Pyrimethamine sensitizes pituitary adenomas cells to temozolomide through cathepsin B-dependent and caspase-dependent apoptotic pathways.

Abstract:

:Invasive pituitary adenomas (PAs) are generally refractory to conventional therapy and salvage treatment with temozolomide (TMZ). In addition to antiprotozoan effects, pyrimethamine (PYR) has recently shown its strong antitumor activity as an antineoplastic agent or in combination with TMZ in metastatic melanoma cells. In this study, the effects of TMZ, PYR or TMZ/PYR combination on rat/mouse PA cell lines αT3-1, GH3, MMQ and ATt-20 as well as GH3 xenograft tumor model were evaluated. TMZ/PYR combination synergistically inhibited proliferation, invasion and induced apoptosis of these PA cell lines in vitro. Strikingly, combination treatment with TMZ and PYR produced synergistic antitumor activity and enhanced the survival rate of GH3 xenograft tumor models without increasing systemic side effects. In addition, TMZ/PYR induced cell cycle arrest, increased DNA damage, upregulated the expression of cathepsin B, BAX, cleaved PARP and phosphorylated histone H2AX as well as elevated caspase3/7, 8 and 9 activities. The decreased expression of Bcl-2, MMP-2 and MMP-9 alone with cytochrome c release from mitochondria into the cytosol was also observed in the TMZ/PYR combination group. The increase in cell apoptosis due to combination with PYR was rescued by leucovorin. These data suggest that PYR may enhance the efficacy of TMZ via triggering both cathepsin B-dependent and caspase-dependent apoptotic pathways. Therefore, combination of PYR and TMZ may provide a novel regimen for invasive PAs refractory to standard therapy and TMZ.

journal_name

Int J Cancer

authors

Dai C,Zhang B,Liu X,Guo K,Ma S,Cai F,Yang Y,Yao Y,Feng M,Bao X,Deng K,Jiao Y,Wei Z,Junji W,Xing B,Lian W,Wang R

doi

10.1002/ijc.28199

subject

Has Abstract

pub_date

2013-10-15 00:00:00

pages

1982-93

issue

8

eissn

0020-7136

issn

1097-0215

journal_volume

133

pub_type

杂志文章
  • Cis-diamminedichloroplatinum(II) inhibits p34cdc2 protein kinase in human lung-cancer cells.

    abstract::cis-Diamminedichloroplatinum(II) (CDDP) induced G2-phase arrest in PC-9 human cancer cells. To elucidate how CDDP acts on cell-cycle regulation, we analyzed the effect of CDDP on cell-cycle regulators such as p34cdc2 protein kinase. p34cdc2 protein kinase activity was maximum in G2 phase and decreased after G2/M trans...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910550417

    authors: Nishio K,Fujiwara Y,Miyahara Y,Takeda Y,Ohira T,Kubota N,Ohta S,Funayama Y,Ogasawara H,Ohata M

    更新日期:1993-10-21 00:00:00

  • Glutamate receptor, ionotropic, kainate 2 silencing by DNA hypermethylation possesses tumor suppressor function in gastric cancer.

    abstract::Aberrant DNA methylation is considered a major mechanism for silencing tumor suppressor genes in gastric cancer. We used CpG microarray and differential methylation hybridization strategies to identify potential tumor suppressor genes and recovered glutamate receptor, ionotropic, kainate 2 (GRIK2) as a novel epigeneti...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24958

    authors: Wu CS,Lu YJ,Li HP,Hsueh C,Lu CY,Leu YW,Liu HP,Lin KH,Hui-Ming Huang T,Chang YS

    更新日期:2010-06-01 00:00:00

  • Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck.

    abstract::Fresh-frozen biopsies were obtained from 61 patients at diagnosis of squamous cell carcinoma of the head and neck (HNSCC) for study of the prevalence and physical status of human papillomavirus (HPV) DNA. The frequency of HPV DNA and genotypes were determined by SPF10 PCR screening with a general probe hybridization a...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.11381

    authors: Koskinen WJ,Chen RW,Leivo I,Mäkitie A,Bäck L,Kontio R,Suuronen R,Lindqvist C,Auvinen E,Molijn A,Quint WG,Vaheri A,Aaltonen LM

    更新日期:2003-11-10 00:00:00

  • Suppression of malignant growth of human breast cancer cells by ectopic expression of integrin-linked kinase.

    abstract::Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cell...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20340

    authors: Chen P,Shen WZ,Karnik P

    更新日期:2004-10-10 00:00:00

  • The role of genotype-specific human papillomavirus detection in diagnosing residual cervical intraepithelial neoplasia.

    abstract::We assessed prospectively whether residual cervical intraepithelial neoplasia (CIN) after treatment for high-grade CIN can be predicted by genotype-specific high-risk HPV (HR-HPV) detection in follow-up cervical scrapes. A broad spectrum, highly sensitive SPF(10)-LiPA-PCR HPV detection technique was used on cervical s...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10691

    authors: Bekkers RL,Melchers WJ,Bakkers JM,Hanselaar AG,Quint WG,Boonstra H,Massuger LF

    更新日期:2002-11-10 00:00:00

  • Epidermal growth factor receptor (EGFR) downstream molecules as response predictive markers for gefitinib (Iressa, ZD1839) in chemotherapy-resistant non-small cell lung cancer.

    abstract::Gefitinib has shown meaningful antitumor activity with tolerable toxicity in chemotherapy-refractory NSCLC in previous studies. Moreover, EGFR expression failed to show a correlation with response. In an attempt to identify predictive markers of response, we have investigated the tumoral expression of key signaling mo...

    journal_title:International journal of cancer

    pub_type: 临床试验,杂志文章

    doi:10.1002/ijc.20550

    authors: Han SW,Hwang PG,Chung DH,Kim DW,Im SA,Kim YT,Kim TY,Heo DS,Bang YJ,Kim NK

    更新日期:2005-01-01 00:00:00

  • Allelic loss at 1p and 19q frequently occurs in association and may represent early oncogenic events in oligodendroglial tumors.

    abstract::The molecular mechanisms underlying the genesis and progression of oligodendroglial tumors are poorly understood, since only restricted information on loss of heterozygosity from isolated cases is available. The commonest alterations appear to involve deletion of 1p and 19q, while loss of heterozygosity for 9p, chromo...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910640311

    authors: Bello MJ,Leone PE,Vaquero J,de Campos JM,Kusak ME,Sarasa JL,Pestaña A,Rey JA

    更新日期:1995-06-22 00:00:00

  • All 4 di-leucine motifs in the first hydrophobic domain of the E5 oncoprotein of human papillomavirus type 16 are essential for surface MHC class I downregulation activity and E5 endomembrane localization.

    abstract::The E5 oncoprotein of human papillomavirus type 16 downregulates surface MHC Class I and interacts with the heavy chain of the MHC complex via the first hydrophobic domain, believed to form the first helical transmembrane region (TM1) of E5. TM1 contains 4 equally spaced di-leucine (LL1-LL4) motifs. Di-leucine motifs ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25004

    authors: Cortese MS,Ashrafi GH,Campo MS

    更新日期:2010-04-01 00:00:00

  • Influence of habitual smoking on gastric cancer by histologic subtype.

    abstract::A comparative case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), with the aim of clarifying whether histologic subtypes of gastric cancer exhibit different risk-factor patterns of habitual smoking. Our study comprised 995 histologically...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19990331)81:1<39::aid-ijc8

    authors: Inoue M,Tajima K,Yamamura Y,Hamajima N,Hirose K,Nakamura S,Kodera Y,Kito T,Tominaga S

    更新日期:1999-03-31 00:00:00

  • Modulation of intra-epithelial expansion of human T24 bladder-carcinoma cells in murine urothelium by growth factors and extracellular-matrix components.

    abstract::The high recurrence rate of bladder cancer is probably due to an efficient repopulation of the bladder by residual transformed cells after resection of the tumour. However, the regenerating capacity of the normal urothelial cells is very high. To study the balance between regenerating normal urothelium and out-growth ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910600523

    authors: Rebel JM,Thijssen CD,Vermey M,Zwarthoff EC,Van der Kwast TH

    更新日期:1995-03-03 00:00:00

  • Menopausal hormone therapy and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition.

    abstract::Menopausal hormone therapy (HT) may influence colorectal cancer risk. A total of 136,275 postmenopausal women from the European Prospective Investigation into Cancer and Nutrition were followed for an average of 9 years, during which time 1,186 colorectal cancers were diagnosed. Hazard ratios (HR) and 95% confidence i...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.25504

    authors: Tsilidis KK,Allen NE,Key TJ,Sanjoaquin MA,Bakken K,Berrino F,Fournier A,Lund E,Overvad K,Olsen A,Tjønneland A,Byrnes G,Chajes V,Rinaldi S,Boutron-Ruault MC,Clavel-Chapelon F,Chang-Claude J,Kaaks R,Bergmann M,Boeing

    更新日期:2011-04-15 00:00:00

  • Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.

    abstract::Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29882

    authors: Zhang L,Huang X,Zhu X,Ge S,Gilson E,Jia R,Ye J,Fan X

    更新日期:2016-03-15 00:00:00

  • Human meningiomas co-express platelet-derived growth factor (PDGF) and PDGF-receptor genes and their protein products.

    abstract::The present studies investigated the expression of the platelet-derived growth factor (PDGF) and PDGF-receptor genes in human meningiomas. Northern blot analysis demonstrated that all meningiomas examined expressed both the c-sis/PDGF-2 proto-oncogene and the PDGF-receptor gene. In situ hybridization localized the c-s...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910460106

    authors: Maxwell M,Galanopoulos T,Hedley-Whyte ET,Black PM,Antoniades HN

    更新日期:1990-07-15 00:00:00

  • Comorbidities, age and period of diagnosis influence treatment and outcomes in early breast cancer.

    abstract::Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7581 s...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31974

    authors: Minicozzi P,Van Eycken L,Molinie F,Innos K,Guevara M,Marcos-Gragera R,Castro C,Rapiti E,Katalinic A,Torrella A,Žagar T,Bielska-Lasota M,Giorgi Rossi P,Larrañaga N,Bastos J,Sánchez MJ,Sant M,European HR Working Group on

    更新日期:2019-05-01 00:00:00

  • Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women.

    abstract::Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.31345

    authors: Kabat GC,Kim MY,Stefanick M,Ho GYF,Lane DS,Odegaard AO,Simon MS,Bea JW,Luo J,Wassertheil-Smoller S,Rohan TE

    更新日期:2018-08-01 00:00:00

  • Ornithine decarboxylase inhibitor attenuates bombesin enhancement of intestinal carcinogenesis and metastasis induced by azoxymethane.

    abstract::The effects of combined administration of bombesin (40 micrograms/kg body weight) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the development of large and small intestinal tumors and the incidence of their metastasis to the peritoneum induced by azoxymethane (AOM, 7.4 mg/kg body weigh...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910580414

    authors: Iishi H,Tatsuta M,Baba M,Uehara H,Nakaizumi A

    更新日期:1994-08-15 00:00:00

  • Decreased expression of phosphorylated JNK in breast infiltrating ductal carcinoma is associated with a better overall survival.

    abstract::Phosphorylation/activation of c-jun NH2-terminal kinase (JNK) has an ambivalent role, pro-proliferation or antiproliferation, in human cancers, which is determined by different cell types and by its crosstalk with other kinases. So far, the role of phosphorylated JNK (p-JNK) in breast cancer is mostly undefined. In th...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21707

    authors: Yeh YT,Hou MF,Chung YF,Chen YJ,Yang SF,Chen DC,Su JH,Yuan SS

    更新日期:2006-06-01 00:00:00

  • IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma.

    abstract::Insulin-like growth factor-binding protein 7 (IGFBP7) functions in several cellular processes including proliferation, senescence and apoptosis. This study analyzed IGFBP7 function in hepatocellular carcinoma (HCC) cells by gene manipulation and investigated the prognostic significance of IGFBP7 expression in clinical...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25994

    authors: Tomimaru Y,Eguchi H,Wada H,Kobayashi S,Marubashi S,Tanemura M,Umeshita K,Kim T,Wakasa K,Doki Y,Mori M,Nagano H

    更新日期:2012-01-15 00:00:00

  • Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency.

    abstract::We investigated whether cilengitide could amplify the antitumor effects of radiotherapy in an orthotopic rat glioma xenograft model. Cilengitide is a specific inhibitor of alphav series integrins, and acts as an antiangiogenic. U251 human glioma cells express alphavbeta3 and alphavbeta5 integrins. We used in vitro ass...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24240

    authors: Mikkelsen T,Brodie C,Finniss S,Berens ME,Rennert JL,Nelson K,Lemke N,Brown SL,Hahn D,Neuteboom B,Goodman SL

    更新日期:2009-06-01 00:00:00

  • How many cervical cancers are prevented by treatment of screen-detected disease in young women?

    abstract::Others have argued that as many as a third of women treated for high-grade cervical intraepithelial neoplasia (CIN) would have developed cervical cancer in the absence of screening and treatment. Under various assumptions and using past data on CIN grade 3 (CIN3) registrations in England and Scotland, we estimate what...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23922

    authors: Sasieni P,Castanon A,Parkin DM

    更新日期:2009-01-15 00:00:00

  • Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990-2006.

    abstract::Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time-integrated glycemia measure, and cancer incidence and mortality in nondiabetic and diabetic men and women. We conducted a prospective study of ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.27394

    authors: Joshu CE,Prizment AE,Dluzniewski PJ,Menke A,Folsom AR,Coresh J,Yeh HC,Brancati FL,Platz EA,Selvin E

    更新日期:2012-10-01 00:00:00

  • Isotype-specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation.

    abstract::Tumor cells express the glycolytic regulator pyruvate kinase subtype M2 (M2-PK), which can occur in a tetrameric form with high affinity to its substrate phosphoenolpyruvate (PEP) and a dimeric form with a low PEP affinity. The transition between both conformations contributes to the control of glycolysis and is impor...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23512

    authors: Spoden GA,Mazurek S,Morandell D,Bacher N,Ausserlechner MJ,Jansen-Dürr P,Eigenbrodt E,Zwerschke W

    更新日期:2008-07-15 00:00:00

  • NF-κ B-dependent upregulation of ICAM-1 by HPV16-E6/E7 facilitates NK cell/target cell interaction.

    abstract::NK cell recognition of tumor cells is mediated by a delicate balance of signals received by MHC class I-binding inhibitory NK cell receptors and activating NK cell receptors, which mainly bind to virus-, stress- or tumor-induced ligands. In addition, adhesion molecules such as the intercellular adhesion molecule-1 (IC...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25442

    authors: Textor S,Accardi R,Havlova T,Hussain I,Sylla BS,Gissmann L,Cerwenka A

    更新日期:2011-03-01 00:00:00

  • Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses.

    abstract::Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconcl...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22604

    authors: Lissowska J,Gaudet MM,Brinton LA,Chanock SJ,Peplonska B,Welch R,Zatonski W,Szeszenia-Dabrowska N,Park S,Sherman M,Garcia-Closas M

    更新日期:2007-06-15 00:00:00

  • Augmentation of natural killer activity by pyran copolymer in mice.

    abstract::Treatment of older mice with pyran copolymer, a known interferon-inducer, was found to result in a rapid boosting of cell-mediated cytolytic activity against YAC-1 tumor target cells. The effector cells were characterized as being non-adherent and were presumed to be natural killer (NK) cells. Augmentation occurred in...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910240520

    authors: Santoni A,Puccetti P,Riccardi C,Herberman RB,Bonmassar E

    更新日期:1979-11-15 00:00:00

  • Nanoparticle-based photothermal and photodynamic immunotherapy for tumor treatment.

    abstract::Nanoparticle-based phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), exhibit strong efficacy, minimal invasion and negligible side effects in tumor treatment. These phototherapies have received considerable attention and been extensively studied in recent years. In addition to directly...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.31717

    authors: Hou X,Tao Y,Pang Y,Li X,Jiang G,Liu Y

    更新日期:2018-12-15 00:00:00

  • Inhibitory effect of linoleic acid on transformation of IEC6 intestinal cells by in vitro azoxymethane treatment.

    abstract::The effect of linoleic acid (LA) on growth and transformation of IEC6 intestinal cells was examined. IEC6 cells expressed mRNAs of 15-lipooxygenase (LOX15) and peroxisome proliferator-activated receptor (PPAR)gamma but not COX-2. Cell growth was suppressed by LA in a dose-dependent manner in IEC6 cells. Three-week tre...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21393

    authors: Sasaki T,Yoshida K,Shimura H,Ichiba M,Sasahira T,Shimomoto T,Denda A,Kuniyasu H

    更新日期:2006-02-01 00:00:00

  • Asthma and risk of lethal prostate cancer in the Health Professionals Follow-Up Study.

    abstract::Inflammation, and more generally, the immune response are thought to influence the development of prostate cancer. To determine the components of the immune response that are potentially contributory, we prospectively evaluated the association of immune-mediated conditions, asthma and hayfever, with lethal prostate ca...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29463

    authors: Platz EA,Drake CG,Wilson KM,Sutcliffe S,Kenfield SA,Mucci LA,Stampfer MJ,Willett WC,Camargo CA Jr,Giovannucci E

    更新日期:2015-08-15 00:00:00

  • Dietary intake of fish, ω-3 and ω-6 fatty acids and risk of colorectal cancer: A prospective study in U.S. men and women.

    abstract::The association between fish, ω-3 and ω-6 polyunsaturated fatty acid (PUFA) intake and risk of colorectal cancer (CRC) remains inconclusive. Recent prospective studies suggest that the relationship may vary by gender, subsite and duration of follow-up. We followed 123,529 US adults (76,386 women and 47,143 men) withou...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.28878

    authors: Song M,Chan AT,Fuchs CS,Ogino S,Hu FB,Mozaffarian D,Ma J,Willett WC,Giovannucci EL,Wu K

    更新日期:2014-11-15 00:00:00

  • Expression of transforming growth factor alpha messenger RNA in the normal and neoplastic gastro-intestinal tract.

    abstract::The presence of TGF alpha mRNA has been reported previously to occur in primary colon cancers. We report the expression of the normal 4.5 kb TGF alpha transcript in the mucosa of the normal human gastro-intestinal tract from oesophagus through to colon. The highest levels of human TGF alpha mRNA occurred in the duoden...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910430305

    authors: Malden LT,Novak U,Burgess AW

    更新日期:1989-03-15 00:00:00