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 assays of adhesion and growth of tumor and endothelial cells to evaluate cytotoxicity and the potential for cilengitide to enhance radiation toxicity. Treatment was then evaluated in an orthotopic model to evaluate synergy with therapeutic radiation in vivo. In vitro, cilengitide blocked cell adhesion, but did not influence the effects of radiation on U251 cells; cilengitide strongly amplified radiation effects on endothelial cell survival. In vivo, radiotherapy prolonged the survival of U251 tumor-bearing rats from 50 to over 110 days. Cotreatment with cilengitide and radiation dramatically amplified the effects of radiation, producing survival over 200 days and triggering an enhanced apoptotic response and suppression of tumor growth by histology at necropsy. Signaling pathways activated in the tumor included NFkappab, a documented mediator of cellular response to radiation. Because cilengitide has a short plasma half-life (t((1/2)) approximately 20 min), antiangiogenic scheduling typically uses daily injections. We found that a single dose of cilengitide (4 mg/kg) given between 4 and 12 hr prior to radiation was sufficient to produce the same effect. Our results demonstrate that blockade of alphav integrins mediates an unanticipated rapid potentiation of radiation, and suggests possible clinical translation for glioma therapy.

journal_name

Int J Cancer

authors

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

doi

10.1002/ijc.24240

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

2719-27

issue

11

eissn

0020-7136

issn

1097-0215

journal_volume

124

pub_type

杂志文章
  • Tobacco smoking, chewing habits, alcohol drinking and the risk of head and neck cancer in Nepal.

    abstract::Although tobacco smoking, pan chewing and alcohol drinking are important risk factors for head and neck cancer (HNC), the HNC risks conferred by products available in Nepal for these habits are unknown. We assessed the associations of tobacco smoking, chewing habits, and alcohol drinking with HNC risk in Nepal. A case...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32823

    authors: Chang CP,Siwakoti B,Sapkota A,Gautam DK,Lee YA,Monroe M,Hashibe M

    更新日期:2020-08-01 00:00:00

  • Vitamin A levels in human bladder cancer.

    abstract::The following studies were undertaken to determine the levels of serum carotene and vitamin A (retinol) in Egyptian patients with intestinal, urinary, hepatosplenic schistosomiasis, and bladder cancer. These studies have shown that both serum carotene and serum retinol levels are significantly reduced in patients with...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910300203

    authors: Mahmoud LA,Robinson WA

    更新日期:1982-08-15 00:00:00

  • Trends in childhood acute lymphoblastic leukemia in Western Australia, 1960-2006.

    abstract::Increases in the incidence of childhood acute lymphoblastic leukemia (ALL) have been reported in some countries, while other reports from similar geographical regions have indicated stable rates. The reasons for the discrepancies have been debated in the literature, with the focus on whether the observed increases are...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23226

    authors: Milne E,Laurvick CL,de Klerk N,Robertson L,Thompson JR,Bower C

    更新日期:2008-03-01 00:00:00

  • Fruit consumption and the risk of bladder cancer: A pooled analysis by the Bladder Cancer Epidemiology and Nutritional Determinants Study.

    abstract::While the association between fruit consumption and bladder cancer risk has been extensively reported, studies have had inadequate statistical power to investigate associations between types of fruit and bladder cancer risk satisfactorily. Fruit consumption in relation to bladder cancer risk was investigated by poolin...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33008

    authors: Jochems SHJ,Reulen RC,van Osch FHM,Witlox WJA,Goossens ME,Brinkman M,Giles GG,Milne RL,van den Brandt PA,White E,Weiderpass E,Huybrechts I,Hémon B,Agudo A,Bueno-de-Mesquita B,Cheng KK,van Schooten FJ,Bryan RT,Wesseliu

    更新日期:2020-10-15 00:00:00

  • Cancer survival in people with AIDS: A population-based study from São Paulo, Brazil.

    abstract::Cancer survival among people with AIDS (PWA) has been described in developed countries, but there is lack of data from developing countries. The aim of this study was to evaluate survival after cancer diagnosis in PWA and compare it with people without AIDS (non-PWA) in São Paulo, Brazil. A probabilistic record linkag...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31081

    authors: Tanaka LF,Latorre MDRDO,Gutierrez EB,Curado MP,Dal Maso L,Herbinger KH,Froeschl G,Heumann C

    更新日期:2018-02-01 00:00:00

  • Serum concentration of thyroid hormones in abnormal and euthyroid ranges and breast cancer risk: A cohort study.

    abstract::The impact of variations in serum thyroid hormone concentration within the euthyroid range on breast cancer risk remains unclear. We investigated the effect of serum thyrotropin (TSH) and thyroid hormone concentration on breast cancer risk. This cohort study involved 62,546 Korean women, aged ≥40 years, who were free ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32283

    authors: Kim EY,Chang Y,Lee KH,Yun JS,Park YL,Park CH,Ahn J,Shin H,Ryu S

    更新日期:2019-12-15 00:00:00

  • Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study.

    abstract::Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose se...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33236

    authors: Stepien M,Keski-Rahkonen P,Kiss A,Robinot N,Duarte-Salles T,Murphy N,Perlemuter G,Viallon V,Tjønneland A,Rostgaard-Hansen AL,Dahm CC,Overvad K,Boutron-Ruault MC,Mancini FR,Mahamat-Saleh Y,Aleksandrova K,Kaaks R,Kühn T,

    更新日期:2021-02-01 00:00:00

  • Physical activity and risk of renal cell cancer.

    abstract::The relation between physical activity and renal cell cancer is unclear. High occupational physical activity has been associated with a decreased risk of renal cell cancer among men-but not among women-in two previous studies, while no association has been found for leisure time physical activity. Our aim was to inves...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:

    authors: Bergström A,Terry P,Lindblad P,Lichtenstein P,Ahlbom A,Feychting M,Wolk A

    更新日期:2001-04-01 00:00:00

  • Impaired general cell-mediated immune functions in vivo and in vitro in patients with nasopharyngeal carcinoma.

    abstract::General cell-mediated immune (CMI) functions in NPC patients were investigated by the in vivo Mantoux and in vitro lymphocyte response to PHA assays. Thirty-eight (50%) of 76 untreated NPC patients were hyporesponsive in the Mantoux assay compared to 27 (25%) of 110 control patients. Forty-three (65.2%) of 66 untreate...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910180202

    authors: Chan SH,Chew TS,Goh EH,Simons MJ,Shanmugaratnam K

    更新日期:1976-08-15 00:00:00

  • Reproductive history and cancer of the biliary tract in women.

    abstract::Although reproductive factors have been shown to be related to the composition of bile and functioning of the biliary system, their relationship with biliary tract cancer has not been studied in detail. Between 1984 and 1987 we conducted a case-control study of 75 women with cancer of the biliary tract and 252 control...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910570203

    authors: Moerman CJ,Berns MP,Bueno de Mesquita HB,Runia S

    更新日期:1994-04-15 00:00:00

  • p53 codon 72 ARG/PRO polymorphism is not related to HPV type or lesion grade in low- and high-grade squamous intra-epithelial lesions and invasive squamous carcinoma of the cervix.

    abstract::A polymorphism at codon 72 of the p53 gene, resulting in either an arginine or a proline residue in the protein, has been reported to affect the susceptibility of p53 to human papillomavirus (HPV) E6-mediated degradation in cultured cells. However, the relevance of this polymorphism to naturally occurring HPV infectio...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19990924)83:1<66::aid-ijc1

    authors: Giannoudis A,Graham DA,Southern SA,Herrington CS

    更新日期:1999-09-24 00:00:00

  • The ability of normal mouse cells to reduce the malignant potential of transformed mouse bladder epithelial cells depends on their somatic origin.

    abstract::Somatic cell hybrids have been made between a transformed mouse bladder carcinoma cell line and normal mouse bladder epithelium and mesenchyme. In the epithelial tumour/mesenchyme hybrids the malignant phenotype was expressed dominantly whereas in the carcinoma/normal epithelium hybrids the malignant potential was gre...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910330517

    authors: Cowell JK,Franks LM

    更新日期:1984-05-15 00:00:00

  • Expression of the ras-related rap genes in human tumors.

    abstract::The expression of the recently described rap genes, closely related in the effector region to the ras proto-oncogenes, was examined by Northern blot analysis in 41 primary human tumors. The structural and in vitro biological properties of the rap gene products suggest their possible antagonistic action in the same eff...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910440608

    authors: Culine S,Olofsson B,Gosselin S,Honore N,Tavitian A

    更新日期:1989-12-15 00:00:00

  • Lymph node metastasis and relation to tumor growth potential and local immune response in advanced gastric cancer.

    abstract::To evaluate the relation between the degree of lymph node metastasis and the growth potential of tumour cells and the local immune function in gastric cancer, we analyzed data on 444 patients with advanced serosally invasive gastric cancer who underwent curative gastrectomy. Tumour growth potential was evaluated based...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19970422)74:2<224::aid-ijc

    authors: Maehara Y,Tomisaki S,Oda S,Kakeji Y,Tsujitani S,Ichiyoshi Y,Akazawa K,Sugimachi K

    更新日期:1997-04-22 00:00:00

  • Association between progression-free survival and patients' quality of life in cancer clinical trials.

    abstract::Quality of life outcomes provide essential information for patients and physicians in oncology care. However, the validity of progression-free survival (PFS) as a surrogate for quality of life, and the inclusion and reporting of quality of life endpoints in clinical trials, is unclear. We performed a retrospective stu...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31957

    authors: Hwang TJ,Gyawali B

    更新日期:2019-04-01 00:00:00

  • The IL-1/IL-1R axis induces greater fibroblast-derived chemokine release in human papillomavirus-negative compared to positive oropharyngeal cancer.

    abstract::Human papillomavirus (HPV) is now recognised as a major aetiological agent in the pathogenesis of oropharyngeal carcinoma (OPC). HPV-positive tumours are associated with better outcomes compared to HPV-negative tumours, possibly due to differences in their aetiology and/or the tumour microenvironment. Increased number...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31852

    authors: Al-Sahaf S,Hunter KD,Bolt R,Ottewell PD,Murdoch C

    更新日期:2019-01-15 00:00:00

  • Genetic analysis of in vitro leukemogenesis induced by thymus epithelial reticulum cells transmitting murine leukemia viruses.

    abstract::Lymphatic leukemia developed in C57BL/6 mice following inoculation of normal thymocytes that and been co-cultured on leukemic thymus epithelial reticulum monolayer cells. Using thymocytes genetically marked in Ly membrane antigens, we showed that the thymomas which developed were produced by the co-cultured thymocytes...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910210119

    authors: Haas M

    更新日期:1978-01-15 00:00:00

  • Tamoxifen modulation of cisplatin cytotoxicity in human malignancies.

    abstract::Recent clinical trials have indicated that addition of tamoxifen (TAM) to a combination of cisplatin (DDP), carmustine and dacarbazine markedly increases the overall objective response rate of patients with metastatic malignant melanoma. Previous studies have determined that there is remarkable synergy between TAM and...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910550623

    authors: McClay EF,Albright KD,Jones JA,Christen RD,Howell SB

    更新日期:1993-12-02 00:00:00

  • Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles.

    abstract::We previously reported that exosomal nanoparticles secreted by human pancreatic tumoral cell lines decrease tumoral cell proliferation through the mitochondria-dependent apoptotic pathway, because of activation of pro-apoptotic phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and of glucose synthase kina...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24375

    authors: Ristorcelli E,Beraud E,Mathieu S,Lombardo D,Verine A

    更新日期:2009-09-01 00:00:00

  • Testicular cancer in nine northern European countries.

    abstract::The incidence of testicular cancer was examined in the Nordic and Baltic countries, Poland and Germany by collaboration among 10 cancer registries. Population-based registers were used to analyze a total of 34,309 cases, diagnosed from the start of registration (varying from 1943 in Denmark to 1980 in Latvia and Lithu...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910590108

    authors: Adami HO,Bergström R,Möhner M,Zatoński W,Storm H,Ekbom A,Tretli S,Teppo L,Ziegler H,Rahu M

    更新日期:1994-10-01 00:00:00

  • Inhibition of breast tumor growth and angiogenesis by a medicinal herb: Ocimum gratissimum.

    abstract::Ocimum sp. is a traditionally used medicinal herb, which shows anti-oxidant, anti-carcinogenic, radio-protective and free radical scavenging properties. So far no detailed studies have been reported on its effects on human cancers. Thus, we analyzed its effects on human breast cancer utilizing in vitro and in vivo met...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22733

    authors: Nangia-Makker P,Tait L,Shekhar MP,Palomino E,Hogan V,Piechocki MP,Funasaka T,Raz A

    更新日期:2007-08-15 00:00:00

  • Oncogenic PIK3CA mutations in colorectal cancers and polyps.

    abstract::Oncogenic PIK3CA mutations contribute to colorectal tumorigenesis by activating AKT signaling to decrease apoptosis and increase tumor invasion. A synergistic association of PIK3CA mutation with KRAS mutation has been suggested to increase AKT signaling and resistance to antiepidermal growth factor receptor inhibitor ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.26440

    authors: Whitehall VL,Rickman C,Bond CE,Ramsnes I,Greco SA,Umapathy A,McKeone D,Faleiro RJ,Buttenshaw RL,Worthley DL,Nayler S,Zhao ZZ,Montgomery GW,Mallitt KA,Jass JR,Matsubara N,Notohara K,Ishii T,Leggett BA

    更新日期:2012-08-15 00:00:00

  • Genes and molecular pathways related to radioresistance of oral squamous cell carcinoma cells.

    abstract::To identify genes associated with radioresistant oral squamous cell carcinoma (OSCC), we compared gene expression signatures between OSCC cell lines exhibiting radioresistance and cells with radiosensitivity after X-ray irradiation in a dose-dependent manner using Affymetrix GeneChip analysis with Human Genome-U133 pl...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22561

    authors: Ishigami T,Uzawa K,Higo M,Nomura H,Saito K,Kato Y,Nakashima D,Shiiba M,Bukawa H,Yokoe H,Kawata T,Ito H,Tanzawa H

    更新日期:2007-05-15 00:00:00

  • Loss of hSef promotes metastasis through upregulation of EMT in prostate cancer.

    abstract::We have previously reported that the negative signaling regulator Similar Expression to FGF (hSef) is downregulated in prostate cancer and its loss is associated with clinical metastasis. Here, we explored the mechanistic basis of this finding. We first confirmed our clinical observation by testing hSef manipulation i...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.30604

    authors: Hori S,Wadhwa K,Pisupati V,Zecchini V,Ramos-Montoya A,Warren AY,Neal DE,Gnanapragasam VJ

    更新日期:2017-04-15 00:00:00

  • Resistance-associated factors in human small-cell lung-carcinoma GLC4 sub-lines with increasing adriamycin resistance.

    abstract::Previous studies have shown that the in vitro-selected adriamycin-resistant human small-cell lung-carcinoma cell line GLC4-ADR150 displays multidrug resistance as the result of 3-fold decreased DNA-topoisomerase II (topo II) activity and a 6-fold reduction in adriamycin accumulation. Not the MDR1 gene, but the MRP gen...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910610317

    authors: Versantvoort CH,Withoff S,Broxterman HJ,Kuiper CM,Scheper RJ,Mulder NH,de Vries EG

    更新日期:1995-05-04 00:00:00

  • Corynebacterium parvum prevents immunization to admixed irradiated tumor cells by a local process.

    abstract::Immunization of mice with 10(6) irradiated LSTRA murine leukemia cells (LX) induced weak immunity to subsequent tumor-cell challenge. Admixture of low doses (1.4-14 micrograms of C. parvum with the LX usually augmented the immunity. Higher doses (1,400-7,000 micrograms) of admixed C. parvum not only failed to augment ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910290617

    authors: Titus MJ,Bartlett GL,Kreider JW

    更新日期:1982-06-15 00:00:00

  • Familial breast cancer in the family-cancer database.

    abstract::We use the population-based Family-Cancer Database from Sweden to study familial breast cancer. The size of the population and the nation-wide registration of cancer offer unique possibilities for epidemiological studies of familial cancer, including complete and unbiased identification of cases in the probands and in...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19980729)77:3<386::aid-ijc

    authors: Hemminki K,Vaittinen P

    更新日期:1998-07-29 00:00:00

  • Cervical nitric oxide release and persistence of high-risk human papillomavirus in women.

    abstract::Nitric oxide may serve as one cofactor for human papillomavirus (HPV)-induced development of cervical cancer. Therefore, we first assessed the levels of cervical fluid nitric oxide metabolite (NOx) in 283 women with and without high-risk (hr) HPV. The NOx level in women with hr HPV (48.4 μmol/L [95% CI: 39.4-56.6], n ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25637

    authors: Rahkola P,Väisänen-Tommiska M,Tuomikoski P,Ylikorkala O,Mikkola TS

    更新日期:2011-06-15 00:00:00

  • Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis.

    abstract::EPLIN is frequently downregulated or lost in various cancers. The purpose of this study was to evaluate the importance of EPLIN in prostate cancer progression, with particular focus on the mechanistic implications to elucidate EPLIN's tumor suppressive function in cancer. EPLIN expression was evaluated in prostate can...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31786

    authors: Collins RJ,Morgan LD,Owen S,Ruge F,Jiang WG,Sanders AJ

    更新日期:2018-11-15 00:00:00

  • Discrepancies between detection of Bcl-2 by in situ hybridization and immunocytochemistry in human prostate cancer tissues.

    abstract::Extensive study of Bcl-2 protein expression in prostate cancer (CaP) tissues by means of immunocytochemistry (IC) has provided evidence that it positively correlates with high grade and stage of CaP and is associated with resistance to anti-androgen hormone therapy. In the present study, we investigated the expression...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19981218)79:6<614::aid-ijc

    authors: Fiorentino M,D'Errico A,Barozzi C,Grigioni WF

    更新日期:1998-12-18 00:00:00