NVP-BEZ235, a dual PI3K/mTOR inhibitor, inhibits osteosarcoma cell proliferation and tumor development in vivo with an improved survival rate.


:Despite recent improvements in chemotherapy and surgery, the problem of non-response osteosarcoma to chemotherapy remains, and is a parameter that is critical for prognosis. The present work investigated the therapeutic value of NVP-BEZ235, a dual class I PI3K/mTOR inhibitor. NVP-BEZ235 inhibited osteosarcoma cell proliferation by inducing G0/G1 cell cycle arrest with no caspase activation. In murine pre-clinical models, NVP-BEZ235 significantly slowed down tumor progression and ectopic tumor bone formation with decreased numbers of Ki67(+) cells and reduced tumor vasculature. Finally, NVP-BEZ235 considerably improved the survival rate of mice with osteosarcoma. Taken together, the results of the present work show that NVP-BEZ235 exhibits therapeutic interest in osteosarcoma and may be a promising adjuvant drug for bone sarcomas.


Cancer Lett


Cancer letters


Gobin B,Battaglia S,Lanel R,Chesneau J,Amiaud J,Rédini F,Ory B,Heymann D




Has Abstract


2014-03-28 00:00:00














  • Mitosis and histopathology in rat liver during methylclofenapate-induced hyperplasia.

    abstract::Liver hyperplasia was induced in rats by daily administration of methylclofenapate (25 mg/kg by gavage). An increase in the incidence of colchicine-arrested metaphases was observed with peaks occurring at 40 h (1.3%), 64 h (6.4%) and 84 h (6.8%) after the start of treatment. This response contrasted with the much larg...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Bybee A,Styles JA,Beck SL,Blackburn D

    更新日期:1990-07-16 00:00:00

  • Effects of COX-2 inhibitor on growth of human gastric cancer cells and its relation to hepatocyte growth factor.

    abstract::It is known that hepatocyte growth factor binding to its receptor regulates gastric cancer progression and metastasis. HGF was found to up-regulate the expression of cyclooxygenase-2 gene and increases prostaglandin (PG) synthesis in gastric mucosa cells. Overexpression of COX-2 and increased PG secretion have also be...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Chen JH,Wu CW,Kao HL,Chang HM,Li AF,Liu TY,Chi CW

    更新日期:2006-08-08 00:00:00

  • USP9X inhibition improves gemcitabine sensitivity in pancreatic cancer by inhibiting autophagy.

    abstract::Gemcitabine is the cornerstone of pancreatic cancer treatment. Although effective in most patients, development of tumor resistance to gemcitabine can critically limit its efficacy. The mechanisms responsible for this phenomenon remain elusive, but evidence suggests that ubiquitin-specific peptidases (USPs) may be key...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Ma T,Chen W,Zhi X,Liu H,Zhou Y,Chen BW,Hu L,Shen J,Zheng X,Zhang S,Zhang B,Li H,Liang T

    更新日期:2018-11-01 00:00:00

  • Significant allelic loss of ANX7region (10q21) in hormone receptor negative breast carcinomas.

    abstract::Loss of heterozygosity (LOH) in the 10q21 region that harbors the tumor suppressor gene ANX7-GTPase gene have been found in 35% of prostate tumors. Therefore, the rationale for this study is that this gene could also be implicated in breast pathogenesis as well. We investigated allelic losses in microsatellites of the...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Leighton X,Srikantan V,Pollard HB,Sukumar S,Srivastava M

    更新日期:2004-07-16 00:00:00

  • Inhibition of NMU-induced mammary tumorigenesis by dietary soy.

    abstract::We previously demonstrated that female Sprague-Dawley rats fed AIN-93G diets containing soy protein isolate (SPI+) had lower DMBA-induced mammary tumor incidence than those fed diets containing casein (CAS), due partly to altered Phase I metabolism with soy. Here, we evaluated the tumor protective effects of these sam...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Simmen RC,Eason RR,Till SR,Chatman L Jr,Velarde MC,Geng Y,Korourian S,Badger TM

    更新日期:2005-06-16 00:00:00

  • Sulforaphane enhances the anticancer activity of taxanes against triple negative breast cancer by killing cancer stem cells.

    abstract::Triple negative breast cancer (TNBC) typically exhibits rapid progression, high mortality and faster relapse rates relative to other breast cancer subtypes. In this report we examine the combination of taxanes (paclitaxel or docetaxel) with a breast cancer stem cell (CSC)-targeting agent sulforaphane for use against T...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Burnett JP,Lim G,Li Y,Shah RB,Lim R,Paholak HJ,McDermott SP,Sun L,Tsume Y,Bai S,Wicha MS,Sun D,Zhang T

    更新日期:2017-05-28 00:00:00

  • Targeting calcium/calmodulin-dependence kinase I and II as a potential anti-proliferation remedy for endometrial carcinomas.

    abstract::Calcium/calmodulin-dependent kinase (CaMK) I and II expression in endometrial cancer cells correlates with the malignant potential of this tumor, and CaMKI and II are potential therapeutic targets in endometrial cancer. CaMKI and II expression was significantly associated with PCNA-labeling index, clinical stage, hist...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Takai N,Ueda T,Nasu K,Yamashita S,Toyofuku M,Narahara H

    更新日期:2009-05-18 00:00:00

  • Combined effects of complex mixtures of potentially anti-carcinogenic compounds on antioxidant enzymes and carcinogen metabolizing enzymes in the rat.

    abstract::The anti-carcinogenic activity of dietary fruit and vegetables observed in several epidemiological and experimental animal studies is likely to be an effect of the combined exposure to a large number of substances acting together. This is plausible, as these compounds are present simultaneously in a diet containing ve...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Vang O,Rasmussen BF,Andersen O

    更新日期:1997-03-19 00:00:00

  • Aiming at the sweet side of cancer: aberrant glycosylation as possible target for personalized-medicine.

    abstract::One of the frontiers in cancer personalized-medicine aims at glycosylation. Cells are covered with a dense sugar coat of glycolipids, glycoproteins and free glycans. In cancer, the characteristic cell surface glycosylation is frequently transformed due to altered expression of glycan-modifying enzymes. This often lead...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Padler-Karavani V

    更新日期:2014-09-28 00:00:00

  • Identification and characterization of zinc finger encoding genes from the tumoral exocrine pancreatic cell line AR42J.

    abstract::Zinc finger transcription factors are DNA-binding proteins that are known to determine the identity of cells by regulating cell-specific gene expression. In addition, mutations in some members of this family have been found to be associated with several neoplasias, including Wilms' tumor and leukemias. Because the mec...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Mesa K,Gebelein B,Cook T,Urrutia R

    更新日期:1996-06-05 00:00:00

  • Synergistic inhibitory effects of interferon-alpha and 5-fluorouracil in meningioma cells in vitro.

    abstract::We have investigated the effects of interferon-alpha (IFN-alpha) and 5-fluorouracil (5-FU) on meningioma cells in two different culture systems, evaluated by the uptake of radiolabelled methionine. With both IFN-alpha and 5-FU an inhibitory effect on the uptake of radiolabelled methionine by the meningioma cells was d...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Zhang ZJ,Wang JL,Muhr C,Smits A

    更新日期:1996-02-27 00:00:00

  • Sox17 regulates proliferation and cell cycle during gastric cancer progression.

    abstract::Sox17, a transcription factor, was considered as an antagonist to inhibit canonical Wnt/β-catenin signaling in several malignant tumors. Extremely little is known about Sox17 in gastric cancer. Therefore, the aim of this study was to elucidate the vital role of Sox17 in the tumorigenesis and progression of gastric can...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Ye YW,Wu JH,Wang CM,Zhou Y,Du CY,Zheng BQ,Cao X,Zhou XY,Sun MH,Shi YQ

    更新日期:2011-08-28 00:00:00

  • Chromosomal imbalances in sporadic neuroendocrine tumours of the thymus.

    abstract::Neuroendocrine (carcinoid) tumours of the thymus are rare neoplasms characterized by a highly malignant clinical behavior. Some of these tumors are associated with MEN1. In this study we evaluated 10 cases of sporadic thymic neuroendocrine tumours using immunohistochemistry and comparative genomic hybridization (CGH)....

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Rieker RJ,Aulmann S,Penzel R,Schnabel PA,Blaeker H,Esposito I,Morresi-Hauf A,Otto HF,Hecker E,Dienemann H,Schirmacher P,Mechtersheimer G

    更新日期:2005-06-01 00:00:00

  • Towards optimal endocrine therapy for hormone-sensitive breast cancer: initial versus sequential adjuvant aromatase inhibition.

    abstract::Patients with hormone-receptor-positive early breast cancer have a significant risk of recurrence despite the use of adjuvant tamoxifen. The third-generation aromatase inhibitors letrozole, anastrozole, and exemestane offer promise as alternative or additional therapy to tamoxifen. As extended adjuvant therapy followi...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Spicer J,Ellis P

    更新日期:2007-04-18 00:00:00

  • Purification and biochemical characterization of a virus-specific reverse transcriptase from human osteosarcoma tissue.

    abstract::A RNA-dependent DNA polymerase (RTase) was purified from human osteosarcoma tissue by successive column chromatography of the microsomal fraction on DEAE-cellulose (DE-23 and DE-52) and phosphocellulose. The purified enzyme has a molecular weight of about 68,000, a pH optimum of 8.1, a Mg2+ optimum of 0.8 mM, Mn2+ opt...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Ebener U,Welte K,Chandra P

    更新日期:1979-08-01 00:00:00

  • Blood group specificity of pancreatic tumor mucin.

    abstract::N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic adenocarcinomas in Syrian hamsters produce considerable amounts of mucin. The mucin is immunogenic in rabbits and is predominately of A blood group antigenic specificity, as determined by immunodiffusion in agar gel. Indirect immunofluorescence studies with human...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Runge RG,Pour P

    更新日期:1980-10-01 00:00:00

  • The possibilities of reproducing effects of benzo[a]pyrene in a transformation test using Syrian hamster fetal lung cells.

    abstract::Various dose levels of benzo[a]pyrene (BP) were tested on short-term cultured foetal hamster lung cells for transforming effects in vitro in 6 similar experiments. The statistical evaluation of the results indicated a weak reproducibility (P = 0.09). Factors which inherently influence such reproducibility were conside...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Richter-Reichhelm HB,Emura M,Schneider P,Mohr U

    更新日期:1979-11-01 00:00:00

  • The cytotoxic properties of malachite green are associated with the increased demethylase, aryl hydrocarbon hydroxylase and lipid peroxidation in primary cultures of Syrian hamster embryo cells.

    abstract::Malachite green (MG), an industrial compound and potential environmental health hazard, is highly cytotoxic to mammalian cells in culture. In an attempt to define the biochemical basis, we have compared the cytotoxic effects and morphological alterations shown by MG in Syrian hamster embryo (SHE) cells with the levels...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Panandiker A,Fernandes C,Rao KV

    更新日期:1992-12-24 00:00:00

  • Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone.

    abstract::The molecular chaperone Hsp90 is not only of major current interest in fundamental biological research but also recognised as an exciting new target for the treatment of cancer and other diseases. In addition to playing an important role in response to proteotoxic heat shock and others stresses, Hsp90 is also critical...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Workman P

    更新日期:2004-04-08 00:00:00

  • MMGZ01, an anti-DLL4 monoclonal antibody, promotes nonfunctional vessels and inhibits breast tumor growth.

    abstract::Increasing evidence suggests that DLL4 (Delta-like 4)-Notch signaling plays a critical role in cell fate determination and differentiation in tissues. Blocking DLL4-Notch signaling results in inhibition of tumor growth, which is associated with increased nonfunctional vessels and poor perfusion in the tumor. We succes...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Xu Z,Wang Z,Jia X,Wang L,Chen Z,Wang S,Wang M,Zhang J,Wu M

    更新日期:2016-03-01 00:00:00

  • Prohibitin: A new player in immunometabolism and in linking obesity and inflammation with cancer.

    abstract::Immunometabolism, which has important implications in cancer biology, has emerged as a major regulator of different immune cell types. Various factors that integrate metabolic switches within immune cells with signal directed program that promote or inhibit their functions remain largely unidentified. Furthermore, sex...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Zi Xu YX,Ande SR,Mishra S

    更新日期:2018-02-28 00:00:00

  • Volatile isoprenoid constituents of fruits, vegetables and herbs cumulatively suppress the proliferation of murine B16 melanoma and human HL-60 leukemia cells.

    abstract::Substantial evidence from epidemiological studies supports the inverse association between the intake of fruits, vegetables and other plant products and cancer incidence. Cancer-preventive constituents of fruits and vegetables may inhibit carcinogen activation, enhance carcinogen detoxification, prevent carcinogens fr...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Tatman D,Mo H

    更新日期:2002-01-25 00:00:00

  • Absence of hSNF5/INI1 mutation in human lung cancer.

    abstract::Frequent occurrence of chromosome 22q deletions in lung cancer indicates the presence of a tumor suppressor gene on this chromosome arm. The hSNF5/INI1 gene at chromosome 22q11.2 has recently been shown to act as a tumor suppressor in rhabdoid tumors. To investigate whether the hSNF5/INI1 gene located on chromosome 22...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Manda R,Kohno T,Hamada K,Takenoshita S,Kuwano H,Yokota J

    更新日期:2000-05-29 00:00:00

  • Frequent loss of heterozygosity on multiple chromosomes in Chinese esophageal squamous cell carcinomas.

    abstract::Analysis of the loss of heterozygosity (LOH) detected by polymerase chain reaction techniques using 18 polymorphic markers localized to chromosomes 3p, 5, 17, and 18q in 40 Hong Kong Chinese esophageal squamous cell carcinoma (ESC) patients showed that multiple alterations on several chromosomes are involved in ESC de...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Ko JM,Wong CP,Tang CM,Lau KW,Lung ML

    更新日期:2001-09-20 00:00:00

  • Antimutagenic activity of anthocyanins isolated from Aronia melanocarpa fruits.

    abstract::Anthocyanins belong to the flavonoid family and are ubiquitous in plants, especially in flower petals and fruit peels. We established that anthocyanins isolated from fruits of Aronia melanocarpa markedly inhibited the mutagenic activity of benzo(a)pyrene and 2-amino fluorene in the Ames test. In the Sister Chromatid E...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Gasiorowski K,Szyba K,Brokos B,Kołaczyńska B,Jankowiak-Włodarczyk M,Oszmiański J

    更新日期:1997-10-28 00:00:00

  • Synergistic inhibition of human gastric carcinoma cell growth by 1-beta-D-arabinofuranosylcytosine and hydroxyurea or 2'-deoxyguanosine in vitro.

    abstract::The cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in combination with hydroxyurea (HU) or 2'-deoxyguanosine (GdR) on human gastric carcinoma MK-1 cells and colon carcinoma HT-15 cells was studied. Synergistic interaction between ara-C and HU on MK-1 cells and HT-15 cells, or ara-C and GdR on MK-1 cells was...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Matsumoto M,Kawahara T,Tsuda M,Ohkubo T,Kamiguchi H,Yamamura M

    更新日期:1992-04-30 00:00:00

  • BAT monoclonal antibody immunotherapy of human metastatic colorectal carcinoma in mice.

    abstract::BAT monoclonal antibody exhibited anti-tumor activity mediated by T and NK cells. We have evaluated the efficacy of murine and humanized BAT for the treatment of human colorectal carcinoma liver metastases in nude mice. HM7, a human colorectal carcinoma was injected into the spleen to colonize the liver. A single intr...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Hardy B,Morgenstern S,Raiter A,Rodionov G,Fadaeev L,Niv Y

    更新日期:2005-11-18 00:00:00

  • Induction of neuroendocrine differentiation in castration resistant prostate cancer cells by adipocyte differentiation-related protein (ADRP) delivered by exosomes.

    abstract::Although overall mortality rate of prostate cancer (PCa) declines in recent years, castration-resistant prostate cancer (CRPC) remains incurable. Clinical evidence indicates that CRPC recurred from hormonal therapy exhibits neuroendocrine differentiated (NED) phenotypes, which could contribute to therapeutic resistanc...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Lin LC,Gao AC,Lai CH,Hsieh JT,Lin H

    更新日期:2017-04-10 00:00:00

  • Autophagy-deficient Kupffer cells promote tumorigenesis by enhancing mtROS-NF-κB-IL1α/β-dependent inflammation and fibrosis during the preneoplastic stage of hepatocarcinogenesis.

    abstract::As a cellular degradation mechanism, autophagy exerts crucial and complicated effects on HCC development. Liver non-parenchymal cells, including hepatic resident macrophage Kupffer cells, also play important roles in this process. However, most associated studies have focused on the influence of the autophagy level in...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Sun K,Xu L,Jing Y,Han Z,Chen X,Cai C,Zhao P,Zhao X,Yang L,Wei L

    更新日期:2017-03-01 00:00:00

  • Circular RNAs (circRNAs) in cancer.

    abstract::Circular RNAs (circRNAs) are a class of non-coding RNAs that do not have 5' end caps or 3' end poly (A) tails. There are more than one hundred thousand genes that encode circRNAs. Clinical data show that there are differences in the expression of circRNAs in a variety of diseases, including cancer, suggesting that cir...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Zhou R,Wu Y,Wang W,Su W,Liu Y,Wang Y,Fan C,Li X,Li G,Li Y,Xiong W,Zeng Z

    更新日期:2018-07-01 00:00:00