Abstract:
BACKGROUND:Deregulated RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways are found in hepatocellular carcinoma (HCC). This study aimed to test the inhibitory effects of PI-103 (a small molecule inhibitor of PI3K and mTOR) and sorafenib as single agents and in combination on HCC tumorigenesis in an in vivo xenograft model. MATERIALS AND METHODS:In vitro study: Huh7 proliferation was assayed by 3H-thymidine incorporation and by thiazolyl blue tetrazolium bromide (MTT) assay. Western blots were used to detect phosphorylation of the key enzymes in the two pathways. In vivo study: Human HCC cell line Huh7 was inoculated into nude mice s.c. and the mice were treated with sorafenib (20 mg/kg/day) and PI-103 (5 mg/kg, every 4 days). Tumor size was measured every other day. Tumors were isolated for western blot and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay detection of apoptosis and signaling pathway enzymes. RESULTS:Our in vitro study found that combination of sorafenib and PI-103 additively inhibited Huh7 proliferation as compared to single-agent treatment. Sorafenib and PI-103 as single agents differentially inhibited or activated key enzymes (MEK, ERK, AKT, mTOR, and S6K) in PI3K/AKT/mTOR and RAS/RAF/MAPK signaling pathways. Combination of sorafenib and PI-103 inhibited all the key enzymes in the two pathways. Our in vivo study demonstrated significant differences between control group, mono-drug groups and drug-combination group (p<0.05). Combination of Sorafenib and PI-103 more efficiently inhibited tumorigenesis as compared to mono-drug treatments (p<0.032). CONCLUSION:The combination of PI-103 and sorafenib has the advantage over mono-drug therapy on inhibition of HCC cell proliferation and tumorigenesis by inhibiting both PI3K/AKT/mTOR and RAS/RAF/MAPK signaling pathways.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Gedaly R,Angulo P,Chen C,Creasy KT,Spear BT,Hundley J,Daily MF,Shah M,Evers BMsubject
Has Abstractpub_date
2012-07-01 00:00:00pages
2531-6issue
7eissn
0250-7005issn
1791-7530pii
32/7/2531journal_volume
32pub_type
杂志文章abstract:BACKGROUND:Endometrial carcinoma is the most common malignancy of the female genital tract and its incidence is increasing. However, treatment results have not improved during the last decades. PATIENTS AND METHODS:Our regional quality register was used to evaluate treatment results for the period between January 1995...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Few investigators have focused on possible interactions among several MMPs collectively. MATERIALS AND METHODS:Immunostaining for MMP-7, MMP-2 and MT1-MMP was performed on 51 early invasive (T1) colorectal carcinomas, and correlations between the expressions of pairs of MMPs were examined. RESULTS:MMP-7 ex...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
abstract::The in vitro antioxidative activity of benzylideneascorbate (SBA) and the in vivo effect on adriamycin (ADR)-induced cardiotoxicity in a mouse model were investigated. The radical-scavenging activity of SBA was assayed in terms of reduction of chemiluminescence induced by O2-, generated in xanthine/xanthine oxidase an...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::The in vitro antitumor activity of a new platinum complex, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II) (SKI 2053R, NSC D644591), cisplatin (CDDP) and carboplatin (CBDCA) was determined against two human lung cancer (PC-9 and PC-14) and two human stomach cancer (MKN-45 and KATO II...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::It is generally agreed that most malignancies, particularly those that arise "spontaneously", are caused by randomly occurring mutations at specific sites of the genome. Hence oncogenesis of these spontaneous tumors can be described by stochastic mathematical models. In this paper we offer a mathematical approach to o...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Immunohistochemical expression of p53 protein was studied in FNA specimens of 20 breast ductal carcinomas, 20 fibroadenomas and 20 atypical ductal hyperplasia of the breast. Nine cases of breast carcinomas (45%), five fibroadenomas (25%) and four atypical ductal hyperplasia (20%) were found to be p53-immuno-positive. ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::Serially propagated fibroblast clones were treated with 25-mM methionine and a thioguanine resistance assay was performed at each passage to measure mutagenesis at the HGPRT locus. The spontaneous frequency of thioguanine resistant mutants before treatment was less than 5 X 10(-6) in four clones and 22 X 10(-6) in one...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::The androgen-signaling pathway plays a critical role in prostate cancer development and progression. We have recently demonstrated that the Wilms' tumor suppressor gene product, WT1, binds to multiple sites in the androgen receptor (AR) promoter and transcriptionally represses the AR gene promoter in vitro. We asked w...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:In the present study, 3 cytotoxic agents were combined as front-line chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. All 3 drugs have been used in other 2-agent combinations and have been shown to be effective as first-line therapy. PATIENTS AND METHODS:Sixty-one (53 male, 8 female, me...
journal_title:Anticancer research
pub_type: 杂志文章,多中心研究
doi:
更新日期:2006-03-01 00:00:00
abstract:BACKGROUND:Previously, the antitumour activity of some flavone-8-acetic acid (FAA) derivatives substituted with an acid function in position 2 of the benzene ring was evaluated. The most active compound resulted the one bearing a fluorine atom in position 7 of the flavone nucleus. In this paper, we evaluated new mono- ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2005-03-01 00:00:00
abstract:BACKGROUND/AIM:To identify predictors of local control and survival after whole-brain irradiation (WBI) for cerebral metastases from cancer of unknown primary (CUP). PATIENTS AND METHODS:In 140 patients receiving WBI alone or following resection, seven factors were investigated including treatment approach, WBI-regime...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.12492
更新日期:2018-04-01 00:00:00
abstract::The value of metabolic proton NMR spectroscopic imaging to detect and classify tumours increases with the spatial resolution and the information content of the spectra. Several factors influencing these quantities are discussed. ...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND:The tumor-suppressive effects of rabbit anti-p53 antibodies on chemically induced rat colon cancer were demonstrated previously (Cancer J, 10:116-120, 1997). METHODS:In this communication, the spleen's role in the immune response of rats to cancer and vaccination was evaluated histologically and immunohisto...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Although cancer belongs to one of the leading causes of death around the world, fortunately studies have shown that tumor cells have various targets that are susceptible to attack. Interestingly, tumor cells are comprised of cellular membranes, which are altered in chemical composition relative to non-neoplastic cells...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND/AIM:Triple-negative breast cancers (TNBC) lack expression of three important receptors, and have limited treatment options. High expression of junctional adhesion molecule-A (JAM-A) has been linked with aggressive tumor phenotypes including TNBC. This study aimed to evaluate the bioactivity of a JAM-A-down-r...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.13230
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:Epithelial protein lost in neoplasm-α (EPLIN-α) is a cytoskeletal protein whose expression is often lost or is aberrant in cancerous cells and tissues and whose loss is believed to be involved in aggressive phenotype. Our current study examined this molecule in human oesophageal tissues and investigated the ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-04-01 00:00:00
abstract::Melanoma is a tumor of continuously increasing incidence for which new methods of imaging and targeted therapy are widely sought. Radioiodinated methylene blue is a promising tracer, showing selective uptake in human pigmented melanoma cells. We performed 131I-labeling of the tracer using 1% methylene blue injection U...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2008-11-01 00:00:00
abstract:BACKGROUND/AIM:In breast cancer (BC) care, radiation therapy (RT) is an efficient treatment to control localized tumor. Radiobiological research is needed to understand molecular differences that affect radiosensitivity of different tumor subtypes and the response variability. The aim of this study was to analyze gene ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.12512
更新日期:2018-05-01 00:00:00
abstract::Development of multidrug-resistance (MDR) remains a major cause of failure in the treatment of cancer with chemotherapeutic agents. In our efforts to explore alternative treatment regimens for multidrug-resistant tumors we have examined the sensitivity of MDR tumor cell lines to lymphokine activated killer (LAK) cells...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::The cytotoxicity of beta-cyclodextrin benzaldehyde inclusion compound (CDBA) against human normal and cancer cell lines was investigated. CDBA showed slightly higher cytotoxicity against human tumor cell lines, as compared to normal cells, with a tumor-specificity index of 2.2. Human myelogenous leukemia cell lines (H...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
abstract::Several human and murine tumor cell lines were evaluated in an in vitro cytotoxicity assay as prescreens for fermentation extracts and pure materials subsequently tested in vivo against P388 leukemia or B16 melanoma. Each material, regardless of its in vitro cytotoxicity, was evaluated in vivo. At the criteria levels ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract:AIM:The evaluation of toxicity after high-dose-rate interstitial brachytherapy (HDR-ISBT) as monotherapy for localized prostate cancer. MATERIALS AND METHODS:We analyzed early and late toxicities in 100 patients treated by HDR-ISBT as monotherapy at the National Hospital Organization Osaka National Hospital using both...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Malignant gliomas still present a medical challenge, despite decades of continuous extensive research with optimization of surgical techniques, radiotherapy and systemic treatments. PATIENTS AND METHODS:From 1999 to 2004, 104 patients with WHO grade III and IVgliomas underwent surgery and received concomita...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2006-11-01 00:00:00
abstract::In the in vivo system, cancer metastasis is a complex multi-step process. We have utilized an in vitro three-dimensional system to study the initial stages of tumour cell invasion. In this communication, the sequence of events in interactions between B16 melanoma cells and normal mouse skin fibroblasts are described. ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract:UNLABELLED:The quantity and quality of circulating DNA fragments was analyzed by quantitative real-time polymerase chain reactions (qPCR) in plasma from patients with esophageal carcinomas, in order to assess their diagnostic value. PATIENTS AND METHODS:Plasma was collected preoperatively from 24 patients with esophag...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2007-07-01 00:00:00
abstract:AIM:Aim of the study was to evaluate feasibility and toxicities of exclusive radiosurgery using tomotherapy in patients with brain oligo-metastases. PATIENTS AND METHODS:Between 2008 and 2013 68 patients underwent stereotactic radiosurgery (SRS). Mean patient age was 63 years. Brain was the only site involved in 32 pa...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2015-12-01 00:00:00
abstract::The mouse/human chimeric antibody Ch F11-39, recently generated by ourselves, shows the same high specificity and affinity for carcinoembryonic antigen (CEA) as those of its parental mouse monoclonal antibody. Ch F11-39 is capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) with human peripheral ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Ovarian tumors of low malignant potential (LMPs) are intermediate between adenomas and ovarian carcinomas (OCs); however, whether an LMP is a precursor of OC or is a unique type of tumor that will not progress to OC is still controversial. To gain better insight into the relationship between LMP and OC, we compared pr...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2003-11-01 00:00:00
abstract::Cisplatin is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. Although the effectiveness of cisplatin is high, its toxicities justify the demand for improved formulations of this drug. A liposomal formulation of cisplatin, Lipoplatin, was developed in o...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2004-07-01 00:00:00
abstract::Eight patients with metastatic hypernephroma were treated with constant infusion recombinant Interleukin-2 (rIL-2), changes in renal and hepatic function and protein levels were monitored during 2 cycles of treatment. The rIL-2 infusion caused a reversible fall in ures and a non-reversible rise in creatinine. Liver fu...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00