CF101, an agonist to the A3 adenosine receptor, enhances the chemotherapeutic effect of 5-fluorouracil in a colon carcinoma murine model.

Abstract:

:NF-kappaB and the upstream kinase PKB/Akt are highly expressed in chemoresistance tumor cells and may hamper the apoptotic pathway. CF101, a specific agonist to the A3 adenosine receptor (A3AR), inhibits the development of colon carcinoma growth in cell cultures and xenograft murine models. Because CF101 has been shown to downregulate PKB/Akt and NF-kappaB protein expression level, we presumed that its combination with chemotherapy will enhance the antitumor effect of the cytotoxic drug. In this study, we utilized 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays and a colon carcinoma xenograft model. It has been shown that a combined treatment of CF101 and 5-fluorouracil (5-FU) enhanced the cytotoxic effect of the latter on HCT-116 human colon carcinoma cell proliferation and tumor growth. Downregulation of PKB/Akt, NF-kappaB, and cyclin D1, and upregulation of caspase-3 protein expression level were observed in cells and tumor lesions on treatment with a combination of CF101 and 5-FU. Moreover, in mice treated with the combined therapy, myelotoxicity was prevented as was evidenced by normal white blood cell and neutrophil counts. These results show that CF101 potentiates the cytotoxic effect of 5-FU, thus preventing drug resistance. The myeloprotective effect of CF101 suggests its development as an add-on treatment to 5-FU.

journal_name

Neoplasia

authors

Bar-Yehuda S,Madi L,Silberman D,Gery S,Shkapenuk M,Fishman P

doi

10.1593/neo.04364

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

85-90

issue

1

eissn

1522-8002

issn

1476-5586

journal_volume

7

pub_type

杂志文章
  • Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro.

    abstract::Transforming growth factor-beta1 (TGF-beta1) can be tumor-suppressive through the activation of the Smad-mediated signaling pathway. TGF-beta1 can also enhance tumor progression by stimulating epithelial-to-mesenchymal transition (EMT) through additional pathways. EMT is characterized by the acquisition of a fibroblas...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04241

    authors: Xie L,Law BK,Chytil AM,Brown KA,Aakre ME,Moses HL

    更新日期:2004-09-01 00:00:00

  • Optical tomography of MMP activity allows a sensitive noninvasive characterization of the invasiveness and angiogenesis of SCC xenografts.

    abstract::For improved tumor staging and therapy control, imaging biomarkers are of great interest allowing a noninvasive characterization of invasiveness. In squamous epithelial skin and cervix lesions, transition to invasive stages is associated with enhanced matrix metalloproteinase (MMP) activity, increased angiogenesis, an...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.03.005

    authors: Al Rawashdeh W,Arns S,Gremse F,Ehling J,Knüchel-Clarke R,Kray S,Spöler F,Kiessling F,Lederle W

    更新日期:2014-03-01 00:00:00

  • In vivo confocal fluorescence imaging of the intratumor distribution of the photosensitizer mono-L-aspartylchlorin-e6.

    abstract::We present an in vivo fluorescence microscopic evaluation of intratumor distribution of the photosensitizer mono-L-aspartylchlorin-e6 (NPe6) in an intradermal mouse EMT6 tumor model. Although the identification of favorable photophysical and pharmacological properties has led to the development of new photosensitizers...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.08104

    authors: Mitra S,Foster TH

    更新日期:2008-05-01 00:00:00

  • Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/β-catenin pathway.

    abstract::Chromobox 4 (CBX4) is a core component of polycomb-repressive complex 1 with important roles in cancer biology and tissue homeostasis. Aberrant expression of CBX4 has been implicated in several human malignancies. However, its role and underlying mechanisms in the tumorigenesis of lung adenocarcinoma (LUAD) have not b...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.12.005

    authors: Wang Z,Fang Z,Chen G,Liu B,Xu J,Li F,Li F,Liu H,Zhang H,Sun Y,Tian G,Chen H,Xu G,Zhang L,Hu L,Ji H

    更新日期:2021-02-01 00:00:00

  • Longitudinal magnetic resonance imaging-based assessment of vascular changes and radiation response in androgen-sensitive prostate carcinoma xenografts under androgen-exposed and androgen-deprived conditions.

    abstract::Prostate cancer (PCa) patients receive androgen-deprivation therapy (ADT) to reduce tumor burden. However, complete eradication of PCa is unusual, and recurrent disease is evident within approximately 2 years in high-risk patients. Clinical evidence suggests that combining ADT with radiotherapy improves local control ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.10484

    authors: Røe K,Seierstad T,Kristian A,Mikalsen LT,Mælandsmo GM,van der Kogel AJ,Ree AH,Olsen DR

    更新日期:2010-10-01 00:00:00

  • Immune Signature-Based Subtypes of Cervical Squamous Cell Carcinoma Tightly Associated with Human Papillomavirus Type 16 Expression, Molecular Features, and Clinical Outcome.

    abstract::Substantial heterogeneity exists within cervical cancer that is generally infected by human papillomavirus (HPV). However, the most common histological subtype of cervical cancer, cervical squamous cell carcinoma (CSCC), is poorly characterized regarding the association between its heterogeneity and HPV oncoprotein ex...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.04.003

    authors: Lu X,Jiang L,Zhang L,Zhu Y,Hu W,Wang J,Ruan X,Xu Z,Meng X,Gao J,Su X,Yan F

    更新日期:2019-06-01 00:00:00

  • Telomere length on chromosome 17q shortens more than global telomere length in the development of breast cancer.

    abstract::It is known that total telomere length is shorter in invasive breast cancer than in normal breast tissue but the status of individual telomere lengths has not been studied. Part of the difficulty is that usually telomere length in interphase cells is measured on all chromosomes together. In this study we compared norm...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07106

    authors: Rashid-Kolvear F,Pintilie M,Done SJ

    更新日期:2007-04-01 00:00:00

  • An alternate splicing variant of the human telomerase catalytic subunit inhibits telomerase activity.

    abstract::Telomerase, a cellular reverse transcriptase, adds telomeric repeats to chromosome ends. In normal human somatic cells, telomerase is repressed and telomeres progressively shorten, leading to proliferative senescence. Introduction of the telomerase (hTERT) cDNA is sufficient to produce telomerase activity and immortal...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900113

    authors: Yi X,White DM,Aisner DL,Baur JA,Wright WE,Shay JW

    更新日期:2000-09-01 00:00:00

  • Current Evidence and Future Perspectives on HuR and Breast Cancer Development, Prognosis, and Treatment.

    abstract::Hu-antigen R (HuR) is an RNA-binding posttranscriptional regulator that belongs to the Hu/ELAV family. HuR expression levels are modulated by a variety of proteins, microRNAs, chemical compounds, or the microenvironment, and in turn, HuR affects mRNA stability and translation of various genes implicated in breast canc...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章,评审

    doi:10.1016/j.neo.2016.09.002

    authors: Kotta-Loizou I,Vasilopoulos SN,Coutts RH,Theocharis S

    更新日期:2016-11-01 00:00:00

  • Progressive genomic instability in the Nup98-HoxD13 model of MDS correlates with loss of the PIG-A gene product.

    abstract::The Nup98-HoxD13 (NHD13) fusion gene was identified in a patient with therapy-related myelodysplastic syndrome (MDS). When transgenically expressed in hematopoietic cells, mice faithfully recapitulate human disease with serial progression from peripheral blood (PB) cytopenias and increased bone marrow (BM) blasts to a...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.07.004

    authors: Byrne M,Bennett RL,Cheng X,May WS

    更新日期:2014-08-01 00:00:00

  • Targeting antiapoptotic Bcl-2 family members with cell-permeable BH3 peptides induces apoptosis signaling and death in head and neck squamous cell carcinoma cells.

    abstract::Head and neck squamous cell carcinomas (HNSCC) are frequently characterized by chemotherapy and radiation resistance, and by overexpression of Bcl-XL, an antiapoptotic member of the Bcl-2 protein family. In this report we examined whether cell-permeable peptides derived from the BH3 domains of proapoptotic Bax, Bad, o...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07394

    authors: Li R,Boehm AL,Miranda MB,Shangary S,Grandis JR,Johnson DE

    更新日期:2007-10-01 00:00:00

  • Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors.

    abstract::The epidermal growth factor receptor (EGFR) has been targeted for inhibition using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in outcome in subsets of patients with head and neck, lung, and colorectal carcinomas. We have previously found that EGFR stability plays a key role in cell survival...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.12986

    authors: Ahsan A,Ramanand SG,Whitehead C,Hiniker SM,Rehemtulla A,Pratt WB,Jolly S,Gouveia C,Truong K,Van Waes C,Ray D,Lawrence TS,Nyati MK

    更新日期:2012-08-01 00:00:00

  • BJ-TSA-9, a novel human tumor-specific gene, has potential as a biomarker of lung cancer.

    abstract::Using bioinformatics, we have identified a novel tumor-specific gene BJ-TSA-9, which has been validated by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). BJ-TSA-9 mRNA was expressed in 52.5% (21 of 40) of human lung cancer tissues and was especially higher in lung adenocarcinoma (...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.05406

    authors: Li Y,Dong X,Yin Y,Su Y,Xu Q,Zhang Y,Pang X,Zhang Y,Chen W

    更新日期:2005-12-01 00:00:00

  • Loss of p12CDK2-AP1 expression in human oral squamous cell carcinoma with disrupted transforming growth factor-beta-Smad signaling pathway.

    abstract::We examined correlations between TGF-beta1, TbetaR-I and TbetaR-II, p12(CDK2-AP1), p21(WAF1), p27(KIP1), Smad2, and p-Smad2 in 125 cases of human oral squamous cell carcinoma (OSCC) to test the hypothesis that resistance to TGF-beta1-induced growth suppression is due to the disruption of its signaling pathway as a con...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.06580

    authors: Peng H,Shintani S,Kim Y,Wong DT

    更新日期:2006-12-01 00:00:00

  • Bypass of tumor drug resistance by antivascular therapy.

    abstract::Multidrug resistance (MDR) presents a major obstacle for the successful chemotherapy of cancer. Its emergence during chemotherapy is attributed to a selective process, which gives a growth advantage to MDR cells within the genetically unstable neoplastic cell population. The pleiotropic nature of clinical MDR poses a ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/s1476-5586(03)80031-3

    authors: Preise D,Mazor O,Koudinova N,Liscovitch M,Scherz A,Salomon Y

    更新日期:2003-11-01 00:00:00

  • Comprehensive Investigation of miRNome Identifies Novel Candidate miRNA-mRNA Interactions Implicated in T-Cell Acute Lymphoblastic Leukemia.

    abstract::T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy originating from T-cell precursors. The genetic landscape of T-ALL has been largely characterized by next-generation sequencing. Yet, the transcriptome of miRNAs (miRNome) of T-ALL has been less extensively studied. Using small RNA sequencing, we ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.01.004

    authors: Dawidowska M,Jaksik R,Drobna M,Szarzyńska-Zawadzka B,Kosmalska M,Sędek Ł,Machowska L,Lalik A,Lejman M,Ussowicz M,Kałwak K,Kowalczyk JR,Szczepański T,Witt M

    更新日期:2019-03-01 00:00:00

  • p27KIP1 deletions in childhood acute lymphoblastic leukemia.

    abstract::The p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK) inhibitor, has been assigned to chromosome band 12p12, a region often affected by cytogenetically apparent deletions or translocations in childhood acute lymphoblastic leukemia (ALL). As described here, fluorescence in situ hybridization (FISH) analysis o...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900033

    authors: Komuro H,Valentine MB,Rubnitz JE,Saito M,Raimondi SC,Carroll AJ,Yi T,Sherr CJ,Look AT

    更新日期:1999-08-01 00:00:00

  • CCL2 is a potent regulator of prostate cancer cell migration and proliferation.

    abstract::Tumor cells in the bone interact with the microenvironment to promote tumor cell survival and proliferation, resulting in a lethal phenotype for patients with advanced prostate cancer. Monocyte chemoattractant protein 1 (CCL2) is a member of the CC chemokine family and is known to promote monocyte chemotaxis to sites ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.06280

    authors: Loberg RD,Day LL,Harwood J,Ying C,St John LN,Giles R,Neeley CK,Pienta KJ

    更新日期:2006-07-01 00:00:00

  • Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells.

    abstract::BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAFV600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current frontline therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactiva...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.02.009

    authors: Mologni L,Costanza M,Sharma GG,Viltadi M,Massimino L,Citterio S,Purgante S,Raman H,Pirola A,Zucchetti M,Piazza R,Gambacorti-Passerini C

    更新日期:2018-05-01 00:00:00

  • Multitargeted low-dose GLAD combination chemoprevention: a novel and promising approach to combat colon carcinogenesis.

    abstract::Preclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD) are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemo...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.13282

    authors: Mohammed A,Janakiram NB,Brewer M,Vedala K,Steele VE,Rao CV

    更新日期:2013-05-01 00:00:00

  • Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas.

    abstract::We recently identified 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate pathway, as a potential therapeutic target of the head and neck squamous cell carcinomas (HNSCC) and cervical carcinomas (CC). The products of this complex biochemical pathway, including de novo...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900247

    authors: Dimitroulakos J,Marhin WH,Tokunaga J,Irish J,Gullane P,Penn LZ,Kamel-Reid S

    更新日期:2002-07-01 00:00:00

  • A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain Tumors.

    abstract::Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors. The survival for patients with glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%, this figure has stagnated over the past few decades and survivors still contend with s...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.02.004

    authors: Endersby R,Whitehouse J,Hii H,Greenall SA,Johns TG,Gottardo NG

    更新日期:2018-05-01 00:00:00

  • Bcl-2 and M-Myc coexpression increases IGF-IR and features of malignant growth in neuroblastoma cell lines.

    abstract::The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 co...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900171

    authors: Jasty R,van Golen C,Lin HJ,Solomon G,Heidelberger K,Polverini P,Opipari A,Feldman E,Castle VP

    更新日期:2001-07-01 00:00:00

  • Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells.

    abstract::Although Chk1 kinase inhibitors are currently under clinical investigation as effective cancer cell sensitizers to the cytotoxic effects of numerous chemotherapeutics, there is still a considerable uncertainty regarding their role in modulation of anticancer potential of platinum-based drugs. Here we newly demonstrate...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.08.002

    authors: Herůdková J,Paruch K,Khirsariya P,Souček K,Krkoška M,Vondálová Blanářová O,Sova P,Kozubík A,Hyršlová Vaculová A

    更新日期:2017-10-01 00:00:00

  • Human pancreatic carcinoma cells activate maspin expression through loss of epigenetic control.

    abstract::The maspin gene is not expressed in normal human pancreas, but its expression is acquired during human pancreatic carcinogenesis. In other normal human cells and their malignant counterparts, maspin expression is controlled through the epigenetic state of its promoter. In studies presented herein, we used bisulfite ge...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/s1476-5586(03)80045-3

    authors: Fitzgerald M,Oshiro M,Holtan N,Krager K,Cullen JJ,Futscher BW,Domann FE

    更新日期:2003-09-01 00:00:00

  • Neoplastic transformation induced by the gep oncogenes involves the scaffold protein JNK-interacting leucine zipper protein.

    abstract::The activated mutants of the α-subunits of G proteins G(12) and G(13) have been designated as the gep oncogenes owing to their ability to stimulate diverse oncogenic signaling pathways that lead to neoplastic transformation of fibroblast cell lines and tumorigenesis in nude mice models. Studies from our laboratory as ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.101622

    authors: Kashef K,Radhakrishnan R,Lee CM,Reddy EP,Dhanasekaran DN

    更新日期:2011-04-01 00:00:00

  • Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia.

    abstract::Anoikis, a cell death mechanism triggered upon cell-matrix detachment, is regarded as a physiological suppressor of metastasis that can be regulated by a diverse array of signals. The protein encoded by GDF2 is BMP9 and is a member of the bone morphogenetic protein family and the transforming growth factor (TGF) β sup...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.11.003

    authors: Varadaraj A,Patel P,Serrao A,Bandyopadhay T,Lee NY,Jazaeri AA,Huang Z,Murphy SK,Mythreye K

    更新日期:2015-11-01 00:00:00

  • A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma.

    abstract::Melanomas are highly radioresistant tumors, mainly due to efficient DNA double-strand break (DSB) repair. Dbait (which stands for DNA strand break bait) molecules mimic DSBs and trap DNA repair proteins, thereby inhibiting repair of DNA damage induced by radiation therapy (RT). First, the cytotoxic efficacy of Dbait i...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.08.008

    authors: Biau J,Devun F,Jdey W,Kotula E,Quanz M,Chautard E,Sayarath M,Sun JS,Verrelle P,Dutreix M

    更新日期:2014-10-23 00:00:00

  • B cells are critical to T-cell-mediated antitumor immunity induced by a combined immune-stimulatory/conditionally cytotoxic therapy for glioblastoma.

    abstract::We have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding the conditional cytotoxic molecule, i.e., HSV1-TK and the immune-stimulatory cytokine, i.e., fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent tumor regression in rod...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.11024

    authors: Candolfi M,Curtin JF,Yagiz K,Assi H,Wibowo MK,Alzadeh GE,Foulad D,Muhammad AK,Salehi S,Keech N,Puntel M,Liu C,Sanderson NR,Kroeger KM,Dunn R,Martins G,Lowenstein PR,Castro MG

    更新日期:2011-10-01 00:00:00

  • An estrogen receptor-alpha/p300 complex activates the BRCA-1 promoter at an AP-1 site that binds Jun/Fos transcription factors: repressive effects of p53 on BRCA-1 transcription.

    abstract::One of the puzzles in cancer predisposition is that women carrying BRCA-1 mutations preferentially develop tumors in epithelial tissues of the breast and ovary. Moreover, sporadic breast tumors contain lower levels of BRCA-1 in the absence of mutations in the BRCA-1 gene. The problem of tissue specificity requires ana...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.05256

    authors: Jeffy BD,Hockings JK,Kemp MQ,Morgan SS,Hager JA,Beliakoff J,Whitesell LJ,Bowden GT,Romagnolo DF

    更新日期:2005-09-01 00:00:00