Abstract:
:Amplification and overexpression of erbB2 (Her-2/neu) proto-oncogene has been linked to human malignancies including tumors of the breast, ovary, and stomach. It has been implicated in tumor growth, sensitivity to standard chemotherapy, prognosis of patients, and disease-free survival. Although the clinical use of trastuzumab (Herceptin) has prolonged the survival of breast cancer patients with erbB2-overexpressing tumors, there is an urgent need for more potent and orally bioavailable small-molecule inhibitors. CP-724,714 is a potent inhibitor of erbB2 receptor autophosphorylation in intact cells and is currently undergoing phase I clinical trials. Here, we describe the effects of CP-724,714 in vitro and in vivo in human breast cancer models. CP-724,714 is selective for inhibiting growth of HER2-driven cell lines. In addition, we show that it induces G1 cell cycle block in erbB2-overexpressing BT-474 human breast carcinoma cells and inhibits erbB2 autophosphorylation in xenografts when administered p.o. to athymic mice. It induces a marked reduction of extracellular signal-regulated kinase and Akt phosphorylation, tumor cell apoptosis, and release of caspase-3. P.o. administration (q.d. or b.i.d.) of CP-724,714 inhibits the growth of erbB2-overexpressing tumors in athymic mice without overt adverse effects.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Jani JP,Finn RS,Campbell M,Coleman KG,Connell RD,Currier N,Emerson EO,Floyd E,Harriman S,Kath JC,Morris J,Moyer JD,Pustilnik LR,Rafidi K,Ralston S,Rossi AM,Steyn SJ,Wagner L,Winter SM,Bhattacharya SKdoi
10.1158/0008-5472.CAN-06-3559subject
Has Abstractpub_date
2007-10-15 00:00:00pages
9887-93issue
20eissn
0008-5472issn
1538-7445pii
67/20/9887journal_volume
67pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Many but not all of the cell surface antigens studied were released into tissue culture medium of human colorectal carcinoma and melanoma cells maintained in vitro. Two groups of monoclonal antibody-defined antigens are described. One group is composed of molecules that are released easily and in large quantitites int...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
abstract::Adult female rat urinary bladders were exposed to N-methyl-N-nitrosourea in vivo. After 12 weeks, urothelial hyperplasia was established. Ultrastructural changes of the luminal plasma membrane were studied with thin sectioning and freeze-fracturing techniques. The mosaic pattern which is a characteristic specializatio...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-09-01 00:00:00
abstract::HT-29 cells express and secrete insulin-like growth factor (IGF)-II and only one of the six IGF-binding proteins, IGFBP-4. In the present study, the physiological role of endogenous IGFBP-4 in regulating the growth response of HT-29 cells to exogenous and endogenous IGFs was examined. Both the basal and the IGF-stimul...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-12-15 00:00:00
abstract::Pheochromocytomas are tumors originating from chromaffin cells, the large majority of which are sporadic neoplasms. The genetic and molecular events determining their tumorigenesis continue to remain unknown. On the other hand, RET germ-line mutations cause the inheritance of familial tumors in multiple endocrine neop...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::After 16 months, an established line of human small cell lung cancer (OH-1) underwent a subtle morphological change which was associated with a virtually complete loss of neuroendocrine differentiation as judged by electron microscopy studies and a 12-fold loss in L-dopa decarboxylase activity. In nude (athymic) mouse...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-04-01 00:00:00
abstract::MEK inhibition is of interest in cancer drug development, but clinical activity in metastatic colorectal cancer (mCRC) has been limited. Preclinical studies demonstrated Wnt pathway overexpression in KRAS-mutant cell lines resistant to the MEK inhibitor, selumetinib. The combination of selumetinib and cyclosporin A, a...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:10.1158/0008-5472.CAN-18-0316
更新日期:2018-09-15 00:00:00
abstract::Retinoic acid inhibits the proliferation of the murine melanoma clone S91-C-2 cells, enhances the glycosylation of specific cell surface sialoglycoproteins, and stimulates sialytransferase activity. Mutant clones, selected from the S91-C-2 cells for resistance to the growth-inhibitory effect of retinoic acid, were use...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-12-01 00:00:00
abstract::We recently reported trophic response of transplantable mouse colon cancer cells (MC-26) to pentagastrin, in vivo, and demonstrated gastrin receptors on MC-26 cells, in vitro. In the present study, growth of MC-26 cells in mice, in response to pentagastrin, was studied in relation to binding kinetics and capacity of g...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-04-01 00:00:00
abstract::Genotoxicity-induced hair loss from chemotherapy and radiotherapy is often encountered in cancer treatment, and there is a lack of effective treatment. In growing hair follicles (HF), quiescent stem cells (SC) are maintained in the bulge region, and hair bulbs at the base contain rapidly dividing, yet genotoxicity-sen...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-0667
更新日期:2017-11-15 00:00:00
abstract::Elimination of both alleles of the gene that encodes the cyclin kinase inhibitor p21(WAF1/cip1) increases the frequency and size of intestinal tumors in Apc1638+/- mice that inherit a mutant allele of the Apc gene, and intermediate effects are seen if a single p21 allele is inactivated. The increased tumor formation i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-01-15 00:00:00
abstract::Signaling through the insulin-like growth factor-I receptor (IGF-IR) is implicated in cellular proliferation, apoptosis, carcinogenesis, metastasis, and resistance to cytotoxic cancer therapies. Targeted disruption of IGF-IR signaling combined with cytotoxic therapy may therefore yield improved anticancer efficacy ove...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-2000
更新日期:2007-02-01 00:00:00
abstract::Glucocorticoids are widely used for the treatment of multiple myeloma. To investigate the direct actions of glucocorticoids on myeloma cells, we have used three cell lines of human multiple myeloma, OPM-1, OPM-2, and RPMI 8226. When growth curves of these cells were examined, OPM-1 cells were resistant, while OPM-2 we...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-03-15 00:00:00
abstract::Melanoma incidence is increasing worldwide, and metastatic melanoma is almost completely resistant to every known therapy. New approaches to treating melanoma are urgently needed, and a greater understanding of the biology of melanoma invasion and metastasis will aid in their creation. A high proportion of invasive me...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1791
更新日期:2007-11-15 00:00:00
abstract::Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-3332
更新日期:2016-05-15 00:00:00
abstract::Microsatellite instability (MSI) has been described in tumors from patients with hereditary nonpolyposis colorectal cancer, sporadic colorectal cancer, and other types of cancers. MSI is caused by the dysfunction of mismatch repairs genes. Loss of expression and mutation in one of the major mismatch repair genes, hMLH...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::The endocrine status of 49 premenopausal women taking tamoxifen after completion of adjuvant chemotherapy for breast cancer was determined by radioimmunoassay from serial blood samples. Of these 49 women, 7 had regular menses, 14 had irregular menses, 23 were amenorrheic, and 5 had undergone hysterectomies. A group of...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-02-15 00:00:00
abstract::Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program "epithelial-mesenchymal transition" (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 pro...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5682
更新日期:2008-01-15 00:00:00
abstract::Benzo(a)pyrene and 210Po were administered both simultaneously and sequentially by intratracheal instillations to Syrian golden hamsters in experiments designed to identify any synergistic interactions between these carcinogens. Their effects were additive after simultaneous administration. A significant synergistic i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00
abstract::The transplantable hormone-responsive rat mammary adenocarcinoma 13762NF was dissociated with collagenase and hyaluronidase. Cells were cloned directly or lines were established from mass cultures and cells from these lines were cloned. Clones differed in cellular morphology, colony morphology on plastic or in collage...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-04-01 00:00:00
abstract::Mismatch repair (MMR) deficiency was reported to increase resistance of mammalian cells to killing by several genotoxic substances. However, although MMR-deficient cells are approximately 100-fold more resistant to killing by S(N)1 type methylating agents than MMR-proficient controls, the sensitivity differences repor...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-0513
更新日期:2004-05-15 00:00:00
abstract::Evaluation of a large panel of radiation-induced rat skin tumors of diverse size and histological type revealed a correlation between c-myc copy number and tumor size. Both the frequency and degree of c-myc gene amplification were increased in large compared to small carcinomas, but none of the sarcomas examined showe...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-05-15 00:00:00
abstract::Options for skin cancer treatment currently include surgery, radiotherapy, topical chemotherapy, cryosurgery, curettage, and electrodessication. Although effective, surgery is costly and unsuitable for certain patients. Radiotherapy can leave a poor cosmetic effect, and current chemotherapy is limited by low cure rate...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-2837
更新日期:2004-04-15 00:00:00
abstract::Normal or immortal epithelial cells are sensitive to a form of apoptosis, commonly referred to as anoikis, which is induced by detachment from the extracellular matrix (ECM). In contrast, development of carcinomas is associated with acquisition of cellular resistance to anoikis. However, whether human cancer cells dep...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-06-15 00:00:00
abstract::Calf thymus DNA was modified in vitro by cis-diamminedichloroplatinum(II) (cisDDP), complexed with methylated bovine serum albumin and used to immunize rabbits. The anti-cisDDP-DNA antiserum obtained was applied in a double peroxidase-antiperoxidase staining procedure to localize cisDDP-DNA and cis-diammine(1,1-cyclob...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-12-15 00:00:00
abstract::Fusarium moniliforme (FM) is a major fungal pathogen of corn and is involved with stalk rot disease. FM is widely spread throughout the world, including the United States. Most strains of FM produce several mycotoxins, the most prominent of which is called fumonisin. Recent epidemiological studies indicated that inges...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-04-15 00:00:00
abstract::A methylcholanthrene-induced fibrosarcoma (3AM) and several of its clones were evaluated for pulmonary metastasis, growth rate, and chromosome composition. Heterogeneity was observed in the three parameters, and no correlation was found between growth rate and metastatic potential. Furthermore, three clones (10, 34, a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::The influences of pure human pluripotent colony-stimulating factor, highly purified pluripoietin alpha, pure recombinant human tumor necrosis factor alpha, pure recombinant human gamma-interferon, and natural prostaglandin E1 (PGE1) were evaluated on colony formation of multipotential and erythroid progenitor cells in...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::Carcinogenic heterocyclic amines are activated by N-acetyltransferase (NAT) enzymes, encoded by NAT1 and NAT2, to genotoxic compounds that can form DNA adducts in the colon epithelium. We have examined the relation of polymorphisms in the genes coding for both enzymes to risk of colorectal cancer and the gene-environm...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::The nucleotide metabolism enzyme ribonucleotide reductase is composed of a regulatory subunit (RRM1) and a catalytic subunit (RRM2). The RRM1 locus has frequent loss of heterozygosity in lung cancers, ectopic expression of RRM1 suppresses proliferation of ras-transformed mouse fibroblasts, and high levels of RRM1 expr...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-4462
更新日期:2006-07-01 00:00:00
abstract::Aneuploidy is invariably associated with poor proliferation of primary cells, but the specific contributions of abnormal karyotypes to cancer, a disease characterized by aneuploidy and dysregulated proliferation, remain unclear. In this study, I demonstrate that the transcriptional alterations caused by aneuploidy in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0749
更新日期:2013-11-01 00:00:00