Abstract:
:CD30 is selectively expressed on the tumor cells of a variety of malignant disorders of the immune system and can therefore be used as a target for an anti-CD30 antibody-based immunotherapy. However, CD30 is cleaved at the cell surface by tumor necrosis factor-alpha converting enzyme (TACE). This metalloproteinase releases the soluble ectodomain of CD30 (sCD30), which is able to neutralize immunotherapeutic agents before these reach their target cells. Such constitutive CD30 cleavage is enhanced after binding of most anti-CD30 antibodies, leading to a downregulation of CD30 and an increase of sCD30 in the cell environment. Here, we demonstrate that CD30 shedding from the cell line Karpas 299 could effectively be blocked by the hydroxamic acid-based metalloproteinase inhibitors BB-3644 (IC50 = 180 nM), BB-2116 (IC50 = 230 nM), BB-94 (batimastat, IC50 = 230 nM) and BB-2516 (marimastat, IC50 = 1 microM). This inhibition reduced the concentration of sCD30 in the cell environment to the background level, prolonged the persistence of the anti-CD30 antibody Ki-3 on Karpas 299 cells and favored its internalization. Moreover, a nontoxic concentration of the inhibitor BB-3644 significantly increased the cytotoxic activity of the anti-CD30 ricin A-chain immunotoxin Ki-3.dgA towards the CD30(+) Hodgkin-derived cell line L540. Hence, the metalloproteinase inhibitor BB-3644 may be a promising compound to improve the immunotherapy of CD30(+) malignancies.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Hansen HP,Matthey B,Barth S,Kisseleva T,Mokros T,Davies SJ,Beckett RP,Foelster-Holst R,Lange HH,Engert A,Lemke Hdoi
10.1002/ijc.10182keywords:
subject
Has Abstractpub_date
2002-03-10 00:00:00pages
210-5issue
2eissn
0020-7136issn
1097-0215pii
10.1002/ijc.10182journal_volume
98pub_type
杂志文章abstract::The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3-methylcholanthrene (3-MCA), was tested in NIH 3T3 transformation assay. Activation of K-ras and N-ras was found in 7 and 3 cases respectively. No H-ras activation was detected. Polymerase chain reaction and oligonucleotide hybridizati...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910470423
更新日期:1991-02-20 00:00:00
abstract::Very late antigen-4 (VLA-4) composed of alpha 4 and beta 1, a member of the beta 1-integrin subfamily, facilitates cell-to-cell interaction with vascular cell-adhesion molecule-1 (VCAM-1) on endothelial cells (EC). Attachment of blood-borne tumor cells to EC is a crucial step for hematogenous metastasis, and VLA-4-pos...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910600604
更新日期:1995-03-16 00:00:00
abstract::The human surface antigen CD24 is over-expressed in small-cell lung cancer. Here we describe the isolation, sequencing and functional characterization of the 5'-flanking region of the human CD24 gene. A sequence (accession number: Y14692) of 3.4 kb regulates the activity of a luciferase reporter gene in CD24-expressin...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19981109)78:4<496::aid-ijc
更新日期:1998-11-09 00:00:00
abstract::Children are especially sensitive to ionizing radiation and chemical carcinogens, and limiting their cancer risk is of great public concern. Calorie restriction (CR) is a potent intervention for suppressing cancer. However, CR is generally not appropriate for children. This study, therefore, examined to see if adult-o...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28751
更新日期:2014-09-01 00:00:00
abstract::Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high-density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that sever...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32138
更新日期:2019-08-15 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is a cell plasticity process required for metastasis and chemoresistance of carcinoma cells. We report a crucial role of the signal adaptor proteins CRK and CRKL in promoting EMT and tumor aggressiveness, as well as resistance against chemotherapy in colorectal and pancreatic ca...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32955
更新日期:2020-09-15 00:00:00
abstract::The expression of two discrete cell properties related to the host natural effector mechanisms, i.e., resistance to damage by H2O2, a cytotoxic product of activated macrophages, and the ability to secrete PGE, which inhibits NK-cell cytotoxicity, has been examined in parental Syrian hamster embryo cells spontaneously ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910440526
更新日期:1989-11-15 00:00:00
abstract::Breast cancer (BC) is the leading cause of cancer in sub-Saharan Africa (SSA) with rapidly increasing incidence rates reported in Uganda and Zimbabwe. However, the magnitude of these rising trends in premenopausal and postmenopausal women is unknown in most African countries. We used data from the African Cancer Regis...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.33014
更新日期:2020-10-15 00:00:00
abstract::Hepatocellular carcinoma (HCC) results from the cumulative effects of deregulated tumor suppressor genes and oncogenes. The tumor suppressor and oncogenes commonly affected include growth factors, receptors and their downstream signaling pathway components. The overexpression of transforming growth factor alpha (TGF-a...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25127
更新日期:2010-09-01 00:00:00
abstract::Salvicine is a diterpenoid quinone derived from a traditional Chinese medication that has been shown to possess potent in vitro and in vivo antitumor effects. This compound, which inhibits the activity of Topoisomerase II, was found to equipotently kill various multidrug-resistant tumor cells and their corresponding p...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.20026
更新日期:2004-07-10 00:00:00
abstract::The tumor microenvironment consists of an immunosuppressive niche created by the complex interactions between cancer cells and surrounding stromal cells. A critical component of this environment are myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells arrested at different stages o...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.30232
更新日期:2016-11-01 00:00:00
abstract::General cell-mediated immune (CMI) functions in NPC patients were investigated by the in vivo Mantoux and in vitro lymphocyte response to PHA assays. Thirty-eight (50%) of 76 untreated NPC patients were hyporesponsive in the Mantoux assay compared to 27 (25%) of 110 control patients. Forty-three (65.2%) of 66 untreate...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910180202
更新日期:1976-08-15 00:00:00
abstract::von Willebrand factor (vWF), a glycoprotein produced uniquely by endothelial cells and megakaryocytes, is routinely used to identify vessels in tissue sections. Vessel density in tumor specimens, as determined by immuno-histochemical staining for vWF or other endothelial cell markers, is a negative prognostic factor f...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(20000115)85:2<281::aid-ijc
更新日期:2000-01-15 00:00:00
abstract::Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals, which are epidemiologically significant chemicals in relation to liver cancer in mammals. The present study was conducted to determine the promoting effects of organic arsenicals related to DMA [monomethylarsonic acid (MMA) and trimethylarsine o...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10471
更新日期:2002-07-10 00:00:00
abstract::Cancer initiation is presumed to occur in utero for many childhood cancers and it has been hypothesized that advanced paternal age may have an impact due to the increasing number of mutations in the sperm DNA with increasing paternal age. We examined the association between paternal age and specific types of childhood...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30677
更新日期:2017-06-01 00:00:00
abstract::Alterations in the gene copy numbers of the proto-oncogenes HER2/neu and c-myc in primary human breast cancer investigated in 73 patients. We detected amplification of HER2/neu in 17 patient samples and amplification of c-myc in 11, while amplification of both was seen in 6 samples. There was no correlation of age, ho...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.2910430218
更新日期:1989-02-15 00:00:00
abstract::A long-term tissue culture cell line has been derived from a human prostate adenocarcinoma metastatic to the brain. The cell line, DU 145, has been passaged 90 times in vitro over a period of 2 years. The cells are epithelial, grow in isolated islands on plastic Petri dishes, and form colonies in soft agar suspension ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910210305
更新日期:1978-03-15 00:00:00
abstract::Although thyroid cancer is suspected to have a nutritional etiology, prospective studies examining the relationship between diet and thyroid cancer are lacking. During 1996-1997, NIH-AARP Diet and Health Study participants, ages 51-72 years, completed a 37-item food frequency questionnaire about diet at ages 12-13 yea...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29600
更新日期:2015-11-15 00:00:00
abstract::Survivin protein is an attractive candidate for cancer immunotherapy since it is abundantly expressed in most common human cancers and mostly absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos or erionite exposure for which no successful therapies are currently avai...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28048
更新日期:2013-08-01 00:00:00
abstract::Epstein-Barr virus (EBV) can be detected in Hodgkin and Reed-Sternberg (HRS) cells in about one-half of cases of Hodgkin's disease (HD) in Western countries. To determine whether EBV is also associated with HD in a developing country such as China, we studied paraffin sections from 28 Chinese cases of HD for expressio...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910550303
更新日期:1993-09-30 00:00:00
abstract::Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis, repair and DNA methylation. The impact of single nucleotide polymorphisms (SNPs) in folate-metabolizing enzymes has been investigated in risk of breast cancer among European or Asian populations, but not among women of African ancestry. We co...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29434
更新日期:2015-08-01 00:00:00
abstract::Twenty-seven human colorectal adenocarcinomas were implanted s.c. into nude mice. A comparative study of chromosomes and DNA between fresh tumor (FT) and xenografted tumor cells (XT) could be performed in 9 cases. Losses or deletions were consistently found in FTs as well as in XTs, particularly on chromosomes 17 and/...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910440521
更新日期:1989-11-15 00:00:00
abstract::Reverse-transcriptase polymerase chain reaction has been used to analyze the expression of 2 latent genes (EBNA-1 and LMP-1) and one replicative gene (BZLF-1) of Epstein-Barr virus in mononuclear cells from bone marrow and peripheral blood of healthy donors. EBV-gene transcription was detected in 8 out of 15 bone-marr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970304)70:5<524::aid-ijc
更新日期:1997-03-04 00:00:00
abstract::Paraffin sections from 190 epithelial ovarian tumours, including 159 malignant and 31 benign epithelial tumours, were analysed immunohistochemically for expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A (p16). Most benign tumours showed no p16 expression in the tumour cells, whereas only...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970220)74:1<57::aid-ijc1
更新日期:1997-02-20 00:00:00
abstract::Six permanent human tumor cell lines (OV-MZ-1 to 6) were established from 6 patients with serous adenocarcinomas of the ovary. These cell lines were derived from both solid tumors and ascites, from pre-treated and untreated patients, and are available over a range of in vitro passage numbers. The tumor cells grow as m...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910520115
更新日期:1992-08-19 00:00:00
abstract::Smoking is indisputably linked to lung cancer, yet only a small fraction of smokers develops this disease. Although previously tobacco-derived carcinogens and enzyme polymorphisms have been identified to increase the risk for smokers, recent epidemiological data suggest even sex-specificity as a new and additional fac...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.32716
更新日期:2020-05-01 00:00:00
abstract::Data from 1,916 cases of oral neoplasms occurring in the Sudan in a 16-year period, from January 1970 to December 1985, were retrieved and analysed. The study revealed a relatively high frequency of oral neoplasms in comparison with neighbouring countries. In this study, squamous-cell carcinoma was the most common ora...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910610202
更新日期:1995-04-10 00:00:00
abstract::The large geographic variations in the incidence of gastric cancer (GC) are likely due to differential environmental exposures, in particular to Helicobacter pylori (H. pylori) infection. We aimed to investigate the impact of H. pylori on the epigenome in normal gastric mucosa and methylation changes associated with c...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31381
更新日期:2018-08-01 00:00:00
abstract::Esophageal cancer is a leading cause of cancer death, especially in developing countries. In high-risk regions, squamous cell carcinoma is the most common type of esophageal cancer, and its etiology remains poorly understood. The purpose of this study was to evaluate the association between human papillomavirus (HPV) ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21980
更新日期:2006-09-15 00:00:00
abstract::The c-met oncogene encodes the receptor for hepatocyte growth factor/scatter factor (HGF/SF), a multifunctional cytokine able to mediate morphogenesis as well as mitogenesis, motogenesis and invasiveness of epithelial cells. HGF/SF has been implicated in branching tubulogenesis of the developing kidney and in regenera...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960621)69:3<212::AID-IJC
更新日期:1996-06-21 00:00:00