Abstract：
:Gene-encoded host defense peptides are used as part of the innate immunity, and many of them act by directly lysing the cell membrane of the pathogen. A few of these peptides showed anticancer activity in vitro but could not be used in vivo because of their inactivation by serum. We designed a 15-amino acid peptide, composed of D- and L-amino acids (diastereomer), which targets both androgen-independent and androgen-dependent human prostate carcinoma cell lines (CL1, 22RV1, and LNCaP). Most importantly, we observed a complete arrest of growth in CL1 and 22RV1 xenografts treated intratumorally with the diastereomer. This was also accompanied by a lowering of prostate-specific antigen serum levels secreted by the 22RV1 xenograft. Furthermore, the diastereomer synergized with conventional chemotherapeutics. In contrast, the parental all l-amino acids peptide was highly active only in vitro and could not discriminate between tumor and nontumor cells. Fluorescent confocal microscopy, histopathologic examination, and cell permeability studies (depolarization of transmembrane potential and release of an encapsulated dye) suggest a necrotic mechanism of killing, after a threshold concentration of peptide has been reached. Its destructive killing effect and the simple sequence of the diastereomer make it an attractive chemotherapeutic candidate possessing a new mode of action, with potential to be developed additionally for the treatment of prostate carcinoma.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Papo N,Braunstein A,Eshhar Z,Shai Ydoi
10.1158/0008-5472.CAN-04-1438subject
Has Abstractpub_date
2004-08-15 00:00:00pages
5779-86issue
16eissn
0008-5472issn
1538-7445pii
64/16/5779journal_volume
64pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Successful systemic gene therapy has been hindered by vector-related limitations, including toxicity and inefficient gene delivery to tumor cells after i.v. administration. To circumvent these problems, we developed a novel formulation between the polycation polyethyleneimine and DNA that mediates high-level tumor cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-07-15 00:00:00
abstract：:Successive B16 melanoma tumor lines were selected for their ability to form pulmonary tumor nodules. This was accomplished by injecting tumor cells i.v. into syngeneic C57BL/6 mice and 2 to 3 weeks later collecting the secondary tumor growths and placing them into tissue culture. These tumor cells were then injected i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-01-01 00:00:00
abstract：:XPC protein is a critical DNA damage recognition factor in nucleotide excision repair for which genetic deficiency confers a predisposition to cancer. In this study, we show that XPC has a function that is independent of its canonical function in DNA repair, potentially altering the interpretation of how XPC deficienc...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-2774
更新日期：2012-02-01 00:00:00
abstract：:Spontaneous tumors in urodele amphibians have been considered uncommon, and this resistance has sometimes been associated with the natural regenerative capacity of tissues in such species. This report describes spontaneous, nonpigmented, benign epitheliomas which were found in 44 of 1586 (2.8%) adult newts, Cynops pyr...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-06-01 00:00:00
abstract：:Genomic analyses of late-stage human cancers have uncovered deletions encompassing 1p36, thereby providing an extensive body of literature supporting the idea that a potent tumor suppressor resides in this interval. Although several genes have been proposed as 1p36 candidate tumor suppressors, convincing evidence that...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-07-2095
更新日期：2008-04-15 00:00:00
abstract：:The effect of retinoic acid (RA) on N-methyl-N'-nitro-N-nitrosoguanidine-induced transformation of primary cultures of rat tracheal epithelial cells was investigated. RA inhibited transformation of rat tracheal epithelial cells by up to 95% at concentrations of 3.3 to 33 nM which did not substantially affect cell surv...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-12-01 00:00:00
abstract：:Solid tumors have a heterogeneous pathophysiology, which directly affects antibody-targeted therapies. Here, we consider the influence of selected tumor parameters on radioimmunotherapy, by comparing the gross biodistribution, microdistribution, and therapeutic efficacy of either radiolabeled or fluorescently labeled ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-2967
更新日期：2007-12-15 00:00:00
abstract：:Methotrexate [(+) amethopterin, L-MTX] has two carboxyl groups in its structure and is eliminated mainly by excretion into urine and bile. To investigate the biliary excretion mechanism of L-MTX, we performed in vivo and in vitro studies using mutant rats, Eisai hyperbilirubinemic rats (EHBRs), whose canalicular multi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-08-15 00:00:00
abstract：:gamma-Interferon (IFN-gamma) was shown to amplify cytotoxin release from murine bone marrow-adherent macrophages in response to an animal lectin as a second stimulus. This stimulation of cytotoxin release was demonstrated both in vitro and in vivo and was maximal 2 h after treatment with IFN-gamma. No change in expres...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-04-01 00:00:00
abstract：:Recent studies indicate that ovarian cancer may be highly responsive to antivascular therapeutics. We have developed an antivascular tumor therapeutic using the F3 peptide to target cisplatin-loaded nanoparticles (F3-Cis-Np) to tumor vessels. We show that although F3-Cis-Np bind with high specificity to both human ova...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1917
更新日期：2010-11-01 00:00:00
abstract：:Increase in dietary fat intake has been reported to be associated with progression of hormone-dependent cancers. To explore its mechanism, we examined the effects of fatty acids on the growth of androgen-dependent SC-3 cells cloned from mouse mammary cancer (Shionogi carcinoma 115). Their androgen-dependent growth was...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-12-15 00:00:00
abstract：:Growth rates of 7,12-dimethylbenz(a)anthracene-induced mammary tumors and the specific 125I-labeled prolactin binding to membrane fractions prepared from livers and tumors were studied in rats made diabetic by streptozotocin injection. Growth was inhibited in a majority of tumors and prolactin binding was reduced in b...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-11-01 00:00:00
abstract：:Gene expression signatures for a basal-like breast cancer (BLBC) subtype have been associated with poor clinical outcomes, but a molecular basis for this disease remains unclear. Here, we report overexpression of the transcription factor FOXC1 as a consistent feature of BLBC compared with other molecular subtypes of b...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-4120
更新日期：2010-05-15 00:00:00
abstract：:Telomerase is a ribonucleoprotein that synthesizes telomeric DNA on chromosomal ends. Telomerase activation has been seen in many immortal cell lines and cancers. Telomerase activity was analyzed in prostate carcinoma; in coexistent prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), atrophy...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-02-15 00:00:00
abstract：:Estramustine is an estradiol-based antimicrotubule agent that accumulates in malignant glioma cells, resulting in a concentration-dependent inhibition of proliferation. This agent has been shown to synchronize human glioma cells at G2-M consistent with its known effects on the mitotic spindle and potentially could be ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-03-15 00:00:00
abstract：:Administration of nerve growth factor (NGF) to the offspring of Sprague-Dawley rats transplacentally exposed to 50 mg/kg ethylnitrosourea on the 20th day of gestation resulted in a significant reduction of trigeminal and peripheral nerve neurinomas. Forty, 60, and 80 micrograms of NGF was administered in five s.c. dos...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-12-15 00:00:00
abstract：:Analysis of human fibrosarcoma cells exposed to radiolabeled monoclonal antibody 19-24, which recognizes sarcoma-associated antigen p102, revealed that over 54% of the cell surface-bound radioactivity was internalized. No modulation of cell surface p102 antigen by monoclonal antibody 19-24 was observed in human fibros...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：:Inflammatory bowel disease (IBD) is a gastrointestinal disorder of unknown etiology or cure. One complication of IBD is an increased risk for development of colon cancer. The aims of this study were to use a previously established rat model of colitis to develop a new model of colitis-associated colon cancer and ascer...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-1418
更新日期：2007-11-15 00:00:00
abstract：:The carcinogenicities of a choline deficient L-amino acid defined (CDAA) diet and a semipurified choline deficient diet were comparatively examined. A total of 60 male Fischer 344 rats, 6 weeks old, were divided into 5 experimental groups each consisting of 12 rats. Group 1 received the CDAA diet chronically to the en...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-09-15 00:00:00
abstract：:The evolution of immune blockades in tumors limits successful antitumor immunity, but the mechanisms underlying this process are not fully understood. Depletion of regulatory T cells (Treg), a T-cell subset that dampens excessive inflammatory and autoreactive responses, can allow activation of tumor-specific T cells. ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-1912
更新日期：2012-11-01 00:00:00
abstract：:The aim of this study was to evaluate to what extent tumor necrosis factor alpha (TNF-alpha) and interleukin 1 may explain the development of experimental cancer cachexia. For this purpose, C57BL/6J mice bearing a transplantable low differentiated rapidly growing tumor were passively immunized every other day with rab...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:The serum half-life of 5-fluorouracil (5-FUra) in humans is best described as a biexponential decay function, with t1/2 alpha = 7.8 +/- 2.6 (S.E.) min and t1/2 beta = 36.8 +/- 13.5 min during initial courses of this drug alone. Pharmacokinetics of 5-FUra during courses of daily therapy (for 5 days) revealed prolongati...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：:The treatment of K562 human myeloblastic leukemia cells and YAC-1 murine lymphoma cells with cadeguomycin at concentrations over 0.6 microM significantly enhanced the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C). The degree of potentiation depended upon the antibiotic concentration. The treatment with 75 ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
abstract：:Mutations in the human adenomatous polyposis (APC) gene are causative for familial adenomatous polyposis (FAP), a rare condition in which numerous colonic polyps arise during puberty and, if left untreated, lead to colon cancer. The APC gene is a tumor suppressor that has been termed the "gatekeeper gene" for colon ca...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-02-15 00:00:00
abstract：:Triple-negative breast cancers (TNBC), which include the basal-like and claudin-low disease subtypes, are aggressive malignancies for which effective therapeutic targets are lacking. NF-κB activation has an established role in breast malignancy, and it is higher in TNBC than other breast cancer subtypes. On this basis...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-3455
更新日期：2015-01-01 00:00:00
abstract：:The sensitivity of the human promyelocytic cell line HL60 to killing by the lysosomotropic detergent N-dodecyl imidazole (C12-Im) has been investigated in the exponential and stationary growth states and before and after differentiation induced by suitable effector molecules. Undifferentiated HL60 cells were more sens...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-02-01 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：:Cells deficient in DNA polymerase beta (beta-pol) are impaired in base excision repair (BER) and hypersensitive to various DNA damaging agents, including methylating mutagens. Hypersensitivity of beta-pol-deficient cells to methylating agents is because of induction of apoptosis (Ochs et al., Cancer Res., 59: 1544-155...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：:We investigated the relationship between age-related changes in natural resistance and antitumor effects using a spontaneously hypertensive rat (SHR rat) strain which shows a progressive decline of the number of T-cells and their functions as a result of aging. The growth of a weakly antigenic mammary adenocarcinoma S...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-07-01 00:00:00
abstract：:We used flow cytometry to measure the expression of human melanoma antigens on cell suspensions dissociated from metastatic masses. The objective was to study the heterogeneity between tumor samples from different patients and between different tumors excised from a single patient. Fifty-three metastases excised from ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-12-01 00:00:00
