Abstract:
:Gefitinib has shown meaningful antitumor activity with tolerable toxicity in chemotherapy-refractory NSCLC in previous studies. Moreover, EGFR expression failed to show a correlation with response. In an attempt to identify predictive markers of response, we have investigated the tumoral expression of key signaling molecules of EGFR (EGFR, p-EGFR, p-Akt, p-Erk, p-STAT3) by immunohistochemistry and analyzed their correlations with response. Of 65 patients who received gefitinib (250 mg/day) for chemotherapy-refractory NSCLC, there were 14 partial responses (21.5%), 21 stable diseases (32.3%) and 21 progressive diseases (32.3%). Median durations of overall survival and time to progression were 6.7 months and 2.8 months, respectively. Immunohistochemistry was performed in 34 patients with evaluable tissue specimens. EGFR was overexpressed (2+ or 3+) in 32.4% and p-EGFR was positive in 26.5%. The expressions of p-Akt, p-Erk and p-STAT3 were positive (1+ or 2+) in 50%, 38.2% and 79.4%, respectively. The EGFR expression was not correlated with p-EGFR or the downstream molecules. EGFR or p-EGFR status did not correlate with response. Positive expression of p-Erk was significantly associated with poor response (38.1% in -, 14.3% in 1+, 0% in 2+; p = 0.046). Furthermore, tumors with positive p-Akt and negative p-Erk nuclear expression exhibited the best response (60%), whereas there was no response in the opposite [p-Akt (-), p-Erk (+)] cases. Intense nuclear staining of p-Akt (2+) was associated with prolonged TTP (HR 0.25, 95% confidence interval [CI] 0.08-0.79, p = 0.018) and OS (HR 0.16, 95% CI 0.04-0.62, p = 0.008). These results support the assumption that gefitinib responsiveness might be predicted by activated EGFR downstream molecules such as p-Akt and p-Erk.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Han SW,Hwang PG,Chung DH,Kim DW,Im SA,Kim YT,Kim TY,Heo DS,Bang YJ,Kim NKdoi
10.1002/ijc.20550keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
109-15issue
1eissn
0020-7136issn
1097-0215journal_volume
113pub_type
临床试验,杂志文章abstract::Long noncoding RNAs (lncRNAs) are involved in the pathology of colorectal cancer (CRC). Current efforts to eradicate CRC predominantly focused on targeting the proliferation of rapidly growing cancer epithelial cells. This is largely ineffective with resistance arising in most tumors after exposure to chemotherapy. De...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32608
更新日期:2020-03-15 00:00:00
abstract::It is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk factor for/or, rather, are a consequence of the tumour. We postulate that malignant tumours are directly involved in an increased catabolism of cholesterol-rich low-density lipoprotein...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910610405
更新日期:1995-05-16 00:00:00
abstract::We conducted a population-based case-control study of 1,447 incident rectal cancer cases and 3,106 population controls aged 20-76 years to assess the effect of recreational physical activity, energy intake and obesity on rectal cancer risk in 7 of 10 Canadian provinces in 1994-97. After adjustment for the effect of va...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11159
更新日期:2003-07-20 00:00:00
abstract::Prostate-specific antigen (PSA) is a serine protease secreted by prostatic epithelial cells and is widely used as a marker for prostate cancer. The tissue specificity of PSA makes it a potential target for active specific immunotherapy, especially in prostate cancer patients who have undergone prostatectomy and in who...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910630215
更新日期:1995-10-09 00:00:00
abstract::PCNA and esophagin have been implicated in the multistep process of carcinogenesis, but simultaneous characterization of these proteins in the early stages of esophageal neoplastic progression has yet to be undertaken. In morphologically normal esophageal epithelium, esophagin stains the granular layer cells, principa...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.20267
更新日期:2004-09-01 00:00:00
abstract::Several observational epidemiological studies have reported inconsistent results on the association between the use of benzodiazepine and the risk of cancer. We investigated the association by using a meta-analysis. We searched PubMed, EMBASE, and the bibliographies of relevant articles to locate additional publicatio...
journal_title:International journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1002/ijc.30443
更新日期:2017-02-01 00:00:00
abstract::The European Study Group for Pancreatic Cancer (ESPAC-1) study is the largest study of adjuvant treatment for pancreatic ductal adenocarcinoma to date and confirmed a survival advantage for adjuvant chemotherapy but not for chemoradiation. The importance of parallel evaluation of survival and quality of life (QoL) has...
journal_title:International journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1002/ijc.24270
更新日期:2009-06-15 00:00:00
abstract::Chemotherapy-induced gastrointestinal toxicity (CIGT) occurs in up to 80% of all patients undergoing cancer treatment, and leads to symptoms such as diarrhoea, abdominal bleeding and pain. There is currently limited understanding of how to predict an individual patient's risk of CIGT. It is believed the gut microbiome...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.31836
更新日期:2019-05-15 00:00:00
abstract::The results of a survey of a population with a high incidence of oral and oesophageal cancer are presented. The population under study appears to have several epidemiologic characteristics, some of which may be associated with a high incidence of oral and oesophageal cancer. A remarkably high proportion (41%) of the m...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910360205
更新日期:1985-08-15 00:00:00
abstract::The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) was found to increase the incidence of phenotypic alterations induced by the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in human endometrial stromal cells. Following carcinogen treatment, changes in saturation density, gamma-glutam...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910320405
更新日期:1983-10-15 00:00:00
abstract::Extranodal, nasal NK/T-cell lymphomas are regularly Epstein-Barr virus (EBV)-positive, with a type II latency pattern, expressing thus EBNA-1 and LMP1. The contribution of EBV to the tumor development is not known. Similarly to normal natural killer (NK) cells, cell lines derived from malignancies with a NK phenotype ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22139
更新日期:2006-12-15 00:00:00
abstract::Langerhans' cells (LCs) are thought to play an important role in presentation of tumour antigens for the induction of anti-tumour immunity. Epidermis overlying some transplanted murine skin tumours contains increased numbers of LCs; however, alterations in LC numbers are not related to tumour antigenicity or host immu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980119)75:2<210::aid-ijc
更新日期:1998-01-19 00:00:00
abstract::140.240, an IgG2a mouse monoclonal antibody raised against a cultured human melanoma cell line, was highly specific for melanoma cells as determined by direct and absorption analyses in a mixed hemadsorption assay. Supernatants of doubly cloned hybridomas producing antibody 140.240 reacted with all cultured and fresh ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910300507
更新日期:1982-11-15 00:00:00
abstract::We previously reported identifying SOX6 as a glioma antigen by serological screening using a testis cDNA library. Its preferential expression and frequent IgG responses in glioma patients indicate that SOX6 may be a useful target for immunotherapy. To examine whether cytotoxic T-lymphocyte (CTL) responses specific for...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23366
更新日期:2008-05-15 00:00:00
abstract::There is strong evidence of a protection of high consumption of plant foods against squamous cell carcinoma of the oesophagus, but the respective role of fruits and vegetables is not well elucidated. In the time period 1996-2003, a case-control study designed in order to address this question was conducted in Uruguay....
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.20950
更新日期:2005-08-10 00:00:00
abstract::Using radioiodinated Staphylococcus aureus protein A [125I]SPA to measure syngeneic, allogeneic and heterogeneic IgG bound to murine tumor cells, we performed a serological analysis of surface antigens of 8 solid tumors and 2 leukemias of BALB/c mice (3 chemically-induced colon carcinomas, 3 chemically-induced sarcoma...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910230317
更新日期:1979-03-15 00:00:00
abstract::Limited penetration of anticancer drugs through tumour tissue is an important factor that may limit therapeutic effects against solid tumours. Here we report studies of the penetration of radiolabelled methotrexate through multicellular layers (MCL) of murine EMT-6 and human MCF-7 cells grown on semiporous teflon memb...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(20010101)91:1<120::aid-ijc1021>3
更新日期:2001-01-01 00:00:00
abstract::The causative role of human papillomaviruses (HPV) and HPV16 variants has been extensively studied in uterine cervix dysplastic lesions and invasive carcinoma; few such studies, however, have been performed in penile tumors. We have investigated HPV genotype and HPV16 variant distribution on 41 penile cancer biopsies ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23062
更新日期:2008-01-01 00:00:00
abstract::Clinical trials utilizing strategies to manipulate tumor oxygenation, blood flow and angiogenesis are under way, although limited quantitative information exists regarding basic tumor pathophysiology. The current study utilized murine KHT fibrosarcomas, spontaneous mammary carcinomas and first-generation spontaneous t...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1401
更新日期:2001-09-01 00:00:00
abstract::During natural metastasis, cancer cells are released continuously into the bloodstream and arrested in target organs; the process is repetitive rather than a single event. In this communication, the effect of preceding on successive "pulses" of cancer cells is discussed in relation to the arrest, retention and tumor f...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910360417
更新日期:1985-10-15 00:00:00
abstract::In our study, we aimed to investigate the expression of N-cadherin and E-cadherin and their dependency on epithelial-mesenchymal transition regulators SNAI1, SIP1 and TWIST in human colon cancer. Expression of E-cadherin and N-cadherin was examined by immunohistochemistry in 80 colon carcinomas by using paraffin embed...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.20317
更新日期:2004-09-20 00:00:00
abstract::The topic of this review is the role of stromal-epithelial interactions in normal and malignant prostatic growth. Because cell-cell interactions and androgens play such key roles in the prostate, the goal of this review will be to apply endocrinologic and developmental concepts to the understanding of normal and malig...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.11335
更新日期:2003-10-20 00:00:00
abstract::Tumor cells interact with endothelial cells during both intra- and extravasation. Understanding how these interactions are modulated could lead to the development of ways to alter the metastatic potential of tumor cells. Three pancreatic cancer cell lines, SW1990, CAPAN-2 and PANC-I, were examined for their ability to...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910570621
更新日期:1994-06-15 00:00:00
abstract::Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox pr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32112
更新日期:2019-07-15 00:00:00
abstract::Cultured cells derived from pregnancy-dependent mouse mammary tumors (plaques) when transplanted into the gland-free mammary fat pad display a heterogeneous developmental potential. They not only gave rise to plaques but also produced normal mammary gland, hyperplastic alvoelar nodules (HAN), and autonomous mammary tu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910230520
更新日期:1979-05-15 00:00:00
abstract::This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Col...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960328)66:1<70::AID-IJC1
更新日期:1996-03-28 00:00:00
abstract::We have previously developed 3 monoclonal anti-idiotypic antibodies (Ab2) of LOU rat origin directed against the binding site of the murine monoclonal IgM LAM8, which recognizes the small-cell lung carcinoma (SCLC)-associated sialoglycoprotein antigen sGP 90-135. The aim of this study was to compare the efficiencies o...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910500118
更新日期:1992-01-02 00:00:00
abstract::An antiserum to SF antigen was shown to be selectively cytotoxic to two human fibroblast lines, while two tumor cell lines (one melanoma and one Hela cell line) were resistant. The selective cytotoxicity was also demonstrable in mixtures of fibroblasts and tumor cells. The cytotoxic effect was abrogated by admixture o...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910180317
更新日期:1976-09-15 00:00:00
abstract::Epidemiological studies of in situ breast cancer are sparse, and the role of reproductive history, an established risk modifier for invasive breast cancer, remains incompletely investigated. To examine possible associations with parity and age at first birth, we undertook a case-control study nested in a nationwide co...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980729)77:3<330::aid-ijc
更新日期:1998-07-29 00:00:00
abstract::Cancers of the stomach, pancreas, colon and rectum are increasingly regarded as being diet-influenced. Migrants to Australia from England, Scotland, Ireland, Poland, Yugoslavia, Greece, and Italy have come from countries with varied dietary backgrounds and gastrointestinal cancer risks. Age-standardized cancer death r...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910250402
更新日期:1980-04-15 00:00:00