Chromosomal signatures of a subset of high-grade premalignant cervical lesions closely resemble invasive carcinomas.

Abstract:

:Cervical cancer develops from precancerous high-grade cervical intraepithelial neoplasia (CIN) harboring a transforming infection with high-risk human papillomavirus, which is characterized by p16(INK4a) overexpression. Once such a lesion has developed, progression toward an invasive squamous cell carcinoma (SCC) may take one or more decades, underlining the heterogeneity of these lesions in terms of duration of existence and progression risk. We performed array-based comparative genomic hybridization (array CGH) on 46 p16(INK4a) immunopositive CIN2/3 lesions to determine whether this heterogeneity is reflected in their chromosomal profiles. Chromosomal profiles of CIN2/3 lesions were related to those of invasive cervical SCC and promoter methylation of CADM1, a tumor suppressor gene known to be functionally involved in the tumorigenic phenotype of cervical cancer cells. Frequent alterations found in CIN2/3 lesions included gains located at chromosome 1, 3, 7, and 20 and losses located at 4, 11, 16, 17, and 19. Unsupervised hierarchical clustering identified two subsets of CIN2/3 lesions, chromosomal profiles of one of which closely resembled invasive SCCs. Gains of 1, 3q, and 20 were characteristic for CIN2/3 lesions with chromosomal signatures resembling carcinomas. In addition, dense promoter methylation of the CADM1 gene was significantly more frequent in these CIN2/3 lesions (P = 0.004). No chromosomal alterations were detected in six CIN1 lesions, five of which were completely p16(INK4a) immunonegative. These findings suggest that biomarkers associated with gains at chromosomes 1, 3q, and 20 are potential hallmarks of advanced p16(INK4a)-positive CIN2/3 lesions with a high short-term risk of progression.

journal_name

Cancer Res

journal_title

Cancer research

authors

Wilting SM,Steenbergen RD,Tijssen M,van Wieringen WN,Helmerhorst TJ,van Kemenade FJ,Bleeker MC,van de Wiel MA,Carvalho B,Meijer GA,Ylstra B,Meijer CJ,Snijders PJ

doi

10.1158/0008-5472.CAN-08-2478

subject

Has Abstract

pub_date

2009-01-15 00:00:00

pages

647-55

issue

2

eissn

0008-5472

issn

1538-7445

pii

69/2/647

journal_volume

69

pub_type

杂志文章
  • CD155/PVR enhances glioma cell dispersal by regulating adhesion signaling and focal adhesion dynamics.

    abstract::We recently identified the immunoglobulin-CAM CD155/PVR (the poliovirus receptor) as a regulator of cancer invasiveness and glioma migration, but the mechanism through which CD155/PVR controls these processes is unknown. Here, we show that expression of CD155/PVR in rat glioma cells that normally lack this protein enh...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-1890

    authors: Sloan KE,Stewart JK,Treloar AF,Matthews RT,Jay DG

    更新日期:2005-12-01 00:00:00

  • Mechanism of action of the microtubule-targeted antimitotic depsipeptide tasidotin (formerly ILX651) and its major metabolite tasidotin C-carboxylate.

    abstract::Tasidotin (ILX-651), an orally active synthetic microtubule-targeted derivative of the marine depsipeptide dolastatin-15, is currently undergoing clinical evaluation for cancer treatment. Tasidotin inhibited proliferation of MCF7/GFP breast cancer cells with an IC(50) of 63 nmol/L and inhibited mitosis with an IC(50) ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3065

    authors: Ray A,Okouneva T,Manna T,Miller HP,Schmid S,Arthaud L,Luduena R,Jordan MA,Wilson L

    更新日期:2007-04-15 00:00:00

  • Macrophage content of spontaneous metastases at different stages of growth.

    abstract::The macrophage content of spontaneous metastases has been quantified morphometrically for a panel of rodent tumors at different stages of metastatic tumor growth. Using a histochemical technique to selectively stain macrophages, we have evaluated the relative content of macrophages in spontaneous pulmonary metastases ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bugelski PJ,Corwin SP,North SM,Kirsh RL,Nicolson GL,Poste G

    更新日期:1987-08-01 00:00:00

  • The interleukin-11 receptor alpha as a candidate ligand-directed target in osteosarcoma: consistent data from cell lines, orthotopic models, and human tumor samples.

    abstract::The interleukin-11 receptor alpha (IL-11Ralpha) is a functional target in bone metastasis. However, its role in primary bone tumors has not been established. As such, here, we evaluated IL-11Ralpha as a candidate target in primary and metastatic human osteosarcoma. First, in an orthotopic mouse model, we showed that I...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-4845

    authors: Lewis VO,Ozawa MG,Deavers MT,Wang G,Shintani T,Arap W,Pasqualini R

    更新日期:2009-03-01 00:00:00

  • Hepatic parenchymal cell glutamylation of methotrexate studied in monolayer culture.

    abstract::A detailed analysis of the gamma-glutamylation of methotrexate has been conducted in primary cultures of rat hepatic parenchymal cells in monolayer culture. The rates of glutamylation are concentration dependent and saturable when measured over a 6-h period at concentrations between 2 and 50 microM. The removal of fol...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Galivan J,Pupons A,Rhee MS

    更新日期:1986-02-01 00:00:00

  • Aptamer identification of brain tumor-initiating cells.

    abstract::Glioblastomas display cellular hierarchies with self-renewing tumor-initiating cells (TIC), also known as cancer stem cells, at the apex. Although the TIC hypothesis remains controversial and the functional assays to define the TIC phenotype are evolving, we and others have shown that TICs may contribute to therapeuti...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-4556

    authors: Kim Y,Wu Q,Hamerlik P,Hitomi M,Sloan AE,Barnett GH,Weil RJ,Leahy P,Hjelmeland AB,Rich JN

    更新日期:2013-08-01 00:00:00

  • Radioresistant cancer cells can be conditioned to enter senescence by mTOR inhibition.

    abstract::Autophagy is frequently activated in radioresistant cancer cells where it provides a cell survival strategy. The mTOR inhibitor rapamycin activates autophagy but paradoxically it also enhances radiosensitivity. In this study, we investigated the mechanisms of these opposing actions in radiation-resistant glioma or par...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-3516

    authors: Nam HY,Han MW,Chang HW,Lee YS,Lee M,Lee HJ,Lee BW,Lee HJ,Lee KE,Jung MK,Jeon H,Choi SH,Park NH,Kim SY,Kim SW

    更新日期:2013-07-15 00:00:00

  • Cancer immunotherapy using in vitro genetically modified targeted dendritic cells.

    abstract::Modest clinical outcomes of dendritic cell (DC) vaccine trials call for novel strategies. In this study, we have created a chimeric CD40 molecule that incorporates a single chain Fv (scFv) molecule specific for human ErbB2 antigen and fusing to the membrane spanning and cytosolic domains of murine CD40. After adenovir...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-6051

    authors: Wei H,Wang H,Lu B,Li B,Hou S,Qian W,Fan K,Dai J,Zhao J,Guo Y

    更新日期:2008-05-15 00:00:00

  • Factors influencing the anticarcinogenic efficacy of selenium in dimethylbenz[a]anthracene-induced mammary tumorigenesis in rats.

    abstract::The present study was designed to investigate the effect of selenium supplementation on dimethylbenz[a]anthracene-induced mammary tumorigenesis in female Sprague-Dawley rats fed either a 5 or 25% corn oil diet, denoted as low fat (LF) or high fat (HF), respectively. Selenium supplementation of LF and HF diets were beg...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ip C

    更新日期:1981-07-01 00:00:00

  • Role of the acetylation polymorphism in determining susceptibility of cultured rabbit hepatocytes to DNA damage by aromatic amines.

    abstract::In humans and rabbits, differences in the rate of N-acetylation of aromatic amines are under polymorphic genetic control. Individuals are classified as either rapid or slow acetylators. In the current study, the relationship between acetylator phenotype and susceptibility to the genotoxicities of benzidine, 4-aminobip...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: McQueen CA,Maslansky CJ,Williams GM

    更新日期:1983-07-01 00:00:00

  • Regression of rat mammary tumors by a potent luteinizing hormone-releasing hormone analogue (leuprolide) administered vaginally.

    abstract::Potent luteinizing hormone-releasing hormone analogues are known to cause regression of hormone-dependent mammary tumors. We have observed that high and long-lasting serum levels of a potent luteinizing hormone-releasing hormone analogue [desglycyl10-(D-leucyl6) luteinizing hormone-releasing hormone ethylamide, leupro...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Okada H,Sakura Y,Kawaji H,Yashiki T,Mima H

    更新日期:1983-04-01 00:00:00

  • Effect of nonspecific phospholipid transfer protein on cholesterol esterification in microsomes from Morris hepatomas.

    abstract::The content of cholesterol and cholesterol ester as well as the levels of acyl coenzyme A:cholesterol acyltransferase activity were determined in the microsomes from Morris hepatomas 7777, 5123D, and 7787. The free cholesterol content, expressed per mg microsomal protein, was significantly increased only in the micros...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: van Heusden GP,van der Krift TP,Hostetler KY,Wirtz KW

    更新日期:1983-09-01 00:00:00

  • Quantitative assessment of generalized epithelial changes in tracheal mucosa following exposure to 7,12-dimethylbenz(a)anthracene.

    abstract::Sequential morphological changes occurring after brief carcinogen exposures of heterotopic tracheal transplants in rats were semiquantitatively studied. Tracheas were exposed to 7,12-dimethylbenz(a)anthracene for 1, 2, or 4 weeks, during which time means of 138, 152, and 160 microgram 7,12-dimethylbenz(a)anthracene, r...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Topping DC,Griesemer RA,Nettesheim P

    更新日期:1979-12-01 00:00:00

  • Establishment of a human B-cell tumor in athymic mice.

    abstract::Human B-cell tumors have been established in athymic, BALB/c mice using the EBV-positive Burkitt lymphoma cell line Namalwa. One-hundred-one of 104 animals (97%) developed tumors 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated human fibrosarcoma (HT-1080) cells. Tumors d...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Leonard JE,Johnson DE,Felsen RB,Tanney LE,Royston I,Dillman RO

    更新日期:1987-06-01 00:00:00

  • Relationship of a Mr 140 fibronectin receptor and other adhesion-related glycoproteins to tumor cell-cell interaction.

    abstract::Primary melanocytes attach poorly to collagen type IV and laminin, in contrast to their firm attachment to collagen type I/III and fibronectin [Gilchrest et al., In vitro (Rockville), 21: 114-120, 1985]. We have now found that metastatic B16 melanoma cells attach well to collagen type IV, laminin, vitronectin, and fib...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rieber M,Gross A,Rieber MS

    更新日期:1987-10-01 00:00:00

  • Immunological detection of Chinese hamster ovary cells expressing a multidrug resistance phenotype.

    abstract::A monoclonal antibody (IgG1) has been prepared that specifically detects Chinese hamster ovary cells expressing a multidrug-resistant phenotype. This antibody recognizes the membrane P-glycoprotein (Mr 170,000) associated with drug resistance as determined by enzyme-linked immunosorbent assay with purified P-glycoprot...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Lathan B,Edwards DP,Dressler LG,Von Hoff DD,McGuire WL

    更新日期:1985-10-01 00:00:00

  • Adjuvant-antigen requirements for active specific immunotherapy of microscopic metastases remaining after surgery.

    abstract::We studied the conditions required for eradication by immunization of occult lymph node metastases which remained after surgical removal of an intradermally transplanted cavian hepatoma. Guinea pigs that received no postsurgical treatment all died with progressively growing lymph node metastases. The growth of these m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ashley MP,Zbar B,Hunter JT,Rapp HJ,Sugimoto T

    更新日期:1980-11-01 00:00:00

  • Pharmacological evaluation of experimental isolated liver perfusion and hepatic artery infusion with 5-fluorouracil.

    abstract::The intention of this study was to estimate the pharmacological advantage of a clinically applicable method of isolated liver perfusion (ILP) over hepatic artery infusion (HAI) administering various doses of 5-fluorouracil (FUra). FUra concentrations were measured using high-performance liquid chromatography in liver ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: de Brauw LM,Marinelli A,van de Velde CJ,Hermans J,Tjaden UR,Erkelens C,de Bruijn EA

    更新日期:1991-03-15 00:00:00

  • Identification and characterization of the insulin receptor in the R3230AC mammary adenocarcinoma of the rat.

    abstract::The binding of labeled insulin to dissociated R3230AC mammary adenocarcinoma cells from diabetic and intact rats was investigated in vitro. At 20 degrees, specific binding (total binding minus binding in the presence of 1000-fold excess or 10(-6) M unlabeled insulin) reached a plateau at 45 to 60 min and was directly ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Harmon JT,Hilf R

    更新日期:1976-11-01 00:00:00

  • Tumor-surrogate blood vessel subtypes exhibit differential susceptibility to anti-VEGF therapy.

    abstract::Antivascular therapy directed against VEGF or its receptors (VEGFR) has been successful when administered at early stages of tumor vessel growth but is less effective when administered later. Tumor blood vessels are heterogeneous, so vessel subpopulations may differ in their requirements for tumor cell-secreted VEGF a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-11-1693

    authors: Sitohy B,Nagy JA,Jaminet SC,Dvorak HF

    更新日期:2011-11-15 00:00:00

  • Presence of simian virus 40 DNA sequences in human lymphoid and hematopoietic malignancies and their relationship to aberrant promoter methylation of multiple genes.

    abstract::The simian polyoma virus SV40 has been detected in specific human tumors including non-Hodgkin's lymphomas, although a causative role for the virus has not been convincingly demonstrated. Aberrant methylation of CpG islands in promoter regions is a frequent method of silencing tumor suppressor genes (TSGs) in cancers ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-03-3307

    authors: Shivapurkar N,Takahashi T,Reddy J,Zheng Y,Stastny V,Collins R,Toyooka S,Suzuki M,Parikh G,Asplund S,Kroft SH,Timmons C,McKenna RW,Feng Z,Gazdar AF

    更新日期:2004-06-01 00:00:00

  • Iododeoxyuridine chemosensitization of cis-diamminedichloroplatinum(II) in human bladder cancer cells.

    abstract::We investigated the effect of iododeoxyuridine (IdUrd) exposure on cis-diamminedichloroplatinum (CDDP) cytotoxicity in the human bladder cancer cell line 647V. Following a 48-h incubation with 2-20 microM IdUrd, a 1-h exposure to 0-120 microM CDDP produced a dose-dependent increase in CDDP cytotoxicity as measured by ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chi KH,Kunugi KA,Kinsella TJ

    更新日期:1994-05-15 00:00:00

  • Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats.

    abstract::Irinotecan hydrochloride (CPT-11), an antitumor camptothecin derivative, causes severe forms of diarrhea clinically. We characterized CPT-11-induced diarrhea histologically and enzymologically and assessed the relationships between intestinal toxicity and the activity of the enzymes that play a key role in the major m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Takasuna K,Hagiwara T,Hirohashi M,Kato M,Nomura M,Nagai E,Yokoi T,Kamataki T

    更新日期:1996-08-15 00:00:00

  • Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

    abstract::Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-1420

    authors: Chinen Y,Kuroda J,Shimura Y,Nagoshi H,Kiyota M,Yamamoto-Sugitani M,Mizutani S,Sakamoto N,Ri M,Kawata E,Kobayashi T,Matsumoto Y,Horiike S,Iida S,Taniwaki M

    更新日期:2014-12-15 00:00:00

  • Induction of release of cytotoxin from murine bone marrow cells by an animal lectin.

    abstract::An animal lectin purified from loach (Misgurnus anguillicaudatus) eggs induced release of cytotoxin from fresh bone marrow cells from mice, although the other lectins tested, wheat germ agglutinin, concanavalin A, and phytohemagglutinin did not. The cytotoxin released from bone marrow cells was a heat-labile protein w...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Okutomi T,Nakajima Y,Sakakibara F,Kawauchi H,Yamazaki M

    更新日期:1987-01-01 00:00:00

  • In silico modeling and in vivo efficacy of cancer-preventive vaccinations.

    abstract::Cancer vaccine feasibility would benefit from reducing the number and duration of vaccinations without diminishing efficacy. However, the duration of in vivo studies and the huge number of possible variations in vaccination protocols have discouraged their optimization. In this study, we employed an established mouse ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-0701

    authors: Palladini A,Nicoletti G,Pappalardo F,Murgo A,Grosso V,Stivani V,Ianzano ML,Antognoli A,Croci S,Landuzzi L,De Giovanni C,Nanni P,Motta S,Lollini PL

    更新日期:2010-10-15 00:00:00

  • Genomic organization and mutation analysis of Hel-N1 in lung cancers with chromosome 9p21 deletions.

    abstract::Allelic loss of chromosome 9p21 is common in small cell lung cancer (SCLC), but inactivation of the tumor suppressor gene CDKN2a is rare, implying the existence of another target gene at 9p21. A recent deletion mapping study of chromosome 9p has also identified a site of deletion in non-small cell lung cancer (NSCLC) ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Cairns P,Okami K,King P,Bonacum J,Ahrendt S,Wu L,Mao L,Jen J,Sidransky D

    更新日期:1997-12-01 00:00:00

  • Translocation and activation of protein kinase C by the plasma cell tumor-promoting alkane pristane.

    abstract::Pristane (2,6,10,14-tetramethylpentadecane) is a C19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Janz S,Gawrisch K,Lester DS

    更新日期:1995-02-01 00:00:00

  • A retroinhibition approach reveals a tumor cell-autonomous response to rapamycin in head and neck cancer.

    abstract::Emerging evidence supporting the activation of the Akt-mammalian target of rapamycin (mTOR) signaling network in head and neck squamous cell carcinoma (HNSCC) progression has provided the rationale for exploring the therapeutic potential of inhibiting this pathway for HNSCC treatment. Indeed, rapamycin, a clinically r...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-1756

    authors: Amornphimoltham P,Patel V,Leelahavanichkul K,Abraham RT,Gutkind JS

    更新日期:2008-02-15 00:00:00

  • Induction of p21 by the Wilms' tumor suppressor gene WT1.

    abstract::WT1 encodes a zinc finger transcription factor that is expressed in the developing kidney and the inactivation of which leads to Wilms' tumor, a pediatric kidney cancer. We have recently shown that inducible expression of WT1 in osteosarcoma cells triggers programmed cell death, an effect that is associated with trans...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Englert C,Maheswaran S,Garvin AJ,Kreidberg J,Haber DA

    更新日期:1997-04-15 00:00:00