Metronomic treatment of temozolomide inhibits tumor cell growth through reduction of angiogenesis and augmentation of apoptosis in orthotopic models of gliomas.

Abstract:

:Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Temozolomide (TMZ), a methylating agent is one of the most effective chemotherapeutic agents against glioblastoma. To overcome the problem that most of these tumors become resistant to chemotherapeutic regimens within a year, we investigated the antitumor efficacy of metronomic administration of low-dose TMZ in in vitro cell proliferation/cytotoxicity assay and in vivo rat and nude mouse orthotopic glioma model. By in vitro assay, we elucidated that C6/LacZ rat glioma cells were more resistant to metronomic treatment of TMZ than U-87MG human glioblastoma cells and bEnd.3 mouse brain endothelial cells. Compared with the conventional chemotherapeutic regimen of TMZ, we found that frequent administration of TMZ at a low dose (metronomic treatment) markedly inhibited angiogenesis as well as tumor growth in a TMZ-resistant C6/LacZ rat glioma model. In addition, metronomic treatment of TMZ significantly augmented apoptosis of tumor cells in this model. For the TMZ-sensitive U-87MG cells, even with a very low dose of TMZ, which is not effective to reduce tumor mass, the metronomic treatment of TMZ reduced the microvessel density, i.e. angiogenesis, in a nude mouse orthotopic model. In conclusion, for both models, the metronomic treatment of TMZ decreased angiogenesis. Especially, in TMZ-resistant glioma cells, this regimen increased apoptosis of tumor cells and decreased tumor growth. The metronomic treatment of TMZ in orthotopic glioma models demonstrated a successful antiangiogenic effect which can overcome the chemoresistance in conventional TMZ chemotherapy.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Kim JT,Kim JS,Ko KW,Kong DS,Kang CM,Kim MH,Son MJ,Song HS,Shin HJ,Lee DS,Eoh W,Nam DH

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

33-9

issue

1

eissn

1021-335X

issn

1791-2431

journal_volume

16

pub_type

杂志文章
  • Effective antitumor immunity against murine gliomas using dendritic cells transduced with hTERTC27 recombinant adenovirus.

    abstract::hTERTC27, a 27-kDa hTERT C-terminal polypeptide has been demonstrated to cause hTERT-positive HeLa cell apoptosis and inhibits the growth of mouse melanoma. hTERTC27 has been associated with telomere dysfunction, regulation of gene-regulated apoptosis, the cell cycle and activation of natural killer (NK) cells, but it...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1619

    authors: Gong HX,He L,Li XP,Wang YD,Li Y,Huang JJ,Wang Z,Xie D,Kung HF,Peng Y

    更新日期:2012-04-01 00:00:00

  • Apigenin inhibits the proliferation and invasion of osteosarcoma cells by suppressing the Wnt/β-catenin signaling pathway.

    abstract::Osteosarcoma (OS) is the most common type of bone cancer. Even with early diagnosis and aggressive treatment, the prognosis for OS is poor. In the present study, we investigated the proliferation and invasion inhibitory effect of apigenin on human OS cells and the possible molecular mechanisms involved. The cell viabi...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4022

    authors: Liu X,Li L,Lv L,Chen D,Shen L,Xie Z

    更新日期:2015-08-01 00:00:00

  • Loss of heterozygosity of nucleotide excision repair factors in sporadic oral squamous cell carcinoma using microdissected tissue.

    abstract::The deficiencies of nucleotide excision repair (NER) factors are involved in rare genetic diseases such as xeroderma pigmentosum (XP) with increased risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (L...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.8.5.1133

    authors: Miyashita H,Mori S,Tanda N,Nakayama K,Kanzaki A,Sato A,Morikawa H,Motegi K,Takebayashi Y,Fukumoto M

    更新日期:2001-09-01 00:00:00

  • Expression of circular RNA CDR1‑AS in colon cancer cells increases cell surface PD‑L1 protein levels.

    abstract::The expression of CDR1‑AS, a representative circular RNA, is closely linked with poor prognosis in gastrointestinal cancers, such as colon, liver, and pancreatic cancers. Although it is well known that CDR1‑AS antagonizes microRNA‑7 function through its sequence similarities in the brain, its biological function and l...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7244

    authors: Tanaka E,Miyakawa Y,Kishikawa T,Seimiya T,Iwata T,Funato K,Odawara N,Sekiba K,Yamagami M,Suzuki T,Ishibashi R,Otsuka M,Koike K

    更新日期:2019-10-01 00:00:00

  • Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis.

    abstract::Oral squamous cell carcinoma (OSCC) cells are relatively resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis during culture. We investigated the role of a proteaosome inhibitor in the survival and apoptosis of these cells. We found that the proteasome inhibitor MG132 markedl...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2010.1127

    authors: Yoshiba S,Iwase M,Kurihara S,Uchida M,Kurihara Y,Watanabe H,Shintani S

    更新日期:2011-03-01 00:00:00

  • Loss of miR-638 promotes invasion and epithelial-mesenchymal transition by targeting SOX2 in hepatocellular carcinoma.

    abstract::Aberrant expression of microRNAs has been identified as regulators of biological processes of hepatocellular carcinoma (HCC) by negatively regulating protein-coding mRNAs. Several studies have demonstrated that miR-638 expression was dysregulated in various human cancers. However, the clinical significance and underly...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5273

    authors: Zhang Y,Zhang D,Jiang J,Dong L

    更新日期:2017-01-01 00:00:00

  • Knockdown of long non-coding RNA HOTAIR inhibits proliferation and invasiveness and improves radiosensitivity in colorectal cancer.

    abstract::Colorectal cancer (CRC) is still one of the most important neoplasias causing human death. Multidisciplinary therapy has won consensus in the management of CRC, of which, radiotherapy occupies an important position. However, radioresistance is still a major obstacle in local control of CRC. Overexpression of long non-...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4397

    authors: Yang XD,Xu HT,Xu XH,Ru G,Liu W,Zhu JJ,Wu YY,Zhao K,Wu Y,Xing CG,Zhang SY,Cao JP,Li M

    更新日期:2016-01-01 00:00:00

  • Fascin is involved in cancer cell invasion and is regulated by stromal factors.

    abstract::The tumor microenvironment plays an important role in cancer growth, invasion and metastasis. The stroma surrounding a tumor is known to contain a variety of factors that can increase angiogenesis, cancer growth and tumor progression. The aim of the present study was to determine the role of fascin in cancer growth an...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6847

    authors: Zhang X,Cho IH,Park JH,Lee MK,Hwang YS

    更新日期:2019-01-01 00:00:00

  • Effect of brachytherapy on NF-κB and VEGF in gastric carcinoma xenografts.

    abstract::Iodine-125 (125I) seed irradiation can be used as an important supplementary treatment for unresectable advanced gastric cancer. However, the radiobiological mechanism underlying brachytherapy remains unclear. Therefore, we investigated the influence of continuous and low-energy 125I irradiation on the cell cycle dist...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3255

    authors: Zhang WF,Jin WD,Li B,Wang MC,Li XG,Mao WY,Luo KY

    更新日期:2014-08-01 00:00:00

  • Restoration of miR-7 expression suppresses the growth of Lewis lung cancer cells by modulating epidermal growth factor receptor signaling.

    abstract::microRNAs are an abundant class of short endogenous non-coding RNAs that function as important regulators of multiple target genes and participate in diverse biological roles in carcinogenesis. However, the role of miR-7 in lung cancer remains unclear and requires further elucidation. In the present study, we found a ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3519

    authors: Li J,Zheng Y,Sun G,Xiong S

    更新日期:2014-12-01 00:00:00

  • Peroxiredoxin2 downregulation enhances hepatocellular carcinoma proliferation and migration, and is associated with unfavorable prognosis in patients.

    abstract::It has been revealed by our previous proteomic study that the expression profile is different between well‑differentiated and poorly differentiated hepatocellular carcinoma (HCC). Among those differently expressed proteins, peroxiredoxin2 (PRDX2) was our protein of interest. The present study aimed to further investig...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.6977

    authors: Bai B,Lin Y,Hu J,Wang H,Li L,Zhao S,Zhang J,Meng W,Yue P,Bai Z,Li X

    更新日期:2019-03-01 00:00:00

  • BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis.

    abstract::BTG1, which belongs to the BTG/Tob family, regulates cell cycle progression in a variety of cell types and appears to play roles in inhibiting proliferation, promoting apoptosis and stimulating cellular differentiation in multiple cell types. However, it remains unclear whether BTG1 is a breast cancer suppressor gene,...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2697

    authors: Zhu R,Zou ST,Wan JM,Li W,Li XL,Zhu W

    更新日期:2013-11-01 00:00:00

  • Possible mechanism of growth inhibition by Scutellaria baicalensis in an estrogen-responsive mouse tumor cell line.

    abstract::We have studied the effects of Saiboku-to, a traditional Chinese medicine having suppressive activities for leukotriene production and release, on the proliferation of the estrogen-responsive mouse Leydig tumor cell line B-1F. In our previous reports, it is shown that Saiboku-to promotes, but Scutellaria baicalensis, ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1196

    authors: Murashima T,Katayama H,Shojiro K,Nishizawa Y

    更新日期:2011-05-01 00:00:00

  • CHST15 promotes the proliferation of TE‑1 cells via multiple pathways in esophageal cancer.

    abstract::Esophageal squamous cell carcinoma (ESCC) is a common type of esophageal cancer and is prevalent worldwide. Understanding the mechanisms underlying its formation and the search for more effective therapeutic strategies are critical due to the occurrence of chemotherapeutic drug resistance. The aim of the present study...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7395

    authors: Wang X,Cheng G,Zhang T,Deng L,Xu K,Xu X,Wang W,Zhou Z,Feng Q,Chen D,Bi N,Wang L

    更新日期:2020-01-01 00:00:00

  • Combined analysis of gene expression, miRNA expression and DNA methylation profiles of osteosarcoma.

    abstract::Osteosarcoma (OS) is a common primary malignancy in children and adolescents with relative high survival rate after chemotherapy. While the toxicity of chemotherapy and personalized different response to chemotherapy makes it difficult for the selection of therapeutics and improvement of diagnosis. In this study, we c...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5324

    authors: Zhang W,Han S,Sun K

    更新日期:2017-02-01 00:00:00

  • Identification of intragenic methylation in the TUSC1 gene as a novel prognostic marker of hepatocellular carcinoma.

    abstract::Patients with hepatocellular carcinoma (HCC) have a poor prognosis, and novel molecular targets for treating recurrence and progression of the disease along with associated biomarkers are urgently required. In the present study, expression and the regulatory mechanism of TUSC1 (tumor suppressor candidate 1) were inves...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2939

    authors: Shimizu D,Kanda M,Nomoto S,Oya H,Takami H,Hibino S,Suenaga M,Inokawa Y,Hishida M,Takano N,Nishikawa Y,Yamada S,Fujii T,Nakayama G,Sugimoto H,Koike M,Fujiwara M,Kodera Y

    更新日期:2014-03-01 00:00:00

  • Antitumor effects of nano-bubble hydrogen-dissolved water are enhanced by coexistent platinum colloid and the combined hyperthermia with apoptosis-like cell death.

    abstract::In order to erase reactive oxygen species (ROS) related with the proliferation of tumor cells by reducing activity of hydrogen, we developed functional water containing nano-bubbles (diameters: <900 nm for 71%/population) hydrogen of 1.1-1.5 ppm (the theoretical maximum: 1.6 ppm) with a reducing ability (an oxidation-...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00001006

    authors: Asada R,Kageyama K,Tanaka H,Matsui H,Kimura M,Saitoh Y,Miwa N

    更新日期:2010-12-01 00:00:00

  • Do Ki67, S-phase, S + G2M and DNA ploidy, evaluated by flow cytometry, reveal locoregional metastasis in oral cavity and oropharynx carcinomas?

    abstract::Tumour cell proliferation is an important biological prognostic parameter to be considered alongside clinical and histopathological parameters. It has been evaluated by immunohistochemistry using proliferative markers (PCNA, Ki67, etc.) and by flow cytometry considering DNA content, growth fraction (S + G2M) and S-pha...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Tirelli G,Sidari L,Giacomarra V,Papanikolla L,Sasso F,Russolo M,Melato M

    更新日期:2002-05-01 00:00:00

  • Sosiho‑tang ameliorates cachexia‑related symptoms in mice bearing colon 26 adenocarcinoma by reducing systemic inflammation and muscle loss.

    abstract::Cachexia accompanied by muscle wasting is a key determinant of poor prognosis in cancer patients and cancer‑related death. Previous studies have demonstrated that inflammatory cytokines such as interleukin‑6 (IL‑6), tumor necrosis factor‑α (TNF‑α), IL‑1 and interferon‑γ (IFN‑γ) secreted from host cells and tumor cells...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4527

    authors: Kim A,Im M,Ma JY

    更新日期:2016-03-01 00:00:00

  • Characterization of proteins secreted by pancreatic cancer cells with anticancer drug treatment in vitro.

    abstract::Pancreatic cancer is one of the most lethal cancers, with an incidence equaling mortality. It is a heterogeneous group of neoplasms in which pancreatic ductal adenocarcinoma is most common. Pancreatic cancer cannot be cured even if detected early. When treatment is initiated, a suit...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2020

    authors: Takata T,Ishigaki Y,Shimasaki T,Tsuchida H,Motoo Y,Hayashi A,Tomosugi N

    更新日期:2012-12-01 00:00:00

  • Active immunotherapy for mouse breast cancer with irradiated whole-cell vaccine expressing VEGFR2.

    abstract::As tumor-associated antigens are not well characterized for the majority of human tumors, polyvalent vaccines prepared with whole-tumor antigens are an attractive approach for tumor vaccination. Vascular endothelial growth factor receptor-2 (VEGFR2), as a model antigen with which to...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2282

    authors: Yan HX,Cheng P,Wei HY,Shen GB,Fu LX,Ni J,Wu Y,Wei YQ

    更新日期:2013-04-01 00:00:00

  • Overexpression of IC53d promotes the proliferation of gastric cancer cells by activating the AKT/GSK3β/cyclin D1 signaling pathway.

    abstract::Cyclin‑dependent kinase 5 regulatory subunit‑​associated protein 3 (CDK5RAP3 or C53) is involved in the development of various types of tumor, and alternative splicing of C53 results in numerous transcription variants that encode different isoforms. The present study aimed to clone human C53 isoform d (IC53d) and expl...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7042

    authors: Lin JX,Xie XS,Weng XF,Qiu SL,Xie JW,Wang JB,Lu J,Chen QY,Cao LL,Lin M,Tu RH,Li P,Huang CM,Zheng CH

    更新日期:2019-05-01 00:00:00

  • Mutation analysis of CTNNB1 (beta-catenin) and AXIN1, the components of Wnt pathway, in cervical carcinomas.

    abstract::The components of the Wnt-signaling pathway are mutated in tumors, but the relationship between these components and cervical cancer has not been elucidated. In this study, we used immunohistochemistry, single strand confirmation polymorphism (SSCP) and direct sequencing methods to analyze the mutation and protein exp...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Su TH,Chang JG,Yeh KT,Lin TH,Lee TP,Chen JC,Lin CC

    更新日期:2003-09-01 00:00:00

  • Prognostic significance of p27/kip1 and apoptosis in patients with colorectal carcinoma.

    abstract::The protein p27/kip1 is a cyclin-dependent kinase inhibitor that regulates cell-cycle progression. In the present study, p27/kip1 expression as well as tumor cell proliferation and apoptosis were investigated in 80 colorectal carcinomas, using anti-p27/kip1 antibodies, in situ apoptosis detection kits and anti-PCNA an...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Noguchi T,Kikuchi R,Ono K,Takeno S,Moriyama H,Uchida Y

    更新日期:2003-07-01 00:00:00

  • In vivo and in situ imaging of head and neck squamous cell carcinoma using near-infrared fluorescent quantum dot probes conjugated with epidermal growth factor receptor monoclonal antibodies in mice.

    abstract::In this study, we applied near-infrared fluorescent quantum dots (NIRF-QDs) for non-invasive in vivo and in situ imaging of head and neck squamous cell carcinoma (HNSCC). The U14 squamous cancer cell line with high expression of epidermal growth factor receptor (EGFR) was implanted subcutaneously into the head and nec...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1705

    authors: Yang K,Zhao C,Cao YA,Tang H,Bai YL,Huang H,Zhao CR,Chen R,Zhao D

    更新日期:2012-06-01 00:00:00

  • Clinicoprognostical features of endometrial cancer patients with somatic mtDNA mutations.

    abstract::Somatic mitochondrial DNA (mtDNA) mutations have been found in a subset of endometrial cancers (EC) from different populations. We have investigated the relationship between mtDNA changes and clinical and pathological variables of women affected by EC. mtDNA mutations were detected both in early (3/32; 9%) and in adva...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Semczuk A,Lorenc A,Putowski L,Futyma K,Bryk J,Miotla P,Bartnik E

    更新日期:2006-11-01 00:00:00

  • Lack of prognostic significance of nm23 expression in human primary breast cancer.

    abstract::This retrospective study was designed to evaluate the prognostic value of immunohistochemically detected nm23-expression in invasive breast cancer. Cellular expression of nm23 was assessed in 325 primary breast cancer tissues by immunohistochemistry. The data were correlated to established functional factors of progno...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Göhring UJ,Eustermann I,Becker M,Neuhaus W,Rein DT,Schöndorf T

    更新日期:2002-11-01 00:00:00

  • MicroRNA-100 promotes migration and invasion through mammalian target of rapamycin in esophageal squamous cell carcinoma.

    abstract::Esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype of esophageal cancer and is characterized by a high mortality rate and geographic differences in incidence. microRNAs (miRNAs) are small, non-coding RNAs that play important roles in the regulation of genes associated with cancer developme...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3389

    authors: Zhang N,Fu H,Song L,Ding Y,Wang X,Zhao C,Zhao Y,Jiao F,Zhao Y

    更新日期:2014-10-01 00:00:00

  • Immunohistochemical characterization of pyrimidine synthetic enzymes, thymidine kinase-1 and thymidylate synthase, in various types of cancer.

    abstract::Thymidine kinase-1 (TK-1) and thymidylate synthase (TS) are key enzymes for salvage and de novo pyrimidine synthesis, respectively. Numerous studies have suggested that increased TS levels are associated closely with resistance to fluoropyrimidine-based chemotherapy. TAS-102 is a novel drug containing trifluorothymidi...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000770

    authors: Shintani M,Urano M,Takakuwa Y,Kuroda M,Kamoshida S

    更新日期:2010-05-01 00:00:00

  • Loss of imprinting of PEG1/MEST in lung cancer cell lines.

    abstract::Paternally expressed imprinted gene 1/mesoderm-specific transcript (PEG1/MEST) is an imprinted gene expressed from the paternal allele. Recently, frequent loss of imprinting (LOI) of PEG1/MEST has been reported in lung adenocarcinomas. It is suggested that the LOI may be involved in pathogenesis of lung adenocarcinoma...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Nakanishi H,Suda T,Katoh M,Watanabe A,Igishi T,Kodani M,Matsumoto S,Nakamoto M,Shigeoka Y,Okabe T,Oshimura M,Shimizu E

    更新日期:2004-12-01 00:00:00