Abstract:
:Preliminary results from a pilot trial on trastuzumab's mechanism of action against operable breast tumors overexpressing Her2 suggested a role for antibody-dependent cell cytotoxicity (ADCC). To examine factors affecting ADCC intensity and variability, we extended this study to the phenotypic and functional analysis of circulating mononuclear cells in 18 patients. ADCC was induced by trastuzumab therapy in 15 of 18 patients (83%). Inability to develop ADCC in three patients did not depend on inadequate levels of trastuzumab because further increase in its concentration in vitro was ineffective. Rather, susceptibility to develop ADCC was fairly predicted by test with trastuzumab before therapy and was correlated to the number of lymphocytes coexpressing CD16 and CD56. Phenotypic analysis at the end of ADCC evaluating down-regulation of CD16, and up-regulation of CD69 and CD107a, confirmed that natural killer (NK) cells and CD56(+) T cells were involved in productive engagement of trastuzumab. Also, the killing efficiency of CD16(+) lymphocytes was influenced by 158 V/F polymorphism of Fc gamma RIII (CD16), whereas variations of CD247 on NK cells were consistent with trends between ADCC before and after therapy. Complete pathologic response was observed in one patient showing ADCC of outstanding intensity, whereas four cases of partial response showed intermediate ADCC; none of the three patients unable to mount ADCC had significant tumor regression. These data indicate that quantity and lytic efficiency of CD16(+) lymphocytes are major factors for ADCC induction by trastuzumab, and confirm that breast cancer responses to short-term trastuzumab monotherapy may depend on involvement of the ADCC mechanism.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Varchetta S,Gibelli N,Oliviero B,Nardini E,Gennari R,Gatti G,Silva LS,Villani L,Tagliabue E,Ménard S,Costa A,Fagnoni FFdoi
10.1158/0008-5472.CAN-07-2068subject
Has Abstractpub_date
2007-12-15 00:00:00pages
11991-9issue
24eissn
0008-5472issn
1538-7445pii
67/24/11991journal_volume
67pub_type
临床试验,杂志文章相关文献
CANCER RESEARCH文献大全abstract::Human breast cancer (HBC) cell growth suppression by okadaic acid (OA) was previously found to involve elevated expression of oncogenes c-myc and c-fos and apoptosis. Since, c-Myc influences diverse pathways of cell growth, we hypothesized that elevated levels of c-Myc are involved in HBC growth suppression. Here, we ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2505
更新日期:2007-11-01 00:00:00
abstract::Infection with Helicobacter pylori is a major cause of gastric cancer (GC). The association likely has been underestimated in the past due to disease-related clearance of the infection. On the other hand, only a minority of the infected individuals develop GC, and better risk stratification is therefore highly desirab...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0596
更新日期:2009-08-01 00:00:00
abstract::Convection enhanced delivery (CED) is potentially a powerful method to improvethe targeting of macromolecules to the central nervous system by applying a pressure gradient to establish bulk flow through the brain interstitium during infusion. The purpose of the present study was to evaluate CED as a means to improve t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-11-15 00:00:00
abstract::Animal models, particularly mouse models, play a central role in the study of the etiology, prevention, and treatment of human prostate cancer. While tissue culture models are extremely useful in understanding the biology of prostate cancer, they cannot recapitulate the complex cellular interactions within the tumor m...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-4213
更新日期:2013-05-01 00:00:00
abstract::Male Wistar rats were given 50 mug of aflatoxin B1 twice a week for 4 weeks, and thereafter 75 mug twice a week for 10 weeks. Their livers were investigated histologically and histochemically for glycogen, RNA, fat, alkaline and acid phosphatases, adenosine triphosphatase, 5'-nucleotidase, glucose-6-phosphatase, gluco...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-10-01 00:00:00
abstract::The relationship between natural cell-mediated cytotoxicity (NCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) was examined in an Epstein-Barr virus-infected target cell system. The total ADCC reactivity to Epstein-Barr virus-infected target cells varied considerably with different effector cells, indicat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-04-01 00:00:00
abstract::Members of cutaneous melanoma (CM) families with dysplastic nevi (DN) are at high risk of developing CM. Using a shuttle vector plasmid, pSP189, cell lines from three patients with CM plus DN were previously found to have elevated post-UV plasmid mutability. To investigate familial occurrence of this cellular phenotyp...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-10-15 00:00:00
abstract::Gli signaling is critical for central nervous system development and is implicated in tumorigenesis. To monitor Gli signaling in gliomas in vivo, we created platelet-derived growth factor-induced gliomas in a Gli-luciferase reporter mouse. We find that Gli activation is found in gliomas and correlates with grade. In a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6350
更新日期:2008-04-01 00:00:00
abstract::Protein kinase C delta (PKCdelta), a Ca(2+)-independent, phospholipid-dependent serine/threonine kinase, is among the novel PKCs (delta, epsilon, and eta) expressed in mouse epidermis. We reported that FVB/N transgenic mice that overexpress ( approximately 8-fold) PKCdelta protein in basal epidermal cells and cells of...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2684
更新日期:2006-01-15 00:00:00
abstract::Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as basigin or CD147, is a glycoprotein that is enriched on the surface of tumor cells and stimulates production of several matrix metalloproteinases by adjacent stromal cells. In this study, we have found that EMMPRIN not only stimulates the producti...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-02-15 00:00:00
abstract::A phase I clinical trial with granulocyte-macrophage colony-stimulating factor tumor cell vaccines in patients with metastatic renal cell carcinoma (RCC) showed immune cell infiltration at vaccine sites and delayed-type hypersensitivity (DTH) responses to autologous tumor cells indicative of T-cell immunity. To furthe...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2005-02-01 00:00:00
abstract::Homogeneously staining regions (HSRs) were found in hypodiploid cells (40%) of a subline of the human melanoma cell line, MeWo, (MeWo-C) but were absent from the hypotetraploid cells (60%). Another subline (MeWo-B) was also shown to contain two populations of cells, 70% hypodiploid and 30% hypotetraploid. None of the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::The altered gene expression seen in cancer could relate to differences in nonhistone chromatin proteins between normal and malignant tumor cells. Phenol-soluble nonhistone chromatin proteins were isolated from human normal and leukemic (chronic lymphocytic leukemia) B-cells, as well as long-term cultured human B-lymph...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::Verapamil has been shown to enhance immunotoxin activity but only at concentrations that are too high for in vivo use. Therefore, four structural analogues of verapamil (D792, D595, D528, and Sz45) were evaluated for their ability to enhance the in vitro activity of immunotoxins made with either ricin A chain or Pseud...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::There are many animal models of glioma, but few that represent the biology of low-grade tumors and allow the study of the genetic mechanisms of glial oncogenesis. We report the in vivo transformation of astrocytic cells in transgenic mice by the SV40 T antigen under the control of the 5'-flanking sequence of the murin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
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 ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-15 00:00:00
abstract::The effect of leukocyte (IFN-alpha), fibroblast (IFN-beta), and immune (IFN-gamma) interferon and/or mezerein on the expression of HLA antigens and melanoma-associated antigens by the melanoma cell line MeWo and its metastatic variant MeM 50-10 was investigated, since this information may contribute to our understandi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-06-01 00:00:00
abstract::Infection by human papillomaviruses (HPV) leads to the formation of benign lesions, warts, and in some cases, cervical cancer. The formation of these lesions is dependent upon increased expression of proangiogenic factors. Angiogenesis is linked to tissue hypoxia through the activity of the oxygen-sensitive hypoxia-in...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2626
更新日期:2011-02-01 00:00:00
abstract::Myeloid-derived suppressor cells (MDSC) represent a primary mechanism of immune evasion in tumors and have emerged as a major obstacle for cancer immunotherapy. The immunoinhibitory activity of MDSC is tightly regulated by the tumor microenvironment and occurs through mechanistic mediators that remain unclear. Here, w...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-0880
更新日期:2019-10-01 00:00:00
abstract::Monoclonal antibodies (McAbs) to human bladder carcinoma were generated by fusion of NS-1 mouse myeloma cells with spleen cells from BALB/c mice immunized with either cultured human bladder cancer cells or cells obtained from a fresh surgically removed bladder tumor. Four hybridomas which reacted strongly with bladder...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::In order to explore whether immune complex (IC) formation and immunoglobulin M-class rheumatoid factor (RF) synthesis are related to tumor progression, solid-phase enzyme immunoassays were used to test for ICs and RF in rats bearing three different syngeneic mammary adenocarcinomas. The mammary adenocarcinoma cell lin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract::Pristane (2,6,10,14-tetramethylpentadecane) is a C19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Combination treatment of SKCO1 human colon carcinoma cells with beta ser-interferon (IFN-beta ser) and gamma-interferon (IFN-gamma) results in a synergistic antiproliferative effect. The role of IFN-beta ser and IFN-gamma receptor modulation was investigated as a possible mechanism for this response. IFN-gamma (0.05-5...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::Precise diagnosis and subtyping of kidney tumors are imperative to optimize and personalize treatment decision for patients. Patients with the most common benign renal tumor, renal oncocytomas, may be overtreated with surgical resection because of limited preoperative diagnostic methods that can accurately identify th...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-2522
更新日期:2020-02-15 00:00:00
abstract::To date, no prospective studies have explored the relationship between the use of aspirin, other nonsteroidal anti-inflammatory medications (NSAID), and acetaminophen and endometrial adenocarcinoma. Of the 82,971 women enrolled in a prospective cohort study, 747 developed medical record-confirmed invasive endometrial ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6257
更新日期:2008-04-01 00:00:00
abstract::The A-240T and I/D polymorphisms in the angiotensin I-converting enzyme (ACE) gene are markers of circulating ACE levels and have been associated with numerous cardiovascular disease outcomes. More recently, the low-activity A and I alleles at these polymorphic sites have been inversely related with breast cancer risk...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-10-15 00:00:00
abstract::For two decades, the antigen recognized by the Pathologische Anatomie Leiden-Endothelium (PAL-E) monoclonal antibody, a standard vascular endothelial cell marker, has remained elusive. Here, we used a combinatorial phage display-based approach ("epitope mapping") to select peptides binding to the original PAL-E antibo...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2737
更新日期:2007-10-15 00:00:00
abstract::Tetracyclines, a class of antibiotics that target bacterial translation, are commonly used in research for inducible gene expression using Tet-ON/Tet-OFF systems. However, such tetracycline-inducible systems carry a risk. Given that mitochondria have a "bacterial" ancestry, these antibiotics also target mitochondrial ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-15-1626
更新日期:2015-11-01 00:00:00
abstract::Previous work in our laboratory has demonstrated that antisera to proteins found in the urine of bladder cancer patients can distinguish between urine samples from these patients and those from normal individuals when tested by a complement-fixation assay. Antisera which were reactive with individual tumor-associated ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
abstract::A gastric choriocarcinoma cell line synthesizing human chorionic gonadotropin (HCG) was established in 1971 by Oboshi et al. and was found to possess human placental alkaline phosphatase. The present paper also deals with the relationship between the cell growth and HCG secretion and with cellular localization of HCG ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-08-01 00:00:00