Abstract:
:3,4-Dihydro-2,2-dimethyl-2H-naptho[1,2,-b]pyran-5,6-dione (beta-lapachone) is a novel DNA repair inhibitor. It was tested for synergistic X-ray-induced lethality in combination with several halogenated pyrimidine radiosensitizers. Logarithmic-phase growing human epidermoid laryngeal carcinoma (HEp-2) cells were allowed to incorporate pyrimidine analogues for 48 h (approximately two cell doublings) and then were X-irradiated and subjected to various posttreatments. beta-Lapachone synergistically increased the dose enhancement ratios (DERs) of all analogues screened, with the exception of the 2'-chloro derivative of 5-bromodeoxyuridine. For example, following 5-bromodeoxycytidine sensitization an X-ray DER value of 1.87 +/- 0.04 at 1% survival was increased to 3.51 +/- 0.42 due to a 4-h post-X-irradiation exposure to 4 microM beta-lapachone. Do and Dq values for halogenated pyrimidine-sensitized human epidermoid laryngeal carcinoma cells were decreased 1.4- to 5.4-fold and 1.4- to 4.0-fold, respectively. beta-Lapachone had little effect upon the cytotoxicities of unirradiated human epidermoid laryngeal carcinoma cells whether or not they were previously exposed to any of the halogenated pyrimidine radiosensitizers. beta-Lapachone treatment following X-irradiation of cells that had not incorporated a pyrimidine analogue exhibited DER values of 1.38 +/- 0.05 and 1.40 +/- 0.01 at 10 and 1% survival levels, respectively. beta-Lapachone enhanced the radiosensitization of deoxycytidine analogues to a greater extent than the structurally related deoxyuridine analogues. Greater DERs and lower Do and Dq values were found for deoxycytidine than for deoxyuridine analogue radiosensitizers following beta-lapachone treatment. This agent may improve presently used radiation therapies and enhance proposed strategies which utilize deoxycytidine analogue radiosensitization together with protection of normal tissues by tetrahydrouridine to achieve tumor-selective radiotherapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Boothman DA,Greer S,Pardee ABsubject
Has Abstractpub_date
1987-10-15 00:00:00pages
5361-6issue
20eissn
0008-5472issn
1538-7445journal_volume
47pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::We have recently found that human pancreatic adenocarcinomas exhibit strong immunostaining for the three mammalian transforming growth factor beta (TGF-beta) isoforms. These important growth-regulating polypeptides bind to a number of proteins, including the type I TGF-beta receptor (T beta R-I), type II TGF-beta rece...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-06-15 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is etiologically linked to the endothelial tumor Kaposi's sarcoma and with two lymphoproliferatve disorders, primary effusion lymphoma and multicentric Castleman's disease. HHV-8 infects a variety of target cells both in vivo and in vitro, binds to the in vitro targ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-2767
更新日期:2004-01-01 00:00:00
abstract::The incidence, distribution, size, and histopathology of grossly visible colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed either a chemically defined fiber-free diet or a nutritionally and calorically equivalent diet containing a purified fiber component, microcrys...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-09-01 00:00:00
abstract::The mammalian target of rapamycin (mTOR) is centrally involved in cell growth, metabolism, and angiogenesis. While showing clinical efficacy in a subset of tumors, rapamycin and rapalogs are specific and allosteric inhibitors of mTOR complex 1 (mTORC1), but they do not directly inhibit mTOR complex 2 (mTORC2), an emer...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0299
更新日期:2009-08-01 00:00:00
abstract::Mice transgenic for the human carcinoembryonic antigen (CEA) gene were prepared for use as a preclinical model for immunotherapy. A 32.6-kb fragment containing the complete human CEA gene and flanking sequences was isolated from a genomic cosmid clone and used to produce transgenic C57BL/6 mice. A homozygous line was ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract::The Bcl-2 homologue Bak is a potent inducer of apoptosis. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the entire coding region of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early-stage and 18 advanced-stage cancers) and 20 primary colorectal cancers (6 ear...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::We previously reported that both sodium butyrate and trichostatin A (TSA), both of which are known as inhibitors of histone deacetylase, arrest human tumor cells at G1 and G2-M and activate the cyclin-dependent kinase inhibitor, the p21/WAF1/Cip1 gene promoter, through the Sp1 sites. In this study, we identified Sp1 a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::We have demonstrated previously that the immunomodulator AS101 can protect mice from acute lethal toxicity mediated by high doses of radiation or chemotherapy. The compound was shown to rescue mice from toxic effects of cyclophosphamide or 5-fluorouracil. The results presented herein demonstrate that pretreatment of m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-12-15 00:00:00
abstract::We have developed a new strain of rats (resistant rat) which exhibit resistance against the carcinogenic action of several carcinogenic compounds. In the present study, we compared the ability of resistant rat liver to activate 3'-methyl-4-dimethylaminoazobenzene and 2-acetylaminofluorene to highly reactive metabolite...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::Expression of resistance to cis-diamminedichloroplatinum(II) (CDDP), one of the most effective chemotherapeutic drugs used to treat a variety of malignancies, remains a serious obstacle for improving cancer treatment. To study possible genetic mechanisms underlying the development of CDDP resistance, we have adopted t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::The microbial alkaloid staurosporine is a potent but nonselective inhibitor of protein kinases. The derivative CGP 41251 has been shown to exert a high degree of selectivity for inhibition of protein kinase C activity. Both compounds are powerful inhibitors of proliferation of both normal and transformed cells in vitr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Single-chain Fv antibody fragments from the CD20-specific murine monoclonal antibody B9E9 were genetically engineered as streptavidin fusions [single-chain Fv-streptavidin (scFvSA) fusion protein] for use in pretargeted radioimmunotherapy. The scFvSA constructs were expressed as soluble, tetrameric species in the peri...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Loss of serine or threonine phosphorylation sites from exon 3 of beta-catenin has been identified in approximately half of colorectal tumors which lack adenomatous polyposis coli (APC) mutations, but the overall contribution of beta-catenin mutations to sporadic colorectal tumorigenesis is unclear. We therefore used P...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::The cytokinetics of an isogeneic, transplantable, lymphoid leukemia, growing as an ascitic tumor in the C57BL/6 mouse, has been investigated during normal growth and during regression induced by weekly injections i.v. of 1.0 mg Bacillus Calmette-Guérin (BCG). Survival was significantly prolonged in the BCG-treated gro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
abstract::Epidemiological data have provided clues to the etiological factors involved in large bowel cancer development. High intake of dietary fat tends to promote colon carcinogenesis. Studies in metabolic epidemiology have shown that the high dietary fat affects the metabolic activity of gut bacteria as well as the levels o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::cis-Diammine(1,1-cyclobutanedicarboxylato)platinum (CBDCA) is a nonnephrotoxic but myelosuppressive analogue of cisplatin (DDP) with greatly reduced protein binding and greatly increased renal excretion. Thus, CBDCA might produce undue toxicity in patients with decreased renal function. Twenty-two patients [14 females...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::Enhanced activation of Akt occurs in Cowden's disease, an inherited syndrome of follicular thyroid, breast, colon, and skin tumors, via inactivation of its regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sporadic thyroid cancer, activation of growth factor pathways that signal through Akt is frequen...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-08-15 00:00:00
abstract::Insulin receptor (IR) exists as two isoforms resulting from the alternative splicing of IR pre-mRNA. IR-B promotes the metabolic effects of insulin, whereas IR-A rather signals proliferative effects. IR-B is predominantly expressed in the adult liver. Here, we show that the alternative splicing of IR pre-mRNA is dysre...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-3824
更新日期:2013-07-01 00:00:00
abstract::The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in patients with VHL disease and in the majority of patients with sporadic renal cell carcinomas (RCCs). RCCs are dependent on insulin-like growth factor-1 receptor-mediated signaling for tumor growth and invasion in vivo. Reintroduction of the VHL gene prod...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::50C10 and 52H10 are two DNA clones previously reported by us to be overexpressed in human colonic mucosa at high risk for development of colonic tumors. This report presents sequencing data that reveal that these clones contain repetitive Alu elements. Each Alu sequence is associated with a 3'-oligoadenylate [oligo(A)...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::The i.p. inoculation of C3H mice with 5 times 10-6 cells of a transplantable ovarian carcinoma invariably evokes accumulation of large amounts of ascitic fluid. Histological and pharmacotherapeutic studies indicate that obstruction to peritoneal lymphatic drainage is a key factor in the formation of carcinomatous asci...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-02-01 00:00:00
abstract::As a specific competitive inhibitor of 5alpha-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone, finasteride is being extensively used for the treatment of benign prostatic hyperplasia and in experimental settings for prostate cancer. In this study, we showed that finasteride markedl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-02-15 00:00:00
abstract::Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4608
更新日期:2007-05-15 00:00:00
abstract::Significant efforts are being devoted toward the development of effective therapeutic vaccines against cancer. Specifically, well-characterized subunit vaccines, which are designed to generate antitumor cytotoxic CD8 T-cell responses. Because CD4 T cells participate at various stages of CD8 T-cell responses, it is imp...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3134
更新日期:2008-12-01 00:00:00
abstract::MicroRNAs (miRNA) are a recently discovered class of noncoding RNAs that negatively regulate gene expression. Recent evidence indicates that miRNAs may play an important role in cancer. However, the mechanism of their deregulation in neoplastic transformation has only begun to be understood. To elucidate the role of t...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1585
更新日期:2007-09-15 00:00:00
abstract::Using whole viable human colon carcinoma HT29 cells as immunogen, we produced a monoclonal antibody (mAb) termed 69-6-5. The antibody was functionally selected on its anti-cell-spreading activity. By immunoprecipitation of surface radiolabeled cell lysates from HT29-D4 cells (an HT29 cell clone), mAb 69-6-5 recognized...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::We have studied the effects of low-power-density microwave (MW) radiation (continuous and pulsed wave with average power density of 10 milliwatts/sq cm and range of 5 to 50 milliwatts/sq cm; frequency, 1.0 GHz) on the uptake and action of methotrexate (MTX), the inhibition of DNA synthesis in L1210 murine leukemia cel...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-04-01 00:00:00
abstract::Medulloblastoma is the most common malignant pediatric brain tumor and is one of the leading causes of cancer-related mortality in children. Treatment failure mainly occurs in children harboring metastatic tumors, which typically carry an isochromosome 17 or gain of 17q, a common hallmark of intermediate and high-risk...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-0592
更新日期:2010-10-15 00:00:00
abstract::Matrix metalloproteinases have been traditionally linked to cancer dissemination through their ability to degrade most extracellular matrix components, thus facilitating invasion and metastasis of tumor cells. However, recent functional studies have revealed that some metalloproteases, including several members of the...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4155
更新日期:2009-06-01 00:00:00
abstract::We have measured the 31P nuclear magnetic resonance spectra of EMT6/Ro multicellular tumor spheroids over a wide range of sizes under constant nutrient conditions which matched those used for culturing the spheroids. The amount of nucleotide triphosphate per cell decreased with spheroid growth, roughly in proportion t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00