Morphological and molecular processes of polyp formation in Apc(delta716) knockout mice.

Abstract:

:Mutations in the human adenomatous polyposis coli (APC) gene are responsible for not only familial adenomatous polyposis but also many sporadic cancers of the digestive tract. Using homologous recombination in embryonic stem cells, we recently constructed Apc gene knockout mice that contained a truncation mutation at codon 716 (Apc(delta716)). The heterozygous mice developed numerous intestinal polyps. All microadenomas dissected from nascent polyps had already lost the wild-type allele, indicating the loss of heterozygosity (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). We also demonstrated that cyclooxygenase 2 is induced in the polyps at an early stage and plays a key role in polyp development (M. Oshima et al., Cell 87: 803-809, 1996). We have analyzed the process of polyp development in these mice both at morphological and molecular levels. A small intestinal microadenoma is initiated as an outpocketing pouch in a single crypt and develops into the inner (lacteal) side of a neighboring villus forming a double-layer nascent polyp. The microadenoma then enlarges and gets folded inside the villus. When it fills the intravillous space, it expands downward and extends into adjoining villi, rather than rupturing into the intestinal lumen. During this course of development, the basement membrane remains intact, and the labeling index of the microadenoma cells is similar to that of the normal crypt epithelium. As in the crypt cells, neither transforming growth factor beta1 nor its receptor type II is expressed in the microadenoma cells. No hot spot mutations in the K-ras gene are found in the microadenoma tissue during these early stages of polyp development. Essentially, the same results have been obtained for the colonic polyps as well. These results suggest that early adenomas in the Apc(delta716) polyps are very similar to the normal proliferating cells of the crypt except for the lack of directed migration along the crypt-villus axis.

journal_name

Cancer Res

journal_title

Cancer research

authors

Oshima H,Oshima M,Kobayashi M,Tsutsumi M,Taketo MM

subject

Has Abstract

pub_date

1997-05-01 00:00:00

pages

1644-9

issue

9

eissn

0008-5472

issn

1538-7445

journal_volume

57

pub_type

杂志文章
  • Biosynthesis and processing of prostatic and lysosomal acid phosphatases in a prostate carcinoma cell line PC-3SF12.

    abstract::The biosynthesis of distinct prostatic and lysosomal acid phosphatases is demonstrated using a human prostatic carcinoma cell line, PC-3SF12. The biosynthesis and maturation of the acid phosphatases was studied by metabolic labeling with radioactive leucine, specific immunoprecipitation, sodium dodecyl sulfate-polyacr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Waheed A,Van Etten RL

    更新日期:1986-09-01 00:00:00

  • Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens.

    abstract::High-resolution magic angle spinning proton (HRMAS 1H) magnetic resonance spectroscopy produces well-resolved spectra of metabolites from intact tissue specimens. Here we report the results of a preliminary study of 19 human brain tumors obtained by applying this method. Among these 19 cases were 2 low-grade astrocyto...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Cheng LL,Chang IW,Louis DN,Gonzalez RG

    更新日期:1998-05-01 00:00:00

  • Nonrandom nature of in vivo methylation of dimethylnitrosamine and the subsequent removal of methylated products from rat liver chromatin DNA.

    abstract::This investigation was designed to study whether methylation of liver chromatin DNA by dimethylnitrosamine (DMN) and the subsequent in vivo removal of DNA-bound methylated products are random. Liver chromatin DNA was fractionated into nuclease-digestible and nondigestible material 4 hr following the administration of ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ramanathan R,Rajalakshmi S,Sarma DS,Farber E

    更新日期:1976-06-01 00:00:00

  • Efforts to control the errant products of a targeted in vivo generator.

    abstract::Alpha-particle immunotherapy by targeted alpha-emitters or alpha-emitting isotope generators is a novel form of extraordinarily potent cancer therapy. A major impediment to the clinical use of targeted actinium-225 (225Ac) in vivo generators may be the radiotoxicity of the systemically released daughter radionuclides....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3096

    authors: Jaggi JS,Kappel BJ,McDevitt MR,Sgouros G,Flombaum CD,Cabassa C,Scheinberg DA

    更新日期:2005-06-01 00:00:00

  • Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity.

    abstract::Small-molecule inhibitors of PARP1/2, such as olaparib, have been proposed to serve as a synthetic lethal therapy for cancers that harbor BRCA1 or BRCA2 mutations. Indeed, in clinical trials, PARP1/2 inhibitors elicit sustained antitumor responses in patients with germline BRCA gene mutations. In hypothesizing that ad...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-2541

    authors: Bajrami I,Frankum JR,Konde A,Miller RE,Rehman FL,Brough R,Campbell J,Sims D,Rafiq R,Hooper S,Chen L,Kozarewa I,Assiotis I,Fenwick K,Natrajan R,Lord CJ,Ashworth A

    更新日期:2014-01-01 00:00:00

  • Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract.

    abstract::Vascular permeability factor (VPF) is one of the most potent known inducers of microvascular hyperpermeability; in addition, it is a selective endothelial cell growth factor, hence its alternate name, vascular endothelial growth factor. VPF exerts its actions on the microvasculature by interacting with specific endoth...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Brown LF,Berse B,Jackman RW,Tognazzi K,Manseau EJ,Senger DR,Dvorak HF

    更新日期:1993-10-01 00:00:00

  • Retroviral insertional mutagenesis as a strategy for the identification of genes associated with cis-diamminedichloroplatinum(II) resistance.

    abstract::Expression of resistance to cis-diamminedichloroplatinum(II) (CDDP), one of the most effective chemotherapeutic drugs used to treat a variety of malignancies, remains a serious obstacle for improving cancer treatment. To study possible genetic mechanisms underlying the development of CDDP resistance, we have adopted t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Lu SJ,Man S,Bani MR,Adachi D,Hawley RG,Kerbel RS,Ben-David Y

    更新日期:1995-03-01 00:00:00

  • Dependence of the cytotoxicity of DNA-damaging agents on the mismatch repair status of human cells.

    abstract::Mismatch repair (MMR) deficiency was reported to increase resistance of mammalian cells to killing by several genotoxic substances. However, although MMR-deficient cells are approximately 100-fold more resistant to killing by S(N)1 type methylating agents than MMR-proficient controls, the sensitivity differences repor...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-0513

    authors: Papouli E,Cejka P,Jiricny J

    更新日期:2004-05-15 00:00:00

  • Inhibition of PAI-1 Limits Tumor Angiogenesis Regardless of Angiogenic Stimuli in Malignant Pleural Mesothelioma.

    abstract::Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor that secretes various angiogenic factors. The main inhibitor of plasminogen activators, PAI-1 (SERPINE1), has been implicated in tumor progression and angiogenesis, and high PAI-1 expression has been associated with poor prognosis in MPM patients. I...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-1796

    authors: Takayama Y,Hattori N,Hamada H,Masuda T,Omori K,Akita S,Iwamoto H,Fujitaka K,Kohno N

    更新日期:2016-06-01 00:00:00

  • Insulin-like growth factor II mRNA expression in human breast cancer.

    abstract::Insulin-like growth factor II is a growth factor important in fetal development. Several cancer tissues and cell lines have been reported to express IGF-II and rat IGF-II is mitogenic for breast cancer cell lines. Using Northern analysis and ribonuclease protection assays, IGF-II mRNA was detected in normal fibroblast...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yee D,Cullen KJ,Paik S,Perdue JF,Hampton B,Schwartz A,Lippman ME,Rosen N

    更新日期:1988-12-01 00:00:00

  • Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide.

    abstract::The pharmacological properties of garlic and its derivatives are long known, and their underling mechanisms are being extensively investigated. In this study we have addressed the effects of diallyl disulfide (DADS), an oil-soluble garlic molecule, on cell growth of neuroblastoma cell SH-SY5Y, focusing on the redox ev...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Filomeni G,Aquilano K,Rotilio G,Ciriolo MR

    更新日期:2003-09-15 00:00:00

  • Comparative metabolism of 2-[bis(2-chloroethyl)amino]tetrahydro-2-H-1,3,2-oxazaphosphorine-2-oxide (cyclophosphamide) and its enantiomers in humans.

    abstract::The comparative metabolism of the enantiomers of cyclo phosphamide and of the racemate has been studied in humans. Four patients were each given, sequentially, the racemate, the (+)-enantiomer, and its (-)-antipode. The plasma levels of parent drug and the urinary output (24 hr) of unchanged drug and of two enzymatica...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Jarman M,Milsted RA,Smyth JF,Kinas RW,Pankiewicz K,Stec WJ

    更新日期:1979-07-01 00:00:00

  • Intrathecal 4-hydroperoxycyclophosphamide: neurotoxicity, cerebrospinal fluid pharmacokinetics, and antitumor activity in a rabbit model of VX2 leptomeningeal carcinomatosis.

    abstract::Dissemination of tumor to the leptomeninges and cerebrospinal fluid represents a common pattern of metastasis for many cancers; however, few chemotherapeutic agents are available for intrathecal (i.t.) use and treatment results are often poor. We studied the neurotoxicity and pharmacokinetics of i.t. 4-hydroperoxycycl...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Phillips PC,Than TT,Cork LC,Hilton J,Carson BS,Colvin OM,Grochow LB

    更新日期:1992-11-15 00:00:00

  • Suramin affects DNA synthesis in HeLa cells by inhibition of DNA polymerases.

    abstract::Suramin, a polysulfonated naphthylurea widely used in the treatment of trypanosomiasis and onchocerciasis, is currently being investigated as an antitumor agent for the treatment of advanced cancer. Suramin exerts a wide variety of biological effects. We have shown that suramin inhibits cell proliferation and DNA synt...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Jindal HK,Anderson CW,Davis RG,Vishwanatha JK

    更新日期:1990-12-15 00:00:00

  • Cross-talk between tumor and endothelial cells involving the Notch3-Dll4 interaction marks escape from tumor dormancy.

    abstract::The Notch ligand Dll4 has a recognized role during both physiologic and tumor angiogenesis, as it contributes to regulate Notch activity in endothelial cells (EC). The effects of Dll4 on Notch signaling in tumor cells expressing Notch receptors remain, however, largely unknown. Here, we report that escape of human T-c...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2791

    authors: Indraccolo S,Minuzzo S,Masiero M,Pusceddu I,Persano L,Moserle L,Reboldi A,Favaro E,Mecarozzi M,Di Mario G,Screpanti I,Ponzoni M,Doglioni C,Amadori A

    更新日期:2009-02-15 00:00:00

  • Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice.

    abstract::The formation of 7-(2-hydroxyethyl)guanine (7-HEG) in DNA of target and nontarget tissues was investigated in male B6C3F1 mice (20/group) and F344 rats (10/group) exposed to 0, 3, 10, 33, 100, or 300 (rats only) ppm ethylene oxide (ETO) by inhalation for 6 h/day for 4 weeks (5 days/week) and mice exposed to 100 ppm ET...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Walker VE,Fennell TR,Upton PB,Skopek TR,Prevost V,Shuker DE,Swenberg JA

    更新日期:1992-08-15 00:00:00

  • Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major adult liver cancers. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathologic intermediate form between HCC and CC, suggests phenotypic overlap between these tumors. Here, we applied an integrative oncogenomic approach...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-2823

    authors: Woo HG,Lee JH,Yoon JH,Kim CY,Lee HS,Jang JJ,Yi NJ,Suh KS,Lee KU,Park ES,Thorgeirsson SS,Kim YJ

    更新日期:2010-04-15 00:00:00

  • Beta 2-microglobulin expression in human embryonal neuroblastoma reflects its developmental regulation.

    abstract::Class I major histocompatibility complex (MHC) antigen expression in neuroblastoma may play a role in the oncogenicity of this embryonal tumor of childhood. Since N-myc amplification in neuroblastoma tumors is associated with rapid tumor progression (33) and N-myc decreases Class I MHC antigen expression in rat neurob...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Cooper MJ,Hutchins GM,Mennie RJ,Israel MA

    更新日期:1990-06-15 00:00:00

  • Histological evaluation of in vitro responses of endometrial adenocarcinoma to progestins and their relation to progesterone receptor levels.

    abstract::In vitro responsiveness of endometrial adenocarcinoma to progestins was evaluated histologically by incubation of tissue fragments in medium containing 10(-6) M medroxyprogesterone acetate. In a series of 19 experiments, formation of sub- and supranuclear vacuoles, which reflects accumulation of glycogen in response t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Holinka CF,Deligdisch L,Gurpide E

    更新日期:1984-01-01 00:00:00

  • Genetic differences in metabolism of benzo(a)pyrene in cultured epidermal and dermal cells of responsive and nonresponsive mice.

    abstract::Genetic differences in metabolism of benzo(a)pyrene (BP) were investigated using cultured epidermal keratinocytes and dermal fibroblasts isolated from four inbred strains of mice: C3H/HeJms and C57BL/6J that are responsive; and DBA/2 and AKR/Jms that are nonresponsive in terms of inducibility of aryl hydrocarbon hydro...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hosomi J,Nemoto N,Kuroki T

    更新日期:1983-08-01 00:00:00

  • Serial sacrifice study of pathogenesis of 210Po-induced lung tumors in Syrian golden hamsters.

    abstract::The pathogenesis of 210Po-induced tumors in the peripheral lung of Syrian golden hamsters has been studied in a serial sacrifice experiment utilizing both plastic (glycol methacrylate) and routine paraffin embedding procedures for lung sections. A rapid progression from hyperplasia of bronchiolar-type cells that appea...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kennedy AR,McGundy RB,Little JB

    更新日期:1978-04-01 00:00:00

  • Growth rates of normal and abnormal human mammary epithelia in cell culture.

    abstract::The in vitro growth rates of different classifications of human mammary epithelium were compared. Samples included 4 established breast cell lines and excised tissue or breast fluid cells originating WOMEN FOR 40 DIFFERENT AND comprising 3 classifications: normal, nonmalignant atypical, and malignant. Growth was quant...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Buehring GC,Williams RR

    更新日期:1976-10-01 00:00:00

  • Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution.

    abstract::A common single nucleotide polymorphism (SNP), rs6983267, at 8q24.21 has recently been shown to associate with colorectal cancer (CRC). Three independent SNP association studies showed that rs6983267 contributes to CRC with odds ratios (OR) of 1.17 to 1.22. Here, we genotyped a population-based series of 1,042 patient...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-5766

    authors: Tuupanen S,Niittymäki I,Nousiainen K,Vanharanta S,Mecklin JP,Nuorva K,Järvinen H,Hautaniemi S,Karhu A,Aaltonen LA

    更新日期:2008-01-01 00:00:00

  • Pathology, Chemoprevention, and Preclinical Models for Target Validation in Barrett Esophagus.

    abstract::Despite esophageal adenocarcinoma (EAC) being the most widespread among gastrointestinal cancers, with an 11-fold increase in the risk of cancer for patients with Barrett esophagus (BE), its prognosis is still poor. There is a critical need to better perceive the biology of cancer progression and identification of spe...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-18-0206

    authors: Urbanska AM,Ponnazhagan S,Mozafari M

    更新日期:2018-07-15 00:00:00

  • Changes in serum putrescine and spermidine levels following local radiation to hepatoma 3924A of the rat.

    abstract::Local irradiation of tumors of rats bearing 3924A hepatomas resulted in more than a doubling of the putrescine levvel and nearly a doubling of spermidine concentration in the serum within 12 hr. Within 24 hr, the putrescine concentration had increased four-fold in the serum, along with a continued increase in the sper...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Russell DH,Looney WB,Kovacs CJ,Hopkins HA,Dattilo JW,Morris HP

    更新日期:1976-02-01 00:00:00

  • A syngeneic variance library for functional annotation of human variation: application to BRCA2.

    abstract::The enormous scope of natural human genetic variation is now becoming defined. To accurately annotate these variants, and to identify those with clinical importance, is often difficult to assess through functional assays. We explored systematic annotation by using homologous recombination to modify a native gene in he...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-6189

    authors: Hucl T,Rago C,Gallmeier E,Brody JR,Gorospe M,Kern SE

    更新日期:2008-07-01 00:00:00

  • Notch signaling in CD66+ cells drives the progression of human cervical cancers.

    abstract::Human epithelial tumor progression and metastasis involve cellular invasion, dissemination in the vasculature, and regrowth at metastatic sites. Notch signaling has been implicated in metastatic progression but its roles have yet to be fully understood. Here we report the important role of Notch signaling in maintaini...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-11-0543

    authors: Bajaj J,Maliekal TT,Vivien E,Pattabiraman C,Srivastava S,Krishnamurthy H,Giri V,Subramanyam D,Krishna S

    更新日期:2011-07-15 00:00:00

  • Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression.

    abstract::Targeting the tyrosine kinase activity of Bcr-Abl is an attractive therapeutic strategy in chronic myeloid leukemia (CML) and in Bcr-Abl-positive acute lymphoblastic leukemia. Whereas imatinib, a selective inhibitor of Bcr-Abl tyrosine kinase, is now used in frontline therapy for CML, second-generation inhibitors of B...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-1008

    authors: Mahon FX,Hayette S,Lagarde V,Belloc F,Turcq B,Nicolini F,Belanger C,Manley PW,Leroy C,Etienne G,Roche S,Pasquet JM

    更新日期:2008-12-01 00:00:00

  • Paclitaxel-associated multimininucleation is permitted by the inhibition of caspase activation: a potential early step in drug resistance.

    abstract::The chemotherapeutic agent paclitaxel disrupts microtubule dynamics causing mitotic arrest, which leads to cell death. However, in paclitaxel-resistant tumor cells, treatment with paclitaxel induces abnormal progression through prophase resulting in a multimininucleated phenotype. Multimininucleation and subsequent po...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Panvichian R,Orth K,Day ML,Day KC,Pilat MJ,Pienta KJ

    更新日期:1998-10-15 00:00:00

  • Quantitative prediction of drug toxicity in humans from toxicology in small and large animals.

    abstract::The mouse, dog, and monkey toxicity data on 30 drugs was retrospectively analyzed in comparison with the actual clinical dose schedules used in man. Animal dose schedules were converted to the human schedule and comparisons were made of the human dose versus the large animal toxic dose low, toxic dose high, and lethal...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Goldsmith MA,Slavik M,Carter SK

    更新日期:1975-05-01 00:00:00