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Sample records for adenomatous polyposis coli

  1. Immunopurification of adenomatous polyposis coli (APC) proteins

    OpenAIRE

    Elliott, Kerryn L.; Catimel, Bruno; Church, Nicole L; Janine L Coates; Antony W Burgess; Layton, Meredith J.; Faux, Maree C.

    2013-01-01

    Background The adenomatous polyposis coli (APC) tumour suppressor gene encodes a 2843 residue (310 kDa) protein. APC is a multifunctional protein involved in the regulation of β-catenin/Wnt signalling, cytoskeletal dynamics and cell adhesion. APC mutations occur in most colorectal cancers and typically result in truncation of the C-terminal half of the protein. Results In order to investigate the biophysical properties of APC, we have generated a set of monoclonal antibodies which enable puri...

  2. Attenuated Familial Adenomatous Polyposis

    Science.gov (United States)

    ... adenomatous polyposis coli. A mutation (alteration) in the APC gene gives a person an increased lifetime risk of developing multiple adenomatous colon polyps, colorectal cancer, and other cancers of the digestive tract. People ...

  3. Familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen

    1989-01-01

    Familial adenomatous polyposis is an autosomal dominant disease that includes early development of up to thousands of colorectal adenomas and several extracolonic manifestations. All untreated patients will develop colorectal adenocarcinoma. The treatment of choice is colectomy and ileorectal ana...... a national or regional polyposis register. The recent detection of a specific gene for familial adenomatous polyposis is a long step forward, and several problems may be solved by increasing international cooperation....

  4. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

    NARCIS (Netherlands)

    Ruane, Peter T; Gumy, Laura F|info:eu-repo/dai/nl/337608334; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J; Hoogenraad, Casper C|info:eu-repo/dai/nl/227263502; Allan, Victoria J

    2016-01-01

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members,

  5. Familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen

    1989-01-01

    of frequent occurrence of premalignant duodenal adenomas. The prognosis is good after prophylactic colectomy in patients without carcinoma. All first degree relatives of affected family members should be examined regularly with proctosigmoidoscopy from the age of ten, and prophylaxis should be organised using...... a national or regional polyposis register. The recent detection of a specific gene for familial adenomatous polyposis is a long step forward, and several problems may be solved by increasing international cooperation....

  6. Deep vein thrombosis in a patient of adenomatous polyposis coli treated successfully with aspirin: A case report

    Science.gov (United States)

    Agrawal, Neha; Santra, Tuhin; Kar, Arnab; Guha, Pradipta; Bar, Mita; Adhikary, Apu; Datta, Sumana

    2016-01-01

    Background: Deep vein thrombosis is an important cause of morbidity and mortality. However, its association with adenomatous polyposis coli is extremely rare. Here we present an interesting case of deep vein thrombosis associated with adenomatous polyposis coli. Case Presentation: A 15 year old female who was having fever and diarrhea for 5 months developed bilateral asymmetric painful swelling of lower limbs for 1 month. Doppler ultrasound of lower limbs revealed presence of thrombosis from inferior vena cava up to popliteal vein. Colonoscopy and biopsy were suggestive of adenomatous polyposis coli. However, she could not tolerate anticoagulant therapy and was put on aspirin therapy for 6 months to which she responded well with the resolution of thrombus. Conclusion: Role of aspirin therapy may be considered whenever a patient of venous thrombosis cannot tolerate anticoagulant therapy. PMID:27386068

  7. Polymorphisms in the adenomatous polyposis coli (APC) gene and advanced colorectal adenoma risk.

    Science.gov (United States)

    Wong, Hui-Lee; Peters, Ulrike; Hayes, Richard B; Huang, Wen-Yi; Schatzkin, Arthur; Bresalier, Robert S; Velie, Ellen M; Brody, Lawrence C

    2010-09-01

    While germline mutations in the adenomatous polyposis coli (APC) gene cause the hereditary colon cancer syndrome (familial adenomatous polyposis (FAP)), the role of common germline APC variants in sporadic adenomatous polyposis remains unclear. We studied the association of eight APC single nucleotide polymorphisms (SNPs), possibly associated with functional consequences, and previously identified gene-environment (dietary fat intake and hormone replacement therapy (HRT) use) interactions, in relation to advanced colorectal adenoma in 758 cases and 767 sex- and race-matched controls, randomly selected from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cases had at least one verified advanced adenoma of the distal colon; controls, a negative sigmoidoscopy. We did not observe an association between genotypes for any of the eight APC SNPs and advanced distal adenoma risk (P(global gene-based)=0.92). Frequencies of identified common haplotypes did not differ between cases and controls (P(global haplotype test)=0.97). However, the risk for advanced distal adenoma was threefold higher for one rare haplotype (cases: 2.7%; controls: 1.6%) (odds ratio (OR)=3.27; 95% confidence interval (CI)=1.08-9.88). The genetic association between D1822V and advanced distal adenoma was confined to persons consuming a high-fat diet (P(interaction)=0.03). Similar interactions were not observed with HRT use. In our large, nested case-control study of advanced distal adenoma and clinically verified adenoma-free controls, we observed no association between specific APC SNPs and advanced adenoma. Fat intake modified the APC D1822V-adenoma association, but further studies are warranted.

  8. Rapid detection of translation-terminating mutations at the adenomatous polyposis coli (APC) gene by direct protein truncation test

    Energy Technology Data Exchange (ETDEWEB)

    Van Der Luut, R.; Khan, P.M.; Van Leeuwen, C.; Tops, C.; Roest, P.; Den Dunnen, J. (Leiden Univ. (Netherlands))

    1994-03-01

    Familial adenomatous polyposis (FAP) is usually associated with protein truncating mutations in the adenomatous polyposis coli (APC) gene. The APC mutations are known to play a major role in colorectal carcinogensis. For the identification of protein truncating mutations of the APC gene, the authors developed a rapid, sensitive, and direct screening procedure. The technique is based on the in vitro transcription and translation of the genomic PCR products and is called the protein truncation test. Samples of DNA from individual FAP patients, members of a FAP family, colorectal tumors, and colorectal tumor-derived cell lines were used to show the effectiveness of this method. 9 refs., 2 figs.

  9. Genetics Home Reference: familial adenomatous polyposis

    Science.gov (United States)

    ... polyposis , in which polyp growth is delayed. The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years. In people with classic familial adenomatous polyposis , the number of polyps increases with age, and hundreds to ...

  10. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

    Science.gov (United States)

    Ruane, Peter T.; Gumy, Laura F.; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J.; Hoogenraad, Casper C.; Allan, Victoria J.

    2016-01-01

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons. PMID:27272132

  11. Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer.

    Science.gov (United States)

    Zhang, Lu; Theodoropoulos, Panayotis C; Eskiocak, Ugur; Wang, Wentian; Moon, Young-Ah; Posner, Bruce; Williams, Noelle S; Wright, Woodring E; Kim, Sang Bum; Nijhawan, Deepak; De Brabander, Jef K; Shay, Jerry W

    2016-10-19

    Mutations in the adenomatous polyposis coli (APC) gene are common in colorectal cancer (CRC), and more than 90% of those mutations generate stable truncated gene products. We describe a chemical screen using normal human colonic epithelial cells (HCECs) and a series of oncogenically progressed HCECs containing a truncated APC protein. With this screen, we identified a small molecule, TASIN-1 (truncated APC selective inhibitor-1), that specifically kills cells with APC truncations but spares normal and cancer cells with wild-type APC. TASIN-1 exerts its cytotoxic effects through inhibition of cholesterol biosynthesis. In vivo administration of TASIN-1 inhibits tumor growth of CRC cells with truncated APC but not APC wild-type CRC cells in xenograft models and in a genetically engineered CRC mouse model with minimal toxicity. TASIN-1 represents a potential therapeutic strategy for prevention and intervention in CRC with mutant APC.

  12. Familial adenomatous polyposis

    Directory of Open Access Journals (Sweden)

    Rozen Paul

    2009-10-01

    Full Text Available Abstract Familial adenomatous polyposis (FAP is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE, desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system. A less aggressive variant of FAP, attenuated FAP (AFAP, is characterized by fewer colorectal adenomatous polyps (usually 10 to 100, later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC gene. Most patients (~70% have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP, which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a

  13. Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

    Energy Technology Data Exchange (ETDEWEB)

    Ashida, Noboru, E-mail: nashida@kuhp.kyoto-u.ac.jp [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Kishihata, Masako [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Tien, Dat Nguyen [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kamei, Kaeko [Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kimura, Takeshi [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Yokode, Masayuki [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan)

    2014-04-04

    Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

  14. Structural basis for the recognition of Asef by adenomatous polyposis coli

    Institute of Scientific and Technical Information of China (English)

    Zhenyi Zhang; Ping Xu; Jian Zhang; Geng Wu; Leyi Chen; Lei Gao; Kui Lin; Liang Zhu; Yang Lu; Xiaoshan Shi; Yuan Gao; Jing Zhou

    2012-01-01

    Adenomatous polyposis coli (APC) regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Aset),which is usually autoinhibited through the binding between its Src homology 3 (SH3) and Dbl homology (DH) domains.The APC-activated Asef stimulates the small GTPase Cdc42,which leads to decreased cell-cell adherence and enhanced cell migration.In colorectal cancers,truncated APC constitutively activates Asef and promotes cancer cell migration and angiogenesis.Here,we report crystal structures of the human APC/Asef complex.We find that the armadillo repeat domain of APC uses a highly conserved surface groove to recognize the APC-binding region (ABR) of Asef,conformation of which changes dramatically upon binding to APC.Key residues on APC and Asef for the complex formation were mutated and their importance was demonstrated by binding and activity assays.Structural superimposition of the APC/Asef complex with autoinhibited Asef suggests that the binding between APC and Asef might create a steric clash between AsefDH domain and APC,which possibly leads to a conformational change in Asef that stimulates its GEF activity.Our structures thus elucidate the molecular mechanism of Asef recognition by APC,as well as provide a potential target for pharmaceutical intervention against cancers.

  15. Identification of APC gene mutations in Italian adenomatous polyposis coli patients by PCR-SSCP analysis

    Energy Technology Data Exchange (ETDEWEB)

    Varesco, L.; Gismondi, V.; James, R.; Casarino, L.; De Benedetti, L.; Bafico, A.; Allegretti, A.; Aste, H. (Istituto Nazionale per la Ricerca sul Cancro, Genoa (Italy)); Robertson, M.; Groden, J.; White, R. (Univ. of Utah, Salt Lake City (United States)); Grammatico, P.; De Sanctis, S.; Sciarra, A.; Del Porto, G. (Universita di Roma, Rome (Italy)); Bertario, L.; Sala, P.; Rossetti, C.; Illeni, M.T. (Istituto Nazionale Tumori, Milan (Italy)); Sassatelli, R.; Ponz de Leon, M. (Universita di Modena (Italy)); Biasco, G. (Universita di Bologna (Italy)); Ferrara, G.B. (Istituto Nazionale per la Ricerca sul Cancro, Genoa (Italy) Universita di Napoli, Naples (Italy))

    1993-02-01

    The APC gene is a putative human tumor-suppressor gene responsible for adenomatous polyposis coli (APC), an inherited, autosomal dominant predisposition to colon cancer. It is also implicated in the development of sporadic colorectal tumors. The characterization of APC gene mutations in APC patients is clinically important because DNA-based tests can be applied for presymptomatic diagnosis once a specific mutation has been identified in a family. Moreover, the identification of the spectrum of APC gene mutations in patients is of great interest in the study of the biological properties of the APC gene product. The authors analyzed the entire coding region of the APC gene by the PCR-single-strand conformation polymorphism method in 42 unrelated Italian APC patients. Mutations were found in 12 cases. These consist of small (5-14 bp) base-pair deletions leading to frameshifts; all are localized within exon 15. Two of these deletions, a 5-bp deletion at position 3183-3187 and a 5-bp deletion at position 3926-3930, are present in 3/42 and 7/42 cases of the series, respectively, indicating the presence of mutational hot spots at these two sites. 17 refs., 2 figs., 1 tab.

  16. High resolution genetic map of the adenomatous polyposis coli gene (APC) region

    Energy Technology Data Exchange (ETDEWEB)

    Olschwang, S.; Laurent-Puig, P.; Melot, T. [Institut Curie, Paris (France)

    1995-05-08

    Familial adenomatous polyposis coli (APC) is a dominantly inherited colorectal cancer susceptibility disease caused by mutation in a gene called APC located on chromosome 5q21. Presymptomatic diagnosis of this condition is recommended because it enables restriction of the efficient but demanding prevention program to those relatives that are genetically affected. The large size of the APC gene makes the direct search for the casual alteration difficult to implement in routine diagnostic laboratories. Because APC appears to be genetically homogeneous with alteration in a single locus causing the disease, cosegregation analysis may represent an alternative efficient method for presymptomatic diagnosis. However, the reliability of the risk estimation by linkage analysis in APC families is hampered by the lack of a short range genetic map of the APC locus. A combined approach including genotyping of 65 APC families, analysis of the CEPH database, and complementary typing of both APC and CEPH families has made it possible to derive the following genetic map: Centromere-[D5S82-D5S49]-0.02-D5S122-0.01-D5S136-0.01-D5S135-0.02-[APC-D5S346-MCC]-0.04-[D5S81-D5S64]-Telomere. This order, which differs from previously proposed genetic maps, is fully compatible with recent physical mapping data. These data should contribute to increase the reliability of the presymptomatic test for APC. 42 refs., 1 fig., 3 tabs.

  17. A Unique Profile of Adenomatous Polyposis Coli Gene Mutations in Iranian Patients Suffering Sporadic Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Mojtaba Hasanpour

    2014-03-01

    Full Text Available Objective: Colorectal cancer (CRC is one of the most common and aggressive cancers worldwide. The majority of CRC cases are sporadic that caused by somatic mutations. The Adenomatous Polyposis Coli (APC; OMIM 611731 is a tumor suppressor gene of Wnt pathway and is frequently mutated in CRC cases. This study was designed to investigate the spectrum of APC gene mutations in Iranian patients with sporadic colorectal cancer. Materials and Methods: In this descriptive study, Tumor and normal tissue samples were obtained from thirty randomly selected and unrelated sporadic CRC patients. We examined the hotspot region of the APC gene in all patients. Our mutation detection method was direct DNA sequencing. Results: We found a total of 8 different APC mutations, including two nonsense mutations (c.4099C>T and c.4348C>T, two missense mutations (c.3236C>G and c.3527C>T and four frame shift mutations (c.2804dupA, c.4317delT, c.4464_4471delATTACATT and c.4468_4469dupCA. The c.3236C>G and c.4468_4469dupCA are novel mutations. The overall frequency of APC mutation was 26.7% (8 of 30 patients. Conclusion: This mutation rate is lower in comparison with previous studies from other countries. The findings of present study demonstrate a different APC mutation spectrum in CRC patients of Iranian origin compared with other populations.

  18. Familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen

    1989-01-01

    anastomosis, but restorative proctocolectomy may be considered in selected cases. Polyposis patients treated with ileorectal anastomosis should be followed for life, with regular proctosigmoidoscopy and destruction of new adenomas. Furthermore, regular gastroduodenoscopy should be carried out because...

  19. Familial adenomatous polyposis: from bedside to benchside.

    LENUS (Irish Health Repository)

    O'Sullivan, M J

    2012-02-03

    Familial adenomatous polyposis (FAP) is a dominantly inherited cancer-predisposition syndrome with an incidence of between 1:17,000 and 1:5,000. The condition has been causally linked to mutation of the adenomatous polyposis coli (APC) gene located at 5q21. Virtually all mutations in the APC gene are truncating mutations, resulting in loss of function of the APC protein. Spontaneous germline mutation of this gene occurs frequently and accounts for the high incidence of FAP. The gene is somatically mutated at an early point in the colorectal adenoma-carcinoma progression. Somatic mutations of the APC gene are also frequently observed in a variety of other human carcinomas. Isolation of the APC gene has led to the recognition of genotype-phenotype correlations and, together with protein studies, has helped to elucidate the structure and function of the APC protein. This report aims to take the reader from a clinical appreciation to a molecular understanding of FAP.

  20. Diagnosis of familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen

    1991-01-01

    Familial adenomatous polyposis (FAP) includes early development of up to thousands of colorectal adenomas and of colorectal adenocarcinoma in all untreated cases. Moreover, a variety of extracolonic manifestations are seen. Proctosigmoidoscopy is used for screening; when adenomas are found, the d...... preclinical diagnosis in the future. A centralized registration of FAP has resulted in an improved prognosis, and the establishment of international groups will contribute to increased research of this disease....

  1. Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia

    NARCIS (Netherlands)

    T. Onouchi (Takanori); K. Kobayashi (Kumiko); D.S. Sakai (Debbie); A. Shimomura (Atsushi); M.J.M. Smits (Ron); C. Sumi-Ichinose (Chiho); M. Kurosumi (Masafumi); M. Takao (Masashi); R. Nomura (Ryuji); A. Iizuka-Kogo (Akiko); H. Suzuki (Hidekazu); K. Kondo; T. Akiyama (Tetsu); T. Miyakawa (Tsuyoshi); R. Fodde (Riccardo); T. Senda (Takao)

    2014-01-01

    textabstractBackground: Loss of adenomatous polyposis coli (APC) gene function results in constitutive activation of the canonical Wnt pathway and represents the main initiating and rate-limiting event in colorectal tumorigenesis. APC is likely to participate in a wide spectrum of biological functio

  2. Herpesvirus saimiri-mediated delivery of the adenomatous polyposis coli tumour suppressor gene reduces proliferation of colorectal cancer cells.

    Science.gov (United States)

    Macnab, Stuart A; Turrell, Susan J; Carr, Ian M; Markham, Alex F; Coletta, P Louise; Whitehouse, Adrian

    2011-11-01

    Colorectal cancer (CRC) is a major cause of cancer-related mortality. A contributing factor to the progression of this disease is sporadic or hereditary mutation of the adenomatous polyposis coli (APC) gene, a negative regulator of the Wnt signalling pathway. Inherited mutations in APC cause the disorder familial adenomatous polyposis (FAP), which leads to CRC development in early adulthood. However, the gene is also disrupted in some 60% of sporadic cancers. Restoration of functional APC may slow the growth of CRC by negatively regulating proliferation-associated genes such as c-myc. Therefore, we have cloned the cDNA of the APC tumour suppressor gene into a replication competent Herpesvirus saimiri (HVS)-based vector to assess APC gene delivery in SW480 and SW620 CRC cell lines. Our results demonstrate that full length APC protein was efficiently expressed from the HVS vector and that transgene expression inhibited proliferation of both the SW480 and the metastatic SW620 cancer cell lines. Moreover, a sustained effect could be observed for at least 8 weeks after initial infection in SW480 cells. In addition, monolayer wounding assays showed a marked reduction in proliferation and migration in HVS-GFP-APC infected cells. We believe that this is the first instance of infectious delivery and APC cDNA expression from a virus-based vector.

  3. Evidence for a novel exon in the coding region of the adenomatous polyposis coli (APC) gene

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Ling; St. Denis, K.A.; Bapat, B. [Univ. of Toronto (Canada)

    1995-08-10

    Germline mutations of the tumor suppressor gene APC cause familial adenomatous polyposis. Somatic APC alterations are involved in several sporadic neoplasma, including colorectal, duodenal, gastric, and esophageal carcinoma. The APC mRNA is encoded by 15 exons. Additional transcripts have been reported, due to alternative splicing of coding as well as noncoding regions. Two mRNA isoforms occur due to a deletion of exon 7 or a partial deletion of exon 9. We have identified a novel exon, flanked by APC exons 10 and 11, which is expressed as an alternatively transcribed product of the gene. Further, we have shown that the novel exon consists of a heptad repeat motif and is conserved across species. 18 refs., 2 figs.

  4. Familial adenomatous polyposis associated APC gene mutation - A case study

    Directory of Open Access Journals (Sweden)

    Avinash Bardia1, Santosh K. Tiwari1, Sandeep K. Vishwakarma1, Md. Aejaz Habeeb1, Pratibha Nallari2, Aleem A. Khan1

    2013-08-01

    Full Text Available Familial adenomatous polyposis (FAP is an autosomal dominant condition characterized by diffuse intestinal polyposis, specific gene mutation, and predisposition for developing colon cancer. Left untreated, patients with FAP will develop colorectal carcinoma during early adulthood. Hence, early detection and surgical intervention are of the utmost importance. Colectomy is required and may include an ileal pouch with ileo-anal anastomosis, which eli-minates the colon and rectal disease while preserving fecal continence and avoidance of a permanent ileostomy. We report a case of colorectal cancer along with FAP showed features consistent with adenomatous polyposis coli and no evidence of malignancy was seen after the surgery.

  5. FAMILIAL ADENOMATOUS POLYPOSIS

    Institute of Scientific and Technical Information of China (English)

    XU Ning; DING Yan-qing; XU Li

    1999-01-01

    @@ Clinical History A 41-year-old female was admitted into Nan Fang Hospital for severe abdominal pain with bloody-mucoid stool for a month. The symptoms started a year ago without obvious causes and she did not have any systemic treatment.The patient felt fatigue and loss of weight for the last three months and increased frequency of bloody-mucoid discharge from 2-4 times/day to 10 times/day for the last month. Two weeks ago the patient had a proctoscope with biopsy in Pan Yu people's Hospital. The pathological diagnosis was rectal villous adenoma with focal malignant changes. Rectal examination in this hospital found a rectal mass, 4 cm from the anus, longitudinal growing and occupying a quarter of the circumference. Further colonofiberscope diagnosis was familial polyposis of colon.Family history showed that her father died of lung cancer,her mother died of colonic cancer and her brother and sister were healthy. A total colo-rectectomy with ileostomy was performed.

  6. Large extent of disorder in Adenomatous Polyposis Coli offers a strategy to guard Wnt signalling against point mutations.

    Directory of Open Access Journals (Sweden)

    David P Minde

    Full Text Available Mutations in the central region of the signalling hub Adenomatous Polyposis Coli (APC cause colorectal tumourigenesis. The structure of this region remained unknown. Here, we characterise the Mutation Cluster Region in APC (APC-MCR as intrinsically disordered and propose a model how this structural feature may contribute to regulation of Wnt signalling by phosphorylation. APC-MCR was susceptible to proteolysis, lacked α-helical secondary structure and did not display thermal unfolding transition. It displayed an extended conformation in size exclusion chromatography and was accessible for phosphorylation by CK1ε in vitro. The length of disordered regions in APC increases with species complexity, from C. elegans to H. sapiens. We speculate that the large disordered region harbouring phosphorylation sites could be a successful strategy to stabilise tight regulation of Wnt signalling against single missense mutations.

  7. Functional comparison of human adenomatous polyposis coli (APC and APC-like in targeting beta-catenin for degradation.

    Directory of Open Access Journals (Sweden)

    Jean Schneikert

    Full Text Available Truncating mutations affect the adenomatous polyposis coli (APC gene in most cases of colon cancer, resulting in the stabilization of β-catenin and uncontrolled cell proliferation. We show here that colon cancer cell lines express also the paralog APC-like (APCL or APC2. RNA interference revealed that it controls the level and/or the activity of β-catenin, but it is less efficient and binds less well to β-catenin than APC, thereby providing one explanation as to why the gene is not mutated in colon cancer. A further comparison indicates that APCL down-regulates the β-catenin level despite the lack of the 15R region known to be important in APC. To understand this discrepancy, we performed immunoprecipitation experiments that revealed that phosphorylated β-catenin displays a preference for binding to the 15 amino acid repeats (15R rather than the first 20 amino acid repeat of APC. This suggests that the 15R region constitutes a gate connecting the steps of β-catenin phosphorylation and subsequent ubiquitination/degradation. Using RNA interference and domain swapping experiments, we show that APCL benefits from the 15R of truncated APC to target β-catenin for degradation, in a process likely involving heterodimerization of the two partners. Our data suggest that the functional complementation of APCL by APC constitutes a substantial facet of tumour development, because the truncating mutations of APC in colorectal tumours from familial adenomatous polyposis (FAP patients are almost always selected for the retention of at least one 15R.

  8. APC gene mutations in individuals with possible attenuated familial adenomatous polyposis coli

    Energy Technology Data Exchange (ETDEWEB)

    Frayling, J.M.; Talbot, J.; Harocopos, C.A. [Imperial Cancer Research Fund Colorectal Cancer Unit, London (United Kingdom)] [and others

    1994-09-01

    Spirio et al. have described an attenuated form of familial adenomatous polyposis (FAP) termed AAPC, where affected individuals have been found to have mutations in exons 3 & 4 of the APC gene. AAPC expression within a family appears to be extremely variable and can overlap clinically with FAP, giving rise to between zero and a few hundred adenomas. The phenotypic range associated with AAPC mutations is undefined and the frequency in the population of such alleles of the APC gene is unknown. In addition, it is as yet unclear how many cases of sporadic colorectal adenomas might have AAPC. In order to address this we have identified 110 individuals having a phenotype compatible with a diagnosis of AAPC, in three groups: (1) 30 individuals (15m, 15f; median age = 55y, range 8-71y) with some or all of the following: colonic adenomas (28 cases); colorectal cancer (12 cases); extra-colonic features of FAP, either desmoid tumours (4 cases, including 2 without colonic adenomas) or sebaceous cysts (2 cases). Sixteen cases had a family history of adenomas/colorectal cancer/extra-colonic features of FAP. (2) 16 individuals (10m, 6f) from the St. Mark`s Polyposis Registry, diagnosed with FAP (including a family history), who had unusually few adenomas (median = 200) at colectomy (median age = 43y, range 17-62y). (3) 64 individuals (43m, 21f) from the St. Mark`s Hospital Adenoma Follow-up Study who either had >4 adenomas at presentation (median total adenomas = 9), or >4 adenomas detected during follow-up (median total adenomas = 9). Genomic DNA was obtained from these individuals and exons 1-4 of the APC gene were amplified by PCR. Chemical cleavage of mismatch was used to screen for mutations, followed by sequencing if variant bands were found. Germ-line mutations have been identified in exons 3 and 4 in a proportion of these individuals, thus extending the clinical spectrum of phenotypes associated with mutations in this region of the APC gene.

  9. Defensin expression in chronic pouchitis in patients with ulcerative colitis or familial adenomatous polyposis coli

    Institute of Scientific and Technical Information of China (English)

    Karlheinz Kiehne; Gabriele Brunke; Franziska Wegner; Tomas Banasiewicz; Ulrich R F(o)lsch; Karl-Heinz Herzig

    2006-01-01

    AIM:Pouchitis develops in ileoanal pouches in up to 50% of patients with ulcerative colitis during the first 10years after pouch surgery while being rare in patients after proctocolectomy for familial adenomatous polyposis coii (FAP) syndrome. Defensins are major components of the innate immune system and play a significant role in gastrointestinal microbial homeostasis. Pouch defensin and cytokine expression were correlated with states of pouch inflammation to study their role in pouchitis.METHODS:Patients with ulcerative colitis and FAP syndrome were stratified into groups with pouches after surgery, pouches without or with pouchitis. Biopsies from terminal ileum from a healthy intestine or from normal terminal ileum of patients with ulcerative colitis served as controls, mRNA from pouches and controls was analysed for defensin and cytokine expression.RESULTS: Expression of defensins was increased in all pouches immediately after surgery, compared to ileum of controls. Initially, pouches in ulcerative colitis revealed higher defensin expression than FAP pouches. Defensin expression declined in both patient groups and increased again slightly in pouchitis in patients with ulcerative colitis. FAP pouches without pouchitis had strong expression of β-defensin hBD-1, while all other defensins remained at low levels. Cytokine expression in ulcerative colitis pouches was high, while FAP pouches showed moderately elevated cytokines only after surgery.CONCLUSION: Development of pouchitis correlates with decreased defensin expression in ulcerative colitis in addition to high expression of cytokines. The low incidence of pouchitis in FAP pouches correlates with increased expression of hBD-1 β- defensin in association with low cytokine levels.

  10. Dental anomalies in pediatric patients with familial adenomatous polyposis.

    Science.gov (United States)

    Septer, Seth; Bohaty, Brenda; Onikul, Robin; Kumar, Vandana; Williams, Karen B; Attard, Thomas M; Friesen, Craig A; Friesen, Lynn Roosa

    2017-09-08

    Familial adenomatous polyposis patients often present with non-malignant extra-intestinal manifestations which include dental anomalies that may be evident prior to the appearance of the colonic adenomas. The aims of this study were to describe the prevalence and type of dental anomalies and the relationships between gene mutations and dental anomalies in these patients. Twenty-two pediatric familial adenomatous polyposis patients and 46 controls, who were age and gender matched participated. Familial adenomatous polyposis patient's had a dental examination with panoramic radiograph and medical record review for age at diagnosis, the presence of the adenomatous polyposis coli gene mutation, and determination of other extra-intestinal manifestations on the body. The control group was identified from a retrospective chart review and selected if there was a current panoramic radiograph. The only significant difference between familial adenomatous polyposis patients and controls were the presence of jaw osteomas and sclerosis (p = .0001). Patients with a mutation in, or upstream of codon 1309 had a higher frequency of osteomas (77.8%) and jaw-bone sclerosis (44.4%), and 77% of these had at least one dental anomaly. This preliminary study showed an association between a genetic variant at, or upstream of codon 1309, and radiographic dental anomalies.

  11. Molecular analysis of mutations for the adenomatous polyposis coli (APC) gene in Romanian patients with colorectal cancer.

    Science.gov (United States)

    Toma, M; Cimponeriu, D; Pompilia, A; Stavarachi, M; Beluşică, L; Radu, I; Gavrilă, L

    2008-01-01

    Mutations in adenomatous polyposis coli (APC) gene have not been previously characterized among Romanian patients with colorectal cancer (CRC). We initiate this study to detect the mutations in APC gene in blood and tumor samples collected from 16 patients (10 men and 6 women) and blood samples from 21 first and second degree relatives of the patients. For this the presence of mutations in exons 6, 7, 12, 13, 14 as well as in regions B, L and W of exon 15 was investigated using PCR multiplex. In the same time, we have searched for 5 bp deletions at codon 1061 of APC gene by PAGE and SSCP methods. These methods allowed us to evidence identification of the presence of mutations in samples from 7 individuals. In one patient, was detected a deletion of exon 13th of APC gene both in DNA extracted from blood and tumor samples. Multiple deletions (e.g. in exon 6, 12, and in 15L and 15W regions) in DNA extracted from the tumor sample were detected, but not in DNA probe obtained from blood cells. We can speculate that these mutations are an example of genomic instability accompanying the malignancy. Till now, no mutation affecting 1061 codon of APC gene was identified in the patients investigated in our study.

  12. A CA-repeat polymorphism close to the adenomatous polyposis coli (APC) gene offers improved diagnostic testing for familial APC

    Energy Technology Data Exchange (ETDEWEB)

    Spirio, L.; Nelson, L.; Ward, K.; Burt, R.; White, R.; Leppert, M. (Univ. of Utah, Salt Lake City (United States))

    1993-02-01

    Presymptomatic genetic testing for the presence of a mutant allele causing familial adenomatous polyposis coli (APC) has been difficult to perform effectively in the past because DNA markers surrounding the APC gene on chromosome 5q have not been very informative. The authors report results of genetic linkage studies on both research families and clinical families by using D5S346, a highly polymorphic dinucleotide (CA)-repeat locus 30-70 kb from the APC gene. Linkage analysis with this marker in a large APC pedigree showed an increase of at least 9.0 LOD units, in likelihood of linkage of the disease-causing allele to the APC locus, when compared with the highest LOD score attained with any other closely linked marker. When the first 14 APC families that requested genotypic analysis by the DNA Diagnostic Laboratory at the University of Utah were tested with D5S346, 20 of the 31 at-risk individuals were identified as either carriers or noncarriers of an APC-predisposing allele. The authors see this marker as an important tool for research studies and for the presymptomatic diagnosis of APC. 28 refs., 3 figs., 2 tabs.

  13. Causes of death in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Galle, T S; Juel, K; Bülow, S

    1999-01-01

    The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due...... to duodenal/periampullary cancer and desmoid tumours. The aim of this study was to examine the causes of death with special emphasis on duodenal/periampullary cancer....

  14. Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas.

    Science.gov (United States)

    Virmani, A K; Rathi, A; Sathyanarayana, U G; Padar, A; Huang, C X; Cunnigham, H T; Farinas, A J; Milchgrub, S; Euhus, D M; Gilcrease, M; Herman, J; Minna, J D; Gazdar, A F

    2001-07-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene associated with both familial and sporadic cancer. Despite high rates of allelic loss in lung and breast cancers, point mutations of the APC gene are infrequent in these cancer types. Aberrant methylation of the APC promoter 1A occurs in some colorectal and gastric malignancies, and we investigated whether the same mechanism occurs in lung and breast cancers. The methylation status of the APC gene promoter 1A was analyzed in 77 breast, 50 small cell (SCLC), and 106 non-small cell (NSCLC) lung cancer tumors and cell lines and in 68 nonmalignant tissues by methylation-specific PCR. Expression of the APC promoter 1A transcript was examined in a subset of cell lines by reverse transcription-PCR, and loss of heterozygosity at the gene locus was analyzed by the use of 12 microsatellite and polymorphic markers. Statistical tests were two-sided. Promoter 1A was methylated in 34 of 77 breast cancer tumors and cell lines (44%), in 56 of 106 NSCLC tumors and cell lines (53%), in 13 of 50 SCLC cell lines (26%), and in 3 of 68 nonmalignant samples (4%). Most cell lines tested contained the unmethylated or methylated form exclusively. In 27 cell lines tested, there was complete concordance between promoter methylation and silencing of its transcript. Demethylation with 5-aza-2'-deoxycytidine treatment restored transcript 1A expression in all eight methylated cell lines tested. Loss of heterozygosity at the APC locus was observed in 85% of SCLCs, 83% of NSCLCs, and 63% of breast cancer cell lines. The frequency of methylation in breast cancers increased with tumor stage and size. In summary, aberrant methylation of the 1A promoter of the APC gene and loss of its specific transcript is frequently present in breast and NSCLC cancers and cell lines and, to a lesser extent, in SCLC cell lines. Our findings may be of biological and clinical importance.

  15. Association between Hepatitis C Virus Infection, p53 Phenotypes, and Gene Variants of Adenomatous Polyposis Coli in Hepatocellular Carcinomas

    Science.gov (United States)

    Council, Leona N; Shanmugam, Chandrakumar; Suswam, Esther A; Katkoori, Venkat R; Heslin, Martine J; Hanna, Alex; Jhala, Nirag C; Varambally, Sooryanarayana; Manne, Upender

    2017-01-01

    Objective To investigate the clinical value of p53 codon 72 single nucleotide polymorphisms (SNPs) and variants of adenomatous polyposis coli (APC) in hepatocellular carcinomas (HCCs). Methods DNA and RNA from 51 HCCs and their matching, uninvolved liver tissues were analyzed for p53 mutations, and the methylation and expression of APC variants were determined. Proliferation of each HCC was assessed by Ki67 immunohistochemistry. The results were correlated with the demographic and clinicopathologic features and patient survival. Results Of 51 HCCs, 12% exhibited missense p53 mutations. SNP analysis of p53 codon 72 demonstrated the highest prevalence of the Arg/Arg (56%) phenotype, followed by Arg/Pro (33%) and Pro/Pro (11%). Four of five cases with the Pro/Pro phenotype were African Americans (AAs). All five cases with the Pro/Pro phenotype had hepatitis C virus (HCV) infections, a high Ki67 index, and lower median survival (15.5 months) compared to those with Arg/Arg or Arg/Pro phenotypes (32 months). The overall frequency of APC methylation was 31%, which was found predominantly in Caucasians. There was lower mRNA expression of APC variants-2 and -3 in both HCCs and corresponding adjacent, uninvolved liver tissues as compared to APC variant-1. The expression of APC variant-3, but not variants-1 and -2, was lower in HCCs relative to uninvolved tissues. Expression of all APC variants was lower in HCCs with APC methylation relative to HCCs without APC methylation, and low expression of APC variant-2 was associated with the Pro/Pro phenotype. Conclusions These findings suggest that, for AA patients with HCCs, the p53 Pro/Pro phenotype and low expression of APC variant-2 are associated with aggressive tumor behavior, HCV infection, and poor clinical outcome.

  16. Deficiency of Adenomatous Polyposis Coli protein in sporadic colorectal adenomas and its associations with clinical phenotype and histology

    Institute of Scientific and Technical Information of China (English)

    Martin Bortlík; Ivana Vítková; Martina Pape(z)ová; Milada Kohoutová; Ale(s) Novotn(y); Stanislav Adamec; Petra Chalupná; Milan Luká(s)

    2006-01-01

    AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to compare the APC status with the characteristics of colorectal adenomas.METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential,location of adenomas, macroscopic appearance and age of the patients.RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5 ± 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 ± 15.5mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P =0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P =0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas.CONCLUSION: Most adenomas expressed full-length APC protein, suggesting that protein expression is not a reliable marker for assessment of APC gene mutation.Complete loss of APC protein did not influence morphology, location, or appearance of adenomas, nor was it affected by the patient's age.

  17. Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of beta-catenin and chromosomal instability.

    Science.gov (United States)

    Pizzi, Silvia; Azzoni, Cinzia; Tamburini, Elisa; Bottarelli, Lorena; Campanini, Nicoletta; D'Adda, Tiziana; Fellegara, Giovanni; Luong, Tu Vinh; Pasquali, Claudio; Rossi, Giulio; Delle Fave, Gianfranco; Camisa, Roberta; Bordi, Cesare; Rindi, Guido

    2008-12-01

    The role of Wnt pathway in digestive endocrine tumours is debated. The aim of this work is to investigate key players in Wnt pathway by a multimodal approach. Sixty cases (49 well-differentiated and 11 poorly differentiated) were investigated for methylation of adenomatous polyposis coli (APC) and E-cadherin promoters, the loss of heterozygosity (LOH) at APC locus and beta-catenin and E-cadherin expression by immunohistochemistry. Tumours showing altered beta-catenin localization were tested for beta-catenin and APC mutations. APC promoter methylation was restricted to gastroduodenal tumours (21 out of 59, 36%), prevalent in poorly differentiated carcinomas (P=0.042) and correlating with aggressive features (high histology grade, P<0.02; tumour death, P=0.026; high fractional allelic loss, P=0.002, in turn correlating with short survival, P=0.017). LOH at APC locus was found in 14 out of 53 cases (26%, 10 gastroduodenal and 4 colorectal), prevalent in poorly differentiated carcinomas (P=0.002) and correlating with histology grade (P=0.012). beta-catenin abnormal expression was found in 41 out of 54 cases (76%), with nuclear staining correlating with APC alteration (P=0.047) and short survival (P=0.006). APC, but not beta-catenin, gene mutations were found (7 out of 35 tumours), 4 of which in the midgut. E-cadherin promoter methylation was rarely detected (2 out of 52 cases), with cytoplasmic expression in 18 out of 43 cases (42%), not correlating with any clinico-pathological feature. In conclusion, Wnt pathway alterations, as represented by abnormal beta-catenin localization, are common events in digestive endocrine tumours, but only nuclear expression correlates with tumour aggressiveness. Though with different alteration mechanisms according to anatomical site, APC plays a major role in Wnt pathway activation and in determining the high chromosomal instability observed in aggressive endocrine carcinomas.

  18. Adenomatous Polyposis Coli Protein Deletion in Efferent Olivocochlear Neurons Perturbs Afferent Synaptic Maturation and Reduces the Dynamic Range of Hearing

    Science.gov (United States)

    Hickman, Tyler T.; Liberman, M. Charles

    2015-01-01

    Normal hearing requires proper differentiation of afferent ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) that carry acoustic information to the brain. Within individual IHCs, presynaptic ribbons show a size gradient with larger ribbons on the modiolar face and smaller ribbons on the pillar face. This structural gradient is associated with a gradient of spontaneous rates and threshold sensitivity, which is essential for a wide dynamic range of hearing. Despite their importance for hearing, mechanisms that direct ribbon differentiation are poorly defined. We recently identified adenomatous polyposis coli protein (APC) as a key regulator of interneuronal synapse maturation. Here, we show that APC is required for ribbon size heterogeneity and normal cochlear function. Compared with wild-type littermates, APC conditional knock-out (cKO) mice exhibit decreased auditory brainstem responses. The IHC ribbon size gradient is also perturbed. Whereas the normal-developing IHCs display ribbon size gradients before hearing onset, ribbon sizes are aberrant in APC cKOs from neonatal ages on. Reporter expression studies show that the CaMKII-Cre used to delete the floxed APC gene is present in efferent olivocochlear (OC) neurons, not IHCs or SGNs. APC loss led to increased volumes and numbers of OC inhibitory dopaminergic boutons on neonatal SGN fibers. Our findings identify APC in efferent OC neurons as essential for regulating ribbon heterogeneity, dopaminergic terminal differentiation, and cochlear sensitivity. This APC effect on auditory epithelial cell synapses resembles interneuronal and nerve–muscle synapses, thereby defining a global role for APC in synaptic maturation in diverse cell types. Significance Statement This study identifies novel molecules and cellular interactions that are essential for the proper maturation of afferent ribbon synapses in sensory cells of the inner ear, and for normal hearing. PMID:26085645

  19. Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

    Directory of Open Access Journals (Sweden)

    Price David J

    2009-01-01

    Full Text Available Abstract Background Adenomatous polyposis coli (Apc is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex. Results We used Emx1Cre to inactivate Apc specifically in proliferating cerebral cortical cells and their descendents starting from embryonic day 9.5. We observed reduction in the size of the mutant cerebral cortex, disruption to its organisation, and changes in the molecular identity of its cells. Loss of Apc leads to a decrease in the size of the proliferative pool, disrupted interkinetic nuclear migration, and increased apoptosis. β-Catenin, pericentrin, and N-cadherin proteins no longer adopt their normal high concentration at the apical surface of the cerebral cortical ventricular zone, indicating that cell polarity is disrupted. Consistent with enhanced Wnt/β-catenin signalling resulting from loss of Apc we found increased levels of TCF/LEF-dependent transcription and expression of endogenous Wnt/β-catenin target genes (Axin2 (conductin, Lef1, and c-myc in the mutant cerebral cortex. In the Apc mutant cerebral cortex the expression of transcription factors Foxg1, Pax6, Tbr1, and Tbr2 is drastically reduced compared to normal and many cells ectopically express Pax3, Wnt1, and Wt1 (but not Wnt2b, Wnt8b, Ptc, Gli1, Mash1, Olig2, or Islet1. This indicates that loss of Apc function causes cerebral cortical cells to lose their normal identity and redirect to fates normally found in more posterior-dorsal regions of the central nervous system. Conclusion Apc is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and

  20. Gastrointestinal Polyposis Syndromes : Clinical and molecular aspects of Familial Adenomatous Polyposis and Juvenile Polyposis

    NARCIS (Netherlands)

    Brosens, L.A.A.

    2008-01-01

    Colorectal cancer (CRC) is an important cause death. In the Netherlands, approximately 10.000 patients are diagnosed with CRC each year. Rare hereditary gastrointestinal polyposis syndromes predisposing to CRC, including familial adenomatous polyposis (FAP), juvenile polyposis (JPS) and Peutz-Jegher

  1. Attenuated familial adenomatous polyposis (AFAP). A review of the literature

    DEFF Research Database (Denmark)

    Knudsen, Anne Lyster; Bisgaard, Marie Luise; Bülow, Steffen

    2003-01-01

    Over the last decade, a subset of familial adenomatous polyposis (FAP) patients with a milder course of disease termed attenuated familial adenomatous polyposis (AFAP) has been described. AFAP is not well-defined as a disease entity - the reports on AFAP are largely casuistic or only deal...

  2. Attenuated familial adenomatous polyposis (AFAP). A review of the literature

    DEFF Research Database (Denmark)

    Knudsen, Anne Lyster; Bisgaard, Marie Luise; Bülow, Steffen

    2003-01-01

    Over the last decade, a subset of familial adenomatous polyposis (FAP) patients with a milder course of disease termed attenuated familial adenomatous polyposis (AFAP) has been described. AFAP is not well-defined as a disease entity - the reports on AFAP are largely casuistic or only deal with a ...

  3. Tumor suppressor genes in familial adenomatous polyposis.

    Science.gov (United States)

    Eshghifar, Nahal; Farrokhi, Naser; Naji, Tahereh; Zali, Mohammadreza

    2017-01-01

    Colorectal cancer (CRC) is mostly due to a series of genetic alterations that are being greatly under the influence of the environmental factors. These changes, mutational or epigenetic modifications at transcriptional forefront and/or post-transcriptional effects via miRNAs, include inactivation and the conversion of proto-oncogene to oncogenes, and/or inactivation of tumor suppressor genes (TSG). Here, a thorough review was carried out on the role of TSGs with the focus on the APC as the master regulator, mutated genes and mal-/dysfunctional pathways that lead to one type of hereditary form of the CRC; namely familial adenomatous polyposis (FAP). This review provides a venue towards defining candidate genes that can be used as new PCR-based markers for early diagnosis of FAP. In addition to diagnosis, defining the modes of genetic alterations will open door towards genome editing to either suppress the disease or reduce its progression during the course of action.

  4. Extra-Abdominal Desmoid Tumors Associated with Familial Adenomatous Polyposis

    Directory of Open Access Journals (Sweden)

    George T. Calvert

    2012-01-01

    Full Text Available Extra-abdominal desmoid tumors are a significant cause of morbidity in patients with familial adenomatous polyposis syndrome. Understanding of the basic biology and natural history of these tumors has increased substantially over the past decade. Accordingly, medical and surgical management of desmoid tumors has also evolved. This paper analyzes recent evidence pertaining to the epidemiology, molecular biology, histopathology, screening, and treatment of extra-abdominal desmoid tumors associated with familial adenomatous polyposis syndrome.

  5. Tissue-Specific Effects of Reduced β-catenin Expression on Adenomatous Polyposis Coli Mutation-Instigated Tumorigenesis in Mouse Colon and Ovarian Epithelium.

    Directory of Open Access Journals (Sweden)

    Ying Feng

    2015-11-01

    Full Text Available Adenomatous polyposis coli (APC inactivating mutations are present in most human colorectal cancers and some other cancers. The APC protein regulates the β-catenin protein pool that functions as a co-activator of T cell factor (TCF-regulated transcription in Wnt pathway signaling. We studied effects of reduced dosage of the Ctnnb1 gene encoding β-catenin in Apc-mutation-induced colon and ovarian mouse tumorigenesis and cell culture models. Concurrent somatic inactivation of one Ctnnb1 allele, dramatically inhibited Apc mutation-induced colon polyposis and greatly extended Apc-mutant mouse survival. Ctnnb1 hemizygous dose markedly inhibited increases in β-catenin levels in the cytoplasm and nucleus following Apc inactivation in colon epithelium, with attenuated expression of key β-catenin/TCF-regulated target genes, including those encoding the EphB2/B3 receptors, the stem cell marker Lgr5, and Myc, leading to maintenance of crypt compartmentalization and restriction of stem and proliferating cells to the crypt base. A critical threshold for β-catenin levels in TCF-regulated transcription was uncovered for Apc mutation-induced effects in colon epithelium, along with evidence of a feed-forward role for β-catenin in Ctnnb1 gene expression and CTNNB1 transcription. The active β-catenin protein pool was highly sensitive to CTNNB1 transcript levels in colon cancer cells. In mouse ovarian endometrioid adenocarcinomas (OEAs arising from Apc- and Pten-inactivation, while Ctnnb1 hemizygous dose affected β-catenin levels and some β-catenin/TCF target genes, Myc induction was retained and OEAs arose in a fashion akin to that seen with intact Ctnnb1 gene dose. Our findings indicate Ctnnb1 gene dose exerts tissue-specific differences in Apc mutation-instigated tumorigenesis. Differential expression of selected β-catenin/TCF-regulated genes, such as Myc, likely underlies context-dependent effects of Ctnnb1 gene dosage in tumorigenesis.

  6. Adenomatous polyposis coli-mediated control of β-catenin is essential for both chondrogenic and osteogenic differentiation of skeletal precursors

    Directory of Open Access Journals (Sweden)

    Löwik Clemens WGM

    2009-04-01

    Full Text Available Abstract Background During skeletogenesis, protein levels of β-catenin in the canonical Wnt signaling pathway determine lineage commitment of skeletal precursor cells to osteoblasts and chondrocytes. Adenomatous polyposis coli (Apc is a key controller of β-catenin turnover by down-regulating intracellular levels of β-catenin. Results To investigate whether Apc is involved in lineage commitment of skeletal precursor cells, we generated conditional knockout mice lacking functional Apc in Col2a1-expressing cells. In contrast to other models in which an oncogenic variant of β-catenin was used, our approach resulted in the accumulation of wild type β-catenin protein due to functional loss of Apc. Conditional homozygous Apc mutant mice died perinatally showing greatly impaired skeletogenesis. All endochondral bones were misshaped and lacked structural integrity. Lack of functional Apc resulted in a pleiotropic skeletal cell phenotype. The majority of the precursor cells lacking Apc failed to differentiate into chondrocytes or osteoblasts. However, skeletal precursor cells in the proximal ribs were able to escape the noxious effect of functional loss of Apc resulting in formation of highly active osteoblasts. Inactivation of Apc in chondrocytes was associated with dedifferentiation of these cells. Conclusion Our data indicate that a tight Apc-mediated control of β-catenin levels is essential for differentiation of skeletal precursors as well as for the maintenance of a chondrocytic phenotype in a spatio-temporal regulated manner.

  7. LKB1-mediated spatial control of GSK3beta and adenomatous polyposis coli contributes to centrosomal forward movement and neuronal migration in the developing neocortex.

    Science.gov (United States)

    Asada, Naoyuki; Sanada, Kamon

    2010-06-30

    Neuronal migration is an essential process for the development of the cerebral cortex. We have previously shown that LKB1, an evolutionally conserved polarity kinase, plays a critical role in neuronal migration in the developing neocortex. Here we show that LKB1 mediates Ser9 phosphorylation of GSK3beta to inactivate the kinase at the leading process tip of migrating neurons in the developing neocortex. This enables the microtubule plus-end binding protein adenomatous polyposis coli (APC) to localize at the distal ends of microtubules in the tip, thereby stabilizing microtubules near the leading edge. We also show that LKB1 activity, Ser9 phosphorylation of GSK3beta, and APC binding to the distal ends of microtubules are required for the microtubule stabilization in the leading process tip, centrosomal forward movement, and neuronal migration. These findings suggest that LKB1-induced spatial control of GSK3beta and APC at the leading process tip mediates the stabilization of microtubules within the tip and is critical for centrosomal forward movement and neuronal migration in the developing neocortex.

  8. Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype

    DEFF Research Database (Denmark)

    Bisgaard, M L; Ripa, R; Knudsen, Anne Louise;

    2004-01-01

    BACKGROUND: Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli (APC) gene in approximately 80% of patients. The APC protein compri...... they do not themselves more often represent an isolated case. CONCLUSIONS: The severe phenotype should be considered when counselling FAP families in which attenuated FAP is excluded and in which a causative APC mutation has not been identified.......BACKGROUND: Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli (APC) gene in approximately 80% of patients. The APC protein...... in patients with a known APC mutation and with the phenotypes characteristic of patients with mutations in specific APC regions and domains. PATIENTS: Data on 121 FAP probands and 149 call up patients from 70 different families were extracted from the Danish Polyposis register. METHODS: Differences in 16...

  9. Thyroid carcinoma associated with familial adenomatous polyposis.

    Science.gov (United States)

    Cetta, F; Toti, P; Petracci, M; Montalto, G; Disanto, A; Lorè, F; Fusco, A

    1997-09-01

    Thyroid carcinoma is an extracolonic manifestation that is present in about 1% to 2% of patients with familial adenomatous polyposis (FAP). Less than 100 cases have been reported in detail. We have investigated the suggestion that FAP associated thyroid carcinoma is significantly different morphologically from both papillary and follicular types and can be considered as a separate entity. Specimens from three patients with FAP associated thyroid tumours, all but one having single nodules, have been analysed. All three patients belonged to an extended kindred (23 siblings in four generations) who had genetic analysis and intensive screening for thyroid nodules. Seven patients had the same APC mutation at codon 1061. Pathological examination revealed a typical papillary carcinoma, encapsulated variant, in all patients, with follicular areas in one case. All thyroid specimens, in addition to histological and immunohistological examinations, were also specifically studied for activation of the RET-PTC oncogene, that seems to be restricted to papillary thyroid carcinoma. Two of the three patients had RET-PTC activation (PTC1 isoform). The findings suggest that the tumours were certainly papillary, at least in the present kindred. Further studies in different families are required for a better understanding of this peculiar tumour and of its biological behaviour.

  10. A common role for various human truncated adenomatous polyposis coli isoforms in the control of beta-catenin activity and cell proliferation.

    Directory of Open Access Journals (Sweden)

    Shree Harsha Vijaya Chandra

    Full Text Available The tumour suppressor gene adenomatous polyposis coli (APC is mutated in most colorectal cancer cases, leading to the synthesis of truncated APC products and the stabilization of β-catenin. Truncated APC is almost always retained in tumour cells, suggesting that it serves an essential function. Here, RNA interference has been used to down-regulate truncated APC in several colorectal cancer cell lines expressing truncated APCs of different lengths, thereby performing an analysis covering most of the mutation cluster region (MCR. The consequences on proliferation in vitro, tumour formation in vivo and the level and transcriptional activity of β-catenin have been investigated. Down-regulation of truncated APC results in an inhibition of tumour cell population expansion in vitro in 6 cell lines out of 6 and inhibition of tumour outgrowth in vivo as analysed in one of these cell lines, HT29. This provides a general rule explaining the retention of truncated APC in colorectal tumours and defines it as a suitable target for therapeutic intervention. Actually, we also show that it is possible to design a shRNA that targets a specific truncated isoform of APC without altering the expression of wild-type APC. Down-regulation of truncated APC is accompanied by an up-regulation of the transcriptional activity of β-catenin in 5 out of 6 cell lines. Surprisingly, the increased signalling is associated in most cases (4 out of 5 with an up-regulation of β-catenin levels, indicating that truncated APC can still modulate wnt signalling through controlling the level of β-catenin. This control can happen even when truncated APC lacks the β-catenin inhibiting domain (CiD involved in targeting β-catenin for proteasomal degradation. Thus, truncated APC is an essential component of colorectal cancer cells, required for cell proliferation, possibly by adjusting β-catenin signalling to the "just right" level.

  11. Oncogenic mutations in adenomatous polyposis coli (Apc activate mechanistic target of rapamycin complex 1 (mTORC1 in mice and zebrafish

    Directory of Open Access Journals (Sweden)

    Alexander J. Valvezan

    2014-01-01

    Full Text Available Truncating mutations in adenomatous polyposis coli (APC are strongly linked to colorectal cancers. APC is a negative regulator of the Wnt pathway and constitutive Wnt activation mediated by enhanced Wnt–β-catenin target gene activation is believed to be the predominant mechanism responsible for APC mutant phenotypes. However, recent evidence suggests that additional downstream effectors contribute to APC mutant phenotypes. We previously identified a mechanism in cultured human cells by which APC, acting through glycogen synthase kinase-3 (GSK-3, suppresses mTORC1, a nutrient sensor that regulates cell growth and proliferation. We hypothesized that truncating Apc mutations should activate mTORC1 in vivo and that mTORC1 plays an important role in Apc mutant phenotypes. We find that mTORC1 is strongly activated in apc mutant zebrafish and in intestinal polyps in Apc mutant mice. Furthermore, mTORC1 activation is essential downstream of APC as mTORC1 inhibition partially rescues Apc mutant phenotypes including early lethality, reduced circulation and liver hyperplasia. Importantly, combining mTORC1 and Wnt inhibition rescues defects in morphogenesis of the anterior-posterior axis that are not rescued by inhibition of either pathway alone. These data establish mTORC1 as a crucial, β-catenin independent effector of oncogenic Apc mutations and highlight the importance of mTORC1 regulation by APC during embryonic development. Our findings also suggest a new model of colorectal cancer pathogenesis in which mTORC1 is activated in parallel with Wnt/β-catenin signaling.

  12. Downregulation of adenomatous polyposis coli by microRNA-663 promotes odontogenic differentiation through activation of Wnt/beta-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Sung; Park, Min-Gyeong; Lee, Seul Ah; Park, Sun-Young; Kim, Heung-Joong; Yu, Sun-Kyoung; Kim, Chun Sung; Kim, Su-Gwan; Oh, Ji-Su; You, Jae-Seek; Kim, Jin-Soo; Seo, Yo-Seob [Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759 (Korea, Republic of); Chun, Hong Sung [Department of Biomedical Science, Chosun University, Gwangju 501-759 (Korea, Republic of); Park, Joo-Cheol [Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749 (Korea, Republic of); Kim, Do Kyung, E-mail: kdk@chosun.ac.kr [Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759 (Korea, Republic of)

    2014-04-18

    Highlights: • miR-663 is significantly up-regulated during MDPC-23 odontoblastic cell differentiation. • miR-663 accelerates mineralization in MDPC-23 odontoblastic cells without cell proliferation. • miR-663 promotes odontoblastic cell differentiation by targeting APC and activating Wnt/β-catenin signaling in MDPC-23 cells. - Abstract: MicroRNAs (miRNAs) regulate cell differentiation by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNAs in odontogenic differentiation is largely unknown. In this present study, we observed that the expression of miR-663 increased significantly during differentiation of MDPC-23 cells to odontoblasts. Furthermore, up-regulation of miR-663 expression promoted odontogenic differentiation and accelerated mineralization without proliferation in MDPC-23 cells. In addition, target gene prediction for miR-663 revealed that the mRNA of the adenomatous polyposis coli (APC) gene, which is associated with the Wnt/β-catenin signaling pathway, has a miR-663 binding site in its 3′-untranslated region (3′UTR). Furthermore, APC expressional was suppressed significantly by miR-663, and this down-regulation of APC expression triggered activation of Wnt/β-catenin signaling through accumulation of β-catenin in the nucleus. Taken together, these findings suggest that miR-663 promotes differentiation of MDPC-23 cells to odontoblasts by targeting APC-mediated activation of Wnt/β-catenin signaling. Therefore, miR-663 can be considered a critical regulator of odontoblast differentiation and can be utilized for developing miRNA-based therapeutic agents.

  13. Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.

    Science.gov (United States)

    Efstathiou, J A; Noda, M; Rowan, A; Dixon, C; Chinery, R; Jawhari, A; Hattori, T; Wright, N A; Bodmer, W F; Pignatelli, M

    1998-03-17

    Intestinal trefoil factor 3 (TFF3) is a member of the trefoil family of peptides, small molecules constitutively expressed in epithelial tissues, including the gastrointestinal tract. TFF3 has been shown to promote migration of intestinal epithelial cells in vitro and to enhance mucosal healing and epithelial restitution in vivo. In this study, we evaluated the effect of recombinant TFF3 (rTFF3) stimulation on the expression and cellular localization of the epithelial (E)-cadherin-catenin complex, a prime mediator of Ca2+ dependent cell-cell adhesion, and the adenomatous polyposis coli (APC)-catenin complex in HT29, HCT116, and SW480 colorectal carcinoma cell lines. Stimulation by rTFF3 (10(-9) M and 10(-8) M) for 20-24 hr led to cell detachment and to a reduction in intercellular adhesion in HT29 and HCT116 cells. In both cell lines, E-cadherin expression was down-regulated. The expression of APC, alpha-catenin and beta-catenin also was decreased in HT29 cells, with a translocation of APC into the nucleus. No change in either cell adhesion or in the expression of E-cadherin, the catenins, and APC was detected in SW480 cells. In addition, TFF3 induced DNA fragmentation and morphological changes characteristic of apoptosis in HT29. Tyrphostin, a competitive inhibitor of protein tyrosine kinases, inhibited the effects of TFF3. Our results indicate that by perturbing the complexes between E-cadherin, beta-catenin, and associated proteins, TFF3 may modulate epithelial cell adhesion, migration, and survival.

  14. Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype

    DEFF Research Database (Denmark)

    Bisgaard, M L; Ripa, R; Knudsen, Anne Louise;

    2004-01-01

    BACKGROUND: Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli (APC) gene in approximately 80% of patients. The APC protein...... comprises several regions and domains for interaction with other proteins, and specific clinical manifestations are associated with the mutation assignment to one of these regions or domains. AIMS: The phenotype in patients without an identified causative APC mutation was compared with the phenotype...... in patients with a known APC mutation and with the phenotypes characteristic of patients with mutations in specific APC regions and domains. PATIENTS: Data on 121 FAP probands and 149 call up patients from 70 different families were extracted from the Danish Polyposis register. METHODS: Differences in 16...

  15. Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype

    DEFF Research Database (Denmark)

    Bisgaard, M L; Ripa, R; Knudsen, Anne Louise

    2004-01-01

    BACKGROUND: Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli (APC) gene in approximately 80% of patients. The APC protein...... in patients with a known APC mutation and with the phenotypes characteristic of patients with mutations in specific APC regions and domains. PATIENTS: Data on 121 FAP probands and 149 call up patients from 70 different families were extracted from the Danish Polyposis register. METHODS: Differences in 16...... clinical manifestations were analysed according to the patient's mutational status. Two sided independent t sample test, two sided chi(2) test, and odds ratios were calculated. RESULTS: Patients without identified APC mutations had a unique and severe phenotype, which was roughly described as: young age...

  16. Desmoid tumour in familial adenomatous polyposis. A review of literature

    DEFF Research Database (Denmark)

    Knudsen, Anne Louise; Bülow, Steffen

    2001-01-01

    Desmoid tumours (DT) are rare benign tumours that do not metastasise, but tend to invade locally. DT are frequently seen in patients with familial adenomatous polyposis (FAP), and diagnosis and treatment are often difficult. Surgical trauma, genetic predisposition and hormonal factors are conside...

  17. The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells.

    Science.gov (United States)

    Mogensen, Mette M; Tucker, John B; Mackie, John B; Prescott, Alan R; Näthke, Inke S

    2002-06-10

    Loss of full-length adenomatous polyposis coli (APC) protein correlates with the development of colon cancers in familial and sporadic cases. In addition to its role in regulating beta-catenin levels in the Wnt signaling pathway, the APC protein is implicated in regulating cytoskeletal organization. APC stabilizes microtubules in vivo and in vitro, and this may play a role in cell migration (Näthke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, and W.J. Nelson. 1996. J. Cell Biol. 134:165-179; Mimori-Kiyosue, Y., N. Shiina, and S. Tsukita. 2000. J. Cell Biol. 148:505-517; Zumbrunn, J., K. Inoshita, A.A. Hyman, and I.S. Näthke. 2001. Curr. Biol. 11:44-49) and in the attachment of microtubules to kinetochores during mitosis (Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C. Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001. Nat. Cell Biol. 3:433-438; Kaplan, K.B., A. Burds, J.R. Swedlow, S.S. Bekir, P.K. Sorger, and I.S. Näthke. 2001. Nat. Cell Biol. 3:429-432). The localization of endogenous APC protein is complex: actin- and microtubule-dependent pools of APC have been identified in cultured cells (Näthke et al., 1996; Mimori-Kiyosue et al., 2000; Reinacher-Schick, A., and B.M. Gumbiner. 2001. J. Cell Biol. 152:491-502; Rosin-Arbesfeld, R., G. Ihrke, and M. Bienz. 2001. EMBO J. 20:5929-5939). However, the localization of APC in tissues has not been identified at high resolution. Here, we show that in fully polarized epithelial cells from the inner ear, endogenous APC protein associates with the plus ends of microtubules located at the basal plasma membrane. Consistent with a role for APC in supporting the cytoskeletal organization of epithelial cells in vivo, the number of microtubules is significantly reduced in apico-basal arrays of microtubule bundles isolated from mice heterozygous for APC.

  18. Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients

    NARCIS (Netherlands)

    Nieuwenhuis, M. H.; Mathus-Vliegen, E. M.; Baeten, C. G.; Nagengast, F. M.; van der Bijl, J.; van Dalsen, A. D.; Kleibeuker, J. H.; Dekker, E.; Langers, A. M.; Vecht, J.; Peters, F. T.; van Dam, R.; van Gemert, W. G.; Stuifbergen, W. N.; Schouten, W. R.; Gelderblom, H.; Vasen, H. F. A.

    2011-01-01

    BACKGROUND: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. METHODS: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management,

  19. Three novel mutations of APC gene in Chinese patients with familial adenomatous polyposis.

    Science.gov (United States)

    Liu, Qi; Li, Xiaoxia; Li, Sen; Qu, Shengqiang; Wang, Yu; Tang, Qingzhu; Ma, Hongwei; Luo, Yang

    2016-08-01

    Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by the development of hundreds to thousands of colonic adenomas and an increased risk of colorectal cancer. Adenomatous polyposis coli (APC), encoding a large multidomain protein involved in antagonizing the Wnt signaling pathway, has been identified as the main causative gene responsible for FAP. In this study, we identified three novel mutations as well as two recurrent mutations in the APC in five Chinese FAP families by sequencing. Immunohistochemical analysis revealed that among these mutations, a nonsense mutation (c.2510C>G) and two small deletions (c.2016_2047del, c.3180_3184del) led to the truncation of the APC protein and the cytoplasmic and nuclear accumulation of β-catenin in the colorectal samples from affected individuals, respectively. Our study expands the database on mutations of APC and provides evidence to understand the function of APC in FAP.

  20. A Patient with Interstitial 5q21 Deletion, Familial Adenomatous Polyposis, Dysmorphic Features, and Profound Neurologic Dysfunction

    Directory of Open Access Journals (Sweden)

    Manoochehr Karjoo

    2017-01-01

    Full Text Available Familial adenomatous polyposis (FAP is a hereditary autosomal dominant cancer syndrome, results from germ line mutation or deletion of the Adenomatous Polyposis Coli (APC gene on chromosome 5q21. Patients with FAP suffer from multiple polyps mainly at the colorectal region as well as other parts of the gastrointestinal tract, which has propensity to transform into carcinoma. FAP has also been well described in association with various syndromic extra-gastrointestinal manifestations. Less commonly, patients with FAP present with varying degrees of cognitive dysfunction and developmental delay, though the reason for the association is unclear. Herein, we report the case of a male patient born with an interstitial deletion of chromosome 5q, 46,XY, del(5 (q14q23, presenting with familial adenomatous polyposis (FAP, profound developmental delay, cognitive dysfunction, and multiple congenital anomalies including talipes equinovarus, agenesis of the corpus callosum, and dysmorphic facial features.

  1. The advances of familial adenomatous polyposis%家族性腺瘤性息肉病研究进展

    Institute of Scientific and Technical Information of China (English)

    张敏; 兰风华

    2014-01-01

    家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)以结直肠内生长成百上千枚息肉为主要特征,不进行治疗的患者几乎100%发展成大肠癌,主要由腺瘤性息肉病基因(adenomatous polyposis coli,APC)突变所致,越来越多学者发现APC基因突变位点和FAP临床表现具有一定相关性.本文将从FAP的分型、临床表现、诊断标准、致病基因APC、基因-表型相关性及治疗监测等方面作一综述.%Familial adenomatous polyposis (FAP) is a common hereditary syndrome that is characterized by the numerous adenomatous polyps in the colon and rectum,and almost all patients will develop colorectal cancer without treatment.It is mainly caused by a germline mutation of adenomatous polyposis coli (APC) gene,and more and more studies have attempted to correlate the location of the mutations on APC gene with clinical phenotypes.The aim of this review is to summarize the current clinical and genetic knowledge of FAP and the genotype-phenotype correlations.

  2. Results of national registration of familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen

    2003-01-01

    BACKGROUND AND AIMS: The Danish Polyposis Register was established in 1971 with the aim of improving the poor prognosis of familial adenomatous polyposis (FAP), and in 1975 the register became national. The aim of the present study was to evaluate the prevalence of colorectal cancer and survival...... and molecular genetic examination, and affected individuals were treated by colectomy. RESULTS: At the end of 2001, the Danish Polyposis Register included 434 patients from 165 families. The incidence rate was 1.90x10(-6) and the prevalence rate 4.65x10(-5). Colorectal cancer on the basis of FAP constituted 0......-2001, demonstrated a decreased prevalence of colorectal cancer from 60% to 27% (p

  3. 应用变性高效液相色谱检测31例家族性腺瘤性息肉病家系结肠腺瘤性息肉病基因突变%Detection of adenomatous polyposis coli gene mutations in 31 familial adenomatous polyposis families by using denaturing high performance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    蔡善荣; 张苏展; 郑树

    2008-01-01

    目的 应用变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)技术检测我国家族性腺瘤性息肉病(familial adenomatons polyposis,FAP)家系的结肠腺瘤性息肉病(adenoinatous pelyposis coli,APC)基因变异特征,研究其病因机制.方法 采集31个家系的先证者、患者和家系成员的外周血淋巴细胞,抽提DNA并以降落式PCR扩增APC基因各外显子和启动子.基因突变检测先由DHPLC进行筛选,发现异常峰者进行测序鉴定并TA克隆鉴定,结果与网络数据进行比对.结果 31个家系中共有15个家系检出了12种不同的突变类型,FAP家系APC基因的突变检出率为48.39%.发现了4种新的突变及3例不同的内含子突变.4个新的突变分别位于255、677、1192、1403密码子,均为移码突变.证明了DHPLC能检出APC基因的突变.在APC基因的突变中,移码突变占86.67%,无义突变占13.33%,说明移码突变是中国人APC基因突变的主要方式.在突变位点上,第15外显子突变最常见,约占86.67%.结论 FAP家系APC基因的突变检出率为48.39%,发现了4种新的导致蛋白编码改变的突变.证实中国人FAP家系中APC基因突变位点以第15外显子最常见,类型以移码突变为主.%Objective To analyze the adenomatous polyposis coli (APC)gene mutations in familial adenomatous polyposis(FAP)in Chinese.Methods DNA was extracted from blood samples taken from 31 FAP families ,and all formance liquid chromatography followed by sequencing if abnormal profile Was detected.Results Twelve categories ofAPC gene mutations were found in 15 FAP families(48.39%)including 4 novel mutations in coding region and 3 mutations in introns.The 4 novel mutations in coding region were frameshift mutations and located in codons 255,677,1192 and 1403 respectively.Most mutations were clustered in exon 15 of APC gene leading to frameshift and accounted for 86.67%.Others were nonsense mutatiom(13.33%).Conclusion The mutation rate

  4. Clinical outcomes of gastric polyps and neoplasms in patients with familial adenomatous polyposis

    Science.gov (United States)

    Nakamura, Keiko; Nonaka, Satoru; Nakajima, Takeshi; Yachida, Tatsuo; Abe, Seiichiro; Sakamoto, Taku; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Oda, Ichiro; Matsuda, Takahisa; Sekine, Shigeki; Kanemitsu, Yukihide; Katai, Hitoshi; Saito, Yutaka; Hirota, Seiichi

    2017-01-01

    Background and study aims Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a germline mutation in the adenomatous polyposis coli (APC) gene, characterized by the presence of more than 100 adenomatous polyps in the colorectum. The upper gastrointestinal tract is an extracolonic site for malignancy in patients with FAP. The frequency of death in Japanese patients with FAP because of gastric cancer is 2.8 % and that because of colon cancer is 60.6 %. Few studies have reported upper gastrointestinal diseases in patients with FAP. In the present study, we investigated the clinical outcomes of patients with FAP diagnosed with gastric neoplasms. Patients and methods We enrolled 80 patients with FAP who underwent esophagogastroduodenoscopy from October 1997 to December 2011. We investigated patient characteristics, endoscopic findings of gastric lesions, treatment outcomes, and long-term courses. Results Fundic gland polyposis was observed in 51 patients (64 %) and gastric neoplasms in 22 patients (28 %), including 20 with non-invasive and 2 with invasive neoplasm. Of the 26 neoplasms, 11 were treated by endoscopic resection (ER) and 4 by surgical resection. Metachronous gastric neoplasms were observed in 7 patients (15 lesions) and treated by ER, except for in 1 patient. No patients died of gastric lesions during a median follow-up period of 6.5 years (range, 0 – 14). Conclusion Because gastric lesions including gastric cancers in patients with FAP did not cause any deaths, they can be considered to have favorable prognoses. Early detection of gastric neoplasms through an appropriate follow-up interval may have contributed to these good outcomes. PMID:28271094

  5. Surveillance and management of upper gastrointestinal disease in Familial Adenomatous Polyposis

    DEFF Research Database (Denmark)

    Gallagher, Michelle C; Phillips, Robin K S; Bülow, Steffen

    2006-01-01

    Almost all patients affected by Familial Adenomatous polyposis (FAP) will develop foregut as well as hindgut polyps, and following prophylactic colectomy duodenal cancer constitutes one of the leading causes of death in screened populations. Without prophylactic colectomy, FAP patients predictabl...

  6. Open versus laparoscopic (assisted) ileo pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis

    NARCIS (Netherlands)

    Ali, Usama Ahmed; Keus, Frederik; Heikens, Joost T.; Bemelman, Willem A.; Berdah, Stephane V.; Gooszen, H. G.; van Laarhoven, Cees J. H. M.

    2009-01-01

    Background Restorative proctocolectomy with ileo pouch anal anastomosis (IPAA) is the main surgical treatment for patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). With the advancements of minimal-invasive surgery this demanding operation is increasingly being performed

  7. Papillary thyroid carcinoma in three siblings with familial adenomatous polyposis.

    Science.gov (United States)

    Civitelli, S; Tanzini, G; Cetta, F; Petracci, M; Pacchiarotti, M C; Civitelli, B

    1996-01-01

    The authors report three siblings (two sisters and their aunt, aged 20, 22 and 36, respectively) with familial adenomatous polyposis (FAP) and papillary thyroid carcinoma. After diagnosis of FAP, a single, non palpable nodule was revealed in each patient by routine screening ultrasonography of the gland. The diagnosis of papillary carcinoma was made by fine-needle-aspiration biopsy of the nodules and confirmed by histologic examination of surgical specimens. A review of the literature reveals about 40 reports of such an association, that is considered not fortuitous. Nevertheless, in this family the association seems to be a distinctive, clinical feature of the syndrome, affecting three out of five members intensively screened for extracolonic lesions.

  8. Surgical treatment of familial adenomatous polyposis: dilemmas and current recommendations.

    Science.gov (United States)

    Campos, Fábio Guilherme

    2014-11-28

    Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps (predisposing to colorectal cancer development) and numerous extracolonic manifestations. The underlying genetic burden generates variable clinical features that may influence operative management. As a precancerous hereditary condition, the rationale of performing a prophylactic surgery is a mainstay of FAP management. The purpose of the present paper is to bring up many controversial aspects regarding surgical treatment for FAP, and to discuss the results and perspectives of the operative choices and approaches. Preferably, the decision-making process should not be limited to the conventional confrontation of pros and cons of ileorectal anastomosis or restorative proctocolectomy. A wide discussion with the patient may evaluate issues such as age, genotype, family history, sphincter function, the presence or risk of desmoid disease, potential complications of each procedure and chances of postoperative surveillance. Therefore, the definition of the best moment and the choice of appropriate procedure constitute an individual decision that must take into consideration patient's preferences and full information about the complex nature of the disease. All these facts reinforce the idea that FAP patients should be managed by experienced surgeons working in specialized centers to achieve the best immediate and long-term results.

  9. Identification of an APC Variant in a Patient with Clinical Attenuated Familial Adenomatous Polyposis

    Directory of Open Access Journals (Sweden)

    Andrew T. Schlussel

    2014-01-01

    Full Text Available Introduction. The objective of this case report is to discuss an unclassified germline variant of the adenomatous polyposis coli (APC gene identified in an older patient with attenuated familial adenomatous polyposis syndrome (AFAP. Methods. We present a case report of a 66-year-old man diagnosed with AFAP. Colonoscopy found multiple polyps and invasive adenocarcinoma arising in the transverse colon. Samples were tested for mutations in the APC gene. Results. DNA sequencing of germline DNA identified a cytosine (C to thymine (T transition at nucleotide 1240, heterozygous. The C to T transition at codon 414 is predicted to convert an arginine residue to a cysteine that is possibly pathogenic. Analysis of the patient’s colon tumor DNA indicated that the tumor had lost the mutant variant allele and retained only the normal allele, suggesting that the variant may not be significant. Conclusions. The p.R414C variant has been described previously as a germline mutation of probable pathogenicity. This substitution should be considered an unclassified variant and possibly not pathogenic. These findings support the need for further genetic testing of tissue, as well as for developing a mechanism for testing all variants, as this could significantly impact the lives of patients and their family members.

  10. Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients

    Directory of Open Access Journals (Sweden)

    Danielidis Ioannis

    2005-04-01

    Full Text Available Abstract Background Familial Adenomatous Polyposis (FAP is caused by germline mutations in the APC (Adenomatous Polyposis Coli gene. The vast majority of APC mutations are point mutations or small insertions / deletions which lead to truncated protein products. Splicing mutations or gross genomic rearrangements are less common inactivating events of the APC gene. Methods In the current study genomic DNA or RNA from ten unrelated FAP suspected patients was examined for germline mutations in the APC gene. Family history and phenotype were used in order to select the patients. Methods used for testing were dHPLC (denaturing High Performance Liquid Chromatography, sequencing, MLPA (Multiplex Ligation – dependent Probe Amplification, Karyotyping, FISH (Fluorescence In Situ Hybridization and RT-PCR (Reverse Transcription – Polymerase Chain Reaction. Results A 250 Kbp deletion in the APC gene starting from intron 5 and extending beyond exon 15 was identified in one patient. A substitution of the +5 conserved nucleotide at the splice donor site of intron 9 in the APC gene was shown to produce frameshift and inefficient exon skipping in a second patient. Four frameshift mutations (1577insT, 1973delAG, 3180delAAAA, 3212delA and a nonsense mutation (C1690T were identified in the rest of the patients. Conclusion Screening for APC mutations in FAP patients should include testing for splicing defects and gross genomic alterations.

  11. Familial Adenomatous Polyposis: Experience from a Study of 1164 Unrelated German Polyposis Patients

    Directory of Open Access Journals (Sweden)

    Friedl Waltraut

    2005-09-01

    Full Text Available Abstract The autosomal-dominant precancerous condition familial adenomatous polyposis (FAP is caused by germline mutations in the tumour suppressor gene APC. Consistent correlations between the site of mutations in the gene and clinical phenotype have been published for different patient groups. We report our experiences of APC mutation analysis and genotype-phenotype correlations in 1166 unrelated polyposis families and discuss our results in the light of literature data. We show that the mutation detection rates largely depend on the family history and clinical course of the disease. We present a list of 315 different point mutations and 37 large deletions detected in 634 of the 1166 index patients. Our results confirm previously published genotype-phenotype correlations with respect to the colorectal phenotype and extracolonic manifestations. However, 'exceptions to the rule' are also observed, and possible explanations for this are discussed. The discovery of autosomal-recessive MUTYH-associated polyposis (MAP as a differential diagnosis to FAP implies that some results have to be reinterpreted and surveillance guidelines in the families have to be reevaluated.

  12. Tumor-associated NH2-terminal fragments are the most stable part of the adenomatous polyposis coli protein and can be regulated by interactions with COOH-terminal domains.

    Science.gov (United States)

    Li, Zhuoyu; Näthke, Inke S

    2005-06-15

    Truncation mutations in the adenomatous polyposis coli (APC) gene are responsible for familial and sporadic colorectal cancer. APC is a large, multifunctional protein involved in cell migration, proliferation, and differentiation. Dominant effects that have been attributed to the NH2-terminal fragments of APC expressed in tumors may result from loss of functions due to lack of COOH-terminal regions or gain of functions due to fewer regulatory interactions. Resolving this issue and determining how structural changes contribute to the multiple functions of the APC protein requires knowledge about the structural organization of the APC molecule. To this end, we used limited proteolysis to distinguish regions of the molecule with limited structure from those that form well-folded domains. We discovered that the NH2-terminal region of APC was most resistant to proteolytic degradation, whereas middle and COOH-terminal regions were significantly more sensitive. Binding of APC to microtubules protected COOH-terminal regions of APC against proteolysis, consistent with the idea that this region of the molecule becomes ordered when bound to microtubules. Furthermore, interactions between the NH2- and COOH-terminal domains of APC were identified in vitro and in vivo, suggesting that NH2-terminal fragments of APC may be regulated by interactions with COOH-terminal domains. Indeed, expressing COOH-terminal APC fragments in tumor cells resulted in changes in the protein interactions of endogenous NH2-terminal fragments in these cells. Thus, the dominant function of NH2-terminal APC fragments found in tumor cells could be explained by loss of this regulation in tumors where COOH-terminal domains are missing.

  13. Desmoids in familial adenomatous polyposis are monoclonal proliferations.

    Science.gov (United States)

    Middleton, S B; Frayling, I M; Phillips, R K

    2000-02-01

    Desmoids are poorly-understood, locally aggressive, non-metastasizing fibromatoses that occur with disproportionate frequency in patients with familial adenomatous polyposis (FAP). Their nature is controversial with arguments for and against a neoplastic origin. Neoplastic proliferations are by definition monoclonal, whereas reactive processes originate from a polyclonal background. We examined clonality of 25 samples of desmoid tissue from 11 female FAP patients by assessing patterns of X-chromosome inactivation to calculate a clonality ratio. Polymerase chain reaction (PCR) amplification of a polymorphic CAG short tandem repeat (STR) sequence adjacent to a methylation-sensitive restriction enzyme site within the human androgen receptor (HUMARA) gene using fluorescent-labelled primers enabled analysis of PCR products by Applied Biosystems Genescan II software. Twenty-one samples from nine patients were informative for the assay. Samples from all informative cases comprised a median of 66% (range 0-75%) clonal cells but from the six patients with a clonality ratio < or =0.5 comprised a median of 71% (65-75%) clonal cells. FAP-associated desmoid tumours are true neoplasms. This may have implications in the development of improved treatment protocols for patients with these aggressive tumours.

  14. Polipose adenomatosa familiar atenuada Attenuated familial adenomatous polyposis

    Directory of Open Access Journals (Sweden)

    Gabriella Oliveira Fernandes

    2007-06-01

    Full Text Available A Polipose Adenomatosa Familiar Atenuada(PAFA é uma síndrome autossômica dominante, de diagnóstico tardio, comparando-se à forma clássica da polipose adenomatosa familiar. Dentre as características da síndrome estão: apresença de menos de 100 pólipos colorretais; b curso brando da doença, com idade tardia do diagnóstico e do aparecimento de câncer; cprevalência maior dos pólipos à direita do cólon; d reto poupado de lesões, na maioria dos casos. Analisar as características clínicas, tratamento e seguimento de 13 pacientes com diagnóstico de PAFA. Dos pacientes estudados, a média de idade ao diagnóstico foi 55 anos. Cinco pacientes apresentavam história familiar de polipose e/ou neoplasia. Nove (69% pacientes já tinham câncer no momento do diagnóstico. A maioria dos pacientes possuía pólipos localizados no cólon direito (31%. Do total, 06 pacientes foram submetidos à ressecção cirúrgica, com proctocolectomia ou colectomia. A média de seguimento dos pacientes foi de 26 meses. O controle foi realizado através de colonoscopias e retossigmoidoscopias, de acordo com o tratamento realizado. O diagnóstico de PAFA foi feito em idade tardia em relação à forma clássica da doença, com a maioria dos pólipos localizados no cólon direito. O controle endoscópico dos pacientes deve ser realizado com rigor. A colectomia com anastomose do íleo-reto é uma boa opção cirúrgica no tratamento dos pacientes, com baixa recidiva de pólipos no reto.Attenuated Familial Adenomatous Polyposis (AFAP is a heritable autosomally dominant syndrome, with later diagnosis than the classical condition of Familial Adenomatous Polyposis. Amid its main features there are : a the presence of less than 100 polyps; b the mild course of the disease and its later diagnosis and development of colon cancer; cthe polyps are more frequent in the right colon; dthe rectum may be relatively or even totally spared. To analyze the clinical

  15. Family history, surgery, and APC mutation are risk factors for desmoid tumors in familial adenomatous polyposis: an international cohort study

    DEFF Research Database (Denmark)

    Nieuwenhuis, Marry H; Lefevre, Jérémie H; Bülow, Steffen

    2011-01-01

    Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice.......Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice....

  16. Mutational studies of adenomatous polyposis coli gene in carcinomas from patients with hereditary non-polyposis colorectal cancers%遗传性非腺瘤病性结直肠癌结肠腺瘤病基因突变研究

    Institute of Scientific and Technical Information of China (English)

    黄建; 金胜航; 张苏展; 郑树

    2003-01-01

    目的分析遗传性非腺瘤病性结直肠癌(hereditary non-polyposis colorectal cancers ,HNPCC)结肠腺瘤病(adenomatous polyposis coli, APC)基因突变的特点及错配修复缺陷对其影响. 方法采用体外蛋白合成试验和序列分析确定19例HNPCC病例APC体细胞突变.结果 19例病例中有11例(13个突变点)发生APC突变,发生率为58%(11/19),其中移码突变9个,无义突变4个,移码突变占多数(69%).所有移码突变表现为1~2个碱基的缺失或插入,大多(7/9)发生在简单核苷酸重复序列,特别是单腺苷酸重复序列(A)n(5/9).检出的由单个碱基替换而导致的无义突变都发生在CpG岛,表现为C向T的转换.结论多于半数的HNPCC发生APC突变,其突变多发生在编码区单核苷酸重复序列(移码突变)或CpG岛(点突变)上,提示APC基因失活在HNPCC为常见的分子事件;错配修复缺陷所致的微卫星DNA不稳定性等内源性机理可能对APC突变产生影响.

  17. The role of pediatricians in families with a history of familial adenomatous polyposis.

    Science.gov (United States)

    Augustyn, Ann Marie; Wallerstein, Robert

    2009-07-01

    Colon cancer is not an entity that pediatricians routinely confront; however, a family history of colon cancer can have pediatric implications when it is part of familial adenomatous polyposis syndrome. Colonic (multiple intestinal polyps) and extracolonic manifestations (such as hepatoblastoma or brain tumors) can be the presenting features in children. The authors present 2 patients from different families with familial adenomatous polyposis who presented with the extracolonic manifestation of this syndrome and a family history of colon cancer. Identification of these families and education of their primary care givers can lead to improved screening and management of these high-risk individuals.

  18. Genotype predicting phenotype in familial adenomatous polyposis: a practical application to the choice of surgery

    DEFF Research Database (Denmark)

    Nieuwenhuis, Marry H; Bülow, Steffen; Björk, Jan

    2009-01-01

    PURPOSE: Genetic information may help preoperatively select patients with familial adenomatous polyposis for either colectomy with ileorectal anastomosis or proctocolectomy with ileal pouch-anal anastomosis. Although complicated, the latter procedure has a low long-term risk of rectal cancer...... the risk of secondary proctectomy after primary colectomy in familial adenomatous polyposis. Patients with severe genotypes have a high risk of reoperation after primary colectomy and will benefit from primary proctocolectomy with ileal pouch-anal anastomosis. The risk of rectal cancer after primary...

  19. Qualitative analysis of Adenomatous Polyposis Coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker

    Directory of Open Access Journals (Sweden)

    Nasseri Negin

    2009-01-01

    Full Text Available Abstract Background Squamous cell carcinoma of esophagus (SCCE occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (APC promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of APC promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and APC promoter methylation. Methods For evaluating the status of APC promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated APC promoter was compared with that of unmethylated patients. Results Assessment of APC promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4% tumor tissues were hypermethylated either in one or both alleles of APC. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of APC. Analyzing two-year survival rate of patients with respect

  20. Exclusion of the APC gene as the cause of a variant form of familial adenomatous polyposis (FAP)

    Energy Technology Data Exchange (ETDEWEB)

    Stella, A.; Resta, N.; Susca, F.; Guanti, G.; Gentile, M. (Universita di Bari (Italy)); Mareni, C.; Montera, P. (Universita di Genova (Italy))

    1993-11-01

    Familial adenomatous polyposis (FAP) is a premalignant disease inherited as an autosomal dominant trait, characterized by hundreds to thousands of polyps in the colorectal tract. Recently, the syndrome has been shown to be caused by mutations in the APC (adenomatous polyposis coli) gene located on chromosome 5q21. The authors studied two families that both presented a phenotype different from that of the classical form of FAP. The most important findings observed in these two kindreds are (a) low and variable number of colonic polyps (from 5 to 100) and (b) a slower evolution of the disease, with colon cancer occurring at a more advanced age than in FAP in spite of the early onset of intestinal manifestations. To determine whether mutations of the APC gene are also responsible for this variant syndrome, linkage studies were performed by using a series of markers both intragenic and tightly linked to the APC gene. The results provide evidence for exclusion of the APC gene as the cause of the variant form of polyposis present in the two families described. 30 refs., 1 fig., 1 tab.

  1. Quality of life and consequences for daily life of familial adenomatous polyposis (FAP) family members

    NARCIS (Netherlands)

    Douma, K.F.L.; Bleiker, E.M.A.; Vasen, H.F.A.; Gundy, C.M.; Aaronson, N.K.

    2011-01-01

    Aim  The study aimed to document the impact of familial adenomatous polyposis (FAP) on health-related quality of life (HRQOL) and several practical aspects of daily life and to identify factors associated significantly with HRQOL. This study is the first to compare HRQOL between FAP-patients, at-ris

  2. Quality of life and consequences for daily life of familial adenomatous polyposis (FAP) family members

    NARCIS (Netherlands)

    Douma, K.F.L.; Bleiker, E.M.A.; Vasen, H.F.A.; Gundy, C.M.; Aaronson, N.K.

    2011-01-01

    The study aimed to document the impact of familial adenomatous polyposis (FAP) on health-related quality of life (HRQOL) and several practical aspects of daily life, and to identify factors significantly associated with HRQOL. This study is the first to compare HRQOL between patients with FAP, at-ri

  3. Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis

    NARCIS (Netherlands)

    Douma, K.F.L.; Aaronson, N.K.; Vasen, H.F.A.; Verhoef, S.; Gundy, C.M.; Bleiker, E.M.A.

    2010-01-01

    Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA tes

  4. Desmoid tumors in a dutch cohort of patients with familial adenomatous polyposis.

    NARCIS (Netherlands)

    Nieuwenhuis, M.H.; Cappel, W De Vos Tot Nede; Botma, A.; Nagengast, F.M.; Kleibeuker, J.H.; Mathus-Vliegen, E.M.H.; Dekker, E. den; Dees, J.; Wijnen, J.; Vasen, H.F.

    2008-01-01

    BACKGROUND & AIMS: Desmoid tumors are a severe extracolonic manifestation in familial adenomatous polyposis (FAP). Identification of risk factors might be helpful in the management of FAP patients with such tumors. The aim of this study was to assess potential risk factors for the development of des

  5. Desmoid tumors in a dutch cohort of patients with familial adenomatous polyposis

    NARCIS (Netherlands)

    Nieuwenhuis, M.H.; Vos to Nederveen Cappel, de W.; Botma, A.; Nagengast, F.M.; Kleibeuker, J.H.; Mathus-Vliegen, E.M.; Dekker, E.; Dees, J.; Wijnen, J.; Vasen, H.F.

    2008-01-01

    Background & Aims: Desmoid tumors are a severe extracolonic manifestation in familial adenomatous polyposis (FAP). Identification of risk factors might be helpful in the management of FAP patients with such tumors. The aim of this study was to assess potential risk factors for the development of

  6. Genotype-phenotype correlations as a guide in the management of familial adenomatous polyposis

    NARCIS (Netherlands)

    Nieuwenhuis, Mary H.; Mathus-Vliegen, Lisbeth M.; Slors, Frederik J.; Griffioen, Gerrit; Nagengast, Fokko M.; Schouten, Wim R.; Kleibeuker, Jan H.; Vasen, Hans F. A.

    2007-01-01

    Background & Aims: The options for prevention of colorectal cancer in familial adenomatous polyposis are either a colectomy with ileorectal anastomosis (IRA) or a total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Rectal cancer risk is eliminated by IPAA, but complication rate is higher

  7. Genotype-phenotype correlations as a guide in the management of familial adenomatous polyposis.

    NARCIS (Netherlands)

    Nieuwenhuis, M.H.; Mathus-Vliegen, L.M.; Slors, F.J.; Griffioen, G.; Nagengast, F.M.; Schouten, W.R.; Kleibeuker, J.H.; Vasen, H.F.

    2007-01-01

    BACKGROUND & AIMS: The options for prevention of colorectal cancer in familial adenomatous polyposis are either a colectomy with ileorectal anastomosis (IRA) or a total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Rectal cancer risk is eliminated by IPAA, but complication rate is higher

  8. Chromosomal and methylation alterations in sporadic and familial adenomatous polyposis-related duodenal carcinomas.

    NARCIS (Netherlands)

    Berkhout, M.; Nagtegaal, I.D.; Cornelissen, S.J.B.; Dekkers, M.M.G.; Molengraft, F.J. van de; Peters, W.H.M.; Nagengast, F.M.; Krieken, J.H.J.M. van; Jeuken, J.W.M.

    2007-01-01

    Primary carcinomas of the small intestine are rare and the mechanism of their pathogenesis is poorly understood. Patients with familial adenomatous polyposis (FAP) have a high risk of developing duodenal carcinomas. The aim of this study is to gain more insight into the development of duodenal carci

  9. Mucosectomy and stapled pouch-anal anastomosis in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, S

    2012-01-01

    In familial adenomatous polyposis, a restorative proctocolectomy with an ileo-anal pouch may be performed either with a mucosectomy and a hand-sewn anastomosis or as a stapled anastomosis without a mucosectomy. The disadvantage of the former is suboptimal bowel function and the disadvantage...

  10. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

    Directory of Open Access Journals (Sweden)

    Leoz ML

    2015-04-01

    Full Text Available Maria Liz Leoz, Sabela Carballal, Leticia Moreira, Teresa Ocaña, Francesc Balaguer Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Barcelona, Catalonia, Spain Abstract: Familial adenomatous polyposis (FAP is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP. FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC, and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP. Keywords: colorectal cancer, familial adenomatous polyposis, MAP, APC, MUTYH

  11. Colorectal adenomatous polyposis syndromes: Genetic determinism, clinical presentation and recommendations for care.

    Science.gov (United States)

    Buecher, Bruno

    2016-02-01

    Colorectal adenomatous polyposis constitutes a diverse group of disorders with different modes of inheritance. Molecular diagnosis of this condition has become more complex. In fact, somatic mosaicism for APC mutations now appears to be more frequent than previously thought and rare germline alterations of this gene may be implicated in patients tested negative for "classical" APC mutations (point mutations and large genomic rearrangements). Moreover, the knowledge concerning several aspects of the MUTYH-associated polyposis has improved since its first description in 2002 and germline mutations in new genes have recently been implicated in some cases of unexplained adenomatous polyposis. Genetic testing in probands and their relatives should be conducted in the context of pre- and post-test genetic counseling. The recent advent of New Generation Sequencing (NGS) techniques affords the opportunity to rapidly screen patients for a comprehensive panel of colorectal cancer susceptibility genes in a cost-effective fashion. This type of approach will probably replace the classical sequential approach based on clinical presumptive diagnoses in the near future. The risk of colorectal cancer is very high in affected patients in the absence of appropriate care. Clinical management is complex and should be provided in centers with special expertise in these diseases. This review focuses on the various colorectal adenomatous polyposis syndromes with special attention to more innovative and important aspects.

  12. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis.

    LENUS (Irish Health Repository)

    Duffy, M

    2012-02-03

    PURPOSE: Ileal pouch-anal anastomosis remains the "gold standard" in surgical treatment of ulcerative colitis and familial adenomatous polyposis. Pouchitis occurs mainly in patients with a background of ulcerative colitis, although the reasons for this are unknown. The aim of this study was to characterize differences in pouch bacterial populations between ulcerative colitis and familial adenomatous pouches. METHODS: After ethical approval was obtained, fresh stool samples were collected from patients with ulcerative colitis pouches (n = 10), familial adenomatous polyposis (n = 7) pouches, and ulcerative colitis ileostomies (n = 8). Quantitative measurements of aerobic and anaerobic bacteria were performed. RESULTS: Sulfate-reducing bacteria were isolated from 80 percent (n = 8) of ulcerative colitis pouches. Sulfate-reducing bacteria were absent from familial adenomatous polyposis pouches and also from ulcerative colitis ileostomy effluent. Pouch Lactobacilli, Bifidobacterium, Bacteroides sp, and Clostridium perfringens counts were increased relative to ileostomy counts in patients with ulcerative colitis. Total pouch enterococci and coliform counts were also increased relative to ileostomy levels. There were no significant quantitative or qualitative differences between pouch types when these bacteria were evaluated. CONCLUSIONS: Sulfate-reducing bacteria are exclusive to patients with a background of ulcerative colitis. Not all ulcerative colitis pouches harbor sulfate-reducing bacteria because two ulcerative colitis pouches in this study were free of the latter. They are not present in familial adenomatous polyposis pouches or in ileostomy effluent collected from patients with ulcerative colitis. Total bacterial counts increase in ulcerative colitis pouches after stoma closure. Levels of Lactobacilli, Bifidobacterium, Bacteroides sp, Clostridium perfringens, enterococci, and coliforms were similar in both pouch groups. Because sulfate-reducing bacteria are

  13. Multiple desmoid tumors in a patient with familial adenomatous polyposis caused by the novel W421X mutation Tumor desmoide múltiple en un paciente con poliposis adenomatosa familiar originada por la nueva mutación W421X

    OpenAIRE

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

    2012-01-01

    Familial adenomatous polyposis (FAP) is a rare syndrome characterized by the presence of hundreds to thousands of colorectal adenomas and is responsible for less than 1% of all colorectal cancers. The syndrome is also characterized by extra-colorectal features including amongst others upper gastrointestinal tract polyps and desmoid tumors. The syndrome is inherited by an autosomal dominant gene, the adenomatous polyposis coli (APC) gene. We present the physical history, clinical presentation,...

  14. Sulphomucin expression in ileal pouches: emerging differences between ulcerative colitis and familial adenomatous polyposis pouches.

    LENUS (Irish Health Repository)

    Bambury, Niamh

    2012-02-03

    PURPOSE: We characterized the expression of sialomucin and sulphomucin in pouches fashioned for familial adenomatous polyposis and ulcerative colitis. We correlated sulphomucin expression with bacterial colonization and mucosal inflammation. METHODS: Ethical approval and informed consent were obtained. Mucosal biopsies from 9 patients with familial adenomatous polyposis and 12 with ulcerative colitis were obtained. Sulphomucin levels were assessed by using the high iron-diamine stain. Mucous gel layer composition was correlated with villous height, crypt depth, and total mucosal thickness. Mucous gel layer composition was correlated with acute and chronic inflammatory infiltrates. Colonization by a panel of seven bacterial species (including sulphate reducing bacteria) was established and correlated with sulphomucin levels. RESULTS: High-iron-diamine positivity (i.e., sulphomucin expression) was greater in ulcerative colitis pouch mucous gel (2.083 +\\/- 0.5 vs. 0.556 +\\/- 0.4, P = 0.003). Sulphomucin expression correlated with reduced crypt depth, villous height, and total mucosal thickness. In the ulcerative colitis group, chronic inflammatory infiltrate scores were significantly greater for high-iron-diamine-positive patients. Colonization by sulphate reducing bacteria was increased in high-iron-diamine-positive patients. CONCLUSIONS: Sulphomucin expression is increased in the mucous gel layer of the ulcerative colitis pouch compared with that of the familial adenomatous polyposis pouch. Sulphomucin expression is associated with colonization by sulphate-reducing bacteria and increased chronic inflammation.

  15. Cribiform variant of papillary thyroid cancer and familial adenomatous polyposis

    Directory of Open Access Journals (Sweden)

    E. Perea del Pozo

    2015-01-01

    Conclusions: The diagnosis of CMV of PTC is very strongly related to the FAP syndrome and must be suspected when a thyroid node appears in FAP patients. Likewise, any patient without known FAP who presents this histology in a surgically biopsied or resected thyroid node should undergo total colonoscopy for screening of colonic polyposis and genetic study of the APC gene sequence.

  16. Primary and secondary restorative proctocolectomy for familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, S; Højen, Helle; Buntzen, Steen

    2013-01-01

    Aim:  The aim of the study was to evaluate intraoperative difficulties, complications, and long-term bowel function in polyposis patients undergoing conversion of an ileorectal anastomosis to an ileoanal pouch, compared with patients with a primary ileoanal pouch operation. Method:  A national...... register based retrospective study was performed with clinical follow-up and a questionnaire concerning long-term bowel function. Results:  There were 84 patients including fifty-nine (70%) who had a primary pouch operation and 25 (30%) in whom a secondary pouch procedure was attempted. This was abandoned...... in one case leaving 24 patients who had a successful secondary RPC.. The median period of follow-up was 123 (0-359) months. Intraoperative difficulties occurred in none of the 59 primary and in 9/25 secondary operations (p...

  17. Filiform serrated adenomatous polyposis arising in a diverted rectum of an inflammatory bowel disease patient

    DEFF Research Database (Denmark)

    Klarskov, Louise; Mogensen, Anne Mellon; Jespersen, Niels

    2011-01-01

    during the adenoma carcinoma sequence included the acquisition of CK7 expression in the malignant portion. Gastric mucin may play a role in the initial step of the neoplastic evolution and CK7 may denote neoplastic progression. This case confirms the notion of a widely variegated morphology of precursor......Klarskov L, Mogensen AM, Jespersen N, Ingeholm P, Holck S. Filiform serrated adenomatous polyposis arising in a diverted rectum of an inflammatory bowel disease patient. APMIS 2011; 119: 393-8. A 54-year-old man, previously colectomized for inflammatory bowel disease, developed carcinoma...... of flat dysplasia. Although a combined gastric and intestinal (positivity for MUC5AC, MUC2, MUC6, CDX2) immunoprofile characterized the adenomatous component, a downregulation of the gastric mucin along with a loss of the serrated attribute accompanied the malignant transformation. An added dynamic shift...

  18. Attenuated Familial Adenomatous Polyposis (AFAP) Results from an international collaborative study

    DEFF Research Database (Denmark)

    Knudsen, A L; Bülow, S; Tomlinson, I

    2010-01-01

    Abstract Aim. The study aimed to describe genetical and clinical features of Attenuated Familial Adenomatous Polyposis (AFAP) and to propose clinical criteria and guidelines for treatment and surveillance. Method. A questionnaire study was carried out of polyposis registries with data on patients...... patients had a colectomy and an ileorectal anastomosis (IRA) and 5/82 (6%) had a secondary proctectomy. The location of the mutation in the APC gene was known in 69/171 (40%) tested patients. Only 15/29 (52%) of mutations in APC were found in parts of the gene usually associated with AFAP (the 5' end, exon...... 9 and 3' end). Conclusions. A subset of FAP patients with a milder phenotype does exist and treatment and surveillance should be modified accordingly. The mutation detection rate is lower than in classic FAP and mutations in AFAP patients are located throughout the APC gene. We propose the following...

  19. Familial adenomatous polyposis with synchronous invasive colonic carcinomas and metastatic jejunal adenocarcinoma in a Nigerian male

    Directory of Open Access Journals (Sweden)

    Emeka Blessius Kesieme

    2010-12-01

    Full Text Available Familial adenomatous polyposis is rare. Three cases were previously reported in Nigeria. An intriguing feature of this case is an ulcerated jejunal carcinoma which was metastatic rather than synchronous carcinoma. This patient presented with partial large bowel obstruction and the pathological analysis revealed 4 invasive adenocarcinomas, 3 in the colon and 1 in the jejunum (Dukes stage D. Palliative pancolectomy and jejunal tumour resection with chemotherapy was offered to him. He died eight months after surgery from disease progression. The challenges of managing a hereditary cancer syndrome in a resource poor country are highlighted.

  20. Pulmonary sclerosing hemangioma detected by fluorodeoxyglucose positron emission tomography in familial adenomatous polyposis: report of a case.

    NARCIS (Netherlands)

    Koning, D.B. de; Drenth, J.P.H.; Oyen, W.J.G.; Wagenaar, M.; Aliredjo, R.P.; Nagengast, F.M.

    2007-01-01

    We present a 53-year-old female suffering from familial adenomatous polyposis, who was found to have a positive nodus, lateral to the hilus of the left lung, on routine FDG-PET scan. This lesion was found to be a sclerosing hemangioma. We found an aberrant beta-catenin expression on immunohistochemi

  1. Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis : a multicentre, randomized controlled trial

    NARCIS (Netherlands)

    van Heumen, Bjorn W. H.; Roelofs, Hennie M. J.; Vink-Borger, M. Elisa; Dekker, Evelien; Mathus-Vliegen, Elisabeth M. H.; Dees, Jan; Koornstra, Jan J.; Langers, Alexandra M. J.; Nagtegaal, Iris D.; Kampman, Ellen; Peters, Wilbert H. M.; Nagengast, Fokko M.

    2013-01-01

    Background: Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of car

  2. Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial

    NARCIS (Netherlands)

    Heumen, van B.W.; Roelofs, H.M.J.; Vink-Börger, M.E.; Dekker, E.; Mathus-Vliegen, E.M.; Dees, J.; Koornstra, J.J.; Langers, A.M.; Nagtegaal, I.D.; Kampman, E.; Peters, W.H.; Nagengast, F.M.

    2013-01-01

    Background Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of card

  3. Pancreas-preserving total duodenectomy versus standard pancreatoduodenectomy for patients with familial adenomatous polyposis and polyps in the duodenum.

    NARCIS (Netherlands)

    Castro, SM de; Eijck, CH van; Rutten, J.P.; Dejong, C.H.; Goor, H. van; Busch, O.R.; Gouma, D.J.

    2008-01-01

    BACKGROUND: Pancreas-preserving total duodenectomy (PPTD) was introduced as a replacement for pancreatoduodenectomy (PD) for familial adenomatous polyposis (FAP). This study analysed the results of PPTD in the Netherlands and reviewed the relevant literature. METHODS: All 26 patients who underwent P

  4. Pulmonary sclerosing hemangioma detected by fluorodeoxyglucose positron emission tomography in familial adenomatous polyposis: report of a case.

    NARCIS (Netherlands)

    Koning, D.B. de; Drenth, J.P.H.; Oyen, W.J.G.; Wagenaar, M.; Aliredjo, R.P.; Nagengast, F.M.

    2007-01-01

    We present a 53-year-old female suffering from familial adenomatous polyposis, who was found to have a positive nodus, lateral to the hilus of the left lung, on routine FDG-PET scan. This lesion was found to be a sclerosing hemangioma. We found an aberrant beta-catenin expression on

  5. Dento-osseous anomalies associated to familial adenomatous polyposis mimicking florid cemento-osseous dysplasia.

    Science.gov (United States)

    Almeida, Fabiana Tolentino; Leite, André Ferreira; de Souza Figueiredo, Paulo Tadeu; Melo, Nilce Santos; Sousa, João Batista; Almeida, Rômulo; Acevedo, Ana Carolina; Silva Guerra, Eliete Neves

    2012-12-01

    Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome characterized by the development of multiple polyps of the colon and rectum with high risk of malignant transformation. The extraintestinal manifestations such as dento-osseous changes are associated with FAP. This is a case report of a 36-year-old female patient who was referred for dental treatment with the initial diagnosis of florid cemento-osseous dysplasia (FCOD). However, the association of the imaging dento-osseous findings with the medical history confirmed the diagnosis of FAP. The paper illustrates the clinical characteristics and imaging findings associated with FAP, and also discusses misdiagnosis based exclusively on imaging features. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  6. Familial Adenomatous Polyposis (FAP):Genotype Correlation to FAP Phenotype With Osteomas and Sebaceous Cysts

    DEFF Research Database (Denmark)

    Bisgaard, Marie Luise; Bülow, Steffen

    2006-01-01

    and familial adenomatous polyposis (FAP). The present study aimed at examining whether a particular APC genotype could be delineated in FAP patients with benign extracolonic manifestations: sebaceous cysts and/or osteomas. A questionnaire was sent to all Danish FAP patients (N = 234) asking for occurrence...... of sebaceous cysts and palpable osteomas. Medical records later verified positive findings, when possible. The results for each patient were correlated to the position of his or her mutation in the APC gene. Positive participation compliance was 77% (N = 180), and in 105 of these patients the pathogenic APC...... mutation was known. Palpable osteomas were reported in 17 of the patients in whom a pathogenic mutation had been identified. Osteomas were only identified in patients with mutations between codon 767 and 1513, a gene area also associated with congenital hypertrophy of the retinal-pigmented epithelium...

  7. Familial adenomatous polyposis (FAP): genotype correlation to FAP phenotype with osteomas and sebaceous cysts

    DEFF Research Database (Denmark)

    Bisgaard, Marie Luise; Bülow, Steffen

    2006-01-01

    and familial adenomatous polyposis (FAP). The present study aimed at examining whether a particular APC genotype could be delineated in FAP patients with benign extracolonic manifestations: sebaceous cysts and/or osteomas. A questionnaire was sent to all Danish FAP patients (N = 234) asking for occurrence...... of sebaceous cysts and palpable osteomas. Medical records later verified positive findings, when possible. The results for each patient were correlated to the position of his or her mutation in the APC gene. Positive participation compliance was 77% (N = 180), and in 105 of these patients the pathogenic APC...... mutation was known. Palpable osteomas were reported in 17 of the patients in whom a pathogenic mutation had been identified. Osteomas were only identified in patients with mutations between codon 767 and 1513, a gene area also associated with congenital hypertrophy of the retinal-pigmented epithelium...

  8. Pouch Salvage Surgery for Treatment of Colitis and Familial Adenomatous Polyposis: Report of Five Cases

    Directory of Open Access Journals (Sweden)

    Derakhshani

    2016-08-01

    Full Text Available Introduction The restorative proctocolectomy (RPC with ileal pouch-anal anastomosis (IPAA is currently the preferred surgical method for most patients with ulcerative colitis and familial adenomatous polyposis and sometimes, functional bowel diseases. Infection around the pouch, remaining rectal stump, stricture at anastomosis site, pouch dysfunction and refractory pouchitis can lead to pouch failure. Pouch salvage surgery could prevent pouch failure in some cases. Case Presentation In this report, five patients were introduced, who underwent pouch salvage surgery after RPC/IPAA surgery failure. Two of the patients were male and three were female and the relevant age range was 16 to 41. Initially, RPC/IPAA surgery was performed on these five patients. Four of the patients underwent RPC/IPAA surgery as a result of ulcerative colitis and, one of the patients as a result of familial adenomatous polyposis. However, due to pouch failure from the RPC/IPAA surgery, pouch-salvage surgery was performed on each of these five patients. Two of the patients underwent pouch-salvage surgery due to infection and pouch fistula, and the other three underwent this surgery due to the remaining rectal stump, anastomosis stenosis and pouch dysfunction. The average time for when pouch-salvage surgery was performed was 3.5 years (three months to five years after the initial operation and the patients were under follow-up care for two to seven years. Conclusions After performing pouch salvage operation, pouch function was acceptable in all patients and we could close ileostomies of all of them.

  9. Multidetector-row CT duodenography in familial adenomatous polyposis: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, S.A.; Halligan, S. E-mail: s.halligan@imperial.ac.uk; Moore, L.; Saunders, B.P.; Gallagher, M.; Phillips, R.K.S.; Bartram, C.I

    2004-10-01

    AIM: To investigate the feasibility of using multidetector-row computed tomography (CT) duodenography to stage duodenal polyposis in patients with familial adenomatous polyposis. MATERIALS AND METHODS: Six patients underwent multidetector-row CT duodenography before upper gastrointestinal endoscopy. A single-blinded radiologist used a surface shaded three-dimensional endoluminal fly though and two-dimensional axial and multiplanar reformats to assign a score for maximum polyp size and number based on the Spigelman classification. Comparison was made with the corresponding Spigelman scores obtained from subsequent endoscopy. RESULTS: CT duodenography was technically successful in five of six patients. The CT derived Spigelman score based on maximum polyp size was accurate in all five patients. The CT derived Spigelman score based on polyp number was accurate in only two cases: Polyp number was overestimated in one patient and underestimated in a further two. In retrospect, fine carpeting of tiny duodenal polyps was poorly visualized with CT. CONCLUSIONS: CT duodenography is technically feasible and accurately predicts maximum polyp size but CT estimates of polyp number are relatively inaccurate. CT duodenography potentially has a useful role for duodenal surveillance in those patients intolerant of conventional endoscopy.

  10. Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes : the worst of two worlds

    NARCIS (Netherlands)

    Scheenstra, R; Rijcken, FEM; Koornstra, JJ; Hollema, H; Fodde, R; Menko, FH; Sijmons, RH; Bijleveld, CMA; Kleibeuker, JH

    2003-01-01

    The two most common inherited forms of colorectal cancer are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Simultaneous inheritance of both an APC gene mutation and a mismatch repair gene (for example, MLH1) mutation has never been described. In the present case repo

  11. Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds.

    NARCIS (Netherlands)

    Scheenstra, R; Rijcken, FE; Koornstra, JJ; Hollema, H; Fodde, R; Menko, F.H.; Sijmons, RH; Bijleveld, CM; Kleibeuker, J.H.

    2003-01-01

    The two most common inherited forms of colorectal cancer are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Simultaneous inheritance of both an APC gene mutation and a mismatch repair gene (for example, MLH1) mutation has never been described. In the present case repo

  12. Clinical characterization and the mutation spectrum in Swedish adenomatous polyposis families

    Directory of Open Access Journals (Sweden)

    Meuller Johan

    2008-04-01

    Full Text Available Abstract Background The dominantly inherited condition familial adenomatous polyposis (FAP is caused by germline mutations in the APC gene. Finding the causative mutations has great implications for the families. Correlating the genotypes to the phenotypes could help to improve the diagnosis and follow-up of patients. Methods Mutation screening of APC and the clinical characterization of 96 unrelated FAP patients from the Swedish Polyposis Registry was performed. In addition to generally used mutation screening methods, analyses of splicing-affecting mutations and investigations of the presence of low-frequency mutation alleles, indicating mosaics, have been performed, as well as quantitative real-time polymerase chain reaction to detect lowered expression of APC. Results Sixty-one different APC mutations in 81 of the 96 families were identified and 27 of those are novel. We have previously shown that 6 of the 96 patients carried biallelic MUTYH mutations. The 9 mutation-negative cases all display an attenuated or atypical phenotype. Probands with a genotype (codon 1250–1464 predicting a severe phenotype had a median age at diagnosis of 21.8 (range, 11–49 years compared with 34.4 (range, 14–57 years among those with mutations outside this region (P 1000 occurred in 75% of the probands with a severe phenotype compared with 30% in those with mutations outside this region. The morbidity in colorectal cancer among probands was 25% at a mean age of 37.5 years and 29% at a mean age of 46.6 years. Conclusion Using a variety of mutation-detection techniques, we have achieved a 100% detection frequency in classical FAP. Probands with APC mutations outside codon 1250–1464, although exhibiting a less-severe phenotype, are at high risk of having a colorectal cancer at diagnosis indicating that age at diagnosis is as important as the severity of the disease for colorectal cancer morbidity.

  13. 5个家族性腺瘤样息肉病家系APC基因突变研究%Analysis of APC mutation in five kindreds of familial adenomatous polyposis

    Institute of Scientific and Technical Information of China (English)

    珠珠; 黄鉴; 董坚; 洪敏; 田晰晰; 杨军; 陈明清

    2012-01-01

    目的 探讨结肠腺瘤病(adenomatous polyposis coli,APC)基因在5个云南省家族性腺瘤样息肉病(Familial adenomatous polyposis,FAP)家系的突变情况.方法 对昆明医科大学第一附属医院住院病例进行统计,查找FAP家系,绘制家系图谱.抽取该家系成员外周静脉血提取DNA,利用PCR方法扩增APC基因,应用DNA自动测序仪进行测序.结果 5个家系(2个白族家系,2个彝族家系,1个汉族家系)中,只有汉族家系查出APC基因1196S>SX(1196号氨基酸由丝氨酸变为了终止密码子)的突变.其余家系均未查出APC基因的无义突变.结论 通过对5个FAP家系进行APC基因测序,发现云南省少数民族家系APC基因的突变率不高,APC基因突变存在民族差异.%Objective To investigate the APC mutation in five kindreds of familial adenomatous polyposis (4 minority nationalities and 1 han nationality) for early diagnosis and provide the basis for family. Methods 1411 pathologically confirmed colorectal cancer patients were collected and screened for familial adenomatous polyposis. The mutations of APC gene in the FAP families were detected. Results One of the FAP families was found APC gene mutation (1196S >SX). All people in the family carried this mutation. Conclusion There is one Han family found mutation of APC.

  14. Gene Expression Profiling in Familial Adenomatous Polyposis Adenomas and Desmoid Disease

    Directory of Open Access Journals (Sweden)

    Bowden Nikola A

    2007-06-01

    Full Text Available Abstract Gene expression profiling is a powerful method by which alterations in gene expression can be interrogated in a single experiment. The disease familial adenomatous polyposis (FAP is associated with germline mutations in the APC gene, which result in aberrant β-catenin control. The molecular mechanisms underlying colorectal cancer development in FAP are being characterised but limited information is available about other symptoms that occur in this disorder. Although extremely rare in the general population, desmoid tumours in approximately 10% of FAP patients. The aim of this study was to determine the similarities and differences in gene expression profiles in adenomas and compare them to those observed in desmoid tumours. Illumina whole genome gene expression BeadChips were used to measure gene expression in FAP adenomas and desmoid tumours. Similarities between gene expression profiles and mechanisms important in regulating formation of FAP adenomas and desmoid tumours were identified. This study furthers our understanding of the mechanisms underlying FAP and desmoid tumour formation.

  15. Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis.

    Science.gov (United States)

    Williams, Patrick A; Bhaijee, Feriyl; Rezeanu, Luminita; Hamilton, Robert D; Vijayakumar, Srinivasan

    2013-01-01

    It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

  16. Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis

    Directory of Open Access Journals (Sweden)

    Patrick A. Williams BS

    2013-04-01

    Full Text Available Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

  17. Desmoid Tumor Associated With Familial Adenomatous Polyposis: Evaluation With 64-Detector CT Enterography

    Directory of Open Access Journals (Sweden)

    Oktay Algin

    2012-03-01

    Full Text Available Desmoid tumors (DTs are benign tumors which are not seen very often, and most of the radiologists and clinicians do not know the characteristics of them very well. Correct and early diagnosis of DTs is important for decreasing mortality and morbidity. Computed tomography enterography (CTE is a new modality for small bowel imaging which combines the improved spatial and temporal resolution of multidetector computed tomography (CT with large volumes of ingested enteric contrast material to permit evaluation of the small bowel wall and lumen and also the entire abdomen. We report a familial adenomatous polyposis (FAP patient with localized mesentery and abdominal wall DTs. We showed the exact location of the DTs and their relation with the small bowel by CTE. In conclusion, CTE is a useful technique for DT localization, the degree of extension and invasion to local structures, presence of partial and complete small bowel obstruction, and the relationship of the tumors with vasculature and whether ischemia ha s occurred as a result or not.

  18. Management strategies in Lynch syndrome and familial adenomatous polyposis: a national healthcare survey in Japan.

    Science.gov (United States)

    Yamano, Tomoki; Hamanaka, Michiko; Babaya, Akihito; Kimura, Kei; Kobayashi, Masayoshi; Fukumoto, Miki; Tsukamoto, Kiyoshi; Noda, Masafumi; Matsubara, Nagahide; Tomita, Naohiro; Sugihara, Kenichi

    2017-02-01

    Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are major sources of hereditary colorectal cancer (CRC) and are associated with other malignancies. There is some heterogeneity in management strategies in Japan. We undertook a survey of management of hereditary CRC in hospitals that are members of the Japan Society of Colorectal Cancer Research. One hundred and ninety departments responded, of which 127 were from designated cancer care hospitals (DCCHs) according to the Japanese government. There were 25 488 operations for CRC in these departments in 2015. The DCCHs performed better with regard to usage of Japan Society of Colorectal Cancer Research guidelines, referring new CRC patients for LS screening, and having in-house genetic counselors and knowledge of treatment for LS. There were 174 patients diagnosed with LS and 602 undergoing follow-up in 2011-2015, which is fewer than the number expected from CRC operations in 2015. These numbers were not affected by whether the institution was a DCCH. Universal screening for LS was carried out in 8% of the departments. In contrast, 541 patients were diagnosed with FAP and 273 received preventive proctocolectomy/colectomy in 2011-2015. The DCCH departments undertook more surgery than non-DCCH departments, although most of the management, including surgical procedures and use of non-steroidal anti-inflammatory drugs, was similar. Management of desmoid tumor in the abdominal cavity differed according to the number of patients treated. In conclusion, there was heterogeneity in management of LS but not FAP. Most patients with LS may be overlooked and universal screening for LS is not common in Japan.

  19. Familial adenomatous polyposis-associated desmoids display significantly more genetic changes than sporadic desmoids.

    Directory of Open Access Journals (Sweden)

    Els Robanus-Maandag

    Full Text Available Desmoid tumours (also called deep or aggressive fibromatoses are potentially life-threatening fibromatous lesions. Hereditary desmoid tumours arise in individuals affected by either familial adenomatous polyposis (FAP or hereditary desmoid disease (HDD carrying germline mutations in APC. Most sporadic desmoids carry somatic mutations in CTNNB1. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumours. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumours, we analysed 17 FAP-associated and 38 sporadic desmoids by array comparative genomic hybridisation and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Recurrent gains at 8q (7% and 20q (5% were almost exclusively found in sporadic tumours. Recurrent losses were observed for a 700 kb region at 5q22.2, comprising the APC gene (11%, a 2 Mb region at 6p21.2-p21.1 (15%, and a relatively large region at 6q15-q23.3 (20%. The FAP-associated desmoids displayed a significantly higher frequency of copy number abnormalities (59% than the sporadic tumours (37%. As predicted by the APC germline mutations among these patients, a high percentage (29% of FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3% seen among sporadic tumours. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumour progression.

  20. Prevention of Aspirin against Recurrence of Polyposis after Operation on Patients with Familial Polyposis Coli

    Institute of Scientific and Technical Information of China (English)

    Zhou Jia-zhen; Liu Tao; Jin Jia-gui; Hu Xian-dian

    2006-01-01

    Objective To investigate how well a combined therapy prevents and treats familial polyposis coli and to observe whether aspirin prevents duodenal polyp development after operation.Methods Aspirin was started one month after the operation on 6 patients with familial polyposis coli. It was given 60 mg once a day for one month, and then was discontinued for one month, then used again for one month, and then discontinued for one month; in this way, aspirin was used every two months for the patient's life. The follow-up was performed for 17 years. Results The combined therapy, which consisted of a surgical operation of cutting the superior mesenteric artery & vein and making anastomosis of the ileum pouch and the anal canal within the muscular sheath of the rectum and an internal medical therapy of nonsteroidal antiinflammatory drugs, had a good therapeutic effect on familial polyposis coli and no duodenal polyp occurred in the 6 patients. Conclusion Our combined therapy can effectively treat familial polyposis coli, and aspirin can prevent duodenal polyp development after the operation.

  1. Clinical value of methylation of plasma adenomatous polyposis coli gene in the molecular diagnosis of hepatocellular carcinoma%腺瘤性结肠息肉病基因甲基化在肝细胞癌分子诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    胡瑜; 华东; 程之红; 吴玉玉; 谢其根; 王琼瑶; 余坚; 黄朝晖

    2011-01-01

    Objective: To establish a method of methylation-sensitive restriction enzymes-quantitative PCR (MSRE-Qpcr) for methylation analysis of adenomatous polyposis coli (APC) gene, and to further assess the clinical value of plasma methylation detection by using this method in diagnosis of hepatocellular carcinoma (HCC). Methods: Hha I was used to digest genomic DNA, and the digestion efficiency was evaluated by using Qpcr technique. Then the optimized MSRE-Qpcr method was established. The methylation levels of APC in 45 liver tissues (20 surgically resected HCC specimens and the matched non-cancerous tissues, as well as 5 normal liver tissues) were detected by MSRE-Qpcr, and then further validated by using bisulfite sequencing PCR (BSP). The results of MSRE-Qpcr were compared with those of methylation-specific PCR (MSP) assay. MSRE-Qpcr method was used to detect the APC methylation status of plasma samples from 72 cases of HCC, 37 cases of benign liver diseases and 41 healthy volunteers. Results: The established MSRE-Qpcr method could detect as low as 1% methylated target sites in given DNA samples. The results of MSRE-Qpcr and MSP showed that APC gene was hypermethylated in HCC tissues. The result of MSRE-Qpcr was verified by BSP, and it was comparable with that of MSP (Kappa=0.955, P<0.000 1). Methylation level of plasma APC in patients with HCC was significant higher than those in patients with benign liver diseases and the healthy volunteers (P<0.000 1).Combined analysis of plasma APC methylation and serum alpha-fetoprotein (AFP) revealed an increased diagnostic efficacy for HCC. Conclusion: MSRE-Qpcr is a method for quantitative analysis of APC methylation level. Methylation analysis of plasma APC is a valuable method for the noninvasive diagnosis of HCC.%目的:建立甲基化敏感性限制性内切酶-定量PCR (methylation-sensitive restriction enzyme-quantitative PCR,MSRE-qPCR)方法,并应用该方法探讨血浆腺瘤性结肠息肉病(adenomatous polyposis

  2. Effects of intervention with sulindac and inulin/VSL#3 on mucosal and luminal factors in the pouch of patients with familial adenomatous polyposis

    NARCIS (Netherlands)

    Friederich, P.; Verschuur, J.; Heumen, B.W. van; Schaap-Roelofs, H.M.J.; Berkhout, M.; Nagtegaal, I.D.; Oijen, M.G.H. van; Krieken, J.H. van; Peters, W.H.M.; Nagengast, F.M.

    2011-01-01

    BACKGROUND/AIM: In order to define future chemoprevention strategies for adenomas or carcinomas in the pouch of patients with familial adenomatous polyposis (FAP), a 4-weeks intervention with (1) sulindac, (2) inulin/VSL#3, and (3) sulindac/inulin/VSL#3 was performed on 17 patients with FAP in a sin

  3. Clinical characteristics and outcomes in familial adenomatous polyposis patients with a long-term treatment of celecoxib: a matched cohort study

    DEFF Research Database (Denmark)

    Huang, Kui; Gutierrez, Lia P; Bülow, Steffen

    2011-01-01

    Familial adenomatous polyposis (FAP) is a rare genetic disease. Without treatment, FAP patients have a 100% lifetime risk of developing colorectal cancer. This study was conducted to evaluate the effect of celecoxib treatment in prolonging the time to FAP-related events and to document the safety...

  4. Diffusion tensor imaging (DTI) of desmoid tumours in familial adenomatous polyposis: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Bhandari, Santosh, E-mail: s.bhandari10@imperial.ac.uk [Polyposis Registry, St. Mark' s Hospital, Watford Road, Harrow, Middlesex HA1 3UJ (United Kingdom); Sinha, Ashish, E-mail: asinha@imperial.ac.uk [Polyposis Registry, St. Mark' s Hospital, Watford Road, Harrow, Middlesex HA1 3UJ (United Kingdom); Tam, Emily, E-mail: Emily.wy.tam@gmail.com [Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN (United Kingdom); Stirling, J. James, E-mail: james.stirling@stricklandscanner.org.uk [Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN (United Kingdom); Simcock, Ian, E-mail: ian.simcock@stricklandscanner.org.uk [Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN (United Kingdom); Clark, Sue, E-mail: s.clark8@nhs.net [Polyposis Registry, St. Mark' s Hospital, Watford Road, Harrow, Middlesex HA1 3UJ (United Kingdom); Goh, Vicky, E-mail: Vicky.goh@kcl.ac.uk [Division of Imaging Sciences and Biomedical Engineering, King' s College London, Imaging 2, Level 1, Lambeth Wing, St. Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH (United Kingdom)

    2012-11-15

    Purpose: To assess the feasibility of diffusion tensor imaging (DTI) of desmoid tumours in familial adenomatous polyposis (FAP). Materials and methods: Following ethical approval and informed consent, FAP patients with desmoids underwent DTI. Fractional anisotropy (FA), relative anisotropy (RA) and apparent diffusion coefficient (ADC) were compared to control muscle using Mann-Whitney test; and to tumour site and signal intensity using one way analysis of variance (ANOVA). Imaging was repeated after 1 year. Results: 15 desmoids (6 intra-abdominal; 6 abdominal wall, 3 extra-abdominal; size range: 1.6-22.9 cm) were evaluated in 9 patients. DTI was successful in 12/15 desmoid tumours. Median (range) of RA, FA and ADC were 0.23 Multiplication-Sign 10{sup -3} mm{sup 2}/s (0.17-0.26); 0.27 Multiplication-Sign 10{sup -3} mm{sup 2}/s (0.21-0.31); and 1.65 Multiplication-Sign 10{sup -3} mm{sup 2}/s (1.39-1.91) for desmoids, significantly different from muscle: 0.27 Multiplication-Sign 10{sup -3} mm{sup 2}/s (0.23-0.40), 0.32 Multiplication-Sign 10{sup -3} mm{sup 2}/s (0.28-0.46), and 1.45 Multiplication-Sign 10{sup -3} mm{sup 2}/s (0.92-1.63) (p = 0.0001, p = 0.0001, p = 0.0016, respectively). There was no difference in RA, FA or ADC between tumour sites, or signal intensity (p > 0.05). One year later, 2 patients had died. Tumour increased in size in 1 patient (+61%). DTI quantification was possible in only 8/13 tumours. FA, RA and ADC were not significantly different from baseline (p = 0.77, 0.71 and 0.34, respectively). Conclusions: Assessment of water diffusion has the potential to provide insight into tumour microstructure and is feasible in desmoids. Desmoid tumours demonstrate anisotropy but diffusion is less restricted and less directional than in muscle.

  5. Polipose gastroduodenal em doentes com polipose adenomatosa familiar Pós-Retocolectomia Gastroduodenal polyposis in patients with familiar adenomatous polyposis after rectocolectomy

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    Raquel Franco Leal

    2007-06-01

    Full Text Available RACIONAL: As manifestações extracólicas, como os pólipos gastroduodenais e o tumor do duodeno, são fatores que influenciam a morbimortalidade dos doentes com polipose adenomatosa familiar no seguimento pós-retocolectomia total. OBJETIVO: Investigar a freqüência destas alterações em doentes com polipose adenomatosa familiar e verificar a eficácia do rastreamento endoscópico. MÉTODO:No período de 1984 a 2005, 62 doentes com polipose adenomatosa familiar pós-retocolectomia foram estudados retrospectivamente pelo Grupo de Coloproctologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, SP. O tempo de seguimento médio pós-operatório foi de 81,9 meses, sendo que em 53 (85,5% foi possível analisar a ocorrência de pólipos gastroduodenais. RESULTADOS: Dos 53 doentes em seguimento, 27 (50,9% apresentavam pólipos gastroduodenais. Em 8 (15,4% os pólipos adenomatosos eram gástricos, 14 (27% pólipos duodenais e 5 (9,6% pólipos gástricos e duodenais. Dois doentes (3,8% desenvolveram adenoma duodenal com displasia de alto grau. E outro (1,9%, adenocarcinoma em papila duodenal. CONCLUSÃO: O rastreamento endoscópico, desta forma, é de grande importância e o objetivo é detectar, o mais precocemente possível, os casos de adenocarcinoma duodenal e pólipos gastroduodenais com displasia de alto grau.BACKGROUND: The extra colonic manifestations, like upper gastrointestinal tract polyps and duodenal cancer are disorders that affect long-term morbidity and mortality of patients with familial adenomatous polyposis, after rectocolectomy. AIM: To describe the frequency of those disorders in patients with familial adenomatous polyposis and to review efficacy of upper gastrointestinal endoscopic surveillance. METHODS: Between 1984 and 2005, 62 patients with familial adenomatous polyposis after rectocolectomy, were studied retrospectively, by Coloproctology Group, Medical Sciences Faculty, State University of Campinas

  6. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

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    Johannsson Oskar

    2008-11-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations. Methods Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify APC gene mutations, which were correlated to the clinical presentations. Results 10 novel APC gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031insAA developed colon cancer at age 72 as the first manifestation of attenuated FAP. Conclusion With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.

  7. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant

    Science.gov (United States)

    Li, Jun; Woods, Susan L.; Healey, Sue; Beesley, Jonathan; Chen, Xiaoqing; Lee, Jason S.; Sivakumaran, Haran; Wayte, Nicci; Nones, Katia; Waterfall, Joshua J.; Pearson, John; Patch, Anne-Marie; Senz, Janine; Ferreira, Manuel A.; Kaurah, Pardeep; Mackenzie, Robertson; Heravi-Moussavi, Alireza; Hansford, Samantha; Lannagan, Tamsin R.M.; Spurdle, Amanda B.; Simpson, Peter T.; da Silva, Leonard; Lakhani, Sunil R.; Clouston, Andrew D.; Bettington, Mark; Grimpen, Florian; Busuttil, Rita A.; Di Costanzo, Natasha; Boussioutas, Alex; Jeanjean, Marie; Chong, George; Fabre, Aurélie; Olschwang, Sylviane; Faulkner, Geoffrey J.; Bellos, Evangelos; Coin, Lachlan; Rioux, Kevin; Bathe, Oliver F.; Wen, Xiaogang; Martin, Hilary C.; Neklason, Deborah W.; Davis, Sean R.; Walker, Robert L.; Calzone, Kathleen A.; Avital, Itzhak; Heller, Theo; Koh, Christopher; Pineda, Marbin; Rudloff, Udo; Quezado, Martha; Pichurin, Pavel N.; Hulick, Peter J.; Weissman, Scott M.; Newlin, Anna; Rubinstein, Wendy S.; Sampson, Jone E.; Hamman, Kelly; Goldgar, David; Poplawski, Nicola; Phillips, Kerry; Schofield, Lyn; Armstrong, Jacqueline; Kiraly-Borri, Cathy; Suthers, Graeme K.; Huntsman, David G.; Foulkes, William D.; Carneiro, Fatima; Lindor, Noralane M.; Edwards, Stacey L.; French, Juliet D.; Waddell, Nicola; Meltzer, Paul S.; Worthley, Daniel L.; Schrader, Kasmintan A.; Chenevix-Trench, Georgia

    2016-01-01

    Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present. PMID:27087319

  8. Restorative proctocolectomy or rectum-preserving surgery in patients with familial adenomatous polyposis: results of a prospective study.

    Science.gov (United States)

    Tonelli, F; Valanzano, R; Monaci, I; Mazzoni, P; Anastasi, A; Ficari, F

    1997-01-01

    Surgical treatment of familial adenomatous polyposis (FAP) is still controversial. From 1984 we carried out a prospective evaluation of total colectomy with ileorectal anastomosis (IRA) and restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) to determine differences in postoperative complications, functional results, occurrence of desmoids, and recurrence of polyps in the rectal stump. IRA was performed below the peritoneal reflection and was indicated in the absence of rectal cancer and in the presence of fewer than 10 polyps or minute polyposis in the last 10 cm of the rectal mucosa. IRA patients underwent a regular endoscopic follow-up and prolonged sulindac administration (100 mg twice daily). When criteria for IRA were absent, IPAA was performed adopting a manual anastomosis at the pectinate line. Fourteen patients were operated with IRA and 24 with IPAA. There was no difference in sex and age between the two groups of patients. The number of rectal polyps was significantly different in the two groups. Immediate postoperative complications were observed in only five IPAA patients, three of whom (12%) required reoperation. Late postoperative complications occurred more frequently in IRA patients (14%) than in IPAA patients (4%). Desmoids developed in both groups (five in the IRA group and four in IPAA group). The number of bowel movements was similar in both groups, but 25% of IPAA patients complained of nocturnal fecal soiling. Fulguration or polypectomy for recurrent polyps was necessary in all but two IRA patients at follow-up. The rectal stump was easily eradicated by polyps in all but four patients with minute polyps at surgery. In the latter patients a diffuse or carpeting rectal polyposis occurred. IPAA can give optimum control of colorectal polyposis in FAP patients with an acceptable incidence of postoperative complications and satisfactory functional results. This type of surgical procedure is indicated in most FAP patients, and IRA

  9. 腺瘤样结肠息肉易感基因蛋白截短与大肠腺瘤及大肠癌早期诊断关系%The relationship between adenomatous polyposis coli gene protein truncation and early diagnosis of colorectal adenoma and colorec-tal cancer

    Institute of Scientific and Technical Information of China (English)

    杨春; 杨宝; 李恒; 樊海燕; 杨银学

    2014-01-01

    Obej ctive To investigate the value of the expression level of adenomatous polyposis coli ( APC) gene truncated in the early diagnosis of colorectal adenoma and colon carcinoma .Methods 34 cases of colorectal cancer specimens were collected as colorectal cancer group ,28 cases of colorectal adenoma specimens as colorectal adenoma group and normal colorectal tissue specimens of 15 cases as normal group .The protein truncation test were used to compare differential expression of APC gene protein in three groups .Results APC protein truncation (+) of normal group was 0%,that of colorectal adenoma group and colorectal cancer group was 42.86%,47.06%,there was not statistically significance between colorectal adenoma and colorectal cancer group (P>0.05);normal tissues and colorectal adenoma , colorectal cancer APC protein truncation (+) but there was significant difference between normal and colorectal adenoma group and between normal and colorectal cancer group (χ2=8.917,P=0.003,χ2=10.481,P=0.001); APC protein truncation (+)of tubular adenoma tissue was 75%,significantly higher than that of villous adenomas (20.00%)and mixed adenoma(16.67%) (P<0.05).Conclusions The trun-cated APC protein (+) expression is different in different tissues in the early stage of APC ,which might play a certain role in the early diag-nosis of colorectal tumor .%目的:探讨腺瘤样结肠息肉( APC)易感基因截短表达水平在大肠腺瘤及大肠癌早期诊断中的价值。方法34例大肠癌病理标本作为大肠癌组、28例大肠腺瘤标本作为大肠腺瘤组及同期正常大肠组织标本15例作为正常组。3组分别采用蛋白截短检测技术,比较APC基因蛋白截短表达差异。结果正常组APC蛋白截短(+)为0%,大肠腺瘤组42.86%,大肠癌组47.06%,大肠腺瘤组和大肠癌组差异不显著( P>0.05);正常组与大肠腺瘤、大肠癌组差异显著(χ2=8.917、 P=0.003,χ2=10.481、 P

  10. 腺瘤性结肠息肉病基因D1822V单核苷酸多态性与结直肠癌风险的关系%Association of colorectal cancer risk and the adenomatous polyposis coli D1822V variant: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    方喜平; 冯茂辉; 谢伟; 陈双倩; 王国洲; 阳芳; 柳琨; 杨倩; 陈大平

    2013-01-01

    Objective To determine whether adenomatous polyposis coli(APC) D1822V variant predisposes to colorectal cancer.Methods NCBI,Medline,VIP,PubMed,ISI web of science and other Literature databases were searched by using the Medical Subjiect Heading term “ D1822V",“Asp1822Val",“APC",“polymorphism",“Asp1822V",“colorectal cancer",“ colorectal carcinoma".Only case-control studies were included.The software Mata 4.2 was used for data analysis.Results Nine studies,involving 8143 patients and 8776 controls were identified.APC D1822V did not show any difference between cases and controls,but when we considered to include Picelli' s study and considered only the super-control,the DV genetype was associated with an odds ratio of 0.96 (95% CI =0.90-1.03)and VV genentype with an odds ratio of 0.84 (95% CI =0.72-0.98).Conclusion APC D1822V variant may reduce the risk of CRC development.%目的 探讨腺瘤性结肠息肉病(APC)基因D1822V单核苷酸多态性与结肠癌风险的关系.方法 以“APC基因”、“多态性”、“结直肠癌”、“D1822V”、“Asp1822Val”、“APC”、“polymorphism”、“D1822V”、“Asp1822Val”、“colorectal cancer”、“colorectal carcinoma”为主题词联合检索中国期刊全文数据库、重庆维普数据库、Medline、Pubmed等数据库.对所获得文献,按纳入、排除标准进行筛选,并对最终所获文献进行异质性和敏感性分析,并以比值比(OR)值为合并效应指标,利用软件进行综合Meta分析.结果 共纳入9篇文献,累计病例数8143例,对照数8776例.当Picelli的这项研究以普通人群为对照时,DV基因型和VV基因型同DD基因型比较,OR值及其95%可信区间分别为0.97(0.91 ~1.03),0.89(0.77~ 1.03);当以超级对照组为对照,其相应的值为0.96(0.90 ~ 1.03)、0.84(0.72 ~0.98).结论 APC基因D1822V单核苷酸多态性,其VV基因型可能降低结直肠癌的风险.

  11. Genetic alterations in thyroid carcinoma associated with familial adenomatous polyposis: clinical implications and suggestions for early detection.

    Science.gov (United States)

    Cetta, F; Olschwang, S; Petracci, M; Montalto, G; Baldi, C; Zuckermann, M; Mariani Costantini, R; Fusco, A

    1998-12-01

    Germ-line mutations of the adenomatous polyposis (APC) gene, responsible for familial adenomatous polyposis (FAP) were analyzed in 15 patients with FAP-associated papillary thyroid carcinomas: 13 had the mutation between codons 778 and 1309 (exon 15), 1 at codon 593 (exon 14), and 1 at codon 140 (exon 3). Therefore APC gene mutations clustered in the genomic area associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE) (codons 463-1387). Ocular patches were documented in 12 patients. In particular, 4 of the 15 patients, all women with a mean age of 23.5 (range 20-32), were found during the study of 15 consecutive kindreds who had undergone systematic screening for extra-colonic manifestations. Three of them belonged to the same kindred and were asymptomatic. These four patients were also screened for loss of heterozygosity of APC in the thyroid tumoral tissue. No biallelic inactivation of the APC gene was found. In contrast, three of these four patients had activation of the ret-PTC oncogene. In particular, there was activation of the ret-PTC1 isoform, a chimeric gene resulting from fusion of a gene named H4 with the RET gene. On histologic examination, three of the four patients showed Hashimoto-like lymphocytic infiltration. Present data suggest that: (1) the incidence of FAP-associated thyroid cancer probably has been underestimated in the past; (2) intensive screening could detect a larger than expected number of thyroid carcinomas; (3) systematic screening is recommended in patients with ocular patches and genetic mutation in exon 15; (4) Hashimoto-like findings do not exclude carcinoma but are a frequent accompanying finding; (5) despite frequent multicentricity and early lymph node involvement, FAP-associated thyroid tumors seem to have an excellent prognosis, in particular those showing ret-PTC activation.

  12. Ability of FDG-PET to detect all cancers in patients with familial adenomatous polyposis, and impact on clinical management

    Energy Technology Data Exchange (ETDEWEB)

    Kouwen, Mariette C.A. van; Drenth, Joost P.H.; Friederich, Pieter; Nagengast, Fokko M. [Radboud University Nijmegen Medical Centre, Department of Gastroenterology and Hepatology, 9101, Nijmegen (Netherlands); Krieken, J. Han J.M. van [Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen (Netherlands); Goor, Harry van [Radboud University Nijmegen Medical Centre, Department of Surgery, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2006-03-15

    Familial adenomatous polyposis (FAP) is characterised by colonic and duodenal adenomatous polyps that carry a risk of malignant transformation. Malignant degeneration of duodenal adenomas is difficult to detect. We speculated that 2-({sup 18}F)-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) might be able to detect early duodenal cancer in FAP. Accordingly, we investigated the role of FDG-PET in the management of FAP patients. FDG-PET was performed in 24 FAP patients. Eight had advanced duodenal adenomas (Spigelman IV), including two patients with duodenal cancer. Scans were defined as positive on the basis of focal FDG accumulation. Pathological FDG accumulation was absent in 19 of 24 patients. All six patients with Spigelman IV duodenal adenomas (without cancer) were negative; two of these underwent a duodenectomy and pathological examination did not reveal duodenal cancer. In five patients, FDG-PET revealed significant uptake, in the duodenum (2), lower abdomen (1), lung (1) and multiple sites in the abdomen (1). These hot spots correlated with duodenal cancer (2), abdominal metastasis (1) and sclerosing haemangioma of the lung (1). We failed to make a histopathological diagnosis in the single patient with multiple intra-abdominal sites of FDG uptake. None of the patients from the FDG-PET-negative group developed cancer during follow-up (mean 2.8 years). (orig.)

  13. The ret/ptc1 oncogene is activated in familial adenomatous polyposis-associated thyroid papillary carcinomas.

    Science.gov (United States)

    Cetta, F; Chiappetta, G; Melillo, R M; Petracci, M; Montalto, G; Santoro, M; Fusco, A

    1998-03-01

    Familial adenomatous polyposis (FAP) is caused by germ-line mutations of the apc gene, and it is associated with an increased risk of developing papillary thyroid carcinomas. We have previously reported that a significant fraction of sporadic human papillary thyroid carcinomas is characterized by gene rearrangements affecting the ret protooncogene. These rearrangements generate chimeric transforming oncogenes designated ret/ptc. By a combined immunohistochemical and RT-PCR approach, we analyzed, for ret/ptc oncogene activation, papillary thyroid carcinomas occurred in two FAP kindreds, both showing typical apc gene mutations. Kindred 1 had seven members affected by FAP, and among these, three patients showed papillary thyroid carcinomas. Kindred 2 had two patients, mother and daughter, affected by colonic polyposis; the 20-yr-old daughter showed also a papillary carcinoma. Here we report that ret/ptc1 oncogene was activated in two of the three papillary carcinomas of FAP kindred 1 and in the papillary carcinoma of FAP kindred 2. These findings document that loss of function of apc coexists with gain of function of ret in some papillary thyroid carcinomas, suggesting that ret/ptc1 oncogene activation could be a progression step in the development of FAP-associated thyroid tumors.

  14. Diagnosis of APC gene mutation in a patient with familiar adenomatous polyposis%1例家族性腺瘤性息肉病患者的 AP C基因突变诊断

    Institute of Scientific and Technical Information of China (English)

    潘红; 高洪柳; 吴秋月; 李卫巍; 李天赋; 夏欣一; 王卫萍; 许豪勤

    2014-01-01

    目的:对1例家族性腺瘤性息肉病患者进行结肠息肉病致病基因( adenomatous polyposis coli ,APC)的突变检测。方法从患者外周血中提取基因组DNA,用目标序列捕获结合二代测序技术对APC致病基因进行测序并用Sanger测序验证。结果患者的APC经分析后发现1个杂合的缺失突变c.3931_3925delAAAAG( p.Ile1307IlefsX6);该突变引起APC基因的编码序列移码突变,产生一个提前终止的密码子,生成一截短的蛋白而影响蛋白功能。结论 APC基因编码区的缺失突变c.3931_3925delAAAAG(p.Ile1307IlefsX6)为该患者的致病原因。%Objective To diagnose the mutation of adenomatous polyposis coli ( APC) in a patient with familiar adenomatous polyposis ( FAP) .Methods Genomic DNA was extracted from peripheral blood of the patient .Target region enrichment combined with next generation sequencing was performed for the patient .The mutation screened by target region capture sequencing was further identi -fied by Sanger sequencing .Results A heterozygous deletion mutation of c .3931_3925delAAAAG,p.Ile1307IlefsX6 in APC was iden-tified,which resulted in a frameshift within the coding sequence and brought about a premature translation termination codon .Conclu-sion The mutation of c.3931_3925delAAAAG (p.Ile1307IlefsX6) in APC gene contributed to the pathogenesis of familiar adenoma-tous polypsis .

  15. Multiple desmoid tumors in a patient with familial adenomatous polyposis caused by the novel W421X mutation Tumor desmoide múltiple en un paciente con poliposis adenomatosa familiar originada por la nueva mutación W421X

    Directory of Open Access Journals (Sweden)

    Orestis Ioannidis

    2012-03-01

    Full Text Available Familial adenomatous polyposis (FAP is a rare syndrome characterized by the presence of hundreds to thousands of colorectal adenomas and is responsible for less than 1% of all colorectal cancers. The syndrome is also characterized by extra-colorectal features including amongst others upper gastrointestinal tract polyps and desmoid tumors. The syndrome is inherited by an autosomal dominant gene, the adenomatous polyposis coli (APC gene. We present the physical history, clinical presentation, diagnosis and treatment of a patient with a novel germline APC mutation, the W421X mutation, which resulted in FAP presenting with about a hundred colorectal polyps, gastric hyperplastic polyps and multiple aggressive intra-abdominal and extra-abdominal desmoid tumors.

  16. Dacarbazine-Doxorubicin therapy ameliorated an extremely aggressive mesenteric desmoid tumor associated with familial adenomatous polyposis: report of a case.

    Science.gov (United States)

    Ezumi, Koji; Yamamoto, Hirofumi; Takemasa, Ichiro; Nomura, Masaya; Ikeda, Masataka; Sekimoto, Mitsugu; Monden, Morito

    2008-03-01

    A 30-year-old man with familial adenomatous polyposis (FAP) underwent prophylactic proctocolectomy by laparoscopy-assisted surgery. After 10 months, we found an intra-abdominal tumor, which grew rapidly to 25 cm in diameter. We performed an emergency operation, which revealed that it was a desmoid tumor derived mainly from colorectal mesenterium. The tumor was removed with three short segments of intestine and the left ureter. A computed tomography (CT) scan done 3 months later showed a 10 cm mesenteric desmoid tumor at the beginning of jejunum, approaching the root of the superior mesenteric artery (SMA). Fortunately, we were able to remove the tumor without injuring the SMA. To our distress, however, another recurrent mesenteric desmoid tumor was discovered in the pelvis one month later, which grew rapidly from 5 cm to 16 cm within 4 months. During this period, we gave the patient several regimens, including antiestrogen (tamoxifen), a nonsteroidal anti-inflammtory drug and imatinib mesylate (Gleevec), which had little or no effect. Finally, when the desmoid occupied the pelvic space, we gave the patient dacarbazine (DTIC) and doxorubicin (DOX). After seven courses, the mesenteric tumor showed an almost complete response (CR). The chemotherapy caused grade 3 to 4 leukocytopenia, but without any hazardous events. No evidence of further recurrence of mesenteric desmoid has been seen for 4 years. This combination chemotherapy is a promising strategy, even against an extremely aggressive, life-threatening mesenteric desmoid associated with FAP.

  17. Colectomy and ileorectal anastomosis is still an option for selected patients with familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen; Bulow, C.; Vasen, H.;

    2008-01-01

    PURPOSE: The risk of rectal cancer after colectomy and ileorectal anastomosis may be reduced in the last decades, as patients with severe polyposis now have an ileoanal pouch. We have reevaluated the risk of rectal cancer and proctectomy for all causes according to the year of operation. METHODS......: On the basis of the year of operation in 776 patients with ileorectal anastomosis and 471 pouch patients in Denmark, Finland, Holland, and Sweden, the "pouch period" was defined to start in 1990. Ileorectal anastomosis follow-up data was captured by May 31, 2006. The cumulative risk of rectal cancer.......17) changed. However, in females the cumulative risk of rectal cancer (p = 0.04) and of proctectomy (p = 0.03) were lower in the pouch period. CONCLUSIONS: Since the introduction of the ileoanal pouch rectal cancer has decreased after ileorectal anastomosis, but only statistically significant in females...

  18. Proctocolectomy and ileal J-pouch anal anastomosis on the surgical treatment of familial adenomatous polyposis and ulcerative colitis: analysis of 49 cases

    Directory of Open Access Journals (Sweden)

    Bruno Amaral Medeiros

    2012-09-01

    Full Text Available OBJECTIVE: To evaluate the results of ileal J-pouch anal anastomosis in ulcerative colitis and familial adenomatous polyposis. METHOD: Retrospective analysis of medical records of 49 patients submitted to ileal J-pouch anal anastomosis. RESULTS: Ulcerative colitis was diagnosed in 65% and familial adenomatous polyposis in 34%. Mean age was 39.5 years. 43% were male. Among familial adenomatous polyposis, 61% were diagnosed with colorectal cancer. Thirty-one percent of patients with ulcerative colitis was submitted to a previous surgical approach and 21% of these had toxic megacolon. Average hospital stay was 10 days. Post-operative complications occurred in 50% of patients with ulcerative colitis and 29.4% with familial adenomatous polyposis. Intestinal diversion was performed in 100% of ulcerative colitis and 88% of familial adenomatous polyposis. Pouchitis occurred in eight cases (seven ulcerative colitis and one FAP, requiring excision of the pouch in three ulcerative colitis. Mortality rate was 7.6%: two cases of carcinoma on the pouch and two post-operative complications. Late post-operative complications occurred in 22.4%: six familial adenomatous polyposis and five ulcerative colitis. Two patients had erectile dysfunction, and one retrograde ejaculation. One patient with severe perineal dermatitis was submitted to excision of the pouch. Incontinence occurred in four patients and two reported soil. Mean bowel movement was five times a day. CONCLUSION: Ileal J-pouch anal anastomosis is a safe surgery with acceptable morbidity and good functional results, if well indicated and performed in referral centers.OBJETIVO: Avaliar resultados da anastomose íleo-anal com bolsa ileal em J na colite ulcerativa e na polipose adenomatosa familiar. MÉTODO: Análise retrospectiva dos prontuários de 49 pacientes submetidos a anastomose íleo-anal com bolsa ileal em J. RESULTADOS: 65% de colite ulcerativa e 34% de polipose adenomatosa familiar. Idade m

  19. Can supplementation of phytoestrogens/insoluble fibers help the management of duodenal polyps in familial adenomatous polyposis?

    Science.gov (United States)

    Calabrese, Carlo; Rizzello, Fernando; Gionchetti, Paolo; Calafiore, Andrea; Pagano, Nico; De Fazio, Luigia; Valerii, Maria Chiara; Cavazza, Elena; Strillacci, Antonio; Comelli, Maria Cristina; Poggioli, Gilberto; Campieri, Massimo; Spisni, Enzo

    2016-06-01

    Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder, and prophylactic colectomy has been shown to decrease the incidence of colorectal cancer (CRC). Duodenal cancer and desmoids are now the leading causes of death in FAP. We evaluate whether 3 months of oral supplementation with a patented blend of phytoestrogens and indigestible insoluble fibers (ADI) help the management of FAP patients with ileal pouch-anal anastomosis (IPAA). In a prospective open label study, we enrolled 15 FAP patients with IPAA and duodenal polyps who underwent upper gastrointestinal endoscopy at baseline and after 3 months of treatment. The primary endpoint was the change in gene expression in polyp mucosa, whereas the secondary endpoint was the reduction in polyp number and size. After 3 months of ADI treatment, all patients showed a reduction in the number and size of duodenal polyps (P = 0.021). Analysis of the expression of CRC promoting/inhibiting genes in duodenal polyps biopsies demonstrated that different CRC-promoting genes (PCNA, MUC1 and COX-2) were significantly downregulated, whereas CRC-inhibiting genes (ER-β and MUC2) were significantly upregulated after ADI treatment. In conclusion, ADI proved to be safe and effective, and its long-term effects on FAP patients need further investigation. Judging from the results we observed on COX-2 and miR-101 expression, the short-term effects of ADI treatment could be comparable with those obtained using COX-2 inhibitors, with the advantage of being much more tolerable in chronic therapies and void of adverse events.

  20. An audit of quality of life and functional outcome following restorative proctocolectomy and ileoanal pouch surgery in familial polyposis coli.

    Science.gov (United States)

    Daniels; Beynon; Carr

    1999-09-01

    We have audited the quality of life and functional outcome from restorative proctocolectomy and ileoanal pouch surgery in patients with familial adenomatous polyposis coli (FAP). By assessing the effect on employment, leisure activity, social life, and sexual function using a questionnaire derived from a modified McMaster Inflammatory Disease Questionnaire we have assessed the functional outcome of the pouch [ 1]. We have shown that although quality of life is maintained from the results of the questionnaire, over 50% of the patients felt that the pouch had not improved their lives. It has been shown that colitic patients have less complete function than polyposis patients, although the former were more satisfied with the results of their surgery [ 2]. Perhaps then the realization of the nature of FAP is not an incentive to surgery, when your life is to be ruled by your bowels. Therefore perhaps we should consider the outcomes in patients with FAP to be different from those in patients who have lived with colitis.

  1. [Proctocolectomy with ileoanal anastomoses and desmoid tumor treated with resection. One case of familial adenomatous polyposis].

    Science.gov (United States)

    Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Méndez-Sashida, Pedro Gonzalo

    2014-01-01

    Introducción: la poliposis adenomatosa familiar (PAF) es una rara enfermedad causada por una mutación en el gen de la poliposis adenomatosa coli (APC). Caso clínico: mujer de 32 años, con dolor y aumento del perímetro abdominal además de evacuaciones melénicas y pérdida de peso. La paciente presentó un tumor de 12 cm de diámetro en la fosa iliaca derecha. Tras la administración de medio de contraste, en una tomografía se apreció el tumor abdominal con reforzamiento compatible con sarcoma frente a tumor desmoide. Se realizó colonoscopia, por medio de la que se encontraron pólipos en el recto y el colon. La biopsia reportó adenomas túbulo-vellosos. Una panendoscopía demostró pólipos en fondo y cuerpo gástrico; el duodeno se encontraba en estado normal. Se realizó resección del tumor en pared abdominal y reconstrucción con malla además de proctocolectomía restaurativa con un reservorio íleo-anal con una ileostomía temporal. Se reportó tumor desmoide en la pared abdominal y se identificaron 152 pólipos túbulo-vellosos que afectaban todas las porciones del colon y el recto. Conclusiones: la PAF es una enfermedad autosómica dominante causada por una mutación en el gen APC que da como resultado el desarrollo de múltiples pólipos tanto en el colon como en el recto. Descrito en 1991, el gen APC se localiza en el cromosoma 5q21. Sin cirugía profiláctica, todos los pacientes desarrollarán cáncer colorrectal en la tercera década de la vida. Los tumores desmoides y los pólipos duodenales son ahora la causa de muerte en los pacientes con PAF.

  2. Evaluación económica de la prueba genética de la poliposis adenomatosa familiar An economic assessment of genetic testing for familial adenomatous polyposis

    Directory of Open Access Journals (Sweden)

    A. Olry de Labry Lima

    2008-08-01

    Full Text Available Objetivo: analizar el coste-utilidad de la prueba genética a familiares de primer grado de pacientes con cáncer de colon para determinar mutaciones del gen APC (Adenomatous Polyposis Coli. Metodología: los análisis se realizaron desde el punto de vista del sistema sanitario. Se utilizó un modelo de Markov. Realización de la prueba genética para el gen APC, causante de la poliposis adenomatosa familiar (PAF, que produce cáncer de colon frente a la no realización de la misma. La medida de efectividad utilizada fueron los años de vida ajustados por calidad (AVAC y la unidad de coste los euros de 2005. Los costes de las intervenciones fueron extraídos de los precios públicos de los servicios sanitarios prestados por centros dependientes del Sistema Sanitario Público Andaluz y los valores de la efectividad y de utilidad de la literatura. Resultados: la realización de la prueba genética se muestra como una estrategia dominante a la no realización de la misma, ya que esta última tiene un coste incremental de 7.676,34 €, además de una menor efectividad. Los análisis de sensibilidad mostraron que la realización de la prueba genética se mantiene como la estrategia dominante dentro de un amplio rango de coste de la prueba y de probabilidad de desarrollar adenocarcinomas. Conclusiones: los análisis mostraron que, para este grupo de pacientes, la realización de la prueba genética para la detección de la mutación del gen APC es en promedio menos costosa y además produce una mejora en AVAC comparado con la no realización de la misma.Objective: to analyze the cost-effectiveness of genetic testing for first-degree relatives of patients with colon cancer to identify mutations in the APC gene (Adenomatous Polyposis Coli. Methodology: analyses were performed from the perspective of the health system. We used a Markov model. We compared genetic testing for the APC gene, the cause of familial adenomatous polyposis (FAP, which results in

  3. [A Case of Familial Adenomatous Polyposis with a Desmoid Tumor Probably Communicating to the Intestinal Lumen That Was Successfully Treated with Non-Surgical Therapy].

    Science.gov (United States)

    Ito, Tetsuya; Chika, Noriyasu; Yamamoto, Azusa; Ogura, Toshiro; Amano, Kunihiko; Ishiguro, Toru; Fukuchi, Minoru; Kumagai, Youichi; Ishibashi, Keiichiro; Eguchi, Hidetaka; Okazaki, Yasushi; Mochiki, Erito; Ishida, Hideyuki

    2016-11-01

    A 44-year-old man with familial adenomatous polyposis underwent laparoscopic-assistedtotal proctocolectomy with ilealpouch anal anastomosis(IPAA). Computed tomography conducted 21 months after IPAA demonstrated bilateral hydronephrosis andan intra-abdominal mass with a maximal diameter of 22 cm, leading to a diagnosis of stage IV desmoid disease, according to the classification by Church and associates. Six courses of combination chemotherapy with doxorubicin plus dacarbazine were administered. Computed tomography after chemotherapy demonstrated marked shrinkage of the desmoidtumor with intraabdominal air andfluidcollection extending just below the skin of the ileostomy closure site. Stoollike fluidoverflowedspontaneously through the site of the ileostomy closure andthe abscess cavity was successfully drained. The patient was discharged 30 days after the start of drainage. The patient is doing well 10 months after the drainage without regrowth of the desmoid tumor, even though a cavity-like lesion encapsulatedby a thick wall remains.

  4. Clinical and ethical implications of genetic counselling in familial adenomatous polyposis Implicaciones clínicas y éticas del consejo genético en la poliposis adenomatosa familiar

    Directory of Open Access Journals (Sweden)

    A. Fernández-Suárez

    2005-09-01

    Full Text Available The association of specific genetic disturbances with the development of hereditary cancer helps us to understand the risk of suffering from it, the possibility of an earlier diagnosis, and the treatment and prevention of this disease. Familial adenomatous polyposis (FAP is a pre-neoplastic syndrome characterized by the presence of hundreds of adenomatous polyps in the colon, which develop into a carcinoma. FAP can be diagnosed using sequencing techniques to detect mutations in the germinal line of the APC (adenomatous polyposis coli gene. The genetic diagnostic approach in families with FAP, previously followed up in the Gastrointestinal Clinic, has both advantages and disadvantages, and places us nearer the disease and patient. Disclosing the results of this genetic test entails relevant problems in clinical practice, which affect the health field and raise legal and ethical issues, along with the familial, occupational, and social implications that knowing the genetic status can have on the patient. Genetic analysis is rare in normal clinical practice, which involves errors in the interpretation of the results obtained, and during the process of genetic counselling. Specialized multidisciplinary units are necessary for the management of patients with FAP undergoing analysis and appropriate genetic counselling, thus providing an individualized service. The creation of FAP registers and protocols for this healthcare process should optimize the management of these patients and their families.La asociación de determinadas alteraciones genéticas con la aparición de cáncer hereditario, nos permite conocer el riesgo de padecerlo, posibilitando el diagnóstico precoz, el tratamiento y la prevención de la enfermedad. La poliposis adenomatosa familiar (PAF es un síndrome preneoplásico que se caracteriza por la presencia de cientos de pólipos adenomatosos en colon, que evolucionarán hacia carcinoma. La PAF puede ser diagnosticada mediante t

  5. Familial Adenomatous Polyposis

    Science.gov (United States)

    ... have a de novo (new) mutation in the APC gene. Most colorectal cancer is sporadic, meaning it occurs by chance, and ... a mutation in the APC gene. If an APC gene mutation is found, other family members may be ... tumor ...

  6. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant

    OpenAIRE

    LI, Jun; Woods, Susan L.; Healey, Sue; Beesley, Jonathan; Chen,Xiaoqing; Lee, Jason S.; Sivakumaran, Haran; Wayte, Nicci; Nones, Katia; Waterfall, Joshua J.; Pearson, John; Patch, Anne-Marie; Senz, Janine; Ferreira, Manuel A.; Kaurah, Pardeep

    2016-01-01

    Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with diseas...

  7. Association between the age and the development of colorectal cancer in patients with familial adenomatous polyposis: a multi-institutional study.

    Science.gov (United States)

    Kobayashi, Hirotoshi; Ishida, Hideyuki; Ueno, Hideki; Hinoi, Takao; Inoue, Yasuhiro; Ishida, Fumio; Kanemitsu, Yukihide; Konishi, Tsuyoshi; Yamaguchi, Tatsuro; Tomita, Naohiro; Matsubara, Nagahide; Watanabe, Toshiaki; Sugihara, Kenichi

    2017-04-01

    To investigate the incidence of colorectal cancer among familial adenomatous polyposis (FAP) patients by phenotype using the latest modalities. We collected data on 303 patients who underwent surgery for FAP at one of 23 institutions between 2000 and 2012. The incidence of colorectal cancer was investigated by phenotype. Colorectal cancer was diagnosed in 115 (38.0 %) of the 303 patients. Overall, colorectal cancer with the attenuated, sparse, and profuse phenotypes was diagnosed at 30, 31, and 28 years of age, respectively, in 10 % of the patients and at 59, 48, and 41 years of age, respectively, in 50 % of the patients (P = 0.013). The patients with colorectal cancer were older than those without colorectal cancer for all phenotypes. The optimal cut-off age for predicting the development of colorectal cancer in the attenuated, sparse, and profuse phenotypes was 46, 31, and 27 years, respectively. Patients with profuse and sparse phenotypes should undergo prophylactic proctocolectomy before their mid-to-late 20 s. On the other hand, the timing and type of surgery for patients with attenuated FAP (AFAP) should be decided individually with reference to the colonoscopic findings.

  8. Comparison between Capsule Endoscopy and Magnetic Resonance Enterography for the Detection of Polyps of the Small Intestine in Patients with Familial Adenomatous Polyposis

    Directory of Open Access Journals (Sweden)

    E. Akin

    2012-01-01

    Full Text Available Objective. The objective of this study was to assess the utility of magnetic resonance enterography (MRE compared with capsule endoscopy (CE for the detection of small-bowel polyps in patients with familial adenomatous polyposis (FAP. Methods. Patients underwent MRE and CE. The polyps were classified according to size of polyp: 10 mm (large size. The location (jejunum or ileum and the number of polyps (1–5, 6–20, >20 detected by CE were also assessed. MRE findings were compared with the results of CE. Results. Small-bowel polyps, were detected by CE in 4 of the 6 (66% patients. Three patients had small-sized polyps and one patient had medium-sized polyps. CE detected polyps in four patients that, were not shown on MRE. Desmoid tumors were detected on anterior abdominal wall by MRE. Conclusion. In patients with FAP, CE can detect small-sized polyps in the small intestine not seen with MRE whereas MRE yields additional extraintestinal information.

  9. Complete deletion of Apc results in severe polyposis in mice

    OpenAIRE

    Cheung, Ann F.; Carter, Alia M.; Kostova, Kamena K.; Woodruff, Joseph F.; Crowley, Denise; Bronson, Roderick T; Haigis, Kevin M.; Jacks, Tyler

    2009-01-01

    The adenomatous polyposis coli (APC) gene product is mutated in the vast majority of human colorectal cancers. APC negatively regulates the WNT pathway by aiding in the degradation of β-catenin, which is the transcription factor activated downstream of WNT signaling. APC mutations result in β-catenin stabilization and constitutive WNT pathway activation, leading to aberrant cellular proliferation. APC mutations associated with colorectal cancer commonly fall in a region of the gene termed the...

  10. Adenomatous polyposis coli regulates axon arborization and cytoskeleton organization via its N-terminus.

    Directory of Open Access Journals (Sweden)

    Youjun Chen

    Full Text Available Conditional deletion of APC leads to marked disruption of cortical development and to excessive axonal branching of cortical neurons. However, little is known about the cell biological basis of this neuronal morphological regulation. Here we show that APC deficient cortical neuronal growth cones exhibit marked disruption of both microtubule and actin cytoskeleton. Functional analysis of the different APC domains revealed that axonal branches do not result from stabilized β-catenin, and that the C-terminus of APC containing microtubule regulatory domains only partially rescues the branching phenotype. Surprisingly, the N-terminus of APC containing the oligomerization domain and the armadillo repeats completely rescues the branching and cytoskeletal abnormalities. Our data indicate that APC is required for appropriate axon morphological development and that the N-terminus of APC is important for regulation of the neuronal cytoskeleton.

  11. Relationship between Fecal Content of Fatty Acids and Cyclooxygenase mRNA Expression and Fatty Acid Composition in Duodenal Biopsies, Serum Lipoproteins, and Dietary Fat in Colectomized Familial Adenomatous Polyposis Patients

    Directory of Open Access Journals (Sweden)

    K. Almendingen

    2010-01-01

    Full Text Available A few familial adenomatous polyposis studies have focused upon faecal sterols and bile acids but none has analysed the fecal content of fatty acids. We report here findings of an observational study on 29 colectomized familial adenomatous polyposis patients that describe the fecal content of fatty acids, and relate this to the proportions of fatty acids and levels of cyclooxygenase mRNA expression in duodenal biopsies, levels of serum lipoproteins, and diet. In the ileostomy group separately (n=12, the fecal content of arachidonic acid was correlated negatively to the proportions of eicosapentaenoic acid and docosahexaenoic acid in duodenal biopsies. Total serum-cholesterol was negatively correlated to the fecal content of saturates and monounsaturates. The fecal palmitoleic acid/palmitic acid ratio was positively correlated to the levels of cyclooxygease-2 expression in duodenal biopsies.In the ileal-pouch-anal anastomosis group separately (n=17, significant correlations were found between the fecal contents of oleic acid, linoleic acid, and alpha-linolenic acid, and the proportions of myristic acid, oleic acid and eicosaenoic acid in duodenal biopsies. Dietary monounsaturates were positively correlated to different fecal fatty acids. Future studies should focus on molecular mechanisms relevant to fatty acid metabolism, inflammation, and angiogenesis, in addition to nutrition.

  12. The establishment of a polyposis register

    DEFF Research Database (Denmark)

    Bülow, Steffen; Burn, J; Neale, K;

    1993-01-01

    Guidelines are presented for the establishment of a regional or national register of patients with familial adenomatous polyposis. The detailed recommendations are based on the work in committees of the "Leeds Castle Polyposis Group" and the "EuroFAP". The aims of national and regional polyposis...

  13. Fibroadenoma of the breast in a man associated with adenocarcinoma of the rectum and polyposis coli.

    Science.gov (United States)

    Adibelli, Z H; Yildirim, M; Ozan, E; Oztekin, O; Kucukzeybek, B

    2010-01-01

    Fibroadenoma of the breast is an uncommon cause of breast lumps in men. Only a few cases have been reported in the literature, the majority of which were prescribed estrogen. We present herein the first case of a fibroadenoma of the breast in a 68-year-old man with adenocarcinoma of the rectum and polyposis coli. In this case, there was neither estrogen treatment nor any other medications which have been discussed in the literature as inducing fibroadenomas. Fibroadenomas in men without hormone treatment and with normal hormone levels are extremely rare and the developmental mechanism of the breast fibroadenoma in this man is under question.

  14. Andalusian Registry for Familial Adenomatous Polyposis: Analysis of patients included Registro Andaluz de la Poliposis Adenomatosa Familiar: Análisis de los pacientes incluidos

    Directory of Open Access Journals (Sweden)

    M. Garzón Benavides

    2010-11-01

    Full Text Available Objective: To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. Material and methods: A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. Results: We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51 and 46 relatives at risk with a mean age of 21.8 years (6-55. Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC at the time of diagnosis (32.2%. Only two affected relatives showed CRC at diagnosis (4.3%, a statistically significant difference (p Objetivos: Valorar las características fenotípicas y genotípicas de los pacientes incluidos en el Registro Andaluz de la poliposis adenomatosa familiar, la relación genotipo/fenotipo y el impacto del Registro en la frecuencia de cáncer colorrectal de los familiares registrados. Material y métodos: Estudio descriptivo de 77 pacientes con PAF, pertenecientes a 33 familias, incluidos en una base de datos centralizada a la que tienen acceso los responsables de los hospitales participantes, previa firma de cartas de confidencialidad. Todos los estudios genéticos se realizan en el Servicio de Inmunología de nuestro Hospital. Resultados: 77 pacientes registrados (50,6% varones: 31 probandos, edad media: 32 años (13-51 y 46 familiares afectos, edad media 21,8 años (6-55. Estudio genético informado en 68/77 con resultado positivo en 92,6%. Cáncer colorrectal al diagnóstico en diez probandos (32,2% y 2 familiares afectos (4,3%, diferencia estad

  15. Diagnosis of familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen

    1991-01-01

    , the diagnostic evaluation includes colonoscopy and gastroduodenoscopy. Screening of first degree relatives should start at the age of 10 years, using proctosigmoidoscopy at regular intervals. The recent detection of a specific FAP gene at chromosome 5 and of congenital retinal pigmentations will allow an early...

  16. MUTYH-Associated Polyposis: The Irish Experience

    LENUS (Irish Health Repository)

    McVeigh, TP

    2016-11-01

    MUTYH is involved in DNA damage repair. Bi-allelic MUTYH mutations predispose to polyposis and gastrointestinal malignancies, distinct genetically from autosomal dominant familial adenomatous polyposis coli. Two common European MUTYH mutations account for 90% of MUTYH-associated polyposis (MAP). We aimed to examine the incidence of MAP in Ireland. A retrospective cohort study was undertaken. Patients undergoing MUTYH testing from 2003-2016 were identified by searching electronic databases using terms "MUTYH" and "MYH". Phenotypic and genotypic details were obtained by chart review. Bi-allelic mutations were confirmed in 26 individuals (17 families), of whom 16 (62%) developed colorectal malignancies, and 22(85%) polyposis. Eleven families had bi-allelic status for one\\/both common European mutations. Regional variation was noted, with over-representation of bi-allelic mutation carriers in the South-west of Ireland. MAP is under-diagnosed in Ireland. Increased awareness is required to facilitate appropriate identification and surveillance of bi-allelic mutation carriers for colorectal pathology.

  17. Surgical treatment of familial adenomatous polyposis: ileoretal anastomosis or restorative proctolectomy? Tratamento cirúrgico da polipose adenomatosa familiar: anastomose íleo-retal ou bolsa ileal?

    Directory of Open Access Journals (Sweden)

    Fábio Guilherme Campos

    2009-12-01

    Full Text Available CONTEXT: Controversy regarding the best operative choice for familial adenomatous polyposis lays between the morbidity of restorative proctocolectomy and the supposed mortality due to rectal cancer after ileorectal anastomosis. OBJECTIVES: To evaluate operative complications and oncological outcome after ileorectal anastomosis and restorative proctocolectomy. METHODS: Charts from patients treated between 1977 and 2006 were retrospectively analyzed. Clinical and endoscopic data, results of treatment, pathological reports and information regarding early and late outcome were recorded. RESULTS: Eighty-eight patients - 41 men (46.6% and 47 women (53.4% - were assisted. At diagnosis, 53 patients (60.2% already had associated colorectal cancer. Operative complications occurred in 25 patients (29.0 %, being 17 (19.7% early and 8 (9.3% late complications. There were more complications after restorative proctocolectomy (48.1% compared to proctocolectomy with ileostomy (26.6% and ileorectal anastomosis (19.0% (P = 0,03. There was no operative mortality. During the follow-up of 36 ileorectal anastomosis, cancer developed in the rectal cuff in six patients (16,6%. Cumulative cancer risk after ileorectal anastomosis was 17.2% at 5 years, 24.1% at 10 years and 43.1% at 15 years of follow-up. Age-dependent cumulative risk started at 30 years (4.3%, went to 9.6% at 40 years, 20.9% at 40 years and 52% at 60 years. Among the 26 patients followed after restorative proctocolectomy, it was found cancer in the ileal pouch in 1 (3.8%. CONCLUSIONS: 1. Operative complications occurred in about one third of the patients, being more frequently after the confection of ileal reservoir; 2. greater age and previous colonic carcinoma were associated with the development of rectal cancer after ileorectal anastomosis; 3. patients treated by restorative proctocolectomy are not free from the risk of pouch degeneration; 4. the disease complexity and the various risk factors

  18. 家族性腺瘤性息肉病伴发上消化道息肉57例分析%Upper-gastrointestinal polyps found in cases of familial adenomatous polyposis

    Institute of Scientific and Technical Information of China (English)

    徐晓东; 傅传刚; 宋宁; 张卫; 刘连杰; 孟荣贵; 于恩达

    2012-01-01

    目的 探讨家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)患者伴发上消化道息肉(胃及十二指肠)的发生率、内镜下的表现特征及其病理学特点.方法 对上海第二军医大学长海医院2004年1月至2010年6月收治的57例临床诊断为FAP患者采用胃镜、十二指肠侧视镜进行上消化道病变的筛查,并对发现的息肉样病灶进行组织学活检,分析FAP伴胃及十二指肠息肉的发病状况.结果 本组57例FAP患者中发生胃内息肉38例,占67%,息肉多数位于胃体和胃窦部,为增生性息肉;十二指肠息肉12例,占21%,其中7例为腺瘤性息肉.结论 上消化道息肉是FAP最常见的大肠外病变,胃内息肉多为增生性息肉;而十二指肠可能伴发腺瘤性息肉,属癌前病变.%Objective To discuss the incidence,endoscopic manifestion and pathological features of the upper-gastrointestinal polyps ( stomach and deodenum) in FAP patients. Methods During 2004 -2010 a total 57 FAP patients at Changhai Hospital underwent screening for polyps in upper-gastrointestinal tract by gastroscopy and sideward-viewing duodenoscopy. Biopsies were taken on the polypoid lesions.Results Gastric polyps were found in 38 patients (67%).Most polyps were located at gastric body and antrum,the pathologic diagnosis was hyperplastic. Duodenal polyps were found in 12 patients (21%) including 7 cases of adenomatous polys. Conclusions Upper- gastrointestinal polyps are the most common extra-colonic manifestion in FAP. Most stomach polyps are located at gastric body and antrum and are hyperplastic.Polyps at duodenum may be adenomatous,which is a precusor of carcinoma.

  19. Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Rohlin, A; Engwall, Y; Fritzell, K

    2011-01-01

    of this promoter in the largest family (Family 1) of the Swedish Polyposis Registry. The mutation leads to an imbalance in allele-specific expression of APC, and transcription from promoter 1B was highly impaired in both normal colorectal mucosa and blood from mutation carriers. To establish the significance...... in a panel of 20 various normal tissues examined. In FAP-related tumors, the APC germline mutation is proposed to dictate the second hit. Mutations leaving two or three out of seven 20-amino-acid repeats in the central domain of APC intact seem to be required for tumorigenesis. We examined adenomas from...

  20. Current status of familial gastrointestinal polyposis syndromes

    Institute of Scientific and Technical Information of China (English)

    Ioan; Jung; Simona; Gurzu; Gligore; Sabin; Turdean

    2015-01-01

    Because of the rarity of familial gastrointestinal cancerpredisposing syndromes,their exploration in literature is not extensive.In this review,an update of the clinicopathological and molecular criteria of gastrointestinal familial polyposis syndromes with potential malignant transformation is performed.In addition,a guide for screening and surveillance was synthesized and a distribution of gene mutations according to the specific syndromes and geographic distribution was included.The following inherited polyposes syndromes were analyzed: familial adenomatous polyposis,the hamartomatous familial polyposes(Juvenile polyposis,Peutz-Jeghers syndrome,Cowden syndrome,BannayanRiley-Ruvalcaba syndrome,hereditary mixed polyposis syndrome,Gorlin syndrome,Birt-Hogg-Dube syndrome,neurofibromatosis type Ⅰand multiple endocrine neoplasia syndrome 2B),Li-Fraumeni syndrome,and MUTYHassociated adenomatous polyposis.For proper medical care,subspecialization of gastroenterologists,pathologists,and genticists in the field of familial diseases should be introduced in the medical curriculum.

  1. A novel SYBR-based duplex qPCR for the detection of gene dosage: detection of an APC large deletion in a familial adenomatous polyposis patient with an unusual phenotype

    Directory of Open Access Journals (Sweden)

    Torrezan Giovana

    2012-07-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is a hereditary colorectal cancer syndrome caused by a loss of function of the APC gene. Large deletions in APC are a common cause of FAP; despite the existence of a variety of gene dosage detection methodologies, most are labor intensive and time and resource consuming. Methods We describe a new duplex qPCR method for gene dosage analysis based on the coamplification of a target and a reference gene in a SYBR Green reaction, followed by a comparison of the ratio between the target and the reference peaks of the melting curve for the test (patient and control samples. The reliability of the described duplex qPCR was validated for several genes (APC, HPRT1, ATM, PTEN and BRCA1. Results Using this novel gene dosage method, we have identified an APC gene deletion in a FAP patient undergoing genetic testing. Comparative genomic hybridization based on microarrays (aCGH was used to confirm and map the extent of the deletion, revealing a 5.2 MB rearrangement (5q21.3-q22.3 encompassing the entire APC and 19 additional genes. Conclusion The novel assay accurately detected losses and gains of one copy of the target sequences, representing a reliable and flexible alternative to other gene dosage techniques. In addition, we described a FAP patient harboring a gross deletion at 5q21.3-q22.3 with an unusual phenotype of the absence of mental impairment and dysmorphic features.

  2. Readthrough of premature termination codons in the adenomatous polyposis coli gene restores its biological activity in human cancer cells.

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    Célia Floquet

    Full Text Available The APC tumor suppressor gene is frequently mutated in human colorectal cancer, with nonsense mutations accounting for 30% of all mutations in this gene. Reintroduction of the WT APC gene into cancer cells generally reduces tumorigenicity or induces apoptosis. In this study, we explored the possibility of using drugs to induce premature termination codon (PTC readthrough (aminoglycosides, negamycin, as a means of reactivating endogenous APC. By quantifying the readthrough of 11 nonsense mutations in APC, we were able to identify those giving the highest levels of readthrough after treatment. For these mutations, we demonstrated that aminoglycoside or negamycin treatment led to a recovery of the biological activity of APC in cancer cell lines, and showed that the level of APC activity was proportional to the level of induced readthrough. These findings show that treatment with readthrough inducers should be considered as a potential strategy for treating cancers caused by nonsense mutations APC gene. They also provide a rational basis for identifying mutations responsive to readthrough inducers.

  3. Maintenance of adenomatous polyposis coli (APC)-mutant colorectal cancer is dependent on Wnt/beta-catenin signaling.

    Science.gov (United States)

    Scholer-Dahirel, Alix; Schlabach, Michael R; Loo, Alice; Bagdasarian, Linda; Meyer, Ronald; Guo, Ribo; Woolfenden, Steve; Yu, Kristine K; Markovits, Judit; Killary, Karen; Sonkin, Dmitry; Yao, Yung-Mae; Warmuth, Markus; Sellers, William R; Schlegel, Robert; Stegmeier, Frank; Mosher, Rebecca E; McLaughlin, Margaret E

    2011-10-11

    Persistent expression of certain oncogenes is required for tumor maintenance. This phenotype is referred to as oncogene addiction and has been clinically validated by anticancer therapies that specifically inhibit oncoproteins such as BCR-ABL, c-Kit, HER2, PDGFR, and EGFR. Identifying additional genes that are required for tumor maintenance may lead to new targets for anticancer drugs. Although the role of aberrant Wnt pathway activation in the initiation of colorectal cancer has been clearly established, it remains unclear whether sustained Wnt pathway activation is required for colorectal tumor maintenance. To address this question, we used inducible β-catenin shRNAs to temporally control Wnt pathway activation in vivo. Here, we show that active Wnt/β-catenin signaling is required for maintenance of colorectal tumor xenografts harboring APC mutations. Reduced tumor growth upon β-catenin inhibition was due to cell cycle arrest and differentiation. Upon reactivation of the Wnt/β-catenin pathway colorectal cancer cells resumed proliferation and reacquired a crypt progenitor phenotype. In human colonic adenocarcinomas, high levels of nuclear β-catenin correlated with crypt progenitor but not differentiation markers, suggesting that the Wnt/β-catenin pathway may also control colorectal tumor cell fate during the maintenance phase of tumors in patients. These results support efforts to treat human colorectal cancer by pharmacological inhibition of the Wnt/β-catenin pathway.

  4. Expression of COX-2 and p53 in juvenile polyposis coli and its correlation with adenomatous changes

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    Shatavisha Das Gupta

    2016-01-01

    Conclusion: We observed significantly higher COX-2 expression in JPC. Establishment of the role of COX-2 in JPC will help us formulate chemopreventive therapies as an adjunct to its surgical management.

  5. Interaction of the MUC1 Tumor Antigen and the Adenomatous Polyposis Coli Tumor Suppressor in Human Breast Cancer

    Science.gov (United States)

    2006-03-01

    then counted manually on the membrane or destained and read in a 96-well plate format, and invasion was determined as the percentage of sample over...Franklin, R.A., Bertrand, F.E., McCubrey, J.A.: JAK/STAT, Raf/ MERK /ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis. Leukemia

  6. Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis.

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    Bin Li

    Full Text Available Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP and 85% of spontaneous colorectal cancers (CRC. FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

  7. Repurposing the FDA-Approved Pinworm Drug Pyrvinium as a Novel Chemotherapeutic Agent for Intestinal Polyposis

    Science.gov (United States)

    Giambelli, Camilla; Fei, Dennis Liang; Han, Lu; Hang, Brian I.; Bai, Feng; Pei, Xin-Hai; Nose, Vania; Burlingame, Oname; Capobianco, Anthony J.; Orton, Darren; Lee, Ethan; Robbins, David J.

    2014-01-01

    Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC) promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP) and 85% of spontaneous colorectal cancers (CRC). FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes. PMID:25003333

  8. Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP

    NARCIS (Netherlands)

    Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian; Peeters, PHM

    2015-01-01

    The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We inv

  9. Colonoscopia com magnificação de imagem no diagnóstico de carcinoma colorretal invasivo da submucosa na polipose adenomatosa familiar Magnifying colonoscopy diagnosis of submucosal invasive colorectal carcinoma in familial adenomatous polyposis

    Directory of Open Access Journals (Sweden)

    Cláudio TARTA

    2000-04-01

    Full Text Available O desenvolvimento da colonoscopia com magnificação de imagem possibilitou o estudo detalhado da mucosa colônica e o diagnóstico diferencial entre lesões neoplásicas e não-neoplásicas, a partir da observação dos pit patterns. Os resultados são comparáveis à estereomicroscopia, sendo possível, assim, presumir o diagnóstico histológico. Foi realizada colonoscopia com magnificação de imagem em paciente portadora de polipose adenomatosa familiar, demonstrando-se com este método, a diversidade de lesões polipóides benignas e as apresentações morfológicas do câncer colorretal precoce. Nesta paciente, a avaliação por magnificação (videocolonoscópio FUJINON 410 - CM -- 40X, combinada à cromoscopia com indigo carmine 0,4%, demonstrou ampla variedade de lesões distribuídas por todo o cólon: lesão de espalhamento lateral no ceco com padrão IIIL + IV, pólipos subpediculados e sésseis distribuídos pelo cólon com padrão tipo IIIL, pólipo subpediculado no cólon transverso com diâmetro aproximado de 2,0 cm e padrão IV + V, lesões plano-elevadas tipo IIIL e no cólon sigmóide lesão IIa + IIc, com padrão V de Kudo. A avaliação dos pit patterns de lesões no cólon transverso e sigmóide permitiu o diagnóstico endoscópico de lesão com invasão de submucosa.The development of colonoscopy with image magnification has enable to study the colonic mucosa in detail and to do differential diagnosis between neoplastic and non-neoplastic lesions from the observation of pit patterns. The results are comparable to stereomicroscopy being possible to predict the histologic diagnosis. In a patient with familial adenomatous polyposis magnifying colonoscopy was performed and this method demonstrated a wide variaton of benign polypoid lesions and the morphological features of early colorectal cancer. In this patient, the evaluation by image magnification, together with indigo carmin 0,4% chromoscopy, showed a wide variety of

  10. Glycoprotein expression by adenomatous polyps of the colon

    Science.gov (United States)

    Roney, Celeste A.; Xie, Jianwu; Xu, Biying; Jabour, Paul; Griffiths, Gary; Summers, Ronald M.

    2008-03-01

    Colon cancer is the second leading cause of cancer related deaths in the United States. Specificity in diagnostic imaging for detecting colorectal adenomas, which have a propensity towards malignancy, is desired. Adenomatous polyp specimens of the colon were obtained from the mouse model of colorectal cancer called adenomatous polyposis coli-multiple intestinal neoplasia (APC Min). Histological evaluation, by the legume protein Ulex europaeus agglutinin I (UEA-1), determined expression of the glycoprotein α-L-fucose. FITC-labelled UEA-1 confirmed overexpression of the glycoprotein by the polyps on fluorescence microscopy in 17/17 cases, of which 13/17 included paraffin-fixed mouse polyp specimens. In addition, FITC-UEA-1 ex vivo multispectral optical imaging of 4/17 colonic specimens displayed over-expression of the glycoprotein by the polyps, as compared to non-neoplastic mucosa. Here, we report the surface expression of α-L-fucosyl terminal residues by neoplastic mucosal cells of APC specimens of the mouse. Glycoprotein expression was validated by the carbohydrate binding protein UEA-1. Future applications of this method are the development of agents used to diagnose cancers by biomedical imaging modalities, including computed tomographic colonography (CTC). UEA-1 targeting to colonic adenomas may provide a new avenue for the diagnosis of colorectal carcinoma by CT imaging.

  11. Juvenile Polyposis Syndrome

    Science.gov (United States)

    ... Types of Cancer > Juvenile Polyposis Syndrome Request Permissions Juvenile Polyposis Syndrome Approved by the Cancer.Net Editorial Board , 12/2015 What is juvenile polyposis syndrome? Juvenile polyposis syndrome (JPS) is a ...

  12. Complicações imediatas e tardias após cirurgia de reservatório ileal na polipose adenomatosa familiar Short-term and long-term postoperative complications after ileal pouch-anal anastomosis in familial adenomatous polyposis

    Directory of Open Access Journals (Sweden)

    Raquel Franco Leal

    2008-06-01

    Full Text Available RACIONAL: A retocolectomia total com confecção de reservatório ileal é cirurgia ideal para o tratamento do cólon e reto dos doentes com polipose adenomatosa familiar, no entanto pode estar associada a complicações no pós-operatório imediato e tardio. OBJETIVO: Estudar as complicações pós-operatórias da cirurgia do reservatório ileal na polipose adenomatosa familiar. MÉTODOS: Estudo retrospectivo de 69 doentes com polipose adenomatosa familiar submetidos a cirurgia de reservatório ileal no período de 1984 a 2006, pelo Grupo de Coloproctologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, SP. O seguimento médio pós-operatório foi de 82 (2-280 meses. Dados de interesse: ocorrência de complicações no pós-operatório. RESULTADOS: A morbidade e mortalidade foram de 63,8% e 2,9%, respectivamente. As complicações mais freqüentes foram obstrução intestinal (17,4%, estenose da anastomose (15,9% e sepse pélvica (10,1%. Outras complicações foram isquemia aguda do reservatório ileal (4,3%, ileíte do reservatório (" pouchitis" (2,9% e fístulas relacionadas ao reservatório (2,9%. CONCLUSÕES: A morbimortalidade foi semelhante à da literatura e aceitável para uma cirurgia complexa como é a do reservatório ileal, realizada em dois tempos operatórios. A obstrução intestinal foi a complicação mais freqüente. Entretanto, isquemia do reservatório, " pouchitis" e sepse pélvica constituíram importantes complicações relacionadas à perda do reservatório ileal.BACKGROUND: Restorative proctocolectomy is the procedure of choice to treat familial adenomatous polyposis, however it can be associated to short-term and long-term postoperative complications. AIM: To evaluate the occurrence of complications related to the surgical treatment of familial adenomatous polyposis with ileal pouch technique. METHODS: Retrospective study of 69 patients with familial adenomatous polyposis after rectocolectomy

  13. Polipose juvenil: relato de 2 casos Juvenile polyposis: case two report

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    Juvenal da Rocha Torres Neto

    2010-06-01

    Full Text Available A Polipose Juvenil é uma afecção rara e faz parte do grupo das poliposes hamartomatosas familiares (PHF. É uma síndrome autossômica dominante que pode ser desencadeada por mutações no gene SMAD4/DPC4 (que codifica um sinalizador intermediário de TGF-b. Caracteriza-se pelo aparecimento de 10 ou mais pólipos hamartomatosos (juvenis no trato gastrintestinal, predominando no cólon. Costuma manifestar-se entre 4 e 14 anos de idade. Alguns pólipos adquirem focos adenomatosos apesar da natureza hamartomatosa das lesões e há chance de malignização. Relato de 2 casos de pacientes portadores de Polipose Juvenil colônica associada a focos de adenoma com displasia e revisão da literatura.Juvenile Polyposis Syndrome is a rare disease and is included in the Hamartomatous Familial Polyposis's (HFP group. It's an autosomal dominant syndrome which can be determinated by SMAD4/DPC4 germline mutations (which codifies an intermediary mediator of TGF-b. It's characterized by 10 or more hamartomatous polyps (juveniles throughout the gastrointestinal tract, especially in the colon. The symptoms usually appears between the ages of 4 and 14 years old. Some polyps can acquire adenomatous changes despite the lesion's hamartomatous nature and there's chance of colorectum malignization. Case report of two patients with Juvenile Polyposis coli associated to adenomatous changes with dysplasia and literature review.

  14. Altered Interactions between the Gut Microbiome and Colonic Mucosa Precede Polyposis in APCMin/+ Mice.

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    Joshua S Son

    Full Text Available Mutation of the adenomatous polyposis coli (APC gene, an early event in the adenoma-carcinoma sequence, is present in 70-80% of sporadic human colorectal adenomas and carcinomas. To test the hypothesis that mutation of the APC gene alters microbial interactions with host intestinal mucosa prior to the development of polyposis, culture-independent methods (targeted qPCR assays and Illumina sequencing of the 16S rRNA gene V1V2 hypervariable region were used to compare the intestinal microbial composition of 30 six-week old C57BL/6 APCMin/+ and 30 congenic wild type (WT mice. The results demonstrate that similar to 12-14 week old APCMin/+ mice with intestinal neoplasia, 6 week old APCMin/+ mice with no detectable neoplasia, exhibit an increased relative abundance of Bacteroidetes spp in the colon. Parallel mouse RNA sequence analysis, conducted on a subset of proximal colonic RNA samples (6 APCMin/+, 6 WT revealed 130 differentially expressed genes (DEGs, fold change ≥ 2, FDR <0.05. Hierarchical clustering of the DEGs was carried out by using 1-r dissimilarity measurement, where r stands for the Pearson correlation, and Ward minimum variance linkage, in order to reduce the number of input variables. When the cluster centroids (medians were included along with APC genotype as input variables in a negative binomial (NB regression model, four of seven mouse gene clusters, in addition to APC genotype, were significantly associated with the increased relative abundance of Bacteroidetes spp. Three of the four clusters include several downregulated genes encoding immunoglobulin variable regions and non-protein coding RNAs. These results support the concept that mutation of the APC gene alters colonic-microbial interactions prior to polyposis. It remains to be determined whether interventions directed at ameliorating dysbiosis in APCMin/+mice, such as through probiotics, prebiotics or antibiotics, could reduce tumor formation.

  15. Appearance of attenuated intestinal polyposis during chronic non-steroidal anti-inflammatory drugs use

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2012-01-01

    Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.

  16. Seguimiento posquirúrgico de los pacientes con poliposis adenomatosa familiar: resultados en una población del sur de España Follow-up after surgical treatment of patients whit familial adenomatous polyposis: Results in Southern Spanish population

    Directory of Open Access Journals (Sweden)

    C. Cordero Fernández

    2007-08-01

    Full Text Available Objetivo: analizar la evolución de la mucosa rectal y del reservorio así como idoneidad de los intervalos de seguimiento y del tratamiento realizado para evitar la aparición del cáncer, en una serie de pacientes con poliposis adenomatosa familiar (PAF, intervenidos. Método: estudio prospectivo de 28 pacientes con PAF intervenidos mediante anastomosis íleo-rectal (20 pacientes y anastomosis íleo-anal con reservorio (8 pacientes. A todos se les había realizado un control endoscópico dos veces al año y análisis del número y características macroscópicas e histológicas de los pólipos antes y después de la cirugía así como del tratamiento realizado, de sus complicaciones y de la adecuación del intervalo de seguimiento. El seguimiento medio fue de 6,47 años (DE = 4,59; rango = 0,72-16,75 años. Resultados: ninguno de los 26 pacientes que cumplimentaron correctamente el protocolo de seguimiento desarrolló cáncer. Sólo dos pacientes lo desarrollaron al 1,75 y los 3 años, respectivamente del abandono del protocolo. Los pacientes que desarrollaron adenomas durante el seguimiento fueron tratados con éxito mediante polipectomía endoscópica, salvo en dos casos que se indicó cirugía. Conclusiones: en nuestra serie, el incumplimiento de las revisiones ha sido el factor que ha condicionado la aparición de cáncer.Objective: the study was to assess changes in the rectal mucosa and pouch in a series of patients with familial adenomatous polyposis (FAP who underwent either subtotal colectomy and ileorectal anastomosis (IRA or proctocolectomy and ileal pouch-anal anastomosis (IPAA, and to evaluate the suitability of the follow-up interval and postoperative treatment employed to prevent the development of cancer. Method: this study involved 28 patients with FAP who underwent IRA (n=20 or IPAA (n=8, and were followed endoscopically over a mean period of 7.47 years. The number and both macroscopic and histological features of polyps

  17. Detection of APC gene germline mutation in Chinese familial adenomatous polyposis by direct sequencing in combination with multiplex ligation-dependent probe amplification%直接测序联合多重连接依赖探针扩增法检测家族性腺瘤性息肉病APC基因胚系突变

    Institute of Scientific and Technical Information of China (English)

    金鹏; 崔伟佳; 盛剑秋; 付蕾; 安贺娟; 李爱琴; 张明智; 韩英; 李世荣

    2010-01-01

    目的 研究中国家族性腺瘤性息肉病(FAP)患者APC基因胚系突变的特点.方法 对来自北京、河北、河南、安徽、内蒙古、山西、福建等地区的14个FAP家系先证者用直接测序法进行APC基因突变检测,对突变检测阴性者应用多重连接依赖探针扩增(MLPA)技术进行APE基因大片段缺失检测.结果 14例先证者中9例(64.3%)检测出APC基因微小突变,其中移码突变6例,剪接区突变2例,无义突变1例;2例(14.3%)检测出APC基因大片段缺失,微小突变与大片段缺失的总检出率为78.6%.c.2336-2337insT、c.3923-3929delAAGAAAA、c.532-2A>T和c.4179-4180GAdelinsT等4个微小突变和外显子11、10A缺失、外显子15 start缺失等2个大片段缺失为首次报道.结论 中国FAP患者APC基因的胚系突变类型多样,以移码突变居多,突变位点以第15外显子居多;直接测序法联合MLPA法检测大片段缺失可提高APC基因突变的检出率.%Objective To investigate the characteristics of APC gene germline mutation in Chinese patients with familial adenomatous polyposis ( FAP). Methods The genomic DNA was extracted from peripheral venous blood drawn from probands of 14 Chinese FAP families from Beijing, Hebei, Henan,Anhui, Inner Mongolia, Shanxi and Fujian. The APC gene was amplified by PCR and underwent direct sequencing. Large fragment deletion was detected by multiplex ligation-dependent probe amplification (MLPA) only in micromutation-negative samples found by sequencing. Results APC gene micromutations were found in 9 probands and the mieromutation detection rate was 64. 3%, including 6 frameshift mutations, 2 splicing mutations and 1 nonsense mutation. Large fragment deletions of APC gene were detected in 2 probands ( 14. 3% ). The total mutation detection rate of micromutation and large fragment deletion was 78. 6%. Four novel micmromutations and 2 novel large fragment deletions were found, including c. 2336-2337insT, c. 3923-3929delAAGAAAA, c

  18. Desmoid tumour in familial adenomatous polyposis. A review of literature

    DEFF Research Database (Denmark)

    Knudsen, Anne Louise; Bülow, Steffen

    2001-01-01

    in combination with tamoxifen. Surgery may be considered in case of a small and well-defined DT with no signs of invasion of vital structures, and in cases of imminent bowel ischaemia or obstruction. The prognosis in mesenteric DT is serious, and improvement of the therapeutic strategy awaits current...

  19. Desmoid tumour in familial adenomatous polyposis. A review of literature

    DEFF Research Database (Denmark)

    Knudsen, Anne Louise; Bülow, Steffen

    2001-01-01

    in combination with tamoxifen. Surgery may be considered in case of a small and well-defined DT with no signs of invasion of vital structures, and in cases of imminent bowel ischaemia or obstruction. The prognosis in mesenteric DT is serious, and improvement of the therapeutic strategy awaits current...... are considered to be correlated with the development and growth of DT. In patients with FAP, 50% of the tumours are localised intra-abdominally, and 85-100% of these are mesenteric. DT frequently present as non- tender, slowly growing masses. The symptoms are abdominal pain, vomiting, diarrhoea or haematochezia...

  20. Guidelines for the clinical management of familial adenomatous polyposis (FAP)

    DEFF Research Database (Denmark)

    Vasen, H.F.; Moslein, G.; Alonso, A.

    2008-01-01

    is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty......-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches...... of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may...

  1. Attenuated familial adenomatous polyposis (AFAP). A review of the literature

    DEFF Research Database (Denmark)

    Knudsen, Anne Lyster; Bisgaard, Marie Luise; Bülow, Steffen

    2003-01-01

    with a few kindreds--and the diagnostic criteria and methods of investigation differ markedly. The true incidence and frequency of AFAP is not known. The mutations in APC associated with AFAP have mainly been detected in three parts of the gene: in the 5' end (the first five exons), in exon 9...

  2. MUTYH Associated Polyposis (MAP)

    DEFF Research Database (Denmark)

    Poulsen, Marie Louise Mølgaard; Bisgaard, M L

    2008-01-01

    MUTYH Associated Polyposis (MAP), a Polyposis predisposition caused by biallelic mutations in the Base Excision Repair (BER) gene MUTYH, confers a marked risk of colorectal cancer (CRC). The MAP phenotype is difficult to distinguish from other hereditary CRC syndromes. Especially from Familial...

  3. Juvenile polyposis syndrome

    Institute of Scientific and Technical Information of China (English)

    Lodewijk AA Brosens; Danielle Langeveld; W Arnout van Hattem; Francis M Giardiello; G Johan A Offerhaus

    2011-01-01

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer.The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34.Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes.Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum,juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis.In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found.Both genes play a role in the BMP/TGF-beta signalling pathway.It has been suggested that cancer in juvenile polyposis may develop through the so-alled "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma.Recognition of this rare disorder is important for patients and their families with regard to treatment,follow-up and screening of at risk individuals.Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome.In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome.

  4. Inherited colorectal polyposis and cancer risk of the APC I1307K polymorphism.

    OpenAIRE

    Gryfe, R; Di Nicola, N; G. Lal; Gallinger, S.; Redston, M

    1999-01-01

    Germ-line and somatic truncating mutations of the APC gene are thought to initiate colorectal tumor formation in familial adenomatous polyposis syndrome and sporadic colorectal carcinogenesis, respectively. Recently, an isoleucine-->lysine polymorphism at codon 1307 (I1307K) of the APC gene has been identified in 6%-7% of the Ashkenazi Jewish population. To assess the risk of this common APC allelic variant in colorectal carcinogenesis, we have analyzed a large cohort of unselected Ashkenazi ...

  5. Juvenile polyposis syndrome

    NARCIS (Netherlands)

    L.A.A. Brosens; D. Langeveld; W.A. van Hattem; F.M. Giardiello; G.J.A. Offerhaus

    2011-01-01

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a

  6. 大肠癌APC、β-catenin、E-cadherin和c-myc的表达及意义%Expression and significance of adenomatous polyposis coli APC,β-catenin,E-cadherin and c-myc in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    戴文斌; 任占平; 陈蔚麟; 杜娟; 石喆; 唐德艳

    2007-01-01

    目的 探讨腺瘤性息肉蛋白(APC)、β-catenin、E-cadherin和c-myc在大肠癌发生、发展中的作用.方法 采用免疫组化法检测正常大肠黏膜、大肠腺瘤、大肠腺瘤恶变及大肠癌组织中上述4种蛋白的表达情况.结果 大肠癌和大肠腺瘤恶变APC阳性率显著低于大肠腺瘤和正常大肠黏膜(P< 0.01).大肠癌、大肠腺瘤恶变和大肠腺瘤β-catenin胞质/胞核异位表达率、c-myc阳性率显著高于正常大肠黏膜(P< 0.01),大肠癌的β-catenin异位表达率显著高于大肠腺瘤(P< 0.01).大肠癌中β-catenin、E-cadherin膜表达缺失率显著高于大肠腺瘤和正常大肠黏膜(P< 0.01).大肠癌中β-catenin异位表达与c-myc阳性表达、E-cadherin阳性表达呈正相关,与APC阳性表达呈负相关.结论 APC失表达和(或)β-catenin异位表达、c-myc过表达与大肠癌的发生相关,β-catenin、E-cadherin膜表达缺失与大肠癌的侵袭、转移有关.

  7. N-Methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA

    Directory of Open Access Journals (Sweden)

    Narayan Satya

    2004-01-01

    Full Text Available Abstract Background Cellular senescence is a state in which mammalian cells enter into an irreversible growth arrest and altered biological functions. The senescence response in mammalian cells can be elicited by DNA-damaging agents. In the present study we report that the DNA-damaging agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG is able to induce senescence in the HCT-116 colon cancer cell line. Results Cells treated with lower concentrations of MNNG (0–25 microM for 50 h showed a dose-dependent increase in G2/M phase arrest and apoptosis; however, cells treated with higher concentrations of MNNG (50–100 microM showed a senescence-like G0/G1 phase arrest which was confirmed by increased expression of β-galactosidase, a senescence induced marker. The G2/M phase arrest and apoptosis were found to be associated with increased levels of p53 protein, but the senescence-like G0/G1 phase arrest was dissociated with p53 protein levels, since the p53 protein levels decreased in senescence-like arrested cells. We further, determined whether the decreased level of p53 was a transcriptional or a translational phenomenon. The results revealed that the decreased level of p53 protein in senescence-like arrested cells was a transcriptional phenomenon since p53 mRNA levels simultaneously decreased after treatment with higher concentrations of MNNG. We also examined the effect of MNNG treatment on other cell cycle-related proteins such as p21, p27, cyclin B1, Cdc2, c-Myc and max. The expression levels of these proteins were increased in cells treated with lower concentrations of MNNG, which supported the G2/M phase arrest. However, cells treated with higher concentrations of MNNG showed decreased levels of these proteins, and hence, may not play a role in cell cycle arrest. We then examined a possible association of the expression of APC protein and telomeric DNA signals with cellular senescence in MNNG-treated cells. We found that protein and mRNA levels of APC were drastically reduced in cells treated with higher concentrations of MNNG. The loss of APC expression might lead to chromosomal instability as well as microtubular disorganization through its dissociation with tubulin. In fact, the protein level of α-tubulin was also drastically decreased in senescence-like arrested cells treated with higher concentrations of MNNG. The levels of telomeric DNA also decreased in cells treated with higher concentrations of MNNG. Conclusions These results suggest that in response to DNA alkylation damage the senescence-like arrest of HCT-116 cells was associated with decreased levels of APC protein, microtubular organization, and telomeric DNA.

  8. Atividade inflamatória em mucosa de reservatório ileal na polipose adenomatosa familiar e retocolite ulcerativa inespecífica: avaliação da expressão de TNF-alfa e IL-1beta, e da ativação NF- kapaB Inflammatory activity in pelvic ileal pouches for familial adenomatous polyposis and ulcerative colitis: expression of TNF-alpha, IL-1beta and the activation of NF- kappaB

    Directory of Open Access Journals (Sweden)

    Raquel Franco Leal

    2006-12-01

    Full Text Available A ileíte do reservatório pós retocolectomia total constitui uma das complicações mais comuns nos doentes com RCUI, apresentando pequena freqüência nos doentes com PAF. OBJETIVO: Avaliar a atividade inflamatória em mucosa de reservatórios ileais endoscopicamente normais, através da expressão de TNF-alfa, NF-kapaB e IL-1beta. CASUÍSTICA E MÉTODOS: Selecionaram-se 20 doentes submetidos à retocolectomia total com reservatório ileal em "J" pelo Grupo de Coloproctologia da UNICAMP, sendo 10 doentes com RCUI e 10 com PAF. O grupo controle foi constituído por íleo terminal de intestino normal. Realizadas biópsias da mucosa do reservatório ileal e do íleo terminal normal, e congeladas em nitrogênio líquido. A expressão de TNF-alfa e IL-1beta foi analisada por extrato total e de NF-kB por meio de imunoprecipitado. A separação protéica foi feita por eletroforese em gel de poliacrilamida. RESULTADOS: Expressão de TNF-alfa e IL-1beta apresentaram níveis maiores nos doentes com RCUI, quando comparados àqueles com PAF (p0.1 e IL-1beta (p > 0.05 sem diferença estatística em relação aos demais grupos. CONCLUSÃO: Os doentes com RCUI apresentaram maiores níveis de expressão das citocinas estudadas, mesmo sem evidência clínica e endoscópica de ileíte do reservatório, podendo justificar maior suscetibilidade dos doentes com RCUI a esta complicação.Pouchitis after total retocolectomy is one of the most common complication of patients with ulcerative colitis (UC, while its frequency is quite rare in familial adenomatous polyposis (FAP. PURPOSE: To evaluate the inflammatory activity in endoscopicaly normal mucosa of the ileal pouch, by determining the expression of TNF-alpha and IL-1beta, and the activation of NF-kappaB. METHODS AND PATIENTS: Twenty patients with "J" pouch after total retocolectomy were studied, being 10 patients with UC and 10 with FAP. The control group was constituted by biopsies from terminal ileum take

  9. Colorectal Polyposis and Immune-Based Therapies

    Directory of Open Access Journals (Sweden)

    Pearl Jacobson-Brown

    2004-01-01

    Full Text Available The progression from precancerous (adenomatous colon polyps to malignant colorectal cancer involves the complex actions of various cytokines on T cell proliferation, cell-cell adhesion, apoptosis and host immunity. A broad spectrum of new treatments, including innovative molecular therapies such as gene therapy and treatment with cytokines, is under experimental and preclinical investigation. Nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors have traditionally been used as inflammation-reducing agents in cases of colon adenoma. Currently, adjuvant immunotherapies such as recombinant gene therapy and antibody-cytokine fusion proteins are assuming a more significant role in the management of colorectal neoplasia. Furthermore, advances in antitumour necrosis factor antibodies for the treatment of ulcerative colitis and Crohn's disease may have potential as chemoprotective agents for the treatment of colon polyposis. The present review aims to discuss the immunological mechanisms underlying colon tumour progression and the molecular and immune-based therapies that are leading to new methods of prognosis and treatment.

  10. Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts.

    Science.gov (United States)

    Koh, Kwang-Joon; Park, Ha-Na; Kim, Kyoung-A

    2016-12-01

    Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome.

  11. Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Kwang Joon; Park, Ha Na; Kim, Kyoung A [Dept. of Oral and Maxillofacial Radiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju (Korea, Republic of)

    2016-12-15

    Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome.

  12. Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts

    Science.gov (United States)

    Park, Ha-Na; Kim, Kyoung-A

    2016-01-01

    Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome. PMID:28035305

  13. Prophylactic colectomy for hyperplastic polyposis.

    LENUS (Irish Health Repository)

    Doran, D

    2011-03-01

    Hyperplastic polyposis (HP) is important to recognise as it increases the risk of adenomata which may develop dysplastic change or frank adenocarcinoma. We present the case of a 58-year-old woman with HP.

  14. Copy number variants associated with 18p11.32, DCC and the promoter 1B region of APC in colorectal polyposis patients

    Directory of Open Access Journals (Sweden)

    Amy L. Masson

    2016-02-01

    Full Text Available Familial Adenomatous Polyposis (FAP is the second most common inherited predisposition to colorectal cancer (CRC associated with the development of hundreds to thousands of adenomas in the colon and rectum. Mutations in APC are found in ~80% polyposis patients with FAP. In the remaining 20% no genetic diagnosis can be provided suggesting other genes or mechanisms that render APC inactive may be responsible. Copy number variants (CNVs remain to be investigated in FAP and may account for disease in a proportion of polyposis patients. A cohort of 56 polyposis patients and 40 controls were screened for CNVs using the 2.7M microarray (Affymetrix with data analysed using ChAS (Affymetrix. A total of 142 CNVs were identified unique to the polyposis cohort suggesting their involvement in CRC risk. We specifically identified CNVs in four unrelated polyposis patients among CRC susceptibility genes APC, DCC, MLH1 and CTNNB1 which are likely to have contributed to disease development in these patients. A recurrent deletion was observed at position 18p11.32 in 9% of the patients screened that was of particular interest. Further investigation is necessary to fully understand the role of these variants in CRC risk given the high prevalence among the patients screened.

  15. Analyses of APC Gene Mutations in Colorectal Adenomatous Polyps by DNA Sequencing%结直肠腺瘤性息肉APC基因突变的DNA测序分析

    Institute of Scientific and Technical Information of China (English)

    李卫; 高枫; 梁君林; 唐宗江; 唐卫中

    2006-01-01

    目的:探索广西地区结直肠腺瘤性息肉组织中腺瘤性息肉病(Adenomatous? polyposis coli,APC)基因的突变类型.方法:应用聚合酶链反应(Polymerase chain reaction,PCR)方法扩增APC基因的相应片段,以制备DNA测序的模板,然后用DNA自动测序仪进行测序.结果:共检出5种APC基因突变类型,即,密码子1322(GGA>TAA)、密码子1379(GAG>TAG)、密码子1396(-TT)、密码子1414(-G)和密码子1429(CAA>TAA).结论:这5种突变中有3种为无义突变,其余2种为移码突变,从而使终止密码提前出现,APC蛋白的生物合成提前终止,由此产生无功能的截短APC蛋白.

  16. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice.

    Science.gov (United States)

    Sonoshita, M; Takaku, K; Sasaki, N; Sugimoto, Y; Ushikubi, F; Narumiya, S; Oshima, M; Taketo, M M

    2001-09-01

    Arachidonic acid is metabolized to prostaglandin H(2) (PGH(2)) by cyclooxygenase (COX). COX-2, the inducible COX isozyme, has a key role in intestinal polyposis. Among the metabolites of PGH(2), PGE(2) is implicated in tumorigenesis because its level is markedly elevated in tissues of intestinal adenoma and colon cancer. Here we show that homozygous deletion of the gene encoding a cell-surface receptor of PGE(2), EP2, causes decreases in number and size of intestinal polyps in Apc(Delta 716) mice (a mouse model for human familial adenomatous polyposis). This effect is similar to that of COX-2 gene disruption. We also show that COX-2 expression is boosted by PGE(2) through the EP2 receptor via a positive feedback loop. Homozygous gene knockout for other PGE(2) receptors, EP1 or EP3, did not affect intestinal polyp formation in Apc(Delta 716) mice. We conclude that EP2 is the major receptor mediating the PGE2 signal generated by COX-2 upregulation in intestinal polyposis, and that increased cellular cAMP stimulates expression of more COX-2 and vascular endothelial growth factor in the polyp stroma.

  17. A proposed staging system and stage-specific interventions for familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Lynch, Patrick M; Morris, Jeffrey S; Wen, Sijin

    2016-01-01

    in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical-benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention...

  18. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen; Christensen, Ib Jarle; Højen, Helle

    2012-01-01

    of cancer development. Method:  Follow-up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included chi(2) test, actuarial method and Kaplan-Meier analysis. Results:  Among 304 patients, 261 (86%) had more than one endoscopy. The median follow-up was 14 years...

  19. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen; Christensen, Ib Jarle; Højen, Helle

    2012-01-01

    of cancer development. Method: Follow-up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included chi(2) test, actuarial method and Kaplan-Meier analysis. Results: Among 304 patients, 261 (86%) had more than one endoscopy. The median follow-up was 14 years...

  20. Attenuated Familial Adenomatous Polyposis (AFAP) Results from an international collaborative study

    DEFF Research Database (Denmark)

    Knudsen, A L; Bülow, S; Tomlinson, I;

    2010-01-01

    with presumed AFAP, defined as having /= 25. Results. One hundred and ninety six patients were included. The median number of adenomas was 25 (0-100) with a uniform distribution of colorectal adenomas and carcinomas (CRC). Age at CRC diagnosis was delayed by 15 years compared with classic FAP. Eighty two...... patients had a colectomy and an ileorectal anastomosis (IRA) and 5/82 (6%) had a secondary proctectomy. The location of the mutation in the APC gene was known in 69/171 (40%) tested patients. Only 15/29 (52%) of mutations in APC were found in parts of the gene usually associated with AFAP (the 5' end, exon...... 9 and 3' end). Conclusions. A subset of FAP patients with a milder phenotype does exist and treatment and surveillance should be modified accordingly. The mutation detection rate is lower than in classic FAP and mutations in AFAP patients are located throughout the APC gene. We propose the following...

  1. Surveillance and management of upper gastrointestinal disease in Familial Adenomatous Polyposis

    DEFF Research Database (Denmark)

    Gallagher, Michelle C; Phillips, Robin K S; Bülow, Steffen

    2006-01-01

    following prophylactic colectomy, the burden of foregut disease (particularly duodenal adenomatosis) will increase. Until recently, the value of upper gastrointestinal surveillance in FAP populations has been contentious, but with improved understanding of the natural history coupled with developments...... in surgery, interventional endoscopy and medical therapy, treatment algorithms for duodenal adenomatosis in FAP are becoming clearer....

  2. A Patient With Desmoid Tumors and Familial FAP Having Frame Shift Mutation of the APC Gene

    Directory of Open Access Journals (Sweden)

    Sanambar Sadighi

    2017-02-01

    Full Text Available Desmoids tumors, characterized by monoclonal proliferation of myofibroblasts, could occur in 5-10% of patients with familial adenomatous polyposis (FAP as an extra-colonic manifestation of the disease. FAP can develop when there is a germ-line mutation in the adenomatous polyposis coli gene. Although mild or attenuated FAP may follow mutations in 5΄ extreme of the gene, it is more likely that 3΄ extreme mutations haveamore severe manifestation of thedisease. A 28-year-old woman was admitted to the Cancer Institute of Iran with an abdominal painful mass. She had strong family history of FAP and underwent prophylactic total colectomy. Pre-operative CT scans revealed a large mass. Microscopic observation showed diffuse fibroblast cell infiltration of the adjacent tissue structures. Peripheral blood DNA extraction followed by adenomatous polyposis coli gene exon by exon sequencing was performed to investigate the mutation in adenomatous polyposis coli gene. Analysis of DNA sequencing demonstrated a mutation of 4 bpdeletions at codon 1309-1310 of the exon 16 of adenomatous polyposis coli gene sequence which was repeated in 3 members of the family. Some of them had desmoid tumor without classical FAP history. Even when there is no familial history of adenomatous polyposis, the adenomatous polyposis coli gene mutation should be investigated in cases of familial desmoids tumors for a suitable prevention. The 3΄ extreme of the adenomatous polyposis coli gene is still the best likely location in such families.

  3. A new conditional Apc-mutant mouse model for colorectal cancer

    NARCIS (Netherlands)

    E.C. Robanus-Maandag (Els); P.J. Koelink (Pim); C. Breukel (Cor); D.C.F. Salvatori (Daniela); S.C. Jagmohan-Changur (Shantie); C.A.J. Bosch (Cathy); H.W. Verspaget; P. Devilee (Peter); R. Fodde (Riccardo); M.J.M. Smits (Ron)

    2010-01-01

    textabstractMutations of the adenomatous polyposis coli (APC) gene predispose individuals to familial adenomatous polyposis (FAP), characterized by multiple tumours in the large intestine. Most mouse models heterozygous for truncating mutant Apc alleles mimic FAP, however, the intestinal tumours occ

  4. Myc deletion rescues Apc deficiency in the small intestine

    NARCIS (Netherlands)

    Sansom, O.J.; Meniel, V.S.; Muncan, V.; Phesse, T.J.; Wilkins, J.A.; Reed, K.R.; Vass, J.K.; Athineos, D.; Clevers, J.C.; Clarke, A.R.

    2007-01-01

    The APC gene encodes the adenomatous polyposis coli tumour suppressor protein, germline mutation of which characterizes familial adenomatous polyposis (FAP), an autosomal intestinal cancer syndrome. Inactivation of APC is also recognized as the key early event in the development of sporadic colorect

  5. Diagnosis and treatment of Gardner syndrome with gastric polyposis: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Guo-Li Gu; Shi-Lin Wang; Xue-Ming Wei; Li Bai

    2008-01-01

    Gardner syndrome (GS) is an autosomal dominant disease characterized by the presence of colonic polyposis, osteoma and soft tissue tumors. It is regarded as a clinical subgroup of familial adenomatous polyposis (FAP) and may present at any age from 2 mo to 70 years with a variety of symptoms, either colonic or extracolonic. We present a case of a 23-year-old female patient with GS who presented with gastric polyposis and was successively treated with restorative proctocolectomy in combination with ileal pouch anal anastomosis (RPC/ IPAA), ileostomy, ileostomy closure operation, snare polypectomy during 8 mo. After operation, the patient took oral traditional Chinese medicine pills made of Fructus mume and Bombyx batryticatu for about 6 mo. The innutrition and anaemia of this patient were gradually improved. Gastroscopy showed that the remnant gastric polypi gradually decreased and finally disappeared 19 mo after the first operation. The patient had 2-3 times of solid stool per day at the time we wrote this paper.

  6. Somatic mutations of APC gene in carcinomas from hereditary non-polyposis colorectal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Jian Huang; Shu Zheng; Shen-Hang Jin; Su-Zhan Zhang

    2004-01-01

    AIM: To investigate the mutational features of adenomatous polyposis coii (APC) gene and its possible arising mechanism in hereditary non-polyposis colorectal cancers (HNPCC).METHODS: PCR-based In Vitro Synthesized Protein Test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC cases. RESULTS: Eleven cases with 13 mutations were determined to harbor APC mutations. The prevalence of APC mutation was 58%(11/19). The mutations consisted of 9 frameshift and 4 nonsense ones, indicating that there were more frameshift mutations (69%). The frameshift mutations allexhibited deletion or insertion of 1-2 bp and most of them (7/9) happened at simple nucleotide repeat sequences, particularly within (A)n tracts (5/9). All point mutations presented C-to-T transitions at CpG sites. CONCLUSION: Mutations of APC gene were detected in more than half of HNPCC, indicating that its mutation was a common molecular event and might play an important role in the tumorigenesis of HNPCC. Locations of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites suggested that many mutations probably derived from endogenous processes including mismatch repair (MMR) deficiency. Defective MMR might affect the nature of APC mutations in HNPCC and likely occur earlier than APC mutational inactivation in some patients.

  7. Colorectal cancer risk in hamartomatous polyposis syndromes

    Science.gov (United States)

    Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real

    2015-01-01

    Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as “hamartomatous polyposis syndromes”, “Peutz-Jeghers syndrome”, “juvenile polyposis syndrome”, “juvenile polyp”, and “PTEN hamartoma tumour syndrome” (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented. PMID:25848489

  8. 粪、血APC及K-ras基因突变联合检测在大肠癌筛查中的作用%Value of fecal and blood adenomatous polyposis coli gene and K-ras gene mutation detection in colorectal neoplasm screening

    Institute of Scientific and Technical Information of China (English)

    詹俊; 李新; 于钟; 袁宇红; 侯婧

    2007-01-01

    目的 通过联合检测粪、血浆中APC和K-ras两种基因的突变,探讨其在大肠癌筛查中的作用.方法 收集本院2003年10月~2004年3月行肠镜检查患者的肝素抗凝血5 ml,大便3~5 g.提取粪便及血浆DNA,采用PCR-SSCP法检测APC和K-ras突变.结果 和结论(1)大肠癌和腺瘤患者血浆APC基因突变分别为41.9%和57.7%(P>0.05),高于正常对照组(P<0.05).粪便APC基因突变分别为51.6%和42.3%(P>0.05),高于正常对照组(P<0.05).两种检测方法具有高度的吻合度(kappa值为0.811,P<0.001).(2)血浆K-ras基因突变在大肠癌、腺瘤和正常对照分别为48.4%、3.8%和0%,粪便K-ras基因突变在3组中分别为54.8%、7.7%和11.1%,大肠癌组高于腺瘤组和正常组(P<0.05),腺瘤组和正常组间无差异(P>0.05).两种方法检测的吻合度一般(kappa值为0.662,P=0.000).(3)联合检测APC及K-ras基因突变可以提高诊断大肠癌的灵敏度.血、粪联合检测检测APC和K-ras基因突变较粪便检测无明显优势.(4)APC基因突变与是否发生肿瘤区域淋巴结转移有关,K-ras基因突变与病变分化程度有关.

  9. Pulmonary Atypical Adenomatous Hyperplasia And Bronchioloalveolar Carcinoma

    Institute of Scientific and Technical Information of China (English)

    MeilinXu; XiaYang; ZhiyaoZhang

    2004-01-01

    OBJECTIVE To study the relationship between atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). METHODS Morphometric, immunohistochemical and ultrastructural analyses were performed in 4 patients with low grade AAH, 5 with high grade AAH and 7 with BAC. RESULTS The mean nuclear areas of high grade AAH and BAC were greater than those of low grade AAH (P<0.05); p53 protein expression was negative in 4 cases of low grade AAH,while the positive rates in high grade AAH and BAC were 40% (2/5) and 57% (4/7), respectively. CONCLUSION The development of BAC is stepwise. AAH appears to be a lesion closely related with BAC, probably as its genuine precursor.

  10. Clinical characteristics of patients with serrated polyposis syndrome in Korea: comparison with Western patients.

    Science.gov (United States)

    Kim, Eun Ran; Jeon, Jaryong; Lee, Jin Hee; Lee, Yoon Jung; Hong, Sung Noh; Chang, Dong Kyung; Kim, Young-Ho

    2017-07-01

    Serrated polyposis syndrome (SPS) has been shown to increase the risk of colorectal cancer (CRC). However, little is known about the characteristics of Asian patients with SPS. This study aimed to identify the clinicopathological features and risk of CRC in Korean patients with SPS as well as the differences between Korean and Western patients based on a literature review. This retrospective study included 30 patients with SPS as defined by World Health Organization classification treated at Samsung Medical Center, Korea, between March 1999 and May 2011. Twenty patients (67%) were male. The median patient age at diagnosis was 56 years (range, 39-76 years). A total of 702 polyps were identified during a median follow-up of 43 months (range, 0-149 months). Serrated polyps were noted more frequently in the distal colon (298/702, 55%). However, large serrated polyps and serrated adenomas were mainly distributed throughout the proximal colon (75% vs. 25% and 81% vs. 19%, respectively); 73.3% had synchronous adenomatous polyps. The incidence of CRC was 10% (3/30 patients), but no interval CRC was detected. A total of 87% of the patients underwent esophagogastroduodenoscopy and 19.2% had significant lesions. The phenotype of SPS in Korean patients is different from that of Western patients. In Korean patients, SPS is more common in men, there were fewer total numbers of serrated adenoma/polyps, and the incidence of CRC was lower than that in Western patients. Korean patients tend to more frequently have abnormal gastric lesions. However, the prevalence of synchronous adenomatous polyps is high in both Western and Korean patients.

  11. Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP

    Science.gov (United States)

    Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Newcomb, Polly A; Casey, Graham; Conti, David V; Schumacher, Fred; Gallinger, Steve; Lindor, Noralane M; Hopper, John; Jenkins, Mark; Hunter, David J; Kraft, Peter; Jacobs, Kevin B; Cox, David G; Yeager, Meredith; Hankinson, Susan E; Wacholder, Sholom; Wang, Zhaoming; Welch, Robert; Hutchinson, Amy; Wang, Junwen; Yu, Kai; Chatterjee, Nilanjan; Orr, Nick; Willett, Walter C; Colditz, Graham A; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Hayes, Richard B; Tucker, Margaret; Gerhard, Daniela S; Fraumeni, Joseph F; Hoover, Robert N; Thomas, Gilles; Chanock, Stephen J; Yeager, Meredith; Chatterjee, Nilanjan; Ciampa, Julia; Jacobs, Kevin B; Gonzalez-Bosquet, Jesus; Hayes, Richard B; Kraft, Peter; Wacholder, Sholom; Orr, Nick; Berndt, Sonja; Yu, Kai; Hutchinson, Amy; Wang, Zhaoming; Amundadottir, Laufey; Feigelson, Heather Spencer; Thun, Michael J; Diver, W Ryan; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Haiman, Christopher A; Henderson, Brian; Kolonel, Laurence; Marchand, Loic Le; Siddiq, Afshan; Riboli, Elio; Key, Timothy J; Kaaks, Rudolf; Isaacs, William; Isaacs, Sarah; Wiley, Kathleen E; Gronberg, Henrik; Wiklund, Fredrik; Stattin, Pär; Xu, Jianfeng; Zheng, S Lilly; Sun, Jielin; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Tucker, Margaret; Gerhard, Daniela S; Hoover, Robert N; Fraumeni, Joseph F; Hunter, David J; Thomas, Gilles; Chanock, Stephen J; Purdue, Mark P; Johansson, Mattias; Zelenika, Diana; Toro, Jorge R; Scelo, Ghislaine; Moore, Lee E; Prokhortchouk, Egor; Wu, Xifeng; Kiemeney, Lambertus A; Gaborieau, Valerie; Jacobs, Kevin B; Chow, Wong-Ho; Zaridze, David; Matveev, Vsevolod; Lubinski, Jan; Trubicka, Joanna; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Péter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Colt, Joanne S; Davis, Faith G; Schwartz, Kendra L; Banks, Rosamonde E; Selby, Peter J; Harnden, Patricia; Berg, Christine D; Hsing, Ann W; Grubb III, Robert L; Boeing, Heiner; Vineis, Paolo; Clavel-Chapelon, Françoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Duell, Eric J; Quirós, José Ramón; Sanchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay-Tee; Allen, Naomi E; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Trichopoulos, Dimitrios; Linseisen, Jakob; Ljungberg, Börje; Overvad, Kim; Tjønneland, Anne; Romieu, Isabelle; Riboli, Elio; Mukeria, Anush; Shangina, Oxana; Stevens, Victoria L; Thun, Michael J; Diver, W Ryan; Gapstur, Susan M; Pharoah, Paul D; Easton, Douglas F; Albanes, Demetrius; Weinstein, Stephanie J; Virtamo, Jarmo; Vatten, Lars; Hveem, Kristian; Njølstad, Inger; Tell, Grethe S; Stoltenberg, Camilla; Kumar, Rajiv; Koppova, Kvetoslava; Cussenot, Olivier; Benhamou, Simone; Oosterwijk, Egbert; Vermeulen, Sita H; Aben, Katja K H; van der Marel, Saskia L; Ye, Yuanqing; Wood, Christopher G; Pu, Xia; Mazur, Alexander M; Boulygina, Eugenia S; Chekanov, Nikolai N; Foglio, Mario; Lechner, Doris; Gut, Ivo; Heath, Simon; Blanche, Hélène; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith; Fraumeni, Joseph F; Skryabin, Konstantin G; McKay, James D; Rothman, Nathaniel; Chanock, Stephen J; Lathrop, Mark; Brennan, Paul; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian

    2015-01-01

    The presence of multiple (5–100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10−7). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have ‘polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients. PMID:24801760

  12. Fungal Agents as a Cause of Nasal Polyposis

    Directory of Open Access Journals (Sweden)

    Mohammad Nejadkazem

    2015-01-01

    Full Text Available Introduction: Sinonasal polyposis is the most common tumor of nasal cavity and sinuses. Its complications are but not limited to sinusitis, breathing difficulties, hyposmia, anosmia and bone erosion. Methods and materials: A total of 98 patients with sinonasal polyposis were examined for suspicious causative fungal agent. Results: Direct microscopy and culture confirmed fungal agent in 8 patients (8.1% from which 3 cases had Alternaria spp, 1 patient Aspergillus spp, 1 patient Bipolaris spp, and 3 patients yeast. Conclusion: Fungi may be considered as a potential cause of sinonasal polyposis.   Keywords: Sinonasal Polyposis, Rhinosinusitis, Fungi

  13. POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance

    Science.gov (United States)

    Bellido, Fernando; Pineda, Marta; Aiza, Gemma; Valdés-Mas, Rafael; Navarro, Matilde; Puente, Diana A.; Pons, Tirso; González, Sara; Iglesias, Silvia; Darder, Esther; Piñol, Virginia; Soto, José Luís; Valencia, Alfonso; Blanco, Ignacio; Urioste, Miguel; Brunet, Joan; Lázaro, Conxi; Capellá, Gabriel; Puente, Xose S.; Valle, Laura

    2016-01-01

    Purpose: Germ-line mutations in the exonuclease domains of POLE and POLD1 have been recently associated with polyposis and colorectal cancer (CRC) predisposition. Here, we aimed to gain a better understanding of the phenotypic characteristics of this syndrome to establish specific criteria for POLE and POLD1 mutation screening and to help define the clinical management of mutation carriers. Genet Med 18 4, 325–332. Methods: The exonuclease domains of POLE and POLD1 were studied in 529 kindred, 441 with familial nonpolyposis CRC and 88 with polyposis, by using pooled DNA amplification and massively parallel sequencing. Genet Med 18 4, 325–332. Results: Seven novel or rare genetic variants were identified. In addition to the POLE p.L424V recurrent mutation in a patient with polyposis, CRC and oligodendroglioma, six novel or rare POLD1 variants (four of them, p.D316H, p.D316G, p.R409W, and p.L474P, with strong evidence for pathogenicity) were identified in nonpolyposis CRC families. Phenotypic data from these and previously reported POLE/POLD1 carriers point to an associated phenotype characterized by attenuated or oligo-adenomatous colorectal polyposis, CRC, and probably brain tumors. In addition, POLD1 mutations predispose to endometrial and breast tumors. Genet Med 18 4, 325–332. Conclusion: Our results widen the phenotypic spectrum of the POLE/POLD1-associated syndrome and identify novel pathogenic variants. We propose guidelines for genetic testing and surveillance recommendations. Genet Med 18 4, 325–332. PMID:26133394

  14. [Long-term results of ileo-rectal anastomosis in familial polyposis].

    Science.gov (United States)

    Sváb, J; Pesková, M; Jirásek, V; Fried, M; Krska, Z

    1999-04-01

    The authors present their experience with 93 patients operated at the First Surgical Clinic of the General Faculty Hospital and First Medical Faculty, Charles University Prague on account of familial adenomatous polyposis (FAP) assembled during 36 year starting in 1962. They analyze 91 patients followed up in collaboration with the First Medical Clinic of the General Faculty Hospital and First Medical Clinic Charles University Prague. Seventy-two of the patients were operated and in 55 of them an ileorectoanastomosis was made following subtotal colectomy. Two important findings were made. From the group of 91 patients incl. primary patients who suffered already from advanced malignant disease of the large bowel a total of 38.5% died. In the rectal stump after ileorectoanastomosis on average within 16 years after operation in 16.4% of the patients a malignant tumour was found. This leads to the belief that patients should be recommended colectomy with ileoanoanastomosis with an ileal reservoir. This operation was performed during the last five years in nine patients with this condition, using a one-stage or two-stage procedure with temporary ileostomy.

  15. International Consensus on Nasal Polyposis 2002-2004.

    Science.gov (United States)

    Mladina, R; Clement, P; Lopatin, A; Mann, W; Passali, D

    2005-06-01

    Seventeen well-known experts in rhinosinusology from various countries tried to achieve consensus on the etiology, conservative approach and surgical approach to nasal polyposis. A Digi-Vote electronic system was used for an immediate computer analysis of expert answers to 23 questions related to the problem of nasal polyposis.

  16. Chronic rhinitis with nasal polyposis associated with sodium glutamate intolerance.

    Science.gov (United States)

    Asero, Riccardo; Bottazzi, Gianna

    2007-01-01

    The study reports a case of perennial rhinitis with bilateral polyposis. A careful diagnostic workup revealed that the disorder was caused by sodium glutamate intolerance. This is the first study showing an association between intolerance to food additives and nasal polyposis. 2007 S. Karger AG, Basel

  17. Oral perfluorooctane sulfonate (PFOS) lessens tumor development in the APC(min) mouse model of spontaneous familial adenomatous polyposis.

    Science.gov (United States)

    Wimsatt, Jeffrey; Villers, Meghan; Thomas, Laurel; Kamarec, Stacey; Montgomery, Caitlin; Yeung, Leo W Y; Hu, Yanqing; Innes, Kim

    2016-12-08

    Colorectal cancer is the second most common cause of cancer deaths for both men and women, and the third most common cause of cancer in the U.S. Toxicity of current chemotherapeutic agents for colorectal cancer, and emergence of drug resistance underscore the need to develop new, potentially less toxic alternatives. Our recent cross-sectional study in a large Appalachian population, showed a strong, inverse, dose-response association of serum perfluorooctane sulfonate (PFOS) levels to prevalent colorectal cancer, suggesting PFOS may have therapeutic potential in the prevention and/or treatment of colorectal cancer. In these preliminary studies using a mouse model of familial colorectal cancer, the APC(min) mouse, and exposures comparable to those reported in human populations, we assess the efficacy of PFOS for reducing tumor burden, and evaluate potential dose-response effects. At 5-6 weeks of age, APC(min) mice were randomized to receive 0, 20, 250 mg PFOS/kg (females) or 0, 10, 50 and 200 mg PFOS/kg (males) via their drinking water. At 15 weeks of age, gastrointestinal tumors were counted and scored and blood PFOS levels measured. PFOS exposure was associated with a significant, dose-response reduction in total tumor number in both male and female mice. This inverse dose-response effect of PFOS exposure was particularly pronounced for larger tumors (r(2) for linear trend = 0.44 for males, p's drinking water can reduce formation of gastrointestinal tumors, and that these reductions are both significant and dose-dependent. If confirmed in further studies, these promising findings could lead to new therapeutic strategies for familial colorectal cancer, and suggest that PFOS testing in both preventive and therapeutic models for human colorectal cancer is warranted.

  18. Identification of five novel modifier loci of ApcMin harbored in the BXH14 recombinant inbred strain

    OpenAIRE

    Nnadi, Stephanie C.; Watson, Rayneisha; Innocent, Julie; Gonye, Gregory E; Buchberg, Arthur M.; Linda D. Siracusa

    2012-01-01

    Every year thousands of people in the USA are diagnosed with small intestine and colorectal cancers (CRC). Although environmental factors affect disease etiology, uncovering underlying genetic factors is imperative for risk assessment and developing preventative therapies. Familial adenomatous polyposis is a heritable genetic disorder in which individuals carry germ-line mutations in the adenomatous polyposis coli (APC) gene that predisposes them to CRC. The Apc Min mouse model carries a p...

  19. A new conditional Apc-mutant mouse model for colorectal cancer.

    OpenAIRE

    Robanus-Maandag, E C; Koelink, P J; Breukel, C; Salvatori, D. C. F.; Jagmohan-Changur, S. C.; Bosch, C. A. J.; Verspaget, H. W.; Devilee, P; Fodde, R.; Smits, R

    2010-01-01

    textabstractMutations of the adenomatous polyposis coli (APC) gene predispose individuals to familial adenomatous polyposis (FAP), characterized by multiple tumours in the large intestine. Most mouse models heterozygous for truncating mutant Apc alleles mimic FAP, however, the intestinal tumours occur mainly in the small intestine. To model large intestinal tumours, we generated a new conditional Apc-mutant allele, Apc15lox, with exon 15 flanked by loxP sites. Similar survival of Apc1638N/15l...

  20. Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition

    OpenAIRE

    Wallis, Y.; Morton, D; McKeown, C; Macdonald, F

    1999-01-01

    BACKGROUND/AIMS—The development of colorectal cancer and a variable range of extracolonic manifestations in familial adenomatous polyposis (FAP) is the result of the dominant inheritance of adenomatous polyposis coli (APC) gene mutations. In this study, direct mutation analysis of the APC gene was performed to determine genotype-phenotype correlations for nine extracolonic manifestations and to investigate the incidence of APC mutations in non-FAP colorectal cancer.
METHODS—The APC gene was a...

  1. Filiform polyposis in the sigmoid colon: A case series

    Institute of Scientific and Technical Information of China (English)

    Chang; Geun; Lee; Yun; Jeong; Lim; Jong; Sun; Choi; Jin; Ho; Lee

    2010-01-01

    Filiform polyposis is a rare condition of uncertain patho-genesis that is usually found in association with Crohn’s disease, ulcerative colitis, intestinal tuberculosis or histiocytosis X. We report seven interesting cases of polyposis with various pathologic components, mainly located in the left side of the colon with no associated inflammatory bowel disease, intestinal tuberculosis or histiocytosis X. Multiple finger-like polypoid lesions with the appearance of stalactites were noted on the left side of ...

  2. Sense of smell in patients with bilateral nasal polyposis

    Directory of Open Access Journals (Sweden)

    Savović Slobodan N.

    2004-01-01

    Full Text Available Introduction Sense of smell is susceptible to various changes, both in physiological and in numerous pathological conditions. Of quantitative disorders of smell, hyposmia and anosmia are quite common, whereas of qualitative disorders parosmia is most frequent. The aim of this paper was to examine impact of bilateral nasal polyposis on olfactory function. Material and methods The research was carried out at the Nose, Ear and Throat Clinic in Novi Sad. It included 80 examinees, 40 (20 male, 20 female with bilateral nasal polyposis, while 40 examinees belonged to the control group (20 male, 20 female without symptoms of nasal polyposes. Fortunato-Niccolini olfactometer was used for this examination. Results and discussion In patients with bilateral nasal polyposis the average perception threshold values for examined odors were 15.50 ccm of odorous air, while in the control group they were 10,20 ccm of odorous air. The average identification threshold values for examined odors in patients with bilateral nasal polyposis were 18.80 ccm of odorous air, while in the control group they were 13.55 ccm of scented air. T-test showed that values of both tresholds were statistically significantly higher (p< 0,01 in patients with bilateral nasal polyposis in relation to the control group. Conclusion Olfactory deficit in patients with bilateral nasal polyposis is explained by difficult or impossible passage of odors into the olfactory region.

  3. Duodenal polyposis secondary to portal hypertensive duodenopathy

    Institute of Scientific and Technical Information of China (English)

    Ananta; Gurung; Philip; E; Jaffe; Xuchen; Zhang

    2015-01-01

    Portal hypertensive duodenopathy(PHD) is a recognized, but uncommon finding of portal hypertension in cirrhotic patients. Lesions associated with PHD include erythema, erosions, ulcers, telangiectasia, exaggerated villous pattern and duodenal varices. However, duodenal polyposis as a manifestation of PHD is rare. We report a case of a 52-year-old man who underwent esophagogastroduodenoscopy and was found with multiple small duodenal polyps ranging in size from 1-8 mm. Biopsy of the representative polyps revealed polypoid fragments of duodenal mucosa with villiform hyperplasia lined by reactive duodenal/gastric foveolar epithelium and underlying lamina propria showed proliferating ectatic and congested capillaries. The features were diagnostic of polyps arising in the setting of PHD.

  4. Multiple lymphomatous polyposis of the gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Maria Isete Fares Franco

    Full Text Available CONTEXT: Gastrointestinal multiple lymphomatous polyposis is a rare type of malignant lymphoma that has aggressive biological behavior, early systemic dissemination and poor prognosis. It is considered to be a manifestation of non-Hodgkin lymphoma and represents the gastrointestinal counterpart of mantle cell nodal lymphoma. OBJECTIVE: A case of gastrointestinal multiple lymphomatous polyposis is presented and the anatomopathological, clinical, diagnostic and treatment aspects of this unusual neoplasia are discussed. CASE REPORT: The patient was a 59-year-old white male with a complaint of asthenia, night sweating, alteration in intestinal habit and weight loss over the preceding two months. The physical examination showed pallid mucosa and a palpable mass in the epigastrium and mesogastrium. Endoscopy of the upper digestive tract showed the presence of gastric and duodenal polyps. An opaque enema showed multiple polypoid lesions, especially in the cecum. A rectal biopsy revealed infiltration of the mucosa and submucosa by diffuse lymphoma consisting of small cleaved cells. Immunohistochemical study showed lymphocytes that expressed the antibody CD20 (L-26 and light-chain kappa (k immunoglobulin, but not light-chain lambda (l immunoglobulin. The patient presented a condition of acute intestinal obstruction with the presence of a mesenteric mass formed by agglutinated lymph nodes that surrounded the proximal ileum, thereby obstructing its lumen. He was submitted to a segmental enterectomy and gastrotomy with excisional biopsies of the gastric polypoid lesions. After two cycles of chemotherapy there was a worsening of the general state, with an increase in the dimensions of the abdominal masses and sepsis, accompanied by progressive respiratory insufficiency, leading to death.

  5. Sebaceous adenomas in an MYH associated polyposis patient of Indian (Gujarati) origin.

    Science.gov (United States)

    Ajith Kumar, Vadakke Kanakath; Gold, June Anne; Mallon, Eleanor; Thomas, Shyamala; Hodgson, Shirley V

    2008-01-01

    MYH associated polyposis is an autosomal recessive polyposis syndrome with a high risk of large bowel cancer, caused by mutations in the DNA repair gene MYH. Founder mutations have been described in different ethnic groups. Muir Torre Syndrome is the association of internal malignancies with sebaceous gland tumours; Lynch Syndrome/Hereditary Non Polyposis Cancer is the best known cause. There has been a previous report of sebaceous gland tumours in an Italian patient with MYH associated polyposis. We describe a man of Indian (Gujarati) descent who has MYH associated polyposis and multiple sebaceous adenomas of the skin.

  6. Mutator gene and hereditary non-polyposis colorectal cancer

    Science.gov (United States)

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    2008-02-05

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  7. SOLITARY VILLO ADENOMATOUS POLYP WITH CARCINOMATOUS CHANGES – RECTUM: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Divvya

    2014-07-01

    Full Text Available olitary villo-adenomatous polyp in the rectum with focal dysplastic changes involving both adenomatous and villous component is very uncommon. This 60 year old male patient presented with intermittent hematochezia. Colonoscopy did not reveal any other polypoidal lesion in the colon.

  8. Increased Cyclooxygenase-2 Expression in Juvenile Polyposis Syndrome

    NARCIS (Netherlands)

    W.A. van Hattem; L.A.A. Brosens; S.Y. Marks; A.N.A. Milne; S. van Eeden; C.A. Iacobuzio-Donahue; A. Ristimäki; F.M. Giardiello; G.J.A. Offerhaus

    2009-01-01

    Background & Aims: Gastrointestinal juvenile polyps may occur in juvenile polyposis syndrome (JPS) or sporadically. JPS is an autosomal-dominant condition caused by a germline defect in SMAD4 or BMPR1A in 50% to 60% of cases, and is characterized by multiple juvenile polyps, predominantly in the col

  9. Multidetector CT diagnosis of massive hemobilia due to gallbladder polyposis in a child with metachromatic leukodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Wanner, Matthew R.; Karmazyn, Boaz [Indiana University School of Medicine, Riley Hospital for Children, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Fan, Rong [Indiana University School of Medicine, Riley Hospital for Children, Department of Pathology and Laboratory Medicine, Indianapolis, IN (United States)

    2015-12-15

    Hemobilia secondary to gallbladder polyposis is rare in children but has been reported in a few children with metachromatic leukodystrophy. We present a case with preoperative multidetector computed tomography (MDCT) diagnosis of massive hemobilia caused by gallbladder polyposis in a patient with metachromatic leukodystrophy. Our report highlights the importance of both awareness of the association of gallbladder polyposis with other syndromes such as metachromatic leukodystrophy as well as the possibility of this entity presenting with life-threatening bleeding. (orig.)

  10. Atypical presentation of pseudomembranous colitis localized in adenomatous polyps.

    Science.gov (United States)

    Hernández-Rocha, Cristian; Barra-Carrasco, Jonathan; Guzmán, Ana María; Paredes-Sabja, Daniel; Lezcano, Gabriel; Zoroquiaín, Pablo; Alvarez-Lobos, Manuel

    2013-01-14

    The most frequent cause of pseudomembranous colitis is Clostridium difficile (C. difficile) infection. This type of colitis is characterized by an endoscopic pattern of numerous small, yellowish or whitish plaques diffusely distributed, which typically compromises the rectum extending to proximal colon. Occasionally, the pseudomembranes compromise only the transverse or right colon, but their exclusive localization over polyps has not been reported. In this case report we have described a patient with symptoms compatible with C. difficile infection and positive for C. difficile toxigenic culture. Colonoscopy examination showed two small polyps with a whitish surface, and histopathological analysis confirmed them to be pseudomembranes over tubular adenomas. The rest of the colonic mucosa was normal and no other cause was demonstrated. We suggest that this particular distribution might be due to a higher affinity for dysplastic cells such as adenomatous polyps of colon by C. difficile and/or its toxins.

  11. Solitary Atypical Adenomatous Hyperplasia in a 12-Year-Old Girl.

    Science.gov (United States)

    Jin, Moran; Lee, Yang-Haeng; Kim, Bomi; Yoon, Young Chul; Wi, Jin Hong

    2016-04-01

    Atypical adenomatous hyperplasia is a premalignant lesion reflecting a focal proliferation of atypical cells. These lesions are usually observed as incidental findings in lungs that have been resected due to other conditions, such as lung cancer. We report the youngest case of atypical adenomatous hyperplasia on record in a 12-year-old girl. In this patient, the lesion was found in association with pneumothorax.

  12. [Nasosinusal polyposis and aspirin intolerance. Fernand Widal-Lermoyez syndrome].

    Science.gov (United States)

    Wayoff, M; Moneret-Vautrin, D; Gazel, P

    1979-01-01

    The authors describe the clinical picture of the aspirin idiosyncrasy and propose to call this peculiar entity: syndrom of Widal and Lermoyez. They compare 25 cases of aspirin nasal polyposis with 26 other cases of various etiologies. Other substances than aspirin seem to be charged. The complications are regular with severe asthma and infection. The pathogenesis is discussed, excluding an allergic mechanism; it remain not quite clear. Essentially prophylactic, the treatment is poor and difficult.

  13. Efficacy of ESS in chronic rhinosinusitis with and without nasal polyposis

    DEFF Research Database (Denmark)

    Lind, Henrik; Joergensen, G.; Lange, Bibi;

    2016-01-01

    Endoscopic sinus surgery (ESS) for patients with severe chronic rhinosinusitis (CRS) has become a well-established treatment in cases where medical therapy fails. Even though CRS patients are divided into two subgroups, CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSs...

  14. Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development

    NARCIS (Netherlands)

    Weren, Robbert DA; Venkatachalam, Ramprasath; Cazier, Jean-Baptiste; Farin, Henner F; Kets, C Marleen; de Voer, Richarda M; Vreede, Lilian; Verwiel, Eugène Tp; van Asseldonk, Monique; Kamping, Eveline J; Kiemeney, Lambertus A; Neveling, Kornelia; Aben, Katja Kh; Carvajal-Carmona, Luis; Nagtegaal, Iris D; Schackert, Hans K; Clevers, Hans; van de Wetering, Marc; Tomlinson, Ian P; Ligtenberg, Marjolijn Jl; Hoogerbrugge, Nicoline; Geurts van Kessel, Ad; Kuiper, Roland P

    2015-01-01

    Heritable genetic variants can significantly affect the lifetime risk of developing cancer, including polyposis and colorectal cancer (CRC). Variants in genes currently known to be associated with a high risk for polyposis or CRC, however, explain only a limited number of hereditary cases. The ident

  15. Survival of MUTYH-associated polyposis patients with colorectal cancer and matched control colorectal cancer patients

    NARCIS (Netherlands)

    M. Nielsen (Maartje); L.N. van Steenbergen (Liza); N. Jones (Natalie); S. Vogt (Stefanie); H.F. Vasen (Hans); H. Morreau (Hans); S. Aretz (Stefan); J. Sampson (Julian); O.M. Dekkers (Olaf); M.L.G. Janssen-Heijnen (Maryska); F.J. Hes (Frederik)

    2010-01-01

    textabstractBackground MUTYH-associated polyposis is a recessively inherited disorder characterized by a lifetime risk of colorectal cancer that is up to 100%. Because specific histological and molecular genetic features of MUTYH-associated polyposis colorectal cancers might influence tumor behavior

  16. Relation between obesity and adenomatous polyps of the large bowel.

    Science.gov (United States)

    Sato, Yumi; Nozaki, Ryoichi; Yamada, Kazutaka; Takano, Masahiro; Haruma, Ken

    2009-07-01

    We compared the prevalence of colorectal adenoma (polyps) in men and women and examined the role of body mass index (BMI) on polyp risk according to patient age and gender. The risk of developing colorectal polyps was studied in 15 380 subjects (7155 men and 8225 women) who underwent colonoscopy for the first time from April 1998 to March 2006 at our 'Human Dry Dock', which is the check-up service provided in Japan. Eligible subjects were 20-86 years old (mean age +/- SD, 47.3 +/- 8.5) and were free of invasive cancer, hyperplastic polyps and familial polyposis. Polyps were found in 1590 subjects (1062 men and 528 women). The odds ratio (OR) of detection of polyps in relation to obesity was determined in all cases by multivariate logistic regression analysis after making an adjustment for gender and age. The OR of polyp detection in obese subjects (BMI >or= 25) versus non-obese subjects (BMI < 25, OR = 1) was 1.34 (P < 0.001) in men and 1.13 (P = 0.26) in women. As the BMI increased in increments of one, the OR in men increased significantly to 1.01 (P < 0.001), whereas the OR in women was unchanged at 1.00 (P = 0.23), which was without significance. We conclude that obesity in men is a risk factor for the development of polyps. These results must be confirmed by additional epidemiological studies.

  17. Analysis of mtDNA sequence variants in colorectal adenomatous polyps

    Directory of Open Access Journals (Sweden)

    Grizzle William

    2010-10-01

    Full Text Available Abstract Colorectal tumors mostly arise from sporadic adenomatous polyps. Polyps are defined as a mass of cells that protrudes into the lumen of the colon. Adenomatous polyps are benign neoplasms that, by definition display some characteristics of dysplasia. It has been shown that polyps were benign tumors which may undergo malignant transformation. Adenomatous polyps have been classified into three histologic types; tubular, tubulovillous, and villous with increasing malignant potential. The ability to differentially diagnose these colorectal adenomatous polyps is important for therapeutic intervention. To date, little efforts have been directed to identifying genetic changes involved in adenomatous polyps. This study was designed to examine the relevance of mitochondrial genome alterations in the three adenomatous polyps. Using high resolution restriction endonucleases and PCR-based sequencing, fifty-seven primary fresh frozen tissues of adenomatous polyps (37 tumors and 20 matched surrounding normal tissues obtained from the southern regional Cooperative Human Tissue Network (CHTN and Grady Memorial Hospital at Atlanta were screened with three mtDNA regional primer pairs that spanned 5.9 kbp. Results from our data analyses revealed the presence of forty-four variants in some of these mitochondrial genes that the primers spanned; COX I, II, III, ATP 6, 8, CYT b, ND 5, 6 and tRNAs. Based on the MITODAT database as a sequence reference, 25 of the 44 (57% variants observed were unreported. Notably, a heteroplasmic variant C8515G/T in the MT-ATP 8 gene and a germline variant 8327delA in the tRNAlys was observed in all the tissue samples of the three adenomatous polyps in comparison to the referenced database sequence. A germline variant G9055A in the MT-ATP 6 gene had a frequency of 100% (17/17 in tubular and 57% (13/23 in villous adenomas; no corresponding variant was in tubulovillous adenomas. Furthermore, A9006G variant at MT-ATP 6 gene was

  18. A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Burn, John; Bishop, D Timothy; Chapman, Pamela D;

    2011-01-01

    a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design......, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum...... and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention...

  19. Sulindac inhibits beta-catenin expression in normal-appearing colon of hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis patients

    NARCIS (Netherlands)

    Koornstra, JJ; Rijcken, FEM; Oldenhuis, CNAM; Zwart, N; van der Sluis, T; Hollema, H; deVries, EGE; Keller, JJ; Offerhaus, JA; Giardiello, FM; Kleibeuker, JH

    2005-01-01

    Sulindac reduces colorectal cancer risk in genetically susceptible humans and animals. The molecular mechanisms underlying these effects are incompletely understood. Many studies suggest an important role for induction of apoptosis involving the mitochondrial pathway and the death receptor pathway.

  20. Emergency total proctocolectomy in an uninsured patient with Familial Adenomatous Polyposis Syndrome and acute lower gastrointestinal hemorrhage in a community hospital: A case report

    Directory of Open Access Journals (Sweden)

    Rodolfo J. Oviedo, MD, FACS

    2016-01-01

    Conclusion: A total proctocolectomy is feasible in the emergency setting in an uninsured patient with lower GI bleeding and FAP. A staged ileal J pouch-anal anastomosis is easier to justify to the hospital compared to a staged completion colectomy with proctectomy. It is essential to monitor the ileo-anal anastomosis with anoscopy.

  1. Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Rohlin, A; Engwall, Y; Fritzell, K

    2011-01-01

    in a panel of 20 various normal tissues examined. In FAP-related tumors, the APC germline mutation is proposed to dictate the second hit. Mutations leaving two or three out of seven 20-amino-acid repeats in the central domain of APC intact seem to be required for tumorigenesis. We examined adenomas from...

  2. APC and chromosome instability in colorectal cancer

    Directory of Open Access Journals (Sweden)

    C. M. Cabrera

    Full Text Available Colon cancer is a common disease that can be sporadic or familial. An inactivated adenomatous polyposis coli (APC suppressor gene is found in over 80% of colorectal tumors, this being an early alteration in the development of adenomatous polyps. APC function is not only critical for tumor initiation and progression, and chromosome instability (CIN is another characteristic dependent at least partly on APC mutations.

  3. Non-adenomatous forms of gastro-oesophageal epithelial dysplasia: an under-recognised entity?

    Science.gov (United States)

    Serra, Stefano; Chetty, Runjan

    2014-10-01

    Foveolar dysplasia is an uncommon form of dysplasia that is encountered in the stomach and oesophagus in the context of Barrett’s oesophagus. Glands displaying foveolar dysplasia also show architectural abnormalities that are similar to those encountered in adenomatous dysplasia. However, from a cytological point of view, foveolar dysplasia glands are lined by low-cuboidal to columnar epithelium, the cytoplasm is often clear with round-to-oval nuclei. Nuclear stratification as seen in adenomatous dysplasia is not common, although there is loss of nuclear polarity, pleomorphism and mitotic activity. It is important to distinguish low-grade foveolar dysplasia from regenerative change.

  4. Radiation-induced intestinal neoplasia in a genetically-predisposed mouse (Min)

    Energy Technology Data Exchange (ETDEWEB)

    Ellender, M.; Larder, S.M.; Harrison, J.D.; Cox, R.; Silver, A.R.J. [National Radiological Protection Board, Chilton (United Kingdom)

    1997-03-01

    A mouse lineage with inherited predisposition to multiple intestinal neoplasia (min) has been proposed as a model to study human colorectal cancer. Min mice are heterozygous for the adenomatous polyposis coli (Apc) gene implicated in human familial adenomatous polyposis (FAP). There is an increased risk of intestinal cancer in humans following radiation exposure and the min mouse model may be used to further our understanding of the molecular mechanisms involved. The present study showed a 2 Gy dose of x-rays doubles the tumour numbers in the murine gastrointestinal tract of F1 min heterozygotes. The distribution of tumours through the gut was also recorded. (authors)

  5. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  6. [Hyperplastic polyposis syndrome: phenotypic diversity and association to colorectal cancer].

    Science.gov (United States)

    Navarro, Matilde; González, Sara; Iglesias, Silvia; Capellá, Gabriel; Rodríguez-Moranta, Francisco; Blanco, Ignacio

    2013-07-21

    Hyperplastic polyposis syndrome (HPS) is an uncommon disorder characterized by hyperplastic polyps (HP) occasionally associated with serrated adenomas (SA) or mixed polyps (MP) and defined by clinical criteria (OMS/Cleveland). HPS is heterogeneous regarding the number and size of polyps, and it is associated with colorectal cáncer (CRC) and a family history. Its genetic basis is unknow. We describe individuals with HPS criteria from a series of families assessed in our Unit of Genetic Advice for colonic polyposis. Our objective is to identify the clinical characteristics of this syndrome. Retrospective study of 197 families with colonic polyposis (1998-2011), identifying patients with HPS criteria. To know the number of polyps, we took into account polypectomies and/or the histologic study of surgical samples. Polyps were classified into adenomas, serrated lesiones (HP and SA) and MP. Genetic studies revealed: microsatellite instability (MSI), MUTYH gene variants (p.Tyr165Cys, p.Gly382Asp and p.Glu396GlyfsX43) and APC gene. Eighteen individuals, with a median age of 51.1 years, had criteria of HPS (11M/7F). Number of HP varied between 14 and 100 coexisting with classical adenomas, SA and MP in 14 individuals (77.8%). Localization of polyps: ascending and descending colon in 13 individuals (72.2%) and only descending colon in 5 (27.8%). A CRC was detected in 10/18 (55.6%) patients, and 3 of them had a double CRC, a family history in 3 patients (16.7%) and a history of HPS in one. IMS was not detected in 8 CRC nor in 3 adenomas studied; we detected 2/13 heterozygous mutations in the MUTYH gene (p.Gly382Asp) and one variant with an unknown biological significance in the APC gene (p.Ser926Pro). The phenotypic variability of HPS difficults its identification, hence it is important to adhere to the clinical criteria established for its classification as well as to establish screening guidelines for CRC on the basis of its high incidence. Copyright © 2012 Elsevier Espa

  7. Hidden colonic adenomas in a patient with a family history of polyposis.

    Science.gov (United States)

    Petros, J G; Chong, F K

    1992-12-01

    We describe an asymptomatic patient with a strong family history of polyposis who was found to have flat and depressed adenomas that were not visible on colonoscopy. The diagnosis required assessment of multiple, randomly obtained biopsy specimens. Partial deflation of the colon during colonoscopy may allow hidden lesions to be seen. Biopsies should be performed in all patients with a family history of polyposis who are examined colonoscopically, even if they are asymptomatic and no lesions are visible through the colonoscope.

  8. Prevalence of colorectal adenomatous polyps in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Chun, Eun Mi; Kim, Seo Woo; Lim, So Yeon

    2015-01-01

    Colorectal adenomatous polyps are precancerous lesions of colorectal cancer. The aim of this study was to assess the prevalence of colorectal adenomatous polyps in chronic obstructive pulmonary disease (COPD) patients and determine whether COPD is associated with colorectal malignant potential. Subjects who had undergone post-bronchodilator spirometry and colonoscopy and were 40 years or older were selected from the hospital database. COPD was defined as a spirometry in which the ratio of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) is prevalence of colorectal adenomatous polyps was 39% (98/251) in the non-COPD group and 66% (54/82) in the COPD group. Among 54 patients with adenomatous polyps in the COPD group, 47 had tubular adenoma and seven had villous adenoma. Multiple logistic regression analyses revealed that only COPD patients whom matched to the criteria of COPD by pulmonary function test (odds ratio 2.1, 95% confidence interval: 1.1-3.8; P=0.019) were independently associated with colorectal malignant potential. The risk of colorectal malignant potential in the COPD group was higher than in the non-COPD group. We may suggest that COPD patients should consider regular colonoscopic evaluation to screen for premalignant colon polyps regardless of smoking.

  9. Association of the DNMT3B polymorphism with colorectal adenomatous polyps and adenocarcinoma.

    Science.gov (United States)

    Guo, Xiaoqing; Zhang, Liwei; Wu, Mingli; Wang, Na; Liu, Yanfeng; Er, Limian; Wang, Shunping; Gao, Yang; Yu, Weifang; Xue, Hui; Xu, Zhibin; Wang, Shijie

    2010-01-01

    DNMT3B is an important enzyme to modulate the methylation status in mammalian cells. The aim of this study is to investigate the correlation of the DNMT3B G39179T polymorphism with the susceptibilities of colorectal adenomatous polyps and adenocarcinoma. This case-control study included 146 colorectal adenomatous polyps, 170 colorectal adenocarcinoma patients, and 157 normal controls. DNMT3B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Family history of colorectal cancer significantly increases the risk of developing colorectal adenomatous polyps and adenocarcinoma. The genotype frequency of DNMT3B polymorphism (T/T and G/T + G/G) in adenocarcinoma patients was significantly different from that in controls (P value = 0.01). Compared with DNMT3B T/T genotype, the G allelotype (G/T + G/G genotype) had lower risk to develop colorectal adenocarcinoma (OR = 0.50, 95% CI = 0.29-0.87); while there was no significant difference between the colorectal adenomatous polyps patients and controls (OR = 0.63, 95% CI = 0.37-1.09), although descending tendency could be found in this polyps group. In the stratification analysis, a significant association was confined to subgroups of age DNMT3B G39179T SNP in different ethnics. DNMT3B G39179T SNP may be a potential genetic susceptibility factor for adenocarcinoma of the colon, especially in younger Chinese Han non-drinker men.

  10. Frequency of Nasal Polyposis in Chronic Rhinosinusitis and Role of Endoscopic Examination in Correct Diagnosis

    Directory of Open Access Journals (Sweden)

    F. Hashemian

    2005-10-01

    Full Text Available Introduction & Objective : Chronic rhinosinusitis (C.R.S. is one of the most common diseases in the world. Polyposis is a complication of C.R.S., due to allergy or inflammation. The purpose of this study was detection of the incidence of polyposis in patients with C.R.S. Materials & Methods : This study was carried out on 192 patients with C.R.S. who underwent functional endoscopic sinus surgery during 2000-2003 in Hamadan. All patients with C.R.S symptoms referred to ENT clinics were examined by otolaryngologist and after establishing diagnosis of C.R.S. they received medical treatment and after nose and para nasal sinuses CT scan, if there was indication, FESS was done. The patients who had polyps were followed up to one year, and the results analyzed with SPSS. Results : According to the results, incidence of polyposis in 192 patients with C.R.S. was 40%, the sex distribution of the patients with polyposis was 60% in male and 40% in female. The age mean was 39.2 year. Involved sinuses in decreasing order of frequency was, anterior ethmoid , maxilla, Posterior ethmaid, sphenoid, sphenoid and frontal. 43% of the patients had history of allergy. Recurrence happened in 6.6% after one year follow up.Conclusion : Because of disabling symptoms and severe complications of nasal polyposis, it is recommended more study in the future to find etiology and preventive ways for nasal polyposis in Hamadan.

  11. Allergic and non-allergic rhinitis: relationship with nasal polyposis, asthma and family history.

    Science.gov (United States)

    Gelardi, M; Iannuzzi, L; Tafuri, S; Passalacqua, G; Quaranta, N

    2014-02-01

    Rhinitis and rhinosinusitis (with/without polyposis), either allergic or non-allergic, represent a major medical problem. Their associated comorbidities and relationship with family history have so far been poorly investigated. We assessed these aspects in a large population of patients suffering from rhinosinusal diseases. Clinical history, nasal cytology, allergy testing and direct nasal examination were performed in all patients referred for rhinitis/rhinosinusitis. Fibre optic nasal endoscopy, CT scan and nasal challenge were used for diagnosis, when indicated. A total of 455 patients (60.7% male, age range 4-84 years) were studied; 108 (23.7%) had allergic rhinitis, 128 (28.1%) rhinosinusitis with polyposis, 107 (23.5%) non-allergic rhinitis (negative skin test); 112 patients had associated allergic and non-allergic rhinitis, the majority with eosinophilia. There was a significant association between non-allergic rhinitis and family history of nasal polyposis (OR = 4.45; 95%CI = 1.70-11.61; p = 0.0019), whereas this association was no longer present when allergic rhinitis was also included. Asthma was equally frequent in non-allergic and allergic rhinitis, but more frequent in patients with polyposis. Aspirin sensitivity was more frequent in nasal polyposis, independent of the allergic (p = 0.03) or non-allergic (p = 0.01) nature of rhinitis. Nasal polyposis is significantly associated with asthma and positive family history of asthma, partially independent of the allergic aetiology of rhinitis.

  12. Serrated polyposis syndrome: Molecular, pathological and clinical aspects

    Institute of Scientific and Technical Information of China (English)

    Carla Guarinos; Cristina Sánchez-Fortún; María Rodríguez-Soler; Cristina Alenda; Artemio Payá; Rodrigo Jover

    2012-01-01

    Hyperplastic polyps have traditionally been considered not to have malignant potential.New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area.Until recently,it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene,but it has been found that this pathway accounts for only approximately 70%-80%of colorectal cancer (CRC) cases.The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability.The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene.Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon.Clinical characteristics,etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet.Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described.Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer.In this review,we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.

  13. Infection and HLA-G Molecules in Nasal Polyposis

    Directory of Open Access Journals (Sweden)

    Roberta Rizzo

    2014-01-01

    Full Text Available Sinonasal polyposis (SNP is a chronic inflammatory pathology with an unclear aetiopathogenesis. Human papillomavirus (HPV infection is one candidate for the development of SNP for its epithelial cell trophism, hyperproliferative effect, and the induction of immune-modulatory molecules as HLA-G. We enrolled 10 patients with SNP without concomitant allergic diseases (SNP-WoAD, 10 patients with SNP and suffering from allergic diseases (SNP-WAD, and 10 control subjects who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA and the expression of membrane HLA-G (mHLA-G and IL-10 receptor (IL-10R and of soluble HLA-G (sHLA-G and IL-10 by polyp epithelial cells. The results showed the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5, all characterized by a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV-11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was observed in HPV negative polyps. These data highlight new aspects of polyposis aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic markers in the follow-up of SNP-WoAD.

  14. Distress in individuals facing predictive DNA testing for autosomal dominant late-onset disorders : Comparing questionnaire results with in-depth interviews

    NARCIS (Netherlands)

    DudokdeWit, AC; Tibben, A; Duivenvoorden, HJ; Niermeijer, MF; Passchier, J; Trijsburg, RW; Lindhout, D; Meijers-Heijboer, EJ; Frets, PG; Frets, PG; Lodder, LN; Zoetewij, MW; Klijn, JGM; Brocker-Vriends, A; van Haeringen, A; Helderman, ATJM; Hilhorst-Hofstee, Y; Kant, S; Maat-Kievit, JA; Oosterwijk, JC; van der Smagt, JJ; Vegter-van der Vlis, M; Vries-van der Weerd, MACS; Zoeteweij, MW; Bakker, E; Devilee, P; Losekoot, M; Tops, C; Cornelisse, CJ; Vasen, HFA

    1998-01-01

    In 50% risk carriers for Huntington disease (n = 41), hereditary cerebral hemorrhage with amyloidosis Dutch-type (n = 9) familial adenomatous polyposis coli (n = 45) and hereditary breast and ovarian cancer (n = 24), pretest intrusion and avoidance (Impact of Event Scale), anxiety and depression

  15. APC mutations in sporadic coloretal carcinomas from The Netherlands Cohort Study

    NARCIS (Netherlands)

    Lüchtenborg, M.; Weijenberg, M.P.; Roemen, G.M.J.M.; Bruïne, A.P. de; Brandt, P.A. van den; Lentjes, M.H.F.M.; Brink, M.; Engeland, M. van; Goldbohm, R.A.; Goeij, A.F.P.M. de

    2004-01-01

    The adenomatous polyposis coli (APC) gene is considered to be a gatekeeper in colorectal tumourigenesis. Inactivating mutations in APC have been reported in 34-70% of sporadic colorectal cancer patients, the majority of which occur in the mutation cluster region (MCR). In this study, tumour tissue f

  16. Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer

    NARCIS (Netherlands)

    Dow, Lukas E; O'Rourke, Kevin P; Simon, Janelle; Tschaharganeh, Darjus F; van Es, Johan H; Clevers, Hans; Lowe, Scott W

    2015-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is mutated in the vast majority of human colorectal cancers (CRC) and leads to deregulated Wnt signaling. To determine whether Apc disruption is required for tumor maintenance, we developed a mouse model of CRC whereby Apc can be conditionally su

  17. Distress in individuals facing predictive DNA testing for autosomal dominant late-onset disorders : Comparing questionnaire results with in-depth interviews

    NARCIS (Netherlands)

    DudokdeWit, AC; Tibben, A; Duivenvoorden, HJ; Niermeijer, MF; Passchier, J; Trijsburg, RW; Lindhout, D; Meijers-Heijboer, EJ; Frets, PG; Frets, PG; Lodder, LN; Zoetewij, MW; Klijn, JGM; Brocker-Vriends, A; van Haeringen, A; Helderman, ATJM; Hilhorst-Hofstee, Y; Kant, S; Maat-Kievit, JA; Oosterwijk, JC; van der Smagt, JJ; Vegter-van der Vlis, M; Vries-van der Weerd, MACS; Zoeteweij, MW; Bakker, E; Devilee, P; Losekoot, M; Tops, C; Cornelisse, CJ; Vasen, HFA

    1998-01-01

    In 50% risk carriers for Huntington disease (n = 41), hereditary cerebral hemorrhage with amyloidosis Dutch-type (n = 9) familial adenomatous polyposis coli (n = 45) and hereditary breast and ovarian cancer (n = 24), pretest intrusion and avoidance (Impact of Event Scale), anxiety and depression (Ho

  18. Prevalence of colorectal adenomatous polyps in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Chun EM

    2015-05-01

    Full Text Available Eun Mi Chun, Seo Woo Kim, So Yeon Lim Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Republic of Korea Background: Colorectal adenomatous polyps are precancerous lesions of colorectal cancer. The aim of this study was to assess the prevalence of colorectal adenomatous polyps in chronic obstructive pulmonary disease (COPD patients and determine whether COPD is associated with colorectal malignant potential.Methods: Subjects who had undergone post-bronchodilator spirometry and colonoscopy and were 40 years or older were selected from the hospital database. COPD was defined as a spirometry in which the ratio of forced expiratory volume in 1 second (FEV1 and forced vital capacity (FVC is <0.7 in post-bronchodilator spirometry. The non-COPD group was matched for both age and sex, and were defined as having an FEV1, FVC, and FEV1/FVC ≥0.7 in spirometry. Finally, 333 patients were retrospectively reviewed; of this group, 82 patients had COPD.Results: Among the subjects, 201 patients (60% were nonsmokers, while 78 (23% were current smokers. The prevalence of colorectal adenomatous polyps was 39% (98/251 in the non-COPD group and 66% (54/82 in the COPD group. Among 54 patients with adenomatous polyps in the COPD group, 47 had tubular adenoma and seven had villous adenoma. Multiple logistic regression analyses revealed that only COPD patients whom matched to the criteria of COPD by pulmonary function test (odds ratio 2.1, 95% confidence interval: 1.1–3.8; P=0.019 were independently associated with colorectal malignant potential.Conclusion: The risk of colorectal malignant potential in the COPD group was higher than in the non-COPD group. We may suggest that COPD patients should consider regular colonoscopic evaluation to screen for premalignant colon polyps regardless of smoking. Keywords: COPD, colorectal adenomatous polyp, smoking, chronic obstructive pulmonary

  19. Tumour spectrum of non-polyposis colorectal cancer (Lynch syndrome) on the island of Tenerife and influence of insularity on the clinical manifestations.

    Science.gov (United States)

    Medina-Arana, V; Barrios, Y; Fernández-Peralta, A; Jiménez, A; Salido, E; González, F; González-Aguilera, J J

    2004-02-01

    Colorectal cancer is a complex disease from a genetic point of view because both genetic and environmental factors interact in its development. Only familial adenomatous polyposis (FAP) follows mendelian genetics, in that mutations of the APC gene lead to development of the tumours. Lynch syndrome is the most frequent form of hereditary colorectal cancer and appears to be associated with other types of extracolonic cancers. The genetic basis has been established as a defect in DNA mismatch repair genes, and there is genetic heterogeneity due to the involvement of several genes in this system. Germinal mutations in these genes predispose to appearance of the syndrome. The aim of this study is to describe the tumoral spectrum of 10 families, comprising a total of 488 individuals, from the island of Tenerife (Canary Islands) and to assess whether the geographical isolation of this population has changed any features of the tumoral spectrum of the syndrome in comparison with studies that cover larger geographical areas with more genetic exchange. From our results we can conclude that the genetic drift and consanguinity in this population with a demographic history of isolation did not significantly alter the tumoral spectrum of the syndrome. Our data confirm that families affected by Lynch syndrome are a high-risk population and should be closely monitored, since their careful supervision has been shown to be useful in preventing cancer. We also emphasize the importance of developing a complete family history that permits these families to be identified together with a mutational screening of DNA mismatch repair genes (mainly MLH1 and MSH2 genes) with the aim of a possible identification of members of a family that should be carefully monitored (the carriers of germline mutations in these genes), whereas the remaining members, originally, are no more at risk than the general population.

  20. Functional Endoscopic Sinus Surgery as a primary modality of treatment for primary and recurrent nasal polyposis.

    Science.gov (United States)

    Gohar, Mohammad Shahid; Niazi, Saleem Asif; Niazi, Sohail Baber

    2017-01-01

    To describe the efficacy of Functional Endoscopic Sinus Surgery(FESS) in our set up in comparison with other published studies to treat primary and recurrent nasal polyposis. This descriptive study was conducted in 02 years at Ear Nose Throat Department Combined Military Hospital (CMH) Multan from October 2013 to October 2015. Convenient sample comprising 116 patients of both sexes of age group from 18 to 60 years were selected from ENT Out Patient Department, with documented diagnosis of nasal polyposis that underwent functional endoscopic sinus surgery. Out of 116 patients, 15 (12.9%) had recurrent nasal polyposis while 101 (87.1%) had primary nasal polyposis. Patients were assessed clinically. Preoperative nasal endoscopy and CT scan of nose and paranasal sinuses were performed in every patient to assess the extent of disease and evaluate the surgical anatomy. Patients were followed up 03 monthly, 06 monthly and after 01 year. Clinical signs of nasal polyposis were evaluated by nasal endoscopy at each follow up visit. There were 116 patients with documented diagnosis of nasal polyposis. Among these, 75 (64.7%) were male and 41 (35.3%) were female patients. Mean age of presentation in males was 39.1 years and that of females was 36.7 years. Only 15 patients (12.9%) developed recurrent disease within a year. Functional endoscopic sinus surgery is preferred as a primary treatment modality for primary and recurrent nasal polyposis. Mucosal polyps can be carefully debrided, the natural ostia enlarged, the ethmoid sinuses are unroofed, and sphenoid sinuses are opened in nasal cavity and sinus nasal mucosa is mostly preserved due to excellent visualization and surgical technique. Improvement in symptoms with minimal chance of recurrence may be expected in more than 90% patients.

  1. Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development.

    Science.gov (United States)

    Weren, Robbert D A; Venkatachalam, Ramprasath; Cazier, Jean-Baptiste; Farin, Henner F; Kets, C Marleen; de Voer, Richarda M; Vreede, Lilian; Verwiel, Eugène T P; van Asseldonk, Monique; Kamping, Eveline J; Kiemeney, Lambertus A; Neveling, Kornelia; Aben, Katja K H; Carvajal-Carmona, Luis; Nagtegaal, Iris D; Schackert, Hans K; Clevers, Hans; van de Wetering, Marc; Tomlinson, Ian P; Ligtenberg, Marjolijn J L; Hoogerbrugge, Nicoline; Geurts van Kessel, Ad; Kuiper, Roland P

    2015-06-01

    Heritable genetic variants can significantly affect the lifetime risk of developing cancer, including polyposis and colorectal cancer (CRC). Variants in genes currently known to be associated with a high risk for polyposis or CRC, however, explain only a limited number of hereditary cases. The identification of additional genetic causes is, therefore, crucial to improve CRC prevention, detection and treatment. We have performed genome-wide and targeted DNA copy number profiling and resequencing in early-onset and familial polyposis/CRC patients, and show that deletions affecting the open reading frame of the tumour suppressor gene FOCAD are recurrent and significantly enriched in CRC patients compared with unaffected controls. All patients carrying FOCAD deletions exhibited a personal or family history of polyposis. RNA in situ hybridization revealed FOCAD expression in epithelial cells in the colonic crypt, the site of tumour initiation, as well as in colonic tumours and organoids. Our data suggest that monoallelic germline deletions in the tumour suppressor gene FOCAD underlie moderate genetic predisposition to the development of polyposis and CRC.

  2. Multiple lymphomatous polyposis of the colon and rectum. Report of a case and review of the literature

    DEFF Research Database (Denmark)

    Mynster, T; Hultberg, B; Bülow, Steffen

    1994-01-01

    BACKGROUND: Multiple lymphomatous polyposis is a non-Hodgkin's centrocytic lymphoma that presents with polyposis of the mucosa and can be found anywhere in the gastrointestinal tract. METHODS: On the basis of a new case and 31 cases in the literature since 1971, the treatment is discussed...

  3. Polipose hiperplásica: relato de caso Hyperplastic polyposis: case report

    Directory of Open Access Journals (Sweden)

    Fabiano de Oliveira Poswar

    2010-09-01

    Full Text Available A polipose hiperplásica é uma condição rara, caracterizada pela presença de pólipos hiperplásicos múltiplos no cólon. Relata-se o caso de um paciente de 29 anos que apresentou polipose hiperplásica associada a pólipos mistos.Hyperplastic polyposis is a rare condition, characterized by the presence of multiple hiperplastic polyps in the colon. It is reported a case of a 29-year-old patient who presented hyperplastic polyposis associated with mixed polyps.

  4. Carcinosarcoma with choriocarcinomatous and osteosarcomatous differentiation in a patient with juvenile polyposis syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Parra-Medina

    2015-09-01

    Full Text Available Juvenile polyposis syndrome (JPS is an infrequent autosomal dominant hereditary predisposition to the occurrence of hamartomatous polyps in the colon and rectum. We describe the case of a 12-year-old boy with JPS associated with an abdominal tumor. Histological sections of the abdominal tumor showed components of adenocarcinoma, osteosarcoma, and choriocarcinoma. Immunohistochemistry was AE1/AE3, CK7, HCG and SALL4 positive. Juvenile polyposis syndrome patients are at increased risk of colorectal adenocarcinoma. However, we present a case of an adenocarcinoma associated with other unusual components. This association has not been reported before.

  5. POSSIBILITY OF PHARMACOMODULATION OF THE HYPERSENSITIVE RHINITIS JOINED WITH THE NASAL POLYPOSIS

    Directory of Open Access Journals (Sweden)

    Dejan Ursulović

    2001-11-01

    Full Text Available The research goai is to examine the effects of the local corticosteroidapplication to the number of eosinophils in the nasal secretion of the patients withhypersensitive rhinitis joined with the nasal polyposis. The study comprises 13patients with hypersensitive rhinitis joined with the nasal polyposis; 9 of them madeup the experimental group. The local corticosteroid (bechomethasone dipropionatein water spray was given at 12 hours in individual doses of 200 micrograms to theexperimental group patients in six weeks. During the treatment it was confirmed thatthere was a highly important reduction of the number of eosinophils of the nasalsecretion in the experimental group patients.

  6. Local IgE production in nonatopic nasal polyposis.

    LENUS (Irish Health Repository)

    Sheahan, Patrick

    2012-02-01

    INTRODUCTION: Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an eosinophilic T-helper 2 inflammatory response. Local production of IgE within nasal polyps (NPs) has been demonstrated, suggesting a role for local IgE in the pathogenesis of NP in atopic CRS patients. We hypothesized that local IgE specific to inhalant allergens may also play a role in the genesis of NP in nonatopic CRS patients. METHODS: Sinus and inferior turbinate tissue was obtained from nonatopic CRSwNP patients (n = 7), chronic rhinosinusitis without nasal polyps (CRSsNP) patients (n = 15), and healthy controls (n = 9) at the time of surgery. ImmunoCAP analysis (Phadia AB, Portage, MI) for 14 common inhalant antigens was performed on tissue homogenates to determine the antigen-specific response. RESULTS: Total IgE levels did not differ in sinus or turbinate tissue between CRSwNP, CRSsNP, or control patients. CRSwNP sinus tissue had higher levels of specific IgE for cockroach and plantain (p = .03) than other groups and elevated Alternaria IgE levels when compared with CRSsNP sinus tissue (p < .05). No significant differences were found for any of the other antigen-specific IgE levels. Fifty-seven percent of CRSwNP polyps demonstrated a polyclonal IgE response, whereas the other 43% had no demonstrable antigen-specific IgE. In contrast, only 17% of CRSsNP patients demonstrated a polyclonal response within sinus tissue, whereas 67% had no detectable antigen-specific IgE. There was no significant difference in levels of IgE in inferior turbinate tissue between the groups (p > .05). CONCLUSIONS: Localized mucosal IgE specific to common inhalant allergens appears to play a role in a subset of CRSwNP patients without evidence of systemic atopy.

  7. Alcoholic beverages and adenomatous polyps of the sigmoid colon: a study of male self-defence officials in Japan.

    Science.gov (United States)

    Kono, S; Ikeda, N; Yanai, F; Shinchi, K; Imanishi, K

    1990-12-01

    The drinking habits of 86 men with adenomatous polyps of the sigmoid colon were compared to those of 1184 men with normal colonoscopy among middle-aged male self-defence officials. After adjustment for rank, smoking history and rice consumption, total ethanol intake was positively associated with the risk of adenomatous polyps. The odds ratio (OR) was 2.4 (95% confidence interval (CI) 1.0-5.5) for men consuming at least 60 ml of ethanol per day. Among five alcoholic beverages (shochu, beer, sake, whiskey and wine), both sake and beer showed a dose-response relationship with the risk of adenomatous polyps although the association with beer was less striking. Shochu was the largest source of ethanol intake in the study population, but there was virtually no association between shochu consumption and adenomatous polyps. Men drinking wine had a significantly increased risk, but these men were too few to examine the relation in detail. The findings suggest that the consumption of specific alcoholic beverages rather than ethanol itself is associated with an increased risk of adenomatous polyps of the sigmoid colon.

  8. Evaluation of skin prick test sensitivity for 37 allergen extracts in atopic patients with nasal polyposis

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    Z A Ashour

    2014-01-01

    Conclusion Negative SPT does not exclude allergy in atopic patients with nasal polyposis. Thus, before delivering a diagnosis of nonallergic rhinitis in patients with negative SPT to common allergen, further tests are needed. We recommend further studies to evaluate the prevalence, immunopathology, and management of local allergic rhinitis.

  9. The risk of brain tumours in hereditary non-polyposis colorectal cancer (HNPCC)

    NARCIS (Netherlands)

    Vasen, HFA; Sanders, EACM; Taal, BG; Nagengast, FM; Griffioen, G; Menko, FH; Kleibeuker, JH; HouwingDuistermaat, JJ; Khan, PM

    1996-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is known to be associated with several extracolonic cancers, e.g., cancers of the endometrium, stomach, urinary tract, small bowel and ovary. An association between HNPCC and brain tumours has also been reported, although previous risk analysis did

  10. Overlapping Spectra of SMAD4 Mutations in Juvenile Polyposis (JP) and JP-HHT Syndrome

    NARCIS (Netherlands)

    Gallione, Carol; Aylsworth, Arthur S.; Beis, Jill; Berk, Terri; Bernhardt, Barbara; Clarks, Robin D.; Clericuzio, Carol; Danesino, Cesare; Drautz, Joanne; Fahl, Jeffrey; Fan, Zheng; Faughnan, Marie E.; Ganguly, Arupa; Garvie, John; Henderson, Katharine; Kini, Usha; Leedom, Trace; Ludman, Mark; Lux, Andreas; Maisenbacher, Melissa; Mazzucco, Sara; Olivieri, Carla; van Amstel, Johannes K. Ploos; Prigoda-Lee, Nadia; Pyeritz, Reed E.; Reardon, Willie; Vandezande, Kirk; Waldman, J. Deane; White, Robert I.; Williams, Charles A.; Marchuk, Douglas A.

    2010-01-01

    Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 and BMPR1A (for JP) and endoglin and ALK1 (for HHT). Recently, a combined syndrome of JP-HHT was described that is also caused by mutations in SMAD4. Although both JP

  11. Gastric Polyposis: A Rare Cause of Iron Deficiency Anemia in a Patient With Portal Hypertension

    Science.gov (United States)

    Macaron, Carole; Pai, Rish K.; Alkhouri, Naim

    2015-01-01

    Portal hypertension leading to gastric polyposis has rarely been reported. More common gastric manifestations of portal hypertension are portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE). We report a case of a patient in whom portal hypertension manifested as bleeding gastric polyps leading to transfusion-dependent iron deficiency anemia. PMID:26157923

  12. The risk of brain tumours in hereditary non-polyposis colorectal cancer (HNPCC)

    NARCIS (Netherlands)

    Vasen, HFA; Sanders, EACM; Taal, BG; Nagengast, FM; Griffioen, G; Menko, FH; Kleibeuker, JH; HouwingDuistermaat, JJ; Khan, PM

    1996-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is known to be associated with several extracolonic cancers, e.g., cancers of the endometrium, stomach, urinary tract, small bowel and ovary. An association between HNPCC and brain tumours has also been reported, although previous risk analysis did

  13. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer).

    NARCIS (Netherlands)

    Vasen, H.F.; Moslein, G.; Alonso, A.; Bernstein, I.; Bertario, L.; Blanco, I.; Burn, J.; Capella, G.; Engel, C.; Frayling, I.; Friedl, W.; Hes, F.J.; Hodgson, S.; Mecklin, J.P.; Moller, P.; Nagengast, F.M.; Parc, Y.; Renkonen-Sinisalo, L.; Sampson, J.R.; Stormorken, A.; Wijnen, J.

    2007-01-01

    Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago,

  14. Tubercular thyroiditis with multinodular goitre with adenomatous hyperplasia: a rare coexistence.

    Science.gov (United States)

    Chaurasia, Jai Kumar; Garg, Cheena; Agarwal, Arjun; Naim, Mohammed

    2013-09-25

    A 32-year-old Indian woman presented with swelling in the anterior part of the neck for the last 3 years. Clinical and radiological examination and fine needle aspiration cytology suggested the diagnosis of multinodular goitre. A subtotal thyroidectomy was performed by the surgeon and the specimen was submitted for the final diagnosis. Histological examination of the specimen revealed multiple caseating tubercular granulomas coexistent with multinodular goitre and adenomatous hyperplasia. The sections demonstrated acid-fast tubercle bacteria, confirming the diagnosis of tubercular thyroiditis. This case emphasises that tubercular thyroiditis should always be considered in patients with thyroid swelling or nodule, in countries where the prevalence of tuberculosis is high.

  15. Adenomatous polyp with intestinal metaplasia of the esophagus (Barrett esophagus) in a dog.

    Science.gov (United States)

    Gibson, C J; Parry, N M A; Jakowski, R M; Cooper, J

    2010-01-01

    Multiple endoscopic biopsy specimens of esophageal mucosa were received from a 13-year-old castrated male standard Poodle. The dog was presented for painful swallowing. Endoscopically, the distal aspect of the esophagus was inflamed with a polypoid mass that protruded into the esophageal lumen. Histologically, the stratified squamous epithelium overlying the mass and lining the adjacent esophageal mucosa was replaced by papillary projections covered by columnar epithelium with goblet cells supported by a fibrous stroma. This article reports a case of spontaneous esophageal adenomatous polyp with intestinal metaplasia (Barrett esophagus) and reviews the pathogenesis of esophageal metaplasia and adenocarcinoma.

  16. Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: correlations with stage and other clinicopathologic features

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, A L; Lyndrup, J;

    1992-01-01

    OBJECTIVE: This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. STUDY DESIGN: One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay...... of International Federation of Gynecology and Obstetrics grade. Age of patient, years since menopause, and previous estrogen treatment were not related to receptor content. In adenomatous hyperplasia high progesterone receptor levels were seen. CONCLUSION: The inverse correlation between clinical stage...... of endometrial carcinoma and content of estrogen and progesterone receptors may reflect tumor biologic behavior....

  17. Gardner’s syndrome presenting as duodenal carcinoma in a young male

    Directory of Open Access Journals (Sweden)

    Sarma YS

    2015-10-01

    Full Text Available Gardners syndrome (GS is a variant of familial adenomatous polyposis (FAP and presents with both colonic and extra colonic manifestations. It is an autosomal dominant disorder and results from mutations in adenomatous polyposis coli (APC gene. Patients with GS if not treated early will invariably develop colonic cancers at a much younger age than those with sporadic colonic carcinoma. These patients also develop other malignant tumours like duodenal cancers, gastric cancer, hepatoblastoma, papillary carcinoma of the thyroid and multifocal cholangiocarcinomas. With early diagnosis and treatment of colonic polyposis, adenocarcinoma of the duodenum has become the leading cause of death in FAP patients. The mean age at which duodenal carcinoma is diagnosed in FAP is 45-52 years. We report the rare occurrence of duodenal carcinoma as the presenting feature of Gardner’s syndrome in a young 25-year-old male with no obvious malignant changes in the colonic adenomas.

  18. High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome

    DEFF Research Database (Denmark)

    Aretz, S; Stienen, D; Uhlhaas, S;

    2007-01-01

    suspected to have JPS. RESULTS: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis...... polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted. Udgivelsesdato: 2007-Nov...

  19. Adenomatous hyperplasia of the mucous glands in captive Archey's frogs (Leiopelma archeyi).

    Science.gov (United States)

    Shaw, S D; Berger, L; Harvey, C; Alley, M R; Bishop, P J; Speare, R

    2017-05-01

    To describe the gross and light microscopic characteristics of skin lesions observed on the ventral skin of captive Archey's frogs (Leiopelma archeyi) between 2000 and 2012, and to investigate their occurrence, possible aetiology and association with survival. Postmortem skin samples were obtained for histological evaluation from 37 frogs, with and without skin lesions, that died while in captivity at Auckland Zoo between 2000 and 2012. Four frogs with skin lesions were biopsied under general anaesthesia and samples used for both light and transmission electron microscopy. The records of 94 frogs held at the University of Otago and Auckland Zoo between 2000-2012 were reviewed, which included some frogs recently collected from the wild. Information about the occurrence of skin lesions, and mortality associated with skin lesions was collated. Grossly the skin lesions varied in appearance; most were circular, pale grey papules, which measured from hyperplasia of the dermal mucous glands. The aetiology of this adenomatous hyperplasia is unknown, but factors associated with the captive environment are the most likely cause. This is the first description of adenomatous hyperplasia of the cutaneous mucous glands in amphibians.

  20. EPITHELIAL-CELL PROLIFERATION IN THE SIGMOID COLON OF PATIENTS WITH ADENOMATOUS POLYPS INCREASES DURING ORAL CALCIUM SUPPLEMENTATION

    NARCIS (Netherlands)

    KLEIBEUKER, JH; WELBERG, JWM; MULDER, NH; VANDERMEER, R; CATS, A; LIMBURG, AJ; KREUMER, WMT; HARDONK, MJ; DEVRIES, EGE

    1993-01-01

    To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementa

  1. Hereditary mixed polyposis syndrome due to a BMPR1A mutation.

    LENUS (Irish Health Repository)

    O'Riordan, J M

    2010-06-01

    The conditions Juvenile Polyposis Syndrome (JPS) and Hereditary Mixed Polyposis Syndrome (HMPS) are associated with an increased risk of colorectal carcinoma. The genetic mechanisms which explain these conditions have until recently been poorly understood. Recent interest has focused on the transforming growth factor (TGF)-beta signalling pathway and, in particular, on mutations in the SMAD4 gene. However, not all cases of JPS and HMPS have mutations in SMAD4 and focus has now shifted to other components of the TGF-beta pathway to clarify the genetic mechanisms involved in these conditions. In this report, we describe the significance of a bone morphogenetic protein receptor type 1A gene mutation in an Irish family.

  2. Inflammatory Duodenal Polyposis Associated with Primary Immunodeficiency Disease: A Novel Case Report

    Science.gov (United States)

    Shera, Irfan Ali; Khurshid, Sheikh Mudassir

    2017-01-01

    Agammaglobulinemia is a rare form of B-cell primary immunodeficiency disease characterized by reduced levels of IgG, IgA, or IgM and recurrent bacterial infections. Agammaglobulinemia is most commonly associated with diffuse nodular lymphoid hyperplasia. Duodenal polyps are a rare entity; however, due to wide use of esophagogastroduodenoscopy, incidental diagnosis of duodenal polyps appears to be increasing. Although inflammatory duodenal polyposis has been reported in the literature, its association with common variable immunodeficiency has not been reported till date to the best of our knowledge. We report a case of a 59-year-old male with chronic symptoms of agammaglobulinemia associated with inflammatory duodenal polyposis. PMID:28163721

  3. Inflammatory Duodenal Polyposis Associated with Primary Immunodeficiency Disease: A Novel Case Report

    Directory of Open Access Journals (Sweden)

    Irfan Ali Shera

    2017-01-01

    Full Text Available Agammaglobulinemia is a rare form of B-cell primary immunodeficiency disease characterized by reduced levels of IgG, IgA, or IgM and recurrent bacterial infections. Agammaglobulinemia is most commonly associated with diffuse nodular lymphoid hyperplasia. Duodenal polyps are a rare entity; however, due to wide use of esophagogastroduodenoscopy, incidental diagnosis of duodenal polyps appears to be increasing. Although inflammatory duodenal polyposis has been reported in the literature, its association with common variable immunodeficiency has not been reported till date to the best of our knowledge. We report a case of a 59-year-old male with chronic symptoms of agammaglobulinemia associated with inflammatory duodenal polyposis.

  4. Adenomatous hyperplasia of the rete testis: A rare intrascrotal lesion managed with limited testicular excision

    Directory of Open Access Journals (Sweden)

    Francesco Catanzariti

    2016-10-01

    Full Text Available Introduction: Testicular cancer is one of the most frequent in young men and its incidence is increasing in recent years because of incidental finding during routine ultrasound exams. Adenomatous hyperplasia of the rete testis is one of the benign and rare pathological types incidentally detected and very few cases are described in the literature. Case report: A 40 years old man come to our attention for a balanoposthitis without testicular pain. During andrological examination we performed palpation of the testes and we noticed a palpable nodule of hard consistency in the left testicle. We then performed an ultrasound exam of the testis which highlighted the presence of an intra-didymus neoformation with diameters of 1.2 x 1.6 cm and with the presence of cysts inside. We also performed blood tests to check tumor markers alpha fetoprotein, beta hCG and LDH which resulted inside the normal range. We then conducted a chest and abdomen CT scan that showed no pathological elements. Therefore, as we suspected that this tumor was benign, we performed an enucleation of the neoplasm. The definitive histological examination revealed the presence of dilated ducts lined with epithelial cubic-columnar cells with clear cytoplasm rich in glycogen and the pathologist so concluded that the tumor could be classified as adenomatous hyperplasia of the rete testis. At three months of follow up, the patient doesn’t have any recurrent lesion to either testicles. Discussion: Adenomatous hyperplasia of the rete testis is a very rare intrascrotal lesion. This histological type is the most frequent between benign lesion of the ovary, but few works in literature reported this histological type in the male gonad and, in most of these works, authors described these lesion at epididymis. Conclusion: We believe that a conservative approach must be considered mandatory in case of testicular lesions 1.5 cm in diameter. A radical approach might have alterate fertility of the

  5. [Association of brownish polyposis and diverticulosis in the sigmoid colon -- a case of mucosal prolapse syndrome].

    Science.gov (United States)

    Karácsony, Tibor; Joó, Judit; Berczi, Lajos; Antal, András

    2011-10-01

    The authors present a case of a 48 year-old man, who was diagnosed with several brownish sigmoid polyps of 1-2 cm size and diverticulosis on colonoscopy. Subsequently, laparoscopic sigmoid resection was carried out due to lower gastrointestinal bleeding. Histological examination revealed diverticulosis associated with polyposis. This rare entity is known in the literature as prolapse-type inflammatory polyp, which is a type of mucosal prolapse syndrome. The brownish discolouration was caused by hemosiderin deposition.

  6. KARTAGENER’S SYNDROME PRESENTED AS PARANASAL POLYPOSIS WITH RECURRENT EPISTAXIS: A RARE CLINICAL CASE REPORT

    Directory of Open Access Journals (Sweden)

    Palaparti Jayakar Babu

    2012-02-01

    Full Text Available Genetically determined syndromes of ciliary dyskinesia prevent normal transport of mucus from the bronchial tree to the mouth and result in serious impairment of lung defence system.male infertility was sometimes associated with Immotile spermatozoa. Approximately half of patients with Primary Ciliary Dyskinesia have full triad of kartgeners’s syndrome, give history of recurrent sinusitis and lower respiratory tract infection from early life to adulthood. Kartagener’s syndrome has been considered to be a sub group in a heterogenous collection of disorders to which Immotile Ciliary Syndrome or Dyskinitic cilia syndrome have been applied. There may also be a link with retinitis pigmentosa and hearing loss. Kartagener’s syndrome with paranasal polyposis is a uncommon presentation shown in our case. We report an adult female of 23 of age having Recurrent sinusitis,Bronchiectasis and Dextrocardia with Situs inversus and with Paranasal polyposis showing recurrent epistaxis. Conclusion: Kartagener’s syndrome with paranasal sinusitis is common but paranasal polyposis with epistaxis is uncommon way of presentation. [National J of Med Res 2012; 2(1.000: 99-101

  7. Predictive gene signatures: molecular markers distinguishing colon adenomatous polyp and carcinoma.

    Science.gov (United States)

    Drew, Janice E; Farquharson, Andrew J; Mayer, Claus Dieter; Vase, Hollie F; Coates, Philip J; Steele, Robert J; Carey, Francis A

    2014-01-01

    Cancers exhibit abnormal molecular signatures associated with disease initiation and progression. Molecular signatures could improve cancer screening, detection, drug development and selection of appropriate drug therapies for individual patients. Typically only very small amounts of tissue are available from patients for analysis and biopsy samples exhibit broad heterogeneity that cannot be captured using a single marker. This report details application of an in-house custom designed GenomeLab System multiplex gene expression assay, the hCellMarkerPlex, to assess predictive gene signatures of normal, adenomatous polyp and carcinoma colon tissue using archived tissue bank material. The hCellMarkerPlex incorporates twenty-one gene markers: epithelial (EZR, KRT18, NOX1, SLC9A2), proliferation (PCNA, CCND1, MS4A12), differentiation (B4GANLT2, CDX1, CDX2), apoptotic (CASP3, NOX1, NTN1), fibroblast (FSP1, COL1A1), structural (ACTG2, CNN1, DES), gene transcription (HDAC1), stem cell (LGR5), endothelial (VWF) and mucin production (MUC2). Gene signatures distinguished normal, adenomatous polyp and carcinoma. Individual gene targets significantly contributing to molecular tissue types, classifier genes, were further characterised using real-time PCR, in-situ hybridisation and immunohistochemistry revealing aberrant epithelial expression of MS4A12, LGR5 CDX2, NOX1 and SLC9A2 prior to development of carcinoma. Identified gene signatures identify aberrant epithelial expression of genes prior to cancer development using in-house custom designed gene expression multiplex assays. This approach may be used to assist in objective classification of disease initiation, staging, progression and therapeutic responses using biopsy material.

  8. Predictive gene signatures: molecular markers distinguishing colon adenomatous polyp and carcinoma.

    Directory of Open Access Journals (Sweden)

    Janice E Drew

    Full Text Available Cancers exhibit abnormal molecular signatures associated with disease initiation and progression. Molecular signatures could improve cancer screening, detection, drug development and selection of appropriate drug therapies for individual patients. Typically only very small amounts of tissue are available from patients for analysis and biopsy samples exhibit broad heterogeneity that cannot be captured using a single marker. This report details application of an in-house custom designed GenomeLab System multiplex gene expression assay, the hCellMarkerPlex, to assess predictive gene signatures of normal, adenomatous polyp and carcinoma colon tissue using archived tissue bank material. The hCellMarkerPlex incorporates twenty-one gene markers: epithelial (EZR, KRT18, NOX1, SLC9A2, proliferation (PCNA, CCND1, MS4A12, differentiation (B4GANLT2, CDX1, CDX2, apoptotic (CASP3, NOX1, NTN1, fibroblast (FSP1, COL1A1, structural (ACTG2, CNN1, DES, gene transcription (HDAC1, stem cell (LGR5, endothelial (VWF and mucin production (MUC2. Gene signatures distinguished normal, adenomatous polyp and carcinoma. Individual gene targets significantly contributing to molecular tissue types, classifier genes, were further characterised using real-time PCR, in-situ hybridisation and immunohistochemistry revealing aberrant epithelial expression of MS4A12, LGR5 CDX2, NOX1 and SLC9A2 prior to development of carcinoma. Identified gene signatures identify aberrant epithelial expression of genes prior to cancer development using in-house custom designed gene expression multiplex assays. This approach may be used to assist in objective classification of disease initiation, staging, progression and therapeutic responses using biopsy material.

  9. Histological study of PIVKA-II expression in hepatocellular carcinoma and adenomatous hyperplasia.

    Science.gov (United States)

    Miskad, U A; Yano, Y; Nakaji, M; Kishi, S; Itoh, H; Kim, S R; Ku, Y; Kuroda, Y; Hayashi, Y

    2001-12-01

    Although serum concentration of protein induced vitamin K absence or antagonist II (PIVKA-II) has been widely used for diagnosing hepatocellular carcinoma (HCC), little information is available concerning tissue PIVKA-II as an immunohistochemical marker for liver histology. In this study, we examined the expression of PIVKA-II in precancerous nodules (adenomatous hyperplasia) and various differentiation grades of HCC by immunohistochemical study using the monoclonal anti-PIVKA-II antibody (MU-3). We examined the relationship between tissue PIVKA-II staining and serum PIVKA-II level, tumor histology and tumor size. PIVKA-II was mainly detected in the cytoplasm of the HCC cells. The positive rates of PIVKA-II were as follows: adenomatous hyperplasia (AH), 0% (0/9); well-differentiated HCC, 65% (15/23); moderately differentiated HCC, 85% (22/26); poorly differentiated HCC, 54% (7/13). The expression of tissue PIVKA-II staining in moderately differentiated HCC was significantly higher than in well- or poorly differentiated HCC, whereas the serum PIVKA-II level in poorly differentiated HCC was higher than well- or moderately differentiated HCC. There was no relationship between the expression of PIVKA-II in cancer tissues and serum levels of PIVKA-II. Immunohistochemical studies revealed that PIVKA-II was expressed even in small-sized or well-differentiated HCC cells, but expression was not detected in AH. It was concluded that PIVKA-II is a useful immunohistochemical marker, even in small-sized or well-differentiated HCC.

  10. Thermal coagulation-induced changes of the optical properties of normal and adenomatous human colon tissues in vitro in the spectral range 400-1100 nm

    Energy Technology Data Exchange (ETDEWEB)

    Ao Huilan; Xing Da; Wei Huajiang; Gu Huaimin [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, ina Normal University, Guangzhou 510631 (China); Wu Guoyong; Lu Jianjun [Department of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China)], E-mail: xingda@scnu.edu.cn

    2008-04-21

    The absorption coefficients, the reduced scattering coefficients and the optical penetration depths for native and coagulated human normal and adenomatous colon tissues in vitro were determined over the range of 400-1100 nm using a spectrophotometer with an internal integrating sphere system, and the inverse adding-doubling method was applied to calculate the tissue optical properties from diffuse reflectance and total transmittance measurements. The experimental results showed that in the range of 400-1100 nm there were larger absorption coefficients (P < 0.01) and smaller reduced scattering coefficients (P < 0.01) for adenomatous colon tissues than for normal colon tissues, and there were smaller optical penetration depths for adenomatous colon tissues than for normal colon tissues, especially in the near-infrared wavelength. Thermal coagulation induced significant increase of the absorption coefficients and reduced scattering coefficients for the normal and adenomatous colon tissues, and significantly reduced decrease of the optical penetration depths for the normal and adenomatous colon tissues. The smaller optical penetration depth for coagulated adenomatous colon tissues is a disadvantage for laser-induced thermotherapy (LITT) and photodynamic therapy (PDT). It is necessary to adjust the application parameters of lasers to achieve optimal therapy.

  11. Microsatellite instability in tumor and nonneoplastic colorectal cells from hereditary non-polyposis colorectal cancer and sporadic high microsatellite-instable tumor patients.

    Science.gov (United States)

    Dietmaier, W; Gänsbauer, S; Beyser, K; Renke, B; Hartmann, A; Rümmele, P; Jauch, K W; Hofstädter, F; Rüschoff, J

    2000-01-01

    Genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) have been frequently studied in various tumor types. Genetic heterogeneity of nonneoplastic cells has not yet been sufficiently investigated. However, genomic instability in normal cells could be a potentially important issue, in particular when these cells are used as reference in LOH and MSI analyses of tumor samples. In order to investigate possible genetic abnormalities in normal colorectal cells of tumor patients, MSI analyses of normal colonic mucosa were performed. Up to 15 different laser-microdissected normal regions containing 50-150 cells were investigated in each of 15 individual microsatellite-stable, sporadic high microsatellite-instable (MSI-H) and hereditary non-polyposis coli cancer (HNPCC) colorectal cancer patients. Frequent MSI and heterogeneity in the MSI pattern were found both in normal and tumor cells from 10 HNPCC and sporadic MSI-H tumor patients whose tumors had defect mismatch repair protein expressions. This observation shows that MSI can also occur in nonneoplastic cells which has to be considered in MSI analyses for molecular HNPCC screening. In addition, considerable genetic heterogeneity was detected in all MSI-H (sporadic and HNPCC) tumors when analyzing five different regions with less than 150 cells, respectively. These differences were not detectable in larger tumor regions containing about 10,000 cells. Thus, heterogeneity of the MSI pattern (e.g. intratumoral MSI) is an important feature of tumors with the MSI-H phenotype.

  12. Importance of the surrounding colonic mucosa in distinguishing between hyperplastic and adenomatous polyps during acetic acid chromoendoscopy

    Institute of Scientific and Technical Information of China (English)

    Jeong Hwan Kim; Sun-Young Lee; Byung Kook Kim; Won Hyeok Choe; So Young Kwon; In-Kyung Sung; Hyung-Seok Park; Choon-Jo Jin

    2008-01-01

    AIM: To examine the characteristics of colonic polyps, where it is difficult to distinguish adenomatous polyps from hyperplastic polyps, with the aid of acetic acid chromoendoscopy.METHODS: Acetic acid spray was applied to colonic polyps smaller than 10 mm before complete excision. Endoscopic images were taken before and 15-30 s after the acetic acid spray. Both pre- and post-sprayed images were shown to 16 examiners, who were asked to interpret the lesions as either hyperplastic or adenomatous polyps. Regression analysis was performed to determine which factors were most likely related to diagnostic accuracy.RESULTS: In 50 cases tested by the 16 examiners, the overall accuracy was 62.4% (499/800). Regression analysis demonstrated that surrounding colonic mucosa was the only factor that was significantly related to accuracy in discriminating adenomatous from hyperplastic polyps (P < 0.001). Accuracy was higher for polyps with linear surrounding colonic mucosa than for those with nodular surrounding colonic mucosa (P < 0.001), but was not related to the shape, location, or size of the polyp.CONCLUSION: The accuracy of predicting histology is significantly related to the pattern of colonic mucosa surrounding the polyp. Making a histological diagnosis of colon polyps merely by acetic acid spray is helpful for colon polyps with linear, regularly patterned surrounding colonic mucosa, and less so for those with nodular, irregularly patterned surrounding colonic mucosa.

  13. Differential RNA-seq analysis comparing APC-defective and APC-restored SW480 colorectal cancer cells

    OpenAIRE

    King, Lauren E.; Love, Christopher G.; Sieber, Oliver M.; Faux, Maree C.; Antony W Burgess

    2016-01-01

    The adenomatous polyposis coli (APC) tumour suppressor gene is mutated in about 80% of colorectal cancers (CRC) Brannon et al. (2014) [1]. APC is a large multifunctional protein that regulates many biological functions including Wnt signalling (through the regulation of beta-catenin stability) Reya and Clevers (2005) [2], cell migration Kroboth et al. (2007), Sansom et al. (2004) [3], [4], mitosis Kaplan et al. (2001) [5], cell adhesion Faux et al. (2004), Carothers et al. (2001) [6], [7] and...

  14. Nuclear APC

    OpenAIRE

    Neufeld, Kristi L.

    2009-01-01

    Mutational inactivation of the tumor suppressor gene APC (Adenomatous polyposis coli) is thought to be an initiating step in the progression of the vast majority of colorectal cancers. Attempts to understand APC function have revealed more than a dozen binding partners as well as several subcellular localizations including at cell-cell junctions, associated with microtubules at the leading edge of migrating cells, at the apical membrane, in the cytoplasm and in the nucleus. The present chapte...

  15. Targeting Prostate Cancer Metastasis

    Science.gov (United States)

    2016-09-01

    allowing for drug administration by immer- sion) [34]. For many purpose screening can be done before the age of free feeding and thus use of zebraf- ish...to combat UM metastases [43]. The results of these studies display the complementary advantages that the zebrafish model provides when it is used...2000). 15 Haramis AP, Hurlstone A, van der Velden Y et al. Adenomatous polyposis coli- deficient zebrafish are susceptible to digestive tract neoplasia

  16. Thoracic Aortic Disease in Two Patients with Juvenile Polyposis Syndrome and SMAD4 mutations

    Science.gov (United States)

    Teekakirikul, Polakit; Milewicz, Dianna M.; Miller, David T.; Lacro, Ronald V.; Regalado, Ellen S.; Rosales, Ana Maria; Ryan, Daniel P.; Toler, Tomi L.; Lin, Angela E.

    2012-01-01

    Dilation or aneurysm of the ascending aorta can progress to acute aortic dissection (Thoracic Aortic Aneurysms and Aortic Dissections, TAAD). Mutations in genes encoding TGF-β related proteins (TGFBR1, TGFBR2, FBN1, and SMAD3) cause syndromic and inherited TAAD. SMAD4 mutations are associated with juvenile polyposis (JPS) and a combined JPS-hereditary hemorrhagic telangiectasia (HHT) known as JPS-HHT. A family with JPS-HHT was reported to have aortic root dilation and mitral valve abnormalities. We report on two patients with JPS-HHT with SMAD4 mutations associated with thoracic aortic disease. The first patient, an 11-year-old boy without Marfan syndrome features, had JPS and an apparently de novo SMAD4 mutation (c.1340_1367dup28). Echocardiography showed mild dilation of the aortic annulus and aortic root, and mild dilation of the sinotubular junction and ascending aorta. Computed tomography confirmed aortic dilation and showed small pulmonary arteriovenous malformations (PAVM). The second patient, a 34-year-old woman with colonic polyposis, HHT, and Marfan syndrome, had a SMAD4 mutation (c.1245_1248delCAGA). Echocardiography showed mild aortic root dilation. She also had PAVM and hepatic focal nodular hyperplasia. Her family history was significant for polyposis, HHT, thoracic aortic aneurysm, and dissection and skeletal features of Marfan syndrome in her father. These two cases confirm the association of thoracic aortic disease with JPS-HHT resulting from SMAD4 mutations. We propose that the thoracic aorta should be screened in patients with SMAD4 mutations to prevent untimely death from dissection. This report also confirms that SMAD4 mutations predispose to TAAD. PMID:23239472

  17. HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME PADA WANITA UMUR 16 TAHUN

    Directory of Open Access Journals (Sweden)

    Asril Zahari

    2011-09-01

    Full Text Available AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC

  18. Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

    Institute of Scientific and Technical Information of China (English)

    Akira Hokama; Nobuyuki Takasu; Jiro Fujita; Takeaki Tomoyose; Yu-ichi Yamamoto; Takako Watanabe; Tetsuo Hirata; Fukunori Kinjo; Seiya Kato; Koichi Ohshima; Hiroshi Uezato

    2008-01-01

    Multiple lymphomatous polyposis (HLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL is reviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

  19. Microsatellite Instability and Relative Gene Expressions in Sporadic and Familial Adenomatous Polyposis Adenomas%结直肠腺瘤的微卫星不稳定状态与相关基因表达的研究

    Institute of Scientific and Technical Information of China (English)

    程蕾; 王慧萍; 黄琼; 来茂德

    2004-01-01

    应用微切割-聚合酶链反应-单链长度多态性(PCR-SSLP)的方法,检测59例62个结直肠腺瘤,包括散发性腺瘤及家族性腺瘤性息肉病(FAP)腺瘤在BAT26等16个微卫星基因座在结直肠腺瘤标本的微卫星不稳定性(MSI)状态;并应用免疫组织化学SP法检测β-连接素(β-catenin)、TP53、BAX等的表达情况,初步探讨错配修复(MMR)基因在结直肠癌发生的早期即腺瘤阶段的作用及其意义.结果显示:(1)腺瘤16个基因座的总MSI发生率为14.4%;同一病人的不同腺瘤在某些相同的基因座表现出不同的MSI状态;(2)5例FAP病人均表现为MSI-L,其中有3例在hMSH3基因座表现为MSI阳性;(3)β-连接素在腺瘤和腺癌细胞膜阳性率分别为42.9%和11.4%,表达差异有显著统计学意义(P<0.001);(4)TP53、D5S346、TCF4(A)9、TGFβ-RⅡ(GT)3、TGFβRⅡ(A)10等微卫星基因座的MSI改变与相应的免疫组织化学指标TP53、β-连接素、TGFβRⅡ等在腺瘤及腺癌中的阳性表达有密切关系.可以推断:(1)在结直肠癌发生发展的早期即腺瘤阶段即可表现微卫星不稳定性,腺瘤中存在1p染色体的改变、APC基因的改变及TGFβ-信号转导途径的异常;(2)随着腺瘤向腺癌的进展,β-连接素的阳性着色由细胞膜转移至细胞内,而且胞浆阳性强度增加;可以推断腺瘤中APC-β-联蛋白-TCF4信号转导途径的异常.

  20. Concomitant hepatocellular adenoma and adenomatous hyperplasia in a patient without cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Chuan-Yuan Hsu; Cheng-Hsin Chu; Shee-Chan Lin; Fee-Shih Yang; Tsen-Long Yang; Kuo-Ming Chang

    2003-01-01

    AIM: Hepatocelluar adenoma (HCA) and adenomatous hyperplasia (AH) are rare benign tumors of the liver. HCA is usually found in women who use oral contraceptives. AH usually occurs in patients with liver cirrhosis. Both tumors have potential for malignant transformation.METHODS: We described a male adult with chronic liver disease (CLD) who had been known to be a hepatitis B carrier (HBV) for years. He was found to have a spaceoccupying lesion with a suspicion of hepatocellular carcinoma (HCC) by abdominal ultrasonography. His α-fetoprotein (AFP)was normal. Angiographic findings were consistent with the diagnosis of HCC, he wished to avoid an operation, was treated with transcatheter hepatic arterial embolization.RESULTS: He subsequently consented to surgery, and a right lobectomy was performed. The liver pathology disclosed HCA with nuclear dysplasia and post-embolization effects.In addition, there were multiple small foci of AH with nuclear dysplasia in the resected liver. Although he had some focal areas of cirrhosis-like change or post-embolization effect,the AH was associated only with normal liver tissue.CONCLUSION: This case confirms that HCA and AH may resemble HCC on imaging studies, and that AH may occur in CLD in the absence of cirrhotic change.

  1. Asymptomatic Multiple Lymphomatous Polyposis Identified during Staging Bidirectional Endoscopy of Mantle Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Sonja P. Dawsey

    2016-10-01

    Full Text Available Multiple lymphomatous polyposis (MLP as an extranodal manifestation of mantle cell lymphoma (MCL in the gastrointestinal tract is rare and not often reported in the literature. We describe the case of a 63-year-old female with asymptomatic MLP found during staging bidirectional endoscopy of MCL. The patient presented only with dyspnea, but was found on physical exam to have diffuse lymphadenopathy, and subsequent positron emission tomography (PET CT showed extensive lymph node adenopathy consistent with lymphoma. Excisional lymph node biopsy revealed high-risk MCL. Prior to therapy, staging bidirectional endoscopy was performed, which revealed duodenal bulb polyps and diffuse polyposis in the colon. Biopsies showed atypical lymphoid infiltrate identical to the initial excisional lymph node biopsy. The patient underwent aggressive induction therapy, chemotherapy and bone marrow transplantation. Four months later, repeat colonoscopy and biopsies showed normal mucosa, and repeat PET CT showed no evidence of systemic disease. Eight months later, the patient began having symptoms consistent with cauda equina syndrome, and she was found to have leptomeningeal recurrence of MCL. In spite of other medical treatment, the patient’s MCL progressed and she passed away 3 years after the initial presentation.

  2. Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps

    Directory of Open Access Journals (Sweden)

    Lu Deng

    2017-06-01

    Full Text Available Background: Colorectal cancer is one of the leading causes of cancer deaths worldwide. The detection and removal of the precursors to colorectal cancer, adenomatous polyps, is the key for screening. The aim of this study was to develop a clinically scalable (high throughput, low cost, and high sensitivity mass spectrometry (MS-based urine metabolomic test for the detection of adenomatous polyps. Methods: Prospective urine and stool samples were collected from 685 participants enrolled in a colorectal cancer screening program to undergo colonoscopy examination. Statistical analysis was performed on 69 urine metabolites measured by one-dimensional nuclear magnetic resonance spectroscopy to identify key metabolites. A targeted MS assay was then developed to quantify the key metabolites in urine. A MS-based urine metabolomic diagnostic test for adenomatous polyps was established using 67% samples (un-blinded training set and validated using the remaining 33% samples (blinded testing set. Results: The MS-based urine metabolomic test identifies patients with colonic adenomatous polyps with an AUC of 0.692, outperforming the NMR based predictor with an AUC of 0.670. Conclusion: Here we describe a clinically scalable MS-based urine metabolomic test that identifies patients with adenomatous polyps at a higher level of sensitivity (86% over current fecal-based tests (<18%.

  3. Increased polyp detection using narrow band imaging compared with high resolution endoscopy in patients with hyperplastic polyposis syndrome

    NARCIS (Netherlands)

    K.S. Boparai; F.J.C. van den Broek; S. van Eeden; P. Fockens; E. Dekker

    2011-01-01

    Hyperplastic polyposis syndrome (HPS) is associated with colorectal cancer and is characterized by multiple hyperplastic polyps, sessile serrated adenomas (SSAs) and adenomas. Narrow band imaging (NBI) may improve the detection of polyps in HPS. We aimed to compare polyp miss rates with NBI with tho

  4. Identification of coding exon 3 duplication in the BMPR1A gene in a patient with juvenile polyposis syndrome.

    Science.gov (United States)

    Yamaguchi, Junya; Nagayama, Satoshi; Chino, Akiko; Sakata, Ai; Yamamoto, Noriko; Sato, Yuri; Ashihara, Yuumi; Kita, Mizuho; Nomura, Sachio; Ishikawa, Yuichi; Igarashi, Masahiro; Ueno, Masashi; Arai, Masami

    2014-10-01

    Juvenile polyposis syndrome is an autosomal dominant inherited disorder characterized by multiple juvenile polyps arising in the gastrointestinal tract and an increased risk of gastrointestinal cancers, specifically colon cancer. BMPR1A and SMAD4 germline mutations have been found in patients with juvenile polyposis syndrome. We identified a BMPR1A mutation, which involves a duplication of coding exon 3 (c.230+452_333+441dup1995), on multiple ligation dependent probe amplification in a patient with juvenile polyposis syndrome. The mutation causes a frameshift, producing a truncated protein (p.D112NfsX2). Therefore, the mutation is believed to be pathogenic. We also identified a duplication breakpoint in which Alu sequences are located. These results suggest that the duplication event resulted from recombination between Alu sequences. To our knowledge, partial duplication in the BMPR1A gene has not been reported previously. This is the first case report to document coding exon 3 duplication in the BMPR1A gene in a patient with juvenile polyposis syndrome.

  5. Escherichia Coli

    Science.gov (United States)

    Goodsell, David S.

    2009-01-01

    Diverse biological data may be used to create illustrations of molecules in their cellular context. I describe the scientific results that support a recent textbook illustration of an "Escherichia coli cell". The image magnifies a portion of the bacterium at one million times, showing the location and form of individual macromolecules. Results…

  6. Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques

    Institute of Scientific and Technical Information of China (English)

    Hua-Jiang Wei; Da Xing; Jian-Jun Lu; Huai-Min Gu; Guo-Yong Wu; Ying Jin

    2005-01-01

    AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods.METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integratingsphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable.RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength,and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength.There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa,and there

  7. Apoplexia hipofisária intradenomatosa Intra-adenomatous pituitary apoplexy

    Directory of Open Access Journals (Sweden)

    Flávio Freinkel Rodrigues

    1997-01-01

    Full Text Available Os autores analisam a literatura sobre apoplexia hipofisária intradenomatosa, enfocando a fisiopatologia, o diagnóstico e a conduta terapêutica. Estudam 5 casos , de uma série de 86 pacientes com tumores hipofisários que desenvolveram esta síndrome e que foram diagnosticados e acompanhados pelos serviços de Neurocirurgia e Endocrinologia do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro. Todos os casos, a partir da suspeita clínica, tiveram o diagnóstico confirmado por estudo de tomografia computadorizada de crânio e/ou ressonância magnética de crânio. O tratamento de escolha foi cirúrgico. As conclusões apontam para as dificuldades diagnósticas desta situação clínica e da urgência na instituição da terapia.The authors review the literature on intra-adenomatous pituitary apoplexy with special emphasis on pathophysiology, diagnosis and therapeutic approach. They present five cases, from a series of 86 patients with pituitary tumors, that developed this syndrome. The patients were diagnosed and followed by the Neurosurgery and Endocrinology Services of Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro. Diagnosis was confirmed by CT-Scan and MRI in all cases , and the treatment of choice was surgical. Conclusions point to the diagnostic difficulties and the urgency of treatment in this clincal setting.

  8. Do mtDNA Deletions Play a Role in the Development of Nasal Polyposis?

    Directory of Open Access Journals (Sweden)

    Arzu Tatar

    2014-04-01

    Full Text Available Objective:Nasal polyposis (NP is an inflammatory disease of the nasal mucosa and paranasal sinuses. Mitochondria are the cellular organelles which produce cellular energy by Oxidative Phosphorylation (OXPHOS, and they have own inheritance material, mtDNA. mtDNA is affected by reactive oxygen samples (ROS which are produced by both OXPHOS and the inflammatory process. The aim of this study was to investigate the 4977 bp and 7400 bp deletions of mtDNA in nasal polyposis tissue, and to indicate the possible association of mtDNA deletions with NP. Methods:Thirty-three patients, aged 15 to 65 years, with nasal polyposis were selected to be assessed for mitochondrial DNA deletions. The patients with possible mtDNA mutations due to mitochondrial disease, being treated with radiotherapy, of advanced age, with a familiar history, aspirin hypersensitivity, or a history of asthma, were excluded. Polyp excision surgery was applied to the treatment of the NP, and after histopathological diagnosis 1x1 cm of polyp tissue samples were used to isolate mtDNA. The 4977 bp and 7400 bp deletion regions, and two control regions of mtDNA were assessed by using four pairs of primers. DNA extractions from the NP tissues and peripheral blood samples of the patients were made, and then Polymerase Chain Reactions (PCR were made. PCR products were separated in 2% agarose gel.Results:No patient had either the 4977 bp deletion or the 7400 bp deletion in their NP tissue, and neither were these deletions evident in their peripheral blood. Two control sequences, one of them from a non-deleted region, and the other from a possible deletion region, were detected in the NP tissues and peripheral blood of all the patients.Conclusions:We had anticipated that some mtDNA deletion might have occurred in NP tissue due to the increased ROS levels caused by chronic inflammation, but we did not detect any deletion. Probably, the duration of inflammation in NP is insufficient to form mt

  9. Role of APC and DNA mismatch repair genes in the development of colorectal cancers

    Directory of Open Access Journals (Sweden)

    Roy Deodutta

    2003-12-01

    Full Text Available Abstract Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP and the hereditary nonpolyposis colorectal cancers (HNPCC. The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC and DNA mismatch repair (MMR genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.

  10. APC基因与结直肠肿瘤

    Institute of Scientific and Technical Information of China (English)

    梁君林; 高枫; 唐宗江

    2001-01-01

    @@ "正常结直肠上皮-腺瘤性息肉-侵袭性癌"病理转变是一个多步骤、多基因参与的过程,涉及到癌基因的激活和抑癌基因的失活.APC基因(adenomatous polyposis coli gene)的改变不仅可引起家族性腺瘤性息肉病(familial adenomatous polyposis,FAP),而且参与散发性结直肠肿瘤的形成.近年随着分子生物学技术的提高,APC基因在结直肠肿瘤发生发展中的机理研究得到不断深入.

  11. Recurrent Fistula between Ileal Pouch and Vagina—Successful Treatment with a Gracilis Muscle Flap

    Directory of Open Access Journals (Sweden)

    Feride Aydin

    2009-01-01

    Full Text Available Fistulae between an ileal pouch and the vagina are an uncommon complication of ileal pouch-anal anastomosis following proctocolectomy and mucosectomy in patients with familial adenomatous polyposis coli. Several reports describe the successful use of muscle flaps to close recurrent pouch-vaginal-fistulae (PVF. However, series only contain small numbers and an optimal management has not yet been determined. We report the case of a 26-year old woman with a third recurrence of a PVF after proctocolectomy for treatment of familial adenomatous polyposis in October 2005. Because local approaches failed, definitive closure of the fistula was achieved by interposition of a gracilis muscle flap between the pouch-anal anastomosis and the vagina. The postoperative course was uneventful; the patient was discharged 7 days after surgery and remained free of recurrence and symptomatic complaints for 22 months now. The gracilis muscle flap proved to be an effective method in the treatment of recurrent PVF.

  12. Adenomatous hyperplasia of the thyroid gland in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary and Hudson Bay, Quebec, Canada.

    Science.gov (United States)

    Mikaelian, I; Labelle, P; Kopal, M; De Guise, S; Martineau, D

    2003-11-01

    We evaluated thyroid gland lesions in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary (n = 16) and Hudson Bay (n = 14). Follicular cysts and nodules of adenomatous hyperplasia of the thyroid gland were found in eight and nine adults from the St. Lawrence Estuary (n = 10), respectively, and in four and six adults from Hudson Bay (n = 14), respectively. The total volume of the lesions of thyroid adenomatous hyperplasia was positively correlated with age in both populations. Comparison between populations could not be performed because of differences in age structures of sample groups. Beluga whales from both populations have unique thyroid lesions among marine mammals.

  13. Genetic mapping of the hereditary mixed polyposis syndrome to chromosome 6q

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, H.J.W.; Whitelaw, S.C.; Hodgson, S.V.; Northover, J.M.A.; Talbot, I.C. [and others

    1996-04-01

    Hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas. HMPS appears to be inherited in an autosomal dominant manner. Genetic linkage analysis has been performed on a large family with HMPS. Data did not support linkage to the APC locus or to any of the loci for hereditary nonpolyposis colorectal cancer. Evidence that the HMPS locus lies on chromosome 6q was, however, provided by significant two-point LOD scores for linkage between HMPS and the D6S283 locus. Analysis of recombinants and multipoint linkage analysis suggested that the HMPS locus lies in a 4-cM interval containing the D6S283 locus and flanked by markers D6S468 and D6S301. 10 refs., 4 figs., 1 tab.

  14. Risk of gynecologic cancers in Danish hereditary non-polyposis colorectal cancer families

    DEFF Research Database (Denmark)

    Boilesen, Astrid Elisabeth Bruun; Bisgaard, Marie Luise; Bernstein, Inge

    2008-01-01

    OBJECTIVE: Women in hereditary non-polyposis colorectal cancer (HNPCC) families have an elevated risk of endometrial and ovarian cancer. The risk in Lynch syndrome families with known mutations in mismatch repair genes (MMR genes) seems to be higher than in familial colorectal cancer (CRC) families...... cancer. Lifetime risk was elevated four times in familial CRC families. In these families, frequency was correlated to the pedigree phenotype, with significantly higher frequency demonstrated in Amsterdam II families compared to Amsterdam I families and families suspected of HNPCC. A total of 39 cases...... of ovarian cancer were identified with a lifetime risk of three to four times the general population. No significant correlation was found between the frequency of ovarian cancer and MMR gene mutation status in the families. CONCLUSION: The benefit of surveillance concerning gynecological cancers seems...

  15. Mantle Cell Lymphoma of Intestine Presenting as Multiple Lymphomatous Polyposis with Intussusception

    Directory of Open Access Journals (Sweden)

    Meena N. Jadhav

    2015-01-01

    Full Text Available Mantle Cell Lymphoma (MCL is a distinct clinicopathological subtype of B-cell non-Hodgkin's lymphoma (NHL accounting for 2-10% of all NHL cases. Gastrointestinal tract (GIT is the predominant site of extranodal MCL which commonly presents as Multiple Lymphomatous Polyposis (MLP. A 60 year old male presented with pain abdomen, diarrhea and weight loss of two months duration. On colonoscopy multiple polyps were found in the entire colon and rectum. Computed tomography revealed ileo-colic intussusception with nodularity in the lead point. Histopathology suggested features of MCL. On immunohistochemistry, the tumor cells were positive for CD20, CD5, Cyclin D1, negative for CD3, CD10, CD23, and CD45 RO

  16. Endoscopic sinus surgery in chronic rhinosinusitis and nasal polyposis: a comparative study.

    Science.gov (United States)

    Nair, Satish; Dutta, Angshuman; Rajagopalan, Ramakrishnan; Nambiar, Sapna

    2011-01-01

    Nasal polyposis are common presentations in patients of chronic rhinosinusitis and are considered to be associated with more severe forms of disease with poor treatment outcome. The presentation and treatment outcome after endoscopic sinus surgery in patients of chronic rhinosinusitis and nasal polyposis have been analysed in this study. A prospective analysis of 90 patients of chronic rhinosinusitis who were classified into two groups depending on presence and absence of nasal polyps was performed in the study. The two groups were evaluated using subjective (patient complaints) and objective (computed tomography scan and endoscopy scores) criteria. Preoperative data were compared with data obtained 12 months post endoscopic sinus surgery. The study included 38 patients of chronic rhinosinusitis and 52 patients of nasal polyps. The patients of nasal polyp group presented with increased severity of symptoms of nasal blockage, nasal discharge and reduced sense of smell as compared to the chronic rhinosinusitis group who had significantly higher presentation of headache and facial pain. The preoperative CT scan revealed significantly higher bilateral disease with increased involvement of multiple sinuses in nasal polyp group. Post endoscopic sinus surgery both the groups showed significant improvement in their symptoms with the nasal polyp group demonstrating reduction in improvement on 1 year follow up. In our study we have found the patients with chronic rhinosinusitis and nasal polyp have varied severity of symptoms with the nasal polyp group having higher nasal symptoms and increased severity as compared to chronic rhinosinusitis group. Though the universal rationale of management by adequate drainage and ventilation of sinus is similar in both groups, there is a reduction in both objective and subjective scores during 1 year follow up in the nasal polyp group.

  17. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

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    Tops Carli MJ

    2009-06-01

    Full Text Available Abstract Background MUTYH-associated polyposis (MAP is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC. Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. Methods From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR of APC, p53, and SMAD4 were analyzed for somatic mutations. Results MAP CRCs frequently localized to the proximal colon (69%, 40/58, were mucinous in 21% (9/42, and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40; all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36 while 64% (23/36 had KRAS2 mutations (22/23 c.34G>T. G>T tranversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. Conclusion MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development but not in P53 and SMAD4 (implicated in tumour progression might indicate a predominant MUTYH effect in early carcinogenesis.

  18. The Value of CT Attenuation in Distinguishing Atypical Adenomatous Hyperplasia from Adenocarcinoma in Situ

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    Binghu JIANG

    2013-11-01

    Full Text Available Background and objective: Advances in high-resolution computed tomography (CT scanning have increased the detection of small ground-glass opacity (GGO nodules and also allowed such images to be investigated in detail. However, it is difficult to differentiate atypical adenomatous hyperplasia (AAH from adenocarcinoma in situ (AIS with CT, even at follow-up, because they share many similar CT manifestations. While AAH is thought to be a precursor or even an early-stage lesion of lung adenocarcinoma, and the stepwise progression from AAH to AIS is thought to be reasonable. Therefore, the hypothesis that the attenuation of GGO is increased gradually from AAH to AIS is proposed. The aim of this study was to distinguish AAH from AIS with CT attenuation in patients with pure GGO nodules. 
Methods: Between January 2010 and December 2012, the CT findings in terms of the greatest diameter and mean CT attenuation (HU were reviewed and correlated with pathology in 56 patients with AAH (n=21 and non-mucinous AIS (n=38 by two independent observers. All the 59 lesions were pure GGO nodules with size of 2 cm or smaller. To determine variability of measuring CT attenuation, we calculated the 95% confidence interval (CI for the limits of agreement by using Bland-Altman analysis. Student t test was used to compare AAH and AIS in terms of diameter and CT attenuation. And receiver operating characteristic (ROC curve was used to determine the optimal cut-off value of mean CT attenuation for differentiating AAH from AIS and obtain the diagnostic value. Two-tailed P value of less than 0.05 was considered to be significant. 
Results: For the manually measured CT attenuation, the 95%CI for the limits of agreement was -40 HU, 50 HU for inter-observer variability. Although there was significant difference in nodule diameter between AAH and AIS (P=0.046, the overlap was considerable. The mean CT attenuation was (-718±53 HU (95%CI: -822, -604 for AAH, which was

  19. DNA methylation changes in atypical adenomatous hyperplasia, adenocarcinoma in situ, and lung adenocarcinoma.

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    Suhaida A Selamat

    Full Text Available BACKGROUND: Aberrant DNA methylation is common in lung adenocarcinoma, but its timing in the phases of tumor development is largely unknown. Delineating when abnormal DNA methylation arises may provide insight into the natural history of lung adenocarcinoma and the role that DNA methylation alterations play in tumor formation. METHODOLOGY/PRINCIPAL FINDINGS: We used MethyLight, a sensitive real-time PCR-based quantitative method, to analyze DNA methylation levels at 15 CpG islands that are frequently methylated in lung adenocarcinoma and that we had flagged as potential markers for non-invasive detection. We also used two repeat probes as indicators of global DNA hypomethylation. We examined DNA methylation in 249 tissue samples from 93 subjects, spanning the putative spectrum of peripheral lung adenocarcinoma development: histologically normal adjacent non-tumor lung, atypical adenomatous hyperplasia (AAH, adenocarcinoma in situ (AIS, formerly known as bronchioloalveolar carcinoma, and invasive lung adenocarcinoma. Comparison of DNA methylation levels between the lesion types suggests that DNA hypermethylation of distinct loci occurs at different time points during the development of lung adenocarcinoma. DNA methylation at CDKN2A ex2 and PTPRN2 is already significantly elevated in AAH, while CpG islands at 2C35, EYA4, HOXA1, HOXA11, NEUROD1, NEUROD2 and TMEFF2 are significantly hypermethylated in AIS. In contrast, hypermethylation at CDH13, CDX2, OPCML, RASSF1, SFRP1 and TWIST1 and global DNA hypomethylation appear to be present predominantly in invasive cancer. CONCLUSIONS/SIGNIFICANCE: The gradual increase in DNA methylation seen for numerous loci in progressively more transformed lesions supports the model in which AAH and AIS are sequential stages in the development of lung adenocarcinoma. The demarcation of DNA methylation changes characteristic for AAH, AIS and adenocarcinoma begins to lay out a possible roadmap for aberrant DNA

  20. The Value of CT Attenuation in Distinguishing Atypical Adenomatous Hyperplasia from Adenocarcinoma in Situ

    Institute of Scientific and Technical Information of China (English)

    Binghu JIANG; Jichen WANG; Peng JIA; Meizhao LE

    2013-01-01

    Background and objective:Advances in high-resolution computed tomography (CT) scanning have increased the detection of small ground-glass opacity (GGO) nodules and also allowed such images to be investigated in detail. However, it is diffcult to differentiate atypical adenomatous hyperplasia (AAH) from adenocarcinoma in situ (AIS) with CT, even at follow-up, because they share many similar CT manifestations. While AAH is thought to be a precursor or even an early-stage lesion of lung adenocarcinoma, and the stepwise progression from AAH to AIS is thought to be reasonable. hTerefore, the hypothesis that the attenuation of GGO is increased gradually from AAH to AIS is proposed. hTe aim of this study was to distinguish AAH from AIS with CT attenuation in patients with pure GGO nodules. Methods:Between January 2010 and December 2012, the CT ifndings in terms of the greatest diameter and mean CT attenuation (HU) were reviewed and correlated with pathology in 56 patients with AAH (n=21) and non-mucinous AIS (n=38) by two independent observers. All the 59 lesions were pure GGO nodules with size of 2 cm or smaller. To determine variability of measuring CT attenuation, we calculated the 95%conifdence interval (CI) for the limits of agreement by using Bland-Altman analysis. Student t test was used to compare AAH and AIS in terms of diameter and CT attenuation. And receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of mean CT attenuation for differentiating AAH from AIS and obtain the diagnostic value. Two-tailed P value of less than 0.05 was considered to be signiifcant. Results:For the manually measured CT attenuation, the 95%CI for the limits of agreement was-40 HU, 50 HU for inter-observer variability. Although there was significant difference in nodule diameter between AAH and AIS (P=0.046), the overlap was considerable. hTe mean CT attenuation was (-718±53) HU (95%CI:-822,-604) for AAH, which was signiifcantly smaller than

  1. Germline variants in Hamartomatous Polyposis Syndrome-associated genes from patients with one or few hamartomatous polyps

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie; Brusgaard, Klaus; Hansen, Tine Plato;

    2016-01-01

    Sequencing, DNA samples from 77 patients with 84 hamartomatous polyps were sequenced. The detected germline variants were classified into pathogenicity classes. RESULTS: We detected several germline variants, among them three in ENG, two in BMPR1A, one in PTEN, and one in SMAD4. Although some of the detected......OBJECTIVE: A subgroup of patients with hamartomatous polyps in the GI tract has a hereditary Hamartomatous Polyposis Syndrome with an increased risk of cancer. The distinction between patients with one or few polyps and patients with a syndrome can be difficult. A pathogenic germline mutation can...... be detected in a majority of HPS patients. This study investigates whether patients with one or few hamartomatous polyps could have a syndrome based on genetic screening of relevant genes. METHODS: We designed a gene panel including 26 hamartomatous polyposis-associated genes. Using targeted Next Generation...

  2. Differentiation of chronical rhinosinusitis with and without nasal polyposis on basis of symptomatology, course of disease, inflammatory mediators and comorbidity

    OpenAIRE

    Traser, Louisa

    2012-01-01

    Recent cytokine and chemokine research has rapidly expanded our understanding of chronic rhinosinusitis (CRS) and underlined that it is necessary to divide this disease into subgroups. The objective of the present study was to investigate the differentiation of CRS patients with (CRSwNP) and without (CRSsNP) nasal polyposis on basis of symptomatology, course of disease, inflammatory mediators and comorbidity. Nasal Polyps (n=16), tissue samples taken from the paranasal sinuses (n=32) and ...

  3. Effects of smell loss on daily life and adopted coping strategies in patients with nasal polyposis with asthma.

    Science.gov (United States)

    Nordin, Steven; Blomqvist, Ebba Hedén; Olsson, Petter; Stjärne, Pär; Ehnhage, Anders

    2011-08-01

    Results from prior studies of quality of life (QoL) in heterogeneous patient groups (regarding disorder type and etiology) with olfactory disorders may be useful also for understanding QoL in homogeneous patient groups. Diagnosis and treatment of smell loss should be given high priority in polyposis with asthma, and coping strategies can be suggested to these patients. To investigate the effects of smell loss on daily life and coping strategies in patients with smell loss without dysosmia and with nasal polyposis with asthma as the only primary etiology, and to compare these results with those from a prior study of a patient group with heterogeneous olfactory disorders and etiology. Fifty patients with smell loss and with nasal polyposis and asthma responded to questions about consequences of smell loss, QoL, psychological well-being and distress, and coping strategies. Negative consequences of smell loss, associated risks, and diminished food enjoyment were commonly reported, and various aspects of QoL were rated as being deteriorated. Psychological well-being was found to be poorer than normal, and use of both problem- and emotion-focused strategies was common. The results from this homogeneous patient group are very similar to those previously obtained from a heterogeneous group.

  4. Administering of pregabalin and acetaminophen on management of postoperative pain in patients with nasal polyposis undergoing functional endoscopic sinus surgery.

    Science.gov (United States)

    Rezaeian, Ahmad

    2017-08-08

    Management of postoperative pain is a common problem in endoscopic sinus surgery. The objective of this study is the evaluation of pregabalin and acetaminophen effects on the management of postoperative pain in patients with nasal polyposis undergoing functional endoscopic sinus surgery (FESS). In this clinical trial, double-blinded study, 70 patients with nasal polyposis who have indication of FESS were enrolled to this study. After operation, patients were divided randomly into pregabalin and acetaminophen therapy groups. The pregabalin group (n = 35) was treated under pregabalin 50 mg TDS and the acetaminophen group (n = 35) was treated under tablet acetaminophen 500 mg/6 h. Each group was administered for 3 d. The visual analogue scale (VAS) was measured in onset, 12, 24, 48 and 72 h after surgery. All data were entered into SPSS software (SPSS Inc., Chicago, IL) and appropriate statistical tests were assessed to every relation. In this study, there was no significant difference between two groups according to VAS in onset (p = .37); however, VAS in 12, 24, 48 and 72 h after operation was significantly lower in the pregabalin group compared with the acetaminophen group (p acetaminophen group (p acetaminophen on the management of postoperative pain in the patients with nasal polyposis undergoing functional endoscopic sinus surgery.

  5. Zileuton, 5-lipoxygenase inhibitor, acts as a chemopreventive agent in intestinal polyposis, by modulating polyp and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Elias Gounaris

    Full Text Available Leukotrienes and prostaglandins, products of arachidonic acid metabolism, sustain both systemic and lesion-localized inflammation. Tumor-associated Inflammation can also contribute to the pathogenesis of colon cancer. Patients with inflammatory bowel disease (IBD have increased risk of developing colon cancer. The levels of 5-lipoxygenase (5-LO, the key enzyme for leukotrienes production, are increased in colon cancer specimens and colonic dysplastic lesions. Here we report that Zileuton, a specific 5-LO inhibitor, can prevent polyp formation by efficiently reducing the tumor-associated and systemic inflammation in APCΔ468 mice.In the current study, we inhibited 5-LO by dietary administration of Zileuton in the APCΔ468 mouse model of polyposis and analyzed the effect of in vivo 5-LO inhibition on tumor-associated and systemic inflammation.Zileuton-fed mice developed fewer polyps and displayed marked reduction in systemic and polyp-associated inflammation. Pro-inflammatory cytokines and pro-inflammatory innate and adaptive immunity cells were reduced both in the lesions and systemically. As part of tumor-associated inflammation Leukotriene B4 (LTB4, product of 5-LO activity, is increased focally in human dysplastic lesions. The 5-LO enzymatic activity was reduced in the serum of Zileuton treated polyposis mice.This study demonstrates that dietary administration of 5-LO specific inhibitor in the polyposis mouse model decreases polyp burden, and suggests that Zileuton may be a potential chemo-preventive agent in patients that are high-risk of developing colon cancer.

  6. Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis

    Science.gov (United States)

    Mur, Pilar; Elena, Sánchez-Cuartielles; Aussó, Susanna; Aiza, Gemma; Rafael, Valdés-Mas; Pineda, Marta; Navarro, Matilde; Brunet, Joan; Urioste, Miguel; Lázaro, Conxi; Moreno, Victor; Capellá, Gabriel; Puente, Xose S.; Valle, Laura

    2016-01-01

    Germline mutations in UNC5C have been suggested to increase colorectal cancer (CRC) risk, thus causing hereditary CRC. However, the evidence gathered thus far is insufficient to include the study of the UNC5C gene in the routine genetic testing of familial CRC. Here we aim at providing a more conclusive answer about the contribution of germline UNC5C mutations to genetically unexplained hereditary CRC and/or polyposis cases. To achieve this goal we sequenced the coding region and exon-intron boundaries of UNC5C in 544 familial CRC or polyposis patients (529 families), using a technique that combines pooled DNA amplification and massively parallel sequencing. A total of eight novel or rare variants, all missense, were identified in eight families. Co-segregation data in the families and association results in case-control series are not consistent with a causal effect for 7 of the 8 identified variants, including c.1882_1883delinsAA (p.A628K), previously described as a disease-causing mutation. One variant, c.2210G > A (p.S737N), remained unclassified. In conclusion, our results suggest that the contribution of germline mutations in UNC5C to hereditary colorectal cancer and to polyposis cases is negligible. PMID:26852919

  7. Novel strategies for comprehensive mutation screening of the APC gene.

    Science.gov (United States)

    Wachsmannova, L; Mego, M; Stevurkova, V; Zajac, V; Ciernikova, S

    2017-03-03

    Colorectal cancer is the 4th most common cause of cancer related deaths worldwide and new possibilities in accurate diagnosis and targeted treatment are highly required. Mutations in adenomatous polyposis coli (APC) gene play a pivotal role in adenoma-carcinoma pathway of colorectal tumorigenesis. The quarter century from its´ first cloning, APC became one of the most frequently mutated, known driver genes in colorectal cancer. Intensive routine molecular testing of APC has brought the benefits for patients with family history of polyposis or colorectal cancer. Nevertheless, multiple mutational disease-causing mechanisms make the genetic testing still challenging. This minireview is focused on implementation of novel APC mutation screening diagnostic strategies for polyposis families according to the current findings. A further understanding and improved algorithms may help to increase the mutation detection rate. APC germline mutations achieve close to 100% penetrance, so more comprehensive approach followed by preventive and therapeutic strategies might reflect in decrease in burden of colorectal cancer.

  8. Analysis of the depolarizing properties of normal and adenomatous polyps in colon mucosa for the early diagnosis of precancerous lesions

    Science.gov (United States)

    Ortega-Quijano, Noé; Fanjul-Vélez, Félix; de Cos-Pérez, Jesús; Arce-Diego, José Luis

    2011-09-01

    Optical characterization of biological tissues by means of polarimetric techniques is an area of growing interest. Polarized light can be used for malignant neoplasms detection. To our knowledge, few studies have so far focused on lesions that are prone to result in cancer. In this work we present a polarimetric study of depolarization in prepathological tissues. Specifically, we will focus on premalignant lesions in human colon due to their clinical relevance. Colonic adenoma, the potential precursor of malignant adenocarcinoma, provokes significant structural modifications in colon mucosa that affect light depolarization. The depolarizing properties of normal and adenomatous polyps mucosa are compared. The average linear degree of polarization is shown to present a strong dependence with the precancerous state of the colonic tissue. This method has the potential to enable an early diagnosis of colon cancer.

  9. Downregulation of peroxisome proliferator-activated receptors (PPARs in nasal polyposis

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    Adner Mikael

    2005-11-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor (PPAR α, βδ and γ are nuclear receptors activated by fatty acid metabolites. An anti-inflammatory role for these receptors in airway inflammation has been suggested. Methods Nasal biopsies were obtained from 10 healthy volunteers and 10 patients with symptomatic allergic rhinitis. Nasal polyps were obtained from 22 patients, before and after 4 weeks of local steroid treatment (fluticasone. Real-time RT-PCR was used for mRNA quantification and immunohistochemistry for protein localization and quantification. Results mRNA expression of PPARα, PPARβδ, PPARγ was found in all specimens. No differences in the expression of PPARs were obtained in nasal biopsies from patients with allergic rhinitis and healthy volunteers. Nasal polyps exhibited lower levels of PPARα and PPARγ than normal nasal mucosa and these levels were, for PPARγ, further reduced following steroid treatment. PPARγ immunoreactivity was detected in the epithelium, but also found in smooth muscle of blood vessels, glandular acini and inflammatory cells. Quantitative evaluation of the epithelial immunostaining revealed no differences between nasal biopsies from patients with allergic rhinitis and healthy volunteers. In polyps, the PPARγ immunoreactivity was lower than in nasal mucosa and further decreased after steroid treatment. Conclusion The down-regulation of PPARγ, in nasal polyposis but not in turbinates during symptomatic seasonal rhinitis, suggests that PPARγ might be of importance in long standing inflammations.

  10. Epidemiological and clinical aspects of nasal polyposis in France; the ORLI group experience.

    Science.gov (United States)

    Rugina, M; Serrano, E; Klossek, J M; Crampette, L; Stoll, D; Bebear, J P; Perrahia, M; Rouvier, P; Peynegre, R

    2002-06-01

    Nasal polyposis (NP) is a common condition in patients consulting ENT practitioners in France. A multicenter prospective study was performed to evaluate symptoms, demography, environmental factors, personal and family history and associated conditions like asthma, and food or drugs sensitivity (FDS) in patients suffering from NP. In each investigation center assessments were performed at the moment of the initial consultation by the same investigator, then updated with complementary exploration results required by the protocol. The chi 2 test and the Fisher test were used for statistical analysis. In this study 224 patients were included. Males were predominant at 63%. Asthma was found in 45% of cases without relevant sex difference. However, FDS, positive in 31% of the patients, was statistically higher in females than in males (42.9% vs. 24.4%). Severe and major symptoms were more frequently found in the female population. Environment and habitat factors did not appear to be relevant. High rates of NP (52.66%) and asthma (43.58%) were found in the family history. Hereditary factors were suggested and lead us to further study the genetic factors potentially involved in this pathology.

  11. Current and future treatment options for adult chronic rhinosinusitis: Focus on nasal polyposis.

    Science.gov (United States)

    Bachert, Claus; Zhang, Luo; Gevaert, Phillippe

    2015-12-01

    Chronic rhinosinusitis (CRS) affects more than 10% of the population in the United States and Europe. Recent findings point to a considerable variation of inflammatory subtypes in patients with CRS with nasal polyps and patients with CRS without nasal polyps. According to current guidelines, glucocorticosteroids and antibiotics are the principle pharmacotherapeutic approaches; however, they fail in a group of patients who share common clinical and laboratory markers. Several clinical phenotypes often leading to uncontrolled disease, including adult nasal polyposis, aspirin-exacerbated respiratory disease, and allergic fungal rhinosinusitis, are characterized by a common endotype: a TH2 bias is associated with a higher likelihood of comorbid asthma and recurrence after surgical treatment. As a consequence, several innovative approaches targeting the TH2 bias with humanized mAbs have been subjected to proof-of-concept studies in patients with CRS with nasal polyps with or without comorbid asthma: omalizumab, reslizumab, mepolizumab, and recently dupilumab. Future concepts using upstream targets, such as GATA-3, also focus on this endotype. This current development might result in advantages in the treatment of patients with the most severe CRS.

  12. Effectiveness of balloon sinuplasty in patients with chronic rhinosinusitis without polyposis,

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    Cassiana Burtet Abreu

    2014-12-01

    Full Text Available Introduction: Balloon sinuplasty is a minimally invasive endoscopic procedure, developed with the aim of restoring patency of the paranasal sinuses ostia with minimal damage to the mucosa. Objective: To evaluate the effectiveness of balloon sinuplasty in patients with chronic rhinosinusitis. Methods: This was a prospective cohort study comprising 18 patients with chronic rhinosinusitis without polyposis who underwent balloon sinuplasty. Patients were evaluated for clinical criteria, quality of life (Sino-Nasal Outcome Questionnaire Test-20 SNOT-20], and computed tomography of the sinuses (Lund–Mackay staging preoperatively and three to six months after the procedure. Results: Out of 18 patients assessed, 13 were included, with a mean age of 39.9 ± 15.6 years. Ostia sinuplasty was performed in 24 ostia (four sphenoid, ten frontal, and ten maxillary sinus. At the follow-up, 22 (92% ostia were patent and there was no major complication. There was symptomatic improvement (SNOT-20, with Cronbach coefficients for consistency of the questionnaire items of 0.86 (95% CI: 0.73–0.94 preoperatively and of 0.88 (95% CI: 0.77–0.95 postoperatively, the difference being statistically significant (p <0.001. In addition, there was marked reduction of the computed tomography signs, an average of 4.2 point score (p <0.001. Conclusion: Sinuplasty is effective in reducing symptoms and improving quality of life as a treatment option for chronic rhinosinusitis in selected patients.

  13. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC

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    Annegret Müller

    2004-01-01

    Full Text Available Genomic instability at simple repeated sequences, termed microsatellite instability (MSI, plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols forMSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.

  14. Hereditary non-polyposis colorectal cancer: The rise and fall of a confusing term

    Institute of Scientific and Technical Information of China (English)

    Jeremy R Jass

    2006-01-01

    The term Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is a poor descriptor of the syndrome described by Lynch. Over the last decade, the term has been applied to heterogeneous groups of families meeting limited clinical criteria, for example the Amsterdam criteria. It is now apparent that not all Amsterdam criteria-positive families have the Lynch syndrome. The term HNPCC has also been applied to clinical scenarios in which CRCs with DNA microsatellite instability are diagnosed but in which there is no vertical transmission of an altered DNA mismatch repair (MMR) gene. A term that has multiple, mutually incompatible meanings is highly problematic, particularly when it may influence the management of an individual family. The Lynch syndrome is best understood as a hereditary predisposition to malignancy that is explained by a germline mutation in a DNA MMR gene. The diagnosis does not depend in an absolute sense on any particular family pedigree structure or age of onset of malignancy.Families with a strong family history of colorectal cancer that do not have Lynch syndrome have been grouped as 'Familial Colorectal Cancer Type-X'. The first step in characterizing these cancer families is to distinguish them from Lynch syndrome. The term HNPCC no longer serves any useful purpose and should be phased out.

  15. Single Incision Laparoscopic Surgery in Treating Patients With Colorectal Disease

    Science.gov (United States)

    2013-11-04

    Adenomatous Polyp; Crohn Disease; Familial Adenomatous Polyposis; Hereditary Intestinal Polyposis Syndrome; Recurrent Colon Cancer; Stage I Colon Cancer; Stage IIA Colon Cancer; Stage IIB Colon Cancer; Stage IIC Colon Cancer; Stage IIIA Colon Cancer; Stage IIIB Colon Cancer; Stage IIIC Colon Cancer

  16. Disease: H01025 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01025 Familial adenomatous polyposis Familial adenomatous polyposis (FAP) is an au...575] ICD-10: D12.6 MeSH: D011125 OMIM: 175100 608456 PMID:19822006 (description, gene) Half E, Bercovich D, Rozen P Familial

  17. Comorbidities in severe asthma: frequency of rhinitis, nasal polyposis, gastroesophageal reflux disease, vocal cord dysfunction and bronchiectasis

    Directory of Open Access Journals (Sweden)

    Carla Bisaccioni

    2009-01-01

    Full Text Available OBJECTIVES: Severe asthma is found in approximately 10% of patients with asthma. Some factors associated with worse asthma control include rhinitis, gastroesophageal reflux disease, vocal cord dysfunction (VCD, nasal polyposis and bronchiectasis. Therefore, we evaluated the prevalence of these illnesses in patients with severe asthma. METHODS: We conducted a retrospective analysis of data obtained from electronic medical records of patients with severe asthma between January 2006 and June 2008. Symptoms of rhinitis and gastroesophageal reflux disease were evaluated as well as intolerance to nonsteroidal anti-inflammatory drugs. We evaluated the results of esophagogastroduodenoscopy, videolaryngoscopy and CT scans of the chest in order to confirm gastroesophageal reflux disease, nasal polyposis, vocal cord dysfunction and bronchiectasis. RESULTS: We evaluated 245 patients. Rhinitis symptoms were present in 224 patients (91.4%; 18 (7.3% had intolerance to nonsteroidal anti-inflammatory drugs, and 8 (3.3% had nasal polyposis. Symptoms of gastroesophageal reflux disease were reported for 173 (70.6% patients, although the diagnosis of gastroesophageal reflux disease was confirmed based on esophagogastroduodenoscopy or laryngoscopy findings in just 58 (33.6% patients. Vocal cord dysfunction was suspected in 16 (6.5% and confirmed through laryngoscopy in 4 (1.6%. The patient records provided CT scans of the chest for 105 patients, and 26 (24.8% showed bronchiectasis. DISCUSSION: Rhinitis and gastroesophageal reflux disease were the most common comorbidities observed, in addition to bronchiectasis. Therefore, in patients with severe asthma, associated diseases should be investigated as the cause of respiratory symptoms and uncontrolled asthma.

  18. Effectiveness of itraconazole on clinical symptoms and radiologic findings in patients with recurrent chronic rhinosinusitis and nasal polyposis

    Directory of Open Access Journals (Sweden)

    Mostafa Hashemi

    2014-01-01

    Full Text Available Background: This study was done to evaluate the effect of itraconazole on clinical symptoms and radiologic findings in patients with chronic rhinosinusitis and nasal polyposis after surgery. Materials and Methods: In a clinical trial which was conducted in Alzahra and Kashani hospitals, from November 2011 to December 2012, 22 patients with recurrent postsurgical chronic sinusitis and polyposis entered the study. At the start of the study demographic data, subjective clinical symptoms (severity of rhinorrhea, nasal obstruction, hyposmia, and dyspnea, quality of life (QoL by sinonasal outcome test-20 (SNOT-20, serum immunoglobulin E (IgE, and score of computed tomography (CT scan (by Lund-Mackay were recorded. Itraconazole (100 mg, twice per day prescribed for 3 months and patients were followed in the 1 st , 3 rd , and 6 th months. Liver enzyme tests and side effects were evaluated monthly. Results: Severity of rhinorrhea, nasal obstruction, hyposmia, dyspnea, and QoL (by SNOT-20 improved during 3 months of treatment. Serum IgE was 265 (±277 at the start of the study, and decrease to 193 (±183 after 3 month. After 3 month, Lund-Mackay score of CT scan lowered from 19 (±4 to 15 (±6 (P < 0.05. At the 6 th month, severity of clinical symptoms except dyspnea and QoL were better than first evaluation. Conclusion: This study showed the beneficial effect of 3-month itraconazole treatment on clinical symptoms and radiologic findings and QoL in patients with recurrent postsurgical chronic rhinosinusitis and nasal polyposis.

  19. Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis

    OpenAIRE

    Pilar Mur; Sánchez-Cuartielles Elena; Susanna Aussó; Gemma Aiza; Valdés-Mas Rafael; Marta Pineda; Matilde Navarro; Joan Brunet; Miguel Urioste; Conxi Lázaro; Victor Moreno; Gabriel Capellá; Puente, Xose S; Laura Valle

    2016-01-01

    Germline mutations in UNC5C have been suggested to increase colorectal cancer (CRC) risk, thus causing hereditary CRC. However, the evidence gathered thus far is insufficient to include the study of the UNC5C gene in the routine genetic testing of familial CRC. Here we aim at providing a more conclusive answer about the contribution of germline UNC5C mutations to genetically unexplained hereditary CRC and/or polyposis cases. To achieve this goal we sequenced the coding region and exon-intron ...

  20. E. Coli and Pregnancy

    Science.gov (United States)

    ... best live chat Live Help Fact Sheets Share E. coli and Pregnancy Thursday, 20 November 2014 In every ... risk. This sheet talks about whether exposure to E. coli may increase the risk for birth defects over ...

  1. E. coli enteritis

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000296.htm E. coli enteritis To use the sharing features on this page, please enable JavaScript. E. coli enteritis is swelling (inflammation) of the small intestine from ...

  2. Genetic polymorphism of antioxidant enzymes in eosinophilic and non-eosinophilic nasal polyposis.

    Science.gov (United States)

    Akyigit, Abdulvahap; Keles, Erol; Etem, Ebru Onalan; Ozercan, Ibrahim; Akyol, Hatice; Sakallioglu, Oner; Karlidag, Turgut; Polat, Cahit; Kaygusuz, Irfan; Yalcin, Sinasi

    2017-01-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the paranasal sinuses, and its pathophysiology is not yet precisely known. It is suggested that oxygen free radicals play an important role in the pathogenesis of nasal polyposis. This study aimed to identify genetic polymorphisms of superoxide dismutase (SOD 2), catalase (CAT), and inducible nitric oxide synthase (iNOS) enzymes in eosinophilic CRSwNP and non-eosinophilic CRSwNP patients; the study also aimed to evaluate the effect of genetic polymorphism of antioxidant enzymes on CRSwNP etiopathogenesis. One hundred thirty patients, who received endoscopic sinus surgery due to CRSwNP, and 188 control individuals were included in this study. Nasal polyp tissues were divided into two groups histopathologically as eosinophilic CRSwNP and non-eosinophilic CRSwNP. Venous blood samples were taken from the patient and control groups. Polymorphisms in the Ala16Va1 gene, which is the most common variation of SOD-2 gene, and 21 A/T polymorphisms in catalase gene were evaluated with the restriction fragment length polymorphism method and -277 C/T polymorphism in the iNOS gene was evaluated with the DNA sequencing method. The GG genotype distribution for the (-277) A/G polymorphism in the iNOS gene was a statistically significant difference between eosinophilic CRSwNP and control groups (p  0.05). The TT genotype distribution for the A/T polymorphism in catalase gene at position -21 was statistically significant differences in eosinophilic CRSwNP and control groups (p levels, which are considered effective factors in the pathogenesis of CRSwNP, can occur due to genetic polymorphism of enzymes in the antioxidant system and genetic polymorphism of antioxidant enzymes in eosinophilic CRSwNP patients might contribute to the pathophysiology.

  3. Change in nasal congestion index after treatment in patients with chronic rhinosinusitis with nasal polyposis

    Science.gov (United States)

    Sahin-Onder, Serap; Oysu, Cagatay; Deveci, Ildem; Sahin, Samil; Aktas, Betul

    2016-01-01

    Background: The management of chronic rhinosinusitis with nasal polyposis (CRSwNP) involves both surgical and medical approaches, and remains a controversial subject. Objective: The objective of this prospective, randomized, controlled trial was to compare the medical and surgical treatments of CRSwNP in terms of their effect on the nasal congestion index (NCI). Methods: Forty-eight patients with CRSwNP were randomized either to medical or surgical therapy. Pretreatment and 3- and 6-month posttreatment assessments of the visual analog scale score, the 20-Item Sino-Nasal Outcome Test, saccharine clearance time, nasal endoscopy, and NCI measurement with acoustic rhinometry were performed. Forty-one subjects were included in the analysis. Results: Both the medical and surgical interventions for CRSwNP resulted in significant improvement in the visual analog scale score, 20-Item Sino-Nasal Outcome Test, saccharine clearance time, and nasal endoscopic examination scores. There was no difference between the two groups in terms of the percentage change from baseline for any of the parameters at the 6-month posttreatment assessment. NCI showed no significant difference from baseline. Similarly, no significant difference was found between the medical and surgical groups in terms of their effect on the NCI (p > 0.05). Conclusion: Because NCI does not correlate with standard subjective measures in outcomes for this group of patients, it cannot be used as an outcome measurement of treatment of subjects with CRSwNP. Results of this prospective randomized study did not find any additional benefit of surgical therapy over medical therapy in subjects with CRSwNP.

  4. [French multicenter prospective epidemiologic study (ORLI Group) of allergic and lung diseases associated with nasal polyposis].

    Science.gov (United States)

    Crampette, L; Serrano, E; Klossek, J M; Rugina, M; Rouvier, P; Peynègre, R; Bébéar, J P; Stoll, D

    2001-01-01

    224 patients presenting with nasal polyposis (NP) were included in a french prospective multicenter study. NP was evaluated by nasal endoscopy and computed tomography. Allergic status was documented using skin prick-tests and/or specific IgE. Pneumologic assessment included spirometry with carbamyl-choline hyper-reactivity test or beta 2 mimetic broncho-dilation test. Minimal follow up period was 1 year. 45% of the whole population were considered as asthmatic. Asthma onset occurred before and after the NP onset in respectively 45.7%, 22.3% and 32% of cases; these two conditions started simultaneously in 32% of patients. Skin prick-tests and/or specific IgE were positive in 32.5% of cases. In most of the cases (80%), patients were polysensitized to house dust mite and/or pollens and/or animal danders and/or fungi. 31% of the population had idiosyncrasy, caused by drugs in general and especially aspirin in 44% of cases. The global population could be divided in two groups according to the occurrence of previous polypectomy or not. The group "polypectomy" and the group "no polypectomy" were similar regarding the frequency, the age of onset, the course and the severity of associated asthma. Familial history (parents, children, brothers and sisters) was of great interest: 58.7% of the patients had one (or more) relative suffering from NP, 43.6% of the patients had one (or more) relative suffering from asthma and 12.2% of the patients had one (or more) relative suffering from idiosyncrasy. These results support a genetic etiology for NP.

  5. Impact of Mucosal Eosinophilia and Nasal Polyposis on Quality of Life Outcomes after Sinus Surgery

    Science.gov (United States)

    Soler, Zachary M.; Sauer, David; Mace, Jess; Smith, Timothy L.

    2009-01-01

    Objective Assess whether the presence of mucosal eosinophilia correlates with surgical outcomes in patients with chronic rhinosinusitis. Study Design Prospective cohort Setting Tertiary medical center Subjects and Methods Adult patients with chronic rhinosinusitis were prospectively enrolled and demographic data and medical comorbidities recorded. Preoperative quality-of-life (QOL) was measured by the Chronic Sinusitis Survey (CSS), Rhinosinusitis Disability Index (RSDI), and Short Form-36 General Health Survey (SF-36). Sinus mucosal specimens were collected at the time of surgery and the degree of eosinophilia quantified. Postoperative QOL was measured and differences in QOL improvement were compared between those with and without eosinophilia. Results A total of 102 patients had both histopathologic and QOL outcome data available for review. Follow-up averaged 16.5 months. Patients with eosinophilia showed significantly less improvement in the RSDI total (17.9 vs 25.0; p=0.044), RSDI functional (5.7 vs 8.8; p=0.018), CSS medication (3.6 vs 17.3; p=0.013), SF-36 general health (0.6 vs 9.6; p=0.008), SF-36 physical role (16.1 vs 34.7; p=0.036), and SF-36 vitality (11.9 vs 21.2; p=0.034) scales than those without eosinophilia. The greatest improvement in QOL was seen in patients without eosinophilia or polyps and the least improvement seen in those with eosinophilia but without polyps. Conclusion The presence of mucosal eosinophilia at the time of surgery consistently predicted less improvement in both disease-specific and general QOL compared to those without eosinophilia. The impact of eosinophilia on outcomes was greatest for patients without nasal polyposis, a group which demonstrated the least improvement in QOL measures. PMID:20096225

  6. E. Coli Infections

    Science.gov (United States)

    E. coli is the name of a type of bacteria that lives in your intestines. Most types of E. coli are harmless. However, some types can make you ... type causes travelers' diarrhea. The worst type of E. coli causes bloody diarrhea, and can sometimes cause kidney ...

  7. Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ripa, R S; Katballe, N; Wikman, F P

    2005-01-01

    The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions of a s....... The results support the hypothesis that N596del is the disease causing mutation and not a clinically silent variation. On this basis, the application of the MSH2 N596del mutation, in presymptomatic screening of HNPCC families, is recommended.......The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...... of a single amino acid codon have previously been published as assumed pathogenic. The objective of this study was to determine if an MSH2 3 base pair in-frame deletion (N596del) could be used in presymptomatic screening of at-risk individuals. We report on five HNPCC families with the N596del mutation...

  8. A Case with Serrated Polyposis Syndrome Controlled by Multiple Applications of Endoscopic Mucosal Resection and Endoscopic Submucosal Dissection

    Science.gov (United States)

    Suzuki, Daisuke; Matsumoto, Satohiro; Mashima, Hirosato

    2017-01-01

    Patient: Male, 66 Final Diagnosis: Serrated polyposis syndrome Symptoms: Positive fecal occult blood test Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Unusual setting of medical care Background: Serrated polyposis syndrome (SPS) is characterized by numerous hyperplastic polyps and sessile serrated adenoma/polyp (SSA/P) in the large intestine. SSA/P is known to transform into malignant lesions through the serrated pathway instead of the adenoma-carcinoma sequence. Early diagnosis with lower gastrointestinal endoscopy and early treatment are now considered to be essential. Case Report: We had an experience with a case of SPS to which endoscopic treatment was applied in multiple sessions. Endoscopic treatment was performed for 16 lesions in total, and the pathological findings were SSA/P for 15 and adenoma for the other lesion. We intend to continue performing endoscopic surveillance for any newly developing lesions. Conclusions: SPS has a potential for malignant transformation, and issues, such as long-term prognosis and optimal therapeutic strategies, await resolution. However, multiple endoscopic treatments are useful for cases with lesions that are controllable employing this modality. PMID:28341823

  9. Very low prevalence of germline MSH6 mutations in hereditary non-polyposis colorectal cancer suspected patients with colorectal cancer without microsatellite instability.

    NARCIS (Netherlands)

    Kets, M.; Krieken, J.H.J.M. van; Hebeda, K.M.; Wezenberg, S.J.; Goossens, M.; Brunner, H.G.; Ligtenberg, M.J.L.; Hoogerbrugge-van der Linden, N.

    2006-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is caused by mutations in one of the mismatch repair genes MLH1, MSH2, MSH6, or PMS2 and results in high-level microsatellite instability (MSI-high) in tumours of HNPCC patients. The MSI test is considered reliable for indicating mutations in MLH1

  10. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer

    NARCIS (Netherlands)

    Niessen, R C; Berends, M J W; Wu, Y; Sijmons, R H; Hollema, H; Ligtenberg, M J L; de Walle, H E K; de Vries, E G E; Karrenbeld, A; Buys, C H C M; van der Zee, A G J; Hofstra, R M W; Kleibeuker, J H

    2006-01-01

    Background: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. Aim: To analyse the value of family history,

  11. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer.

    NARCIS (Netherlands)

    Niessen, R.C.; Berends, M.J.; Wu, Y.; Sijmons, R.H.; Hollema, H.; Ligtenberg, M.J.L.; Walle, H.E. de; Vries, E.G.F. de; Karrenbeld, A.; Buys, C.H.C.M.; Zee, A.G. van der; Hofstra, R.M.; Kleibeuker, J.H.

    2006-01-01

    BACKGROUND: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. AIM: To analyse the value of family history,

  12. APC and chromosome instability in colorectal cancer APC e inestabilidad cromosómica en el cáncer de colon

    Directory of Open Access Journals (Sweden)

    C. M. Cabrera

    2005-10-01

    Full Text Available Colon cancer is a common disease that can be sporadic or familial. An inactivated adenomatous polyposis coli (APC suppressor gene is found in over 80% of colorectal tumors, this being an early alteration in the development of adenomatous polyps. APC function is not only critical for tumor initiation and progression, and chromosome instability (CIN is another characteristic dependent at least partly on APC mutations.El cáncer de colon es una enfermedad frecuente que puede ser esporádica o familiar. La inactivación del gen supresor de tumores APC (adenomatous polyposis coli se ha encontrado en más del 80% de los casos descritos de tumores colorrectales, apareciendo como una alteración temprana durante el desarrollo del pólipo adenomatoso. La inactivación del gen APC no es únicamente crítica en el proceso de iniciación y desarrollo del tumor, sino que igualmente la inestabilidad cromosómica (CIN es otra característica dependiente al menos en parte de la presencia de mutaciones en APC.

  13. Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report.

    Science.gov (United States)

    Choi, Jeong-hwa; Yates, Zoe; Martin, Charlotte; Boyd, Lyndell; Ng, Xiaowei; Skinner, Virginia; Wai, Ron; Veysey, Martin; Lucock, Mark

    2015-01-01

    Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.

  14. Thyroid adenomatous nodule with bizarre nuclei: a case report and mutation analysis of the p53 gene.

    Science.gov (United States)

    Sato, Katsuaki; Shimode, Yuzo; Hirokawa, Mitsuyoshi; Ueda, Yoshimichi; Katsuda, Shogo

    2008-01-01

    We present a rare case of adenomatous nodule with bizarre nuclei. The patient was incidentally found to have a nodule in the left lobe of the thyroid gland by ultrasonographic examination. Papillary thyroid carcinoma was suspected by fine needle aspiration cytology, and hemithyroidectomy was performed. The demarcated 1.5-cm nodule had a multinodular appearance with various features, including micro- and macrofollicular components, cystic degeneration, a hyalinized area, and a papillary structure. Hyperchromatic bizarre nuclei with cytoplasmic inclusions were restrictively observed in the microfollicular area. The bizarre nuclei demonstrated diffuse p53 protein immmunoreactivity, but no mutation in exons 5-9 of the p53 gene was detected. The bizarre nuclei were reactive for anti-5-methyl-2'-deoxycytidine antibody, indicating the enclosure of presumably inactive methylated DNA. The intranuclear cytoplasmic inclusions (ICIs) were proven to contain vimentin and beta-catenin by immunohistochemistry. In this case, a degenerative process is involved in the formation of bizarre nuclei because of the compression by surrounding micronodules, unidentifiable mitotic figures, and a quite low proliferative activity. This case suggests that bizarre nuclei and ICIs, which might be identical to those of papillary carcinomas, can be seen in benign thyroid lesions, and overdiagnosis should be avoided regardless of immunohistochemical overexpression of p53.

  15. Effects of cumene hydroperoxide on adenosine diphosphate ribosyl transferase in mononuclear leukocytes of patients with adenomatous polyps in the colon.

    Science.gov (United States)

    Markowitz, M M; Johnson, D B; Pero, R W; Winawer, S J; Miller, D G

    1988-03-01

    We have studied the effects of plasma and of cumene hydroperoxide (CUM) on adenosine diphosphate ribosyl transferase (ADPRT) from mononuclear leukocytes (HML) of patients with colonic adenomatous polyps (n = 22), with colonic hyperplastic polyps (n = 5) and with neither type of polyp (controls) (n = 6). ADPRT was measured after incubation of HML with plasma alone (termed the plasma value), and with plasma plus CUM (50 microM) (the activated value); the difference elicited by CUM was termed the induced value. There was no significant difference in values between the control and hyperplastic polyp groups: these were combined for further analysis. The plasma (P = 0.038), activated (P = 0.009) and induced (P = 0.0024) values of the combined group all differed significantly from those of the adenoma group. At low exposures, CUM stimulated both ADPRT and unscheduled DNA synthesis and, at higher exposures, inactivated both. Pretreatment of HML with vitamin E protected against these effects of CUM, while pretreatment with diamide (which depletes GSH) accentuated the effects. This study demonstrates a differential reaction of ADPRT in patients harboring colonic adenomas and suggests that the origin of this difference may lie in cellular responses to oxidative stress.

  16. ANALISIS CEMARAN BAKTERI Escherichia coli ANALISIS CEMARAN BAKTERI Escherichia coli ANALISIS CEMARAN BAKTERI Escherichia coli

    OpenAIRE

    ANGGREINI, RAHAYU

    2015-01-01

    2015 RAHAYU ANGGREINI coli Penelitian ini bertujuan untuk melakukan identifikasi cemaran bakteri E. coli O157:H7 pada daging sapi di kota Makassar. Sampel pada penelitian ini sebanyak 72 sampel Kata Kunci : Daging sapi, pasar tradisional, E. coli, E. coli O157:H7, kontaminasi bakteri, identifikasi E. coli O157:H7.

  17. ANALISIS CEMARAN BAKTERI Escherichia coli ANALISIS CEMARAN BAKTERI Escherichia coli ANALISIS CEMARAN BAKTERI Escherichia coli

    OpenAIRE

    ANGGREINI, RAHAYU

    2015-01-01

    2015 RAHAYU ANGGREINI coli Penelitian ini bertujuan untuk melakukan identifikasi cemaran bakteri E. coli O157:H7 pada daging sapi di kota Makassar. Sampel pada penelitian ini sebanyak 72 sampel Kata Kunci : Daging sapi, pasar tradisional, E. coli, E. coli O157:H7, kontaminasi bakteri, identifikasi E. coli O157:H7.

  18. Expression of alpha-Methylacyl-CoA racemase (P504S) in atypical adenomatous hyperplasia of the prostate.

    Science.gov (United States)

    Yang, Ximing J; Wu, Chin-Lee; Woda, Bruce A; Dresser, Karen; Tretiakova, Maria; Fanger, Gary R; Jiang, Zhong

    2002-07-01

    Atypical adenomatous hyperplasia (AAH) of the prostate, also known as adenosis, is characterized by a proliferation of prostatic glands with abnormal architectural patterns, but without significant cytologic atypia. In some cases it may be difficult to distinguish AAH from prostatic carcinoma. Additionally, it is not clear whether AAH is a precursor lesion of prostatic adenocarcinoma. P504S, a protein highly expressed in prostatic adenocarcinoma, has been recently shown to be a marker of prostate cancer. The goal of this study is to examine the expression of P504S in AAH by immunohistochemistry. A total of 80 prostate specimens, including 40 cases of AAH (prostatectomy N = 30, biopsy N = 6, transurethral resection N = 4), 20 cases of prostatic adenocarcinomas, and 20 cases of benign prostatic hyperplasia, were studied. Immunohistochemistry for a prostate cancer marker alpha-methylacyl-CoA racemase (P504S) and a basal cell-specific marker 34betaE12 was performed in all the cases. The 34betaE12 stain confirmed the presence of patchy basal cells in all 40 cases of AAH. P504S was undetectable in the majority of AAHs (33 of 40, 82.5%), focally expressed in four of 40 (10.0%), or diffusely positive only in three of 40 (7.5%) cases of AAH. Interestingly, two of seven P504S-positive AAHs were found adjacent to adenocarcinoma. In contrast, all benign prostatic hyperplasias (20 of 20, 100%) were negative for P504S, and all 20 cases of prostatic carcinomas (100%) showed a diffuse P504S staining pattern. These findings suggest that AAH is a heterogenous entity. The biologic significance of P504S expression in a small subset of AAH remains to be determined. Because most cases of AAH are negative for P504S, immunostaining of P504S is also of diagnostic value in distinguishing the majority of AAHs from prostatic adenocarcinoma.

  19. Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ripa, Rasmus S.; Katballe, Niels; Wikman, Friedrik P.;

    2005-01-01

    The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...... of a single amino acid codon have previously been published as assumed pathogenic. The objective of this study was to determine if an MSH2 3 base pair in-frame deletion (N596del) could be used in presymptomatic screening of at-risk individuals. We report on five HNPCC families with the N596del mutation....... The results support the hypothesis that N596del is the disease causing mutation and not a clinically silent variation. On this basis, the application of the MSH2 N596del mutation, in presymptomatic screening of HNPCC families, is recommended....

  20. A case of mucosa-associated lymphoid tissue lymphoma forming multiple lymphomatous polyposis in the small intestine

    Institute of Scientific and Technical Information of China (English)

    Naoto Hirata; Shiro Nakamura; Nobuhide Oshitani; Kazuhide Higuchi; Tetsuo Arakawa; Kazunari Tominaga; Kensuke Ohta; Kaori Kadouchi; Hirotoshi Okazaki; Tetsuya Tanigawa; Masatsugu Shiba; Toshio Watanabe; Yasuhiro Fujiwara

    2007-01-01

    A 50-year old woman suffering from diabetes had a CT scan that revealed a diffuse thickening of small intestinal wall and swollen paraaortic lymph nodes. An esophago gastroduodenoscopy (EGD) confirmed multiple polypoid lesions in the duodenum and small intestine, and conventional histological testing revealed non-specific inflammatory changes. Further examinations including the immunohistochemical profiles of the biopsied specimens led us to diagnose the lesion as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, forming multiple lymphomatous polyposis sequentially spreading from duodenal bulb to terminal ileum. According to Lugano's classification, its staging was clinically diagnosed as stage Ⅱ. Two courses of a standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and predonisolone)regimen with rituximab reduced the lesion and the patient had a almost complete response. A 5-year follow-up EGD and histological examinations detected no recurrence of the disease.

  1. Zoonotic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Wasteson Yngvild

    2002-03-01

    Full Text Available Escherichia coli is a normal inhabitant of the gastrointestinal tract of all warm-blooded animals, but variants of this species is also among the important etiological agents of enteritis and several extraintestinal diseases. The E. coli strains that cause diarrhoeal illness are categorised into pathogenicity groups based on virulence properties, mechanisms of pathogenicity, clinical symptoms and serology. The five main categories include enterotoxinogenic E. coli (ETEC, enteropathogenic E. coli (EPEC, enteroaggregative E. coli (EAggEC, enteroinvasive E. coli (EIEC and Shiga (Vero toxin-producing E. coli (STEC/VTEC. From a zoonotic point of view, STEC is the only E. coli pathogenicity group of major interest, as the shiga toxin-producing strains are able to cause severe disease in humans when being transmitted through the food chain from their animal reservoirs. The focus of this manuscript is therefore on STEC; pathogenicity factors, disease, the reservoirs and on-farm ecology, transmission into the food chain, growth and survival in food and in the environment, and the shiga toxin-encoding bacteriophages.

  2. PATHOGENIC ESCHERICHIA COLI

    Science.gov (United States)

    Escherichia coli is a bacterial species which inhabits the gastrointestinal tract of man and warm-blooded animals. Because of the ubiquity of this bacterium in the intestinal flora, it serves as an important indicator organism of fecal contamination. E. coli, aside from serving a...

  3. Mapping of multiple intestinal neoplasia (Min) to proximal chromosome 18 of the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Luongo, C.; Gould, K.A.; Moser, A.R. (Univ. of Wisconsin, Madison (United States)); Su, Likuo; Kinzler, K.W.; Vogelstein, B. (Johns Hopkins Oncology Center, Baltimore, MD (United States)); Dietrich, W.; Lander, E.S. (MIT, Cambridge (United States))

    1993-01-01

    The Min (multiple intestinal neoplasia) mutation of the mouse has been mapped by analyzing the inheritance of restriction fragment length polymorphisms and simple sequence length polymorphisms in progeny from two intraspecific crosses segregating for the Min mutation. Min, a mutant allele of Apc, the mouse homo- log of the human APC (adenomatous polyposis coli) gene, maps to proximal chromosome 18. The synteny between Apc and Mcc, the mouse homolog of the human MCC (mutated in colorectal cancer) gene, is conserved between mouse and human, although the gene order in the Apc to Mcc interval is different from that in the APC to MCC interval. 29 refs., 3 figs.

  4. Prosthodontic management of a patient with Gardner′s syndrome: A clinical case report

    Directory of Open Access Journals (Sweden)

    Kunwarjeet Singh

    2014-01-01

    Full Text Available Gardner′s syndrome is a genetic condition demonstrating an autosomal dominant trait and characterized by the multiple colonic polyps (familial adenomatous polyposis coli with sebaceous cysts and jaw osteomas. Various dental abnormalities present in patient′s suffering with this syndrome includes multiple impacted or unerupted teeth, supernumerary teeth, hypodontia, compound odontomes and dentigerous cyst. In this case report, a patient with Gardner′s syndrome who suffered from functional and psychological problems owing to multiple impacted, unerupted teeth and hypodontia was presented. Patient was treated with a maxillary conventional overdenture opposing mandibular custom bar supported overdentures.

  5. Wnt/Myc interactions in intestinal cancer: partners in crime.

    Science.gov (United States)

    Myant, Kevin; Sansom, Owen J

    2011-11-15

    Loss of the APC (adenomatous polyposis coli) gene in colorectal cancer leads to a rapid deregulation of TCF/LEF target genes. Of all these target genes, the transcription factor c-MYC appears the most critical. In this review we will discuss the interplay of Wnt and c-MYC signaling during intestinal homeostasis and transformation. Furthermore, we will discuss recent data showing that further deregulation of c-MYC levels during colorectal carcinogenesis may drive tumor progression. Moreover, understanding these additional control mechanisms may allow targeting of c-MYC during colorectal carcinogenesis.

  6. Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy

    Science.gov (United States)

    Joshi, Bishnu P.; Miller, Sharon J.; Lee, Cameron; Gustad, Adam; Seibel, Eric J.; Wang, Thomas D.

    2012-02-01

    We demonstrate a multi-spectral scanning fiber endoscope (SFE) that collects fluorescence images in vivo from three target peptides that bind specifically to murine colonic adenomas. This ultrathin endoscope was demonstrated in a genetically engineered mouse model of spontaneous colorectal adenomas based on somatic Apc (adenomatous polyposis coli) gene inactivation. The SFE delivers excitation at 440, 532, 635 nm with advance early cancer detection and image-guided therapy in human patients by simultaneously visualizing multiple over expressed molecular targets unique to dysplasia.

  7. Chronic epithelial NF-κB activation accelerates APC loss and intestinal tumor initiation through iNOS up-regulation

    OpenAIRE

    Shaked, Helena; Hofseth, Lorne J.; Chumanevich, Alena; Chumanevich, Alexander A.; Wang, Jin; Wang, Yinsheng; Taniguchi, Koji; Guma, Monica; Shenouda, Steve; Clevers, Hans; Curtis C Harris; Karin, Michael

    2012-01-01

    The role of NF-κB activation in tumor initiation has not been thoroughly investigated. We generated Ikkβ(EE)IEC transgenic mice expressing constitutively active IκB kinase β (IKKβ) in intestinal epithelial cells (IECs). Despite absence of destructive colonic inflammation, Ikkβ(EE)IEC mice developed intestinal tumors after a long latency. However, when crossed to mice with IEC-specific allelic deletion of the adenomatous polyposis coli (Apc) tumor suppressor locus, Ikkβ(EE)IEC mice exhibited m...

  8. Diarrheagenic Escherichia coli.

    Science.gov (United States)

    Gomes, Tânia A T; Elias, Waldir P; Scaletsky, Isabel C A; Guth, Beatriz E C; Rodrigues, Juliana F; Piazza, Roxane M F; Ferreira, Luís C S; Martinez, Marina B

    2016-12-01

    Most Escherichia coli strains live harmlessly in the intestines and rarely cause disease in healthy individuals. Nonetheless, a number of pathogenic strains can cause diarrhea or extraintestinal diseases both in healthy and immunocompromised individuals. Diarrheal illnesses are a severe public health problem and a major cause of morbidity and mortality in infants and young children, especially in developing countries. E. coli strains that cause diarrhea have evolved by acquiring, through horizontal gene transfer, a particular set of characteristics that have successfully persisted in the host. According to the group of virulence determinants acquired, specific combinations were formed determining the currently known E. coli pathotypes, which are collectively known as diarrheagenic E. coli. In this review, we have gathered information on current definitions, serotypes, lineages, virulence mechanisms, epidemiology, and diagnosis of the major diarrheagenic E. coli pathotypes.

  9. Engineering E. coli-E. coli cocultures for production of muconic acid from glycerol

    National Research Council Canada - National Science Library

    Zhang, Haoran; Li, Zhengjun; Pereira, Brian; Stephanopoulos, Gregory

    2015-01-01

    .... In this study, we aim to explore the potential of the E. coli-E. coli coculture system to use a single renewable carbon source, glycerol, for the production of value-added product cis, cis-muconic acid...

  10. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy enhances real-time in vivo diagnosis of adenomatous polyps during colonoscopy.

    Science.gov (United States)

    Bergholt, Mads Sylvest; Lin, Kan; Wang, Jianfeng; Zheng, Wei; Xu, Hongzhi; Huang, Qingwen; Ren, Jian-Lin; Ho, Khek Yu; Teh, Ming; Srivastava, Supriya; Wong, Benjamin; Yeoh, Khay Guan; Huang, Zhiwei

    2016-04-01

    Colorectal cancer can be prevented if detected early (e.g., precancerous polyps-adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have little or no risk of malignant transformation) and adenomas (that have prominent malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy is an optical vibrational technique capable of probing biomolecular changes of tissue associated with neoplastic transformation. This work aims to apply a fiber-optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy technique for real-time in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber-optic Raman endoscopic technique capable of simultaneously acquiring both the FP (i.e., 800-1800 cm(-1)) and HW (i.e., 2800-3600 cm(-1)) Raman spectra from colorectal tissue subsurface (Raman spectra were acquired from 50 patients with 17 colorectal polyps during clinical colonoscopy. Prominent Raman spectral differences (p Raman endoscopy provides a diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman technique alone. This study shows that simultaneous FP/HW Raman spectroscopy technique has the potential to be a clinically powerful tool for improving early diagnosis of adenomatous polyps in vivo during colonoscopic examination. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Fibromatosis in vertical rectus abdominis myocutaneous flap imitating tumor recurrence after surgery for locally advanced rectal cancer: case report.

    Science.gov (United States)

    Goscinski, Mariusz Adam; Hole, Knut Håkon; Tønne, Elin; Ryder, Truls; Grøholt, Krystyna Kotanska; Flatmark, Kjersti

    2016-03-03

    Abdominoperineal excision is performed in patients with locally advanced, low rectal carcinoma. Reconstruction of the dorsal vagina and perineum using the vertical rectus abdominis myocutaneous flap following extensive surgery results in favorable surgical outcome and quality of life. However, the rectus abdominis muscle, as part of the anterior abdominal wall, may develop fibrous lesions also as a transplant. A 39-year-old female patient with low rectal cancer and extensive colorectal polyposis was treated with neoadjuvant chemoradiotherapy followed by colectomy and abdominoperineal excision with resection of the dorsal vaginal wall and subsequent reconstruction of the perineum using the vertical rectus abdominis myocutaneous flap. At the 6-month follow-up, a suspected 2 × 2 cm tumor recurrence was detected in the transposed tissue and was subsequently surgically removed. Histologic examination concluded with fibromatosis. Genetic testing revealed a known disease-causing mutation in the adenomatous polyposis coli gene, confirming the diagnosis of familial adenomatous polyposis. Fibromatosis may affect the anterior abdominal wall, that is the rectus abdominis muscle, at the primary site or may develop in the muscle after its transposition into the perineum at pelvic reconstruction. Fibromatosis in the muscle flap after pelvic reconstruction may present a difficult diagnostic challenge for the multidisciplinary team.

  12. AXIN1 and AXIN2 Variants in Gastrointestinal Cancers

    Science.gov (United States)

    Mazzoni, Serina M.; Fearon, Eric R.

    2014-01-01

    Mutations in the APC (adenomatous polyposis coli) gene, which encodes a multi-functional protein with a well-defined role in the canonical Wnt pathway, underlie familial adenomatous polypsosis, a rare, inherited form of colorectal cancer (CRC) and contribute to the majority of sporadic CRCs. However, not all sporadic and familial CRCs can be explained by mutations in APC or other genes with well-established roles in CRC. The AXIN1 and AXIN2 proteins function in the canonical Wnt pathway, and AXIN1/2 alterations have been proposed as key defects in some cancers. Here, we review AXIN1 and AXIN2 sequence alterations reported in gastrointestinal cancers, with the goal of vetting the evidence that some of the variants may have key functional roles in cancer development. PMID:25236910

  13. E. Coli and Pregnancy

    Science.gov (United States)

    ... best live chat Live Help Fact Sheets Share E. coli and Pregnancy Thursday, 20 November 2014 In ... pregnancy and while breastfeeding. Donate Sign Up For E-Newsletter Full Name * Email Address * Enter The Code: ...

  14. Correlation of the nuclear accumulation of CTNNB1 and colonic tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    QIU Zhe-fu; Maruyama Keiji; HAN De-min; Nakamura Satoshi

    2006-01-01

    @@ CTNNB1 (or beta-catenin) is regarded as a central effecter in molecules of the wingless/Wnt signalling pathway. It is a key component of the cadherin mediated cell to cell adhesion system and forms a complex with the protein product of adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β) and conductin.1 One mutation of APC is also responsible for activation of wingless/Wnt signalling pathway and accumulation of free beta-catenin in the cell. Beta-catenin upregulates oncogenes, such as cyclin D1 and c-myc.2 Beta-catenin expression in cytoplasm and nuclei was reported to increase in many cases of intestinal tumorigenesis.3,4 In addition, the hyperexpression of integrin linked kinase (ILK) in colonic polyposis has been demonstrated.5

  15. Taxonomy Icon Data: Escherichia coli [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Escherichia coli Escherichia coli Escherichia_coli_L.png Escherichia_coli_NL.png Escherich...ia_coli_S.png Escherichia_coli_NS.png http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Escherichia+co...li&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Escherichia+coli&t=NL http://biosciencedbc.jp/taxono...my_icon/icon.cgi?i=Escherichia+coli&t=S http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Escherichia+coli&t=NS ...

  16. Freqüência de pólipos em doentes operados de câncer colorretal Frequency of adenomatous polyps after surgical resection of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Beatriz Pinho ROCHA

    2000-01-01

    Full Text Available Introdução - Estudos epidemiológicos e gênicos mostram que os pólipos colônicos do tipo adenoma são lesões pré-neoplásicas. O seguimento de um paciente com câncer colorretal visa principalmente o diagnóstico e retirada de pólipos adenomatosos. Objetivo - Estudar a freqüência do aparecimento de pólipos adenomatosos em doentes com câncer colorretal em acompanhamento clínico após ressecção tumoral. Casuística e Métodos - Foi estudada, retrospectivamente, a freqüência de pólipos do tipo adenoma em 68 pacientes com idade média de 59 anos, submetidos a cirurgia curativa para tratamento de câncer colorretal e a colonoscopia de controle. Resultados - A incidência de pólipos adenomatosos foi de 18%, sendo maior acima de 45 anos (20% e no cólon esquerdo (38%. Em relação ao tipo histológico, 61% eram tubulares, 22% vilosos e 17% túbulo-vilosos. Discussão - Assim como em outros relatos da literatura, a incidência de pólipos foi superior em indivíduos com mais de 45 anos, sendo em mais da metade do tipo tubular. A freqüência de pólipos foi maior nos dois primeiros anos de acompanhamento.Introduction - Epidemiologic and molecular biologic studies have already demonstrated that adenomatous colonic polyps are precancerous diseases. The main indication of the colonoscopy in the surveillance of colorectal cancer treated patients is the diagnosis and resection of adenomatous polyps. Aim - To study the frequency of adenomatous polyps after surgically resection of colorectal cancer. Material and Methods - Sixty eight patients, mean age 59 years old, with total resection of colorectal cancer, submitted to various colonoscopies during the follow up were studied retrospectively. The histological type and the characteristics of the polyp were described. Results - The frequency of polyps was 18%, being higher in the patients with more than 45 years (20%. The site of the polyps was in the left colon in 38% of the patients with

  17. Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling: Influence of smoking

    Institute of Scientific and Technical Information of China (English)

    Rhonda M Brand; David D Jones; Henry T Lynch; Randall E Brand; Patrice Watson; Ramesh Ashwathnayaran; Hemant K Roy

    2006-01-01

    AIM: To investigate whether a fuzzy logic model could predict colorectal cancer (CRC) risk engendered by smoking in hereditary non-polyposis colorectal cancer(HNPCC) patients.METHODS: Three hundred and forty HNPCC mismatch repair (MMR) mutation carriers from the Creighton University Hereditary Cancer Institute Registry were selected for modeling. Age-dependent curves were generated to elucidate the joint effects between gene mutation (hMLH1 or hMSH2), gender, and smoking status on the probability of developing CRC.RESULTS: Smoking significantly increased CRC risk in male hMSH2 mutation carriers (P<0.05). hMLH1 mutations augmented CRC risk relative to hMSH2 mutation carriers for males (P < 0.05). Males had a significantly higher risk of CRC than females for hMLH1 non smokers (P<0.05), hMLH1 smokers (P < 0.1) and hMSH2 smokers (P < 0.1). Smoking promoted CRC in a dose-dependent manner in hMSH2 in males (P<0.05).Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history (P<0.05).CONCLUSION: CRC promotion by smoking in HNPCC patients is dependent on gene mutation, gender and age. These data demonstrate that fuzzy modeling may enable formulation of clinical risk scores, thereby allowing individualization of CRC prevention strategies.

  18. How does measured olfactory function correlate with self-ratings of the sense of smell in patients with nasal polyposis?

    Science.gov (United States)

    Nguyen, Duc Trung; Nguyen-Thi, Phi-Linh; Jankowski, Roger

    2012-05-01

    The objectives of this study were to investigate correlations, before and after surgery, between olfactory function self-ratings and measurements, and self-ratings of nasal obstruction and smell; and to establish cutoff points of self-rating scores for smell reduction in patients with nasal polyposis (NP). Prospective study. A total of 80 patients with NP (36 women, 44 men; aged 49 ± 4 years) were enrolled. Self-ratings (0- to 10-point scale) and measurements of olfactory function with standardized Sniffin' Sticks odor threshold and identification tests were assessed 1 day before surgery, and at 6 weeks (26-78 days) and 7 months (132-318 days) after surgery. Relationships were studied with Spearman correlation coefficients. Cutoff points of self-rating scores for olfactory deficit were established using the receiver operating characteristic curve. Overall, olfactory function self-ratings and measurements correlated strongly preoperatively (r = -0.66, P smell were not correlated when two complaints were dissociated. Cutoff points of self-rating scores for smell reduction were nine units preoperatively and five units postoperatively. Self-ratings and measurements of olfactory function correlated well before and after surgery in NP patients with olfactory deficits. Self-ratings were not reliable pre- and postoperatively in normosmic patients. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  19. A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Joel Johansson

    2015-01-01

    Full Text Available Juvenile polyposis syndrome (JPS is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency.

  20. A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia

    Science.gov (United States)

    Johansson, Joel; Sahin, Christofer; Pestoff, Rebecka; Ignatova, Simone; Forsberg, Pia; Edsjö, Anders; Ekstedt, Mattias; Stenmark Askmalm, Marie

    2015-01-01

    Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency. PMID:25705527

  1. A rare case of asymptomatic radioiodine-avid renal and brain metastases 20 years after hemi-thyroidectomy for adenomatous goiter.

    Science.gov (United States)

    Santhosh, Sampath; Bhattacharya, Anish; Verma, Roshan Kumar; Lal, Anupam; Mittal, Bhagwant Rai

    2016-01-01

    A 65-year-old patient, with a history of left hemi-thyroidectomy for adenomatous goiter 20 years previously, was found to have pulmonary lesions on chest X-ray, a brain lesion on computerized tomography (CT), and elevated serum thyroglobulin (Tg). While completion thyroidectomy revealed that no pathological evidence of thyroid malignancy, radioiodine-avid pulmonary, brain, and renal and bone lesions were identified on diagnostic as well as posttherapy whole body planar scintigraphy and single photon emission computed tomography-CT. Subsequent ultrasonography-guided biopsy of a renal nodule showed thyroid follicular cells. This case suggests that metastatic differentiated thyroid carcinoma should be suspected in asymptomatic patients with incidentally detected lesions, raised serum Tg, and history of thyroid lesions.

  2. taenia coli de cobaye

    African Journals Online (AJOL)

    AKA BOKO

    of the rhythmical contraction of guinea pig Taenia coli smooth muscle. ... déterminer le mécanisme d'action de ces composés. 2. Matériel et ..... [34, 35]. Il rappelle les effets de l'acétylcholine sur les muscles lisses viscéraux [36- 38]. Pour cela.

  3. The benefits of a laparoscopic approach in ileal pouch anal anastomosis formation: a single institutional retrospective case-matched experience.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-06-01

    A laparoscopic approach to ileoanal pouch formation is novel. By using prospectively gathered data, laparoscopic and open restorative proctocolectomy procedures in mucosal ulcerative colitis (UC) and familial adenomatous polyposis (FAP) patients were compared using a case-matched design.

  4. Sporadic Giant Mesenteric Fibromatosis

    National Research Council Canada - National Science Library

    Sinukumar, Snita; Gomes, Rachel M; Kumar, Rajiv K; Desouza, Ashwin; Saklani, Avanish

    2014-01-01

    Mesenteric fibromatosis is an uncommon tumour which is locally aggressive without any metastatic potential and can occur as a sporadic event or in association with familial adenomatous polyposis syndrome...

  5. Autologous serum skin test reactivity and basophil histamine release test in patients with nasal polyposis: preliminary results.

    Science.gov (United States)

    Zambetti, G; Ciofalo, A; Soldo, P; Fusconi, M; Romeo, R; Greco, A; Altissimi, G; Macri, G F; Marinelli, C; Pagliuca, G; De Vincentiis, M

    2010-01-01

    An eosinophilic inflammatory process is generally observed in patients suffering from nasal polyposis (NP), however its onset has not yet been defined. It has been suggested that immune activation of inflammatory cells may be the cause. The aim of this study is to verify whether autoantibodies and/or histamine-releasing factors are present in the serum of patients suffering from NP. In fact, we assume that autoantibodies and/or histamine-releasing factors, as already demonstrated in chronic idiopathic urticaria and asthma, may be involved in the pathogenesis of NP. In this case-control analytical study 40 patients with NP and 27 control subjects underwent the in vivo autologous serum skin test (ASST). The sera from 6 patients suffering from NP and 9 control group subjects, who had all been previously studied and randomly selected, underwent basophil histamine release assay from normal donor as a pilot study. The ASST showed positive results in 55% of patients suffering from NP versus 8% of the control group (p= .00006), the basophil histamine release test (BHRT) turned out positive in all patients tested and in 11% of the control group. We found a weak positive correlation between the percentage of histamine release and the wheal diameter. ASST reactivity is very frequent in patients suffering from NP, thus suggesting the presence of histamine-releasing factors in the blood stream. The BHRT was positive in the serum of all patients, thus suggesting the presence of anti-FcepsilonRI, anti-IgE autoantibodies and/or other histamine-releasing factors, the presence of which can play a role in triggering and maintaining the eosinophilic inflammatory process in NP.

  6. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zeilstra, Jurrit; Joosten, Sander P.J. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Wensveen, Felix M. [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Dessing, Mark C.; Schuetze, Denise M. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Eldering, Eric [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Spaargaren, Marcel [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Pals, Steven T., E-mail: s.t.pals@amc.uva.nl [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands)

    2011-03-04

    Research highlights: {yields} Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. {yields} Expression profiling of apoptosis-related genes in Apc{sup Min/+} mice revealed the differential expression of pro-apoptotic Bok and Bax. {yields} APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. {yields} Blocking of {beta}-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or {beta}-catenin causes constitutively active {beta}-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc{sup Min/+} mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of {beta}-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which

  7. PTT analysis of polyps from FAP patients reveals a great majority of APC truncating mutations

    Energy Technology Data Exchange (ETDEWEB)

    Luijt, R.B. van der; Khan, P.M.; Tops, C.M.J. [Leiden Univ., (Netherlands)] [and others

    1994-09-01

    The adenomatous polyposis coli (APC) gene plays an important role in colorectal carcinogenesis. Germline APC mutations are associated with familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer, characterized by the development of numerous adenomatous polyps in the large intestine. In order to investigate whether somatic inactivation of the remaining APC allele is necessary for adenoma formation, we collected multiple adenomatous polyps from individual FAP patients and investigated the presence of somatic mutations in the APC gene. The analysis of somatic APC mutations in these tumor samples was performed using a rapid and sensitive assay, called the protein truncation test (PTT). Chain-terminating somatic APC mutations were detected in the great majority of the tumor samples investigated. As expected, these mutations were mainly located in the mutation cluster region (MCR) in exon 15. Our results confirm that somatic mutation of the second APC allele is required for adenoma formation in FAP. Interestingly, in the polyps investigated in our study, the second APC allele is somatically inactivated through point mutation leading to a stop codon rather than by loss of heterozygosity. The observation that somatic second hits in APC are required for tumor development in FAP is in apparent accordance with the Knudson hypothesis for classical tumor suppressor genes. However, it is yet unknown whether chain-terminating APC mutations lead to a truncated protein exerting a dominant-negative effect or whether these mutations result in a null allele. Further investigation of this important issue will hopefully provide a better understanding of the mechanism of action of the mutated APC alleles in colorectal carcinogenesis.

  8. PART I. ESCHERICHIA COLI

    Directory of Open Access Journals (Sweden)

    Sanaa Mahdi Oraibi

    2016-11-01

    Full Text Available The presence of Escherichia coli in the air of facilities involved in management and composting of post-slaughter poultry wastes in selected plants of West Western Pomerania region was studied. Measurements were made on four dates in a variety of weather conditions during the year. The study was conducted at 5 objects that differ in the type of waste and the degree of preparation for composting. These were: chemical treatment and preliminary processing plant, liquid wastes reservoir, platform for preparation of materials for composting, storage of biological sediments, and composting facility. Measurement of bacteria count was carried out in accordance with the applicable procedures on selective chromogenic TBX medium. The assays revealed the presence of E. coli at all test objects, but not always on all measurement dates. It has been shown that the presence of E. coli was from 20 to 3047 CFU∙m-3 of air, although the largest quantities were most frequently detected in the air of the building for post-slaughter waste pre-treatment in chemical treatment plant.

  9. HMGA1 induces intestinal polyposis in transgenic mice and drives tumor progression and stem cell properties in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Amy Belton

    Full Text Available BACKGROUND: Although metastatic colon cancer is a leading cause of cancer death worldwide, the molecular mechanisms that enable colon cancer cells to metastasize remain unclear. Emerging evidence suggests that metastatic cells develop by usurping transcriptional networks from embryonic stem (ES cells to facilitate an epithelial-mesenchymal transition (EMT, invasion, and metastatic progression. Previous studies identified HMGA1 as a key transcription factor enriched in ES cells, colon cancer, and other aggressive tumors, although its role in these settings is poorly understood. METHODS/PRINCIPAL FINDINGS: To determine how HMGA1 functions in metastatic colon cancer, we manipulated HMGA1 expression in transgenic mice and colon cancer cells. We discovered that HMGA1 drives proliferative changes, aberrant crypt formation, and intestinal polyposis in transgenic mice. In colon cancer cell lines from poorly differentiated, metastatic tumors, knock-down of HMGA1 blocks anchorage-independent cell growth, migration, invasion, xenograft tumorigenesis and three-dimensional colonosphere formation. Inhibiting HMGA1 expression blocks tumorigenesis at limiting dilutions, consistent with depletion of tumor-initiator cells in the knock-down cells. Knock-down of HMGA1 also inhibits metastatic progression to the liver in vivo. In metastatic colon cancer cells, HMGA1 induces expression of Twist1, a gene involved in embryogenesis, EMT, and tumor progression, while HMGA1 represses E-cadherin, a gene that is down-regulated during EMT and metastatic progression. In addition, HMGA1 is among the most enriched genes in colon cancer compared to normal mucosa. CONCLUSIONS: Our findings demonstrate for the first time that HMGA1 drives proliferative changes and polyp formation in the intestines of transgenic mice and induces metastatic progression and stem-like properties in colon cancer cells. These findings indicate that HMGA1 is a key regulator, both in metastatic

  10. Investigating the potential role of genetic and epigenetic variation of DNA methyltransferase genes in hyperplastic polyposis syndrome.

    Directory of Open Access Journals (Sweden)

    Musa Drini

    Full Text Available BACKGROUND: Hyperplastic Polyposis Syndrome (HPS is a condition associated with multiple serrated polyps, and an increased risk of colorectal cancer (CRC. At least half of CRCs arising in HPS show a CpG island methylator phenotype (CIMP, potentially linked to aberrant DNA methyltransferase (DNMT activity. CIMP is associated with methylation of tumor suppressor genes including regulators of DNA mismatch repair (such as MLH1, MGMT, and negative regulators of Wnt signaling (such as WIF1. In this study, we investigated the potential for interaction of genetic and epigenetic variation in DNMT genes, in the aetiology of HPS. METHODS: We utilized high resolution melting (HRM analysis to screen 45 cases with HPS for novel sequence variants in DNMT1, DNMT3A, DNMT3B, and DNMT3L. 21 polyps from 13 patients were screened for BRAF and KRAS mutations, with assessment of promoter methylation in the DNMT1, DNMT3A, DNMT3B, DNMT3L MLH1, MGMT, and WIF1 gene promoters. RESULTS: No pathologic germline mutations were observed in any DNA-methyltransferase gene. However, the T allele of rs62106244 (intron 10 of DNMT1 gene was over-represented in cases with HPS (p<0.01 compared with population controls. The DNMT1, DNMT3A and DNMT3B promoters were unmethylated in all instances. Interestingly, the DNMT3L promoter showed low levels of methylation in polyps and normal colonic mucosa relative to matched disease free cells with methylation level negatively correlated to expression level in normal colonic tissue. DNMT3L promoter hypomethylation was more often found in polyps harbouring KRAS mutations (p = 0.0053. BRAF mutations were common (11 out of 21 polyps, whilst KRAS mutations were identified in 4 of 21 polyps. CONCLUSIONS: Genetic or epigenetic alterations in DNMT genes do not appear to be associated with HPS, but further investigation of genetic variation at rs62106244 is justified given the high frequency of the minor allele in this case series.

  11. Effect of Folate on Colorectal Adenomatous Polyps%叶酸对结直肠腺瘤性息肉的影响

    Institute of Scientific and Technical Information of China (English)

    高占娟; 胡晓娜

    2012-01-01

    叶酸是广泛存在于绿叶蔬菜中的水溶性B族维生素,在DNA的合成和复制中起重要作用.研究显示在正常结直肠黏膜中,叶酸缺乏易导致腺瘤性息肉发生;如结直肠腺瘤性息肉已形成,叶酸补充可能增加其进展风险.800μg/d的适量叶酸摄入是有益的,应不会增加结直肠腺瘤性息肉的发生风险.%Folate, a water-soluble B vitamin, is widely existed in green leafy vegetables. It plays important role in DNA synthesis and replication. Studies have demonstrated that lack of folate in normal colorectal mucosa appears to predispose to neoplastic transformation. However, if the colorectal neoplasms have already established, folic acid supplementation has a tumor promotion effect. Modest level (800 μg/d) of folic acid supplementation is considered to be beneficial and may not increase the risk of coloreclal adenomatous polyps.

  12. Colorectal cancer risk variants at 8q23.3 and 11q23.1 are associated with disease phenotype in APC mutation carriers

    NARCIS (Netherlands)

    Ghorbanoghli, Z.; Nieuwenhuis, M. H.; Houwing-Duistermaat, J. J.; Jagmohan-Changur, S.; Hes, F. J.; Tops, C. M.; Wagner, A.; Aalfs, C. M.; Verhoef, S.; Garcia, E. B. Gomez; Sijmons, R. H.; Menko, F. H.; Letteboer, T. G.; Hoogerbrugge, N.; van Wezel, T.; Vasen, H. F. A.; Wijnen, J. T.

    2016-01-01

    Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC). The severity of polyposis is correlated with the site of th

  13. Sulindac treatment in hereditary non-pollyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.

    2007-01-01

    Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised dou

  14. [DNA-based diagnosis of hereditary tumour predisposition

    NARCIS (Netherlands)

    Menko, F.H.; Ligtenberg, M.J.L.; Brouwer, T.; Hahn, D.E.; Ausems, M.G.E.M.

    2007-01-01

    Of all forms of cancer, approximately 5% are caused by factors leading to a strong genetic predisposition. DNA diagnosis is currently used in families with hereditary tumour syndromes, such as familial adenomatous polyposis, hereditary non-polyposis colorectal carcinoma (Lynch syndrome), and heredit

  15. Asymptomatic bacteriuria Escherichia coli strains

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Nielsen, E.M.; Klemm, Per

    2006-01-01

    Urinary tract infections (UTIs) affect millions of people each year. Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU) in humans. Persons affected by ABU may carry a particular E. coli strain for extended periods of time without any symptoms. In contrast...

  16. Asymptomatic bacteriuria Escherichia coli strains

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Nielsen, E.M.; Klemm, Per

    2006-01-01

    Urinary tract infections (UTIs) affect millions of people each year. Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU) in humans. Persons affected by ABU may carry a particular E. coli strain for extended periods of time without any symptoms. In contrast...

  17. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2012-02-01

    BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC). AIM: To determine the role played by APC gene in the genesis of cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance\\/loss of heterozygosity (AI\\/LOH) was examined in twenty-two histologically confirmed cutaneous squamous cell carcinomas (SCC) using microsatellite markers, proximal to the APC gene. Immunohistochemical analysis of APC protein expression was also examined in the cutaneous SCC. RESULTS: AI\\/LOH was detected in 60% of the SCC samples using D5S346 marker (proximal to the APC gene). Ninty-five percent of the SCC samples showed positive reduced APC expression, however the localization of the APC protein was abnormal. CONCLUSION: The abnormal expression of APC suggests that APC gene may play a role in cutaneous SCC development.

  18. Role of heterozygous APC mutation in niche succession and initiation of colorectal cancer--a computational study.

    Directory of Open Access Journals (Sweden)

    Roschen Sasikumar

    Full Text Available Mutations in the adenomatous polyposis coli (APC gene are found in most colorectal cancers. They cause constitutive activation of proliferative pathways when both alleles of the gene are mutated. However studies on individuals with familial adenomatous polyposis (FAP have shown that a single mutated APC allele can also create changes in the precancerous colon crypt, like increased number of stem cells, increased crypt fission, greater variability of DNA methylation patterns, and higher somatic mutation rates. In this paper, using a computational model of colon crypt dynamics, we evolve and investigate a hypothesis on the effect of heterozygous APC mutation that explains these different observations. Based on previous reports and the results from the computational model we propose the hypothesis that heterozygous APC mutation has the effect of increasing the chances for a stem cell to divide symmetrically, producing two stem cell daughters. We incorporate this hypothesis into the model and perform simulation experiments to investigate the consequences of the hypothesis. Simulations show that this hypothesis links together the changes in FAP crypts observed in previous studies. The simulations also show that an APC(+/- stem cell gets selective advantages for dominating the crypt and progressing to cancer. This explains why most colon cancers are initiated by APC mutation. The results could have implications for preventing or retarding the onset of colon cancer in people with inherited or acquired mutation of one APC allele. Experimental validation of the hypothesis as well as investigation into the molecular mechanisms of this effect may therefore be worth undertaking.

  19. A new conditional Apc-mutant mouse model for colorectal cancer.

    Science.gov (United States)

    Robanus-Maandag, Els C; Koelink, Pim J; Breukel, Cor; Salvatori, Daniela C F; Jagmohan-Changur, Shantie C; Bosch, Cathy A J; Verspaget, Hein W; Devilee, Peter; Fodde, Riccardo; Smits, Ron

    2010-05-01

    Mutations of the adenomatous polyposis coli (APC) gene predispose individuals to familial adenomatous polyposis (FAP), characterized by multiple tumours in the large intestine. Most mouse models heterozygous for truncating mutant Apc alleles mimic FAP, however, the intestinal tumours occur mainly in the small intestine. To model large intestinal tumours, we generated a new conditional Apc-mutant allele, Apc(15lox), with exon 15 flanked by loxP sites. Similar survival of Apc(1638N/15lox) and Apc(1638N/+) mice indicated that the normal function of Apc was not impaired by the loxP sites. Deletion of exon 15, encoding nearly all functional Apc domains and containing the polyadenylation signal, resulted in a mutant allele expressing low levels of a 74 kDa truncated Apc protein. Germ line Cre-mediated deletion of exon 15 resulted in Apc(Delta15/+) mice, showing a severe Apc(Min/+)-like phenotype characterized by multiple tumours in the small intestine and early lethality. In contrast, conditional Cre-mediated deletion of exon 15 specifically directed to the epithelia of distal small and large intestine of FabplCre;Apc(15lox/+) mice led to longer survival and to tumours that developed predominantly in the large intestine, mimicking human FAP-associated colorectal cancer and sporadic colorectal cancer. We conclude that the FabplCre;Apc(15lox/+) mouse should be an attractive model for studies on prevention and treatment of colorectal cancer.

  20. Downregulation of anti-oncomirs miR-143/145 cluster occurs before APC gene aberration in the development of colorectal tumors.

    Science.gov (United States)

    Kamatani, Akemi; Nakagawa, Yoshihito; Akao, Yukihiro; Maruyama, Naoko; Nagasaka, Mitsuo; Shibata, Tomoyuki; Tahara, Tomomitsu; Hirata, Ichiro

    2013-09-01

    Accumulating data indicate that some microRNAs (miRNAs or miRs) can function as tumor suppressors or oncogenes and as such are important in cancer development. We previously reported that miR-143 and -145 are frequently downregulated in colon adenomas and cancers, acting as tumor suppressors. In this present study, we investigated the relationship between the downregulation of the miR-143/145 cluster and genetic aberrations of adenomatous polyposis coli (APC), which are early genetic events in the development of colorectal tumors. The expression levels of both miRs were determined by performing real-time PCR on tissue samples of familial adenomatous polyposis (FAP), colorectal adenoma, colorectal cancer, and paired non-tumorous tissues. Also, the expression of C- or N-terminus of the APC protein and that of the p53 protein in these tissues were examined immunohistochemically. Our data clearly indicated that the decreased expression of miR-143 and -145 frequently occurred before APC gene aberrations. The downregulation of miR-143 and -145 is thus an important genetic event for the initiation step in colorectal tumor development.

  1. [A Case of Metachronous Multiple Thyroid Papillary Carcinoma with FAP].

    Science.gov (United States)

    Tajima, Yusuke; Kumamoto, Kensuke; Yamamoto, Azusa; Chika, Noriyasu; Watanabe, Yuichiro; Matsuzawa, Takeaki; Ishibashi, Keiichiro; Mochiki, Erito; Iwama, Takeo; Akagi, Kiwamu; Ishida, Hideyuki

    2015-11-01

    Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year-old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence.

  2. Report of 1 case of adult nasopharyngeal gland polyposis%成人鼻咽部腺体样息肉1例报告

    Institute of Scientific and Technical Information of China (English)

    王成义; 张梅

    2015-01-01

    收治成人鼻咽部腺体息肉患者1例,给予手术治疗。根据病理回报,有腺体组织分布,考虑为咽部黏膜固有层组织及腺体增生、肥大,突出于上皮组织形成。该病例报道较少,还需进一步积累病例及研究。%1 case of adult nasopharyngeal gland polyposis was treated in our hospital.According to the pathological changes of the glandular tissue distribution,taking into account the inherent layer of the pharyngeal mucosa tissue and glandular hyperplasia, hypertrophy,the formation of the epithelial tissue.The case report is less,but also need to further accumulate cases and research.

  3. Cytogenetic findings in lung cancer that illuminate its biological history from adenomatous hyperplasia to bronchioalveolar carcinoma to adenocarcinoma: A case report.

    Science.gov (United States)

    Bettio, Daniela; Cariboni, Umberto; Venci, Anna; Valente, Marialuisa; Spaggiari, Paola; Alloisio, Marco

    2012-12-01

    The biological and chronological evolution of lung cancer remain to be fully elucidated. A multi-step carcinogenesis hypothesis suggests a progression from atypical adenomatous hyperplasia (AAH) through bronchioalveolar carcinoma (BAC) to invasive adenocarcinoma (AC), but to date this has not been formally demonstrated. We report a case of a patient diagnosed by computed tomography (CT) with lung cancer in the superior right lobe who also presented with a pure ground-glass opacity (GGO) in the inferior lobe, while the middle lobe appeared normal. Following pneumonectomy, cytogenetic analysis successfully performed on spontaneous metaphases obtained by the direct method from samples of the three lung lobes showed the presence of three clonal cell populations, each progressively having increased karyotype complexity. Fluorescence in situ hybridization (FISH), performed using ALK (2p23) break probe and ALK/EML4 t(2;2);inv(2) fusion probe, showed a normal pattern for all specimens. Histological evaluation confirmed the presence of AC in the superior right lobe and classified the GGO lesion as BAC and the normal tissue of the middle lobe as AAH. To the best of our knowledge, this is the first case in which the cytogenetic study of spontaneous metaphases showed a clear clonal relationship among AC, BAC and AAH present simultaneously in different lobes of the same lung. This case appears to indicate that the entire lung was somehow predisposed to a neoplastic transformation starting with a diffuse AAH characterized by high proliferative activity. Moreover, the 5q13 region involved in the translocation shared by BAC and AC contains at least 4 genes encoding important regulators of the cell cycle that may be considered new molecular markers of lung cancer.

  4. Thiophene metabolism by E. coli

    Energy Technology Data Exchange (ETDEWEB)

    Clark, D.P.

    1990-01-01

    The objective of this project is to investigate the mechanism of degradation of sulfur containing heterocyclic molecules such as those found in coal, by mutants of Escherichia coli K-12. We previously isolated multiple mutants of E. coli which were selected for improved oxidation of furan and thiophene derivatives. We have focused on the thdA mutation in our subsequent research as it appears to be of central importance in thiophene oxidation. We hope that analysis of the thd genes of E. coli will lead to improvement of our thiophene metabolizing bacterial strains. 1 tab.

  5. Toward Network Biology in E. coli Cell.

    Science.gov (United States)

    Mori, Hirotada; Takeuchi, Rikiya; Otsuka, Yuta; Bowden, Steven; Yokoyama, Katsushi; Muto, Ai; Libourel, Igor; Wanner, Barry L

    2015-01-01

    E. coli has been a critically important model research organism for more than 50 years, particularly in molecular biology. In 1997, the E. coli draft genome sequence was published. Post-genomic techniques and resources were then developed that allowed E. coli to become a model organism for systems biology. Progress made since publication of the E. coli genome sequence will be summarized.

  6. Escherichia coli Uropathogenesis In Vitro

    DEFF Research Database (Denmark)

    Andersen, Thomas E; Khandige, Surabhi; Madelung, Michelle

    2012-01-01

    Uropathogenic Escherichia coli (UPEC) strains are capable of invading bladder epithelial cells (BECs) on the bladder luminal surface. Based primarily on studies in mouse models, invasion is proposed to trigger an intracellular uropathogenic cascade involving intracellular bacterial proliferation...

  7. Epidermal growth factor receptor and alveolar epithelial atypical adenomatous hyperplasia%表皮生长因子受体与肺泡上皮不典型腺瘤样增生的关系

    Institute of Scientific and Technical Information of China (English)

    黄谦

    2012-01-01

    Lung cancer is a common malignant tumor and lung adenocarcinoma is the main type of it. Bronchioloalveolar lung carcinoma (BAC) is a special type of lung adenocarcinoma. Research indicates that alveolar epithelial atypical adenomatous hyperplasia (AAH) in BAC or adenocarcinoma may be a precancerous lesion, even in the early stage of cancer. Overexpression and/or mutatioin of epidermal growth factor receptor (EGFR) is closely related to the occurrence, development, invasion and metastasis of lung cancer, especially in non-small-cell lung cancer (NSCLC). But there are few studies reported about EGFR in the precancerous lesion of non-small-cell lung cancer.%肺癌是人类常见的恶性肿瘤,肺腺癌是其主要类型之一.细支气管肺泡癌(bronchioloalveolar lung carcinoma,BAC)是肺腺癌的一个特殊类型.肺泡上皮不典型腺瘤样增生(atypical adenomatous hyperplasia,AAH)可能是BAC或腺癌的癌前病变,甚至是其早期癌.表皮生长因子受体(epidermal growth factor receptor,EGFR)的过表达和(或)突变与肺癌尤其是非小细胞肺癌(non-small-cell lung cancer,NSCLC)的发生、发展、侵袭和转移等密切相关.

  8. Tumor odontogênico adenomatóide associado a cisto dentígero: relato de um caso incomum Adenomatoid odontogenic tumour associated with dentigerous cyst: unusual case report

    Directory of Open Access Journals (Sweden)

    Cassiano Francisco Weege Nonaka

    2007-02-01

    Full Text Available O tumor odontogênico adenomatóide é uma lesão relativamente incomum, que acomete preferencialmente indivíduos do sexo feminino durante a segunda década de vida, exibindo como sítio de predileção a região anterior da maxila. A lesão geralmente está associada à coroa de um dente incluso, comumente o canino. Neste trabalho é relatado o caso de um tumor odontogênico adenomatóide associado a cisto dentígero ocorrendo na região maxilar esquerda, em paciente do sexo feminino com 13 anos de idade, discutindo-se, ainda, as características clínicas, radiográficas, histopatológicas e terapêuticas do caso.The adenomatoid odontogenic tumor is a relatively uncommon lesion which mainly affects females in their second decade of life, exhibiting predilection for the anterior region of the maxilla. The lesion is usually associated with the crown of an enclosed tooth, most commonly the maxillary canine. In this paper we present a case of adenomatoid odontogenic tumor associated with a dentigerous cyst affecting the left maxillary region in a 13-year-old female. The authors also discuss clinical, radiographic, histopathologic and therapeutic features of the case.

  9. Diarrheagenic Escherichia coli Markers and Phenotypes among Fecal E. coli Isolates Collected from Nicaraguan Infants ▿

    OpenAIRE

    Reyes, Daniel; Vilchez, Samuel; Paniagua, Margarita; Colque-Navarro, Patricia; Weintraub, Andrej; Möllby, Roland; Kühn, Inger

    2010-01-01

    We analyzed the prevalence of diarrheagenic Escherichia coli (DEC) markers and common phenotypes in 2,164 E. coli isolates from 282 DEC-positive samples. Enteropathogenic E. coli (EPEC) and enteroaggregative E. coli (EAEC) were very diverse and were not correlated with diarrhea. Enterotoxigenic E. coli (ETEC) estA and enterohemorrhagic E. coli (EHEC) belonged to a few phenotypes and were significantly correlated with diarrhea.

  10. Diarrheagenic Escherichia coli Markers and Phenotypes among Fecal E. coli Isolates Collected from Nicaraguan Infants ▿

    OpenAIRE

    2010-01-01

    We analyzed the prevalence of diarrheagenic Escherichia coli (DEC) markers and common phenotypes in 2,164 E. coli isolates from 282 DEC-positive samples. Enteropathogenic E. coli (EPEC) and enteroaggregative E. coli (EAEC) were very diverse and were not correlated with diarrhea. Enterotoxigenic E. coli (ETEC) estA and enterohemorrhagic E. coli (EHEC) belonged to a few phenotypes and were significantly correlated with diarrhea.

  11. Identification of five novel modifier loci of Apc(Min) harbored in the BXH14 recombinant inbred strain.

    Science.gov (United States)

    Nnadi, Stephanie C; Watson, Rayneisha; Innocent, Julie; Gonye, Gregory E; Buchberg, Arthur M; Siracusa, Linda D

    2012-08-01

    Every year thousands of people in the USA are diagnosed with small intestine and colorectal cancers (CRC). Although environmental factors affect disease etiology, uncovering underlying genetic factors is imperative for risk assessment and developing preventative therapies. Familial adenomatous polyposis is a heritable genetic disorder in which individuals carry germ-line mutations in the adenomatous polyposis coli (APC) gene that predisposes them to CRC. The Apc ( Min ) mouse model carries a point mutation in the Apc gene and develops polyps along the intestinal tract. Inbred strain background influences polyp phenotypes in Apc ( Min ) mice. Several Modifier of Min (Mom) loci that alter tumor phenotypes associated with the Apc ( Min ) mutation have been identified to date. We screened BXH recombinant inbred (RI) strains by crossing BXH RI females with C57BL/6J (B6) Apc ( Min ) males and quantitating tumor phenotypes in backcross progeny. We found that the BXH14 RI strain harbors five modifier loci that decrease polyp multiplicity. Furthermore, we show that resistance is determined by varying combinations of these modifier loci. Gene interaction network analysis shows that there are multiple networks with proven gene-gene interactions, which contain genes from all five modifier loci. We discuss the implications of this result for studies that define susceptibility loci, namely that multiple networks may be acting concurrently to alter tumor phenotypes. Thus, the significance of this work resides not only with the modifier loci we identified but also with the combinations of loci needed to get maximal protection against polyposis and the impact of this finding on human disease studies.

  12. Polipose nasossinusal em criança com síndrome de Peutz-Jeghers Sinusonasal polyposis in a child with Peutz-Jeghers syndrome

    Directory of Open Access Journals (Sweden)

    Adriana C. Perez-Bóscollo

    2002-05-01

    Full Text Available A síndrome de Peutz-Jeghers (SPJ é uma doença autossômica dominante, caracterizada por polipose hamartomatosa intestinal em associação com pigmentação mucocutânea característica. Peutz (1921, na primeira publicação da síndrome que tem o seu nome, apresentou dois casos com pólipos em nasofaringe. Desde então, poucos desses casos foram publicados e com o passar do tempo a associação foi esquecida. Esse relato descreve uma variante rara da SPJ em um menino de quatorze anos de idade, identificada pela presença de polipose nasal bilateral, sinusite crônica e polipose hamartomatosa intestinal, previamente operado de oclusão intestinal. Macroscopicamente, foram encontradas múltiplas formações polipóides em cavidades nasais, branco-pardacentas, de consistência amolecida e com cavidades císticas. Histologicamente, esses pólipos mostravam características inflamatórias acompanhadas de metaplasia escamosa atípica. Na população pediátrica, a polipose nasal apresenta interesse específico. É uma condição infreqüente que requer investigação diagnóstica cuidadosa. O objetivo desse trabalho é mostrar uma doença rara (SPJ com associação em Cirurgia Pediátrica e ORL, chamando a atenção de cirurgiões, pediatras e especialistas para a importância de se investigar a etiologia da polipose nasossinusal nos pacientes pediátricos.Peutz-Jeghers syndrome (PJS is an autosomal dominant disease, characterized by in association with characteristic mucocutaneous pigmentation. Peutz (1921, in his first publication about the syndrome that has his name, presented two cases having polyps in the nasopharynx. Ever since, a few of those cases were published, as time goes, by association was forgotten. This report describes a rare variant of PJS in a fourteen years-old boy, identified by the presence of bilateral nasal polyposis, chronic sinusitis and hamartomatous intestinal polyposis, in an operated patient previously by intestinal

  13. Shiga Toxin Producing Escherichia coli.

    Science.gov (United States)

    Bryan, Allen; Youngster, Ilan; McAdam, Alexander J

    2015-06-01

    Shiga toxin-producing Escherichia coli (STEC) is among the common causes of foodborne gastroenteritis. STEC is defined by the production of specific toxins, but within this pathotype there is a diverse group of organisms. This diversity has important consequences for understanding the pathogenesis of the organism, as well as for selecting the optimum strategy for diagnostic testing in the clinical laboratory. This review includes discussions of the mechanisms of pathogenesis, the range of manifestations of infection, and the several different methods of laboratory detection of Shiga toxin-producing E coli.

  14. Experimental evolution of E. coli

    Science.gov (United States)

    Zhang, Mengshi

    The evolution from unicellular to multicellular behavior is an essential step in the history of life. Our aim is to investigate the emergence of collective behavior in the model organism Escherichia coli (E. coli) and its selection advantages, such as better utilization of public goods. Our preliminary results suggest that the evolution of collective behavior may be a natural response to stressed conditions. Mailing address: Room 306 Science Centre North Block, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong SAR. Phone: +852-3943-6354. Fax: +852-2603-5204. E-mail: mengshi0928@gmail.com.

  15. Expression in E. coli systems

    DEFF Research Database (Denmark)

    Krogsdam, Anne-M; Kristiansen, Karsten; Nøhr, Jane

    2003-01-01

    intracellularly in soluble form. In E. coli, proteins containing disulfide bonds are best produced by secretion because the disulfide forming foldases reside in the periplasm. Likewise, a correct N-terminus is more likely to be obtained upon secretion. Moreover, potentially toxic proteins are more likely......Owing to cost advantage, speed of production, and often high product yield (up to 50% of total cell protein), expression in Escherichia coli is generally the first choice when attempting to express a recombinant protein. Expression systems exist to produce recombinant protein intracellularly...

  16. Pathogenomics of uropathogenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    J Agarwal

    2012-01-01

    Full Text Available Subset of faecal E. coli that can enter, colonize urinary tract and cause infection are known as uropathogenic E. coli (UPEC. UPEC strains act as opportunistic intracellular pathogens taking advantage of host susceptibility using a diverse array of virulence factors. Presence of specific virulence associated genes on genomic/pathogenicity islands and involvement of horizontal gene transfer appears to account for evolution and diversity of UPEC. Recent success in large-scale genome sequencing and comparative genomics has helped in unravelling UPEC pathogenomics. Here we review recent findings regarding virulence characteristics of UPEC and mechanisms involved in pathogenesis of urinary tract infection.

  17. Vitamin D decreases the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 in fibroblasts derived from Taiwanese patients with chronic rhinosinusitis with nasal polyposis.

    Science.gov (United States)

    Wang, Ling-Feng; Tai, Chih-Feng; Chien, Chen-Yu; Chiang, Feng-Yu; Chen, Jeff Yi-Fu

    2015-05-01

    Vitamin D and its derivatives have modulatory effects in immunological and inflammatory responses. Such properties suggest that they might have an impact on chronic inflammatory airway diseases, including nasal polyposis. The aim of this study was to understand the role of vitamin D in chronic rhinosinusitis with nasal polyps (CRSwNP) by investigating its effect on the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9 in nasal polyp-derived fibroblasts. Two primary fibroblast cultures were established from nasal polyp tissues obtained during surgery. The nasal polyp-derived fibroblasts were stimulated with tumor necrosis factor-α (TNF-α; 10 ng/mL) for 24 hours, followed by replacement with media alone or with vitamin D derivatives (calcitriol or tacalcitol; 10μM) and incubated for another 24 hours. After the treatments, the levels of MMP-2 and MMP-9 secreted were evaluated by both enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. ELISA results revealed that TNF-α could substantially stimulate the secretion of MMP-2 (p MMP-2 and p MMP-2 and MMP-9). The ELISA results were also confirmed by Western blot analysis. The inhibitory effect of vitamin D derivatives on MMP-2 and MMP-9 secretion could potentiate their application in pharmacotherapy of Taiwanese CRSwNP patients.

  18. Effect of the premedication with oral clonidine on surgical comfort in patients undergoing fess due to advanced nasal polyposis: A randomized double blind clinical trial.

    Science.gov (United States)

    Tugrul, Selahattin; Dogan, Remzi; Senturk, Erol; Kocak, Ilker; Sezen, Seda; Bakan, Mefkur; Ozturan, Orhan

    OBJECTıVE: The objective of this randomized double blind study was to evaluate effect of the premedication with oral clonidine on blood pressure, cleaning of surgical site and bleeding in the ESS performed due to advanced NP. A total of 52 patients who underwent functional endoscopic sinus surgery (FESS) due to Kennedy grade 4 nasal polyposis (NP) were included. Patients were randomized into two groups. Group 1 (n=26) received 0.2mg oral clonodine one hour before the operation in addition to standard anesthesia procedure. Group 2 (n=26) was administered standard anesthesia procedure alone. The amount of bleeding during surgery, cleaning of surgical site and surgeon's satisfaction were evaluated in comparison between the groups. The amount of bleeding and mean arterial pressure were significantly lower in the Group 1 compared to the Group 2. The cleaning of surgical site was found to be significantly better and surgeon's satisfaction significantly higher in the Group 1 than in the Group 2. Systolic, diastolic and mean arterial pressures during surgery were significantly lower in the Group 1 compared to the Group 2. Premedication with oral clonidine provides a clearer view of surgical site, reduces the amount of bleeding and significantly increases surgeon's satisfaction during the operation in FESS performed due to NP. Premedication with oral clonidine is a safe, inexpensive and effective methods in order to increase the surgical success and comfort and reduce complications in the FESS surgery. Copyright © 2016. Published by Elsevier Inc.

  19. Infektionen mit darmpathogenen Escherichia coli.

    NARCIS (Netherlands)

    Friedrich, Alexander; Stein, Jürgen; Dignass, Axel

    2001-01-01

    E. coli ist ein wesentlicher Bestandteil der physiologischen Darmflora des Menschen. Die üblicherweise im Darm vorkommenden Kolibakterien sind apathogen und für den Menschen eher nützlich (Sonnenborn u. Greinwald 1990). Allerdings kennen wir bei dieser Bakterienspezies auch ein breites Spektrum von

  20. Expression in E. coli systems

    DEFF Research Database (Denmark)

    Krogsdam, Anne-M; Kristiansen, Karsten; Nøhr, Jane

    2003-01-01

    intracellularly in soluble form. In E. coli, proteins containing disulfide bonds are best produced by secretion because the disulfide forming foldases reside in the periplasm. Likewise, a correct N-terminus is more likely to be obtained upon secretion. Moreover, potentially toxic proteins are more likely...

  1. Cribriform-Morular Variant of Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Bahar AKKAYA

    2009-09-01

    Full Text Available Cribriform-morular variant of papillary thyroid carcinoma is a rare histological subtype of papillary thyroid carcinoma. This subtype is commonly reported in patients with familial adenomatous polyposis. However, cases not associated with polyposis have also been reported. The differential diagnosis of this entity from other aggressive thyroid neoplasms is important. A 29-year old man presented with a solitary mass in the left thyroid lobe underwent total thyroidectomy. Pathologic examination of the specimen revealed cribriform-morular variant of papillary thyroid carcinoma. After diagnosis, colonoscopy revealed a normal colon without polyposis. Herein, we report a case not associated with polyposis and discuss with the literature.

  2. Histopathological characteristics of human non-tumor thyroid tissues in a long-term model of adenomatous goiter xenografts in the NOD/Shi-scid, IL-2Rγ(null) mouse.

    Science.gov (United States)

    Fujii, Etsuko; Kato, Atsuhiko; Chen, Yu Jau; Matsubara, Koichi; Ohnishi, Yasuyuki; Suzuki, Masami

    2014-07-01

    There is a growing need for modeling the human thyroid to link data obtained from animals to humans because of its sensitivity to radiation exposure and endocrine disruption chemicals. In a scid mouse model produced by transplanting human thyroid tissues, leakiness and thymic lymphoma that occurs spontaneously in the scid mouse can complicate the interpretation of experimental results. Considering that the NOD.Cg-Prkdc(scid)Il2rg(tm1Sug)/Jic mouse (NOD/Shi-scid, IL-2Rγ(null) or NOG mouse) may be a better host because this strain has low incidence of leakiness and thymic lymphoma, we have evaluated the potential of a model that allows long-term observation of non-tumor human thyroid tissues in this mouse. We transplanted tissues of human adenomatous goiter into NOG mice and examined the tissues histopathologically. The morphology of human adenomatous goiter tissues was maintained from 24 to 44 weeks after transplantation in NOG mice with no noted differences between donor-matched tissues or the weeks after transplantation. The tissues expressed thyroglobulin protein and mRNA as well as thyroperoxidase. Endothelial cells originating from human were found in the transplanted tissues and were thought to be a characteristic of this model. The intactness of the tissues before transplantation was found to affect the rate of tissue engraftment. From the present results we have concluded that transplanted thyroid tissues in NOG mice maintain the histopathological characteristics of their origin for long terms. Therefore this model was thought feasible for toxicity evaluation. Copyright © 2014 Elsevier GmbH. All rights reserved.

  3. Tumor odontogênico adenomatóide em mandíbula Tumor odontógeno adenomatoide de la mandíbula Adenomatoid odontogenic tumor in mandible

    Directory of Open Access Journals (Sweden)

    Roberto de Almeida Azevedo

    2011-06-01

    Full Text Available Tumor odontogênico adenomatóide é uma lesão relativamente incomum, que acomete preferencialmente indivíduos do sexo feminino durante a segunda década de vida. Exibe como sítio de predileção a região anterior da maxila, é geralmente associado à coroa de um dente incluso. Este trabalho tem o objetivo de apresentar um caso clínico de tumor odontogênico adenomatóide. Este se apresenta localizado em região anterior da mandíbula. Pretende-se ainda abordar suas características clínicas, radiográficas e histológicas, além do tratamento cirúrgico conservador de eleição.El tumor odontógeno adenomatoide es una lesión relativamente infrecuente que afecta principalmente a las mujeres durante la segunda década de vida, porque su sitio predilecto es la región anterior de la mandíbula, con una lesión por lo general asociada con la corona del diente. Se reporta un caso de tumor odontógeno adenomatoide en la región anterior de la mandíbula junto con sus resultados clínicos, radiológicos e histológicos así como su tratamiento quirúrgico.Adenomatoid odontogenic tumor is a relatively uncommon lesion, which affects mainly individuals of the female during the second decade due, showing as a site of predilection for the anterior region of the maxilla presenting lesion usually associated with the crown of a tooth incluso. Os authors report a case of an adenomatoid odontogenic tumor in the anterior region of mandible, together with their clinical, radiographic and histological and its surgical treatment.

  4. Endogenous conversion of ω-6 to ω-3 polyunsaturated fatty acids in fat-1 mice attenuated intestinal polyposis by either inhibiting COX-2/β-catenin signaling or activating 15-PGDH/IL-18.

    Science.gov (United States)

    Han, Young-Min; Park, Jong-Min; Cha, Ji-Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-05-01

    Omega-3 polyunsaturated fatty acids (ω-3PUFAs) have inhibitory effects in various preclinical cancer models, but their effects in intestinal polyposis have never been examined. As attempts have been made to use nutritional intervention to counteract colon cancer development, in this study we evaluated the effects of ω-3 PUFAs on intestinal polyposis in the Apc(Min/+) mouse model. The experimental groups included wild-type C56BL/6 mice, Apc(Min/+) mice, fat-1 transgenic mice expressing an n-3 desaturase to enable ω-3 PUFA synthesis, and Apc(Min/+) × fat-1 double-transgenic mice; all mice were 20 weeks of age. Small intestines were collected for gross and pathologic evaluation, including assessment of polyp number and size, followed by immunohistochemical staining and Western blotting. After administration of various concentrations of ω-3 PUFAs, PUFA levels were measured in small intestine tissue by GC/MS/MS analysis to compare with PUFA synthesis of between C57BL6 and fat-1mice. As a result, ω-3 PUFAs significantly attenuated Apc mutation-induced intestinal polyposis accompanied with significant inhibition of Wnt/β-catenin signaling, COX-2 and PGE2, but induced significant levels of 15-PGDH. In addition, significant induction of the inflammasome-related substrates as IL-1β and IL-18 and activation of caspase-1 was observed in Apc(Min/+) × fat-1 mice. Administration of at least 3 g/60 kg ω-3 PUFAs was equivalent to ω-3 PUFAs produced in fat-1 mice and resulted in significant increase in the expression of IL-1β, caspase-3 and IL-18, as seen in Apc(Min/+) × fat-1 mice. We conclude that ω-3PUFAs can prevent intestinal polyp formation by inhibition of Wnt/β-catenin signaling, but increased levels of 15-PGDH and IL-18.

  5. Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors

    Directory of Open Access Journals (Sweden)

    Huiling Xu

    2014-12-01

    Full Text Available Loss of heterozygosity (LOH of the adenomatous polyposis coli (APC gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC. We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1 retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer.

  6. Fibersol-2 induces apoptosis of Apc-deficient colorectal Cancer (SW480) cells and decreases polyp formation in Apc MIN mice.

    Science.gov (United States)

    Sancho, Sara Cuesta; Olson, Susan Losee; Young So, Eui; Shimomura, Kazuhiro; Ouchi, Toru; Preuss, Fabian

    2016-06-02

    The consumption of dietary fibers has been implicated with a lowered risk of human colorectal cancer. Proposed mechanisms involve alterations in the stool consistency, transit time, and formation of short-chain fatty acid by dietary fiber fermentation, and the reorganization of gut microbiota. Here we show that Fibersol-2, a digest-resistant maltodextrin, not only inhibits proliferation of colorectal SW480 cancer cell lines by increasing reactive oxygen species (ROS), but decreases the numbers of the adenoma count in Multiple Intestinal Neoplasia (MIN) mice carrying a mutation in the Adenomatous Polyposis Coli gene by 84 d of age. These observations provide direct evidence that Fibersol-2 intrinsically contains anti-cancer activity, independent of the intestinal metabolism and any potential interactions with the microbiota.

  7. Restoration of APC gene function in colorectal cancer cells by aminoglycoside- and macrolide-induced read-through of premature termination codons.

    Science.gov (United States)

    Zilberberg, Alona; Lahav, Lital; Rosin-Arbesfeld, Rina

    2010-04-01

    Adenomatous polyposis coli (APC) is a multifunctional tumour suppressor protein that negatively regulates the Wnt signalling pathway. The APC gene is ubiquitously expressed in tissues and organs, including the large intestine and central nervous system. The majority of patients with sporadic and hereditary colorectal cancer have mutations in the gene encoding APC. Approximately 30% of these mutations are single nucleotide changes that result in premature stop codons (nonsense mutations). A potential therapeutic approach for treatment of this subset of patients is the use of aminoglycosides and macrolides that induce nonsense mutation read-through and restore levels of full-length protein. We have used reporter plasmids and colorectal cancer cell lines to demonstrate that several aminoglycosides and tylosin, a member of the macrolide family, induced read-through of nonsense mutations in the APC gene. In xenograft experiments and in the Apc(Min/+) mouse model, these compounds ameliorated the tumorigenic clinical symptoms caused by nonsense mutations in the APC gene.

  8. The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma.

    Science.gov (United States)

    Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques

    2016-01-01

    To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student's t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (pbeta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted. Avaliar o complexo de destruição da betacatenina no carcinoma colorretal e no adenoma do colo pela expressão das proteínas betacatenina, adenomatous polyposis coli, GSK3β, axina e ubiquitina. Amostras de tecidos de 64 doentes com carcinoma colorretal e de 53 pacientes com adenoma do colo foram analisadas. Blocos de tecidos foram submetidos ao estudo imuno-histoquímico com anticorpos policlonais nos tecidos do carcinoma, mucosa não neoplásica adjacente e adenoma. A imunorreatividade foi avaliada pela porcentagem de positividade de células coradas e pela intensidade do grau de coloração das proteínas no citoplasma e no núcleo das células. Na análise estatística, foram

  9. Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Junxiong Chen

    2015-10-01

    Full Text Available The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX and some of its analogues, the secondary metabolites from marine fungus Neosartorya pseufofischeri, acted as inhibitors of the Wnt signaling pathway. In addition, we found that GTX downregulated the β-catenin levels in colorectal cancer cells with inactivating mutations of adenomatous polyposis coli (APC or activating mutations of β-catenin. Furthermore, we demonstrated that GTX induced growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway. Together, we illustrated a practical approach to identify small-molecule inhibitors of the Wnt signaling pathway and our study indicated that GTX has therapeutic potential for the prevention or treatment of Wnt dependent cancers and other Wnt related diseases.

  10. Chromosomal features of Escherichia coli serotype O2:K2, an avian pathogenic E. coli

    DEFF Research Database (Denmark)

    Jørgensen, Steffen L; Kudirkiene, Egle; Li, Lili

    2017-01-01

    Escherichia coli causing infection outside the gastrointestinal system are referred to as extra-intestinal pathogenic E. coli. Avian pathogenic E. coli is a subgroup of extra-intestinal pathogenic E. coli and infections due to avian pathogenic E. coli have major impact on poultry production economy...... and welfare worldwide. An almost defining characteristic of avian pathogenic E. coli is the carriage of plasmids, which may encode virulence factors and antibiotic resistance determinates. For the same reason, plasmids of avian pathogenic E. coli have been intensively studied. However, genes encoded...... by the chromosome may also be important for disease manifestation and antimicrobial resistance. For the E. coli strain APEC_O2 the plasmids have been sequenced and analyzed in several studies, and E. coli APEC_O2 may therefore serve as a reference strain in future studies. Here we describe the chromosomal features...

  11. Mecanismos de ação dos corticosteróides na polipose rinossinusal Mechanism of action of glucocorticoids in nasal polyposis

    Directory of Open Access Journals (Sweden)

    Atílio Maximino Fernandes

    2008-04-01

    Full Text Available Os glicocorticóides (GC são drogas de escolha no tratamento clínico da polipose nasossinusal conforme recomendação da literatura. Entretanto, seus mecanismos de ação nas regressões dos sintomas clínicos e dos pólipos não são totalmente compreendidos. Sabe-se que a administração tópica e ou sistêmica dos glicocorticóides leva a variações na expressão de citocinas, quimiocinas e linfocinas, além das alterações celulares. Assim, os GC suprimem a expressão de citocinas pró-inflamatórias, de quimiocinas, de moléculas de adesão, além de estimular a transcrição de citocinas antiinflamatórias. Citocinas pró-fibróticas como a IL-11, fator básico de crescimento do fibroblasto (b-FGF e fator de crescimento endotelial vascular (VEGF, relacionados com o crescimento do pólipo, também são suprimidos pela ação do GC. Tal ação depende fundamentalmente da interação com os seus receptores (GR, pois alguns indivíduos apresentam algum grau de resistência celular ao seu efeito, que parece estar relacionada com a presença da isoforma b do GR. Genes envolvidos nas fases de produção de imunoglobulinas, apresentação e processamento do antígeno também sofrem ação dos GC de forma variada. OBJETIVOS: Fazer uma revisão da literatura sobre os mecanismos de ação do GC na PNS. CONCLUSÃO: A compreensão desses mecanismos implicará no desenvolvimento de drogas mais eficazes na sua terapêutica.Glucocorticoids (GC are the drugs of choice for the clinical treatment of nasal polyposis, according to the medical literature. Its mechanism of action in the regression of clinical symptoms and polyps, however, is not fully understood. The topical and/or systemic use of glucocorticoids lead to variable expression of cytokines, chemokines and lymphokines, as well as changes in cells. It is known that GC suppresses the expression of pro-inflammatory cytokines, chemokines and adhesion molecules such as ICAM-1 and E-selectin; GC also

  12. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

    Directory of Open Access Journals (Sweden)

    Faraz Bishehsari

    2016-12-01

    Full Text Available Background: Colorectal cancer (CRC is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APClox468 mice underwent (a an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2 and 6 (MCP6 histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal/mMCP2 (intraepithelial mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

  13. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota.

    Science.gov (United States)

    Bishehsari, Faraz; Saadalla, Abdulrahman; Khazaie, Khashayarsha; Engen, Phillip A; Voigt, Robin M; Shetuni, Brandon B; Forsyth, Christopher; Shaikh, Maliha; Vitaterna, Martha Hotz; Turek, Fred; Keshavarzian, Ali

    2016-12-02

    Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption-a frequent habit of majority of modern societies-increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption-another modern life style habit-in promoting alcohol-associated CRC. TS4Cre × adenomatous polyposis coli (APC)(lox468) mice underwent (a) an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b) an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD) cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2) and 6 (MCP6) histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal)/mMCP2 (intraepithelial) mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

  14. Thiophene metabolism by E. coli

    Energy Technology Data Exchange (ETDEWEB)

    Clark, D.P.

    1991-01-01

    The objective of this project is to investigate the mechanism of degradation of sulfur-containing heterocyclic molecules by mutant strains of Escherichia coli K-12. We have previously isolated multiple mutants of E. coli which had gained the capacity to oxidize thiophene compounds and their furan analogs. We have focused on the thdA mutation in our subsequent research, as this appears to be in a regulatory gene central to the thiophene/furan oxidation system. The thdF gene appears to be more directly involved in the oxidation reactions, whereas thdC and thdD are apparently required for increased protection against the toxic effects of thiophene and furan compounds. 4 tabs.

  15. Multiplex PCR Assay for Identification of Human Diarrheagenic Escherichia coli

    OpenAIRE

    Toma, Claudia; Lu, Yan; Higa, Naomi; Nakasone, Noboru; Isabel CHINEN; Baschkier, Ariela; Rivas, Marta; Iwanaga, Masaaki

    2003-01-01

    A multiplex PCR assay for the identification of human diarrheagenic Escherichia coli was developed. The targets selected for each category were eae for enteropathogenic E. coli, stx for Shiga toxin-producing E. coli, elt and est for enterotoxigenic E. coli, ipaH for enteroinvasive E. coli, and aggR for enteroaggregative E. coli. This assay allowed the categorization of a diarrheagenic E. coli strain in a single reaction tube.

  16. Multiplex PCR Assay for Identification of Human Diarrheagenic Escherichia coli

    OpenAIRE

    2003-01-01

    A multiplex PCR assay for the identification of human diarrheagenic Escherichia coli was developed. The targets selected for each category were eae for enteropathogenic E. coli, stx for Shiga toxin-producing E. coli, elt and est for enterotoxigenic E. coli, ipaH for enteroinvasive E. coli, and aggR for enteroaggregative E. coli. This assay allowed the categorization of a diarrheagenic E. coli strain in a single reaction tube.

  17. Estudio clínico e histológico de la poliposis nasal Clinical and histological study of nasal polyposi

    Directory of Open Access Journals (Sweden)

    Eulalia Alfonso Muñoz

    2004-12-01

    Full Text Available Se realiza un estudio de 50 pacientes que padecieron de poliposis nasal. La mayoría de los pacientes están comprendidos en la 4ta. y 5ta. décadas de la vida, con predominio del sexo masculino. El tiempo de evolución de la enfermedad que predominó en los pacientes fue de 1 a 4 años. Los antecedentes alérgicos y la eosinofilia sanguínea estuvieron presentes en nuestros casos. Todos los pacientes recibieron tratamiento quirúrgico, que consistió en polipectomía nasal anterior, en ocasiones asociada a la técnica de maxiloetmoidectomía. En las muestras obtenidas predominó, desde el punto de vista macroscópico, el aspecto polipoide, la mucosa engrosada y la secreción mucoserosa. Asimismo, en el análisis histopatológico se observó hipertrofia epitelial, engrosamiento de la membrana basal, edema e hiperplasia glandular en la lámina propiaA study of 50 patients suffering from nasal polyposis was conducted. Most of the patients were 40 and 50 years old. It was observed a predominance of males. The time of the evolution of the disease prevailing among the patients was from 1 to 4 years. The allergy history and blood eosynophilia were present in our cases. All the patients underwent surgery, which consisted in anterior nasal polypectomy on occasions associated with the maxilloethmoidectomy technique. In the samples obtained it was observed a predominance, from the macroscopical point of view, of the polypoid aspect, the thickened mucosa and the mucoserous secretion. Likewise, epithelial hypertrophy, thickening of the nasal membrane, edema and glandular hyperplasia in the own lamina were found in the histopathological analysis

  18. Two novel germline mutations of MLH1 and investigation of their pathobiology in hereditary non-polyposis colorectal cancer families in China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To detect germline mutations of MLH1, and investigate microsatellite instability and expression of MLH1 in tumor tissues of hereditary non-polyposis colorectal cancer (HNPCC) with two novel germline mutations, and further investigate the pathobiology of the two novel mutations of MLH1.METHODS: RNA was extracted from the peripheral blood of 12 patients from 12 different families that fulfilled the Amsterdam Ⅱ Criteria for HNPCC. Germline mutations of MLH1 were determined by RT-PCR,followed by cDNA sequencing analysis. PCR-GeneScan analysis was used to investigate microsatellite instability with a panel of five microsatellite markers (BAT26,BAT25, D5S346, D2S123 and mfd15), along with immunohistochemical staining to detect the expression of MLH1 protein in two patients' tumor tissues with novel mutations.RESULTS: Three germline mutations were found in four patients, one of the mutations has previously been reported, but the other two, CGC→TGC at codon 217 of exon 8 and CCG→CTG at codon 581 of exon 16, have not been reported. The two patients' tumor tissues with novel mutations had high-frequency microsatellite instability that showed more than two unstable loci, and both tumors lost their MLH1 protein expression.CONCLUSION: The two novel germline mutations of MLH1 in HNPCC families i.e. CGC→TGC at codon 217 of exon 8 and CCG→CTG at codon 581 of exon 16, are very likely to have pathological significance.

  19. Enterohemorrhagic E. coli (EHEC) pathogenesis

    OpenAIRE

    Vanessa eSperandio; Y eNguyen

    2012-01-01

    Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is a human pathogen responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide. Conventional antimicrobials trigger an SOS response in EHEC that promotes the release of the potent Shiga toxin that is responsible for much of the morbidity and mortality associated with EHEC infection. Cattle are a natural reservoir of EHEC, and approximately 75% of EHEC outbreaks are linked to the consumption of contamina...

  20. Robust growth of Escherichia coli.

    Science.gov (United States)

    Wang, Ping; Robert, Lydia; Pelletier, James; Dang, Wei Lien; Taddei, Francois; Wright, Andrew; Jun, Suckjoon

    2010-06-22

    The quantitative study of the cell growth has led to many fundamental insights in our understanding of a wide range of subjects, from the cell cycle to senescence. Of particular importance is the growth rate, whose constancy represents a physiological steady state of an organism. Recent studies, however, suggest that the rate of elongation during exponential growth of bacterial cells decreases cumulatively with replicative age for both asymmetrically and symmetrically dividing organisms, implying that a "steady-state" population consists of individual cells that are never in a steady state of growth. To resolve this seeming paradoxical observation, we studied the long-term growth and division patterns of Escherichia coli cells by employing a microfluidic device designed to follow steady-state growth and division of a large number of cells at a defined reproductive age. Our analysis of approximately 10(5) individual cells reveals a remarkable stability of growth whereby the mother cell inherits the same pole for hundreds of generations. We further show that death of E. coli is not purely stochastic but is the result of accumulating damages. We conclude that E. coli, unlike all other aging model systems studied to date, has a robust mechanism of growth that is decoupled from cell death.

  1. Chromosomal features of Escherichia coli serotype O2:K2, an avian pathogenic E. coli.

    Science.gov (United States)

    Jørgensen, Steffen L; Kudirkiene, Egle; Li, Lili; Christensen, Jens P; Olsen, John E; Nolan, Lisa; Olsen, Rikke H

    2017-01-01

    Escherichia coli causing infection outside the gastrointestinal system are referred to as extra-intestinal pathogenic E. coli. Avian pathogenic E. coli is a subgroup of extra-intestinal pathogenic E. coli and infections due to avian pathogenic E. coli have major impact on poultry production economy and welfare worldwide. An almost defining characteristic of avian pathogenic E. coli is the carriage of plasmids, which may encode virulence factors and antibiotic resistance determinates. For the same reason, plasmids of avian pathogenic E. coli have been intensively studied. However, genes encoded by the chromosome may also be important for disease manifestation and antimicrobial resistance. For the E. coli strain APEC_O2 the plasmids have been sequenced and analyzed in several studies, and E. coli APEC_O2 may therefore serve as a reference strain in future studies. Here we describe the chromosomal features of E. coli APEC_O2. E. coli APEC_O2 is a sequence type ST135, has a chromosome of 4,908,820 bp (plasmid removed), comprising 4672 protein-coding genes, 110 RNA genes, and 156 pseudogenes, with an average G + C content of 50.69%. We identified 82 insertion sequences as well as 4672 protein coding sequences, 12 predicated genomic islands, three prophage-related sequences, and two clustered regularly interspaced short palindromic repeats regions on the chromosome, suggesting the possible occurrence of horizontal gene transfer in this strain. The wildtype strain of E. coli APEC_O2 is resistant towards multiple antimicrobials, however, no (complete) antibiotic resistance genes were present on the chromosome, but a number of genes associated with extra-intestinal disease were identified. Together, the information provided here on E. coli APEC_O2 will assist in future studies of avian pathogenic E. coli strains, in particular regarding strain of E. coli APEC_O2, and aid in the general understanding of the pathogenesis of avian pathogenic E. coli.

  2. Presence of Shiga toxin-producing Escherichia coli, Enteroinvasive E. coli, Enteropathogenic E. coli, and Enterotoxigenic E. coli on tomatoes from public markets in Mexico.

    Science.gov (United States)

    Gómez-Aldapa, Carlos A; Torres-Vitela, M Del Refugio; Acevedo-Sandoval, Otilio A; Rangel-Vargas, Esmeralda; Villarruel-López, Angélica; Castro-Rosas, Andjavier

    2013-09-01

    Diarrheagenic Escherichia coli pathotypes (DEP) are important foodborne pathogens in various countries, including Mexico. However, no data exist on the presence of DEP on fresh tomatoes (Solanum lycopericum) from Mexico. The frequency of fecal coliforms (FC), E. coli, and DEP were determined for two tomato varieties. One hundred samples of a saladette tomato variety and 100 samples of a red round tomato variety were collected from public markets in Pachuca, Mexico. Each tomato sample consisted of four whole tomatoes. For the 100 saladette samples, coliform bacterial, FC, E. coli, and DEP were identified in 100, 70, 60, and 10% of samples, respectively. For the 100 red round samples, coliform bacterial, FC, E. coli, and DEP were identified in 100, 75, 65, and 11% of samples, respectively. Identified DEP included Shiga toxin-producing E. coli (STEC), enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). STEC were isolated from 6% of saladette samples and 5% of red round samples. ETEC were isolated from 3% of saladette samples and 4% of red round samples. EPEC were isolated from 2% of saladette samples and 3% of red round samples, and EIEC were isolated from 1% of saladette samples. Both STEC and ETEC were identified in two saladette samples and 1 red round sample. E. coli O157:H7 was not detected in any STEC-positive samples.

  3. Escherichia coli in Europe: An Overview

    Directory of Open Access Journals (Sweden)

    Nerino Allocati

    2013-11-01

    Full Text Available Escherichia coli remains one of the most frequent causes of several common bacterial infections in humans and animals. E. coli is the prominent cause of enteritis, urinary tract infection, septicaemia and other clinical infections, such as neonatal meningitis. E. coli is also prominently associated with diarrhoea in pet and farm animals. The therapeutic treatment of E. coli infections is threatened by the emergence of antimicrobial resistance. The prevalence of multidrug-resistant E. coli strains is increasing worldwide principally due to the spread of mobile genetic elements, such as plasmids. The rise of multidrug-resistant strains of E. coli also occurs in Europe. Therefore, the spread of resistance in E. coli is an increasing public health concern in European countries. This paper summarizes the current status of E. coli strains clinically relevant in European countries. Furthermore, therapeutic interventions and strategies to prevent and control infections are presented and discussed. The article also provides an overview of the current knowledge concerning promising alternative therapies against E. coli diseases.

  4. Gardner's syndrome: Genetic testing and colonoscopy are indicated in adolescents and young adults with cranial osteomas: A case report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We present a case of a 25-year-old female with diagnosed familial adenomatous polyposis and elevated carcinoembryonic antigen with negative family history.The suspicion of Gardner's syndrome was raised because extirpation of an osteoma of the left temporo-occipital region was made 10 years ago. Restorative proctocolectomy and ileal pouch anal anastomosis was made but histology delineated adenocarcinoma of the rectum (Dukes C stage). We conclude that cranial osteomas often precede gastrointestinal manifestations of familial adenomatous polyposis or Gardner's syndrome and such patients should be evaluated with genetic testing followed by colonoscopy if results are positive to prevent the development of colorectal carcinoma. If the diagnosis is positive all family members should be evaluated for familial adenomatous polyposis.

  5. Annual Surveillance Summary: Escherichia coli (E. coli) Infections in the Military Health System (MHS), 2016

    Science.gov (United States)

    2017-06-30

    Annual Surveillance Summary: Escherichia coli (E. coli) Infections in the Military Health System (MHS...and prevalence among all beneficiaries seeking care within the Military Health System (MHS). This report describes demographics, clinical...linked to assess descriptive and clinical factors related to E. coli. Health Level 7 (HL7)-formatted Composite Health Care System (CHCS) microbiology data

  6. neonatal infections caused by escherichia coli at the national ...

    African Journals Online (AJOL)

    boaz

    Knowledge about common infections caused by E.coli as well as its antibiotics susceptibility pattern will guide ... Keywords: Neonates, E.coli Infections, Antibiotics Resistance, Abuja. ..... Resistance in E.coli 0157 Strains and the Public Health.

  7. Study on the origin and nature of the adenomatoid odontogenic tumor by immunohistochemistry Estudo da origem e natureza do tumor odontogênico adenomatóide pela imunoistoquímica

    Directory of Open Access Journals (Sweden)

    Marcelo Macedo Crivelini

    2005-12-01

    Full Text Available The adenomatoid odontogenic tumor (AOT is a clinically benign lesion. Discussions about the AOT hamartomatous or neoplastic nature, and the probable odontogenic epithelial cell it originates from still exist. This research aimed to study and discuss the subject by the immunohistochemical detection of cytokeratins, laminin, collagen IV, PCNA and p53 in 8 tumor samples and 8 dental follicle samples containing reduced enamel epithelium. The results have shown that CK14 labelling indicated differentiation grades for secreting ameloblasts or ameloblasts in the post-secreting stage in the adenomatoid structure of AOT. Laminin, found on the luminal surface of adenomatoid structures, was compatible with the reduced enamel epithelium during the "protective stage of amelogenesis". PCNA specifically labelled the spindled areas and peripheral cords of the AOT, indicating that these areas are responsible for tumor growth. After considerations about pathogenesis, the authors suggested that the nature of AOT is hamartomatous with histogenesis from the reduced enamel epithelium.O tumor odontogênico adenomatóide (TOA é uma lesão clinicamente benigna, cujas discussões acerca de sua natureza hamartomatosa ou neoplásica, e provável célula epitelial odontogênica de origem ainda existem. Este projeto de pesquisa teve por objetivo estudar o assunto através da detecção imuno-histoquímica das citoqueratinas, laminina, colágeno IV, PCNA e p53, utilizando-se para isso 08 amostras do tumor e 08 amostras de folículo pericoronário contendo epitélio reduzido do órgão do esmalte (EROE. Os resultados mostraram que a marcação da CK14 sinalizou graus de diferenciação para ameloblastos secretores ou pós-secretores nas estruturas adenomatóides do TOA, e a laminina presente em sua superfície luminal foi compatível com o EROE durante o "estágio protetor" da amelogênese. O PCNA marcou especificamente áreas enoveladas e cordões periféricos do TOA

  8. Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities.

    Science.gov (United States)

    Silva, Patrícia; Albuquerque, Cristina; Lage, Pedro; Fontes, Vanessa; Fonseca, Ricardo; Vitoriano, Inês; Filipe, Bruno; Rodrigues, Paula; Moita, Susana; Ferreira, Sara; Sousa, Rita; Claro, Isabel; Nobre Leitão, Carlos; Chaves, Paula; Dias Pereira, António

    2016-09-01

    Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0.027) and a more heterogeneous histological pattern of lesions (p=0.032) than the patients with sporadic SPP. We identified two molecular forms of SPP-FHP/CRC, according to the preferential location of the lesions: proximal/whole-colon or distal colon. Mismatch repair (MMR) gene methylation [mutS homolog 6 (MSH6)/mutS homolog 3 (MSH3)] or loss of heterozygosity (LOH) of D2S123 (flanking MSH6) were detected exclusively in the former (p=3.0x10-7), in most early lesions. Proximal/whole‑colon SPP-FHP/CRC presented a higher frequency of O-6-methylguanine-DNA methyltransferase (MGMT) methylation/LOH, microsatellite instability (MSI) and Wnt mutations (19/29 vs. 7/17; 16/23 vs. 1/14, p=2.2x10-4; 15/26 vs. 2/15, p=0.006; 14/26 vs. 4/20, p=0.02) but a lower frequency of B-raf proto-oncogene, serine/threonine kinase (BRAF) mutations (7/30 vs. 12/20, p=0.0089) than the distal form. CRC was more frequent in cases of Kirsten rat sarcoma viral oncogene homolog (KRAS)-associated proximal/whole-colon SPP-FHP/CRC than in the remaining cases (4/4 vs. 1/8, p=0.01). Thus, SPP-FHP/CRC appears to be a specific entity, presenting two forms, proximal/whole-colon and distal, which differ in the underlying tumor initiation pathways. Early MGMT and MMR gene deficiency in the former may underlie an inherited susceptibility to genotoxic stress.

  9. Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue

    Directory of Open Access Journals (Sweden)

    Dourisboure Ricardo J

    2006-01-01

    Full Text Available Abstract Background Hereditary non-polyposis colon cancer (HNPCC is an autosomal dominant syndrome predisposing to the early development of various cancers including those of colon, rectum, endometrium, ovarium, small bowel, stomach and urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair genes, mostly hMSH2 or hMLH1. In this study, we report the analysis for genetic counseling of three first-degree relatives (the mother and two sisters of a male who died of colorectal adenocarcinoma at the age of 23. The family fulfilled strict Amsterdam-I criteria (AC-I with the presence of extracolonic tumors in the extended pedigree. We overcame the difficulty of having a proband post-mortem non-tumor tissue sample for MSI testing by studying the alleles carried by his progenitors. Methods Tumor MSI testing is described as initial screening in both primary and metastasis tumor tissue blocks, using the reference panel of 5 microsatellite markers standardized by the National Cancer Institute (NCI for the screening of HNPCC (BAT-25, BAT-26, D2S123, D5S346 and D17S250. Subsequent mutation analysis of the hMLH1 and hMSH2 genes was performed. Results Three of five microsatellite markers (BAT-25, BAT-26 and D5S346 presented different alleles in the proband's tumor as compared to those inherited from his parents. The tumor was classified as high frequency microsatellite instability (MSI-H. We identified in the HNPCC family a novel germline missense (c.1864C>A mutation in exon 12 of hMSH2 gene, leading to a proline 622 to threonine (p.Pro622Thr amino acid substitution. Conclusion This approach allowed us to establish the tumor MSI status using the NCI recommended panel in the absence of proband's non-tumor tissue and before sequencing the obligate carrier. According to the Human Gene Mutation Database (HGMD and the International Society for Gastrointestinal Hereditary Tumors (InSiGHT Database this is the first report of this mutation.

  10. E. coli survival in waters: temperature dependence

    Science.gov (United States)

    Knowing the survival rates of water-borne Escherichia coli is important for evaluating microbial contamination and in making appropriate management decisions. E. coli survival rates are dependent on temperature; this dependency is routinely expressed using an analog of the Q10 model. This suggestion...

  11. Genes under positive selection in Escherichia coli

    DEFF Research Database (Denmark)

    Petersen, Lise; Bollback, J.P.; Dimmic, Matt

    2007-01-01

    We used a comparative genomics approach to identify genes that are under positive selection in six strains of Escherichia coli and Shigella flexneri, including five strains that are human pathogens. We find that positive selection targets a wide range of different functions in the E. coli genome...

  12. Third International E. coli genome meeting

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    Proceedings of the Third E. Coli Genome Meeting are provided. Presentations were divided into sessions entitled (1) Large Scale Sequencing, Sequence Analysis; (2) Databases; (3) Sequence Analysis; (4) Sequence Divergence in E. coli Strains; (5) Repeated Sequences and Regulatory Motifs; (6) Mutations, Rearrangements and Stress Responses; and (7) Origins of New Genes. The document provides a collection of abstracts of oral and poster presentations.

  13. Fosfomycin Resistance in Escherichia coli, Pennsylvania, USA.

    Science.gov (United States)

    Alrowais, Hind; McElheny, Christi L; Spychala, Caressa N; Sastry, Sangeeta; Guo, Qinglan; Butt, Adeel A; Doi, Yohei

    2015-11-01

    Fosfomycin resistance in Escherichia coli is rare in the United States. An extended-spectrum β-lactamase-producing E. coli clinical strain identified in Pennsylvania, USA, showed high-level fosfomycin resistance caused by the fosA3 gene. The IncFII plasmid carrying this gene had a structure similar to those found in China, where fosfomycin resistance is commonly described.

  14. Fimbrial adhesins from extraintestinal Escherichia coli

    DEFF Research Database (Denmark)

    Klemm, Per; Hancock, Viktoria; Schembri, Mark A.

    2010-01-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) represent an important subclass of E. coli that cause a wide spectrum of diseases in human and animal hosts. Fimbriae are key virulence factors of ExPEC strains. These long surface located rod-shaped organelles mediate receptor-specific attachment...

  15. Infectious endocarditis caused by Escherichia coli

    DEFF Research Database (Denmark)

    Lauridsen, Trine Kiilerich; Arpi, Magnus; Fritz-Hansen, Thomas

    2011-01-01

    Although Escherichia coli is among the most common causes of Gram-negative bacteraemia, infectious endocarditis (IE) due to this pathogen is rare. A 67-y-old male without a previous medical history presented with a new mitral regurgitation murmur and persisting E. coli bacteraemia in spite of broad...

  16. Survival of Escherichia coli in stormwater biofilters.

    Science.gov (United States)

    Chandrasena, G I; Deletic, A; McCarthy, D T

    2014-04-01

    Biofilters are widely adopted in Australia for stormwater treatment, but the reported removal of common faecal indicators (such as Escherichia coli (E. coli)) varies from net removal to net leaching. Currently, the underlying mechanisms that govern the faecal microbial removal in the biofilters are poorly understood. Therefore, it is important to study retention and subsequent survival of faecal microorganisms in the biofilters under different biofilter designs and operational characteristics. The current study investigates how E. coli survival is influenced by temperature, moisture content, sunlight exposure and presence of other microorganisms in filter media and top surface sediment. Soil samples were taken from two different biofilters to investigate E. coli survival under controlled laboratory conditions. Results revealed that the presence of other microorganisms and temperature are vital stressors which govern the survival of E. coli captured either in the top surface sediment or filter media, while sunlight exposure and moisture content are important for the survival of E. coli captured in the top surface sediment compared to that of the filter media. Moreover, increased survival was found in the filter media compared to the top sediment, and sand filter media was found be more hostile than loamy sand filter media towards E. coli survival. Results also suggest that the contribution from the tested environmental stressors on E. coli survival in biofilters will be greatly affected by the seasonality and may vary from one site to another.

  17. Genes under positive selection in Escherichia coli

    DEFF Research Database (Denmark)

    Petersen, Lise; Bollback, J.P.; Dimmic, Matt

    2007-01-01

    We used a comparative genomics approach to identify genes that are under positive selection in six strains of Escherichia coli and Shigella flexneri, including five strains that are human pathogens. We find that positive selection targets a wide range of different functions in the E. coli genome...

  18. Prevalence of Escherichia coli O157

    NARCIS (Netherlands)

    Abdissa, Rosa; Haile, Woynshet; Fite, Akafete Teklu; Beyi, Ashenafi Feyisa; Agga, Getahun E.; Edao, Bedaso Mammo; Tadesse, Fanos; Korsa, Mesula Geloye; Beyene, Takele; Beyene, Tariku Jibat; Zutter, De Lieven; Cox, Eric; Goddeeris, Bruno Maria

    2017-01-01

    Background: There is paucity of information regarding the epidemiology of Escherichia coli O157: H7 in developing countries. In this study, we investigated the occurrence of E. coli O157: H7 associated with beef cattle at processing plants and at retail shops in Ethiopia. Methods: Various samples

  19. Escherichia coli survival in waters: Temperature dependence

    Science.gov (United States)

    Knowing the survival rates of water-borne Escherichia coli is important in evaluating microbial contamination and making appropriate management decisions. E. coli survival rates are dependent on temperature, a dependency that is routinely expressed using an analogue of the Q10 mo...

  20. Strategies for Protein Overproduction in Escherichia coli.

    Science.gov (United States)

    Mott, John E.

    1984-01-01

    Examines heterologous expression in Escherichia coli and the role of regulatory sequences which control gene expression at transcription resulting in abundant production of messenger RNA and regulatory sequences in mRNA which promote efficient translation. Also examines the role of E. coli cells in stabilizing mRNA and protein that is…

  1. The unexhausted potential of E. coli.

    Science.gov (United States)

    Blount, Zachary D

    2015-03-25

    E. coli's hardiness, versatility, broad palate and ease of handling have made it the most intensively studied and best understood organism on the planet. However, research on E.coli has primarily examined it as a model organism, one that is abstracted from any natural history. But E. coli is far more than just a microbial lab rat. Rather, it is a highly diverse organism with a complex, multi-faceted niche in the wild. Recent studies of 'wild' E. coli have, for example, revealed a great deal about its presence in the environment, its diversity and genomic evolution, as well as its role in the human microbiome and disease. These findings have shed light on aspects of its biology and ecology that pose far-reaching questions and illustrate how an appreciation of E. coli's natural history can expand its value as a model organism.

  2. Guiding E.coli to nanosensors

    Science.gov (United States)

    Park, Dong-Won; So, Hye-Mi; Kim, Beom Soo; Kong, Ki-Jeong; Chang, Hyunju; Lee, Jeong-O.

    2009-03-01

    Electronic nanosensors based on nanomaterials such as carbon nanotubes and nanowires are expected to have ultimate sensitivity. However, as an inherent problem of nanosensors, they have extremely small sensor surface for reaction. Therefore, simple diffusion of target biomolecules is not enough for such nanosensors, and the problem is even more serious in the case of motile bacteria. Previously, we have shown that we could estimate the titer of E.coli with arrays of single-walled carbon nanotube field effect transistors (SWNT-FET) combined with statistical method. Still, sensitivity of our method is inferior compared with incubation method, due to the limited sensor surface area. In this work, we actively guide E.coli to the sensor surface using micro-fabricated channels. Arrow-shaped and funnel shaped microstructures were fabricated in the channel to guide E. coli to the sensor surface, and we used green fluorescent protein expressed E.coli to monitor the guiding of E.coli.

  3. Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing

    DEFF Research Database (Denmark)

    Rohlin, Anna; Rambech, Eva; Kvist, Anders;

    2016-01-01

    sixteen pathogenic or likely pathogenic variants and 30 variants of unknown clinical significance. Four of the pathogenic or likely pathogenic variants were found in BMPR1A in patients with unexplained familial adenomatous polyposis or atypical adenomatous polyposis, which extends the genotype......-phenotype spectrum for this gene. Nine patients had more than one variant remaining after the filtration, including three with truncating mutations in BMPR1A, PMS2 and AXIN2. CNVs were found in three patients, in upstream regions of SMAD4, MSH3 and CTNNB1, and one additional individual harbored a 24.2 kb duplication......Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel...

  4. Thin-section computed tomography-histopathologic comparisons of pulmonary focal interstitial fibrosis, atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma with pure ground-glass opacity.

    Science.gov (United States)

    Si, Ming-Jue; Tao, Xiao-Feng; Du, Guang-Ye; Cai, Ling-Ling; Han, Hong-Xiu; Liang, Xi-Zi; Zhao, Jiang-Min

    2016-10-01

    To retrospectively compare focal interstitial fibrosis (FIF), atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) with pure ground-glass opacity (GGO) using thin-section computed tomography (CT). Sixty pathologically confirmed cases were reviewed including 7 cases of FIF, 17 of AAH, 23of AIS, and 13 of MIA. All nodules kept pure ground glass appearances before surgical resection and their last time of thin-section CT imaging data before operation were collected. Differences of patient demographics and CT features were compared among these four types of lesions. FIF occurred more frequently in males and smokers while the others occurred more frequently in female nonsmokers. Nodule size was significant larger in MIA (P0.05) in age, malignant history, attenuation value, location, and presence of bubble-like lucency. A nodule size >7.5mm increases the possibility of MIA. A concave margin could be useful for differentiation of FIF from the other malignant or pre-malignant GGO nodules. The presence of spiculation or pleural indentation may preclude the diagnosis of AAH. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Escherichia coli transcriptional regulatory network

    Directory of Open Access Journals (Sweden)

    Agustino Martinez-Antonio

    2011-06-01

    Full Text Available Escherichia coli is the most well-know bacterial model about the function of its molecular components. In this review are presented several structural and functional aspects of their transcriptional regulatory network constituted by transcription factors and target genes. The network discussed here represent to 1531 genes and 3421 regulatory interactions. This network shows a power-law distribution with a few global regulators and most of genes poorly connected. 176 of genes in the network correspond to transcription factors, which form a sub-network of seven hierarchical layers where global regulators tend to be set in superior layers while local regulators are located in the lower ones. There is a small set of proteins know as nucleoid-associated proteins, which are in a high cellular concentrations and reshape the nucleoid structure to influence the running of global transcriptional programs, to this mode of regulation is named analog regulation. Specific signal effectors assist the activity of most of transcription factors in E. coli. These effectors switch and tune the activity of transcription factors. To this type of regulation, depending of environmental signals is named the digital-precise-regulation. The integration of regulatory programs have place in the promoter region of transcription units where it is common to observe co-regulation among global and local TFs as well as of TFs sensing exogenous and endogenous conditions. The mechanistic logic to understand the harmonious operation of regulatory programs in the network should consider the globalism of TFs, their signal perceived, coregulation, genome position, and cellular concentration. Finally, duplicated TFs and their horizontal transfer influence the evolvability of members of the network. The most duplicated and transferred TFs are located in the network periphery.

  6. Structure of Escherichia coli tryptophanase.

    Science.gov (United States)

    Ku, Shao Yang; Yip, Patrick; Howell, P Lynne

    2006-07-01

    Pyridoxal 5'-phosphate (PLP) dependent tryptophanase has been isolated from Escherichia coli and its crystal structure has been determined. The structure shares the same fold with and has similar quaternary structure to Proteus vulgaris tryptophanase and tyrosine-phenol lyase, but is found in a closed conformation when compared with these two enzymes. The tryptophanase structure, solved in its apo form, does not have covalent PLP bound in the active site, but two sulfate ions. The sulfate ions occupy the phosphoryl-binding site of PLP and the binding site of the alpha-carboxyl of the natural substrate tryptophan. One of the sulfate ions makes extensive interactions with both the transferase and PLP-binding domains of the protein and appears to be responsible for holding the enzyme in its closed conformation. Based on the sulfate density and the structure of the P. vulgaris enzyme, PLP and the substrate tryptophan were modeled into the active site. The resulting model is consistent with the roles of Arg419 in orienting the substrate to PLP and acidifying the alpha-proton of the substrate for beta-elimination, Lys269 in the formation and decomposition of the PLP quinonoid intermediate, Arg230 in orienting the substrate-PLP intermediates in the optimal conformation for catalysis, and His463 and Tyr74 in determining substrate specificity and suggests that the closed conformation observed in the structure could be induced by substrate binding and that significant conformational changes occur during catalysis. A catalytic mechanism for tryptophanase is proposed. Since E. coli tryptophanase has resisted forming diffraction-quality crystals for many years, the molecular surface of tryptophanase has been analyzed in various crystal forms and it was rationalized that strong crystal contacts occur on the flat surface of the protein and that the size of crystal contact surface seems to correlate with the diffraction quality of the crystal.

  7. Structure of Escherichia Coli Tryptophanase

    Energy Technology Data Exchange (ETDEWEB)

    Ku,S.; Yip, P.; Howell, P.

    2006-01-01

    Pyridoxal 5'-phosphate (PLP) dependent tryptophanase has been isolated from Escherichia coli and its crystal structure has been determined. The structure shares the same fold with and has similar quaternary structure to Proteus vulgaris tryptophanase and tyrosine-phenol lyase, but is found in a closed conformation when compared with these two enzymes. The tryptophanase structure, solved in its apo form, does not have covalent PLP bound in the active site, but two sulfate ions. The sulfate ions occupy the phosphoryl-binding site of PLP and the binding site of the {alpha}-carboxyl of the natural substrate tryptophan. One of the sulfate ions makes extensive interactions with both the transferase and PLP-binding domains of the protein and appears to be responsible for holding the enzyme in its closed conformation. Based on the sulfate density and the structure of the P. vulgaris enzyme, PLP and the substrate tryptophan were modeled into the active site. The resulting model is consistent with the roles of Arg419 in orienting the substrate to PLP and acidifying the {alpha}-proton of the substrate for {beta}-elimination, Lys269 in the formation and decomposition of the PLP quinonoid intermediate, Arg230 in orienting the substrate-PLP intermediates in the optimal conformation for catalysis, and His463 and Tyr74 in determining substrate specificity and suggests that the closed conformation observed in the structure could be induced by substrate binding and that significant conformational changes occur during catalysis. A catalytic mechanism for tryptophanase is proposed. Since E. coli tryptophanase has resisted forming diffraction-quality crystals for many years, the molecular surface of tryptophanase has been analyzed in various crystal forms and it was rationalized that strong crystal contacts occur on the flat surface of the protein and that the size of crystal contact surface seems to correlate with the diffraction quality of the crystal.

  8. The evolution of the Escherichia coli phylogeny.

    Science.gov (United States)

    Chaudhuri, Roy R; Henderson, Ian R

    2012-03-01

    Escherichia coli is familiar to biologists as a classical model system, ubiquitous in molecular biology laboratories around the world. Outside of the laboratory, E. coli strains exist as an almost universal component of the lower-gut flora of humans and animals. Although usually a commensal, E. coli has an alter ego as a pathogen, and is associated with diarrhoeal disease and extra-intestinal infections. The study of E. coli diversity predates the availability of molecular data, with strains initially distinguished by serotyping and metabolic profiling, and genomic diversity illustrated by DNA hybridisation. The quantitative study of E. coli diversity began with the application of multi-locus enzyme electrophoresis (MLEE), and has progressed with the accumulation of nucleotide sequence data, from single genes through multi-locus sequence typing (MLST) to whole genome sequencing. Phylogenetic methods have shed light on the processes of genomic evolution in this extraordinarily diverse species, and revealed the origins of pathogenic E. coli strains, including members of the phylogenetically indistinguishable "genus"Shigella. In May and June 2011, an outbreak of haemorrhagic uraemic syndrome in Germany was linked to a strain of enterohaemorrhagic E. coli (EHEC) O104:H4. Application of high-throughput sequencing technologies allowed the genome and origins of the outbreak strain to be characterised in real time as the outbreak was in progress.

  9. Germline Missense Changes in the APC Gene and Their Relationship to Disease

    Directory of Open Access Journals (Sweden)

    Scott Rodney J

    2004-05-01

    Full Text Available Abstract Familial adenomatous polyposis (FAP is characterized by the presence of hundreds to thousands of adenomas that carpet the entire colon and rectum. Nonsense and frameshift mutations in the adenomatous polyposis coli (APC gene account for the majority of mutations identified to date and predispose primarily to the typical disease phenotype. Some APC mutations are associated with a milder form of the disease known as attenuated FAP. Virtually all mutations that have been described in the APC gene result in the formation of a premature stop codon and very little is known about missense mutations apart from a common Ashkenazi Jewish mutation (1307 K and a British E1317Q missense change. The incidence of missense mutations in the APC gene has been underreported since the APC gene lends itself to analysis using an artificial transcription and translation assay known as the Protein Truncation Test (PTT or the In Vitro Synthetic Protein assay (IVSP. In this report we have used denaturing high performance liquid chromatography to analyse the entire coding sequence of the APC gene to determine if a cohort of patients adhering to the diagnostic criteria of FAP to assess the frequency of missense mutations in the APC gene. Altogether 112 patients were studied and 22 missense mutations were identified. From the total of 22 missense changes, 13 were silent changes and the remaining 9 resulted in amino acid substitutions. One or more of these changes were identified multiple times in 62.5% of the population under study. The results reveal that missense mutations in the APC gene appear not to radically alter protein function but may be associated with more subtle processing of RNA transcripts which in turn could result in the expression of differentially spliced forms of the APC gene which may interfere with the functional activity of the APC protein.

  10. Chromosome 19q13 disruption alters expressions of CYP2A7, MIA and MIA-RAB4B lncRNA and contributes to FAP-like phenotype in APC mutation-negative familial colorectal cancer patients.

    Science.gov (United States)

    Thean, Lai Fun; Wong, Yu Hui; Lo, Michelle; Loi, Carol; Chew, Min Hoe; Tang, Choong Leong; Cheah, Peh Yean

    2017-01-01

    Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. Our ability to exhaustively screen for APC mutations identify microsatellite-stable and APC-mutation negative familial CRC patients, enabling us to search for novel genes. We performed genome-wide scan on two affected siblings of one family and 88 ethnicity- and gender-matched healthy controls to identify deletions shared by the siblings. Combined loss of heterozygosity, copy number and allelic-specific copy number analysis uncovered 5 shared deletions. Long-range polymerase chain reaction (PCR) confirmed chromosome 19q13 deletion, which was subsequently found in one other family. The 32 kb deleted region harbors the CYP2A7 gene and was enriched with enhancer, repressor and insulator sites. The wildtype allele was lost in the polyps of the proband. Further, real-time RT-PCR assays showed that expressions of MIA and MIA-RAB4B located 35 kb upstream of the deletion, were up-regulated in the polyps compared to the matched mucosa of the proband. MIA-RAB4B, the read-through long non-coding RNA (lncRNA), RAB4B, PIM2 and TAOK1 share common binding site of a microRNA, miR-24, in their 3'UTRs. PIM2 and TAOK1, two target oncogenes of miR-24, were co-ordinately up-regulated with MIA-RAB4B in the polyps, suggesting that MIA-RAB4B could function as competitive endogenous RNA to titrate miR-24 away from its other targets. The data suggest that the 19.13 deletion disrupted chromatin boundary, leading to altered expression of several genes and lncRNA, could contribute to colorectal cancer via novel genetic and epigenetic mechanisms.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer.

    Science.gov (United States)

    Kim-Schulze, Seunghee; Kim, Hong Sung; Wainstein, Alberto; Kim, Dae Won; Yang, Wein Cui; Moroziewicz, Dorota; Mong, Phyllus Y; Bereta, Michal; Taback, Bret; Wang, Qin; Kaufman, Howard L

    2008-12-01

    The gastrointestinal mucosa contains an intact immune system that protects the host from pathogens and communicates with the systemic immune system. Absorptive epithelial cells in the mucosa give rise to malignant tumors although the interaction between tumor cells and the mucosal immune system is not well defined. The pathophysiology of colorectal cancer has been elucidated through studies of hereditary syndromes, such as familial adenomatous polyposis, a cancer predisposition syndrome caused by germline mutations in the adenomatous polyposis coli tumor suppressor gene. Patients with FAP develop adenomas and inevitably progress to invasive carcinomas by the age of 40. To better delineate the role of mucosal immunity in colorectal cancer, we evaluated the efficacy of intrarectal recombinant vaccinia virus expressing the human carcinoembryonic Ag (CEA) in a murine FAP model in which mice are predisposed to colorectal cancer and also express human CEA in the gut. Mucosal vaccination reduced the incidence of spontaneous adenomas and completely prevented progression to invasive carcinoma. The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs. Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments. Thus, intrarectal vaccination induces mucosal and systemic antitumor immunity and prevents progression of spontaneous colorectal cancer. These results have implications for the prevention of colorectal cancer in high-risk individuals.

  13. Extra nuchal-type fibroma associated with elastosis, traumatic neuroma, a rare APC gene missense mutation, and a very rare MUTYH gene polymorphism: a case report and review of the literature*.

    Science.gov (United States)

    Linos, Konstantinos; Sedivcová, Monika; Cerna, Katerina; Sima, Radek; Kazakov, Dmitry V; Nazeer, Tipu; Glazyrin, Alexey; Valerian, Brian T; Carlson, J Andrew

    2011-11-01

    We report a case of an extra nuchal-type fibroma in a 51-year-old male suspected to have attenuated familial adenomatous polyposis (Gardner's syndrome), who presented with a longstanding buttock mass excised due to enlargement and pain. Histopathologically, lobules of haphazard, hypocellular, hyalinized collagen bundles replaced the dermis and subcutis and entrapped nerve bundles, mimicking Morton neuroma. Ramifying nerve twigs found around larger nerve fascicles showed the co-existence of traumatic neuroma. Elastic tissue stain revealed elastosis characterized by large, arborizing fibers lying between and within the hyalinized collagen bundles. Modified Masson's trichrome stain showed light blue staining of collagen bundles producing the hyalinized nodules with irregular, light red staining of collagen bundles at their periphery and within tumor collagen. Compression and/or degeneration of collagen and secondary elastosis with later entrapment by tumor collagen could explain this microscopic phenotype. By immunohistochemistry, tumor spindle cells expressed nuclear β-catenin and cyclin D1, mostly within regions of fibrosis implicating activation of the adenomatous polyposis coli (APC)-Wnt pathway. Genetic analysis showed a missense mutation in APC gene (c.7504G>A, p.G2502S in exon 15) and a functional homozygous polymorphism in the MUTYH gene (c.36+325G>C, (IVS1+5G/C)). Nuchal-type fibroma has been associated with Gardner's syndrome and trauma. In this patient, genetic predisposition coupled with repetitive, localized trauma and collagen degeneration may have provided the stimulus for the development of extra nuchal-type fibroma.

  14. Effect of bile on growth, peritoneal absorption, and blood clearance of Escherichia coli in E coli peritonitis

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, R.; Schalen, C.; Tranberg, K.G. (Department of Surgery, Lund University, Lund (Sweden))

    1991-06-01

    The effect of intraperitoneal bile on growth, peritoneal absorption, and clearance of Escherichia coli was determined in E coli peritonitis in the rat. In E coli peritonitis, intraperitoneal bacterial counts gradually decreased, whereas they increased (after 2 hours) with subsequent development of bacteremia in E coli plus bile peritonitis. After an intraperitoneal injection of labeled bacteria, blood radioactivity was only initially lower in E coli plus bile peritonitis compared with E coli peritonitis. Clearance from blood was lower in E coli plus bile peritonitis than in E coli peritonitis. Organ localization was similar in E coli peritonitis and E coli plus bile peritonitis with decreased splenic, increased pulmonary, and unchanged hepatic uptakes compared with controls. Impaired peritoneal absorption of bacteria, together with impaired local host defense, is likely to enhance the noxious effect of bile in E coli peritonitis.

  15. Tumor maligno do sistema nervoso central associado a polipose do cólon com degeneração maligna Malignant tumor of the central nervous system associated with polyposis of the colon with malignant degeneration: a case report

    Directory of Open Access Journals (Sweden)

    Luiz C. Mattosinho França

    1969-03-01

    Full Text Available É relatado um caso caracterizado pela associação de tumor do sistema nervoso central e polipose do cólon. Foram encontrados apenas dois casos dessa natureza na literatura médica, relatados por Turcot e col. em dois irmãos, nos quais a afecção teve início na puberdade, caracterizando-se pela presença de tumor do sistema nervoso central associado a polipose do cólon; nos dois casos o tumor do sistema nervoso era da linha gliomatosa e ocorreu transformação carcinomatosa dos polipos. No caso aqui relatado, a moléstia teve início aos 14 anos de idade e, do ponto de vista histológico, foi encontrado um espongioblastoma polar no tronco cerebral associado a polipos múltiplos do cólon, alguns com degeneração carcinomatosa. Até o momento, a paciente estudada representa caso isolado em sua família.A case of central nervous system tumor associated with polyposis of the colon is reported. A review of the literature shows two other such cases, reported by Turcot et al., and concerning two brothers. The symptoms of this association usually begin during puberty. All tumors described untill now are gliomas and colonic polyps have always suffered carcinomatous degeneration. The patient here concerned, a girl aged fourteen, had a spongioblastoma polare of brain stem with multiple polyposis of the colon and carcinoma in some of them. There are no other cases in the family.

  16. The utility of Apc-mutant rats in modeling human colon cancer

    Directory of Open Access Journals (Sweden)

    Amy A. Irving

    2014-11-01

    Full Text Available Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc and Kyoto Apc Delta (KAD strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.

  17. The utility of Apc-mutant rats in modeling human colon cancer

    Science.gov (United States)

    Irving, Amy A.; Yoshimi, Kazuto; Hart, Marcia L.; Parker, Taybor; Clipson, Linda; Ford, Madeline R.; Kuramoto, Takashi; Dove, William F.; Amos-Landgraf, James M.

    2014-01-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer. PMID:25288683

  18. Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth.

    Directory of Open Access Journals (Sweden)

    Elias Gounaris

    Full Text Available It has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR fluorescent probes were utilized to visualize intestinal polyps of mice hemizygous for a novel truncation of the Adenomatous Polyposis coli (APC gene. Laser Scanning Confocal Microscopy in live mice allowed visualization of cathepsin activity in richly vascularized benign dysplastic lesions. Using biotinylated suicide inhibitors we quantified increased activities of the Cathepsin B & Z in the polyps. More than (3/4 of the probe signal was localized in CD11b(+Gr1(+ myeloid derived suppressor cells (MDSC and CD11b(+F4/80(+ macrophages infiltrating the lesions. Polyposis was attenuated through genetic ablation of cathepsin B, and suppressed by neutralization of TNFalpha in mice. In both cases, diminished probe signal was accounted for by loss of MDSC. Thus, in vivo NIR imaging of focal cathepsin activity reveals inflammatory reactions etiologically linked with cancer progression and is a suitable approach for monitoring response to therapy.

  19. Advances in genoserotyping and subtyping of Escherichia coli

    Science.gov (United States)

    E. coli plays an important role as a member of the gut microbiota; however, pathogenic strains also exist, including various diarrheagenic E. coli pathotypes and extraintestinal pathogenic E. coli that cause illness outside of the GI-tract. E. coli have traditionally been serotyped using antisera a...

  20. 21 CFR 866.3255 - Escherichia coli serological reagents.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Escherichia coli serological reagents. 866.3255... coli serological reagents. (a) Identification. Escherichia coli serological reagents are devices that consist of antigens and antisera used in serological tests to identify Escherichia coli from...

  1. Protective effects of indigenous Escherichia coli against a pathogenic E. coli challenge strain in pigs.

    Science.gov (United States)

    Vahjen, W; Cuisiniere, T; Zentek, J

    2017-10-03

    To investigate the inhibitory effect of indigenous enterobacteria on pathogenic Escherichia coli, a challenge trial with postweaning pigs was conducted. A pathogenic E. coli strain was administered to all animals and their health was closely monitored thereafter. Faecal samples were taken from three healthy and three diarrhoeic animals. Samples were cultivated on MacConkey agar and isolates were subcultured. A soft agar overlay assay was used to determine the inhibitory activity of the isolates. A total of 1,173 enterobacterial isolates were screened for their ability to inhibit the E. coli challenge strain. Colony forming units of enterobacteria on MacConkey agar were not different between healthy and diarrhoeic animals in the original samples. Furthermore, numbers of isolates per animal were also not significantly different between healthy (482 isolates) and diarrhoeic animals (691 isolates). A total of 43 isolates (3.7%) with inhibitory activity against the pathogenic E. coli challenge strain were detected. All inhibitory isolates were identified as E. coli via MALDI-TOF. The isolates belonged to the phylotypes A, C and E. Many isolates (67.4%) were commensal E. coli without relevant porcine pathogenic factors, but toxin- and fimbrial genes (stx2e, fae, estIb, elt1a, fas, fan) were detected in 14 inhibitory isolates. Healthy animals showed significantly (P=0.003) more inhibitory isolates (36 of 482 isolates; 7.5%) than diseased animals (7 of 691 isolates; 1.0%). There were no significant correlations regarding phylotype or pathogenic factors between healthy and diseased animals. This study has shown that a small proportion of indigenous E. coli is able to inhibit in vitro growth of a pathogenic E. coli strain in pigs. Furthermore, healthy animals possess significantly more inhibitory E. coli strains than diarrhoeic animals. The inhibition of pathogenic E. coli by specific indigenous E. coli strains may be an underlying principle for the containment of pathogenic

  2. Differentiation between Shigella, enteroinvasive Escherichia coli (EIEC) and noninvasive Escherichia coli.

    Science.gov (United States)

    van den Beld, M J C; Reubsaet, F A G

    2012-06-01

    Shigella causes bacillary dysentery and is classified into four species based on their antigen characteristics. This classification does not reflect genetic relatedness; in fact, Shigella species are so related to Escherichia coli , they should be classified as one distinctive species in the genus Escherichia. The differentiation of Shigella and E. coli is even more complicated with the description of enteroinvasive E. coli (EIEC). EIEC are strains that possess some of the biochemical characteristics of E. coli and have the ability to cause dysentery using the same method of invasion as Shigella does. Sequencing of multiple housekeeping genes indicates that EIEC is more related to Shigella than to non-invasive E. coli. Shigella and EIEC evolved from the same ancestor and form a single pathovar within E. coli. Shigella and EIEC could be separated from other E. coli by a PCR targeting the ipaH-gene; this is a multicopy gene exclusively found in all Shigella and EIEC. It is possible to differentiate Shigella and all E. coli, including EIEC, by using multiple tests, including ipaH-gene PCR, physiological and biochemical typing and serological typing. Based on literature study, a key is designed for daily use in diagnostic laboratories to identify Shigella and all E. coli.

  3. Biofuels from E. Coli: Engineering E. coli as an Electrofuels Chassis for Isooctane Production

    Energy Technology Data Exchange (ETDEWEB)

    None

    2010-07-16

    Electrofuels Project: Ginkgo Bioworks is bypassing photosynthesis and engineering E. coli to directly use carbon dioxide (CO2) to produce biofuels. E. coli doesn’t naturally metabolize CO2, but Ginkgo Bioworks is manipulating and incorporating the genes responsible for CO2 metabolism into the microorganism. By genetically modifying E. coli, Ginkgo Bioworks will enhance its rate of CO2 consumption and liquid fuel production. Ginkgo Bioworks is delivering CO2 to E. coli as formic acid, a simple industrial chemical that provides energy and CO2 to the bacterial system.

  4. antimicrobial susceptibility and plasmids from escherichia coli ...

    African Journals Online (AJOL)

    2001-10-10

    Oct 10, 2001 ... transmission to humans of E. coli containing antibiotic resistance plasmids ... resistant micro-organisms, which may in turn transfer resistance to .... cells were washed with sterile normal saline to remove leached. Я-lactamase ...

  5. ANTIMICIROBIAL SUSCEPTIBILITY PATTERNS OF Escherichia coli ...

    African Journals Online (AJOL)

    DR. AMINU

    aetiological agents of diarrhoea diseases of humans in developing ... Pathogenic organisms have developed a number of elaborate .... reported that E.coli isolated from animals haboured plasmids .... coil 0157:H7 as a model of entry of a new.

  6. First international E. coli genome meeting

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-31

    This volume is a collection of abstracts of oral presentations and poster sessions of studies reported at the First International E. Coli Genome Meeting, held September 10-14, 1992 at the University of Wisconsin.

  7. First international E. coli genome meeting

    Energy Technology Data Exchange (ETDEWEB)

    1992-01-01

    This volume is a collection of abstracts of oral presentations and poster sessions of studies reported at the First International E. Coli Genome Meeting, held September 10-14, 1992 at the University of Wisconsin.

  8. Experimental induced avian E. coli salpingitis

    DEFF Research Database (Denmark)

    Olsen, Rikke Heidemann; Thøfner, Ida; Pors, Susanne Elisabeth

    2016-01-01

    Several types of Escherichia coli have been associated with extra-intestinal infections in poultry, however, they may vary significantly in their virulence potential. The aim of the present study was to investigate the virulence of five strains of E. coli obtained from different disease......) had a distinct ability to cause disease. Results of the study shows major differences in virulence of different strains of E. coli in ascending infections; however, there was no indication of tissue-specific adaptation, since strains obtained from lesions unrelated to the reproductive system were...... fully capable of causing experimental infection. In conclusion, the study provides evidence for the clinical outcome of infection with E. coli in poultry is largely influenced by the specific strain as well as individual host factors....

  9. Prevalence of diarrheagenic Escherichia coli in suckling rabbits

    OpenAIRE

    2016-01-01

    Diarrheagenic Escherichia coli (E. coli) in suckling rabbit causes collibacillosis, which is characterized by sever yellow diarrhea, poor growth and high mortalities. This study was undertaken to investigate the prevalence of diarrheagenic E. coli in suckling rabbits in Egypt. Additionally, expression of some virulence-associated genes in the isolated E. coli serotypes were examined using the polymerase chain reaction. Finally, antibiogram of the identified E. coli serotypes was also investig...

  10. Methane production from kitchen waste using Escherichia coli.

    Science.gov (United States)

    Jayalakshmi, S; Joseph, Kurian; Sukumaran, V

    2007-04-01

    Escherichia coli (E. coli) strain isolated from biogas plant sludge was examined for its ability to enhance biogas from kitchen waste during solid phase anaerobic digestion. The laboratory experiments were conducted for total solid concentrations of 20% and 22%. Kitchen waste was characterized for physico-chemical parameters and laboratory experiments were conducted with and without E. coli strain. It was found that the reactor with E. coli produced 17% more biogas than the reactors that are operated without E. coli strain.

  11. Synergistic effects in mixed Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Reisner, A.; Holler, B.M.; Molin, Søren

    2006-01-01

    the strongest effects was most often linked to conjugative transmission of natural plasmids carried by the E. coli isolates (70%). Thus, the capacity of an isolate to promote the biofilm through cocultivation was (i) transferable to the K-12 strain, (ii) was linked with the acquisition of conjugation genes...... promotion in this system is not dependent on the laboratory strain and that the described model system could provide relevant insights on mechanisms of biofilm development in natural E. coli populations....

  12. Native valve Escherichia coli endocarditis following urosepsis.

    Science.gov (United States)

    Rangarajan, D; Ramakrishnan, S; Patro, K C; Devaraj, S; Krishnamurthy, V; Kothari, Y; Satyaki, N

    2013-05-01

    Gram-negative organisms are a rare cause of infective endocarditis. Escherichia coli, the most common cause of urinary tract infection and gram-negative septicemia involves endocardium rarely. In this case report, we describe infection of native mitral valve by E. coli following septicemia of urinary tract origin in a diabetic male; subsequently, he required prosthetic tissue valve replacement indicated by persistent sepsis and congestive cardiac failure.

  13. Detection of attaching and effacing virulence gene of E. coli

    Directory of Open Access Journals (Sweden)

    Maratu Soleha

    2013-07-01

    Full Text Available AbstrakLatar belakang: Bakteri Escherichia coli (E. coli ada yang telah bermutasi menjadi patogen yang menimbulkan berbagai penyakit seperti hemorrhagic colitis (HC, hemolytic uremic syndrome (HUS, sepsis, pnemonia, neonatal meningitis, dan infeksi saluran kemih. Mutasi terjadi karena bakteri ini menerima transfer gen yang virulen dari bakteri lain yang hidup di sekitarnya. E. coli yang biasanya hidup normal di dalam usus manusia telah beradaptasi sehingga bisa hidup di tanah, makanan, dan saluran kemih. Penelitian ini mendeteksi gene yang virulen pada DNA isolat E. coli. Metode: Untuk deteksi E. coli yang virulen pada penelitian ini digunakan metode Real-time PCR dengan mencocokkan hasil sekuensing dengan sekuens E. coli virulen yang telah di publikasikan sebagai rujukan. Hasil: Sekuens RT PCR menggambarkan DNA gen eae pada BLAST mempunyai kesesuaian dengan rujukan segmen E. coli yang virulen. Dari sampel yang berasal dari E. coli di sekitar perairan lingkungan didapatkan gen Eae sebagai gen yang menyebabkan E. coli menjadi virulen sebesar 7,3%. Kesimpulan: E. coli yang virulen ditemukan pada sampel E. coli yang berasal dari perairan lingkungan dengan metode realtime PCR. (Health Science Indones 2013;1:41-6 Kata kunci: gen virulen E. coli, real-time PCR, perairan lingkunganAbstractBackground: Escherichia coli(E. coli bacteria have developed into pathogenic bacteria that caused diseases such as hemorrhagic colitis (HC, hemolytic uremic syndrome (HUS, sepsis, pneumonia, neonatal meningitis, and urinary tract infections. Pathogenic E. coli have acquired pathogenic/virulence genes from other bacteria in their environment. E. coli that normally lived in the human gut had adapted to other niches such as soil, food and the urinary tract. This study investigated the presence of pathogenic E. coli from water samples by examining E. coli virulence genes present in E. coli genomes of water sourced isolates. Methods:This study used Real-time PCR to detect

  14. Detection of attaching and effacing virulence gene of E. coli

    Directory of Open Access Journals (Sweden)

    Maratu Soleha

    2013-07-01

    Full Text Available AbstrakLatar belakang: Bakteri Escherichia coli (E. coli ada yang telah bermutasi menjadi patogen yang menimbulkan berbagai penyakit seperti hemorrhagic colitis (HC, hemolytic uremic syndrome (HUS, sepsis, pnemonia, neonatal meningitis, dan infeksi saluran kemih. Mutasi terjadi karena bakteri ini menerima transfer gen yang virulen dari bakteri lain yang hidup di sekitarnya. E. coli yang biasanya hidup normal di dalam usus manusia telah beradaptasi sehingga bisa hidup di tanah, makanan, dan saluran kemih. Penelitian ini mendeteksi gene yang virulen pada DNA isolat E. coli. Metode: Untuk deteksi E. coli yang virulen pada penelitian ini digunakan metode Real-time PCR dengan mencocokkan hasil sekuensing dengan sekuens E. coli virulen yang telah di publikasikan sebagai rujukan. Hasil: Sekuens RT PCR menggambarkan DNA gen eae pada BLAST mempunyai kesesuaian dengan rujukan segmen E. coli yang virulen. Dari sampel yang berasal dari E. coli di sekitar perairan lingkungan didapatkan gen Eae sebagai gen yang menyebabkan E. coli menjadi virulen sebesar 7,3%. Kesimpulan: E. coli yang virulen ditemukan pada sampel E. coli yang berasal dari perairan lingkungan dengan metode realtime PCR. (Health Science Indones 2013;1:41-6 Kata kunci: gen virulen E. coli, real-time PCR, perairan lingkunganAbstractBackground: Escherichia coli(E. coli bacteria have developed into pathogenic bacteria that caused diseases such as hemorrhagic colitis (HC, hemolytic uremic syndrome (HUS, sepsis, pneumonia, neonatal meningitis, and urinary tract infections. Pathogenic E. coli have acquired pathogenic/virulence genes from other bacteria in their environment. E. coli that normally lived in the human gut had adapted to other niches such as soil, food and the urinary tract. This study investigated the presence of pathogenic E. coli from water samples by examining E. coli virulence genes present in E. coli genomes of water sourced isolates. Methods:This study used Real-time PCR to detect

  15. Siderophore production by uropathogenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Vagrali Manjula

    2009-01-01

    Full Text Available Urinary tract infection (UTI is one of the most frequently encountered problems in ambulatory medicine. The present study was designed to determine siderophore production as the urovirulence factor of Escherichia coli isolated from the patients of UTI. A total of 160 strains of E. coli isolated from urine of patients with clinically diagnosed UTI were included in the study and 50 fecal isolates of E. coli, siderophore production was seen in 156 (97.5%. In 50 fecal isolates, siderophore production was seen in 2 (4%. Siderophore production has been shown to be more frequent in E. coli from patients with UTI, than in fecal isolates. The results suggest that siderophore production positive strains can be considered as UPEC. Thus, although a great deal has been learned regarding E. coli virulence mechanisms in UTI, much remains to be learned and the practical application of our growing understanding of E. coli virulence factors to the prevention and treatment of UTI has to be continued.

  16. E. coli on the move

    Science.gov (United States)

    Calne, S.

    2012-04-01

    Lynn Grove High School in Great Yarmouth, UK has been awarded a Royal Society partnership grant. Lynn Grove pupils aged between 11 and 16 years will carry out an investigation collaborating with scientists at the John Innes Centre in Norwich, UK to investigate the distribution of E.coli and other coliform bacteria within a school. The information will be used as an evidence base to educate pupils about the transmission of microbes and about methods of control. Through this work pupils will gain an appreciation of the diversity of microbial biochemistry and the chemistry behind chromogenic detection methodologies for specific bacterial enzymes. Inferences from the use of diagnostic selective media will be confirmed by carrying out DNA isolation and PCR to identify the genes responsible for the biochemical reactions. PCR will also be used to identify species of coliforms by reference to genomic sequence databases. These techniques will allow pupils to look into an unseen world in a way which has direct relevance to their everyday lives. Furthermore this partnership study will demonstrate to pupils that solving scientific questions requires the integration of a variety of scientific disciplines. The project will run from January 2012 until June 2012. We will present our preliminary results from the investigation and outline our future plans.

  17. Enterohemorrhagic E. coli (EHEC pathogenesis

    Directory of Open Access Journals (Sweden)

    Vanessa eSperandio

    2012-07-01

    Full Text Available Enterohemorrhagic Escherichia coli (EHEC serotype O157:H7 is a human pathogen responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome worldwide. Conventional antimicrobials trigger an SOS response in EHEC that promotes the release of the potent Shiga toxin that is responsible for much of the morbidity and mortality associated with EHEC infection. Cattle are a natural reservoir of EHEC, and approximately 75% of EHEC outbreaks are linked to the consumption of contaminated bovine-derived products. This review will discuss how EHEC causes disease in humans but is asymptomatic in adult ruminants. It will also analyze factors utilized by EHEC as it travels through the bovine gastrointestinal tract that allow for its survival through the acidic environment of the distal stomachs, and for its ultimate colonization in the recto-anal junction. Understanding the factors crucial for EHEC survival and colonization in cattle will aid in the development of alternative strategies to prevent EHEC shedding into the environment and consequent human infection.

  18. The pangenome structure of Escherichia coli: comparative genomic analysis of E. coli commensal and pathogenic isolates.

    Science.gov (United States)

    Rasko, David A; Rosovitz, M J; Myers, Garry S A; Mongodin, Emmanuel F; Fricke, W Florian; Gajer, Pawel; Crabtree, Jonathan; Sebaihia, Mohammed; Thomson, Nicholas R; Chaudhuri, Roy; Henderson, Ian R; Sperandio, Vanessa; Ravel, Jacques

    2008-10-01

    Whole-genome sequencing has been skewed toward bacterial pathogens as a consequence of the prioritization of medical and veterinary diseases. However, it is becoming clear that in order to accurately measure genetic variation within and between pathogenic groups, multiple isolates, as well as commensal species, must be sequenced. This study examined the pangenomic content of Escherichia coli. Six distinct E. coli pathovars can be distinguished using molecular or phenotypic markers, but only two of the six pathovars have been subjected to any genome sequencing previously. Thus, this report provides a seminal description of the genomic contents and unique features of three unsequenced pathovars, enterotoxigenic E. coli, enteropathogenic E. coli, and enteroaggregative E. coli. We also determined the first genome sequence of a human commensal E. coli isolate, E. coli HS, which will undoubtedly provide a new baseline from which workers can examine the evolution of pathogenic E. coli. Comparison of 17 E. coli genomes, 8 of which are new, resulted in identification of approximately 2,200 genes conserved in all isolates. We were also able to identify genes that were isolate and pathovar specific. Fewer pathovar-specific genes were identified than anticipated, suggesting that each isolate may have independently developed virulence capabilities. Pangenome calculations indicate that E. coli genomic diversity represents an open pangenome model containing a reservoir of more than 13,000 genes, many of which may be uncharacterized but important virulence factors. This comparative study of the species E. coli, while descriptive, should provide the basis for future functional work on this important group of pathogens.

  19. The asymptomatic bacteriuria Escherichia coli strain 83972 outcompetes uropathogenic E. coli strains in human urine

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Ulett, G.C.; Schembri, M.A.

    2006-01-01

    Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU). In contrast to uropathogenic E. coli (UPEC), which causes symptomatic urinary tract infections (UTI), very little is known about the mechanisms by which these strains colonize the human urinary tract...

  20. Identification and Prevalence of Escherichia coli and Escherichia coli O157: H7 in Foods

    Directory of Open Access Journals (Sweden)

    Ancuta Mihaela Rotar

    2013-11-01

    Full Text Available The objective of this study is to investigate the incidence of Escherichia coli in animal and non-animal foods, and mainly the incidence of the serotype O157: H7 producing verotoxin. The presence of common Escherichia coli and Escherichia coli O157: H7 in various foods (of animal and non animal origin was performed in Transylvania area. We analyzed a total of one hundred forty-one samples of minced meat, one hundred twenty-six samples of meat , twenty six samples of meat products, five samples of alcoholic beverages, three samples of seafood, one hundred samples of cheese from pasteurized milk, seventeen samples of butter, four samples of vegetables and one sample of milk powder, using the standard cultural method and Vidas Eco method for E. coli O157: H7 strains. E. coli was identified in 50 samples of minced meat, 55 samples of meat prepared, 4 samples of meat products, 2 samples of alcoholic beverages, 25 samples of cheese from pasteurized milk, 6 samples of butter and 1 sample of vegetables. In this study were not been identified any foods contaminated with the E. coli O157: H7 serotype. The results of this reasearch have demostrated that E. coli wich represents a hygienic indicator of recent food contamination, can be destroyed with heat treatment and hygienic handling of foods. Our country over the years has been among the few countries where the incidence of the E. coli O157: H7 serotype has been minimal.