Abstract：
:DAB486IL-2, a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with interleukin-2 (IL-2), has displayed significant activity in patients with chemotherapy refractory hematological cancers. To further investigate the safety and antitumor effect of this agent, we conducted a single arm, dose escalation study of a 90-min infusion of DAB486IL-2 daily for 5 days. Patients with cancers of a histology previously reported to express the p55 component of the IL-2 receptor and who could not receive potentially more effective therapy were eligible for enrollment. Fifteen men and 8 women with a median age of 49 years were given a total of 51 courses of DAB486IL-2. The maximum tolerated dose was 0.3 mg/kg/day defined by renal insufficiency associated with hemolysis and thrombocytopenia. The clearance of DAB486IL-2 from serum fit a one-compartment model with a half-life of 11.5 +/- 4.3 (SD) min at the 0.2-mg/kg dose. Two patients sustained a partial response and 4 patients had tumor reduction not qualifying for an objective response. No tumors that were negative for expression of the p55 subunit of the receptor responded to DAB486IL-2 treatment. Reduction in size occurred in 2 tumors in which p55 expression was unknown and 4 patients with tumors that were known to be p55 positive. Dosing determined by specific activity rather than mass also appeared to be an important determinant of response. This study suggests that the presence of p55 expression on tumor cells is necessary, but alone may not be sufficient to achieve a tumor response. The correlation of additional variables such as specific activity of DAB486IL-2 and tumor expression of the p75 subunit of the IL-2 receptor and receptor function will also require further study.
journal_name
Cancer Resjournal_title
Cancer researchauthors
LeMaistre CF,Craig FE,Meneghetti C,McMullin B,Parker K,Reuben J,Boldt DH,Rosenblum M,Woodworth Tsubject
Has Abstractpub_date
1993-09-01 00:00:00pages
3930-4issue
17eissn
0008-5472issn
1538-7445journal_volume
53pub_type
临床试验,杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Most squamous cell carcinomas of the head and neck (HNSCC) overexpress ERBB1/EGFR, but EGF receptor (EGFR)-targeted therapies have yielded disappointing clinical results in treatment of this cancer. Here, we describe a novel interaction between EGFR and the ligand EphrinB1 (EFNB1), and we show that EFNB1 phosphorylati...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-0760
更新日期：2013-09-15 00:00:00
abstract：:Antibodies were produced against 220,000-molecular-weight proteins of Syrian hamster embryo cells. The antiserum containing these antibodies is capable of immunologically staining the surfaces and a fibrillar network around untransformed Syrian hamster embryo cells. The staining is removed by adsorption of the antiser...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-09-01 00:00:00
abstract：:Multidrug-resistant cells are thought to maintain low intracellular cytotoxic drug concentration though the active efflux of drugs across the cell membrane. It is presently believed that P-glycoprotein mediates this energy-dependent drug efflux by interacting directly with various lipophilic compounds. In this report,...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-12-15 00:00:00
abstract：:Lymphoid cell subpopulations infiltrating into autografts of methylcholanthrene-induced sarcomas in rats immunized with autologous tumor cells were identified in terms of immunohistochemical and cytofluorographic techniques using various monoclonal antibodies raised against different classes of rat lymphohemopoietic c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:Dehydroepiandrosterone, an adrenal steroid that has been reported to be produced in subnormal amounts and found in lower plasma concentrations in women with benign and malignant breast tumors, protects cultured rat liver epithelial-like cells against aflatoxin B1-induced cytotoxicity and protects hamster embryonic fib...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-09-01 00:00:00
abstract：:Retinoids have chemopreventive activity for epithelial tumors in a variety of systems, including the two-stage tumorigenesis system of mouse skin in which only the promotion stage is inhibited. We asked whether dietary vitamin A deficiency could affect the skin tumorigenic response, prior to major changes in body weig...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:We searched for potential suppressors of tumor metastasis by identifying the genes that are frequently down-regulated in hepatocellular carcinomas (HCC) while being negatively correlated with clinical parameters relevant to tumor metastasis, and we report here on the identification of N-myc downstream regulated gene 2...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5040
更新日期：2008-06-01 00:00:00
abstract：:Although the ability of Taxol to stabilize cellular microtubules is well accepted, the mechanisms by which Taxol induces growth arrest and cell death remain unclear. Recent evidence indicates that Taxol alters specific intracellular signal transduction events, such as the activation of Raf-1 kinase, that may be essent...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-08-15 00:00:00
abstract：:It has been proposed by MacMahon, on the basis of the variations among populations in the age distribution of fatal Hodgkin's disease, that there are two etiological factors, one important in young adults and the other important in middle-aged and elderly people. Correa has extended this by suggesting that those who d...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-12-01 00:00:00
abstract：:Sequential morphological changes occurring after brief carcinogen exposures of heterotopic tracheal transplants in rats were semiquantitatively studied. Tracheas were exposed to 7,12-dimethylbenz(a)anthracene for 1, 2, or 4 weeks, during which time means of 138, 152, and 160 microgram 7,12-dimethylbenz(a)anthracene, r...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-12-01 00:00:00
abstract：:FET cells, derived from an early-stage colon carcinoma, are nontumorigenic in athymic mice. Stable transfection of a dominant-negative transforming growth factor beta (TGFbeta) type II receptor (DNRII) into FET cells that express autocrine TGFbeta shows loss of TGFbeta signaling and increased tumorigenicity in vivo in...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5348
更新日期：2008-05-01 00:00:00
abstract：:We developed a novel orthotopic mouse tumor model of renal cell carcinoma to collect and characterize cells spontaneously shed from SN12C (renal cell carcinoma) and SN12L1 (high metastatic variant of SN12C) tumors grown in kidneys of severe combined immunodeficient mice. Viability of the shed cell population was great...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-0256
更新日期：2004-04-01 00:00:00
abstract：:The effect of overexpression of p21waf1 on drug sensitivity was studied in an osteosarcoma cell line (SaOs-2) lacking both p53 and functional retinoblastoma protein using a tetracycline (TC)-inducible expression system. p21waf1 expression was barely detectable in SaOS-2 cells incubated in the presence of TC. After TC ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
abstract：:In this paper, we describe the role of chemokine receptor CXCR4 activation by its natural ligand, the chemokine stromal cell-derived factor (SDF-1) (CXCL12), in glioblastoma cell growth in vitro. We show that both CXC chemokine receptor 4 (CXCR4) and SDF-1 mRNA are expressed in several human glioblastoma multiforme tu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-04-15 00:00:00
abstract：:Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens o...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-2353
更新日期：2010-10-01 00:00:00
abstract：:High-risk human papilloma viruses are known to be associated with cervical cancers. We have reported previously that the high-risk human papillomavirus (HPV) E6 oncoprotein interacts with E6TP1, a novel Rap GTPase-activating protein (RapGAP). Similar to p53 tumor suppressor protein, the high-risk HPV E6 oncoproteins t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-06-01 00:00:00
abstract：:We have obtained evidence for the existence of genes controlling invasion and metastasis by somatic cell fusion studies. Noninvasive, nonmetastatic mouse BW5147 T-lymphoma cells were fused with invasive human T-cells. The human cells were either activated normal peripheral blood lymphocytes or leukemic T-lymphoblasts....
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-12-15 00:00:00
abstract：:Bone marrow cells freshly aspirated from the 10 consecutive untreated adult patients with acute nonlymphocytic leukemia were cultured by 2 different methods: the conventional agar culture method for myeloid colony formation and its modification by daily feeding with culture medium. In 5 patients, colonies grew in much...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-12-01 00:00:00
abstract：:Adenocarcinoma of the rete testis is an exceptionally rare and malignant testicular neoplasm. Although treatment of pregnant women with diethylstilbestrol (DES) results in reproductive tract abnormalities in their male offspring, increased incidence of testicular tumors has not been verified. However, recently three c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：:In a recent study, we showed that the plant alkaloid camptothecin (CPT) and its derivatives 9-nitro-CPT (9NC) and 9-amino-CPT (9AC) inhibit growth of both human melanocytes (MEL cells) and their malignant counterparts, malignant melanoma (BRO) cells in vitro. This growth inhibition was accompanied by an increase in th...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:Cancer-secreted, extracellular vesicle (EV)-encapsulated miRNAs enable cancer cells to communicate with each other and with noncancerous cells in tumor pathogenesis and response to therapies. Here, we show that treatment with a sublethal dose of chemotherapeutic agents induces breast cancer cells to secrete EV with th...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-4055
更新日期：2019-07-15 00:00:00
abstract：:We have used culture conditions which simulate the microenvironment of breast tumors for the isolation and propagation of primary breast tumor cells in vitro. In this monolayer setup, the mixture of cells dissociated from primary breast tumors is subjected to self-created gradients of oxygen and nutrients as well as m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-06-15 00:00:00
abstract：:Fischer X Copenhagen rats bearing Dunning R3327-AT tumors were treated with hematoporphyrin derivative and red light (630 nm from an argon-driven dye laser) alone or in combination with the hypoxic cell radiosensitizer, misonidazole (MISO). In vitro studies had suggested that hypoxia might significantly decrease the c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:The adhesive characteristics of cultured acute lymphocytic leukemia cells (CCRF-CEM), lymphoma cells (Raji), and freshly isolated acute lymphocytic leukemia cells to human cultured endothelial cells were studied. An assay system was used whereby these neoplastic cells were allowed to interact with endothelial cells wh...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1978-08-01 00:00:00
abstract：:Inactivating effects caused by vincristine alone or in combination with another mitotic inhibitor, 1-propargyl-5-chloropyrimidin-2-one, were studied as loss of colony-forming ability in exponentially growing or synchronized populations of the human cell line NHIK 3025. Treatment with 4 ng vincristine per ml(4.3 nM) in...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-06-01 00:00:00
abstract：:The carcinogenic effectiveness of a number of nitrosoalkylamides related to nitrosoethylurea and nitroso-n-propylurea has been compared by topical application to Swiss mice and by intragastric administration to F344 rats. Nitrosohydroxyethylurea and the related cyclic nitrosamide, nitrosooxazolidone, were as potent as...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
abstract：:DNA synthesis was studied in mouse ascites sarcoma cells using a permeable cell system. The sarcoma was induced by the Schmidt-Ruppin strain of Rous sarcoma virus. The cells were made permeable to nucleoside triphosphates by treatment with a hypotonic buffer containing 10 mM Tris Cl, 4 mM MgCl2, 1 mM EDTA, and 6 mM 2-...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-01-01 00:00:00
abstract：:Proteolysis-inducing factor (PIF) is a sulfated glycoprotein produced by cachexia-inducing tumors, which induces atrophy of skeletal muscle. PIF has been shown to bind specifically with high affinity (K(d), in nanomolar) to sarcolemma membranes from skeletal muscle of both the mouse and the pig, as well as murine myob...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-2602
更新日期：2007-12-01 00:00:00
abstract：:Induction of an apoptotic cell death was studied in a mouse T-cell hybridoma. Apoptosis was induced in these cells following exposure to dexamethasone, X-radiation, 43 degrees C heat shock, A254 light, and hydrogen peroxide. In 5-Gy-exposed cells, a radiation-induced G2 phase cell cycle progression block was maximum b...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-02-15 00:00:00
abstract：:Vaccine strategies for treatment of human papillomavirus-induced cervical cancer are based on either the recombinant E7 fusion oncoprotein or E7 CTL peptides. The therapeutic potential of the E7-based vaccine depends on the use of different adjuvants. In this study, we describe for the first time the expression of the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-07-01 00:00:00
