Abstract:
:Human squamous cell carcinomas frequently overexpress the epidermal growth factor receptor (EGFR) and this is often associated with poor prognosis in patients with these cancers. The high level of expression of the EGFR provides an important target for therapy and we and others have shown that monoclonal antibodies (mAbs) which block the activation of the receptor by the EGF family of ligands inhibit the growth of EGFR overexpressing tumours in vitro and induce the regression of established tumours grown as xenografts in athymic mice. Inhibitors of the tyrosine kinase associated with the EGFR have also been shown to block receptor activation and prevent tumour cell proliferation. Using the EGFR-overexpressing head and neck carcinoma cell line HN5, we have compared the biological consequences of treatment with an inhibitor of EGFR tyrosine kinase (PD153035) with anti-EGFR monoclonal antibodies (mAbs) ICR63 or ICR80. We found that both the anti-EGFR mAbs and the TK inhibitor produce similar biological changes namely, they inhibit the EGF and TGFá-induced tyrosine phosphorylation of the receptor and the growth in culture of HN5 cells. At concentrations above 100 nM, the TK inhibitor prevented the growth in culture of HN5 cells completely with an IC50 of 40 nM. With the anti-EGFR mAbs, growth of HN5 cells was inhibited completely at concentrations above 4 nM with an IC50 of 1 nM. More importantly we found that, like the anti-EGFR mAbs, treatment with the TK inhibitor directs HN5 cells to undergo terminal differentiation as monitored by the expression of cytokeratin 10. In addition, our results indicate that the growth inhibitory effects of the anti-EGFR agents also lead to induction of apoptosis as determined by 7-amino actinomycin D staining (7-AAD). We conclude that EGFR blockade by anti-EGFR mAbs or TK inhibitor influences the growth in culture of EGFR overexpressing tumours by directing terminal differentiation and inducing apoptosis.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Modjtahedi H,Affleck K,Stubberfield C,Dean Cdoi
10.3892/ijo.13.2.335subject
Has Abstractpub_date
1998-08-01 00:00:00pages
335-42issue
2eissn
1019-6439issn
1791-2423journal_volume
13pub_type
杂志文章abstract::Chemotherapy (CT) resistance in ovarian cancer is related to multiple factors, and assessment of these factors is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 21,000 genes using DNA microarray screening in ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-07-01 00:00:00
abstract::IL-10 has been shown to play a crucial role in immunosuppression in cancer patients. We explored the regulation of IL-10 production by TNF-alpha, IL-1 beta, IL-6, IL-8, and IFN-gamma in human colon carcinoma COLO205 cells. Northern analysis revealed a marked expression of IL-10 mRNA after stimulation by IL-6, and a ma...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::Although it has been shown that the cross-talk between osteoblasts and tumor cells stimulates proliferation and invasion of prostate carcinoma (PCa) cells, the molecular mechanisms underlying this event are largely unknown. In this study, we demonstrated that the PCa cells, PC3, derived from bone metastasis, undergo c...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-04-01 00:00:00
abstract::In recent years major progress has been made in understanding the molecular steps of death receptor and mitochondrial pathway of apoptosis. Mechanisms of NF-kappaB-mediated survival (anti-apoptotic) signal have been delineated. A novel anti-apoptotic mechanism of FLIP in the recruitment of RIP and TRAF-1 and TRAF-2 to...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
更新日期:2003-01-01 00:00:00
abstract::New aromatase inhibitors are an exciting treatment option for postmenopausal women with hormone sensitive breast cancer. They have been shown to reduce tumors in a significant number of patients, and exhibit definite antitumor activity at a relatively low daily dose, and are highly potent, highly selective, and well-t...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.17.5.1037
更新日期:2000-11-01 00:00:00
abstract::Overexpression of HIF-1α, a transcription factor responsive to hypoxia, is frequently observed in malignant tumors, which sometimes show resistance to chemotherapy and radiation therapy. Consequently, decrease of HIF-1α through virotherapy offers a logical strategy for the treatment of aggressive tumors. In this study...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2922
更新日期:2015-05-01 00:00:00
abstract::We have developed a new type of drug delivery system (DDS) comprising a complex of porous hydroxyapatite (HAP) with the anticancer drug doxorubicin hydrochloride (DOX) and the glutathione inhibitor buthionine sulfoximine (BSO) (DOX and BSO-HAP complex). We then studied the antitumour effect of DOX and BSO-HAP combined...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.10.5.961
更新日期:1997-05-01 00:00:00
abstract::The in situ formation of cytotoxic metabolites by an enzyme-catalyzed reaction is a recent approach in cancer therapy. The present results show that multidrug-resistant human colon adenocarcinoma cells (LoVo) are significantly more sensitive than corresponding wild-type cells to hydrogen peroxide and aldehydes, the pr...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-10-01 00:00:00
abstract::Cisplatin is widely used for chemotherapy of a variety of human cancers. Cisplatin exerts its toxic effect by covalently binding to DNA, resulting in monofunctional adducts, intrastrand crosslinks, and interstrand crosslinks. Several recent reports suggest that the cellular capacity for DNA repair, especially nucleoti...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.9.6.1121
更新日期:1996-12-01 00:00:00
abstract::The development of carcinoma is associated with alterations in the expression of many cell adhesion molecules. Syndecan-1 is a cell surface proteoglycan that binds cells to the extracellular matrix and changes its expression following malignant transformation in some tumors. Our purpose was to examine the pattern of s...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::Chemokine-mediated activation of G protein-coupled receptors CXCR1/2 promotes tumor growth, invasion, inflammation and metastasis. Repertaxin, a CXCR1/2 small-molecule inhibitor, has been shown to attenuate many of these tumor-associated processes. The present study aimed to investigate the effects of repertaxin alone...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3371
更新日期:2016-04-01 00:00:00
abstract::Oxidative stress due to intratumoral hypoxia in solid cancer has been shown to be associated with increased mortality. Phosphoglycerate kinase 1 (PGK1) is an enzyme of the glycolytic pathway, which is regulated by hypoxia-inducible factor-1α (HIF-1α) and has been described for its role in tumor progression and metasta...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1971
更新日期:2013-08-01 00:00:00
abstract::Metal-containing compounds have been extensively studied for many years as potent proteasome inhibitors. The 20S proteasome, the main component of the ubiquitin proteasome pathway, is one of the excellent targets in anticancer drug development. We recently reported that several copper complexes were able to inhibit ca...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3542
更新日期:2016-08-01 00:00:00
abstract::To overcome the poor tumor transduction efficiency of adenovirus serotype 5 (Ad5) observed in several types of cancer, the fiber region of Ad5, apart from its tail, was replaced by adenovirus serotype 35 (Ad35). The chimeric Ad5/F35 adenoviral vector did not exhibit any significant enhancement of transduction efficien...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1812
更新日期:2013-04-01 00:00:00
abstract::The last decade has brought increased awareness to prostate cancer as a significant health problem. Prostate cancer is very heterogeneous in its etiology and progression, but androgen signaling appears to be a common key element in its development and progression. Blocking of androgen signaling results in a decrease i...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.23.4.1095
更新日期:2003-10-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1603
更新日期:2012-11-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4916
更新日期:2020-01-01 00:00:00
abstract::The Warburg effect is a unique metabolic feature of the majority of tumor cells and is closely related to chemotherapeutic resistance. Pyruvate dehydrogenase kinase 1 (PDK1) is considered a 'switch' that controls the fate of pyruvate in glucose metabolism. However, to date, to the best of our knowledge, there are only...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.5098
更新日期:2020-09-01 00:00:00
abstract::Licochalcone A (LCA) is a natural product derived from the roots of Glycyrrhiza inflata exhibiting a wide range of bioactivities such as antitumor, anti-oxidant and anti-bacterial effects. Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer with a poor prognosis because of its rapid progress...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2839
更新日期:2015-03-01 00:00:00
abstract::Pristimerin (PM), a quinonemethide triterpenoid, is a promising anticancer agent with potent antiproliferative and apoptosis-inducing activities against cancer cell lines. However, the anticancer activity and mechanisms of PM in prostate cancer cells have not been adequately investigated. Here we report that the degra...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2561
更新日期:2014-10-01 00:00:00
abstract::Breast cancer remains the second most common disease worldwide. Radiotherapy, alone or in combination with chemotherapy, is widely used after surgery as a treatment for cancer with proven therapeutic efficacy manifested by reduced incidence of loco-regional and distant recurrences. However, clinical evidence indicates...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.4125
更新日期:2017-11-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2699
更新日期:2015-01-01 00:00:00
abstract::To determine the relation between apoptosis and cytotoxicity the number of apoptotic (AP) cells was measured in MOLT-4 and HL-60 cultures treated with adriamycin, etoposide, cisplatin and 1-B-D-arabinofuranosylcytosine (ara-C) in the dose range inducing 20-95% growth inhibition. DNA degradation in individual AP cells ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.4.2.481
更新日期:1994-02-01 00:00:00
abstract::The microtubule associated tumor suppressor gene 1 (MTUS1) is a recently published tumor suppressor gene, which has also been shown to act as an early component in the growth inhibitory signaling cascade of the angiotensin II type 2 receptor (AT2R). In this study we report the generation of MTUS1 knock-out (KO) mice, ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1311
更新日期:2012-04-01 00:00:00
abstract::Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. To evaluate the efficacy of dietary resveratrol in vivo, 5-week-old NOD.CB17-Prkdcscid/J mice were fed a control diet or a d...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1650
更新日期:2012-12-01 00:00:00
abstract::Many clinical studies highlight the dichotomous role of PRDXs in human cancers, where they can exhibit strong tumor-suppressive or tumor-promoting functions. Recent evidence suggests that lower expression of PRDXs correlates with cancer progression in colorectal cancer (CRC) or in esophageal squamous carcinoma. In the...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2208
更新日期:2014-02-01 00:00:00
abstract::Cutaneous infantile hemangioma progresses through proliferation and involution phases. Since treatment with interferon, a negative regulator of angiogenesis, accelerates the involution phase, we hypothesized that cutaneous infantile hemangioma is associated with an imbalance between endogenous positive and negative re...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.14.3.401
更新日期:1999-03-01 00:00:00
abstract::One of the early events of apoptosis is proteolysis. The enzyme(s) involved in this event appear to be the serine protease(s), inasmuch as the reversible or irreversible inhibitors of serine proteases prevent DNA degradation and abrogate other signs of apoptosis in several cell systems (Gorczyca et al, Int J Oncol 1: ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.4.627
更新日期:1993-10-01 00:00:00
abstract::A herbal preparation denoted PC SPES(R) is available in 'natural food' or 'health food' stores in the United States. This mixture (patent pending, US Serial number 08/697,920) consists of extracts from 8 different herbs, 7 originating from China and one from America, and is sold as a dietary supplement. Although sever...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.3.437
更新日期:1997-09-01 00:00:00
abstract::Thirty-one patients with metastatic breast cancer not responding or progressing after initial response to adriamycin + cyclophosphamide (AC) treatment entered a phase 11 study with oral lonidamine in association to AC. Objective clinical responses were observed in 10 patients (32%) and consisted of 1 complete + 9 part...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.2.213
更新日期:1993-08-01 00:00:00