Hybrids of aneuploid human cancer cells permit complementation of simple and complex cancer defects.

Abstract:

:Causes for the complex phenotypes of cancers, such as altered differentiation, invasion and metastasis, are not known, and multigenic defects are likely. In contrast, well-defined deficiencies, such as those affecting DNA-repair mechanisms and enzymatic pathways, are simple, typically caused by one or a few gene mutations. Complementation by introducing defined genetic elements is used to study simple cancer phenotypes, while complementation by the fusion of whole cells is employed occasionally for complex ones. Hybrids formed solely from the common lines (aneuploid due to chromosomal instability, CIN) are rarely reported. We created stable hybrids of two CIN lines, producing a nearly complete genetic sum of the parental karyotypes. Complementation of a simple cancer phenotype, a Fanconi anemia pathway defective in both parental lines, occurred in all hybrids, restoring the normal drug-resistance phenotype. The grossly defective mitotic spindle checkpoint present in both parental lines was partially corrected in some hybrids, supporting a multigenic origin rather than a single gene defect. Using Affymetrix 100K SNP chips, we mapped chromosomal loci differing among the phenotypically distinct hybrid clones. Fusing CIN cell lines to form mapped hybrids offers new tools for positional cloning or classification of simple and complex cancer phenotypes, including mechanical defects and altered drug responses.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Dezentje DA,Arking DE,Kortenhorst MS,West K,Chakravarti A,Kern SE

doi

10.4161/cbt.8.4.7346

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

347-55

issue

4

eissn

1538-4047

issn

1555-8576

pii

7346

journal_volume

8

pub_type

杂志文章
  • Use of methotrexate-based peptide substrates to characterize the substrate specificity of prostate-specific membrane antigen (PSMA).

    abstract::Prostate-Specific Membrane Antigen (PSMA) is a glutamate carboxypeptidase II that is highly expressed by both normal and malignant prostate epithelial cells and by the neovasculature of many tumor types but is not expressed by endothelial cells in normal tissue. PSMA possesses the hydrolytic properties of an N-acetyla...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.3.6.846

    authors: Mhaka A,Gady AM,Rosen DM,Lo KM,Gillies SD,Denmeade SR

    更新日期:2004-06-01 00:00:00

  • Cancer stem cell and cancer stemloids: from biology to therapy.

    abstract::It has become a cliché that cancer therapy fails because it does not target rare cancer stem cells (CSCs). Here we are discuss that this is not how therapy fails and not any cancer cell with stem-like properties is CSC. Paradoxically, CSCs must be resting to explain their resistance to therapy yet must be cycling to e...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.6.11.5167

    authors: Blagosklonny MV

    更新日期:2007-11-01 00:00:00

  • Regulation of Myc function by ARF: checkpoint for Myc-induced oncogenesis.

    abstract::The alterative reading frame (ARF) protein is unique in its capacity to interact with Mdm2 thus facilitating p53-dependent cell cycle arrest and apoptosis. ARF also acts in a p53-independent manner in which it binds to Myc and interferes with transcriptional activation by Myc thereby inhibiting Myc-induced cell prolif...

    journal_title:Cancer biology & therapy

    pub_type: 评论,杂志文章

    doi:10.4161/cbt.5.6.2939

    authors: Sarkar D,Fisher PB

    更新日期:2006-06-01 00:00:00

  • Inhibition of MCL-1 in breast cancer cells promotes cell death in vitro and in vivo.

    abstract::The present studies have examined approaches to suppress MCL-1 function in breast cancer cells, as a means to promote tumor cell death. Treatment of breast cancer cells with CDK inhibitors (flavopiridol; roscovitine) enhanced the lethality of the ERBB1 inhibitor lapatinib in a synergistic fashion. CDK inhibitors inter...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.10.9.13273

    authors: Mitchell C,Yacoub A,Hossein H,Martin AP,Bareford MD,Eulitt P,Yang C,Nephew KP,Dent P

    更新日期:2010-11-01 00:00:00

  • Targeting hypoxia and angiogenesis through HIF-1alpha inhibition.

    abstract::Hypoxia is an important phenomenon in the tumor microenvironment. Hypoxic tumors are more aggressive and resistant to anti-neoplastic treatments. HIF-1alpha plays a major role in the response of tumors to hypoxia, and it is mainly responsible for the "angiogenic switch". HIF-1alpha contributes to tumor aggressiveness,...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.4.10.2195

    authors: Diaz-Gonzalez JA,Russell J,Rouzaut A,Gil-Bazo I,Montuenga L

    更新日期:2005-10-01 00:00:00

  • Small interfering RNA-induced CHFR silencing sensitizes oral squamous cell cancer cells to microtubule inhibitors.

    abstract::Alterations in the function of cell cycle checkpoints are frequently detected in oral squamous cell carcinomas (OSCCs), and are often associated with the sensitivity of the cancer cells to chemotherapeutic drugs. Recently, a mitotic checkpoint gene, Chfr, was shown to be inactivated by promoter methylation and point m...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.7.1896

    authors: Ogi K,Toyota M,Mita H,Satoh A,Kashima L,Sasaki Y,Suzuki H,Akino K,Nishikawa N,Noguchi M,Shinomura Y,Imai K,Hiratsuka H,Tokino T

    更新日期:2005-07-01 00:00:00

  • The genetics of FANCC and FANCG in familial pancreatic cancer.

    abstract::Patients with Fanconi anemia (FA) display a wide variety of defects including bone marrow failure and a high risk of developing cancer. Multiple Fanconi genes exist whose proteins form a complex that along with BRCA1 is important for the translocalization of FANCD2 to nuclear foci. With BRCA2 and RAD51, this complex i...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.3.2.609

    authors: Rogers CD,van der Heijden MS,Brune K,Yeo CJ,Hruban RH,Kern SE,Goggins M

    更新日期:2004-02-01 00:00:00

  • Mitogen-activated protein kinase phosphatase-1 inhibition and sustained extracellular signal-regulated kinase 1/2 activation in camptothecin-induced human colon cancer cell death.

    abstract::Camptothecins are commonly used chemotherapeutics; in some models, they enhance signaling via the mitogen-activated protein kinase (MAPK) pathway through effects on upstream kinases. To evaluate the impact of camptothecin (CPT) on MAPKs in human colon cancer, we studied HCT116 and CaCo2 colon cancer cells. We found th...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.26044

    authors: Lee M,Young Kim S,Kim J,Kim HS,Kim SM,Kim EJ

    更新日期:2013-11-01 00:00:00

  • DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.

    abstract::Current treatment modalities for pancreatic carcinoma afford only modest survival benefits. TRAIL, as a potent and specific inducer of apoptosis in cancer cells, would be a promising new treatment option. However, since not all pancreatic cancer cells respond to TRAIL, further improvements and optimizations are still ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/15384047.2014.972183

    authors: Yu R,Albarenque SM,Cool RH,Quax WJ,Mohr A,Zwacka RM

    更新日期:2014-01-01 00:00:00

  • Endometrial cancer with congenital uterine anomalies: 3 case reports and a literature review.

    abstract:BACKGROUND:Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present 3 cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.1080/15384047.2017.1281495

    authors: Gao J,Zhang J,Tian W,Teng F,Zhang H,Zhang X,Wang Y,Xue F

    更新日期:2017-03-04 00:00:00

  • Troglitazone-mediated sensitization to TRAIL-induced apoptosis is regulated by proteasome-dependent degradation of FLIP and ERK1/2-dependent phosphorylation of BAD.

    abstract::Resistance to apoptosis is one reason for the poor response of malignant brain tumors to therapy. The PPARgamma-modulating drug Troglitazone downregulates the anti-apoptotic FLIP protein and sensitizes glioblastoma cells to apoptosis induced by the death ligand TRAIL. To investigate the molecular basis of an experimen...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.7.12.6966

    authors: Grund K,Ahmadi R,Jung F,Funke V,Gdynia G,Benner A,Sykora J,Walczak H,Joos S,Felsberg J,Reifenberger G,Wiestler OD,Herold-Mende C,Roth W

    更新日期:2008-12-01 00:00:00

  • Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1, a novel epithelial-mesenchymal transition inducer in pancreatic cancer.

    abstract::Epithelial-mesenchymal transition (EMT) is a critical early event in tumorigenesis. The contribution of heparan sulfate (HS) to EMT has not been fully elucidated. HS D-glucosaminyl 3-O-sulfotransferase-3B1 (3-OST-3B1) participates in the final step of HS fine structure biosynthesis, whose involvement in cancer has yet...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.5.15957

    authors: Song K,Li Q,Jiang ZZ,Guo CW,Li P

    更新日期:2011-09-01 00:00:00

  • Absence of SV40 in Austrian tumors correlates with low incidence of mesotheliomas.

    abstract::Between 1955 and 1963 millions of people were worldwide vaccinated with polio-vaccines that were contaminated with the simian virus 40 (SV40). This tumor-inducing virus has subsequently been detected in several human tumors. In Austria, polio mass vaccination started in winter 1961/62 with a presumably SV40-free Briti...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:

    authors: Leithner A,Weinhaeusel A,Windhager R,Schlegl R,Waldner P,Lang S,Dominkus M,Zoubek A,Popper HH,Haas OA

    更新日期:2002-07-01 00:00:00

  • Downregulation of c-FLIP, XIAP and Mcl-1 protein as well as depletion of reduced glutathione contribute to the apoptosis induction of glycyrrhetinic acid derivatives in leukemia cells.

    abstract::The antiproliferative effects and apoptosis inducing abilities of four 18beta-glycyrrhetinic acid (GA) derivatives, methyl 2-cyano-3,11-dioxooleana-1,12-dien-30-oate (CDODO-Me-11), methyl 2-cyano-3,12-dioxooleana-1,12-dien-30-oate (CDODO-Me-12) and their non-esters were investigated in human leukemia cells. Methyl est...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.9.2.10287

    authors: Song D,Gao Y,Wang R,Liu D,Zhao L,Jing Y

    更新日期:2010-01-01 00:00:00

  • Functional significance of VEGF-a in human ovarian carcinoma: role in vasculogenic mimicry.

    abstract::Ovarian cancer is a silent killer, and shows early extensive tumor invasion and peritoneal metastasis. The microcirculation of most tumors includes cooperation of pre-existing vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis and vasculogenic mimicry (VM). VM is critical...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.7.5.5765

    authors: Wang JY,Sun T,Zhao XL,Zhang SW,Zhang DF,Gu Q,Wang XH,Zhao N,Qie S,Sun BC

    更新日期:2008-05-01 00:00:00

  • Phase II trial of bevacizumab and dose/dense chemotherapy with cisplatin and metronomic daily oral etoposide in advanced non-small-cell-lung cancer patients.

    abstract::Bevacizumab, is a humanized monoclonal antibody to vasculo-endothelial-growth-factor, with anticancer activity in non-small-cell-lung cancer (NSCLC) patients. Our previous results from a dose/finding phase I trial in NSCLC patients, demonstrated the anti-angiogenic effects and toxicity of a newest bevacizumab-based co...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.2.15722

    authors: Correale P,Botta C,Basile A,Pagliuchi M,Licchetta A,Martellucci I,Bestoso E,Apollinari S,Addeo R,Misso G,Romano O,Abbruzzese A,Lamberti M,Luzzi L,Gotti G,Rotundo MS,Caraglia M,Tagliaferri P

    更新日期:2011-07-15 00:00:00

  • Lenalidomide in combination with gemcitabine as first-line treatment for patients with metastatic carcinoma of the pancreas: a Sarah Cannon Research Institute phase II trial.

    abstract:OBJECTIVES:To evaluate the 6-mo overall survival, safety and tolerability of lenalidomide in combination with standard gemcitabine as first-line treatment for patients with metastatic pancreatic cancer. METHODS:Eligibility included: previously untreated metastatic adenocarcinoma of the pancreas with metastases incurab...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,多中心研究

    doi:10.4161/cbt.23625

    authors: Infante JR,Arkenau HT,Bendell JC,Rubin MS,Waterhouse D,Jones GT,Spigel DR,Lane CM,Hainsworth JD,Burris HA 3rd

    更新日期:2013-04-01 00:00:00

  • Sunitinib inhibits papillary thyroid carcinoma with RET/PTC rearrangement but not BRAF mutation.

    abstract::Sunitinib, a multi-targeted tyrosine kinase inhibitor, is frequently incorporated into the management of papillary thyroid carcinoma refractory to standard therapies. Although clinical trials are in progress, the mechanism of action in papillary thyroid carcinomas is not clear, especially regarding the effect on BRAF ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.5.16303

    authors: Jeong WJ,Mo JH,Park MW,Choi IJ,An SY,Jeon EH,Ahn SH

    更新日期:2011-09-01 00:00:00

  • Chimeric cytokine receptor enhancing PSMA-CAR-T cell-mediated prostate cancer regression.

    abstract::Objective: Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated an unprecedented therapeutic efficacy in hematological malignancies; however, its effectiveness in solid tumors remains elusive. In order to enable CAR-T cells more effective to solid tumors, a inverted chimeric cytokine receptor (ICR) was de...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2020.1739952

    authors: Weimin S,Abula A,Qianghong D,Wenguang W

    更新日期:2020-06-02 00:00:00

  • Down-regulation of KLF5 in cancer-associated fibroblasts inhibit gastric cancer cells progression by CCL5/CCR5 axis.

    abstract::It was well known that cancer-associated fibroblasts (CAFs) were an essential factor in tumor progression. However, the actual mechanism of stromal fibroblasts activation and tumor promoting effects remain unclear. Here, we showed that KLF5 expression was more frequently observed in gastric cancer-associated fibroblas...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2017.1373219

    authors: Yang T,Chen M,Yang X,Zhang X,Zhang Z,Sun Y,Xu B,Hua J,He Z,Song Z

    更新日期:2017-10-03 00:00:00

  • New paradigms for cancer drug discovery.

    abstract::Discovering drugs has never been an easy task. Traditionally, this task has exclusively been undertaken by large pharmaceutical companies that recovered their high research and development costs by selling expensive medications. Despite the huge amount of time and effort devoted towards drug discovery over the last de...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.2.4.448

    authors: Sager JA,Lengauer C

    更新日期:2003-07-01 00:00:00

  • Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with nilotinib against BCR-ABL-positive leukemia cells involves the ABL kinase domain mutation.

    abstract::Imatinib, an ABL tyrosine kinase inhibitor (TKI), has shown clinical efficacy against chronic myeloid leukemia (CML). However, a substantial number of patients develop resistance to imatinib treatment due to the emergence of clones carrying mutations in the protein BCR-ABL. The phosphoinositide 3 kinase (PI3K)/Akt/mam...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.26725

    authors: Okabe S,Tauchi T,Tanaka Y,Kitahara T,Kimura S,Maekawa T,Ohyashiki K

    更新日期:2014-02-01 00:00:00

  • Epidermal growth factor receptor plays a significant role in hepatocyte growth factor mediated biological responses in mammary epithelial cells.

    abstract::Breast cancers often have deregulated hepatocyte growth factor (HGF) and c-Met signaling that results in increased tumor growth and invasion. Elucidating the mechanism responsible for HGF/c-Met action in breast cancer progression has been difficult as c-Met communicates with a number of secondary receptors that can le...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.4.3851

    authors: Bonine-Summers AR,Aakre ME,Brown KA,Arteaga CL,Pietenpol JA,Moses HL,Cheng N

    更新日期:2007-04-01 00:00:00

  • Increasing the therapeutic index of 5-fluorouracil and 6-thioguanine by targeting loss of MTAP in tumor cells.

    abstract::Methylthioadenosine phosphorylase (MTAP), a key enzyme in the catabolism of 5'-deoxy-5'-methylthioadenosine (MTA), catalyzes the formation of adenine and 5-methylthioribose-1-phosphate. MTAP is expressed in all cells throughout the body, but a significant percentage of human tumors have lost MTAP expression, thereby m...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.21115

    authors: Tang B,Testa JR,Kruger WD

    更新日期:2012-09-01 00:00:00

  • Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

    abstract:BACKGROUND AND AIM:Widespread applicability of tissue-based mRNA expression screening for Barrett esophagus (BE) is likely to require (1) accurate methods for assaying archival formalin-fixed, paraffin-embedded (FFPE) histopathology specimens taken at endoscopy, and (2) validation studies of promising biomarkers in dif...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.10.2.12166

    authors: Botelho NK,Schneiders FI,Lord SJ,Freeman AK,Tyagi S,Nancarrow DJ,Hayward NK,Whiteman DC,Lord RV

    更新日期:2010-07-15 00:00:00

  • Synergistic effect of resveratrol and HSV-TK/GCV therapy on murine hepatoma cells.

    abstract::Despite its low transfer efficiency, suicide gene therapy with HSV-TK is known for its bystander killing effect. The connexin-based gap junction is believed to mediate the bystander effect. Recently, we found that resveratrol, a polyphenol compound, increased the expression of Cx26 and Cx43, which are connexins and im...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2018.1523094

    authors: Xiao J,Wang X,Wu Y,Zhao Q,Liu X,Zhang G,Zhao Z,Ning Y,Wang K,Tan Y,Du B

    更新日期:2019-01-01 00:00:00

  • Hes1: a key role in stemness, metastasis and multidrug resistance.

    abstract::Hes1 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability. Recent studies have shown that Hes1 functions in the maintenance of cancer stem cells (CSCs)...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.1080/15384047.2015.1016662

    authors: Liu ZH,Dai XM,Du B

    更新日期:2015-01-01 00:00:00

  • Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses.

    abstract::As a kinase at the crossroads of numerous metabolic and cell growth signaling pathways, glycogen synthase kinase-3 beta (GSK-3β) is a highly desirable therapeutic target in cancer. Despite its involvement in pathways associated with the pathogenesis of several malignancies, no selective GSK-3β inhibitor has been appro...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.1080/15384047.2019.1595283

    authors: Sahin I,Eturi A,De Souza A,Pamarthy S,Tavora F,Giles FJ,Carneiro BA

    更新日期:2019-01-01 00:00:00

  • A targeted IL-15 fusion protein with potent anti-tumor activity.

    abstract::IL-15 has been actively investigated for its potential in tumor immunotherapy. To enhance the anti-tumor activity of IL-15, the novel PFC-1 construct was designed, which comprises the following 3 parts: (1) IL-15Rα fused with IL-15 to enhance IL-15 activity, (2) an Fc fragment to increase protein half-life, and (3) an...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1071739

    authors: Chen S,Huang Q,Liu J,Xing J,Zhang N,Liu Y,Wang Z,Li Q

    更新日期:2015-01-01 00:00:00

  • A prospective comparision of sequential chemoradiation vs concurrent chemoradiation in locally advanced oropharyngeal carcinomas.

    abstract:PURPOSE:Induction chemotherapy has shown to provide consistent benefit for local control in primary treatment of advanced oropharyngeal cancer. The beneficial role of chemoradiation following induction chemotherapy over concurrent chemoradiation has not been evaluated. Present study evaluates the same prospectively. R...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,随机对照试验

    doi:10.4161/cbt.8.3.7484

    authors: Gupta D,Shukla P,Bisht SS,Dhawan A,Pant MC,Bhatt ML,Gupta S,Gupta R,Negi MP

    更新日期:2009-02-01 00:00:00