Abstract:
:We observed that photodynamic therapy (PDT) induces the expression and phosphorylation of the inhibitor of apoptosis (IAP) protein survivin in murine and human cancer cells and tumors. Survivin inhibits caspase-9, blocks apoptosis, and is associated with resistance to chemotherapy and radiation. Survivin is a client protein for the 90-kDa heat shock protein (Hsp-90), and the binding of survivin to Hsp-90 assists in the maturation, proper folding, assembly, and transport of this IAP protein. A derivative of the antibiotic geldanamycin, 17-allylamino-17-demethoxygeldanamycin (17-AAG), interferes with proper binding of client proteins, such as survivin, to Hsp-90 and leads to misfolding of client proteins, ubiquination, and proteasome degradation. We hypothesized that PDT efficacy may be reduced by treatment-mediated expression and phosphorylation of survivin, and therefore, targeting the survivin pathway could increase PDT responsiveness. To address this hypothesis, we examined cellular and molecular responses following exposure to PDT, 17-AAG, and the combination of PDT plus 17-AAG in human BT-474 breast cancer cells using Photofrin and NPe6 as photosensitizers. Cells treated with the combination of PDT and 17-AAG exhibited decreased expression of the Hsp-90 client proteins phosphorylated survivin, phosphorylated Akt, and Bcl-2. The decreased expression of these client proteins was accompanied by higher apoptotic indexes and increased cytotoxicity. To confirm a specific role for survivin in modulating PDT, we used a human melanoma cell line, YUSAC2/T34A-C4, stably transfected with an inducible dominant-negative survivin gene under the control of a tetracycline-regulated (tet-off) promoter. PDT treatment of melanoma cells expressing the dominant-negative survivin resulted in increased cleavage of the caspase substrate poly(ADP-ribose) polymerase, apoptosis, and cytotoxicity when compared with results following PDT of the same melanoma cell line expressing wild-type survivin. These results show for the first time that targeting survivin and possibly other Hsp-90 client proteins improves in vitro PDT responsiveness and suggest that manipulation of the antiapoptotic pathway maintained by survivin may enhance PDT-mediated cancer therapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Ferrario A,Rucker N,Wong S,Luna M,Gomer CJdoi
10.1158/0008-5472.CAN-06-4785subject
Has Abstractpub_date
2007-05-15 00:00:00pages
4989-95issue
10eissn
0008-5472issn
1538-7445pii
67/10/4989journal_volume
67pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Increased sialylation and branching of asparagine-linked oligosaccharides have recently been associated with both neoplastic transformation and the metastatic phenotype. Swainsonine, an inhibitor of Golgi alpha-mannosidase II blocks the synthesis of sialylated tri- and tetraantennary asparagine-linked oligosaccharides...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::Chinese hamster ovary cells exposed to the sulfhydryl compound cysteamine combined with heat treatment at 44 degrees C developed thermotolerance within 8 h. After initial treatment either with 15 min cysteamine (0.4 mM) at 37 degrees C immediately followed by 15 min heat at 44 degrees C or with 15 min cysteamine (0.4 ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract::The BCR/ABL fusion protein is a constitutively active tyrosine kinase that is responsible for the pathogenesis of chronic myelogenous leukemia (CML). Clinically, CML is characterized by a chronic phase (CP) that eventually terminates into a blast crisis (BC). BC transformation is associated with accumulation of CD34+ ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::Neoplasms in fish normally show poor abilities for metastasis, and there are no reports on intestinal cancer with metastasis to other organs. In aquaculture production, carnivorous salmonids in Northern Europe receive commercial feeds with plant ingredients. Such contents have been shown to cause chronic intestinal in...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4877
更新日期:2009-05-15 00:00:00
abstract::A total of 10 primary malignant lymphomas of the brain were examined for deletion, mutation, and 5' CpG island methylation of the p16 gene, which is a candidate tumor suppressor gene with CDK-inhibitory function. In Southern blot analysis, p16 gene deletion was suggested in nine cases, homozygously (five cases) or hem...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-03-15 00:00:00
abstract::Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK), includ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-0459
更新日期:2018-08-01 00:00:00
abstract::The relationship between adenosine deaminase (ADA) and a human membrane thymus leukemia (HTL) antigen-detected by an antithymocyte serum was explored. A freeze-thaw extract of the T-cell-derived cell line, MOLT 4, was applied to an immunoabsorbant column of a rabbit antiserum to calf ADA. The bound MOLT 4 ADA was elut...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
abstract::It is anticipated that this report will serve as a nucleus for stimulating meaningful studies of the biology of prostate cancer. Such studies will be essential for the control and ultimately the prevention of prostate cancer. The present focus was arrived at by consensus of an expert panel on prostate cancer. It is no...
journal_title:Cancer research
pub_type:
doi:
更新日期:1991-05-01 00:00:00
abstract::The toxicity and pharmacokinetics of cis-diamminedichloroplatinum (cisplatin) (90 mg/sq m) administered as a single 4-hr peritoneal dialysis, with or without concurrent i.v. infusion of sodium thiosulfate, 0.43 or 2.13 g/sq m/hr for 12 hr, were studied on 20 courses of treatment. When given without thiosulfate, the to...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::Cytogenetic analysis has indicated that deletion of chromosome 9p occurs in a significant number of non-small cell lung and mesothelioma tumors. Using paired oligonucleotide primers, we have undertaken an extensive analysis of 9p markers to determine homozygous and heterozygous loss of marker sequences. Homozygous los...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::Antibody-based cancer treatment depends upon distribution of the targeting macromolecule throughout tumor tissue, and spatial heterogeneity could significantly limit efficacy in many cases. Antibody distribution in tumor tissue is a function of drug dosage, antigen concentration, binding affinity, antigen internalizat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-3018
更新日期:2008-05-01 00:00:00
abstract::Malignant astrocytoma is one of the most deadly primary central nervous system tumors. Although significant progress has been made in understanding the molecular pathways that lead to the development of these tumors in adults, comparatively little analysis has been done in childhood astrocytomas, which are less common...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:
更新日期:2001-10-15 00:00:00
abstract::The bispecific murine monoclonal antibody (MAb) 1A10 has specificity for the human transferrin receptor (TfR) and the human tumor-associated antigen gp40. This antibody, therefore, functions as an "antigen fork" by binding to two distinct antigens on the same malignant cell. Highly purified 1A10 inhibits the growth of...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surv...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-17-0428
更新日期:2017-06-01 00:00:00
abstract::Phorbol ester tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) alter the morphology and differentiated states of numerous cell types in vitro. It is likely that these molecules are teratogenic for vertebrate embryos in which cytodifferentiation, cell-tissue interactions, and cellular motility are pro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
abstract::Previously, we had reported that a single i.p. injection of 15 mg cyclophosphamide (CY) per kg cured most mice bearing large MOPC-315 tumors (20 to 25 mm; Day 12 to Day 16 tumors) but rarely cured mice bearing nonpalpable tumors (Day 4 tumors). Also, mice that were not cured if treated with CY, 15 mg/kg, when they had...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::Cancer cells with germline deleterious mutations of BRCA1 or BRCA2 are deficient in homologous recombination repair and therefore sensitive to PARP inhibitor treatment. However, wild-type BRCA1/2-expressing cells with defects in other DNA damage repair pathway components may also exhibit "BRCAness," which in combinati...
journal_title:Cancer research
pub_type: 评论,杂志文章
doi:10.1158/0008-5472.CAN-20-1451
更新日期:2020-07-15 00:00:00
abstract::Primary melanocytes attach poorly to collagen type IV and laminin, in contrast to their firm attachment to collagen type I/III and fibronectin [Gilchrest et al., In vitro (Rockville), 21: 114-120, 1985]. We have now found that metastatic B16 melanoma cells attach well to collagen type IV, laminin, vitronectin, and fib...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Data on biodistribution and pharmacokinetics of Na2B12H11SH are few and lack in standardization. This study comprises a uniform series of 10 patients with glioblastoma administered Na2B12H11SH i.v. 24 h before surgery at a dose level used in earlier therapeutical trials (75 mg/kg body weight). Boron concentrations in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-12-15 00:00:00
abstract::Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting arginine metabolism, either by blocking cationic amino acid transporter 1 (CA...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-2139
更新日期:2019-02-01 00:00:00
abstract::In 1956, Otto Warburg proposed that the origin of cancer cells was closely linked to a permanent respiratory defect that bypassed the Pasteur effect (i.e., the inhibition of anaerobic fermentation by oxygen). Since then, permanent defects in oxygen consumption that could explain the dependence of cancer cells on aerob...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0555
更新日期:2008-07-01 00:00:00
abstract::Experiments were performed to assess the role of liver cell necrosis in the induction of early steps in liver carcinogenesis with diethylnitrosamine, as measured by the appearance of foci of resistant hepatocytes that stain for gamma-glutamyl transpeptidase and that are presumptive preneoplastic lesions in the rat. Wi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::A full-length cDNA for a novel isoform of the human receptor tyrosine phosphatase gamma gene (PTPRG) was overexpressed in Sf9 insect cells, and the gene product, PTP gamma, was purified and characterized. The protein was expressed as a M(r) approximately 185,000 protein accompanied by a M(r) approximately 120,000 puta...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Continued monitoring of a family for new malignant tumors has revealed diverse immunological and neoplastic disorders during a 15-year period. In 1966, the proband developed lymphoma. In 1975, his antibody titers to Epstein-Barr virus (EBV) became elevated, and again, he developed a malignant lymphoma. He also had bor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract::ADAMTS metalloprotease family member ADAMTS9 maps to 3p14.2 and shows significant associations with the aerodigestive tract cancers esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). However, the functional impact of ADAMTS9 on cancer development has not been explored. In this study, we eval...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-4510
更新日期:2010-07-01 00:00:00
abstract::A major objective of the emerging field of exercise-oncology research is to determine the efficacy of, and biological mechanisms by which, aerobic exercise affects cancer incidence, progression, and/or metastasis. There is a strong inverse association between self-reported exercise and the primary incidence of several...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-16-0887
更新日期:2016-07-15 00:00:00
abstract::Chlorozotocin, 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose, is a newly synthesized, water-soluble nitrosourea antitumor agent that is active against L1210 leukemia in mice. A 701% and a 401% increase in life-span were attained with a dose that was lethal to 10% of the animals (15 to 20 mg/kg, i.p.) in mice t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-03-01 00:00:00
abstract::Thyroid neoplasms show a wide variety of lesions varying from slowly growing differentiated adenocarcinomas to rapidly proliferating undifferentiated carcinomas. There has been some histopathological evidence that the undifferentiated thyroid carcinomas are derived from differentiated carcinomas. Moreover, it is suspe...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::The formation and persistence of O6-ethylguanine, O4-ethylthymine, and O2-ethylthymine were quantitated in the genomic DNA of human lymphoblasts exposed to 1.0 mM N-ethyl-N-nitrosourea using immunoslot-blot. The three cell lines used included one which lacks O6-alkylguanine-DNA alkyltransferase, one deficient in nucle...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::Energy restriction (ER) inhibits mammary carcinogenesis and results in a marked reduction in tumor size, effects likely to be explained by ER-mediated induction of apoptosis. The goal of this study was to investigate the molecular mechanism(s) accounting for apoptosis induction. To do this, chemically induced mammary ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-3108
更新日期:2004-02-15 00:00:00