Abstract:
:We tested the efficacy of gefitinib in the prevention of HER2/neu-mediated breast cancer development in BALB-NeuT transgenic mice. Oral administration of gefitinib to female transgenic mice from 5 to 14 weeks of age reduced tumor multiplicity from 9.6 +/- 0.82 to 0.58 +/- 1.1 (83%). We observed a decrease in the number and size of lobules and lobular nodules in treated mice with a reduction in the overall disease burden per gland. Normal duct development in the mammary glands was not affected by gefitinib. The development of acinic cell carcinoma in the parotid glands of these animals was also reduced coincident with decreased stromal involvement during progression. Gefitinib eliminated phosphorylation of HER2 and HER3 and signaling through MAPK and Akt in lobular hyperplasias and carcinomas. At the same time MAPK activity and cytokine production in splenocytes and lymph nodes was increased in gefitinib-treated animals coincident with an increase in lymph node size. Delaying gefitinib treatment until mammary glands exhibited atypical lobular hyperplasias reduced efficacy. These studies demonstrate the critical role of HER2 signal transduction in the onset and progression of HER2/neu-dependent breast cancer and suggest a role for specific inhibitors to prevent the outgrowth of early hyperplastic disease.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Piechocki MP,Dibbley SK,Lonardo F,Yoo GHdoi
10.1002/ijc.23231subject
Has Abstractpub_date
2008-04-15 00:00:00pages
1722-9issue
8eissn
0020-7136issn
1097-0215journal_volume
122pub_type
杂志文章abstract::Stimulated by a report on elevated IgA levels in nasopharyngeal carcinoma (NPC), we tested a total of 372 sera from patients with NPC, other carcinomas of head and neck or elsewhere, Burkitt's lymphoma (BL), infectious mononucleosis (IM) or healthy controls. The sera were titrated in indirect immunofluorescence tests ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910170102
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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更新日期:2007-09-15 00:00:00
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journal_title:International journal of cancer
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更新日期:2012-07-15 00:00:00
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journal_title:International journal of cancer
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doi:10.1002/ijc.25004
更新日期:2010-04-01 00:00:00
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journal_title:International journal of cancer
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doi:10.1002/ijc.2910570421
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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abstract::Epidermal growth factor receptor (EGFR) plays an important role in essential cellular processes such as proliferation, survival and migration. Aberrant activation of EGFR is frequently found in human cancers of various origins and has been implicated in cancer pathogenesis. The therapeutic antibody cetuximab (Erbitux)...
journal_title:International journal of cancer
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abstract::In a case-control study of gastric cancer (GC) in high-risk and low-risk areas of Italy, 923 GCs were systematically categorized by one pathologist according to the Lauren classification distinguishing 2 main histologic types, intestinal (55%) and diffuse (23%). Intestinal types outnumbered diffuse types by a 3 to 1 m...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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abstract::Subtype-specific incidence patterns in populations at high risk of lymphoma offer insight into lymphomagenesis. The incidence profiles for the 2 most common non-Hodgkin lymphoma subtypes were compared for 2 immunodeficient populations, adults receiving a kidney transplant 1982-2003 (n = 7,730) or diagnosed with human ...
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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abstract::Immortalized and cancer cells maintain their telomeres by activation of a telomere maintenance mechanism (TMM). In approximately 85% of cancers telomerase is activated (TA) but in some tumours, in particular sarcomas, an alternative lengthening of telomeres (ALT) pathway is used. Liposarcomas are the most common soft-...
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abstract::The development of cervical carcinoma is closely associated with HPV infection. However, other genetic alterations also play an important role. In this study, we analyzed copy number alterations of several oncogene loci in a panel of 84 cervical tumors. Sixty-five (77%) tumors were HPV DNA-positive, and most were infe...
journal_title:International journal of cancer
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abstract::Squamous cell carcinoma of the conjunctiva (SCCC) has been associated with HIV infection in equatorial Africa, but the evidence for association with HIV in developed countries, where SCCC is rarer, is controversial. We investigated the risk for SCCC and other eye cancers in the updated U.S. HIV/AIDS Cancer Match Regis...
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abstract::We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum sp...
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abstract::Laboratory and epidemiological data have linked vitamin D to breast cancer prevention. Beside dietary intake, endogenous production of vitamin D substantially contributes to a subject's vitamin D status. Most studies, however, have assessed dietary intake only. Although differential effects of vitamin D on premenopaus...
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journal_title:International journal of cancer
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abstract::Oncogenic HPV types are the major cause of worldwide cervical cancer, but only a small proportion of infected women will develop high-grade cervical intraepithelial neoplasia or cancer (CIN2/3+). We performed a prospective study including 781 women with normal, atypical squamous cells of undetermined significance (ASC...
journal_title:International journal of cancer
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