In vivo analysis of insulin-like growth factor type 1 receptor humanized monoclonal antibody MK-0646 and small molecule kinase inhibitor OSI-906 in colorectal cancer.

Abstract:

:The development and characterization of effective anticancer drugs against colorectal cancer (CRC) is of urgent need since it is the second most common cause of cancer death. The study was designed to evaluate the effects of two IGF-1R antagonists, MK-0646, a recombinant fully humanized monoclonal antibody and OSI-906, a small molecule tyrosine kinase inhibitor on CRC cells. Xenograft study was performed on IGF-1R-dependent CRC cell lines for analyzing the antitumor activity of MK-0646 and OSI-906. Tumor proliferation and apoptosis were assessed using Ki67 and TUNEL assays, respectively. We also performed in vitro characterization of MK-0646 and OSI-906 treatment on CRC cells to identify mechanisms associated with drug-induced cell death. Exposure of the GEO and CBS tumor xenografts to MK-0646 or OSI-906 led to a decrease in tumor growth. TUNEL analysis showed an increase of approximately 45-55% in apoptotic cells in both MK-0646 and OSI-906 treated tumor samples. We report the novel finding that treatment with IGF-1R antagonists led to downregulation of X-linked inhibitor of apoptosis (XIAP) protein involved in cell survival and inhibition of cell death. In conclusion, IGF-1R antagonists (MK-0646 and OSI-906) demonstrated single agent inhibition of subcutaneous CRC xenograft growth. This was coupled to pro-apoptotic effects resulting in downregulation of XIAP and inhibition of cell survival. We report a novel mechanism by which MK-0646 and OSI-906 elicits cell death in vivo and in vitro. Moreover, these results indicate that MK-0646 and OSI-906 may be potential anticancer candidates for the treatment of patients with IGF-1R-dependent CRC.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Leiphrakpam PD,Agarwal E,Mathiesen M,Haferbier KL,Brattain MG,Chowdhury S

doi

10.3892/or.2013.2819

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

87-94

issue

1

eissn

1021-335X

issn

1791-2431

journal_volume

31

pub_type

杂志文章
  • microRNA-520a-3p inhibits proliferation and cancer stem cell phenotype by targeting HOXD8 in non-small cell lung cancer.

    abstract::Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigenesis, tumour recurrence and therapy resistance and microRNA is essential for the development of the biological traits of CSCs and the increased cells proliferation. Studying molecular mechanism of tumorigenesis, tumour rec...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.5149

    authors: Liu Y,Miao L,Ni R,Zhang H,Li L,Wang X,Li X,Wang J

    更新日期:2016-12-01 00:00:00

  • PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells.

    abstract::Glioblastoma is the most common type of primary brain tumour in adults, and its pathogenesis is particularly complicated. Among the many possible mechanisms underlying its pathogenesis, hyperactivation of the PI3K/Akt pathway is essential to the occurrence and development of glioma through the loss of PTEN or somatic ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6845

    authors: Xu PF,Yang JA,Liu JH,Yang X,Liao JM,Yuan FE,Liu BH,Chen QX

    更新日期:2019-01-01 00:00:00

  • Lactoferrin immunoexpression in endometrial carcinomas: relationships with sex steroid hormone receptors (ER and PR), proliferation indices (Ki-67 and AgNOR) and survival.

    abstract::We have investigated Lf immunoexpression as well as its biological meaning in 71 formalin-fixed, paraffin-embedded surgical samples of endometrial carcinomas (EC); 64 EC were endometrioid type, whereas 7 were non-endometrioid carcinomas. Immunohistochemistry was performed by primary antibodies against Lactoferrin (Lf)...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Giuffrè G,Arena F,Scarfì R,Simone A,Todaro P,Tuccari G

    更新日期:2006-08-01 00:00:00

  • Possible predictive markers related to micro-metastasis in breast cancer patients.

    abstract::Despite significant advances in micro-metastasis detection methods, little is known about the relationship between micro-metastasis and primary tumors. The purpose of this study was to assess the ability of expression of the breast cancer-related markers, HER-2/neu, COX-2, VEGF and PDGF-B, as a predictor for micro-met...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Zhu L,Loo WT,Cheng CW,Chow LW

    更新日期:2006-05-01 00:00:00

  • Oleanolic acid enhances the radiosensitivity of tumor cells under mimetic hypoxia through the reduction in intracellular GSH content and HIF-1α expression.

    abstract::We previously found that oleanolic acid (OA), a naturally pentacyclic triterpenoid, enhances the radiosensitizing effect on tumor cells. However, it is unclear whether or not OA enhances the radiosensitivity of hypoxic cells. Therefore, the aim of the present study was to further observe the influence of OA on hypoxic...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3064

    authors: Qi R,Jin W,Wang J,Yi Q,Yu M,Xu S,Jin W

    更新日期:2014-05-01 00:00:00

  • Angiotensin II receptor type 1 blockers suppress the cell proliferation effects of angiotensin II in breast cancer cells by inhibiting AT1R signaling.

    abstract::Chronic stress and a high-fat diet are well-documented risk factors associated with the renin-angiotensin system in the development of breast cancer. The angiotensin II type 1 receptor (AT1R) is a novel component of the renin-angiotensin system. Several recent studies have focused on the function of AT1R in cell proli...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1720

    authors: Du N,Feng J,Hu LJ,Sun X,Sun HB,Zhao Y,Yang YP,Ren H

    更新日期:2012-06-01 00:00:00

  • Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells.

    abstract::Chemokine C-C motif ligand 5 (CCL5) is an important marker related to the progression of breast cancer and is upregulated in cancer cells. However, the mechanism of the overexpression of CCL5 in tumours has not yet been clarified. The present study aimed to investigate the role of endoplasmic reticulum (ER) stress in ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3479

    authors: Zhang Y,Liao S,Fan W,Wei W,Wang C,Sun S

    更新日期:2014-12-01 00:00:00

  • Cancer patients treated with the Banerji protocols utilising homoeopathic medicine: a Best Case Series Program of the National Cancer Institute USA.

    abstract::Although many studies have been conducted on the role of alternative medicine in the treatment of cancer, only a few reports have been published regarding the total regression of malignant tumors. At the PBH Research Foundation (PBHRF), two of the authors have used homoeopathic therapy to treat many patients with vari...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Banerji P,Campbell DR,Banerji P

    更新日期:2008-07-01 00:00:00

  • Perillyl alcohol causes G1 arrest through p15(INK4b) and p21(WAF1/Cip1) induction.

    abstract::The monoterpene perillyl alcohol (POH) is a naturally occurring compound derived from citrus fruits, mint and herbs. It exhibited chemotherapeutic potential against various malignant tumors in preclinical models and is currently being tested in clinical trials in patients with refractory advanced cancers. POH inhibits...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2167

    authors: Koyama M,Sowa Y,Hitomi T,Iizumi Y,Watanabe M,Taniguchi T,Ichikawa M,Sakai T

    更新日期:2013-02-01 00:00:00

  • In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human colon cancer cell HCT 116 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry.

    abstract::Colorectal cancer is the second most deadly cancer in the United States. When diagnosed early, current treatments bring a limited success; however, once metastasis occurs, radiation and chemotherapy are generally ineffective. Structural changes in the ECM are necessary for cell migration during tissue remodeling. Matr...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Roomi MW,Ivanov V,Kalinovsky T,Niedzwiecki A,Rath M

    更新日期:2005-03-01 00:00:00

  • Pentoxifylline promotes development of murine colon adenocarcinoma-derived metastatic tumors in liver.

    abstract::Pentoxifylline is commonly used in the treatment of peripheral vascular diseases. It improves microcirculatory flow and tissue perfusion. Moreover, pentoxifylline displays some immunomodulatory properties that presumably might affect the anticancer response. Therefore, the aim of the present study was to evaluate the ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Grzela T,Lazarczyk M,Niderla J,Golab J,Lazarczyk MA,Skopinski P

    更新日期:2003-11-01 00:00:00

  • Changes of the O6-methylguanine-DNA methyltransferase promoter methylation and MGMT protein expression after adjuvant treatment in glioblastoma.

    abstract::The aim of this study was to evaluate variations of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and protein expression after adjuvant treatment in glioblastoma patients. Sixteen patients with a glioblastoma underwent 34 microsurgeries including 18 re-operations. After surgery, patients underwent...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000760

    authors: Jung TY,Jung S,Moon KS,Kim IY,Kang SS,Kim YH,Park CS,Lee KH

    更新日期:2010-05-01 00:00:00

  • Quercetin-induced autophagy flux enhances TRAIL-mediated tumor cell death.

    abstract::Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer therapeutic agent and autophagy mediator. We investigated whether quercetin enhances TRAIL-induced tumor cell death and...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.3991

    authors: Moon JH,Eo SK,Lee JH,Park SY

    更新日期:2015-07-01 00:00:00

  • Plumbagin reduces chronic lymphocytic leukemia cell survival by downregulation of Bcl-2 but upregulation of the Bax protein level.

    abstract::Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis rates. The aberration of apoptosis-related genes in CLL cells results in defective apoptosis of CLL cells i...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4950

    authors: Fu C,Gong Y,Shi X,Sun Z,Niu M,Sang W,Xu L,Zhu F,Wang Y,Xu K

    更新日期:2016-09-01 00:00:00

  • Cross-validation of genes potentially associated with overall survival and drug resistance in ovarian cancer.

    abstract::Ovarian cancer is the leading cause of death among malignancies of the female reproductive system. The 5-year survival rates of ovarian cancer (OC) patients are very poor as a result of recurrent disease and emergence of drug resistance; thus, studies to find predictive markers and factors for drug resistance are ongo...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5534

    authors: Gao Y,Liu X,Li T,Wei L,Yang A,Lu Y,Zhang J,Li L,Wang S,Yin F

    更新日期:2017-05-01 00:00:00

  • Combined oncolytic and vaccination activities of parvovirus H-1 in a metastatic tumor model.

    abstract::Oncolytic viruses have emerged as a novel class of potent anticancer agents offering an improvement on chemo- and radiotherapy in terms of tumor targeting and reduction of side-effects. Among these agents, autonomous parvoviruses have attracted the attention of researchers for their ability to preferentially replicate...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Raykov Z,Grekova S,Galabov AS,Balboni G,Koch U,Aprahamian M,Rommelaere J

    更新日期:2007-06-01 00:00:00

  • Immunotherapy with irradiated autologous leukemic cells in patients with B-CLL in early stages.

    abstract::In this study 10(7) peripheral blood mononuclear cells including on average 78.56% CD19+/CD5+ lymphocytes were irradiated, and then administered intradermally as an anti-cancer vaccine to seventeen patients with B-cell chronic lymphocytic leukemia (B-CLL) at early stages (twelve injections, four at a weekly interval f...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Hus I,Kawiak J,Tabarkiewicz J,Radej S,Hoser G,Bojarska-Junak A,Schmitt M,Giannopoulos K,Dmoszynska A,Rolinski J

    更新日期:2008-08-01 00:00:00

  • Inhibition of pancreatic cancer and potentiation of gemcitabine effects by the extract of Pao Pereira.

    abstract::Lack of effective therapy is a major problem in the treatment of pancreatic cancer. In the present study, we investigated a natural product, the extract of Pao Pereira (Pao), for its anti-pancreatic cancer effect in vitro and in vivo, either alone or in combination with the first-line chemotherapeutic drug gemcitabine...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2461

    authors: Yu J,Drisko J,Chen Q

    更新日期:2013-07-01 00:00:00

  • AZD8055 induces cell death associated with autophagy and activation of AMPK in hepatocellular carcinoma.

    abstract::AZD8055 is a potent inhibitor of mTORC1 and mTOR2 and shows inhibitory effects in several types of cancer cells in vitro and in vivo. However, the effect of AZD8055 on hepatocellular carcinoma (HCC) cells has not been studied. We report that AZD8055 inhibits cell proliferation and colony formation of Hep3B and Huh7 ce...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2890

    authors: Hu M,Huang H,Zhao R,Li P,Li M,Miao H,Chen N,Chen M

    更新日期:2014-02-01 00:00:00

  • Treatment with HER-2 phosphorylation agonists enhance tumor ability to stimulate epitope specific CTL in vitro.

    abstract::The transmembrane (TM) receptor encoded by the HER-2 proto-oncogene (HER-2) is amplified in several types of human carcinomas and premalignant states and provides an important target for cancer therapy. While overexpression of HER-2 should lead to increased CTL epitope formation due to the attendant increase in higher...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Castilleja A,Ward NE,Epstein RB,Kudelka AP,Gershenson DM,Efferson CL,O'Brian CA,Ioannides CG

    更新日期:2002-09-01 00:00:00

  • Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: a randomized control trial.

    abstract::Insulin resistance (IR) is reportedly involved in the progression of hepatocellular carcinoma (HCC). Since neovascularization plays an important role in hepatocarcinogenesis and IR, an angiostatic therapy may be considered as one of the promising approaches for chemoprevention again...

    journal_title:Oncology reports

    pub_type: 杂志文章,随机对照试验

    doi:10.3892/or.2011.1433

    authors: Yoshiji H,Noguchi R,Ikenaka Y,Kaji K,Aihara Y,Yamazaki M,Yamao J,Toyohara M,Mitoro A,Sawai M,Yoshida M,Morioka C,Fujimoto M,Uemura M,Fukui H

    更新日期:2011-12-01 00:00:00

  • High-risk HPV L1 capsid protein as a marker of cervical intraepithelial neoplasia in high-risk HPV-positive women with minor cytological abnormalities.

    abstract::Human papillomavirus (HPV) L1 capsid protein is only produced during a productive HPV infection at the end of the natural viral life cycle and is a major target of the immune response in women with HPV-related squamous intraepithelial lesions. We evaluated the usefulness of L1 detection by immunocytochemistry in high-...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2538

    authors: Norman I,Hjerpe A,Andersson S

    更新日期:2013-08-01 00:00:00

  • MicroRNA‑203a‑3p is a candidate tumor suppressor that targets thrombospondin 2 in colorectal carcinoma.

    abstract::The aim of the present study was to investigate the role of miR‑203a‑3p in colorectal cancer (CRC) and identify the target gene of microRNA (miR)‑203a‑3p. A total of 59 sets of cancer tissues and corresponding adjacent non‑tumor tissues were collected from CRC patients (aged 31‑78 years) between October 2016 and May 2...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2019.7310

    authors: Qian Z,Gong L,Mou Y,Han Y,Zheng S

    更新日期:2019-11-01 00:00:00

  • Pilot trial of autologous dendritic cells loaded with tumor lysate(s) from allogeneic tumor cell lines in patients with metastatic medullary thyroid carcinoma.

    abstract::Immunotherapy with autologous dendritic cells (DCs) loaded with tumor lysate(s) from allogeneic tumor cell lines is a novel strategy to induce immune responses in cancer patients. We report on a pilot trial of autologous DCs pulsed with tumor cell lysate derived from allogeneic medullary thyroid carcinoma (MTC) cell l...

    journal_title:Oncology reports

    pub_type: 临床试验,杂志文章

    doi:10.3892/or_00000391

    authors: Bachleitner-Hofmann T,Friedl J,Hassler M,Hayden H,Dubsky P,Sachet M,Rieder E,Pfragner R,Brostjan C,Riss S,Niederle B,Gnant M,Stift A

    更新日期:2009-06-01 00:00:00

  • Mechanism of the inhibition of the STAT3 signaling pathway by EGCG.

    abstract::Signal transducer and activator of transcription 3 (STAT3) is an oncogene that promotes cell survival, proliferation, and motility. In the present study, we explored the mechanism involved in the inhibition by epigallocatechin-3-gallate (EGCG) of STAT3 signaling as detected by surface plasmon resonance (SPR)-binding a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2743

    authors: Wang Y,Ren X,Deng C,Yang L,Yan E,Guo T,Li Y,Xu MX

    更新日期:2013-12-01 00:00:00

  • Antitumor effects of IDN5109 on head and neck squamous cell carcinoma.

    abstract::Taxanes, a new class of antitumor drugs, are effective against a large number of human tumors, although there are problems with drug resistance. The novel taxane, IDN5109, is characterized by its high tolerability, antitumor efficacy, ability to overcome multidrug resistance, and oral bioavailabilty. We investigated t...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Sano D,Matsuda H,Ishiguro Y,Nishimura G,Kawakami M,Tsukuda M

    更新日期:2006-02-01 00:00:00

  • Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway.

    abstract::Several studies have shown that curcumin can induce apoptosis and inhibit growth in human A549 lung adenocarcinoma cells. However, the mechanism is not completely understood yet. The present study was designed to investigate the effects of curcumin on A549 cells to better understand its apoptosis and apoptosis-related...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Chen Q,Wang Y,Xu K,Lu G,Ying Z,Wu L,Zhan J,Fang R,Wu Y,Zhou J

    更新日期:2010-02-01 00:00:00

  • Radioiodine-labeled anti-epidermal growth factor receptor binding bovine serum albumin-polycaprolactone for targeting imaging of glioblastoma.

    abstract::The aim of this study was to look for a new medicine in diagnosing and treating of glioblastoma. Radioiodine-labeled anti-epidermal growth factor receptor (EGFR) binding nanoparticles were constructed. In vitro cell-binding assays were confirmed by confocal microscopy and flow cytometry. Cell cytotoxicity assays were ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5937

    authors: Li C,Tan J,Chang J,Li W,Liu Z,Li N,Ji Y

    更新日期:2017-11-01 00:00:00

  • ABL-N may induce apoptosis of human prostate cancer cells through suppression of KLF5, ICAM-1 and Stat5b, and upregulation of Bax/Bcl-2 ratio: An in vitro and in vivo study.

    abstract::Identification of novel botanicals that can selectively induce apoptosis and arrest growth of cancer cells without producing cytotoxic effects is highly appreciable for cancer therapy. The present study aimed to investigate the possibility of acetylbritannilactone (ABL) derivative 5-(5-(ethylperoxy)pentan-2-yl)-6-meth...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.4293

    authors: Zhang Y,Liu K,Zhang Y,Qi J,Lu B,Shi C,Yin Y,Cai W,Li W

    更新日期:2015-12-01 00:00:00

  • PMA/IONO affects diffuse large B-cell lymphoma cell growth through upregulation of A20 expression.

    abstract::Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. A20 and mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) are known to be related to DLBCL pathogenesis and progression. This study aimed to assess the effects of phorbol myristate acetate/ionomycin (PMA/IONO) on the growth a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4899

    authors: Yang W,Li Y,Li P,Wang L

    更新日期:2016-08-01 00:00:00