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Sample records for adenomatous polyposis coli

  1. Adenomatous Polyposis Coli Mutation Leads to Myopia Development in Mice

    Liu, Zhen; Qiu, Fangfang; Li, Jing; Zhu, Zhenzhen; Yang, Wenzhao; Zhou, Xiangtian; An, Jianhong; Huang, Furong; Wang, Qiongsi; Reinach, Peter S.; Li, Wei; Chen, Wensheng; Liu, Zuguo

    2015-01-01

    Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP), havean adenomatous polyposis coli (APC) mutation and a higher incidence of myopia. To clarify this possible ass...

  2. Structural basis of the Axin–adenomatous polyposis coli interaction

    Spink, Katharine Eklof; Polakis, Paul; Weis, William I.

    2000-01-01

    Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-oncogene β-catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3β (GSK3β) and several other proteins. Both Axin and APC are known to be critical for β-catenin regulation, and truncations in APC that eliminate the Axin-b...

  3. Adenomatous Polyposis Coli Mutation Leads to Myopia Development in Mice.

    Zhen Liu

    Full Text Available Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP, havean adenomatous polyposis coli (APC mutation and a higher incidence of myopia. To clarify this possible association, we determined whether the changes in pertinent biometric and biochemical parameters underlying postnatal refractive error development in APCMin mice are relevant for gaining insight into the pathogenesis of this disease in humans. The refraction and biometrics in APCMin mice and age-matched wild-type (WT littermates between postnatal days P28 and P84 were examined with eccentric infrared photorefraction (EIR and customized optical coherence tomography (OCT. Compared with WT littermates, the APCMin mutated mice developed myopia (average -4.64 D on P84 which was associated with increased vitreous chamber depth (VCD. Furthermore, retinal and scleral changes appear in these mice along with: 1 axial length shortening; 2 increased retinal cell proliferation; 3 and decreased tyrosine hydroxylase (TH expression, the rate-limiting enzyme of DA synthesis. Scleral collagen fibril diameters became heterogeneous and irregularly organized in the APCMin mice. Western blot analysis showed that scleral alpha-1 type I collagen (col1α1 expression also decreased whereas MMP2 and MMP9 mRNA expression was invariant. These results indicate that defective APC gene function promotes refractive error development. By characterizing in APCMin mice ocular developmental changes, this approach provides novel insight into underlying pathophysiological mechanisms contributing to human myopia development.

  4. Adenomatous Polyposis Coli Mutation Leads to Myopia Development in Mice

    Li, Jing; Zhu, Zhenzhen; Yang, Wenzhao; Zhou, Xiangtian; An, Jianhong; Huang, Furong; Wang, Qiongsi; Reinach, Peter S.; Li, Wei; Chen, Wensheng; Liu, Zuguo

    2015-01-01

    Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP), havean adenomatous polyposis coli (APC) mutation and a higher incidence of myopia. To clarify this possible association, we determined whether the changes in pertinent biometric and biochemical parameters underlying postnatal refractive error development in APCMin mice are relevant for gaining insight into the pathogenesis of this disease in humans. The refraction and biometrics in APCMin mice and age-matched wild-type (WT) littermates between postnatal days P28 and P84 were examined with eccentric infrared photorefraction (EIR) and customized optical coherence tomography (OCT). Compared with WT littermates, the APCMin mutated mice developed myopia (average -4.64 D) on P84 which was associated with increased vitreous chamber depth (VCD). Furthermore, retinal and scleral changes appear in these mice along with: 1) axial length shortening; 2) increased retinal cell proliferation; 3) and decreased tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of DA synthesis. Scleral collagen fibril diameters became heterogeneous and irregularly organized in the APCMin mice. Western blot analysis showed that scleral alpha-1 type I collagen (col1α1) expression also decreased whereas MMP2 and MMP9 mRNA expression was invariant. These results indicate that defective APC gene function promotes refractive error development. By characterizing in APCMin mice ocular developmental changes, this approach provides novel insight into underlying pathophysiological mechanisms contributing to human myopia development. PMID:26495845

  5. Familial adenomatous polyposis

    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.......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...... 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...

  6. The Pancreas in Familial Adenomatous Polyposis

    Alaa Elkharwily; Klaus Gottlieb

    2008-01-01

    Familial adenomatous polyposis is an archetypal disease illustrating the genetic basis of human cancer. The adenomatouspolyposis coli gene functions as a tumor suppressor with hundreds of known mutations that result in a defective adenomatous polyposis coli protein. In addition to the certain fate of colon cancer without colectomy, patients with familialadenomatous polyposis are also at increased risk for other types of neoplasms, including those which affect the pancreas. This review focuses...

  7. The Pancreas in Familial Adenomatous Polyposis

    Alaa Elkharwily

    2008-01-01

    Full Text Available Familial adenomatous polyposis is an archetypal disease illustrating the genetic basis of human cancer. The adenomatouspolyposis coli gene functions as a tumor suppressor with hundreds of known mutations that result in a defective adenomatous polyposis coli protein. In addition to the certain fate of colon cancer without colectomy, patients with familialadenomatous polyposis are also at increased risk for other types of neoplasms, including those which affect the pancreas. This review focuses on periampullary and ampullary tumors, benign and malignant pancreatic neoplasms that are associated with familial adenomatous polyposis and Gardner syndrome and pancreatitis in these patients. An individualized surveillance regimen is suggested which for certain patients could include endoscopic ultrasound.

  8. A novel function of adenomatous polyposis coli (APC) in regulating DNA repair

    Jaiswal, Aruna S.; Narayan, Satya

    2008-01-01

    Prevailing literature suggests diversified cellular functions for the adenomatous polyposis coli (APC) gene. Among them a recently discovered unique role of APC is in DNA repair. The APC gene can modulate the base excision repair (BER) pathway through an interaction with DNA polymerase β (Pol-β) and flap endonuclease 1 (Fen-1). Taken together with the transcriptional activation of APC gene by alkylating agents and modulation of BER activity, APC may play an important role in carcinogenesis an...

  9. Characterization of Adenomatous Polyposis Coli Protein Dynamics and Localization at the Centrosome

    Christina Lui; Myth T. S. Mok; Henderson, Beric R.

    2016-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is a multifunctional regulator of Wnt signaling and acts as a mobile scaffold at different cellular sites. APC was recently found to stimulate microtubule (MT) growth at the interphase centrosome; however, little is known about its dynamics and localization at this site. To address this, we analysed APC dynamics in fixed and live cells by fluorescence microscopy. In detergent-extracted cells, we discovered that APC was only weakly retained...

  10. Familial adenomatous polyposis

    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 polyposisis a long step forward, and several problems may be solved by increasing international cooperation.......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...... 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...

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

    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

  12. Desmoid tumours in familial adenomatous polyposis.

    Gurbuz, A K; Giardiello, F.M.; Petersen, G M; Krush, A J; Offerhaus, G. J.; Booker, S V; Kerr, M.C.; Hamilton, S R

    1994-01-01

    Desmoids are rare, benign fibromatous lesions, which can arise in patients with familial adenomatous polyposis (FAP), a disorder caused by germline adenomatous polyposis coli (APC) gene mutation. This study investigated the risk of desmoids in FAP, the relation between specific APC gene mutations and desmoid formation, and the clinical characteristics of FAP patients with desmoids. Eighty three of 825 FAP patients (10%) from 49 of 161 kindreds (30%) had desmoids. The absolute risk of desmoids...

  13. Familial adenomatous polyposis

    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

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

    Price David J; Mason John O; Chen Yijing; Ivaniutsin Uladzislau; Pratt Thomas

    2009-01-01

    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 proliferat...

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

    Ivaniutsin, Uladzislau; CHEN, Yijing; John O. MASON; Price, David; Pratt, Thomas

    2009-01-01

    Background: Adenomatous polyposis coli (Apc) is a large multifunctional protein known to be important for Wnt/beta-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 Emx1(Cre) to inactivate Apc specifically in proliferating...

  16. Different Roles for the Axin Interactions with the SAMP versus the Second Twenty Amino Acid Repeat of Adenomatous Polyposis Coli

    Schneikert, Jean; Ruppert, Jan Gustav; Behrens, Jürgen; Wenzel, Eva Maria

    2014-01-01

    Wnt signalling is prevented by the proteosomal degradation of β-catenin, which occurs in a destruction complex containing adenomatous polyposis coli (APC), APC-like (APCL), Axin and Axin2. Truncating mutations of the APC gene result in the constitutive stabilisation of β-catenin and the initiation of colon cancer, although tumour cells tolerate the expression of wild-type APCL. Using the colocalisation of overexpressed Axin, APC and APCL constructs as a readout of interaction, we found that A...

  17. The Adenomatous polyposis coli tumour suppressor is essential for Axin complex assembly and function and opposes Axin's interaction with Dishevelled

    Mendoza-Topaz, Carolina; Mieszczanek, Juliusz; Bienz, Mariann

    2011-01-01

    Most cases of colorectal cancer are linked to mutational inactivation of the Adenomatous polyposis coli (APC) tumour suppressor. APC downregulates Wnt signalling by enabling Axin to promote the degradation of the Wnt signalling effector β-catenin (Armadillo in flies). This depends on Axin's DIX domain whose polymerization allows it to form dynamic protein assemblies (‘degradasomes’). Axin is inactivated upon Wnt signalling, by heteropolymerization with the DIX domain of Dishevelled, which rec...

  18. Adenomatous polyposis coli mutants dominantly activate Hsf1-dependent cell stress pathways through inhibition of microtubule dynamics

    Davies, Alexander E.; Kortright, Kaitlyn; Kaplan, Kenneth B.

    2015-01-01

    Cancer cells up-regulate cell stress pathways, including the protein chaperone Hsp90. Increases in Hsp90 are believed “buffer” mutant protein activities necessary for cancer phenotypes. Activation of the cell stress pathway also alters the transcriptional landscape of cells in ways that are critical for cancer progression. However, it is unclear when and how the cell stress pathway is de-regulated during cancer progression. Here we report that mutations in adenomatous polyposis coli (APC) fou...

  19. Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype

    Van der Auwera, I; Laere, S.J.; Van den Bosch, S M; Van den Eynden, G. G.; Trinh, B X; van Dam, P A; Colpaert, C G; van Engeland, M; Van Marck, E A; Vermeulen, P B; Dirix, L Y

    2008-01-01

    Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter occurs in about 40% of breast tumours and has been correlated with reduced APC protein levels. To what extent epigenetic alterations of the APC gene may differ according to specific breast cancer phenotypes, remains to be elucidated. Our aim was to explore the role of APC methylation in the inflammatory breast cancer (IBC) phenotype. The status of APC gene promoter hypermethylation was investigated in DNA from normal b...

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

    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

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

    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.

  2. Characterization of Adenomatous Polyposis Coli Protein Dynamics and Localization at the Centrosome.

    Lui, Christina; Mok, Myth T S; Henderson, Beric R

    2016-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is a multifunctional regulator of Wnt signaling and acts as a mobile scaffold at different cellular sites. APC was recently found to stimulate microtubule (MT) growth at the interphase centrosome; however, little is known about its dynamics and localization at this site. To address this, we analysed APC dynamics in fixed and live cells by fluorescence microscopy. In detergent-extracted cells, we discovered that APC was only weakly retained at the centrosome during interphase suggesting a rapid rate of exchange. This was confirmed in living cells by fluorescence recovery after photobleaching (FRAP), which identified two pools of green fluorescent protein (GFP)-APC: a major rapidly exchanging pool (~86%) and minor retained pool (~14%). The dynamic exchange rate of APC was unaffected by C-terminal truncations implicating a targeting role for the N-terminus. Indeed, we mapped centrosome localization to N-terminal armadillo repeat (ARM) domain amino acids 334-625. Interestingly, the rate of APC movement to the centrosome was stimulated by intact MTs, and APC dynamics slowed when MTs were disrupted by nocodazole treatment or knockdown of γ-tubulin. Thus, the rate of APC recycling at the centrosome is enhanced by MT growth, suggesting a positive feedback to stimulate its role in MT growth. PMID:27144584

  3. Characterization of Adenomatous Polyposis Coli Protein Dynamics and Localization at the Centrosome

    Christina Lui

    2016-04-01

    Full Text Available The adenomatous polyposis coli (APC tumor suppressor is a multifunctional regulator of Wnt signaling and acts as a mobile scaffold at different cellular sites. APC was recently found to stimulate microtubule (MT growth at the interphase centrosome; however, little is known about its dynamics and localization at this site. To address this, we analysed APC dynamics in fixed and live cells by fluorescence microscopy. In detergent-extracted cells, we discovered that APC was only weakly retained at the centrosome during interphase suggesting a rapid rate of exchange. This was confirmed in living cells by fluorescence recovery after photobleaching (FRAP, which identified two pools of green fluorescent protein (GFP-APC: a major rapidly exchanging pool (~86% and minor retained pool (~14%. The dynamic exchange rate of APC was unaffected by C-terminal truncations implicating a targeting role for the N-terminus. Indeed, we mapped centrosome localization to N-terminal armadillo repeat (ARM domain amino acids 334–625. Interestingly, the rate of APC movement to the centrosome was stimulated by intact MTs, and APC dynamics slowed when MTs were disrupted by nocodazole treatment or knockdown of γ-tubulin. Thus, the rate of APC recycling at the centrosome is enhanced by MT growth, suggesting a positive feedback to stimulate its role in MT growth.

  4. Familial adenomatous polyposis: from bedside to benchside.

    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.

  5. Diagnosis of familial adenomatous polyposis

    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....

  6. The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling

    Kunttas-Tatli, Ezgi; Von Kleeck, Ryan A.; Greaves, Bradford D.; Vinson, David; Roberts, David M.; McCartney, Brooke M.

    2015-01-01

    The colon cancer tumor suppressor Adenomatous polyposis coli (APC) negatively regulates Wnt signaling destruction complex by binding to β-catenin and facilitating its phosphorylation and degradation. The two SAMP repeats and their phosphorylation state in Drosophila APC2 play distinct roles in negatively regulating Wnt signaling.

  7. FAMILIAL ADENOMATOUS POLYPOSIS

    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.

  8. Apical Membrane Localization of the Adenomatous Polyposis Coli Tumor Suppressor Protein and Subcellular Distribution of the β-Catenin Destruction Complex in Polarized Epithelial Cells

    Reinacher-Schick, Anke; Gumbiner, Barry M.

    2001-01-01

    The adenomatous polyposis coli (APC) protein is implicated in the majority of hereditary and sporadic colon cancers. APC is known to function as a tumor suppressor through downregulation of β-catenin as part of a high molecular weight complex known as the β-catenin destruction complex. The molecular composition of the intact complex and its site of action in the cell are still not well understood. Reports on the subcellular localization of APC in various cell systems have differed significant...

  9. Chemoprevention of familial adenomatous polyposis.

    Lynch, Patrick M

    2016-07-01

    Familial adenomatous polyposis (FAP) has always been first and foremost a surgical disease, whose treatment with colectomy has long been known to reduce risk of premature cancer death. The notion of reducing polyp burden and potentially delaying surgical intervention has spawned a host of "chemoprevention" trials. In this paper I selectively review the findings from these studies, highlighting trial design issues and in particular some of the limitations of historical and existing trial endpoint measures. Nonsteroidal anti-inflammatory agents have been the most commonly employed chemopreventive agents. Sulindac, largely by historical accident, has been the most extensively studied, and is widely considered the standard of care when a clinical decision to intervene medically is made. Newer trials are evaluating combinations of agents in order to take advantage of differing mechanisms of action, in the hope of achieving synergy, as no single agent predictably or completely suppresses adenoma growth. Some of these studies and other single-agent interventions are discussed, though an exploration of the various mechanisms of action is beyond the scope of this paper. It is essential that future trials focus on the issue of "clinical benefit", not simply because the US Food and Drug Administration has insisted on it, but because only real evidence-based advances can improve the standard of medical care for FAP patients. Hence my focus on issues of trial design and clinically relevant endpoints. PMID:27083160

  10. Adenomatous polyposis coli (APC) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (GSK-3) activity.

    Valvezan, Alexander J; Zhang, Fang; Diehl, J Alan; Klein, Peter S

    2012-02-01

    Glycogen synthase kinase-3 (GSK-3) is essential for many signaling pathways and cellular processes. As Adenomatous Polyposis Coli (APC) functions in many of the same processes, we investigated a role for APC in the regulation of GSK-3-dependent signaling. We find that APC directly enhances GSK-3 activity. Furthermore, knockdown of APC mimics inhibition of GSK-3 by reducing phosphorylation of glycogen synthase and by activating mTOR, revealing novel roles for APC in the regulation of these enzymes. Wnt signaling inhibits GSK-3 through an unknown mechanism, and this results in both stabilization of β-catenin and activation of mTOR. We therefore hypothesized that Wnts may regulate GSK-3 by disrupting the interaction between APC and the Axin-GSK-3 complex. We find that Wnts rapidly induce APC dissociation from Axin, correlating with β-catenin stabilization. Furthermore, Axin interaction with the Wnt co-receptor LRP6 causes APC dissociation from Axin. We propose that APC regulates multiple signaling pathways by enhancing GSK-3 activity, and that Wnts induce APC dissociation from Axin to reduce GSK-3 activity and activate downstream signaling. APC regulation of GSK-3 also provides a novel mechanism for Wnt regulation of multiple downstream effectors, including β-catenin and mTOR. PMID:22184111

  11. The Adenomatous polyposis coli tumour suppressor is essential for Axin complex assembly and function and opposes Axin's interaction with Dishevelled.

    Mendoza-Topaz, Carolina; Mieszczanek, Juliusz; Bienz, Mariann

    2011-11-01

    Most cases of colorectal cancer are linked to mutational inactivation of the Adenomatous polyposis coli (APC) tumour suppressor. APC downregulates Wnt signalling by enabling Axin to promote the degradation of the Wnt signalling effector β-catenin (Armadillo in flies). This depends on Axin's DIX domain whose polymerization allows it to form dynamic protein assemblies ('degradasomes'). Axin is inactivated upon Wnt signalling, by heteropolymerization with the DIX domain of Dishevelled, which recruits it into membrane-associated 'signalosomes'. How APC promotes Axin's function is unclear, especially as it has been reported that APC's function can be bypassed by overexpression of Axin. Examining apc null mutant Drosophila tissues, we discovered that APC is required for Axin degradasome assembly, itself essential for Armadillo downregulation. Degradasome assembly is also attenuated in APC mutant cancer cells. Notably, Axin becomes prone to Dishevelled-dependent plasma membrane recruitment in the absence of APC, indicating a crucial role of APC in opposing the interaction of Axin with Dishevelled. Indeed, co-expression experiments reveal that APC displaces Dishevelled from Axin assemblies, promoting degradasome over signalosome formation in the absence of Wnts. APC thus empowers Axin to function in two ways-by enabling its DIX-dependent self-assembly, and by opposing its DIX-dependent copolymerization with Dishevelled and consequent inactivation. PMID:22645652

  12. Causes of death in familial adenomatous polyposis

    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 du...... 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....

  13. different Roles for the axin interactions with the SAMP versus the second twenty amino acid repeat of adenomatous polyposis coli.

    Schneikert, Jean; Ruppert, Jan Gustav; Behrens, Jürgen; Wenzel, Eva Maria

    2014-01-01

    Wnt signalling is prevented by the proteosomal degradation of β-catenin, which occurs in a destruction complex containing adenomatous polyposis coli (APC), APC-like (APCL), Axin and Axin2. Truncating mutations of the APC gene result in the constitutive stabilisation of β-catenin and the initiation of colon cancer, although tumour cells tolerate the expression of wild-type APCL. Using the colocalisation of overexpressed Axin, APC and APCL constructs as a readout of interaction, we found that Axin interacted with the second twenty amino acid repeat (20R2) of APC and APCL. This interaction involved a domain adjacent to the C-terminal DIX domain of Axin. We identified serine residues within the 20R2 of APCL that were involved in Axin colocalisation, the phosphorylation of truncated APCL and the down-regulation of β-catenin. Our results indicated that Axin, but not Axin2, displaced APC, but not APCL, from the cytoskeleton and stimulated its incorporation into bright cytoplasmic dots that others have recognised as β-catenin destruction complexes. The SAMP repeats in APC interact with the N-terminal RGS domain of Axin. Our data showed that a short domain containing the first SAMP repeat in truncated APC was required to stimulate Axin oligomerisation. This was independent of Axin colocalisation with 20R2. Our data also suggested that the RGS domain exerted an internal inhibitory constraint on Axin oligomerisation. Considering our data and those from others, we discuss a working model whereby β-catenin phosphorylation involves Axin and the 20R2 of APC or APCL and further processing of phospho-β-catenin occurs upon the oligomerisation of Axin that is induced by binding the SAMP repeats in APC. PMID:24722208

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

    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

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

    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.

  16. Rare combination of familial adenomatous polyposis and gallbladder polyps

    MORI, YASUHISA; Sato, Norihiro; Matayoshi, Nobutaka; Tamura, Toshihisa; Minagawa, Noritaka; Shibao, Kazunori; Higure, Aiichiro; Nakamoto, Mitsuhiro; Taguchi, Masashi; Yamaguchi, Koji

    2014-01-01

    Familial adenomatous polyposis is associated with a high incidence of malignancies in the upper gastrointestinal tract (particularly ampullary adenocarcinomas). However, few reports have described a correlation between familial adenomatous polyposis and gallbladder neoplasms. We present a case of a 60-year-old woman with familial adenomatous polyposis who presented with an elevated mass in the neck of the gallbladder (measuring 16 mm × 8 mm in diameter) and multiple small cholecystic polyps. ...

  17. Surgical treatment in familial adenomatous polyposis

    Tudyka, Vera N.; Clark, Susan K.

    2012-01-01

    Familial adenomatous polyposis (FAP) is a dominantly inherited condition caused by germline mutation of the APC gene resulting in formation of numerous large bowel adenomas in late childhood or adolescence. Unless these are removed, colorectal cancer inevitably develops. Prophylactic surgical treatment is required to prevent this. In surgical decision making, considerations should include genotype-phenotype correlation, perioperative morbidity and risk of impaired sexual and reproductive func...

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

    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...

  19. HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction.

    Tran, Hoanh; Bustos, Daisy; Yeh, Ronald; Rubinfeld, Bonnee; Lam, Cynthia; Shriver, Stephanie; Zilberleyb, Inna; Lee, Michelle W; Phu, Lilian; Sarkar, Anjali A; Zohn, Irene E; Wertz, Ingrid E; Kirkpatrick, Donald S; Polakis, Paul

    2013-02-01

    The adenomatous polyposis coli (APC) protein functions as a negative regulator of the Wnt signaling pathway. In this capacity, APC forms a "destruction complex" with Axin, CK1α, and GSK3β to foster phosphorylation of the Wnt effector β-catenin earmarking it for Lys-48-linked polyubiquitylation and proteasomal degradation. APC is conjugated with Lys-63-linked ubiquitin chains when it is bound to Axin, but it is unclear whether this modification promotes the APC-Axin interaction or confers upon APC an alternative function in the destruction complex. Here we identify HectD1 as a candidate E3 ubiquitin ligase that modifies APC with Lys-63 polyubiquitin. Knockdown of HectD1 diminished APC ubiquitylation, disrupted the APC-Axin interaction, and augmented Wnt3a-induced β-catenin stabilization and signaling. These results indicate that HectD1 promotes the APC-Axin interaction to negatively regulate Wnt signaling. PMID:23277359

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

    Perea del Pozo, E.; Ramirez Plaza, C.; J. Padillo Ruiz; J.M. Martos Martínez

    2015-01-01

    Background: Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome characterised by the progressive development of multiple colorectal adenomatous polyps and an increased incidence of colorectal carcinoma. It is often accompanied by other benign or malignant extracolonic manifestations, including gastric and duodenal tumours, osteomas, desmoid tumours, retinal pigmentation, and thyroid and adrenocortical tumours Methods and results: We report the case ...

  1. Results of national registration of familial adenomatous polyposis

    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 ...

  2. Reversible modification of adenomatous polyposis coli (APC) with K63-linked polyubiquitin regulates the assembly and activity of the β-catenin destruction complex.

    Tran, Hoanh; Polakis, Paul

    2012-08-17

    The adenomatous polyposis coli (APC) tumor suppressor forms a complex with Axin and GSK3β to promote the phosphorylation and degradation of β-catenin, a key co-activator of Wnt-induced transcription. Here, we establish that APC is modified predominantly with K63-linked ubiquitin chains when it is bound to Axin in unstimulated HEK293 cells. Wnt3a stimulation induced a time-dependent loss of K63-polyubiquitin adducts from APC, an effect synchronous with the dissociation of Axin from APC and the stabilization of cytosolic β-catenin. RNAi-mediated depletion of Axin or β-catenin, which negated the association between APC and Axin, resulted in the absence of K63-adducts on APC. Overexpression of wild-type and phosphodegron-mutant β-catenin, combined with analysis of thirteen human cancer cell lines that harbor oncogenic mutations in APC, Axin, or β-catenin, support the hypothesis that a fully assembled APC-Axin-GSK3β-phospho-β-catenin complex is necessary for the K63-polyubiquitylation of APC. Intriguingly, the degree of this modification on APC appears to correlate inversely with the levels of β-catenin in cells. Together, our results indicate that K63-linked polyubiquitin adducts on APC regulate the assembly and/or efficiency of the β-catenin destruction complex. PMID:22761442

  3. The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling.

    Kunttas-Tatli, Ezgi; Von Kleeck, Ryan A; Greaves, Bradford D; Vinson, David; Roberts, David M; McCartney, Brooke M

    2015-12-01

    The tumor suppressor Adenomatous polyposis coli (APC) plays a key role in regulating the canonical Wnt signaling pathway as an essential component of the β-catenin destruction complex. C-terminal truncations of APC are strongly implicated in both sporadic and familial forms of colorectal cancer. However, many questions remain as to how these mutations interfere with APC's tumor suppressor activity. One set of motifs frequently lost in these cancer-associated truncations is the SAMP repeats that mediate interactions between APC and Axin. APC proteins in both vertebrates and Drosophila contain multiple SAMP repeats that lack high sequence conservation outside of the Axin-binding motif. In this study, we tested the functional redundancy between different SAMPs and how these domains are regulated, using Drosophila APC2 and its two SAMP repeats as our model. Consistent with sequence conservation-based predictions, we show that SAMP2 has stronger binding activity to Axin in vitro, but SAMP1 also plays an essential role in the Wnt destruction complex in vivo. In addition, we demonstrate that the phosphorylation of SAMP repeats is a potential mechanism to regulate their activity. Overall our findings support a model in which each SAMP repeat plays a mechanistically distinct role but they cooperate for maximal destruction complex function. PMID:26446838

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

    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.

  5. Lymphoid enhancer factor-1 blocks adenomatous polyposis coli-mediated nuclear export and degradation of beta-catenin. Regulation by histone deacetylase 1.

    Henderson, Beric R; Galea, Melanie; Schuechner, Stefan; Leung, Louie

    2002-07-01

    The oncogenic protein beta-catenin is overexpressed in many cancers, frequently accumulating in nuclei where it forms active complexes with lymphoid enhancer factor-1 (LEF-1)/T-cell transcription factors, inducing genes such as c-myc and cyclin D1. In normal cells, nuclear beta-catenin levels are controlled by the adenomatous polyposis coli (APC) protein through nuclear export and cytoplasmic degradation. Transient expression of LEF-1 is known to increase nuclear beta-catenin levels by an unknown mechanism. Here, we show that APC and LEF-1 compete for nuclear beta-catenin with opposing consequences. APC can export nuclear beta-catenin to the cytoplasm for degradation. In contrast, LEF-1 anchors beta-catenin in the nucleus by blocking APC-mediated nuclear export. LEF-1 also prevented the APC/CRM1-independent nuclear export of beta-catenin as revealed by in vitro assays. Importantly, LEF-1-bound beta-catenin was protected from degradation by APC and axin in SW480 colon cancer cells. The ability of LEF-1 to trap beta-catenin in the nucleus was down-regulated by histone deacetylase 1, and this correlated with a decrease in LEF1 transcription activity. Our findings identify LEF-1 as key regulator of beta-catenin nuclear localization and stability and suggest that overexpression of LEF-1 in colon cancer and melanoma cells may contribute to the accumulation of oncogenic beta-catenin in the nucleus. PMID:11986304

  6. Culture of primary epithelial adenoma cells from familial adenomatous polyposis patients

    Fostira, F.; Apessos, A.; Oikonomou, E.; Kouklis, P.; Baratsis, S.; Manifikos, G.; Anděra, Ladislav; Yannoukakos, D.; Pintzas, A.; Nasioulas, G.

    2008-01-01

    Roč. 28, 2A (2008), s. 843-846. ISSN 0250-7005 Institutional research plan: CEZ:AV0Z50520514 Keywords : colorectal neoplasia * adenomatous polyposis coli * epithelial cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.390, year: 2008

  7. The postsynaptic adenomatous polyposis coli (APC) multiprotein complex is required for localizing neuroligin and neurexin to neuronal nicotinic synapses in vivo.

    Rosenberg, Madelaine M; Yang, Fang; Mohn, Jesse L; Storer, Elizabeth K; Jacob, Michele H

    2010-08-18

    Synaptic efficacy requires that presynaptic and postsynaptic specializations align precisely and mature coordinately. The underlying mechanisms are poorly understood, however. We propose that adenomatous polyposis coli protein (APC) is a key coordinator of presynaptic and postsynaptic maturation. APC organizes a multiprotein complex that directs nicotinic acetylcholine receptor (nAChR) localization at postsynaptic sites in avian ciliary ganglion neurons in vivo. We hypothesize that the APC complex also provides retrograde signals that direct presynaptic active zones to develop in register with postsynaptic nAChR clusters. In our model, the APC complex provides retrograde signals via postsynaptic neuroligin that interacts extracellularly with presynaptic neurexin. S-SCAM (synaptic cell adhesion molecule) and PSD-93 (postsynaptic density-93) are scaffold proteins that bind to neuroligin. We identify S-SCAM as a novel component of neuronal nicotinic synapses. We show that S-SCAM, PSD-93, neuroligin and neurexin are enriched at alpha3*-nAChR synapses. PSD-93 and S-SCAM bind to APC and its binding partner beta-catenin, respectively. Blockade of selected APC and beta-catenin interactions, in vivo, leads to decreased postsynaptic accumulation of S-SCAM, but not PSD-93. Importantly, neuroligin synaptic clusters are also decreased. On the presynaptic side, there are decreases in neurexin and active zone proteins. Further, presynaptic terminals are less mature structurally and functionally. We define a novel neural role for APC by showing that the postsynaptic APC multiprotein complex is required for anchoring neuroligin and neurexin at neuronal synapses in vivo. APC human gene mutations correlate with autism spectrum disorders, providing strong support for the importance of the association, demonstrated here, between APC, neuroligin and neurexin. PMID:20720115

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

    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

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

    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.

  10. Attenuated familial adenomatous polyposis presenting as ampullary adenocarcinoma

    Trimbath, J.D.; Griffin, C; Romans, K; Giardiello, F M

    2003-01-01

    The risk of periampullary cancer in patients with classic familial adenomatous polyposis (FAP) is significantly increased compared with the general population. However, the incidence of this extracolonic manifestation in attenuated FAP (AFAP) is unknown. We report the case of a 38 year old woman with no known family history of polyposis or colorectal cancer, who presented with ampullary adenocarcinoma. Diagnosis of AFAP was made only after evaluation of the patient’s extended family history a...

  11. Pigmented mesenteric lymphadenopathy in familial adenomatous polyposis - an unusual cause of intraoperative abandonment of ileo-anal pouch.

    Pranesh, N; Haboubi, N Y; O'Dwyer, S T

    2005-01-01

    Familial adenomatous polyposis (FAP) is an autosomal dominant condition with near complete penetrance, characterised by the presence of numerous adenomatous polyps of the colon and rectum. Melanosis coli describes the brownish-black discolouration of the colon resulting from the accumulation of a granular pigment in the phagosomes of macrophages in the colonic lamina propria. The presence of melanosis pigment in pericolonic lymph nodes has been reported in patients with coincidental melanosis...

  12. Age and manifestation related symptoms in familial adenomatous polyposis

    Hohenberger Werner; Reingruber Bertram; Brueckl Wolfgang M; Croner Roland S; Guenther Klaus

    2005-01-01

    Abstract Background To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. Methods We undertook a retrospective study of 143 FAP patients treated at the Department of...

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

    Vasen, H.F.; Moslein, G.; Alonso, A.; Aretz, S.; Bernstein, I.; Bertario, L.; Blanco, I.; Bulow, S.; Burn, J.; Capella, G.; Colas, C.; Engel, C.; Frayling, I.; Friedl, W.; Hes, F.J.; Hodgson, S.; Jarvinen, H.; Mecklin, J.P.; Moller, P.; Myrhoi, T.; Nagengast, F.M.; Parc, Y.; Phillips, R.; Clark, S.K.; Leon, M.P. de; Renkonen-Sinisalo, L.; Sampson, J.R.; Stormorken, A.; Tejpar, S.; Thomas, H.J.; Wijnen, J.; Vasen, H F A; Möslein, G; Alonso, A; Aretz, S; Bernstein, Inge Thomsen; Bertario, L; Blanco, I; Bülow, Steffen; Burn, J; Capella, G; Colas, C; Engel, C; Frayling, I; Friedl, W; Hes, F J; Hodgson, S; Järvinen, H; Mecklin, J-P; Møller, P; Myrhøi, T; Nagensgast, F M; Parc, Y; Phillips, R; Clark, S K; Ponz de Leon, M; Renkonen-Sinisalo, L; Sampson, J R; Stormorken, A; Tejpar, S; Thomas, H J W; Wijnen, J

    2008-01-01

    BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC...... typical FAP. The gene 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...

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

    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...... 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....... Mesenteric DT can cause small bowel obstruction or ischaemia, hydronephrosis or form fistulas. Diagnosis is obtained through biopsy and the extension is determined by a CT-scan. Surgical excision is recommended in patients with DT in the abdominal wall. First line treatment of mesenteric DT is a NSAID in...

  15. Galangin suppresses the proliferation of β-catenin response transcription-positive cancer cells by promoting adenomatous polyposis coli/Axin/glycogen synthase kinase-3β-independent β-catenin degradation.

    Gwak, Jungsug; Oh, Jingyo; Cho, Munju; Bae, Soo Kyung; Song, Im-Sook; Liu, Kwang-Hyeon; Jeong, Yongsu; Kim, Dong-Eun; Chung, Young-Hwa; Oh, Sangtaek

    2011-06-01

    Galangin is a naturally occurring bioflavonoid with anticancer activity against certain human cancers, yet little is known about its mechanism of action. Here, we used a chemical biology approach to reveal that galangin suppresses β-catenin response transcription (CRT), which is aberrantly up-regulated in colorectal and liver cancers, by promoting the degradation of intracellular β-catenin. Inhibition of glycogen synthase kinase-3β (GSK-3β) activity or mutation of the GSK-3β-targeted sequence from β-catenin was unable to abrogate the galangin-mediated degradation of β-catenin. In addition, galangin down-regulated the intracellular β-catenin levels in cancer cells with inactivating mutations of adenomatous polyposis coli (APC) or Axin, which are components of the β-catenin destruction complex. Galangin repressed the expression of β-catenin/T-cell factor-dependent genes, such as cyclin D1 and c-myc, and thus inhibited the proliferation of CRT-positive cancer cells. Structure-activity data indicated that the major structural requirements for galangin-mediated β-catenin degradation are hydroxyl groups at positions 3, 5, and 7. Our findings suggest that galangin exerts its anticancer activity by promoting APC/Axin/GSK-3β-independent proteasomal degradation of β-catenin. PMID:21406604

  16. Adenomatous polyposis coli (APC) membrane recruitment 3, a member of the APC membrane recruitment family of APC-binding proteins, is a positive regulator of Wnt-β-catenin signalling.

    Brauburger, Katharina; Akyildiz, Senem; Ruppert, Jan G; Graeb, Michael; Bernkopf, Dominic B; Hadjihannas, Michel V; Behrens, Jürgen

    2014-02-01

    The adenomatous polyposis coli (APC) membrane recruitment (Amer) family proteins Amer1/Wilms tumour gene on the X chromosome and Amer2 are binding partners of the APC tumour suppressor protein, and act as negative regulators in the Wnt signalling cascade. So far, nothing has been known about the third member of the family, Amer3. Here we show that Amer3 binds to the armadillo repeat domain of APC, similarly to Amer1 and Amer2. Amer3 also binds to the Wnt pathway regulator conductin/axin2. Furthermore, we identified Amer1 as binding partner of Amer3. Whereas Amer1 and Amer2 are linked to the plasma membrane by an N-terminal membrane localization domain, Amer3 lacks this domain. Amer3 localizes to the cytoplasm and nucleus of epithelial cells, and this is dependent on specific nuclear import and export sequences. Functionally, exogenous Amer3 enhances the expression of a β-catenin/T-cell factor-dependent reporter gene, and knockdown of endogenous Amer3 reduces Wnt target gene expression in colorectal cancer cells. Thus, Amer3 acts as an activator of Wnt signalling, in contrast to Amer1 and Amer2, which are inhibitors, suggesting a nonredundant role of Amer proteins in the regulation of this pathway. Our data, together with those of previous studies, provide a comprehensive picture of similarities and differences within the Amer protein family. PMID:24251807

  17. Variation of a variation: Case report of attenuated familial adenomatous polyposis

    Bhatnagar, P; Tetzlaff, H.; Izatt, L; Devlin, J; Heaton, N. D.

    2006-01-01

    Background. First described in 1988, attenuated familial adenomatous polyposis (AFAP) is a rare autosomal dominant precancerous condition of the gastrointestinal tract. Few reports have described adenocarcinomatous change in the gastroduodenal region thus far. Case outlineWe report a case of AFAP presenting with extensive gastric polyposis and ampullary adenocarcinoma in absence of a positive family history of gastrointestinal cancer and a novel mutation.

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

    Knudsen, A L; Bülow, S; Tomlinson, I; Möslein, G; Heinimann, K; Christensen, I J

    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...

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

    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. 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). 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. Screening for APC mutations in FAP patients should include testing for splicing defects and gross genomic alterations

  20. Adenoma development in familial adenomatous polyposis and MUTYH-associated polyposis: somatic landscape and driver genes.

    Rashid, Mamunur; Fischer, Andrej; Wilson, Cathy H; Tiffen, Jessamy; Rust, Alistair G; Stevens, Philip; Idziaszczyk, Shelley; Maynard, Julie; Williams, Geraint T; Mustonen, Ville; Sampson, Julian R; Adams, David J

    2016-01-01

    Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient, and a further 63 adenomas by capillary sequencing (41 FAP, 22 MAP). With these data we examined the profile of mutated genes, the mutational signatures and the somatic mutation rates, observing significant diversity in the constellations of mutated driver genes in different adenomas, and loss-of-function mutations in WTX (9%; p < 9.99e-06), a gene implicated in regulation of the WNT pathway and p53 acetylation. These data extend our understanding of the early events in colorectal tumourigenesis in the polyposis syndromes. PMID:26414517

  1. [Familial adenomatous polyposis: establishing a registry and genetic and molecular analysis].

    Shomrat, R; Bruchim, R; Galanty, Y; Samuel, Z; Legum, C; Rabau, M; Rozen, P

    1997-01-15

    Familial adenomatous polyposis (FAP), a dominantly inherited disease, is caused by a mutation in the adenomatous polyposis coli gene in chromosome 5q21. The gene has 15 exons, a physical length of 10 Kb and an open reading frame of 8.5 Kb. Exon 15 codes 66% of the mRNA and has a mutation cluster region which accounts for over 50% of mutations. The disease usually leads to the appearance of hundreds of adenomatous polyps in the transverse and descending colon between puberty and age 20 years and to colon cancer before the age of 40. Early detection is essential to prevent the development of metastasizing cancer. Since 1994 we have recruited 23 families for genetic counseling. DNA was obtained from 19 unrelated FAP patients and 219 high risk relatives in 19 unrelated families following confirmation of the diagnosis. In addition to linkage studies, direct mutational analysis was performed using the protein truncation test for most of exon 15 and single strand conformation polymorphism analysis for the other exons. These exons account for most of the mutations identified to date. Of 19 unrelated probands, 14 had detectable mutations. Exon 15 accounted for 6 families, exons 5, 7 and 14 for 1 each, exon 9 for 3, and exon 8 for 2. Combined mutational and linkage analysis identified 18 presymptomatic carriers who received genetic and clinical counseling. Our FAP patients did not differ significantly from those of larger studies in other countries with regard to the distribution of the mutations, gender and genotype-phenotype correlation, or ethnic distribution. PMID:9119305

  2. Clinicopathological features of familial adenomatous polyposis in Korean patients

    Jung, Sung Min; Yoon, Yong Sik; Lim, Seok-Byeong; Yu, Chang Sik; Kim, Jin Cheon

    2016-01-01

    AIM: To identify prognostic factors and to correlate APC mutations with clinical features, including extracolic manifestations. METHODS: One hundred thirty-five patients who underwent surgical procedures for familial adenomatous polyposis (FAP) were included. FAP was diagnosed when the number of adenomatous polyps was > 100. Data related to patient, extracoloic manifestations, cancer characteristics, operative procedure, follow up and surveillance were collected. APC mutation testing was performed in the 30 most recent patients. DNA was extracted from peripheral blood and polymerase chain reaction products using 31 primer pairs on APC gene were sequenced. A retrospective study was performed to investigate a causal relationship between prognosis and feature of patient. RESULTS: The mean age of the 51 patients with colorectal cancer (CRC) was older than that of those without CRC (30.5 vs 36.9, P = 0.002). Older individuals were more likely to have colon cancer at the time of FAP diagnosis [odds ratio, 4.75 (95%CI: 1.71-13.89) and 5.91(1.76-22.12) for 40-49 years and age > 50 vs age < 30). The number of confirmed deaths was 13 and the median age at death was 40 years (range, 27 to 85 years). Ten of the deaths (76.9%) were from CRC. Another cause of two cases of death were desmoid tumors (15.4%). Development of cancer on remnant rectal or ileal mucosa after surgery was not observed. The APC mutation testing revealed 23 pathogenic mutations and one likely pathogenic mutation, among which were four novel mutations. The correlation between mutational status and clinical manifestations was investigated. Mutations that could prodict poor prognosis were at codon 1309 which located on mutation cluster region, codon 1465 and codon 1507. CONCLUSION: Identification of APC mutations should aid in the diagnosis and counseling of family members in terms of early diagnosis and management of FAP. PMID:27158207

  3. Age and manifestation related symptoms in familial adenomatous polyposis

    Hohenberger Werner

    2005-03-01

    Full Text Available Abstract Background To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. Methods We undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups. Results FAP was diagnosed clinically on the basis of symptoms in 84% (120/143 of these patients. Most presented with intestinal symptoms such as colonic bleeding (68% and diarrhea (42%. All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76, whereas in those over 40 years old the prevalence was 76% (35/46. Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40. Conclusion The commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery.

  4. 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

    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. 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. 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 to promoter hypermethylation showed a lower rate of

  5. [Adenomatous polyposis of the gallbladder and Gardner's syndrome. A rare association].

    Brevet, Marie; Brehant, Olivier; Dumont, Frédéric; Regimbeau, Jean-Marc; Dupas, Jean-Louis; Chatelain, Denis

    2007-04-01

    We report one case of adenomatous polyposis of the gallbladder in a 57 year-old woman with Gardner's syndrome presenting with cholangitis. On gross examination the gallbladder contained two calculi and numerous flat or polypoid adenomas less than 1 cm in size. On microscopic examination, the adenomas showed low and high grade intraepithelial neoplasia. Only 10 cases of gallbladder adenomas have been reported in the literature in patients presenting with familial adenomatous polyposis (FAP). Cholecystectomy is usually performed for cholecystitis or cholangitis. These adenomatous gallbladder lesions are discovered late, often when the patient is older than 40. Pathogenesis of gallbladder adenomas is still unclear. It is difficult to assess the risk of malignancy: only 6 cases of gallbladder adenocarcinomas have been reported in patients with FAP. PMID:17483782

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

    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. PMID:26805944

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

    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

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

    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

  9. Familial adenomatous polyposis in pediatrics: natural history, emerging surveillance and management protocols, chemopreventive strategies, and areas of ongoing debate.

    Septer, Seth; Lawson, Caitlin E; Anant, Shrikant; Attard, Thomas

    2016-07-01

    Familial adenomatous polyposis (FAP) is a hereditary condition with a near 100 % lifetime risk of colorectal cancer without prophylactic colectomy. Most patients with FAP have a mutation in the adenomatous polyposis coli gene on chromosome 5q22. This condition frequently presents in children with polyps developing most frequently in the second decade of life and surveillance colonoscopy is required starting at age ten. Polyps are found not only in the colon, but in the stomach and duodenum. Knowledge of the natural history of FAP is important as there are several extra-colonic sequelae which also require surveillance. In infants and toddlers, there is an increased risk of hepatoblastoma, while in teenagers and adults duodenal carcinomas, desmoid tumors, thyroid cancer and medulloblastoma are more common in FAP than in the general population. Current chemopreventive strategies include several medications and natural products, although to this point there is no consensus on the most efficacious and safe agent. Genetic counseling is an important part of the diagnostic process for FAP. Appropriate use and interpretation of genetic testing is best accomplished with genetic counselor involvement as many families also have concerns regarding future insurability or discrimination when faced with genetic testing. PMID:27056662

  10. Controversies in the surgery of patients with familial adenomatous polyposis and Lynch syndrome.

    Church, James M

    2016-07-01

    Dominantly inherited syndromes of colorectal cancer predisposition are characterized by multifocal neoplasia with an early age of onset. The risk of colorectal cancer is high in affected patients and care of the patients is based on the aims of cancer prevention and cancer cure. At the same time, quality of life should be disturbed as little as possible. Because patients are generally young, the stakes are high. Injudicious decision-making can have unfortunate effects on patients and families. In this article the controversial aspects of surgery in familial adenomatous polyposis and Lynch syndrome are discussed. Specifically the controversies in familial adenomatous polyposis include the timing and the type of surgery while for Lynch syndrome discussion revolves about prophylactic surgery, primary, secondary and tertiary. PMID:26869170

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

    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.

  12. Subsequent Adenomas of Ileal Pouch and Anorectal Segment after Prophylactic Surgery for Familial Adenomatous Polyposis

    M'Koma, A.E.; Herline, A.J.; Adunyah, S.E.

    2013-01-01

    Familial adenomatous polyposis (FAP) is an autosomally dominant disease characterized by the early development of colorectal adenomas and carcinoma in untreated patients. Patients with FAP may develop rectal cancer at their initial presentation (primary) or after prophylactic surgery (secondary). Controversies exist regarding which surgical procedure represents the best first-line treatment. The options for FAP are ileorectal anastomosis (IRA) or a restorative proctocolectomy (RPC) with eithe...

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

    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.

  14. Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis.

    Adam, Ronja; Spier, Isabel; Zhao, Bixiao; Kloth, Michael; Marquez, Jonathan; Hinrichsen, Inga; Kirfel, Jutta; Tafazzoli, Aylar; Horpaopan, Sukanya; Uhlhaas, Siegfried; Stienen, Dietlinde; Friedrichs, Nicolaus; Altmüller, Janine; Laner, Andreas; Holzapfel, Stefanie; Peters, Sophia; Kayser, Katrin; Thiele, Holger; Holinski-Feder, Elke; Marra, Giancarlo; Kristiansen, Glen; Nöthen, Markus M; Büttner, Reinhard; Möslein, Gabriela; Betz, Regina C; Brieger, Angela; Lifton, Richard P; Aretz, Stefan

    2016-08-01

    In ∼30% of families affected by colorectal adenomatous polyposis, no germline mutations have been identified in the previously implicated genes APC, MUTYH, POLE, POLD1, and NTHL1, although a hereditary etiology is likely. To uncover further genes with high-penetrance causative mutations, we performed exome sequencing of leukocyte DNA from 102 unrelated individuals with unexplained adenomatous polyposis. We identified two unrelated individuals with differing compound-heterozygous loss-of-function (LoF) germline mutations in the mismatch-repair gene MSH3. The impact of the MSH3 mutations (c.1148delA, c.2319-1G>A, c.2760delC, and c.3001-2A>C) was indicated at the RNA and protein levels. Analysis of the diseased individuals' tumor tissue demonstrated high microsatellite instability of di- and tetranucleotides (EMAST), and immunohistochemical staining illustrated a complete loss of nuclear MSH3 in normal and tumor tissue, confirming the LoF effect and causal relevance of the mutations. The pedigrees, genotypes, and frequency of MSH3 mutations in the general population are consistent with an autosomal-recessive mode of inheritance. Both index persons have an affected sibling carrying the same mutations. The tumor spectrum in these four persons comprised colorectal and duodenal adenomas, colorectal cancer, gastric cancer, and an early-onset astrocytoma. Additionally, we detected one unrelated individual with biallelic PMS2 germline mutations, representing constitutional mismatch-repair deficiency. Potentially causative variants in 14 more candidate genes identified in 26 other individuals require further workup. In the present study, we identified biallelic germline MSH3 mutations in individuals with a suspected hereditary tumor syndrome. Our data suggest that MSH3 mutations represent an additional recessive subtype of colorectal adenomatous polyposis. PMID:27476653

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

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

    2006-01-01

    develop colorectal cancer, but the lifetime risk of upper gastrointestinal cancer is lower, estimated at approximately 5%. Management of the upper gastrointestinal cancer risk is one of the greatest challenges facing clinicians involved in the care of Polyposis families, and with improved survival......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 predictably...... 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...

  16. Genetic basis of hereditary colorectal cancers: Hereditary nonpolyposis colorectal cancer and Familial adenomatous polyposis

    Renkonen, Elise

    2006-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are characterized by a high risk and early onset of colorectal cancer (CRC). HNPCC is due to a germline mutation in one of the following MMR genes: MLH1, MSH2, MSH6 and PMS2. A majority of FAP and attenuated FAP (AFAP) cases are due to germline mutations of APC, causing the development of multiple colorectal polyps. To date, over 450 MMR gene mutations and over 800 APC mutations have been identified. Mo...

  17. 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

    Nilbert, Mef; Kristoffersson, Ulf; Ericsson, Mats; Johannsson, Oskar; Rambech, Eva; Mangell, Peter

    2008-01-01

    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 ...

  18. Two cases of 5q deletions in patients with familial adenomatous polyposis: possible link with Caroli's disease.

    Hodgson, S V; Coonar, A S; P. J. Hanson; Cottrell, S; Scriven, P N; Jones, T; Hawley, P R; Wilkinson, M L

    1993-01-01

    Two cases are reported of patients with deletions of chromosome 5q. Both have familial adenomatous polyposis (FAP) and mild mental retardation. In both, macroscopic polyposis was confined to the proximal colon in adult life (in their thirties) although microscopic adenomatosis was shown in the more distal colon with occasional single polyps. Both subjects had dermoid cysts, and congenital hypertrophy of the retinal pigment epithelium (CHRPE) was seen in case 2. Case 1 has gastroduodenal polyp...

  19. Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis

    Hes, F.J.; Ruano, D.; Nieuwenhuis, M.; Tops, C.M.; Schrumpf, M.; Nielsen, M.; Huijts, P.E.; Wijnen, J.T.; Wagner, A.; Garcia, E.B.; Sijmons, R.H.; Menko, F.H.; Letteboer, T.G.; Hoogerbrugge, N.; Harryvan, J.; Kampman, E.; Morreau, H.; Vasen, H.F.; Wezel, T. van

    2014-01-01

    BACKGROUND: Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20-30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC

  20. Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis

    Hes, Frederik J.; Ruano, Dina; Nieuwenhuis, Marry; Tops, Carli M.; Schrumpf, Melanie; Nielsen, Maartje; Huijts, Petra E. A.; Wijnen, Juul T.; Wagner, Anja; Gomez Garcia, Encarna B.; Sijmons, Rolf H.; Menko, Fred H.; Letteboer, Tom G. W.; Hoogerbrugge, Nicoline; Harryvan, Jan; Kampman, Ellen; Morreau, Hans; Vasen, Hans F. A.; van Wezel, Tom

    2014-01-01

    Background Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20-30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC

  1. Familial Adenomatous Polyposis in Three Generations of a Single Family: A Case Study

    Jure Murgic

    2014-05-01

    Full Text Available Background: Familial adenomatous polyposis (FAP is an autosomal dominantly inherited syndrome characterized by the development of numerous polyps in the colon and rectum. If left untreated, the affected patients inevitably develop colon cancer by the age of 40 years. A resection of the colon (colectomy or of the colon and rectum (proctocolectomy is needed to minimize the risk of cancer. Case Presentation: We report a case of FAP through three generations of a single family, in which the grandmother and granddaughter underwent total colectomy with ileoanal anastomosis and did not develop colon cancer, while the son underwent subtotal colectomy with ileorectal anastomosis and developed recurrent rectal cancer. Data regarding timely surgery, surveillance, and chemoprevention are discussed. Conclusion: The FAP phenotype determines the type of treatment. In severe polyposis, proctocolectomy with ileoanal anastomosis seems to be the optimal method for minimizing the risk of cancer development. This case report advocates complete rectal removal, especially in cases of poor patient compliance with colonoscopic surveillance.

  2. Dietary Putrescine Reduces the Anticarcinogenic Intestinal Activity of Sulindac in a Murine Model of Familial Adenomatous Polyposis

    Ignatenko, Natalia A.; Besselsen, David G; Basu Roy, Upal K.; Stringer, David E.; Blohm-Mangone, Karen A.; Padilla-Torres, Jose L.; Guillen-R, Jose M.; Gerner, Eugene W.

    2006-01-01

    The nonsteroidal antiinflammatory drug sulindac displays chemopreventive activity in patients with familial adenomatous polyposis (FAP). Sulindac metabolites induce apoptosis in colon tumor cells, in part, by a polyamine-dependent mechanism that can be suppressed with exogenous putrescine. To determine the relevance of this mechanism in animals, we treated ApcMin/+ mice, a model of human FAP, with sulindac alone or in combination with dietary putrescine. Sulindac increased steady-state RNA le...

  3. Colonic Crypt Changes during Adenoma Development in Familial Adenomatous Polyposis : Immunohistochemical Evidence for Expansion of the Crypt Base Cell Population

    Boman, Bruce M; Walters, Rhonda; Fields, Jeremy Z.; Kovatich, Albert J.; Zhang, Tao; Isenberg, Gerald A.; Goldstein, Scott D.; Palazzo, Juan P.

    2004-01-01

    Familial adenomatous polyposis patients, who have a germline APC mutation, develop adenomas in normal-appearing colonic mucosa, and in the process usually acquire a mutation in the other APC allele as well. Nonetheless, the cellular mechanisms that link these initiating genetic changes with the earliest tissue changes (upward shift in the labeling index) in colon tumorigenesis are unclear. Based on the tenet that colorectal cancer originates from crypt stem cells (SCs) and on our kinetic mode...

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

    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 has occurred as a result or not

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

    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.

  6. The challenge of developmentally appropriate care: predictive genetic testing in young people for familial adenomatous polyposis.

    Duncan, Rony E; Gillam, Lynn; Savulescu, Julian; Williamson, Robert; Rogers, John G; Delatycki, Martin B

    2010-03-01

    Predictive genetic tests for familial adenomatous polyposis (FAP) are routinely offered to young people during early adolescence. While this is not controversial, due to the medical benefit conferred by the test, it is nonetheless challenging as a consequence of the stage of life of the young people, and the simultaneous involvement of multiple family members. Despite these challenges, it is possible to ensure that the test is offered in such a way that it actively acknowledges and facilitates young people's developing autonomy and psychosocial well-being. In this paper we present findings from ten in-depth interviews with young people who have undergone predictive genetic testing for FAP (four male, six female; five gene-positive, five gene-negative; aged 10-17 years at the time of their predictive test; aged 12-25 years at the time of their research interview). We present five themes that emerged from the interviews which highlight key ethical challenges associated with such testing. These are: (1) the significance of the test; (2) young people's lack of involvement in the decision to be tested; (3) young people's limited understanding; (4) provision of the blood test at the first visit; and (5) group testing of family members. We draw on these themes to make eight recommendations for future practice. Together, these recommendations highlight the importance of providing developmentally appropriate care to young people undergoing predictive genetic testing for FAP. PMID:19760114

  7. Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis

    Hes, Frederik J; Ruano, Dina; Nieuwenhuis, Marry; Tops, Carli M; Schrumpf, Melanie; Nielsen, Maartje; Huijts, Petra E A; Wijnen, Juul T; Wagner, Anja; Gómez García, Encarna B; Sijmons, Rolf H; Menko, Fred H; Letteboer, Tom G W; Hoogerbrugge, Nicoline; Harryvan, Jan; Kampman, Ellen; Morreau, Hans; Vasen, Hans F A; van Wezel, Tom

    2013-01-01

    Background Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20–30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC risk variants play a role in patients with >10 adenomas. Methods We analysed a total of 16 SNPs with a reported association with CRC in a cohort of 252 genetically unexplained index patients with >10 colorectal adenomas and 745 controls. In addition, we collected detailed clinical information from index patients and their first-degree relatives (FDRs). Results We found a statistically significant association with two of the variants tested: rs3802842 (at chromosome 11q23, OR=1.60, 95% CI 1.3 to 2.0) and rs4779584 (at chromosome 15q13, OR=1.50, 95% CI 1.2 to 1.9). The majority of index patients (84%) had between 10 and 100 adenomas and 15% had >100 adenomas. Only two index patients (1%), both with >100 adenomas, had FDRs with polyposis. Forty-one per cent of the index patients had one or more FDRs with CRC. Conclusions These SNPs are the first common, low-penetrant variants reported to be associated with adenomatous polyposis not caused by a defect in the APC, MUTYH, POLD1 and POLE genes. Even though familial occurrence of polyposis was very rare, CRC was over-represented in FDRs of polyposis patients and, if confirmed, these relatives will therefore benefit from surveillance. PMID:24253443

  8. Endoscopic Submucosal Dissection for the Complete Resection of the Rectal Remnant Mucosa in a Patient With Familial Adenomatous Polyposis

    Akiyama, Hitoshi; Suzuki, Koyu; Fujita, Yoshiyuki

    2016-01-01

    A 47-year-old woman underwent prophylactic subtotal colectomy with ileorectal anastomosis (IRA) for familial adenomatous polyposis (FAP) 18 years ago. She underwent 5 transanal endoscopic microsurgeries for rectal remnant polyps, and was referred for the treatment of rectal remnant polyp recurrence. Endoscopic submucosal dissection (ESD) was performed to remove multiple polypoid lesions that circumferentially extended throughout the rectal remnant with lesions spreading onto the anastomotic site. The rectal remnant mucosa was resected in 2 pieces without complication. Specimens showed high-grade adenoma but no malignancy. Follow-up colonoscopy showed no recurrence. PMID:27144195

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

    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.

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

    A. Olry de Labry Lima; L. Sordo del Castillo; L. García Mochón; Epstein, D; C. Bermúdez Tamayo; R. Villegas Portero

    2008-01-01

    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 efe...

  11. Colonic and duodenal flat adenomas in children with classical familial adenomatous polyposis.

    Cohen, Marta; Thomson, Mike; Taylor, Chris; Donatone, Jorge; Quijano, Graciela; Drut, Ricardo

    2006-04-01

    Flat adenomas of the colon and duodenum have been described as associating with familial adenomatous polyposis (FAP), its attenuated variant, and the so-called hereditary nonpolyposis colorectal cancer. There seem to be no report on the occurrence of flat adenomas in pediatric patients with family history of FAP. We are reporting 4 children from 2 cancer-prone families in whom colonic and duodenal moderately dysplastic flat adenomas were found. Gastrointestinal endoscopy and biopsies were performed in 3 female siblings (7, 9, and 11 years old) and 1 male (9 years old) when referred for screening owing to familial history of bowel cancer (family 1) or evidence of bilateral congenital hypertrophy of the retinal pigment epithelium (CHRPE), which is known to be associated with FAP (family 2). Endoscopic visualization of the mucosa was improved by use of 0.2% indigo carmine solution spray. Biopsies were routinely processed for H&E and immunohistochemistry staining. Present patients were asymptomatic, with the exception of 2 weeks rectal bleeding in 1 of them. The colonic videoendoscopy showed in 2/3 siblings hundreds of flat or slightly raised plaques less than 1 cm in diameter as well as some classic polyps throughout the colon. The other sibling showed 40 flat-topped lesions with minimal elevation and central umbilication in the cecum. Upper endoscopy demonstrated a few flat lesions in the nonperiampullary area of the duodenum in 2/4 patients. The colonic videoendoscopy performed on the 9-year-old boy revealed multiple small sessile polyps. Microscopic study demonstrated tubular adenomas with a few neoplastic crypts, slight disarray of the overall architecture, and moderate (low-grade) dysplasia of the epithelium. These features were more obvious at the center and superficial areas of the adenomas. The 4 children had multiple flat adenomas of the colon and duodenum (2/4) matching with those described in adult patients. Flat adenomas in the context of FAP probably

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

    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

  13. 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

    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.

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

    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

    2016-05-01

    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

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

    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-(18F)-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.)

  16. Comparison of proctocolectomy and ileal pouch-anal anastomosis to colectomy and ileorectal anastomosis in familial adenomatous polyposis.

    Koskenvuo, L; Mustonen, H; Renkonen-Sinisalo, L; Järvinen, H J; Lepistö, A

    2015-06-01

    Prophylactic surgical options for familial adenomatous polyposis (FAP) are either colectomy and ileorectal anastomosis (IRA) or proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this study was to analyse the short-term and long-term outcomes of these two operative techniques. All patients with FAP in Finland have been prospectively recorded in a database since 1963 were retrospectively reviewed in this analysis. Altogether 140 (61%) colectomies with IRA and 88 (39%) proctocolectomies with IPAA have been performed. Complications occurred in 28 (21%) patients after IRA and in 26 (30%) patients after IPAA. There were 15 (11%) severe complications for IRA and 5 (6%) for IPAA. Twenty-one (15%) patients of the IRA group ended up in conventional ileostomy whereas 3 (3.4%) patients of the IPAA group had their ileal reservoir converted to an ileostomy (p = 0.01). Cumulative survival for IRA was lower than for the IPAA (p = 0.03), but if accounting only for operations made after the IPAA era had commenced, there was no significant difference. IPAA was associated with improved long-term survival without an increase in postoperative complications. The risk of death after colectomy and IRA seemed to be predominantly related to the remaining risk of rectal cancer. Therefore, we favour proctocolectomy with IPAA as the prophylactic surgical procedure for FAP with intermediate or severe polyposis. PMID:25504366

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

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

    2016-01-01

    scores were within ±1 stage of the mode. Sixty percent agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. CONCLUSIONS: The proposed FAP colon polyposis staging system and stage-specific intervention is based on a high degree of agreement on the part of experts in the...... 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...... classification scheme for lower GI tract polyposis. METHODS: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case using the proposed system and chose a stage-specific intervention for...

  18. Stability of colon stem cell methylation after neo-adjuvant therapy in a patient with attenuated familial adenomatous polyposis

    Shibata Darryl

    2005-06-01

    Full Text Available Abstract Background Methylation at certain human CpG rich sequences increases with age. The mechanisms underlying such age-related changes are unclear, but methylation may accumulate slowly in a clock-like manner from birth and record lifetime numbers of stem cell divisions. Alternatively, methylation may fluctuate in response to environmental stimuli. The relative stability of methylation patterns may be inferred through serial observations of the same colon. Case presentation A 22 year-old male with attenuated familial adenomatous polyposis received neo-adjuvant chemotherapy and radiation prior to surgery for rectal adenocarcinoma. Colon crypt methylation patterns before and after neo-adjuvant therapy (62 days apart were essentially identical with respect to percent methylation and diversity. Consistent with previous studies, methylation patterns recorded no evidence for enhanced colon crypt stem cell survival with a germline mutation (codon 215 proximal to the mutation cluster region of APC. Conclusion The inability of neo-adjuvant therapy to significantly alter crypt methylation patterns suggests stem cells are relatively protected from transient environmental changes. Age-related methylation appears to primarily reflect epigenetic errors in stem cells that slowly accumulate in a clock-like manner from birth. Therefore, life-long human stem cell histories are potentially written within and may be read from somatic cell epigenomes.

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

    Bülow, Steffen; Bulow, C.; Vasen, H.; Jarvinen, H.; Bjork, J.; Christensen, Ib Jarle

    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...... and proctectomy was compared before and after 1990 by Kaplan-Meier analysis. RESULTS: In the prepouch period 56/576 patients (10 percent) developed rectal cancer, vs. 4/200 (2 percent) in the pouch period. Neither the cumulative risk of rectal cancer (p = 0.07) nor the cumulative risk of proctectomy...

  20. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome.

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53). PMID:25549704

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

    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. PMID:27207660

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

    Akin, E.; Demirezer Bolat, A.; Buyukasik, S.; Algin, O.; Selvi, E; Ersoy, O.

    2012-01-01

    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...

  3. Attenuated Familial Adenomatous Polyposis

    ... procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known ... AFAP is suspected when a person has a history of more than 20, but fewer than 100, ...

  4. Familial Adenomatous Polyposis

    ... the inside of a person’s colon form a mass on the inside of the intestinal tract. The ... that does not metastasize; papillary thyroid cancer ; pancreatic , adrenal , and bile duct tumors; and a type of ...

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

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

    2011-01-01

    significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus......Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually 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...

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

    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

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

    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

  8. Characterization of an APC Promoter 1B deletion in a Patient Diagnosed with Familial Adenomatous Polyposis via Whole Genome Shotgun Sequencing [v1; ref status: indexed, http://f1000r.es/5i1

    Ted Kalbfleisch

    2015-06-01

    Full Text Available Recently, deletions have been identified and published as causal for Familial Adenomatous Polyposis in the 1B promoter region of the APC gene.  Those deletions were measured using multiplex ligation-dependent probe amplification.  Here, we present and characterize an ~11kb deletion identified by whole genome shotgun sequencing.  The deletion occurred in a patient diagnosed with Familial Adenomatous Polyposis, and was located on chr5, between bases 112,034,824 and 112,045,845, fully encompassing the 1B promoter region of the APC gene.   Results are presented here that include the sequence evidence supporting the presence of the deletion as well as base level characterization of the deletion site.  These results demonstrate the capacity of whole genome sequencing for the detection of large structural variants in single individuals.

  9. 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

    Nilbert, Mef; Kristoffersson, Ulf; Ericsson, Mats;

    2008-01-01

    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_5031ins......AA) 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....

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

    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.

  11. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Roelofs, Hennie M.J.; Morsche, Rene H.M. te [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marian, Brigitte [Institute of Cancer Research, Wien University, Vienna (Austria); Nagengast, Fokko M.; Peters, Wilbert H.M. [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-04-15

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  12. Mutations of the adenomatous polyposis coli and p53 genes in a child with Turcot's syndrome.

    Barel, D; Cohen, I J; Mor, C; Stern, S; Shapiro, R; Shomrat, R; Galanti, Y; Legum, C; Zaizov, R; Avigad, S

    1998-10-23

    Turcot's syndrome is a rare heritable complex that is characterized by an association between a primary neuroepithelial tumor of the central nervous system and multiple colonic polyps. The aim of this study was to analyze genetic alterations in a case of Turcot's syndrome in a 10.5-year-old boy in whom a colorectal tumor developed 3.5 years following astrocytoma. An APC germline non-sense mutation at codon 1284 leading to a truncated protein was identified, as was a somatic p53 mutation in the colorectal carcinoma in exon 7, codon 244. The latter was not identified in the primary astrocytoma. However, immunohistochemistry revealed high p53 protein expression in both tumors, suggesting an additional p53 mutation in the primary astrocytic tumor. The diverse p53 mutations observed in this unique syndrome in two different sites and stages of the disease may shed light on the multistep progression of the malignant events. PMID:10397462

  13. Is epidermal growth factor involved in development of duodenal polyps in familial polyposis coli?

    Poulsen, Steen Seier

    1988-01-01

    Duodenal adenomas are a frequent extracolonic manifestation in patients with familial polyposis coli (FPC). Epidermal growth factor (EGF), a polypeptide that stimulates cellular growth and differentiation, is localized in Paneth cells in the small intestine. In two patients with FPC, we found EGF...... immunoreactivity in duodenal adenomas. Numerous EGF immunoreactive Paneth cells were localized, not as usually, in the bottom of the crypts, but scattered along the crypts alone or in clusters. We do not know whether EGF is involved in the development of duodenal polyps in FPC patients, or whether the present...... findings represent secondary changes in duodenal polyps....

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

    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. MUTYH Associated Polyposis (MAP)

    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...... Adenomatous Polyposis (FAP) and to a lesser extend Lynch Syndrome, which are caused by germline mutations in the APC and Mismatch Repair (MMR) genes, respectively.Here we review research findings regarding MUTYH interactions, genotypic and phenotypic characteristics of MAP, as well as surveillance and...... treatment of the disease. The applied papers, published between 1/1 2002- 1/2 2008, were found through PubMed.The exact role of MUTYH in CRC tumorgenesis is still uncertain, although MAP tumors show distinct molecular features, including somatic G:C>T:A transversions in the APC gene. Furthermore...

  16. 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

    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.

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

    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.

  18. 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

    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

  19. Glycoprotein expression by adenomatous polyps of the colon

    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.

  20. Colorectal neoplasia in juvenile polyposis or juvenile polyps.

    Giardiello, F.M.; Hamilton, S R; Kern, S. E.; Offerhaus, G. J.; Green, P A; Celano, P.; Krush, A J; Booker, S V

    1991-01-01

    Juvenile (retention) polyps are usually solitary lesions in the colorectum but may be multiple in juvenile polyposis. The association between juvenile polyps and colorectal neoplasia is controversial. We present three patients with juvenile polyposis who had colorectal adenomas or adenomatous epithelium in juvenile polyps at ages 3, 4, and 7 years. In a retrospective study of 57 additional patients with one or more juvenile polyps, 10 patients (18%) had colorectal neoplasia including three wi...

  1. Manifestações extracolônicas da polipose adenomatosa familiar: incidência e impacto na evolução da doença Extracolonic manifestations of familial adenomatous polyposis: incidence and impact on the disease outcome

    Fábio Guilherme Campos

    2003-06-01

    Full Text Available RACIONAL: A polipose adenomatosa familiar é doença hereditária de caráter autossômico dominante, que freqüentemente se associa a numerosas manifestações extracolônicas. OBJETIVOS: Relatar a incidência de manifestações extracolônicas em nosso meio e analisar seu impacto na evolução da doença. PACIENTES E MÉTODOS: Revisão dos prontuários de pacientes com polipose adenomatosa familiar tratados no período de 1977 a 2001, relatando as manifestações extracolônicas associadas e suas complicações. RESULTADOS: Dos 59 pacientes com polipose adenomatosa familiar, 23 (38,9% apresentaram alguma manifestação extracolônica por ocasião do diagnóstico ou no seguimento. Foram registradas 37 diferentes manifestações (1,6 por paciente. As mais comuns foram osteomas e alterações na pigmentação da retina, diagnosticadas em 25% e 20% dos pacientes pesquisados, respectivamente. Outras manifestações extracolônicas achadas foram adenomas do trato digestivo superior, cistos epidermóides, tumores desmóides (sete cada, câncer gástrico (três e câncer de tireóide (dois. Complicações importantes diretamente relacionadas aos tumores desmóides foram reportadas em seis pacientes, sendo obstrução intestinal em quatro e hidronefrose em dois. Registraram-se óbitos em dois pacientes (28,5%. CONCLUSÕES: A incidência de manifestações extracolônicas é alta (40%, podendo afetar a evolução da doença e a qualidade de vida dos pacientes. Por esses motivos, torna-se de fundamental importância a pesquisa, a prevenção e o tratamento adequado dessas manifestações na polipose adenomatosa familiar.BACKGROUND: Familial adenomatous polyposis is a hereditary disease with autossomic and dominant features, frequently associated to many extracolonic manifestations. AIM: To report extracolonic manifestations incidence and to analyze its impact on the disease's outcome. PATIENTS AND METHODS: Revision of patient charts treated from 1977 to

  2. 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

    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

  3. Cronkhite-Canada Syndrome: an unusual finding of gastro-intestinal adenomatous polyps in a syndrome characterized by hamartomatous polyps

    Flannery, Christopher M.; Lunn, John A.

    2014-01-01

    Cronkhite-Canada syndrome is a rare, hamartomatous polyposis syndrome of unknown etiology. Hamartomatous gastro-intestinal polyps, alopecia, onychodystrophy, cutaneous hyperpigmentation, abdominal pain, diarrhea, and complications of weight loss are typical of the syndrome. In this report, we describe a pathological finding of colonic adenomatous polyposis as opposed to hamartomatous polyposis. We also describe our treatment, long-term therapeutic plan, and the need for further research.

  4. Duodenal adenoma surveillance in patients with familialadenomatous polyposis

    2015-01-01

    Familial adenomatous polyposis (FAP) is a hereditarydisorder caused by Adenomatous Polyposis Genemutations that lead to the development of colorectalpolyps with great malignant risk throughout life. Moreover,numerous extracolonic manifestations incorporatedifferent clinical features to produce varied individualphenotypes. Among them, the occurrence of duodenaladenomatous polyps is considered an almost inevitableevent, and their incidence rates increase as a patient'sage advances. Although the majority of patients exhibitdifferent grades of duodenal adenomatosis as theyage, only a small proportion (1%-5%) of patients willultimately develop duodenal carcinoma. Within thiscontext, the aim of the present study was to reviewthe data regarding the epidemiology, classification,genetic features, endoscopic features, carcinogenesis,surveillance and management of duodenal polyps inpatients with FAP.

  5. Colonic polyp patterns in familial polyposis.

    Bartram, C I; Thornton, A

    1984-02-01

    The diagnosis of familial polyposis depends on there being more than 100 adenomatous polyps in the large bowel. The polyps are the result of intramucosal microadenomatous growth. The age at which this occurs varies, and in the early stages of polyp development relatively few larger polyps may be seen. The numbers and size of the polyps as seen on double-contrast barium enema were compared with the macroscopic findings on the resected specimens in 27 patients with proven polyposis. Of these patients, 23 (83%) were diagnosed when polyps were first found at sigmoidoscopy. Radiologically the predominant polyp size was more than 5 mm in only four cases, 2-5 mm in 22 (81%), and less than 2 mm in one. Of the 22 with predominately 2-5 mm polyps, eight had significant numbers of nodules smaller than 2 mm and three had considerable numbers of polyps larger than 5 mm. Eleven (41%) were thought to have fewer than 70 polyps. Pathologically the nodular pattern (less than 2 mm) predominated in 11 (41%) and 14 had polyps of 2-5 mm. More than 100 polyps were present in each case, with fewer than 500 polyps in eight. In the 11 patients thought radiologically to have fewer than 70 polyps, the nodular pattern predominated in nine. In the initial stages of polyp growth, the larger polyps are less numerous, and the background nodular pattern is a useful diagnostic feature of familial polyposis. PMID:6607595

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

    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.

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

    Knudsen, Anne Louise; Bülow, Steffen

    2001-01-01

    combination with tamoxifen. Surgery may be considered in case of a small and well-defined DT with no signs of invasionof 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...

  8. [Juvenile recto-colonic polyposis. Apropos of a case in Madagascar].

    Alandry, G; Le Quellec, B; Philippon, G; Gouot, E; Ribault, L

    1987-01-01

    The authors relate the first case of juvenile polyposis coli noticed in Madagascar. It is a sporadic case developing a serious clinic picture with an accidentally fatal end in a 7 years old Malagasy girl. They recall the principal epidemiological, anatomopathological, clinic and evolutive features which are typical of this polyposis. They wish that the way to medical progress will soon lead to better knowledge of the place of the intestinal polyposis in African countries. PMID:3586969

  9. Hamartomatous polyposis syndromes

    Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus;

    2014-01-01

    -intestinal symptoms and types of cancers differs.Clinical awareness and early diagnosis of HPS is important, as affected patients and at-risk family members should be offered genetic counselling and surveillance. Surveillance in children with HPS might prevent or detect intestinal or extra-intestinal complications......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as......-intestinal cancer. The syndromes are rare and inherited in an autosomal dominant manner.The diagnosis of HPS has traditionally been based on clinical criteria, but can sometimes be difficult as the severity of symptoms range considerably from only a few symptoms to very severe cases - even within the same family...

  10. Disease: H01025 [KEGG MEDICUS

    Full Text Available tosomal dominantly inherited disorder characterized by the early onset of hundreds to thousands of adenomas throughou... polyposis coli (APC) gene. In a subset of individuals, a MUTYH mutation causes a reces...Rozen P Familial adenomatous polyposis. Orphanet J Rare Dis 4:22 (2009) PMID:21884696 (des...H01025 Familial adenomatous polyposis Familial adenomatous polyposis (FAP) is an au...fter the appearance of the polyps. The genetic defect in FAP is a germline mutation in the adenomatous

  11. 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

    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.

  12. Prophylactic colectomy for hyperplastic polyposis.

    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.

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

    Bisgaard, Marie Luise; Bülow, Steffen

    2006-01-01

    Gardner syndrome is characterized by the triad of colorectal adenomas, soft and hard tissue tumors. This disorder was regarded as a separate disease until the identification of the APC gene when it was recognized that mutations in the APC gene were the underlying cause of both Gardner syndrome and...

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

    Bisgaard, Marie Luise; Bülow, Steffen

    2006-01-01

    Gardner syndrome is characterized by the triad of colorectal adenomas, soft and hard tissue tumors. This disorder was regarded as a separate disease until the identification of the APC gene when it was recognized that mutations in the APC gene were the underlying cause of both Gardner syndrome and...

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

    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...

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

    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...

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

    Oktay Algin; Sehnaz Evrimler; Evrim Ozmen; Melike Metin; Osman Ersoy; Mustafa Karaoglanoglu

    2012-01-01

    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 p...

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

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

    2012-01-01

    Background and aim: Duodenal adenomatosis in FAP results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study is to present results of long-term duodenal surveillance and to evaluate the risk of...... (interquartile range 9-17). The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI 84-93), and of Spigelman stage IV 35% (95% CI 25-45). The Spigelman stage improved in 32 (12%), remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty patients (7%) had duodenal cancer at a median age of...

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

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

    2012-01-01

    Background and aim:  Duodenal adenomatosis in FAP results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study is to present results of long-term duodenal surveillance and to evaluate the risk of...... (interquartile range 9-17). The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI 84-93), and of Spigelman stage IV 35% (95% CI 25-45). The Spigelman stage improved in 32 (12%), remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty patients (7%) had duodenal cancer at a median age of...

  20. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis.

    Scanlan, Pauline D; Shanahan, Fergus; Clune, Yvonne; Collins, John K; O'Sullivan, Gerald C; O'Riordan, Micheal; Holmes, Elaine; Wang, Yulan; Marchesi, Julian R

    2008-03-01

    A role for the intestinal microbiota is routinely cited as a potential aetiological factor in colorectal cancer initiation and progression. As the majority of bacteria in the gut are refractory to culture we investigated this ecosystem in subjects with colorectal cancer and with adenomatous polyposis who are at high risk of developing colorectal cancer, using culture-independent methods. Twenty colorectal cancer and 20 polypectomized volunteers were chosen for this analysis. An exploration of the diversity and temporal stability of the dominant bacteria and several bacterial subgroups was undertaken using 16S rRNA gene denaturing gradient gel electrophoresis and ribosomal intergenic spacer analysis (RISA). Metabonomic analysis of the distal gut microbiota's environment was also undertaken. A significantly reduced temporal stability and increased diversity for the microbiota of subjects with colorectal cancer and polyposis was evident. A significantly increased diversity of the Clostridium leptum and C. coccoides subgroups was also noted for both disease groups. A clear division in the metabonome was observed for the colorectal cancer and polypectomized subjects compared with control volunteers. The intestinal microbiota and their metabolites are significantly altered in both colorectal cancer and polypectomized subjects compared with controls. PMID:18237311

  1. Hyperplastic polyposis associated with two asynchronous colon cancers

    Masaya Kurobe; Kuniko Abe; Naoe Kinoshita; Masanobu Anami; Hirotaka Tokai; Yoshinori Ryu; Chun Yang Wen; Takashi Kanematsu; Tomayoshi Hayashi

    2007-01-01

    We report a patient with hyperplastic polyposis who had two asynchronous colon cancers, a combined adenoma-hyperplastic polyp, a serrated adenoma, and tubular adenomas. Hyperplastic polyposis is thought to be a precancerous lesion; and adenocarcinoma arises from hyperplastic polyposis through the hyperplastic polyp-adenoma-carcinoma sequence. Most polyps in patients with hyperplastic polyposis present as blandlooking hyperplastic polyps, which are regarded as nonneoplastic lesions; however, the risk of malignancy should not be underestimated. In patients with multiple hyperplastic polyps, hyperplastic polyposis should be identified and followed up carefully in order to detect malignant transformation in the early stage.

  2. Fungal Agents as a Cause of Nasal Polyposis

    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

  3. Sinonasal polyposis: investigation by direct coronal CT

    To demonstrate the typical clinical and CT features of sinonasal polyposis, we reviewed the clinical records and preoperative direct coronal CT scans of 35 patients with surgically proven disease. Symptoms included progressive nasal stuffiness (100 %), rhinorrhea (69 %), facial pain (60 %), headache (43 %) and anosmia (17 %). We found associations with rhinitis (46 %), asthma (29 %) and aspirin sensitivity (9 %). Coronal CT features included polypoid masses in the nasal cavity (91 %), partial or complete pansinus opacification (90 %), enlargement of infundibula (89 %), bony attenuation of the ethmoid trabeculae (63 %) and nasal septum (37 %), opacified ethmoid sinuses with convex lateral walls (51 %) and air-fluid levels (43 %). The latter feature correlated with symptoms and signs of acute sinusitis in only 40 % of patients. Recognition of sinonasal polyposis is important to the endoscopic surgeon since it can be the most troubling sinonasal inflammatory disease to manage due to its aggressive nature and tendency to recur despite appropriate treatment. (orig.)

  4. Clinical aspects of patients with nasal polyposis

    Crespo, Cassio Caldini

    2009-09-01

    Full Text Available Introduction: The nasal Polyposis is a non-neoplastic chronic inflammatory process of the nasal mucosa. It causes a large impact to the patients' life quality. Objective: To analyze the characteristics of patients with polyposis in the Brazilian population. Method: 50 records of patients followed up in a tertiary hospital and submitted to surgical treatment of nasal polyposis were reviewed. The following variables were analyzed: age, sex, smoking, presence of asthma, presence of AAS intolerance and also the clinical manifestations: anterior and posterior rhinorrhea, nasal obstruction, hyposmia, sneezing and pruritus. The tomographic evaluation system applied was that of Lund-McKay. For statistical analysis we applied the chi-square test with p<0.05. Results: Out of 50 patients evaluated, 28 were male and 22 were female. The mean age range was of 40.8 years. The main clinical manifestation was nasal obstruction in 100% of the patients. In the tomographic evaluation, according to the Lund-McKay system, the average scoring was of 10.9. Discussion: No statistically significant difference was obtained in the patients' general symptoms compared to the patients with asthma or AAS intolerance. The difference in the Lund-McKay score was statistically significant in the populations studied. The symptoms were similar to the frequency of symptoms of other works. Conclusion: We concluded that the main complaint of the patients with nasal polyposis is nasal obstruction, the most affected age is of about 40 years old, without preference of sex. The severity of tomographic findings is higher in patients with asthma and AAS intolerance.

  5. Successful treatment of cap polyposis with infliximab.

    Bookman, Ian D; Redston, Mark S; Greenberg, Gordon R

    2004-06-01

    Cap polyposis is a disorder characterized by bloody diarrhea with rectosigmoid polyps covered by a cap of fibropurulent exudate. The pathogenesis is unknown, but histological features suggest that mucosal prolapse may play a role. Drug therapies are usually unsuccessful, and treatment requires sigmoid resection or, if the disease recurs after initial surgical resection, panproctocolectomy. We report the case of a 36-year-old woman with characteristic clinical, endoscopic, and histological features of cap polyposis. Investigations included normal anorectal manometry and defecography, without evidence of prolapse. The patient's disease was unresponsive to treatment with mesalamine, antibiotics, lidocaine enemas, and corticosteroids. One infusion of infliximab 5 mg/kg provided dramatic symptomatic improvement but minimal endoscopic or histological change. After 4 infliximab infusions at 8-week intervals, endoscopy of the rectum and sigmoid colon was normal, and biopsies showed complete histological resolution of the inflammatory process. Well-being with normal endoscopy and histology has been maintained at 38 months, without further treatment. It was concluded that infliximab is effective therapy for cap polyposis and avoids the requirement for surgery. No clinical evidence was obtained to support mucosal prolapse as a causative factor, but the response to infliximab suggests a role for tumor necrosis factor-alpha in the pathogenesis of this disorder. PMID:15188181

  6. Colectomy in a patient with pneumatosis coli

    Karlsen, Stine; Bregendahl, Sidse; Tøttrup, Anders;

    2014-01-01

    Pneumatosis coli (PC) is a rare condition which may be difficult to diagnose. We report a case of PC in a 46-year-old woman, where colonoscopy and biopsies showed signs of widespread polyposis. She had a prophylactic colectomy. Pathologic examination of the specimen showed multiple air-filled cysts...

  7. Duodenal polyposis secondary to portal hypertensive duodenopathy

    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.

  8. Sense of smell in patients with bilateral nasal polyposis

    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.

  9. Familiær adenomatøs polypose

    Bülow, Steffen

    2013-01-01

    identification of gene carriers by DNA analysis or endoscopy the prognosis is good after early colectomy, but life-long surveillance of the rectum and the duodenum is necessary. The Danish Polyposis Register coordinates prophylactic examination and treatment in the families, and serves as basis for research....

  10. Segmental resection with primary anastomosis is not always safe in splenic flexure perforation

    Weledji, Elroy P; Mokake, Martin D.; Sinju, Motaze

    2016-01-01

    Background Familial adenomatous polyposis (FAP) is caused by a rare mutation of the adenomatous polyposis coli gene on Chromosome 5q. The risk of colorectal cancer in patients with FAP is nearly 100 % and intensive endoscopic surveillance or prophylactic colectomy are mandatory. If extensive endoscopic surveillance is chosen, there is a cumulative risk of perforation and bleeding especially after polypectomy. We discussed the problems and options in the management of the late diagnosis of an ...

  11. Targeting Stem Cell Behavior in Desmoid Tumors (Aggressive Fibromatosis) by Inhibiting Hedgehog Signaling1

    Ghanbari-Azarnier, Ronak; Sato, Shingo; Wei, Qingxia; Al-Jazrawe, Mushriq; Alman, Benjamin A.

    2013-01-01

    Desmoid tumor (also called aggressive fibromatosis) is a lesion of mesenchymal origin that can occur as a sporadic tumor or a manifestation of the preneoplastic syndrome, familial adenomatous polyposis caused by a mutation in adenomatous polyposis coli (APC). This tumor type is characterized by the stabilization of β-catenin and activation of Tcf-mediated transcription. Cell transplantation data suggest that desmoid tumors are derived from mesenchymal progenitor cells (MSCs). As such, modulat...

  12. Influence of Chronic Moderate Sleep Restriction and Exercise on Inflammation and Carcinogenesis in Mice

    Zielinski, Mark R.; Davis, J. Mark; Fadel, James R.; YOUNGSTEDT, SHAWN D.

    2012-01-01

    The effects of chronic moderate sleep restriction and exercise training on carcinogenesis were examined in adenomatous polyposis coli multiple intestinal neoplasma (APC Min+/-) mice, a genetic strain which is predisposed to developing adenomatous polyposis. The mice were randomized to one of four 11 week treatments in a 2×2 design involving sleep restriction (by 4 h/day) vs. normal sleep and exercise training (1 h/day) vs. sedentary control. Wild-type control mice underwent identical experime...

  13. Successful outcome after laparoscopic surgery for sporadic colonic desmoid tumor with β-catenin mutation: a case report

    Gunji, Shutaro; Kawada, Kenji; Kawada, Mayumi; Hasegawa, Suguru; Sakai, Yoshiharu

    2013-01-01

    Introduction Desmoid tumors (also called aggressive fibromatosis) are histologically benign, but have a strong tendency to recur locally after resection. They are rare neoplastic tumors that may occur sporadically or in association with familial adenomatous polyposis caused by a germline mutation in the adenomatous polyposis coli gene. The etiology of desmoid tumors is unknown, but their association with a history of abdominal surgery, trauma, and estrogen therapy is well known. Case presenta...

  14. Contralateral recurrence of aggressive fibromatosis in a young woman: A case report and review of the literature

    SCHMOYER, CHRISTOPHER J.; Brereton, Harmar D; BLOMAIN, ERIC W.

    2015-01-01

    Aggressive fibromatosis (AF) is a benign non-encapsulated tumor of mesenchymal origin, with a tendency for local spread along fascial planes. Local invasion can lead to extensive morbidity and even mortality due to destruction of the bones, organs and soft tissues. This rare lesion is observed 1,000 times more frequently in patients with familial adenomatous polyposis or Gardner's syndrome due to the inheritance of the adenomatous polyposis coli (APC) gene. While AF does not metastasize, loca...

  15. Mutator gene and hereditary non-polyposis colorectal cancer

    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.

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

    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.

  17. Familial adenomatous patients with desmoid tumours show increased expression of miR-34a in serum and high levels in tumours

    Walton, Sarah-Jane; Lewis, Amy; Jeffery, Rosemary; Thompson, Hannah; Feakins, Roger; Giannoulatou, Eleni; Yau, Christopher; Lindsay, James O.; Clark, Susan K.; Silver, Andrew

    2016-01-01

    Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy to prevent cancer. DTs are a major cause of morbidity and mortality. The absence of markers to monitor progression and a lack of treatment options are significant limitations to clinical management. We investigated microRNAs (miRNA) levels in DTs and serum using expression array analysis on two independent cohorts of FAP patients (total, n=24). Each comprised equal numbers of patients who had formed DTs (cases) and those who had not (controls). All controls had absence of DTs confirmed by clinical and radiological assessment over at least three years post- colectomy. Technical qPCR validation was performed using an expanded cohort (29 FAP patients; 16 cases and 13 controls). The most significant elevated serum miRNA marker of DTs was miR-34a-5p and in-situ hybridisation (ISH) showed most DTs analysed (5/6) expressed miRNA-34a-5p. Exome sequencing of tumour and matched germline DNA did not detect mutations within the miR-34a-5p transcript sites or 3′-UTR of target genes that would alter functional miRNA activity. In conclusion, miR-34a-5p is a potential circulatory marker and therapy target. A large prospective world-wide multi-centre study is now warranted. PMID:27489864

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

    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.)

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

    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.)

  20. A case of gastric polyposis in antral area of stomach following prolonged proton-pump therapy

    Alqutub, Adel Nazmi

    2010-01-01

    Full Text Available We describe the clinical scenario of a young male with history of non ulcer dyspepsia who had endoscopic evidence of gastric polyposis in antral area. The polyps disappeared four months after proton pump inhibitors were stopped. Proton pump inhibitors have been linked to gastric fundal polyposis and not antral gland polyposis. This is the first report originating from an Asian country describing antral gland polyposis (AGPs in a patient on long-term PPI therapy with no evidence of Helicobacter pylori. A case report with brief review is presented.

  1. Hereditary hemorrhagic telangiectasia and juvenile polyposis: an overlap of syndromes

    Poletto, Erica D.; Levin, Terry L. [Montefiore Medical Center, Department of Radiology, Bronx, NY (United States); Trinh, Angela M. [Albert Einstein College of Medicine, Bronx, NY (United States); Loizides, Anthony M. [Children' s Hospital at Montefiore, Department of Pediatric Gastroenterology, Bronx, NY (United States)

    2010-07-15

    Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu syndrome) is a syndrome characterized by multiorgan telangiectases and arteriovenous malformations. A subset of patients with a mutation in the MADH4 gene on chromosome 18 exhibits an overlapping syndrome of HHT and juvenile polyposis (JPS). We present one such family. Genetic testing is warranted when either HHT or JPS is diagnosed, as early recognition of this syndrome overlap allows appropriate management of these patients. (orig.)

  2. AN OVERVIEW OF SINONASAL POLYPOSIS: A PROSPECTIVE STUDY

    Kabikanta

    2016-03-01

    Full Text Available INTRODUCTION Sinonasal polyposis, one of the most common inflammatory mass lesions of the nose affecting up to 40% of the population. They present with nasal obstruction, anosmia, rhinorrhoea, post-nasal drip, and less commonly headache. Their aetiology remains unclear, but they are known to have associations with allergy, asthma, infection, fungus, cystic fibrosis, and aspirin sensitivity. Strong genetic factors are implicated in the pathogenesis of SNP, but genetic and molecular alterations required for its development and progression are still unclear. Management of SNP involves a combination of conservative treatment and surgical treatment. There is good evidence for the use of corticosteroids (systematic and topical, both as primary treatment and as postoperative prophylaxis against recurrence, but the prolonged course of the disease and adverse effect of systematic steroid limits their use. Surgical treatment has been refined significantly over the past 20 years with the advent of endoscopic sinus surgery and, in general, is reserved for cases refractory to medical treatment. Recurrence of the polyposis is common with severe disease recurring in up to 10% of patients. Over the last two decades, increasing insights in the pathophysiology of nasal polyposis opens prospective for new pharmacological treatment options, with eosinophilic inflammation, IgE, fungi and staphylococcus aureus as potential targets. A better understanding of the pathophysiology underlying the persistent inflammatory state in SNP is necessary to ultimately develop novel pharmacotherapeutic approaches. Here, we present the newer treatment options available for better control and possibly cure of the disease.

  3. Sensitivity to mitomycin-C and radiation of cells derived from patients with familial colon polyposis: an autosomal dominant hereditary disease

    This study was undertaken to investigate the sensitivity to mitomycin-C (MMC) of skin fibroblasts derived from patients with adenomatosis coli (AC), especially familial colon polyposis. The sensitivity to X rays and ultraviolet rays of AC cells cultured at RERF was similar to that of normal human diploid cells. However, there were large individual differences in sensitivity to MMC. DNA elongation in cells sensitive to MMC was found to be inhibited after MMC treatment. Sites highly sensitive to MMC were considered to be involved in the initial stages of DNA synthesis. (author)

  4. Adenomatous Polyps Of The Gallbladder” Adenomas oF the Gallbladder

    Attilio Maria Farinon; Antonio Pacella; Francesco Cetta; Mario Sianesi

    1991-01-01

    The finding of adenomatous polyps of the gallbladder is a rare occurrence and an unusual clinical problem. Among 2,145 patients who underwent cholecystectomy for gallbladder disease only 9 (0.4 per cent) presented with adenomatous polyps. There were 6 women and 3 men, aged 17 to 70 years. Preoperative ultrasonographic diagnosis was made in only 1 of 7 patients with gallstones, in contrast polypoid lesions within a gallbladder without stones were easily confirmed by both ultrasonography and or...

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

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

    2016-01-01

    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.

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

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

    2016-01-01

    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. PMID:27065090

  7. Germline Mutations in the Polyposis-Associated Genes BMPR1A, SMAD4, PTEN, MUTYH and GREM1 Are Not Common in Individuals with Serrated Polyposis Syndrome.

    Mark Clendenning

    Full Text Available Recent reports have observed that individuals with serrated polyps, some of whom meet the clinical diagnostic criteria for Serrated Polyposis Syndrome (SPS, are among those who carry germline mutations in genes associated with polyposis syndromes including; (1 genes known to underlie hamartomatous polyposes (SMAD4, BMPR1A, and PTEN, (2 MUTYH-associated polyposis and (3 GREM1 in Hereditary Mixed Polyposis Syndrome (HMPS. The aim of this study was to characterise individuals fulfilling the current WHO criteria for SPS for germline mutations in these polyposis-associated genes.A total of 65 individuals with SPS (fulfilling WHO criteria 1 or 3, were recruited to the Genetics of Serrated Neoplasia study between 2000 and 2012, through multiple Genetics or Family Cancer Clinics within Australia, or from the New Zealand Familial Gastrointestinal Cancer Service. Individuals with SPS were tested for coding mutations and large deletions in the PTEN, SMAD4, and BMPR1A genes, for the MUTYH variants in exons 7 (Y179C and 13 (G396D, and for the duplication upstream of GREM1.We found no variants that were likely to be deleterious germline mutations in the SPS cases in the PTEN, SMAD4, and BMPR1A genes. A novel variant in intron 2 (c.164+223T>C of PTEN was identified in one individual and was predicted by in silico analysis to have no functional consequences. One further individual with SPS was found to be mono-allelic for the MUTYH G396D mutation. No individuals carried the recently reported duplication within GREM1.Genes involved in the gastrointestinal hamartomatous polyposis, Hereditary Mixed Polyposis Syndrome and MUTYH-associated polyposis syndromes are not commonly altered in individuals with SPS.

  8. Structural and Functional Characterization of the Wnt Inhibitor APC Membrane Recruitment 1 (Amer1)*

    Tanneberger, Kristina; Pfister, Astrid S.; Kriz, Vitezslav; Bryja, Vitezslav; Schambony, Alexandra; Behrens, Jürgen

    2011-01-01

    Amer1/WTX binds to the tumor suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing β-catenin degradation. We show here that Amer1 directly interacts with the armadillo repeats of β-catenin via a domain consisting of repeated arginine-glutamic acid-alanine (REA) motifs, and that Amer1 assembles the β-catenin destruction complex at the plasma membrane by recruiting β-catenin, adenomatous polyposis coli, and Axin/Conductin. Deletion or specific mutations of ...

  9. Decreased Expression of FOXP3 in Nasal Polyposis

    Roongrotwattanasiri, Kannika; Pawankar, Ruby; KIMURA, SATOKO; Mori, Sachiko; Nonaka, Manabu; Yagi, Toshiaki

    2011-01-01

    Purpose The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulator...

  10. Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling

    Zhang, Junfang; Cao, Hailong; Zhang, Bing; CAO, HANWEI; Xu, Xiuqin; Ruan, Hang; Yi, Tingting; Tan, Li; Qu, Rui; Song, Gang; Wang, Bangmao; Hu, Tianhui

    2013-01-01

    As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and...

  11. Analysis of mtDNA sequence variants in colorectal adenomatous polyps

    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

  12. Multiple lymphomatous polyposis of the gastrointestinal tract ; report of three cases

    In 1961, Cornes first introduced the term multiple lymphomatous polyposis (MLP), and since then, this very rare disease has been considered as a malignant lymphoma originating in the mantle zone of gastrointestinal lymphoid tissue. MLP presents with a 0.5-2.0 cm sized polypoid tumor, which affects long segments of the alimentary tract and frequently invades the mesenteric lymph nodes. It often consists of a dominant mass rather than polyps. We describe three cases of endoscopically proven multiple lymphomatous polyposis, and include a review of the literature. In differentiating multiple lymphomatous polyposis and other types of multiple polyposis in the gastrointestinal tract, the following features are helpful : the smooth surface of polyps, which is similar to a gem seen during a barium examination; the typical appearance of a gastric submucosal tumor and hypertrophied gastric mucosal folds in UGI; the presence of enlarged lymph nodes, as seen on abdominal CT scanning. (author). 9 refs., 2 tabs., 3 figs

  13. Hereditary non-polyposis colorectal cancer : Identification of mutation carriers and assessing pathogenicity of mutations

    Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH

    2004-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations

  14. Effect of Helicobacter pylori eradication on gastric hyperplastic polyposis in Cowden's disease

    Hajime Isomoto; Hisashi Furusu; Ken Ohnita; Yusuke Takehara; Chun-Yang Wen; Shigeru Kohno

    2005-01-01

    A 21-year-old woman with complaints of hematochezia was diagnosed as having Cowden's disease (CD), an autosomal dominant condition characterized by multiple hamartomas, since facial papules and gingival papillomas were identified. On endoscopy, multiple hyperplastic polyps were seen in the rectum and left-side colon. There were also esophageal glycogenic acanthosis and hyperplastic polyposis in the antrum accompanied by Helicobacter pylorirelated gastritis. Although gastric hyperplastic polyposis had by no means regressed with unsuccessful first-line eradication therapy for H pylori, following cure of the infection with salvage therapy consisting of rabeprazole,amoxicillin and metronidazole, the polyposis lesions almost disappeared. Follow-up gastroscopy 2 and 3 years after cessation of the second-line eradication therapy revealed almost complete regression of the polyposis lesions with no evidence of H pylori infection. We recommend eradication treatment for CD patients with gastric hyperplastic polyps and the infection, as the occurrence of gastric carcinoma among hyperplastic polyps has been described.

  15. Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

    Wu, T. T.; Rezai, B.; Rashid, A.; Luce, M.C.; Cayouette, M. C.; Kim, C.; Sani, N.; Mishra, L; Moskaluk, C A; Yardley, J. H.; Hamilton, S R

    1997-01-01

    Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of ...

  16. [Hereditary non-polyposis colorectal cancer. Report of four siblings].

    Zárate, Alejandro; Alvarez, Karin; Wielandt, Ana María; Hevia, Montserrat; De la Fuente, Marjorie; Carvallo, Pilar; López-Köstner, Francisco

    2008-06-01

    Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome is an autosomic dominant syndrome involving 596-1096 of colorectal cancer patients. Mutations in MLH1 and MSH2 genes account for most cases. These two genes participate in the DNA mismatch repair pathway. Therefore mutation carriers show microsatellite instability (MSI) in tumors. This syndrome is characterized by the early development of colorectal cancer (before 50 years) and an increased incidence of cancer in other organs. We report four siblings from a family diagnosed with HNPCC. All of them were subjected to colonic surgery for colorectal cancer Moreover, one patient developed an ampulloma after her colon surgery. The molecular-genetic analysis revealed three brothers with microsatellite instability in the tumor tissue, the absence of the MLH1 protein, and the presence of a germ line mutation localized in introm 15 of the MLH1 gene. PMID:18769833

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

    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.

  18. Infection and HLA-G Molecules in Nasal Polyposis

    Rizzo, Roberta; Malagutti, Nicola; Bortolotti, Daria; Gentili, Valentina; Rotola, Antonella; Fainardi, Enrico; Pezzolo, Teresa; Aimoni, Claudia; Pelucchi, Stefano; Di Luca, Dario; Pastore, Antonio

    2014-01-01

    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. PMID:24741599

  19. Infection and HLA-G Molecules in Nasal Polyposis

    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.

  20. Evaluation of asthma improvement after endoscopic sinus surgery in nasal polyposis

    fariba Rezaeetalab

    2008-07-01

    Full Text Available Introduction: Asthma is characterized by airway inflammation, airway hyper responsiveness, and reversible airflow limitation. The prevalence of the disease has increased over 2 decades to approximately 5 to 10% of the population. The presence of nasal polyposis in asthma patients is associated with increase in asthma severity. We attempted to determine the efficacy of endoscopic sinus surgery in patients with asthma and nasal polyposis. Materials and Methods: We performed a prospective, cross-sectional study from 2001 until 2006. This study included 50 patients with severe persistent asthma and nasal polyposis. The severity of asthma (in NHLBI and NAPP and FEV1 before and after endoscopic nasal polypectomy was recorded. We used paired simple T test for comparation of data mean.The gathered data were analyzed with SPSS software. Results: In this study, median ages are 32.5 ± 14.3  years. Male to female is 2.3 to 1. All of patients have severe persistent asthma and nasal polyposis. From 50 patients with asthma and nasal polyposis, in 38 cases asthma severity and FEV1 were improved. (mean of  FEV1 before endoscopic  sinus polypectomy = 1.68 L ,  mean of FEV1 after endoscopic sinus polypectomy = 2.52 L.  Conclusion: Opening of upper airway and improvement of breathing through sinus endoscopy induce betterment of asthma severity, though the possibility of nasal polyposis should be investigated and treatment with endoscopic sinus surgery planned accordingly.  

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

    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).

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

    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)

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

    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

  4. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development.

    Goessling, W.; North, T.E.; Lord, A.M.; Ceol, C.; Lee, S.; Weidinger, G.; Bourque, C.; Strijbosch, R.; Haramis, A.P.; Puder, M.; Clevers, H.; Moon, R.T.; Zon, L.I.

    2008-01-01

    Developmental signaling pathways hold the keys to unlocking the promise of adult tissue regeneration, and to inhibiting carcinogenesis. Patients with mutations in the Adenomatous Polyposis Coli (APC) gene are at increased risk of developing hepatoblastoma, an embryonal form of liver cancer, suggesti

  5. APC binds the Miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane

    Mills, Kate M.; Brocardo, Mariana G.; Henderson, Beric R.

    2016-01-01

    The role of adenomatous polyposis coli (APC) tumor suppressor at mitochondria is unclear. We show that APC associates with the Miro/Milton/kinesin complex to stimulate anterograde transport of mitochondria. This identifies the first regulatory role of APC in organelle transport. APC cancer mutations block this activity.

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

    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

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

    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

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

    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. PMID:25712196

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

    Nyholm, H C; Nielsen, A L; Lyndrup, J; Norup, P; Thorpe, S M

    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 ...

  10. Pathogenesis and management of nasal polyposis in cystic fibrosis.

    Mainz, Jochen G; Koitschev, Assen

    2012-04-01

    Beginning in preschool age, during their lives, upto 50% of cystic fibrosis (CF) patients experience obstructing nasal polyposis (NP), which is rare in non-CF children. Pathogenetic factors of NP in general and especially in CF are still obscure. However, defective epithelial ion transport from mucosal glands plays a central role in CF, and viscous secretions impair mucociliary clearance, promoting chronic pathogen colonization and neutrophil-dominated chronic inflammation.Presently, CF-NP is not curable but can be clinically stabilized,though the large variety of proposed treatment modalities indicates a lack of standardization and of evidence of treatment efficacy. When conservative measures are exhausted, surgical intervention combining individually adapted endoscopic sinus surgery and supportive conservative treatment is performed. Topical steroids, approved as the gold standard for non-CF NP, may be beneficial, but they are discussed to be less effective in neutrophilic inflammation,and CF-specific antimicrobial and mucolytic therapy, as is true of all treatment modalities, urgently requires evaluation by controlled clinical trials within interdisciplinary networks. PMID:23520643

  11. E. Coli

    ... General Information E. coli O157 Infections Linked to Alfalfa Sprouts Protect Yourself Learn about E. coli infections ... toxin-producing Escherichia coli O157 Infections Linked to Alfalfa Sprouts Produced by Jack & The Green Sprouts Multistate ...

  12. Bmp signaling in colonic mesenchyme regulates stromal microenvironment and protects from polyposis initiation.

    Allaire, Joannie M; Roy, Sébastien A B; Ouellet, Camille; Lemieux, Étienne; Jones, Christine; Paquet, Marilène; Boudreau, Francois; Perreault, Nathalie

    2016-06-01

    In the colon, myofibroblasts are primary contributors in the establishment of the microenvironment involved in tissue homeostasis. Alterations in myofibroblast functions lead to changes resulting in a toxic microenvironment nurturing tumorigenesis. Bone morphogenetic proteins (Bmps) are morphogens known to play key roles in adult gut homeostasis. Studies in genetically-modified mice have shown that Bmp disruption in all cell layers leads to the development of gut polyposis. In contrast, our studies showed that loss of Bmp exclusively in the gastrointestinal epithelium resulted in increased epithelial proliferation without polyposis initiation, thus suggesting a key role for mesenchymal Bmp signaling in polyposis initiation. In order to identify the role of mesenchymal Bmp signaling on the microenvironment and its impact on colonic mucosa, a mouse model was generated with suppression of Bmp signaling exclusively in myofibroblasts (Bmpr1aΔMES). Bmpr1aΔMES mice exhibited increased subepithelial proliferation with changes in cellular composition leading to the development of a primed stroma with modulation of extracellular matrix proteins, immune cells and cytokines as early as 90 days of age. This microenvironmental deregulation was associated with increased polyposis initiation at one year of age. These results are the first to demonstrate that mesenchymal Bmpr1a inactivation alone is sufficient to prompt an expansion of myofibroblasts leading to the development of a reactive mesenchyme that contributes to polyposis initiation in the colon. These findings support the novel concept that inhibition of Bmp signaling in mesenchymal cells surrounding the normal epithelium leads to important changes instructing a toxic microenvironment sufficient to induce colonic polyposis. PMID:26773796

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

    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.

  14. Frequency of fungal infection in the nasal polyposis patients undergoing polypectomy in a tertiary care unit

    Objective: To determine the frequency of fungal infection in nasal polyposis patients undergoing polypectomy in a tertiary care ENT unit. Methodology: This cross sectional study was conducted in the department of ENT, Pakistan Institute of Medical Sciences, Islamabad. A total of 60 patients with nasal polyposis were enrolled. Patients who did not give consent, with sinonasal malignancy, diabetes, and pregnant or lactating women were excluded from study. All the patients were operated and specimens of polypectomies were sent to the Department of Pathology for fungal culture, direct microscopy and histopathology. Data was entered and analysed using SPSS version 20. (author)

  15. Effects of vitamin antioxidant supplementation on cell kinetics of patients with adenomatous polyps.

    Cahill, R J; O'Sullivan, K R; Mathias, P M; Beattie, S.; Hamilton, H; O'Morain, C

    1993-01-01

    Colonic crypt cell proliferation is used as an indicator of risk of colorectal carcinoma. Subjects with adenomatous polyps and cancer have an increased cell proliferation and a shift of the proliferative zone towards the apex of the crypt. Epidemiological and in vitro studies have confirmed a link between vitamins A, E, C, beta-carotene, and colorectal cancer. In vitro bromodeoxyuridine immunohistochemical technique was used to assess the effect of daily oral supplementation with vitamin E (1...

  16. Local IgE production in nonatopic nasal polyposis.

    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.

  17. Management of Peutz-Jeghers syndrome. Experience with patients from the Danish Polyposis Register

    Rebsdorf Pedersen, I; Hartvigsen, A; Fischer Hansen, B;

    1994-01-01

    Danish patients with Peutz-Jeghers syndrome are registered in the Danish Polyposis Register. We have initiated a new follow-up programme based on recent literature including our own cases. This has been adjusted to the regrowth rate of the polyps whereby patients with no symptoms and low regrowth...

  18. Hereditary non-polyposis colorectal cancer: clinical features and survival. Results from the Danish HNPCC register

    Myrhøj, T; Bisgaard, M L; Bernstein, Inge Thomsen; Svendsen, L B; Søndergaard, J O; Bülow, Steffen

    1997-01-01

    BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by the development of colorectal cancer (CRC) and other carcinomas. Our aim was to evaluate tumour parameters and survival in HNPCC. METHODS: One hundred and eight Danish HNPCC patients...

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

    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) famili...

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

    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.

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

    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. [Future of the remaining rectum after treatment of familial polyposis (author's transl)].

    Aboulola, M; Boukheloua, B; Bouhadef, A; Illoul, G

    1978-01-01

    In the treatment of familial polyposis the conservation of the rectum is essential to assure a convenient control and rhythm of defecation. Meanwhile the future of resting polyps deserves the attention of the surgeon. Certain authors are optimistic and claim that spontaneous regression of the polyps is possible. Our experience illustrates that the rectal mucosa tends to fabricate new crops of polyps. The prolonged post operative observation of more than 4 years of polyposis in one family has permitted us to follow the evolution of the rectal mucosa and to deduce that gravity of the lesion is quite variable. The polypotique character of the rectal mucosa must influence the choice of certain surgical technic specially that nine of them achieve entire satisfaction yet. PMID:709703

  3. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC)

    Annegret Müller; Tina Bocker Edmonston; Wolfgang Dietmaier; Reinhard Büttner; Richard Fishel; Josef Rüschoff

    2004-01-01

    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 Nationa...

  4. [Clinical significance of telomerase activity in precancerous lesion of the liver (adenomatous hyperplasia)].

    Nishimoto, A; Miura, N; Oshimura, M

    1998-05-01

    To understand the role of telomere dynamics in hepatocellular carcinogenesis, we examined the lengths of terminal restriction fragments (TRFs) in hepatocellular carcinoma (HCC) and surrounding tissues with chronic active hepatitis (CAH), liver cirrhosis (LC) and atypical adenomatous hyperplasia (AAH). The peak TRFs in all HCCs were significantly shorter than those of the surrounding tissues (CAH, LC). TRF in AAH was shortened and similar to that of HCC. Telomerase was examined in CAH, LC, AH, and HCC, and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AH was similar to that of HCC. Thus, the progressive shortening of telomere and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease. PMID:9613131

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

    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.

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

    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.

  7. p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior

    Shanmugam, Chandrakumar; Katkoori, Venkat R.; Jhala, Nirag C.; Grizzle, William E.; Gene P Siegal; Manne, Upender

    2008-01-01

    For subsets of colorectal adenocarcinoma (CRC) patients, nuclear accumulation of p53 (p53nac) and Bcl-2 expression are prognostic indicators. To understand their role in the progression of CRC we evaluated 90 CRCs and their contiguous adenomatous components (CAdCs) for immunohistochemical expression of these markers. In general, p53nac and Bcl-2 expression was significantly increased when comparing normal colonic epithelia to CAdCs and CRCs. Thirteen (14%) CAdCs that demonstrated p53nac conti...

  8. AXIN1 and AXIN2 Variants in Gastrointestinal Cancers

    Serina M. Mazzoni; 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 ...

  9. A case of cap polyposis remission by betamethasone enema after antibiotics therapy including Helicobacter pylori eradication.

    Suzuki, Hideo; Sato, Masashi; Akutsu, Daisuke; Sugiyama, Hiroaki; Sato, Taiki; Mizokami, Yuji

    2014-06-01

    We report the case of a 58-year-old woman who was referred to our hospital due to frequent bloody mucus diarrhea. She was diagnosed with cap polyposis based on typical endoscopic and histological findings. Colonoscopy revealed multiple, reddish, mucus-capped polypoid lesions from the rectum to the sigmoid colon. A pathological examination revealed that the polyps were covered by erosive and inflamed granulation tissue with decreased crypt cells. Laboratory data indicated positive values for Helicobacter pylori immunoglobulin G antibody and hypoproteinemia. Metronidazole, H. pylori eradication, and levofloxacin therapies were not effective; however, the subsequent administration of betamethasone enema dramatically improved the clinical symptoms and endoscopic findings. The hypoproteinemia was normalized after the therapy. The dose of the betamethasone enema was tapered gradually, and no recurrence was observed 6 months after discontinuation of the treatment. This case suggests that betamethasone enema may be considered as the second treatment choice for cap polyposis patients after H. pylori eradication, metronidazole or levofloxacin therapy. PMID:24949613

  10. Identification of the Modifier of Min 2 (Mom2) Locus, a New Mutation That Influences Apc-Induced Intestinal Neoplasia

    Silverman, Karen A.; Koratkar, Revati; Linda D. Siracusa; Buchberg, Arthur M.

    2002-01-01

    Min (Multiple intestinal neoplasia) mice carry a dominant mutation in the adenomatous polyposis coli (Apc) gene and develop multiple adenomas throughout their intestinal tract (Moser et al. 1990; Su et al. 1992). Polyp multiplicity in Min mice is greatly influenced by genetic background. A modifier locus, Mom1 (Modifier of Min 1), was identified and localized to distal mouse chromosome 4 (Moser et al. 1992; Dietrich et al. 1993), and accounts for some of the genetic variance in polyp multipli...

  11. Deconstructing the ßcatenin destruction complex: mechanistic roles for the tumor suppressor APC in regulating Wnt signaling

    Roberts, David M.; Pronobis, Mira I.; Poulton, John S; Waldmann, Jon D.; Stephenson, Elise M.; Hanna, Shahnaz; Peifer, Mark

    2011-01-01

    Negatively regulating signaling by targeting key effectors for ubiquitina­tion/destruction is essential for development and oncogenesis. The tumor suppressor adenomatous polyposis coli (APC), an essential negative regulator of Wnt signaling, provides a paradigm. APC mutations occur in most colon cancers. Acting in the “destruction complex” with Axin, glycogen synthase kinase 3, and casein kinase, APC targets ßcatenin (ßcat) for phosphorylation and recognition by an E3 ubiquitin-ligase. Despit...

  12. Wnt/beta-catenin/Tcf signaling: A critical pathway in gastrointestinal tumorigenesis

    Kolligs, F. T.; Bommer, G; Göke, B

    2002-01-01

    Cancers of the gastrointestinal tract, including the liver, bile ducts, and pancreas, constitute the largest group of malignant tumors. Colorectal cancer is one of the most common neoplastic diseases in Western countries and one of the leading causes of cancer-related deaths. Inactivation of the adenomatous polyposis coli (APC) tumor-suppressor gene during early adenoma formation is thought to be the first genetic event in the process of colorectal carcinogenesis followed by mutations in onco...

  13. APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and cytoskeletal regulation

    Poulton, John S; Mu, Frank W.; Roberts, David M.; Peifer, Mark

    2013-01-01

    To ensure the accurate transmission of genetic material, chromosome segregation must occur with extremely high fidelity. Segregation errors lead to chromosomal instability (CIN), with deleterious consequences. Mutations in the tumor suppressor adenomatous polyposis coli (APC) initiate most colon cancers and have also been suggested to promote disease progression through increased CIN, but the mechanistic role of APC in preventing CIN remains controversial. Using fly embryos as a model, we inv...

  14. β-Catenin—A Linchpin in Colorectal Carcinogenesis?

    Wong, Newton Alexander Chiang Shuek; Pignatelli, Massimo

    2002-01-01

    An important role for β-catenin pathways in colorectal carcinogenesis was first suggested by the protein’s association with adenomatous polyposis coli (APC) protein, and by evidence of dysregulation of β-catenin protein expression at all stages of the adenoma-carcinoma sequence. Recent studies have, however, shown that yet more components of colorectal carcinogenesis are linked to β-catenin pathways. Pro-oncogenic factors that also release β-catenin from the adherens complex and/or encourage ...

  15. Funktionelle und molekulare Charakterisierung von Amer3: ein neuer Regulator des Wnt/beta-catenin-Signalwegs

    Brauburger, Katharina

    2013-01-01

    Das Tumorsuppressorprotein APC (adenomatous polyposis coli) ist ein wichtiger negativer Regulator des Wnt/beta-catenin-Signalwegs und spielt im Darm eine entscheidende Rolle in der Proliferation und Differenzierung von Epithelzellen. Mutationen, die zu C-terminal verkürzten APC-Molekülen führen, sind die Hauptursache für die Adenom- und Karzinom-Entwicklung in Darmkrebspatienten. Mit Amer1 und Amer2 wurden zwei Plasmamembran-assoziierte APC-Interaktoren identifiziert, welche di...

  16. HSP105 Recruits Protein Phosphatase 2A To Dephosphorylate β-Catenin

    Yu, Nancy; Kakunda, Michael; Pham, Victoria; Lill, Jennie R.; Du, Pan; Wongchenko, Matthew; Yan, Yibing; Firestein, Ron; Huang, Xiaodong

    2015-01-01

    The Wnt/β-catenin pathway causes accumulation of β-catenin in the cytoplasm and its subsequent translocation into the nucleus to initiate the transcription of the target genes. Without Wnt stimulation, β-catenin forms a complex with axin (axis inhibitor), adenomatous polyposis coli (APC), casein kinase 1α (CK1α), and glycogen synthase kinase 3β (GSK3β) and undergoes phosphorylation-dependent ubiquitination. Phosphatases, such as protein phosphatase 2A (PP2A), interestingly, also are component...

  17. Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex

    Kunttas-Tatli, Ezgi; Roberts, David M.; McCartney, Brooke M.

    2014-01-01

    The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling through its activity in the destruction complex with Axin, GSK3β, and CK1 that targets β-catenin/Armadillo (β-cat/Arm) for proteosomal degradation. The destruction complex forms macromolecular particles we termed the destructosome. Whereas APC functions in the complex through its ability to bind both β-cat and Axin, we hypothesize that APC proteins play an additional role in destructosome...

  18. An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.

    M. Kitagawa; Hatakeyama, S.; Shirane, M; Matsumoto, M; ISHIDA, N.; K. Hattori; Nakamichi, I; Kikuchi, A; Nakayama, K.

    1999-01-01

    beta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen syntha...

  19. Mutations in the WTX - gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers

    Scheel Silvio K; Porzner Marc; Pfeiffer Sabine; Ormanns Steffen; Kirchner Thomas; Jung Andreas

    2010-01-01

    Abstract Background Genetically, colorectal cancers (CRCs) can be subdivided into tumors with chromosomal instability (CIN) or microsatellite instability (MSI). In both types of CRCs genes that are involved in the degradation of β-CATENIN are frequently mutated. Whereas in CIN CRCs APC (Adenomatous Polyposis Coli) is affected in most cases, high grade MSI (MSI-H) CRCs frequently display mutations in various genes, like the APC-, AXIN2- or CTNNBI (β-CATENIN) gene itself. Recently in Wilms tumo...

  20. Inhibition of WNT Signaling by G Protein-Coupled Receptor (GPCR) Kinase 2 (GRK2)

    WANG, LIMING; Gesty-Palmer, Diane; Fields, Timothy A.; Spurney, Robert F.

    2009-01-01

    Activation of Wnt signaling pathways causes release and stabilization of the transcription regulator β-catenin from a destruction complex composed of axin and the adenomatous polyposis coli (APC) protein (canonical signaling pathway). Assembly of this complex is facilitated by a protein-protein interaction between APC and a regulator of G protein signaling (RGS) domain in axin. Because G protein-coupled receptor kinase 2 (GRK2) has a RGS domain that is closely related to the RGS domain in axi...

  1. Dysregulation of Wnt/β-catenin Signaling in Gastrointestinal Cancers

    White, Bryan D.; Chien, Andy J.; Dawson, David W.

    2011-01-01

    Aberrant Wnt/β-catenin signaling is widely implicated in numerous malignancies, including cancers of the gastrointestinal (GI) tract. Dysregulation of signaling is traditionally attributed to mutations in Axin, APC (adenomatous polyposis coli), and β-catenin that lead to constitutive hyperactivation of the pathway. However, Wnt/β-catenin signaling is also modulated through various other mechanisms in cancer, including crosstalk with other altered signaling pathways. A more complex view of Wnt...

  2. Domains of Axin Involved in Protein–Protein Interactions, Wnt Pathway Inhibition, and Intracellular Localization

    Fagotto, François; Jho, Eek-hoon; Zeng, Li; Kurth, Thomas; Joos, Thomas; Kaufmann, Christine; Costantini, Frank

    1999-01-01

    Axin was identified as a regulator of embryonic axis induction in vertebrates that inhibits the Wnt signal transduction pathway. Epistasis experiments in frog embryos indicated that Axin functioned downstream of glycogen synthase kinase 3β (GSK3β) and upstream of β-catenin, and subsequent studies showed that Axin is part of a complex including these two proteins and adenomatous polyposis coli (APC). Here, we examine the role of different Axin domains in the effects on axis formation and β-cat...

  3. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

    Parisi, Alice; Lacour, Floriane; Giordani, Lorenzo; Colnot, Sabine; Maire, Pascal; Le Grand, Fabien

    2015-01-01

    The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle ste...

  4. Targeting the DNA replication checkpoint by pharmacologic inhibition of Chk1 kinase: a strategy to sensitize APC mutant colon cancer cells to 5-fluorouracil chemotherapy

    Martino-Echarri, Estefania; Henderson, Beric R.; Brocardo, Mariana G.

    2014-01-01

    5-fluorouracil (5-FU) is the first line component used in colorectal cancer (CRC) therapy however even in combination with other chemotherapeutic drugs recurrence is common. Mutations of the adenomatous polyposis coli (APC) gene are considered as the initiating step of transformation in familial and sporadic CRCs. We have previously shown that APC regulates the cellular response to DNA replication stress and recently hypothesized that APC mutations might therefore influence 5-FU resistance. T...

  5. The ins and outs of APC and β-catenin nuclear transport

    Henderson, Beric R.; Fagotto, Francois

    2002-01-01

    Adenomatous polyposis coli (APC) and β-catenin, two key interacting proteins implicated in development and cancer, were recently found to traffic into and out of the nucleus in response to internal and external signals. The two proteins can enter and exit the nucleus independently, a discovery that has prompted debate about the previously proposed role of APC as a β-catenin chaperone. Here, we review the regulation of APC and β-catenin subcellular localization, in particular in cancer cells. ...

  6. Redefining the subcellular location and transport of APC: new insights using a panel of antibodies

    Brocardo, Mariana; Näthke, Inke S.; Henderson, Beric R.

    2005-01-01

    Adenomatous polyposis coli (APC) is a tumour suppressor involved in colon cancer progression. We and others previously described nuclear–cytoplasmic shuttling of APC. However, there are conflicting reports concerning the localization of endogenous wild-type and tumour-associated, truncated APC. To resolve this issue, we compared APC localization using immunofluorescence (IF) microscopy and cell fractionation with nine different APC antibodies. We found that three commonly used APC antibodies ...

  7. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene

    Martínez, María Elena; O'Brien, Thomas G.; Fultz, Kimberly E.; Babbar, Naveen; Yerushalmi, Hagit; Qu, Ning; Guo, Yongjun; Boorman, David; Einspahr, Janine; Alberts, David S.; Gerner, Eugene W.

    2003-01-01

    Most sporadic colon adenomas acquire mutations in the adenomatous polyposis coli gene (APC) and show defects in APC-dependent signaling. APC influences the expression of several genes, including the c-myc oncogene and its antagonist Mad1. Ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is a transcriptional target of c-myc and a modifier of APC-dependent tumorigenesis. A single-nucleotide polymorphism exists in intron 1 of the human ODC gene, which lies between t...

  8. Differential gene expression profile reveals deregulation of pregnancy specific β1 glycoprotein 9 early during colorectal carcinogenesis

    Gallinger Steven; Chetty Runjan; Goncalves Jason; Salahshor Sima; Woodgett James R

    2005-01-01

    Abstract Background APC (Adenomatous polyposis coli) plays an important role in the pathogenesis of both familial and sporadic colorectal cancer. Patients carrying germline APC mutations develop multiple colonic adenomas at younger age and higher frequency than non-carrier cases which indicates that silencing of one APC allele may be sufficient to initiate the transformation process. Methods To elucidate the biological dysregulation underlying adenoma formation we examined global gene express...

  9. Giant mediastinal thymolipoma in a patient with Gardner’s syndrome

    Pei, Guotian; Han, Yi; Zhou, Shijie; Liu, Zhidong

    2015-01-01

    Gardner’s syndrome is a hereditary disorder inherited as an autosomal dominant with high penetrance and variable expression that is caused by a mutation of the adenomatous polyposis coli gene. It is characterized by gastrointestinal polyps associated with multiple osteomas, dental anomalies, and skin and soft tissue tumors. We present a case of 30-year-old female patient with Gardner’s syndrome who presented with a giant mediastinal thymolipoma. The tumor was completely excised through a bila...

  10. Wnt Signaling Regulates the Lineage Differentiation Potential of Mouse Embryonic Stem Cells through Tcf3 Down-Regulation

    Yaser Atlasi; Rubina Noori; Claudia Gaspar; Patrick Franken; Andrea Sacchetti; Haleh Rafati; Tokameh Mahmoudi; Charles Decraene; Calin, George A; Merrill, Bradley J.; Riccardo Fodde

    2013-01-01

    Canonical Wnt signaling plays a rate-limiting role in regulating self-renewal and differentiation in mouse embryonic stem cells (ESCs). We have previously shown that mutation in the Apc (adenomatous polyposis coli) tumor suppressor gene constitutively activates Wnt signaling in ESCs and inhibits their capacity to differentiate towards ecto-, meso-, and endodermal lineages. However, the underlying molecular and cellular mechanisms through which Wnt regulates lineage differentiation in mouse ES...

  11. Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

    Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D; John L R Rubenstein

    2014-01-01

    Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tan...

  12. Nuclear APC

    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...

  13. High Quality Assessment of DNA Methylation in Archival Tissues from Colorectal Cancer Patients Using Quantitative High-Resolution Melting Analysis

    Balic, Marija; Pichler, Martin; Strutz, Jasmin; Heitzer, Ellen; Ausch, Christoph; Samonigg, Hellmut; Cote, Richard J.; Dandachi, Nadia

    2009-01-01

    High-resolution melting (HRM) analysis is a novel tool for analysis of promoter methylation. The aim of the present study was to establish and validate HRM analysis for detection of promoter methylation on archival formalin-fixed paraffin-embedded tissues from colorectal cancer patients. We first evaluated HRM assays for O6-methylguanine-DNA methyltransferase (MGMT) and adenomatous polyposis coli (APC) promoter methylation on a methylated DNA dilution matrix and DNA extracted from eight fresh...

  14. Neighborhood analysis of low magnification structures (glands) in healthy, adenomatous, and carcinomatous colon mucosa.

    Kayser, K; Shaver, M; Modlinger, F; Postl, K; Moyers, J J

    1986-05-01

    A new algorithm analyzing neighborhood conditions of adenomatous tissue is is introduced. Using O'Callaghan's definition of neighborhoods, a graph theory approach for measuring histomorphological structures can be created as follows: glands are defined as vertices and the coherence of neighboring glands as edges. The procedure leads to an unoriented, well-defined graph which contains information usually not measurable by conventional morphometric analysis. Measurements on healthy mucosa, tubulo-villous adenoma and highly to moderately differentiated adenocarcinoma of colon revealed statistically significant differences (p less than or equal to 0.05) for the following parameters: number of vertices, number of edges, frequency distribution of n-stars and of n-closed paths. Correct separation and reclassification of 83% of cases could be carried out using discriminant analysis. 11/15 cases (73%) could be classified correctly in a prospective group based upon the learning set. The significance of these findings for automatic pattern recognition in histopathology is discussed. PMID:3737471

  15. Escherichia Coli

    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…

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

    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

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

    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

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

    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. 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. 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. 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

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

    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.

  20. A typical adenomatous hyperplasia of the lung: correlation of radiographic and pathologic findings

    Objective: To study radiographic features of atypical adenomatous hyperplasia (AAH) of lung and correlate them with their pathologic findings, so as to improve the imaging diagnose. Methods: The imaging features of 8 patients with pathology- proved AAH were reviewed. All patients were women with age ranging from 35 to 74 years. All cases had chest radiography and HRCT. The radiographic findings were studied retrospectively and correlated with those of pat hology. Results: On chest X-ray, the foci in five patients presented as nodule-like area of a bit high attenuation, while the chest radiograph in the other three patients were negative. On HRCT, all 8 patients presented as non-solid nodules. All lesions were round or oval shaped with well-defined margin (n=4) or poor-defined margin (n=3). The greatest dimension of the lesions ranged from 5.0 mm to 20.0 mm. Their CT value ranged from -362.7 HU to -485.6 HU, the mean CT value was (-423.0 ± 47.0) HU. Air bronchograms and/or bubbles were seen in 5 lesions. Coarse spiculation and pleural tag was not seen in any lesion. Before operation, all the nodules did not change in size over a follow-up period from one month to six months. Pathologic findings showed atypical epithelial cell proliferation along thickened alveolar septa without alveolar collapse. Conclusion: AAH should be considered in cases with the following features: (1) nodules ate found in lung cancer screening or incidentally detected; (2) the diameter of the nodule is usually less than 10 mm; (3) the lesion presented as non-solid nodule on HRCT, air bronchogram and/or bubble sign can be seen; (4) no coarse spiculation and plural tag was seen. (authors)

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

    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.

  2. Melanosis coli

    Siang-Tong Kew

    2012-07-01

    Full Text Available Melanosis coli denotes brownishdiscoloration of the colonic mucosa found on endoscopyor histopathologic examination. The condition hasno specific symptom on its own. It is a fairly frequentincidental finding of colonic biopsies and resectionspecimens. The pigmentation is caused by apoptotic cellswhich are ingested by macrophages and subsequentlytransported into the lamina propria, where lysosomesuse them to produce lipofuscin pigment, not melaninas the name suggests. Melanosis coli develops in over70% of persons who use anthraquinone laxatives (egcascara sagrada, aloe, senna, rhubarb, and frangula,often within 4 months of use. Long-term use is generallybelieved to be necessary to cause melanosis coli.The condition is widely regarded as benign andreversible, and disappearance of the pigment generallyoccurs within a year of stopping laxatives. Althoughoften due to prolonged use of anthraquinone, melanosiscan probably result from other factors or exposure toother laxatives. It has been reported as a consequenceof longstanding inflammatory bowel disease. Someinvestigators suggested that increase in apoptosis ofcolonic mucosa by anthraquinone laxatives increased therisk of colonic cancer. Recent data, including those fromlarge-scale retrospective, prospective and experimentalstudies, did not show any increased cancer risk.

  3. Investigating the Potential Role of Genetic and Epigenetic Variation of DNA Methyltransferase Genes in Hyperplastic Polyposis Syndrome

    Drini, Musa; Nicholas C. Wong; Hamish S Scott; Craig, Jeffrey M; Dobrovic, Alexander; Chelsee A Hewitt; Dow, Christofer; Young, Joanne P; Jenkins, Mark A; Saffery, Richard; Macrae, Finlay A.

    2011-01-01

    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...

  4. Regulation of Arachidonic Acid Pathway and Eosinophilic Inflammation in Chronic Rhinosinusitis/ Nasal Polyposis. Potential Role of Staphylococcus aureus Enterotoxins

    Pérez Novo, C

    2006-01-01

    linked to inflammation. Furthermore, EP2 and EP4 receptor expression was increased in chronic rhinosinusitis and nasal polyp subjects in contrast to EP1 and EP3, which were down regulated in the polyp group, suggesting a distinctive role of these receptors in the pathophysiology of nasal polyposis. Finally, based on our previous findings and parallel work of our group, we studied the influence of S. aureus enterotoxins in the regulation of both eosinophilic inflammatory and eicosanoid pathway...

  5. Rapid microsatellite analysis of paraffin embedded tumour specimens from patients with hereditary non-polyposis colorectal cancer.

    Raedle, J; Brieger, A; Trojan, J; Herrmann, G.; Zeuzem, S

    1998-01-01

    In screening for hereditary non-polyposis colorectal cancer (HNPCC)--an autosomal dominant disorder characterised by mutations in mismatch repair genes--detection of microsatellite instability is an important diagnostic criterion. The mono- or dinucleotide repeat DNA sequences are usually amplified from formalin fixed, paraffin embedded tissue by polymerase chain reaction after numerous time consuming steps including deparaffinisation, DNA extraction, and purification. A rapid single step met...

  6. Comorbidities in Severe Asthma: Frequency of Rhinitis, Nasal Polyposis, Gastroesophageal Reflux Disease, Vocal Cord Dysfunction and Bronchiectasis

    Carla Bisaccioni; Marcelo Vivolo Aun; Edcarlos Cajuela; Jorge Kalil; Rosana Câmara Agondi; Pedro Giavina-Bianchi

    2009-01-01

    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 20...

  7. The differentiation and prognostic implication of the solitary colonic polyp and the polyposis syndromes: A radiologic, histologic, and pathologic approach

    The differential diagnosis of the solitary colonic polyp and the implications and prognostic significance of the solitary colonic polyp and the polyposis syndromes are frequently confusing because of imprecise and overlapping terminology. Such confusion may lead to misdiagnosis or overdiagnosis and improper patient treatment and surveillance. In the first part of this course, basic terms are defined to acquaint all participants with current common ground. The most frequently occurring solitary polyps (e.g., the colonic adenoma, hyperplastic polyp, Peutz-Jeghers hamartoma, juvenile hamartoma, and inflammatory polyp) are illustrated in detail with radiologic-histologic-pathologic correlation. The prognostic significance of each type of lesion and a scheme for proper colonic surveillance is discussed. In the second part of the session, there is a thorough discussion of multiple colonic polyps and the polyposis syndromes. Radiologic-pathologic correlation are used to illustrate these entities, and therapeutic and diagnostic implications are thoroughly covered. The differential diagnosis of the polyposis syndromes, including lymphoid abnormalities, pneumatosis intestinalis, and colitis cystica profunda, are mentioned. The participant should expect to gain a full understanding of the solitary and multiple colonic polyp states and algorithms for prognosis and treatment

  8. Manifestations of juvenile polyposis syndrome in SMAD4 mutation carriers of a kindred.

    Schwetz, Verena; Uhrig, Sabine; Spuller, Ekkehard; Deutschmann, Andrea; Högenauer, Christoph

    2012-08-01

    The autosomal dominantly inherited juvenile polyposis syndrome (JPS) leads to the development of multiple hamartomatous polyps in the gastrointestinal tract and is a precancerous condition. In a large family with a newly identified SMAD4 mutation (c.543delC), we describe the clinical manifestations of JPS. Nine affected SMAD4 mutation-positive family members were screened and treated for manifestations of JPS. Two family members were symptomatic at the time of diagnosis; seven were asymptomatic - independent of the severity of the manifestation. Each mutation carrier presented with colonic juvenile polyps, seven out of nine with additional gastric manifestations. One asymptomatic patient had early gastric cancer; another patient had a villous adenoma with high-grade intraepithelial neoplasia in the colon. Three patients had biliary lesions including a bile duct hamartoma in one and gallbladder polyps in two. Three patients had gastrointestinal vascular malformations. All mutation carriers were affected by JPS. Interestingly, the manifestations and their severity differed considerably between the patients, suggesting secondary factors influencing JPS manifestations such as Helicobacter pylori infection. PMID:22617360

  9. EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis

    Ephrin receptor B2 (EPHB2) has recently been proposed as a novel tumor suppressor gene in colorectal cancer (CRC). Inactivation of the gene has been shown to correlate with progression of colorectal tumorigenesis, and somatic mutations have been reported in both colorectal and prostate tumors. Here we have analyzed the EPHB2 gene for germline alterations in 101 individuals either with 1) CRC and a personal or family history of prostate cancer (PC), or 2) intestinal hyperplastic polyposis (HPP), a condition associated with malignant degeneration such as serrated adenoma and CRC. Four previously unknown missense alterations were observed, which may be associated with the disease phenotype. Two of the changes, I361V and R568W, were identified in Finnish CRC patients, but not in over 300 Finnish familial CRC or PC patients or more than 200 population-matched healthy controls. The third change, D861N, was observed in a UK HPP patient, but not in additional 40 UK HPP patients or in 200 UK healthy controls. The fourth change R80H, originally identified in a Finnish CRC patient, was also found in 1/106 familial CRC patients and in 9/281 healthy controls and is likely to be a neutral polymorphism. We detected novel germline EPHB2 alterations in patients with colorectal tumors. The results suggest a limited role for these EPHB2 variants in colon tumor predisposition. Further studies including functional analyses are needed to confirm this

  10. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC

    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.