Abstract:
:Quinocarmycin monicitrate (KW2152) and its analogue, DX-52-1, demonstrated specificity for melanomas in the National Cancer Institute in vitro human tumor cell line drug screen. In contrast to most cell lines, a 50% reduction in tumor cell burden (as measured protein) at the end of a 48-h drug incubation was produced in five of eight melanoma lines by KW2152 concentrations (LC50s) ranging from 0.49 to 10.93 microM and by DX-52-1 concentrations ranging from 0.71 to 7.33 microM. Using the COMPARE algorithm, the patterns of differential cytotoxicity for both agents at the LC50 level of effect most closely resembled those for actinomycin D, mithramycin, and Adriamycin. In in vivo studies, both KW2152 (40 mg/kg/day) and DX-52-1 (90 mg/kg/day) caused partial and complete regressions of staged s.c.-implanted LOX IMVI melanoma xenografts following i.p. administration on days 5, 9, and 13 and produced tumor growth delays of 231 and 181%, respectively (P < 0.001). Activity was augmented by more prolonged therapy. Statistically significant growth inhibition of SK-MEL-2, UACC-62, UACC-257, and M14, but not SK-MEL-5 and MALME-3M, melanoma xenografts also was observed following every fourth or seventh day i.p. treatments. Based on these findings, DX-52-1 has been selected by the National Cancer Institute for development to clinical trial especially against melanomas. This agent represents one of the first to be selected for preclinical development based on disease-panel specificity discovered in the National Cancer Institute cancer drug screen.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Plowman J,Dykes DJ,Narayanan VL,Abbott BJ,Saito H,Hirata T,Grever MRsubject
Has Abstractpub_date
1995-02-15 00:00:00pages
862-7issue
4eissn
0008-5472issn
1538-7445journal_volume
55pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::9-beta-D-Arabinofuranosyladenine (ara-A) is an inhibitor of DNA replication with antitumor and antiviral activity. The molecular basis for this inhibitory effect has remained unclear. The present work has examined the effects of 9-beta-D-arabinofuranosyladenine-triphosphate on DNA polymerase-beta. These studies were p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-04-15 00:00:00
abstract::Glycine N-methyltransferase (GNMT) affects genetic stability by (a) regulating the ratio of S-adenosylmethionine to S-adenosylhomocystine and (b) binding to folate. Based on the identification of GNMT as a 4 S polyaromatic hydrocarbon-binding protein, we used liver cancer cell lines that expressed GNMT either transien...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-03-3726
更新日期:2004-05-15 00:00:00
abstract::A sound rationale exists for antibody targeting of the MET receptor tyrosine kinase, but therapeutic agents that can broadly block HGF ligand binding and exon 14-mutated or amplified MET to induce receptor degradation have yet to be reported. Here we report the identification of several MET monoclonal antibodies (mAb)...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0026
更新日期:2016-10-01 00:00:00
abstract::Cell aggregation is frequently impaired during the growth of primary tumors and the formation of metastatic lesions. Cell aggregation depends on cell-cell adhesion; however, no rigorous approach exists to monitor and quantify it accurately in the absence of the confounding factors of cell-substrate adhesion and the re...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-3534
更新日期:2015-06-15 00:00:00
abstract::The effect of heat on 1,4-dihydroxy-5,8-bis[2-[(2-hydroxyethyl)amino]ethylamino]-9, 10-anthracenedione dihydrochloride (DHAD; mitoxantrone, NSC 301739) cytotoxicity was studied in V79 Chinese hamster cells. An overnight exposure to the drug at 40 degrees C enhanced drug damage in chromosome aberrations, culture growth...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::A monoclonal immunoglobulin M (IgM) antibody (38-13) which recognizes Burkitt's lymphoma (BL) cells, by reacting with the neutral glycolipid Gal alpha 1 leads to 4-Gal beta 1 leads to 4-Glc beta 1 leads to 1-ceramide, was recently characterized. This monoclonal IgM was coupled to either ricin A chain or gelonin. The t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Neuroblastoma (NB), a common pediatric neoplasm, consists of two main cell populations: neuroblastic/ganglionic cells and Schwann cells. NB tumors with abundant Schwannian stroma display a more benign clinical behavior than stroma-poor tumors. Recent studies suggest that Schwann cells influence NB tumor growth via sec...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-12-15 00:00:00
abstract::The presence of specific antitumor immunity was examined by the tube leukocyte adherence inhibition (LAI) assay in patients with carcinomas of the larynx. Peripheral blood leukocytes (PBL) from patients with larynx cancer gave positive reactions in the LAI assay with the antigen prepared from the carcinoma of the lary...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::In the absence of excision repair, doxorubicin caused a striking (41-fold) increase in the frequency of large deletion mutations extending from the lac operator (lacO) into the lac repressor gene (lacI) of Escherichia coli. In contrast, there was only a 2-fold increase in the frequency of small deletions despite a 3-f...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::Phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT) and Fms-like tyrosine kinase 3 (FLT3) signaling are aberrantly activated in acute myelogenous leukemia (AML) cells. Constitutively activated AKT and FLT3 regulate leukemia cell survival and resistance to chemotherapy. In this study, we investigated the effects of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1278
更新日期:2006-04-01 00:00:00
abstract::We examined the therapeutic effect of lipopolysaccharide (LPS), a differentiation inducer, in combination with daunomycin, an antileukemia drug possessing differentiation-inducing potential, on a rat myelomonocytic leukemia (c-WRT-7). c-WRT-7 cells were found to differentiate into macrophage-like cells and to lose the...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-03-15 00:00:00
abstract::Mitogen-activated protein kinases function in signal transduction pathways that are involved in controlling key cellular processes in many organisms. A mammalian member of this kinase family, MKK4/JNKK1/SEK1, has been reported to link upstream MEKK1 to downstream stress-activated protein kinase/JNK1 and p38 mitogen-ac...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characterist...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0786
更新日期:2008-12-15 00:00:00
abstract::Despite esophageal adenocarcinoma (EAC) being the most widespread among gastrointestinal cancers, with an 11-fold increase in the risk of cancer for patients with Barrett esophagus (BE), its prognosis is still poor. There is a critical need to better perceive the biology of cancer progression and identification of spe...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-18-0206
更新日期:2018-07-15 00:00:00
abstract::Anti-VEGF therapy prolongs recurrence-free survival in patients with glioblastoma but does not improve overall survival. To address this discrepancy, we investigated immunologic resistance mechanisms to anti-VEGF therapy in glioma models. A screening of immune-associated alterations in tumors after anti-VEGF treatment...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-1577
更新日期:2020-02-01 00:00:00
abstract::Radioimmunoassay has been used to measure acetylated and deacetylated deoxyguanosine C-8 DNA adducts of 2-acetylaminofluorene in liver and kidney DNA of male Wistar-Furth rats fed a dietary regimen of 0.02 or 0.04% 2-acetylaminofluorene. When adduct formation was monitored during continuous feeding up to 60 days, subs...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-04-01 00:00:00
abstract::Human B-cell tumors have been established in athymic, BALB/c mice using the EBV-positive Burkitt lymphoma cell line Namalwa. One-hundred-one of 104 animals (97%) developed tumors 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated human fibrosarcoma (HT-1080) cells. Tumors d...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::N,N-Dimethylformamide treatment of cell cultures established from a transplantable murine rhabdomyosarcoma-induced morphological differentiation and a marked reduction in the tumorigenicity of the sarcoma cells. Fourteen of 17 CE/J mice receiving injections of inducer-treated cells did not develop tumors after 6 month...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::[D-Arg1,D-Trp5,7,9,Leu11]Substance P (SP) was identified out of a panel of novel SP analogues as the most potent inhibitor of small cell lung cancer (SCLC) cell growth. This analogue inhibited proliferation of H-510 and H-69 SCLC cells in liquid culture and in semisolid media (IC50, 5 microM). Colony formation stimula...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Milk from a number of species (e.g., man, mouse, rat, dog, and cow) contains inhibitors of the RNA-directed DNA polymerase. When attempts are made to isolate virions from the milk, part of the inhibitors follow the virions in the purification. The amount of inhibitors varies in different milk samples. These inhibitors...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-02-01 00:00:00
abstract::BCL2 suppresses apoptosis by binding the BH3 domain of proapoptotic factors and thereby regulating outer mitochondrial membrane permeabilization. Many tumor types, including B-cell lymphomas and chronic lymphocytic leukemia, are dependent on BCL2 for survival but become resistant to apoptosis after treatment. Here, we...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-4204
更新日期:2012-08-15 00:00:00
abstract::The growth and survival of many types of cancer cells are known to be supported by specific growth factor/cytokine systems. Among these, the activation of c-kit receptor and its ligand steel factor participates in several types of human carcinogenesis. W mutations of laboratory mouse strains are loss of functional mut...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::The reactivities of two anti-bladder cancer monoclonal antibodies, AN43 and BB369, were characterized. AN43 and BB369 reacted with a majority (greater than 50%) of bladder cancer tissue sections tested by immunoperoxidase staining. When tested against a panel of 27 normal human tissues, AN43 and BB369 reacted only wit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::The neu oncogene has been demonstrated to be a potent transforming gene in rodent fibroblasts. The overexpression of the human erbB-2/neu oncogene has been implicated in the development and/or prognosis of several human carcinomas including that of the prostate. To assess the transforming potential of the activated ra...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy-based sequencing and reverse-phase protein arrays to 547 human breast cancers and 41 cell lines, we determined the subtype specificity and signaling effects of PIK3CA, AKT, and PTEN mutations and the effect...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6854
更新日期:2008-08-01 00:00:00
abstract::Eighteen-day-old fetal urogenital sinus mesenchyme (UGM), 0-day-old neonatal seminal vesicle mesenchyme (SVM), 0-day-old neonatal bulbourethral gland mesenchyme (BUG-M), and 3-day-old neonatal urinary bladder mesenchyme (BLM) were isolated from rats and combined in vitro with 0.5-mm cubes of the R3327 androgen-depende...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::The development of a supportive vasculature is essential for tumor progression. In a mouse model of breast cancer, we found that tumor-associated macrophages that are recruited to the tumor just before malignant conversion are essential for the angiogenic switch. These findings establish a causal linkage to explain we...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0912
更新日期:2007-06-01 00:00:00
abstract::The tumor suppressor gene p53 regulates G1 checkpoint prior to the initiation of DNA synthesis, which can either induce G1 arrest or signal apoptosis. The involvement of p53 in apoptosis may also be related to its ability to down-regulate transcription of the bcl-2 gene. The bcl-2 gene product prevents most types of a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-10-15 00:00:00
abstract::Many tumor types have p53 and/or RB mutations, and it is unclear what role the mutations of these tumor suppressor genes have on the efficacy of chemotherapeutic agents. The effect of p53 and RB inactivation on sensitivity to chemotherapeutic drugs was examined using a model system in which p53 or RB was inactivated i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-02-15 00:00:00
abstract::Studies demonstrate that some colon cancers possess receptors for various gastrointestinal hormones or neurotransmitters, the occupation of which can affect growth. These results are limited because frequently only a small number of tumors are studied, only 1 or 2 receptors are sought, and the effect on cell function ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00