Abstract:
:The major obstacle for the treatment of gastric cancer is recurrence and metastasis; yet, its molecular mechanism is largely unknown. 2-methoxyestradiol (2-ME), a metabolite of the estradiol-17beta, has recently been demonstrated to have multifactorial effects against tumor proliferation and angiogenesis; how these effects are interrelated and act cooperatively is the key question to be elucidated. Akt activation was shown to promote cancer cell invasiveness, and inhibition of Akt phosphorylation by 2-ME was also noted. We herein investigated the significance of PI3K/Akt activation in gastric cancer metastasis and the anti-metastatic effect of 2-ME through attenuation of Akt activity. Immunohistochemistry of PI3K, phosphorylated Akt (p-Akt) and phosphorylated Erk (p-Erk) was performed in tumors from 56 gastric cancer patients, and a significant correlation between PI3K/p-Akt and tumor stage/prognosis was demonstrated (p < 0.05). An in vitro study of 7 gastric cancer cell lines showed a remarkable correlation between PI3K and p-Akt. PI3K/p-Akt overexpression was associated with invasiveness/migration; in contrast, phosphorylation of Erk was not shown to be correlated with invasiveness. In addition, metastatic gastric cancer clones expressed a higher level of PI3K/p-Akt. The anti-metastatic effect of a low dose of 2-ME and inactivation of Akt was demonstrated. 2-ME also exhibited an ability to inhibit gastric cancer cell proliferation and induce G2/M cell cycle arrest at a higher concentration than that required for inhibition of migration. We conclude that the activation of PI3K/Akt pathway is involved in the late-stage progression and metastasis of gastric cancer, and attenuation of p-Akt by 2-ME suppresses metastasis.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Lin HL,Yang MH,Wu CW,Chen PM,Yang YP,Chu YR,Kao CL,Ku HH,Lo JF,Liou JP,Chi CW,Chiou SHdoi
10.1002/ijc.22963subject
Has Abstractpub_date
2007-12-01 00:00:00pages
2547-55issue
11eissn
0020-7136issn
1097-0215journal_volume
121pub_type
杂志文章abstract::Murine mammary aplastic carcinoma, when it is passed from one alloxan-diabetic animal to another, after several passages becomes conditioned to hypoinsulinemia by secreting its own substance(s) immunologically cross-reactive with insulin (SICRI). Although not cytotoxic, the total daily dose of 2.5 mg of synthetic line...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910290614
更新日期:1982-06-15 00:00:00
abstract::Cancer-related cachexia is a metabolic syndrome characterized by a wasting disorder of adipose and skeletal muscle and is accompanied by body weight loss and systemic inflammation. The treatment options for cancer cachexia are limited, and the molecular mechanism remains poorly understood. Circular RNAs (circRNAs) are...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31977
更新日期:2019-05-15 00:00:00
abstract::The effects of concomitant administration of bombesin and of the diuretic drug amiloride on the development of large and small intestinal tumors induced by azoxymethane (AOM), the incidence of their metastasis to the peritoneum and the labeling index of intestinal adenocarcinomas were investigated in inbred Wistar rat...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910630518
更新日期:1995-11-27 00:00:00
abstract::A population-based case-control study of esophageal cancer was conducted in urban Shanghai involving interviews with 902 cases and 1,552 controls. Risk of esophageal cancer was increased among tobacco smokers and alcohol drinkers. Odds ratios (OR) for smoking were 2.1 and 1.6 for men and women, respectively, and incre...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910580208
更新日期:1994-07-15 00:00:00
abstract::Glioma invasion into the surrounding brain tissue is still a major obstacle for any therapeutical approach. As in other solid tumors, matrix-metalloproteases (MMPs) have been suggested as being involved. The aim of this study was to evaluate whether the use of MMP inhibitors to target the protease-mediated invasion pr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990301)80:5<764::aid-ijc
更新日期:1999-03-01 00:00:00
abstract::Histone deacetylases (HDAC) extensively contribute to the c-Myc oncogenic program, pointing to their inhibition as an effective strategy against c-Myc-overexpressing cancers. We, thus, studied the therapeutic activity of the new-generation pan-HDAC inhibitor ITF2357 (Givinostat®) against c-Myc-overexpressing human B-c...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28852
更新日期:2014-11-01 00:00:00
abstract::Activation-induced cytidine deaminase (AID) plays a role as a genome mutator in activated B cells, and inappropriate expression of AID has been implicated in the immunopathological phenotype of human B-cell malignancies. Notably, we found that the transgenic mice overexpressing AID developed lung adenocarcinoma and he...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22292
更新日期:2007-02-01 00:00:00
abstract::We have previously described an inverse relationship between Cu-Zn superoxide dismutase (SOD) activity and invasiveness of a clone of human tongue cancer cells. In these cells, suppression of Cu-Zn SOD activity by transfection with anti-sense cDNA enhanced motility in vitro. The present studies were undertaken to dete...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19971009)73:2<187::aid-ijc
更新日期:1997-10-09 00:00:00
abstract::Loss of heterozygosity (LOH) at chromosome 3p21 is frequent in cervical cancers. The candidate tumor suppressor gene, RASSF1A located at 3p21.3, is found to be inactivated in several major human cancers, implicating its significance in carcinogenesis. We aimed to investigate the status of RASSF1A in cervical cancers. ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11051
更新日期:2003-06-10 00:00:00
abstract::Dendritic cells (DCs) cross-present antigen (Ag) to initiate T-cell immunity against most infections and tumors. Natural killer (NK) cells are innate cytolytic lymphocytes that have emerged as key modulators of multiple DC functions. Here, we show that human NK cells promote cross-presentation of tumor cell-derived Ag...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29087
更新日期:2015-03-01 00:00:00
abstract::More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis weight change and prognosis in postmenopausal long-term breast cancer survivors. We used data from a prospective populat...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.33181
更新日期:2021-01-01 00:00:00
abstract::In 1927 Otto Warburg established that tumours derive energy primarily from the conversion of glucose to lactic acid and only partially through cellular respiration involving oxygen. In the 1950s he proposed that all causes of cancer reflected different mechanisms of disabling cellular respiration in favour of fermenta...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.29012
更新日期:2015-10-01 00:00:00
abstract::PGP9.5 is a controversial molecule from an oncologic point of view. We recently identified frequent methylation of PGP9.5 gene exclusively in primary head and neck squamous cell carcinoma (HNSCC), suggesting that it could be a tumor suppressor gene. On the other hand, PGP9.5 was reported to be overexpressed in a subse...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23354
更新日期:2008-08-15 00:00:00
abstract::The Swedish Family-Cancer Database was used to analyze concordant (same site) and discordant (different site) second primary neoplasms in 633,964 cancer patients diagnosed from 1958 to 1996. Cases of second malignant neoplasms were extracted from the Database if the diagnosis date of the first and second cancer differ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1317
更新日期:2001-07-15 00:00:00
abstract::To investigate the association between hysterectomy and thyroid cancer subtypes based on histopathology. They did a nationwide, population-based, cohort study from 1973 to 2009 in Sweden. All women above 18 years of age during the period between January 1, 1973 and December 31, 2009 from the Register of Population (n ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30606
更新日期:2017-04-15 00:00:00
abstract::Infection with erbB-2 (E) of Ha-ras (H) oncogene-transfected cells has been previously shown to cooperatively induce anchorage-independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene-transformed MCF10A are able to halt in the...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910630612
更新日期:1995-12-11 00:00:00
abstract::A cytogenetic study, including prophase-prometaphase chromosome analysis, of a patient with EBV-genome-negative acute lymphocytic leukemia of B-cell type with Burkitt-type cells is presented. All bone-marrow mitoses examined had a 14q+ marker chromosome which was identified as a reciprocal 8;14 translocation of exactl...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910240106
更新日期:1979-07-15 00:00:00
abstract::An important goal in prostate cancer research is to define specific molecular and cellular alterations that are associated with malignant progression. The mouse prostate reconstitution model is a relevant and useful system as it allows the study of early events in cancer progression under conditions where oncogene-ini...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910600321
更新日期:1995-01-27 00:00:00
abstract::Cancer initiation is presumed to occur in utero for many childhood cancers and it has been hypothesized that advanced paternal age may have an impact due to the increasing number of mutations in the sperm DNA with increasing paternal age. We examined the association between paternal age and specific types of childhood...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30677
更新日期:2017-06-01 00:00:00
abstract::UDP-glucuronosyltransferase 1A1 (UGT1A1) is an enzyme which catalyses not only the glucuronidation of tobacco smoke carcinogens like benzopyrene, but also of the endogenous substrate bilirubin. Bilirubin for a long time was considered to be only a toxic waste product of hemoglobin degradation, but recent findings have...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25296
更新日期:2010-12-15 00:00:00
abstract::We have surveyed the incidence of adult T-cell leukemia/lymphoma (ATLL) in an endemic area of 290,464 inhabitants for 7 years. We now revise our previous results on the basis of additional findings and estimate the age- and sex-specific cumulative rate for HTLV-I carriers, the adoption of which is recommended by curre...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910430618
更新日期:1989-06-15 00:00:00
abstract::A new non peptidic farnesyltransferase inhibitor, RPR-115135, in combination with 5-FU was studied in 10 human colon cancer cell lines (HCT-116, RKO, DLD-1, Colo-320, LoVo, SW-620, HT-29, HCT-15, Colo-205 and KM-12) carrying several mutations but well characterized for p53 and Ras status. We found that there was a sli...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10461
更新日期:2002-07-20 00:00:00
abstract::Burkitt's lymphoma cells that vary in their phenotypic characteristics show significantly different degrees of susceptibility to radiation-induced apoptosis. Propensity to undergo apoptosis is reflected in the degradation of substrates such as DNA-dependent protein kinase but the status of bcl-2, c-myc and p53 has bee...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980831)77:5<755::aid-ijc
更新日期:1998-08-31 00:00:00
abstract::Abnormal cell adhesion is an important contributing factor in invasion and metastasis. Here, we show that morphologically 'normal' cell-cell and cell-substratum adhesion can be restored to a poorly differentiated carcinoma cell line by activation of protein kinase C (PKC). This cell line, VACO 10MS, grows as multicell...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990129)80:3<455::aid-ijc
更新日期:1999-01-29 00:00:00
abstract::There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histolog...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30766
更新日期:2017-08-01 00:00:00
abstract::CD30 is selectively expressed on the tumor cells of a variety of malignant disorders of the immune system and can therefore be used as a target for an anti-CD30 antibody-based immunotherapy. However, CD30 is cleaved at the cell surface by tumor necrosis factor-alpha converting enzyme (TACE). This metalloproteinase rel...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10182
更新日期:2002-03-10 00:00:00
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
更新日期:2008-03-01 00:00:00
abstract::MAGE genes are frequently expressed in several types of human malignancy and code for antigens recognized by cytotoxic T lymphocytes. We have previously described a monoclonal antibody (MAb), named 6C1, that recognizes the MAGE-1 protein and cross-reacts with a 72-kDa protein present in lysates of melanoma cells such ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990909)82:6<901::aid-ijc
更新日期:1999-09-09 00:00:00
abstract::Kaposi sarcoma (KS) is among the most common childhood malignancies in central, eastern, and southern Africa. Although its unique clinical features have been established, biological mechanisms related to the causative agent, KS-associated herpes-virus (KSHV), have yet to be explored in children. We performed a prospec...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31863
更新日期:2019-01-01 00:00:00
abstract::FTY720, a derivative of fungus, has demonstrated dramatic anticancer effect in several malignancies recently. Our study evaluates the therapeutic potential of FTY720 in the treatment of androgen-independent prostate cancer using a human prostate cancer xenograft in nude mice. CWR22R, an androgen-independent human pros...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21243
更新日期:2005-12-20 00:00:00