A. caviae strain can colonize the murine intestinal tract and cause what has been described by others as a dysregulatory cytokine response. This response could explain why a number of diarrheal waterborne disease cases have been attributed to A. caviae even though it lacks obvious enteropathogenic properties.

Foreign body-associated intestinal pyogranuloma resulting in intestinal obstruction in four dogs.

Science.gov (United States)

Papazoglou, L G; Tontis, D; Loukopoulos, P; Patsikas, M N; Hermanns, W; Kouti, V; Timotheou, T; Liapis, I; Tziris, N; Rallis, T S

2010-04-17

Intestinal obstruction resulting from an intramural foreign body-associated pyogranuloma was diagnosed in four dogs. Vomiting and weight loss were the main clinical signs. On physical examination, a mass in the abdomen was detected in three dogs. Abdominal radiography demonstrated the presence of soft tissue opacity in three of the dogs and gas-filled dilated intestinal loops in all four dogs. Abdominal ultrasonography showed hyperkinetic fluid-filled dilated intestinal loops and a hypoechoic small intestinal mass in all the dogs. Exploratory coeliotomy confirmed the presence of a jejunal mass, which was removed by resection and anastomosis in all the dogs. In one of the dogs a linear foreign body was also found cranial to the mass and was removed through a separate enterotomy incision. The lesions were diagnosed as foreign body-associated intestinal pyogranulomas on histological examination. Three dogs recovered without complications, but the fourth showed signs of septic peritonitis four days after surgery and was euthanased at the owner's request. The other three dogs remained disease-free 12 to 42 months after surgery.

(--Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance

Directory of Open Access Journals (Sweden)

Eleonora Cremonini

2018-04-01

Full Text Available Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (--epicatechin (EC supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2–20 mg/kg body weight mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption. Keywords: Intestinal permeability, (--Epicatechin, Steatosis, Insulin resistance, Endotoxemia, NADPH oxidase

Diet and host-microbial crosstalk in postnatal intestinal immune homeostasis.

Science.gov (United States)

Jain, Nitya; Walker, W Allan

2015-01-01

Neonates face unique challenges in the period following birth. The postnatal immune system is in the early stages of development and has a range of functional capabilities that are distinct from the mature adult immune system. Bidirectional immune-microbial interactions regulate the development of mucosal immunity and alter the composition of the microbiota, which contributes to overall host well-being. In the past few years, nutrition has been highlighted as a third element in this interaction that governs host health by modulating microbial composition and the function of the immune system. Dietary changes and imbalances can disturb the immune-microbiota homeostasis, which might alter susceptibility to several autoimmune and metabolic diseases. Major changes in cultural traditions, socioeconomic status and agriculture are affecting the nutritional status of humans worldwide, which is altering core intestinal microbial communities. This phenomenon is especially relevant to the neonatal and paediatric populations, in which the microbiota and immune system are extremely sensitive to dietary influences. In this Review, we discuss the current state of knowledge regarding early-life nutrition, its effects on the microbiota and the consequences of diet-induced perturbation of the structure of the microbial community on mucosal immunity and disease susceptibility.

Incidentally discovered goblet cell carcinoid clinically presenting as acute intestinal obstruction: A case report with review of literature

Directory of Open Access Journals (Sweden)

Nishat Afroz

2014-01-01

Full Text Available Goblet cell carcinoid (GCC is a rare variant of carcinoid tumor that exclusively involves the appendix. It usually occurs in 5 th -6 th decade with the most common clinical presentation being acute appendicitis. The natural history of this tumor is intermediate between carcinoids and adenocarcinomas. We here report a case of GCC diagnosed incidentally in a patient presenting with acute intestinal obstruction. Ultrasonographic examination supported the clinical diagnosis of acute intestinal obstruction, following which the patient underwent laparotomy and resection of ileum along with appendix was done. On gross pathological examination, a nodular growth was present on the tip and body of appendix that was yellow in color with a semi-solid to mucoid consistency on cut section. On microscopy, lakes of mucin with few acinar structures floating in them were seen. The submucosa as well as serosa were infiltrated by clusters of goblet cells and well-formed acini, with little atypia. Glands and nests were positive for per-iodic acid Schiff and immunohistochemistry showed focal chromogranin positivity in glandular structures, thereby confirming the diagnosis of GCC. Although the prognosis of GCC is better than adenocarcinomas, it is one of the carcinoids having a poorer outcome when compared with other variants of carcinoid tumor. Therefore, it is important to rule out other differential diagnoses of goblet cell carcinoid, the most important being mucinous adenocarcinomas.

Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

Science.gov (United States)

Schrader, Kasmintan A; Cheng, Donavan T; Joseph, Vijai; Prasad, Meera; Walsh, Michael; Zehir, Ahmet; Ni, Ai; Thomas, Tinu; Benayed, Ryma; Ashraf, Asad; Lincoln, Annie; Arcila, Maria; Stadler, Zsofia; Solit, David; Hyman, David M; Hyman, David; Zhang, Liying; Klimstra, David; Ladanyi, Marc; Offit, Kenneth; Berger, Michael; Robson, Mark

2016-01-01

Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well. To estimate the burden of germline variants identified through routine clinical tumor sequencing. Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014. The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors. The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99

NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis.

Science.gov (United States)

Hirota, Simon A; Ng, Jeffrey; Lueng, Alan; Khajah, Maitham; Parhar, Ken; Li, Yan; Lam, Victor; Potentier, Mireille S; Ng, Kelvin; Bawa, Misha; McCafferty, Donna-Marie; Rioux, Kevin P; Ghosh, Subrata; Xavier, Ramnik J; Colgan, Sean P; Tschopp, Jurg; Muruve, Daniel; MacDonald, Justin A; Beck, Paul L

2011-06-01

Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18. In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis. Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota. Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

Science.gov (United States)

Korpela, Katri; Mutanen, Annika; Salonen, Anne; Savilahti, Erkki; de Vos, Willem M; Pakarinen, Mikko P

2017-02-01

Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

The plain film roentgenographic findings in diagnosis of intestinal volvulus

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Chung, Gyung Ho; Seo, Yeon Hee; Sohn, Myung Hee; Kim, Chong Soo; Choi, Ki Chul; Jeon, Doo Sung [Chunbuk National University College of Medicine, Chunju (Korea, Republic of)

1988-08-15

Intestinal volvulus indicates the twisting of a loop of bowel around the axis of its own mesentery and implies interference of the blood supply associated with the obstruction. It is the purpose of this communication to review the clinical and plain roentgen manifestation on the basis of which the diagnosis can be established. In this regard, the authors have reviewed 60 cases of intestinal volvulus which have been treated from Jan, 1976 to Dec, 1987 at Chunbuk National University and Chunju presbyterian Medical Center. The results were as follows: 1) The most frequent type of intestinal volvulus was volvulus of small intestine (50%), followed by sigmoid volvulus (40%), compound volvulus (5%), cecal volvulus (3.3%), and transverse colon volvulus (1.7%). 2) The sex distribution of intestinal vovulus assumed a male to female ratio of 2.9:1. The incidence ratio of male to female was 3.4:1 in the volvulus of small intestine, 1.67:1 in sigmoid volvulus. All patients with cecal volvulus, compound volvulus, and transverse volvulus were male. 3) Of the age distribution, the youngest case was an infant of 8 months, the oldest one in 79 years. There happened even age distribution in the volvulus of small intestine at any age group, and old age distribution in colon volvulus. 4) In 30 cases of small intestine, the predisposing factors were previous abdominal operation in 20 cases (66.7%), congenital band in 3 cases (10%), malrotation in 3 cases (10%), tumor in 1 case (3.3%), and Meckel's diverticulum in 1 case (3.3%). In 24 cases of sigmoid volvulus, the predisposing factors were redundant mobile bowel in 18 cases (75%), previous operation in 4 cases (16.7%), and pelvic inflammation and adhesion in 2 cases (8.4%). In 2 cases of cecal volulus, 1 case had the history of previous operation, and 1 case had long redundant cecal loop. In 3 cases of compound volvulus, 2 cases had redundant mobile sigmoid, and 1 case had previous operation. 5) In 30 cases of the volulus of small

The plain film roentgenographic findings in diagnosis of intestinal volvulus

International Nuclear Information System (INIS)

Chung, Gyung Ho; Seo, Yeon Hee; Sohn, Myung Hee; Kim, Chong Soo; Choi, Ki Chul; Jeon, Doo Sung

1988-01-01

Intestinal volvulus indicates the twisting of a loop of bowel around the axis of its own mesentery and implies interference of the blood supply associated with the obstruction. It is the purpose of this communication to review the clinical and plain roentgen manifestation on the basis of which the diagnosis can be established. In this regard, the authors have reviewed 60 cases of intestinal volvulus which have been treated from Jan, 1976 to Dec, 1987 at Chunbuk National University and Chunju presbyterian Medical Center. The results were as follows: 1) The most frequent type of intestinal volvulus was volvulus of small intestine (50%), followed by sigmoid volvulus (40%), compound volvulus (5%), cecal volvulus (3.3%), and transverse colon volvulus (1.7%). 2) The sex distribution of intestinal vovulus assumed a male to female ratio of 2.9:1. The incidence ratio of male to female was 3.4:1 in the volvulus of small intestine, 1.67:1 in sigmoid volvulus. All patients with cecal volvulus, compound volvulus, and transverse volvulus were male. 3) Of the age distribution, the youngest case was an infant of 8 months, the oldest one in 79 years. There happened even age distribution in the volvulus of small intestine at any age group, and old age distribution in colon volvulus. 4) In 30 cases of small intestine, the predisposing factors were previous abdominal operation in 20 cases (66.7%), congenital band in 3 cases (10%), malrotation in 3 cases (10%), tumor in 1 case (3.3%), and Meckel's diverticulum in 1 case (3.3%). In 24 cases of sigmoid volvulus, the predisposing factors were redundant mobile bowel in 18 cases (75%), previous operation in 4 cases (16.7%), and pelvic inflammation and adhesion in 2 cases (8.4%). In 2 cases of cecal volulus, 1 case had the history of previous operation, and 1 case had long redundant cecal loop. In 3 cases of compound volvulus, 2 cases had redundant mobile sigmoid, and 1 case had previous operation. 5) In 30 cases of the volulus of small

A noninvasive multimodal technique to monitor brain tumor vascularization

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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.

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

[Right Hemi-Colectomy for a Metastatic Transverse Colon Tumor from Breast Cancer Following Bilateral Breast Cancer Resection - A Case Report].

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Okamura, Shu; Yanagisawa, Tetsu; Ohishi, Kazuhito; Murata, Kohei; Nushijima, Yoichiro; Hamano, Rie; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

2016-11-01

We herein report the case of a 75-year-old female patient who underwent 4 surgeries for bilateral breast cancer and its recurrence. When she presented at a clinic with an irritable colon, a fist-sized tumor was palpated in the right upper abdomen at her first medical examination. Abdominal CT scan at the clinic revealed a tumor with a maximum diameter of 10 cm on the right side of the transverse colon and multiple swollen mesenteric lymph nodes. Therefore, the patient was referred to our hospital for surgery. Colonoscopy revealed stenosis of the same lesion with an edematous mucosa and sclerosis. Using immunohistochemistry, a biopsy specimen from the lesion tested positive for CK AE1+AE3, and negative for CD20(-)and CD3 (-). As a result, the tumor was diagnosed as a poorly differentiated adenocarcinoma. We performed right hemicolectomy to avoid her intestinal obstruction. Tumor cells were mainly present at the subserosa, according to HEstaining. Using immunostaining, the cells were tested for the following markers: CDX2(-), GCDFP15(weakly positive), CK7(strongly positive), CD20(partially positive), E R(+), PgR(-), and HER2(1+), characterizing the tumor as metastasis of breast cancer. Although gastro-intestinal metastasis from breast cancer is rare, and colon metastasis is even rarer, it might be necessary to rule out the possibility of a metastatic colon tumor from breast cancer when treating patients with a colon tumor who have undergone surgery for breast cancer.

Primary intestinal lymphangiectasia.

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Suresh, N; Ganesh, R; Sankar, Janani; Sathiyasekaran, Malathi

2009-10-01

Primary intestinal lymphangiectasia (PIL) is a rare disease of intestinal lymphatics presenting with hypoproteinemia, bilateral lower limb edema, ascites, and protein losing enteropathy. We report a series of 4 children from Chennai, India presenting with anasarca, recurrent diarrhea, hypoproteinemia and confirmatory features of PIL on endoscopy and histopathology.

Epidermal Growth Factor Improves Intestinal Integrity and Survival in Murine Sepsis Following Chronic Alcohol Ingestion.

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Klingensmith, Nathan J; Yoseph, Benyam P; Liang, Zhe; Lyons, John D; Burd, Eileen M; Margoles, Lindsay M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

2017-02-01

Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. Six-week-old FVB/N mice were randomized to receive 20% alcohol or water for 12 weeks. All mice then underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive either intraperitoneal injection of EGF (150 μg/kg/day) or normal saline. Water-fed mice given EGF had decreased 7-day mortality compared with water-fed mice (18% vs. 55%). Alcohol-fed mice given EGF also had decreased 7-day mortality compared with alcohol-fed mice (48% vs. 79%). Notably, while systemic EGF improved absolute survival to a similar degree in both water-fed and alcohol-fed mice, mortality was significantly higher in alcohol+EGF mice compared with water+EGF mice. Compared with water-fed septic mice, alcohol-fed septic mice had worsened intestinal integrity with intestinal hyperpermeability, increased intestinal epithelial apoptosis, decreased proliferation and shorter villus length. Systemic administration of EGF to septic alcohol-fed mice decreased intestinal permeability compared with septic alcohol-fed mice given vehicle, with increased levels of the tight junction mediators claudin-5 and JAM-A. Systemic administration of EGF to septic alcohol-fed mice also decreased intestinal apoptosis with an improvement in the Bax/Bcl-2 ratio. EGF also improved both crypt proliferation and villus length in septic alcohol-fed mice. EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore

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

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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

Si-Jun-Zi Decoction Treatment Promotes the Restoration of Intestinal Function after Obstruction by Regulating Intestinal Homeostasis

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Xiangyang Yu

2014-01-01

Full Text Available Intestinal obstruction is a common disease requiring abdominal surgery with significant morbidity and mortality. Currently, an effective medical treatment for obstruction, other than surgical resection or decompression, does not exist. Si-Jun-Zi Decoction is a famous Chinese medicine used to replenish qi and invigorate the functions of the spleen. Modern pharmacological studies show that this prescription can improve gastrointestinal function and strengthen immune function. In this study, we investigated the effects of a famous Chinese herbal formula, Si-Jun-Zi Decoction, on the restoration of intestinal function after the relief of obstruction in a rabbit model. We found that Si-Jun-Zi Decoction could reduce intestinal mucosal injury while promoting the recovery of the small intestine. Further, Si-Jun-Zi Decoction could regulate the intestinal immune system. Our results suggest that Si-Jun-Zi Decoction promotes the restoration of intestinal function after obstruction by regulating intestinal homeostasis. Our observations indicate that Si-Jun-Zi Decoction is potentially a therapeutic drug for intestinal obstruction.

Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status.

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Hanyuda, Akiko; Cao, Yin; Hamada, Tsuyoshi; Nowak, Jonathan A; Qian, Zhi Rong; Masugi, Yohei; da Silva, Annacarolina; Liu, Li; Kosumi, Keisuke; Soong, Thing Rinda; Jhun, Iny; Wu, Kana; Zhang, Xuehong; Song, Mingyang; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Nishihara, Reiko

2017-05-01

Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32 years and 1528 rectal and colon cancer cases with available tumor pathological data were documented. The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly-differentiated foci (P heterogeneity  = 0.006). Higher BMI was associated with a higher risk of colorectal carcinoma without poorly-differentiated foci (≥30.0 vs. 18.5-22.4 kg/m 2 : multivariable-adjusted hazard ratio, 1.87; 95% confidence interval, 1.49-2.34; P trend   0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.

Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice.

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Lea-Maxie Haag

Full Text Available BACKGROUND: The zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition. METHODOLOGY/PRINCIPAL FINDINGS: Since the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis. CONCLUSION/SIGNIFICANCE: Murine colonization resistance against C. jejuni is abrogated by changes in the microbiota composition towards elevated E. coli loads during intestinal inflammation as well as in infant mice. Intestinal inflammation and microbiota shifts thus represent potential risk factors for C. jejuni infection. Corresponding interplays between C. jejuni and microbiota might

Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity.

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Trump, D L; Livingston, J N; Baylin, S B

1977-10-01

A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.

Gastric and intestinal surgery.

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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.

The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine.

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Sveta Chakrabarti

2014-09-01

Full Text Available The p38 mitogen-activated protein (MAP kinase signaling cassette has been implicated in stress and immunity in evolutionarily diverse species. In response to a wide variety of physical, chemical and biological stresses p38 kinases phosphorylate various substrates, transcription factors of the ATF family and other protein kinases, regulating cellular adaptation to stress. The Drosophila genome encodes three p38 kinases named p38a, p38b and p38c. In this study, we have analyzed the role of p38c in the Drosophila intestine. The p38c gene is expressed in the midgut and upregulated upon intestinal infection. We showed that p38c mutant flies are more resistant to infection with the lethal pathogen Pseudomonas entomophila but are more susceptible to the non-pathogenic bacterium Erwinia carotovora 15. This phenotype was linked to a lower production of Reactive Oxygen Species (ROS in the gut of p38c mutants, whereby the transcription of the ROS-producing enzyme Duox is reduced in p38c mutant flies. Our genetic analysis shows that p38c functions in a pathway with Mekk1 and Mkk3 to induce the phosphorylation of Atf-2, a transcription factor that controls Duox expression. Interestingly, p38c deficient flies accumulate lipids in the intestine while expressing higher levels of antimicrobial peptide and metabolic genes. The role of p38c in lipid metabolism is mediated by the Atf3 transcription factor. This observation suggests that p38c and Atf3 function in a common pathway in the intestine to regulate lipid metabolism and immune homeostasis. Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila. It also reveals that many roles initially attributed to p38a are in fact mediated by p38c.

The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine.

Science.gov (United States)

Chakrabarti, Sveta; Poidevin, Mickaël; Lemaitre, Bruno

2014-09-01

The p38 mitogen-activated protein (MAP) kinase signaling cassette has been implicated in stress and immunity in evolutionarily diverse species. In response to a wide variety of physical, chemical and biological stresses p38 kinases phosphorylate various substrates, transcription factors of the ATF family and other protein kinases, regulating cellular adaptation to stress. The Drosophila genome encodes three p38 kinases named p38a, p38b and p38c. In this study, we have analyzed the role of p38c in the Drosophila intestine. The p38c gene is expressed in the midgut and upregulated upon intestinal infection. We showed that p38c mutant flies are more resistant to infection with the lethal pathogen Pseudomonas entomophila but are more susceptible to the non-pathogenic bacterium Erwinia carotovora 15. This phenotype was linked to a lower production of Reactive Oxygen Species (ROS) in the gut of p38c mutants, whereby the transcription of the ROS-producing enzyme Duox is reduced in p38c mutant flies. Our genetic analysis shows that p38c functions in a pathway with Mekk1 and Mkk3 to induce the phosphorylation of Atf-2, a transcription factor that controls Duox expression. Interestingly, p38c deficient flies accumulate lipids in the intestine while expressing higher levels of antimicrobial peptide and metabolic genes. The role of p38c in lipid metabolism is mediated by the Atf3 transcription factor. This observation suggests that p38c and Atf3 function in a common pathway in the intestine to regulate lipid metabolism and immune homeostasis. Collectively, our study demonstrates that p38c plays a central role in the intestine of Drosophila. It also reveals that many roles initially attributed to p38a are in fact mediated by p38c.

Intestinal epithelium in inflammatory bowel disease

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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.

Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy.

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Shannon R M Kinney

Full Text Available IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g. exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs, and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs. In

Comparative study of pulsed-continuous arterial spin labeling and dynamic susceptibility contrast imaging by histogram analysis in evaluation of glial tumors.

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Arisawa, Atsuko; Watanabe, Yoshiyuki; Tanaka, Hisashi; Takahashi, Hiroto; Matsuo, Chisato; Fujiwara, Takuya; Fujiwara, Masahiro; Fujimoto, Yasunori; Tomiyama, Noriyuki

2018-06-01

Arterial spin labeling (ASL) is a non-invasive perfusion technique that may be an alternative to dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for assessment of brain tumors. To our knowledge, there have been no reports on histogram analysis of ASL. The purpose of this study was to determine whether ASL is comparable with DSC-MRI in terms of differentiating high-grade and low-grade gliomas by evaluating the histogram analysis of cerebral blood flow (CBF) in the entire tumor. Thirty-four patients with pathologically proven glioma underwent ASL and DSC-MRI. High-signal areas on contrast-enhanced T 1 -weighted images or high-intensity areas on fluid-attenuated inversion recovery images were designated as the volumes of interest (VOIs). ASL-CBF, DSC-CBF, and DSC-cerebral blood volume maps were constructed and co-registered to the VOI. Perfusion histogram analyses of the whole VOI and statistical analyses were performed to compare the ASL and DSC images. There was no significant difference in the mean values for any of the histogram metrics in both of the low-grade gliomas (n = 15) and the high-grade gliomas (n = 19). Strong correlations were seen in the 75th percentile, mean, median, and standard deviation values between the ASL and DSC images. The area under the curve values tended to be greater for the DSC images than for the ASL images. DSC-MRI is superior to ASL for distinguishing high-grade from low-grade glioma. ASL could be an alternative evaluation method when DSC-MRI cannot be used, e.g., in patients with renal failure, those in whom repeated examination is required, and in children.

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

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Zhou, Xing; Zhao, Yang; Chen, Siyu; Han, Songling; Xu, Xiaoqiu; Guo, Jiawei; Liu, Mengyu; Che, Ling; Li, Xiaohui; Zhang, Jianxiang

2016-08-08

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Impact of intestinal ischemia/reperfusion and lymph drainage on distant organs in rats

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He, Gui-Zhen; Zhou, Kai-Guo; Zhang, Rui; Wang, Yu-Kang; Chen, Xue-Feng

2012-01-01

AIM: To investigate the impact of intestinal ischemia/reperfusion (I/R) injury and lymph drainage on distant organs in rats. METHODS: Thirty-two Sprague-Dawley male rats, weighing 280-320 g, were randomly divided into blank, sham, I/R, and ischemia/reperfusion and drainage (I/R + D) groups (n = 8). All rats were subjected to 60 min ischemia by clamping the superior mesenteric artery, followed by 120 min reperfusion. The rats in the I/R + D group received intestinal lymph drainage for 180 min. In the sham group, the abdominal cavity was opened for 180 min, but the rats received no treatment. The blank group served as a normal and untreated control. A chromogenic limulus assay kit was used for quantitative detection of serum endotoxin. The serum concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, soluble cell adhesion molecules (sICAM-1), and high mobility group protein box 1 (HMGB1) were determined with an enzyme-linked immunosorbent assay kit. Histological evaluations of the intestine, liver, kidney, and lung were performed by hematoxylin and eosin staining and immunohistochemistry. HMGB1 protein expression was assayed by western blot analysis. RESULTS: The serum levels of endotoxin and HMGB1 in the I/R and I/R + D groups were significantly higher than those in the sham group (endotoxin, I/R and I/R + D vs sham: 0.033 ± 0.004 EU/mL, 0.024 ± 0.003 EU/mL vs 0.017 ± 0.009 EU/mL, respectively, P drainage could block the “gut-lymph” pathway, improve intestinal barrier function, and attenuate distant organ injury incurred by intestinal I/R. PMID:23326132

Could imatinib replace surgery in esophageal gastrointestinal stromal tumor

International Nuclear Information System (INIS)

Al-Salam, Suhail N.; El-Teraifi, Hassan A.; Taha, Mazen S.

2006-01-01

Gastrointestinal stromal tumors (GISTs) are cellular spindle, or epithelioid tumors that occur in the stomach, intestine and rarely in the esophagus. A 61-years-old man was complaining of resistant dry cough with dysphagia for one month duration. Upper gastrointestinal tract endoscopic examination showed a polypoid mass 30 cm from the incisors obstructing 50% of the lumen, where multiple biopsies were taken. Magnetic resonance imaging (MRI) showed a mass in the wall of the esophagus extending into the thoracic cavity. Histologically, the stained sections with routine hematoxylin and eosin as well as the immunohistochemical stainsfor CD117, CD34, S100, vimentin and smooth muscle actin confirmed the diagnosis of esophageal GIST. The patient was treated with imatinib 400mg/day. There was a dramatic reduction in the size of the tumor with successful improvement of his symptoms after 2 months of treatment, which was confirmed by reapeated upper GIT endoscopy, and MRI. (author)

Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs

DEFF Research Database (Denmark)

Jacobsen, Mette Juul; Kracht, Steffen Skaarup; Esteso, G.

2009-01-01

Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility....../resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used...... for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markes. By a targeted approach, the candidate...

Glycoprotein A33 deficiency: a new mouse model of impaired intestinal epithelial barrier function and inflammatory disease

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Benjamin B. Williams

2015-08-01

Full Text Available The cells of the intestinal epithelium provide a selectively permeable barrier between the external environment and internal tissues. The integrity of this barrier is maintained by tight junctions, specialised cell-cell contacts that permit the absorption of water and nutrients while excluding microbes, toxins and dietary antigens. Impairment of intestinal barrier function contributes to multiple gastrointestinal disorders, including food hypersensitivity, inflammatory bowel disease (IBD and colitis-associated cancer (CAC. Glycoprotein A33 (GPA33 is an intestinal epithelium-specific cell surface marker and member of the CTX group of transmembrane proteins. Roles in cell-cell adhesion have been demonstrated for multiple CTX family members, suggesting a similar function for GPA33 within the gastrointestinal tract. To test a potential requirement for GPA33 in intestinal barrier function, we generated Gpa33−/− mice and subjected them to experimental regimens designed to produce food hypersensitivity, colitis and CAC. Gpa33−/− mice exhibited impaired intestinal barrier function. This was shown by elevated steady-state immunosurveillance in the colonic mucosa and leakiness to oral TRITC-labelled dextran after short-term exposure to dextran sodium sulphate (DSS to injure the intestinal epithelium. Gpa33−/− mice also exhibited rapid onset and reduced resolution of DSS-induced colitis, and a striking increase in the number of colitis-associated tumours produced by treatment with the colon-specific mutagen azoxymethane (AOM followed by two cycles of DSS. In contrast, Gpa33−/− mice treated with AOM alone showed no increase in sporadic tumour formation, indicating that their increased tumour susceptibility is dependent on inflammatory stimuli. Finally, Gpa33−/− mice displayed hypersensitivity to food allergens, a common co-morbidity in humans with IBD. We propose that Gpa33−/− mice provide a valuable model to study the mechanisms

Combined value of susceptibility weighted imaging and dynamic susceptibility-weighted contrast-enhanced MR perfusion-weighted imaging in brain astrocytoma grading

International Nuclear Information System (INIS)

Wang Xiaochun; Zhang Hui; Qin Jiangbo; Wang Le; Wu Xiaofeng

2012-01-01

Objective: To assess the value of combination of susceptibility weighted imaging (SWI) and dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion-weighted magnetic resonance imaging in astrocytoma grading. Methods: SWI and DSC scans were performed in 82 patients with pathologically confirmed astrocytoma. The patient group consisted of grade Ⅱ (15), grade Ⅲ (10), and grade Ⅳ (57). The intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max were used to determine the grade of astrocytomas by Kruskal Wallis test, Welch test, Spearman correlation coefficients, Pearson correlation coefficients, and receiver operating characteristic curve (ROC)statistic methods. Results: There were no ITSS in 14 cases of low-grade astrocytomas, the degree of ITSS were grade 1 to 3 in anaplastic astrocytomas, the degree of ITSS were grade 3 in all of the glioblastomas, the degree of ITSS were significant difference in all grades (H=71.96, P<0.01). rCBV max in grade Ⅱ, grade Ⅲ and grade Ⅳ astrocytomas were 1.26 ± 0.42, 3.59 ± 2.09 and 8.34 ± 1.16 respectively, rCBV max were significant difference in all grades (F'=681.72, P<0.01). ITSS showed significant correlation with rCBV max (r=0.72, P<0.01) and tumor grades (r=0.89, P<0.01), and rCBV and tumor grades showed significant correlation (r=0.78, P<0.01). Area under the ROC curve application SWI, DSC, SWI and DSC in differentiation of the grade Ⅱ and grade Ⅲ astrocytomas were 0.99, 0.93, 1.00, differentiate grade Ⅲ from grade Ⅳ were 0.70, 0.94, 0.94, and differentiate high-grade from low-grade astrocytomas were 1.00, 0.99, 1.00. Conclusions: ITSS is helpful to determine the grade of astrocytomas. The use of SWI in combination with DSC may improve the diagnostic accuracy of astrocytoma grading. (authors)

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

Recurrent small intestine intussusception in a patient with Peutz-Jeghers syndrome Invaginación recurrente del intestino delgado en un paciente con síndrome de Pentz-Jeghers

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Orestis Ioannidis

2012-01-01

Full Text Available Peutz-Jeghers syndrome is a rare hereditary autosomal dominant disease caused by a mutation of the tumor suppressor gene serine/threonine kinase 11 located in chromosome 19p13.3. It is characterized by the presence of extensive mucocutaneous pigmentation, especially of the lips and the occurrence of hamartomatous polyps throughout the gastrointestinal tract. Gastrointestinal hamartomas occur predominantly in the small intestine and can become symptomatic leading usually to intestinal obstruction and abdominal pain. We present a case of recurrent intestinal obstruction caused by small bowel intussusception treated by reduction, enterotomy and polypectomy and followed by intraoperative enteroscopy and endoscopic polypectomy.

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

Presentation of a nationwide multicenter registry of intestinal failure and intestinal transplantation

NARCIS (Netherlands)

Neelis, E. G.; Roskott, A. M.; Dijkstra, G.; Wanten, G. J.; Serlie, M. J.; Tabbers, M. M.; Damen, G.; Olthof, E. D.; Jonkers, C. F.; Kloeze, J. H.; Ploeg, R. J.; Imhann, F.; Nieuwenhuijs, V. B.; Rings, E. H. H. M.

Background & aims: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date

Presentation of a nationwide multicenter registry of intestinal failure and intestinal transplantation

NARCIS (Netherlands)

Neelis, E.G.; Roskott, A.M.; Dijkstra, G.; Wanten, G.J.A.; Serlie, M.J.; Tabbers, M.M.; Damen, G.M.; Olthof, E.D.; Jonkers, C.F.; Kloeze, J.H.; Ploeg, R.J.; Imhann, F.; Nieuwenhuijs, V.B.; Rings, E.H.

2016-01-01

BACKGROUND & AIMS: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date

Gastrointestinal stromal tumors: retrospective analysis of the computer-tomographic aspects.

Science.gov (United States)

Lupescu, Ioana G; Grasu, Mugur; Boros, Mirela; Gheorghe, Cristian; Ionescu, Mihnea; Popescu, Irinel; Herlea, Vlad; Georgescu, Serban A

2007-06-01

To describe the computer-tomographic (CT) aspects of gastrointestinal stromal tumors (GISTs) in correlation to their histology. The medical records of all patients at our hospital with a histologic diagnosis of GIST between January 2002 and June 2006, and investigated before surgery by CT, were reviewed. Two radiologists with knowledge of the diagnosis reviewed the CT findings. Amongst 15 cases of GISTs, 9 cases involved the stomach and 4 cases the small intestine. Location of the primary tumor could not be determined for 2 of 15 tumors, because of the presence of extensive peritoneal metastases. Most primary tumors were predominantly extraluminal (13 cases) while two were clearly endoluminal. The mean diameter of the primary tumor was 8 cm. The tumor margin was well defined in 12 patients and irregular in 3 cases. Central fluid attenuation was present in 11 tumors, while central gas was seen in two cases. Metastases were seen in 2 cases at presentation and in another 2 patients during follow-up. Spread was exclusive to the liver or peritoneum. Visceral obstruction was absent even in extensive peritoneal metastatic disease. Ascites was an unusual finding. CT plays an important role not only in the detection and the localization but also in the evaluation of the extension and follow-up of theses tumors. Using only CT aspects, we can only suspect the diagnosis to GISTs. Often other soft-tissue tumors with gastrointestinal involvement can mimic GISTs. In all cases histological diagnosis is essential.

Effects of resveratrol, an important component of red wine, on intestinal cancer development

Directory of Open Access Journals (Sweden)

Xiaoying Zhang

2009-04-01

Full Text Available Xiaoying Zhang1, Jan Anderson1, Radhey S Kaushik2,3, Chandradhar Dwivedi11Department of Pharmaceutical Sciences; 2Department of Veterinary Sciences; 3Department of Biology/Microbiology, South Dakota State University, Brookings, SD, USAAbstract: Resveratrol, a natural product derived from grapes and an important component of red wine, has been shown to inhibit cyclooxygenase and prevent various cancers. The purpose of this study is to investigate the effects of dietary grape extract, a source of resveratrol on intestinal cancer development in rats and to determine effects of resveratrol on cell growth in human colonic adenocarcinoma (Caco-2 cells, thus elucidating possible mechanisms of action of resveratrol. Results showed that dietary grape extract (5%, about 7 μg resveratrol consumed daily significantly decreased the incidence and multiplicity of tumors in small intestine in rats and resveratrol significantly inhibited cell viability and cell proliferation in Caco-2 cells.Keywords: resveratrol, grapes, colonic adenocarcinoma, Caco-2 cells

Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature review

Institute of Scientific and Technical Information of China (English)

William; J; Salyers; Kenneth; J; Vega; Juan; Carlos; Munoz; Bruce; W; Trotman; Silvio; S; Tanev

2014-01-01

Neuroendocrine tumors(NET)previously called carcinoid tumors are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid syndrome.The annual incidence of patients with NET is 8.4 per 100000;yet many NET remain asymptomatic and clinically undetected.A majority of NET follows a benign course;however,some will display malignant characteristics.NET most commonly occur in the gastrointestinal tract(67%)and bronchopulmonary system(25%).Gastrointestinal NET occur within the stomach,small intestine,liver,and rectum.We report a retrospective study of 11 subjects:Eight with benign carcinoid tumors:duodenal bulb(n=2),terminal ileum(n=1),sigmoid colon(n=2),and rectum(n=3);three with malignant carcinoid:liver(n=1)and intra-abdominal site(n=2).The diagnosis,endoscopic images,outcome,treatment and review of the literature are presented.

Comparison between the concentration of mast cells and risk criteria of malignancy in intestinal adenomas

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Bruna Luz Custódio Camargo

2012-03-01

Full Text Available Intestinal adenomas are benign neoplasms that present a risk of malignancy associated with three independent characteristics: the polyp size, the histological architecture and the severity of epithelial dysplasia (or atypia. Current evidence suggests that mast cells (CM contribute to the tumorigenesis of colorectal carcinomas. Objective: Compare the concentration of CM in intestinal adenomas and risk criteria for malignancy in these tumors (size, histological type and degree of cellular atypia. METHODS: We conducted a retrospective study with 102 anatomopathological reports of intestinal adenoma excision. We selected paraffin blocks with the central area of the tumor. The CM were stained with toluidine blue. RESULTS: In most cases (89.2%, n=91, the mast cells concentration (MC was less than 6 CM/10 high power field (HPF (p=0.0001. Most adenomas, regardless of their histological type, showed 0 CM/10 HPF (p=0.083. In most adenomas, regardless of their size, MC was 0 CM/10 HPF (p=0.665. Presence or absence of atypia was associated, in most cases, with MC of 0 CM/10 HPF (p=0.524. Conclusion: This study did not show association between the MC and histological type, size or presence of atypical cells in intestinal adenomas.Adenomas intestinais são neoplasias benignas que apresentam risco de malignização relacionado a três características independentes: o tamanho do pólipo, a arquitetura histológica e a gravidade da displasia (ou atipia epitelial. Evidências atuais sugerem que os mastócitos contribuem para a tumorigênese do carcinoma colorretal. OBJETIVO: Analisar comparativamente a concentração de mastócitos em adenomas intestinais e os critérios de risco para malignização nesses tumores (tamanho, tipo histológico e grau de atipia celular. Métodos: Realizou-se um estudo retrospectivo, com seleção de 102 laudos anatomopatológicos de exérese de adenoma intestinal. Foram selecionados os blocos de parafina com a área central da

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...

Non-Meckel Small Intestine Diverticulitis