JAK kinase inhibition abrogates STAT3 activation and head and neck squamous cell carcinoma tumor growth.

Abstract:

:Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC). AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in several cancer models. In the present study, the in vitro and in vivo effects of AZD1480 were evaluated in HNSCC preclinical models to test the potential use of JAK kinase inhibition for HNSCC therapy. AZD1480 treatment decreased HNSCC proliferation in HNSCC cell lines with half maximal effective concentration (EC50) values ranging from 0.9 to 4 μM in conjunction with reduction of pSTAT3(Tyr705) expression. In vivo antitumor efficacy of AZD1480 was demonstrated in patient-derived xenograft (PDX) models derived from two independent HNSCC tumors. Oral administration of AZD1480 reduced tumor growth in conjunction with decreased pSTAT3(Tyr705) expression that was observed in both PDX models. These findings suggest that the JAK1/2 inhibitors abrogate STAT3 signaling and may be effective in HNSCC treatment approaches.

journal_name

Neoplasia

authors

Sen M,Pollock NI,Black J,DeGrave KA,Wheeler S,Freilino ML,Joyce S,Lui VW,Zeng Y,Chiosea SI,Grandis JR

doi

10.1016/j.neo.2015.01.003

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

256-64

issue

3

eissn

1522-8002

issn

1476-5586

pii

S1476-5586(15)00014-7

journal_volume

17

pub_type

杂志文章
  • Interdependence of gemcitabine treatment, transporter expression, and resistance in human pancreatic carcinoma cells.

    abstract::Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU) alters the cellular transporter expression profile and that modulation of the exp...

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

    pub_type: 杂志文章

    doi:10.1593/neo.10576

    authors: Hagmann W,Jesnowski R,Löhr JM

    更新日期:2010-09-01 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

  • Isolation of a novel human gene, MARKL1, homologous to MARK3 and its involvement in hepatocellular carcinogenesis.

    abstract::Activation of the Wnt-signaling pathway is known to play a crucial role in carcinogenesis of various human organs including the colon, liver, prostate, and endometrium. To investigate the mechanisms underlying hepatocellular carcinogenesis, we attempted to identify genes regulated by beta-catenin/Tcf complex in a huma...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900132

    authors: Kato T,Satoh S,Okabe H,Kitahara O,Ono K,Kihara C,Tanaka T,Tsunoda T,Yamaoka Y,Nakamura Y,Furukawa Y

    更新日期:2001-01-01 00:00:00

  • Strain background determines lymphoma incidence in Atm knockout mice.

    abstract::About 10% to 30% of patients with ataxia-telangiectasia (A-T) develop leukemias or lymphomas. There is considerable interpatient variation in the age of onset and leukemia/lymphoma type. The incomplete penetrance and variable age of onset may be attributable to several factors. These include competing mortality from o...

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

    pub_type: 杂志文章

    doi:10.1593/neo.131980

    authors: Genik PC,Bielefeldt-Ohmann H,Liu X,Story MD,Ding L,Bush JM,Fallgren CM,Weil MM

    更新日期:2014-02-01 00:00:00

  • FOXF1 Induces Epithelial-Mesenchymal Transition in Colorectal Cancer Metastasis by Transcriptionally Activating SNAI1.

    abstract::Forkhead Box F1 (FOXF1) has been recently implicated in cancer progression and metastasis of lung cancer and breast cancer. However, the biological functions and underlying mechanisms of FOXF1 in the regulation of the progression of colorectal cancer (CRC) are largely unknown. We showed that FOXF1 was up-regulated in ...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.08.004

    authors: Wang S,Yan S,Zhu S,Zhao Y,Yan J,Xiao Z,Bi J,Qiu J,Zhang D,Hong Z,Zhang L,Huang C,Li T,Liang L,Liao W,Jiao H,Ding Y,Ye Y

    更新日期:2018-10-01 00:00:00

  • Circulating endothelial cells, endothelial progenitor cells, and endothelial microparticles in cancer.

    abstract::Cancer, a proliferative disease hallmarked by abnormal cell growth and spread, is largely dependent on tumor neoangiogenesis, with evidence of vascular endothelial dysfunction. Novel ways to assess vascular function in cancer include measuring levels of circulating endothelial cells (CEC). Rare in healthy individuals,...

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

    pub_type: 杂志文章,评审

    doi:10.1593/neo.05592

    authors: Goon PK,Lip GY,Boos CJ,Stonelake PS,Blann AD

    更新日期:2006-02-01 00:00:00

  • Protein Phosphatase 1 Regulatory Subunit SDS22 Inhibits Breast Cancer Cell Tumorigenesis by Functioning as a Negative Regulator of the AKT Signaling Pathway.

    abstract::Protein phosphatases play a crucial role in cell cycle progression, cell survival, cellular signaling, and genomic integrity. The protein phosphatase 1 (PP1) regulatory subunit SDS22 plays a significant role in cell cycle progression. A recent study showed that SDS22 plays a vital role in epithelial integrity and tumo...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.10.009

    authors: Paul D,Bargale AB,Rapole S,Shetty PK,Santra MK

    更新日期:2019-01-01 00:00:00

  • Tel, a frequent target of leukemic translocations, induces cellular aggregation and influences expression of extracellular matrix components.

    abstract::Tel is an Ets transcription factor that is the target of chromosome translocations in lymphoid and myeloid leukemias and in solid tumors. It contains two functional domains, a pointed oligomerization domain and a DNA-binding domain. Retroviral transduction of a wild-type Tel cDNA into a clonal subline of NIH3T3 fibrob...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900064

    authors: Van Rompaey L,Dou W,Buijs A,Grosveld G

    更新日期:1999-12-01 00:00:00

  • Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma.

    abstract::Slits are a group of secreted glycoproteins that play a role in the regulation of cell migration. Previous studies suggested that Slit2 might be a tumor-suppressor gene. However, it remained to be determined whether Slit2 suppressed tumor growth and metastasis in animal models. We showed that Slit2 expression was decr...

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

    pub_type: 杂志文章

    doi:10.1593/neo.08804

    authors: Kim HK,Zhang H,Li H,Wu TT,Swisher S,He D,Wu L,Xu J,Elmets CA,Athar M,Xu XC,Xu H

    更新日期:2008-12-01 00:00:00

  • TGFBR2 mediated phosphorylation of BUB1 at Ser-318 is required for transforming growth factor-β signaling.

    abstract::BUB1 (budding uninhibited by benzimidazoles-1) is required for efficient TGF-β signaling, through its role in stabilizing the TGFBR1 and TGFBR2 complex. Here we demonstrate that TGFBR2 phosphorylates BUB1 at Serine-318, which is conserved in primates. S318 phosphorylation abrogates the interaction of BUB1 with TGFBR1 ...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.02.001

    authors: Nyati S,Gregg BS,Xu J,Young G,Kimmel L,Nyati MK,Ray D,Speers C,Rehemtulla A

    更新日期:2020-04-01 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

  • 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

  • Gene expression signature for spontaneous cancer regression in melanoma pigs.

    abstract::Incomplete spontaneous regression of melanoma is common. However, complete melanoma regression is still a very rare phenomenon. Because melanoma is the most immunogenic human malignancy, the mechanisms leading to regression, based on accumulative evidence, are the host's immune responses. Unfortunately, therapies aimi...

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

    pub_type: 杂志文章

    doi:10.1593/neo.08344

    authors: Rambow F,Piton G,Bouet S,Leplat JJ,Baulande S,Marrau A,Stam M,Horak V,Vincent-Naulleau S

    更新日期:2008-07-01 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

  • Comparison of tumor and microenvironment secretomes in plasma and in platelets during prostate cancer growth in a xenograft model.

    abstract::To survive and metastasize, tumors interact with surrounding tissues by secreting growth factors and cytokines. In return, surrounding host tissues respond by changing their secretome. Numerous factors theoretically function as therapeutic targets or biomarkers of cancer growth and metastatic risk. However, it is uncl...

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

    pub_type: 杂志文章

    doi:10.1593/neo.10166

    authors: Kerr BA,Miocinovic R,Smith AK,Klein EA,Byzova TV

    更新日期:2010-05-01 00:00:00

  • Tumor interstitial fluid pressure-a link between tumor hypoxia, microvascular density, and lymph node metastasis.

    abstract::High microvascular density (MVD) in the primary tumor has been shown to be associated with increased incidence of lymph node metastases and poor clinical outcome. Other investigations have revealed that a large fraction of hypoxic tissue in the primary tumor is associated with metastatic disease and impaired survival....

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.07.003

    authors: Rofstad EK,Galappathi K,Mathiesen BS

    更新日期:2014-07-01 00:00:00

  • PODXL1 promotes metastasis of the pancreatic ductal adenocarcinoma by activating the C5aR/C5a axis from the tumor microenvironment.

    abstract::Pancreatic invasive ductal adenocarcinoma (PDAC) is a representative intractable malignancy under the current cancer therapies, and is considered a scirrhous carcinoma because it develops dense stroma. Both PODXL1, a member of CD34 family molecules, and C5aR, a critical cell motility inducer, have gained recent attent...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.09.003

    authors: Saito K,Iioka H,Maruyama S,Sumardika IW,Sakaguchi M,Kondo E

    更新日期:2019-12-01 00:00:00

  • Valproic acid, an antiepileptic drug with histone deacetylase inhibitory activity, potentiates the cytotoxic effect of Apo2L/TRAIL on cultured thoracic cancer cells through mitochondria-dependent caspase activation.

    abstract::Inhibitors of histone deacetylases have been shown to enhance the sensitivity of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand TRAIL-mediated cytotoxicity. Valproic acid (VA), a commonly used antiepileptic agent whose pharmacokinetics and toxicity profiles are well described, is a histone dea...

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

    pub_type: 杂志文章

    doi:10.1593/neo.05823

    authors: Ziauddin MF,Yeow WS,Maxhimer JB,Baras A,Chua A,Reddy RM,Tsai W,Cole GW Jr,Schrump DS,Nguyen DM

    更新日期:2006-06-01 00:00:00

  • Cytokines and chemokines are expressed at different levels in small and large murine colon-26 tumors following intratumoral injections of CpG ODN.

    abstract::Direct tumor injections of (CpG ODN) into murine colon tumor 26 (CT-26) tumors can induce a potent antitumor response. Tumor size at the beginning of treatment determines the final therapeutic outcome, with smaller tumors responding favorably to CpG ODN therapy whereas large tumors do not. CpG ODN injections in small ...

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

    pub_type: 杂志文章

    doi:10.1593/neo.04166

    authors: Sharma S,Karakousis CP,Takita H,Shin K,Brooks SP

    更新日期:2004-09-01 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

  • Characterizing tumors using metabolic imaging: PET imaging of cellular proliferation and steroid receptors.

    abstract::Treatment decisions in oncology are increasingly guided by information on the biologic characteristics of tumors. Currently, patient-specific information on tumor biology is obtained from the analysis of biopsy material. Positron emission tomography (PET) provides quantitative estimates of regional biochemistry and re...

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

    pub_type: 杂志文章,评审

    doi:10.1038/sj.neo.7900075

    authors: Mankoff DA,Dehdashti F,Shields AF

    更新日期:2000-01-01 00:00:00

  • GALNT6 Stabilizes GRP78 Protein by O-glycosylation and Enhances its Activity to Suppress Apoptosis Under Stress Condition.

    abstract::We previously reported that overexpression of an O-type glycosyltransferase, GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) played critical roles in mammary carcinogenesis. To further investigate the biological function of GALNT6, we screened a substrate protein(s) of GALNT6 using a VVA (Vicia villosa agglut...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2016.11.007

    authors: Lin J,Chung S,Ueda K,Matsuda K,Nakamura Y,Park JH

    更新日期:2017-01-01 00:00:00

  • Detection of colorectal adenomas using a bioactivatable probe specific for matrix metalloproteinase activity.

    abstract::A significant proportion of colorectal adenomas, in particular those that lack an elevated growth component, continue to escape detection during endoscopic surveillance. Elevation of the activity of matrix metalloproteinases (MMPs), a large family of zinc endopeptidases, in adenomas serves as a biomarker of early tumo...

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

    pub_type: 杂志文章

    doi:10.1593/neo.11400

    authors: Clapper ML,Hensley HH,Chang WC,Devarajan K,Nguyen MT,Cooper HS

    更新日期:2011-08-01 00:00:00

  • Elevated estrogen receptor-α in VHL-deficient condition induces microtubule organizing center amplification via disruption of BRCA1/Rad51 interaction.

    abstract::Since loss of VHL is frequently detected early phase genetic event in human renal cell carcinoma, pVHL is assumed to be indispensable for suppression of tumor initiation step. However, induction of HIF-1α, target of pVHL E3 ligase, is more adequate to angiogenesis step after tumor mass formation. Concerning this, it h...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.09.013

    authors: Jung YS,Chun HY,Yoon MH,Park BJ

    更新日期:2014-12-01 00:00:00

  • Neoplasia: the second decade.

    abstract::This issue marks the end of the 10-year anniversary of Neoplasia where we have seen exciting growth in both number of submitted and published articles in Neoplasia. Neoplasia was first published in 1999. During the past 10 years, Neoplasia has dynamically adapted to the needs of the cancer research community as techno...

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

    pub_type: 杂志文章

    doi:10.1593/neo.81372

    authors: Rehemtulla A

    更新日期:2008-12-01 00:00:00

  • Association of the actin-binding protein transgelin with lymph node metastasis in human colorectal cancer.

    abstract::Metastatic dissemination of primary tumors is responsible for 90% of colorectal cancer (CRC) deaths. The presence of positive lymph nodes, which separates stage I/II from stage III CRC, is a particularly key factor in patient management. Here, we describe results of a quantitative proteomic survey to identify molecula...

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

    pub_type: 杂志文章

    doi:10.1593/neo.09542

    authors: Lin Y,Buckhaults PJ,Lee JR,Xiong H,Farrell C,Podolsky RH,Schade RR,Dynan WS

    更新日期:2009-09-01 00:00:00

  • Radiocurability is associated with interstitial fluid pressure in human tumor xenografts.

    abstract::Interstitial fluid pressure (IFP) has been shown to be an independent prognostic parameter for disease-free survival in cervical carcinoma patients treated with radiation therapy. However, the underlying mechanisms are not fully understood. The main aims of this study were to investigate whether tumor radiocurability ...

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

    pub_type: 杂志文章

    doi:10.1593/neo.91152

    authors: Rofstad EK,Gaustad JV,Brurberg KG,Mathiesen B,Galappathi K,Simonsen TG

    更新日期:2009-11-01 00:00:00

  • Up-regulation of FOXM1 by E6 oncoprotein through the MZF1/NKX2-1 axis is required for human papillomavirus-associated tumorigenesis.

    abstract:PURPOSE:Foxhead box M1 (FOXM1) expression has been shown to be linked with human papillomavirus (HPV) 16/18-infected cervical cancer. However, the mechanism underlying the induction of FOXM1 in HPV 16/18-infected cancers remains elusive. EXPERIMENTAL DESIGN:The mechanistic actions of FOXM1 induced by the E6/NKX2-1 axi...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.09.010

    authors: Chen PM,Cheng YW,Wang YC,Wu TC,Chen CY,Lee H

    更新日期:2014-11-20 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

  • The roles of telomerase in the generation of polyploidy during neoplastic cell growth.

    abstract::Polyploidy contributes to extensive intratumor genomic heterogeneity that characterizes advanced malignancies and is thought to limit the efficiency of current cancer therapies. It has been shown that telomere deprotection in p53-deficient mouse embryonic fibroblasts leads to high rates of polyploidization. We now sho...

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

    pub_type: 杂志文章

    doi:10.1593/neo.121398

    authors: Christodoulidou A,Raftopoulou C,Chiourea M,Papaioannou GK,Hoshiyama H,Wright WE,Shay JW,Gagos S

    更新日期:2013-02-01 00:00:00