Abstract:
:E2F-1, a key transcription factor necessary for cell growth, DNA repair, and differentiation, is an attractive target for development of anticancer drugs in tumors that are E2F "oncogene addicted". We identified a peptide isolated from phage clones that bound tightly to the E2F-1 promoter consensus sequence. The peptide was coupled to penetratin to enhance cellular uptake. Modeling of the penetratin-peptide (PEP) binding to the DNA E2F-1 promoter demonstrated favorable interactions that also involved the participation of most of the penetratin sequence. The penetratin-peptide (PEP) demonstrated potent in vitro cytotoxic effects against a range of cancer cell lines, particularly against Burkitt lymphoma cells and small cell lung cancer (SCLC) cells. Further studies in the H-69 SCLC cell line showed that the PEP inhibited transcription of E2F-1 and also several important E2F-regulated enzymes involved in DNA synthesis, namely, thymidylate synthase, thymidine kinase, and ribonucleotide reductase. As the PEP was found to be relatively unstable in serum, it was encapsulated in PEGylated liposomes for in vivo studies. Treatment of mice bearing the human small cell lung carcinoma H-69 with the PEP encapsulated in PEGylated liposomes (PL-PEP) caused tumor regression without significant toxicity. The liposome encapsulated PEP has promise as an antitumor agent, alone or in combination with inhibitors of DNA synthesis.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Xie X,Kerrigan JE,Minko T,Garbuzenko O,Lee KC,Scarborough A,Abali EE,Budak-Alpdogan T,Johnson-Farley N,Banerjee D,Scotto KW,Bertino JRdoi
10.4161/cbt.25184subject
Has Abstractpub_date
2013-08-01 00:00:00pages
742-51issue
8eissn
1538-4047issn
1555-8576pii
25184journal_volume
14pub_type
杂志文章abstract::The objective of the present study was to evaluate CA19-9 and CK8/18 expression patterns in pancreatic cancer cell lines induced by 5-fluorouracil (5-Fu), and in circulating tumor cells (CTCs) in peripheral blood of patients previously untreated with advanced pancreatic cancer. Furthermore, the goal was to test the re...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.8.15960
更新日期:2011-10-15 00:00:00
abstract::Cyclin D1 is frequently overexpressed in esophageal squamous cell carcinoma (ESCC) and is considered a key driver of this disease. Mutations in FBXO4, F-box specificity factor that directs SCF-mediated ubiquitylation of cyclin D1, occur in ESCC with concurrent overexpression of cyclin D1 suggesting a potential tumor s...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1026512
更新日期:2015-01-01 00:00:00
abstract::Vitamin D derivatives can induce differentiation of human acute myeloid leukemia (AML) cells. Here, we investigated if the G₁ cell cycle block associated with monocytic differentiation is modulated by the p53 status of the cells treated with 1,25D, alone or with plant antioxidants carnosic acid (C) or silibinin (S), a...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.4.12366
更新日期:2010-08-15 00:00:00
abstract::Historically, ErbB3 has been overlooked within the ErbB receptor family due to its perceived lack of tyrosine kinase activity. We have previously demonstrated that in pancreatic cancer ErbB3 is the preferred dimerization partner of EGFR, ErbB3 protein expression level directly correlates with the anti-proliferative ef...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.6.12532
更新日期:2010-09-15 00:00:00
abstract::The enzyme 8-oxoguanine glycosylase 1 (OGG1) repairs 8-oxo-2-deoxyguanosine residue (8-oxodG) an oxidatively damaged promutagenic base. Genetic variations in OGG1 gene have been shown to modulate DNA repair capacity and are related risk of tumor development. However, epidemiologic findings have been inconsistent. The ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.1.5120
更新日期:2008-01-01 00:00:00
abstract::Histone H1.2, a housekeeping protein that binds nucleosomal linkers, has recently been identified as an apoptogenic factor released from the nucleus to the cytosol in response to double strand DNA breaks. In the cytosol, it promotes the activation of proapoptotic Bcl-2 family proteins, mitochondrial cytochrome c relea...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.1.738
更新日期:2004-01-01 00:00:00
abstract::The alterative reading frame (ARF) protein is unique in its capacity to interact with Mdm2 thus facilitating p53-dependent cell cycle arrest and apoptosis. ARF also acts in a p53-independent manner in which it binds to Myc and interferes with transcriptional activation by Myc thereby inhibiting Myc-induced cell prolif...
journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.5.6.2939
更新日期:2006-06-01 00:00:00
abstract::IL-15 has been actively investigated for its potential in tumor immunotherapy. To enhance the anti-tumor activity of IL-15, the novel PFC-1 construct was designed, which comprises the following 3 parts: (1) IL-15Rα fused with IL-15 to enhance IL-15 activity, (2) an Fc fragment to increase protein half-life, and (3) an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1071739
更新日期:2015-01-01 00:00:00
abstract::Recently, we showed that the metal chelator TPEN targets colon cancer cells through redox cycling of copper. Here, we studied the DNA damage potential of TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in 3 human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the ro...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1235658
更新日期:2016-11-01 00:00:00
abstract::Current treatment modalities for pancreatic carcinoma afford only modest survival benefits. TRAIL, as a potent and specific inducer of apoptosis in cancer cells, would be a promising new treatment option. However, since not all pancreatic cancer cells respond to TRAIL, further improvements and optimizations are still ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972183
更新日期:2014-01-01 00:00:00
abstract::Farnesyl transferase inhibitors (FTIs) exhibit limited cytotoxic effects against human cancer cells, perhaps explaining the limited efficacy of FTIs in clinical trials. Learning how these well-tolerated drugs trigger p53-independent apoptosis in mouse models of cancer might therefore benefit efforts to leverage their ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.9.4546
更新日期:2007-09-01 00:00:00
abstract::The PROfound trial highlights that there is a benefit in testing genes involved in homologous recombination (HR) and forms the rationale for testing in all patients with metastatic, castration-resistant prostate cancer (mCRPC). This trial also demostrates that olaparib improves progression free survival (PFS), objecti...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1809913
更新日期:2020-10-02 00:00:00
abstract::Hypermethylation at certain CpG-rich promoters and hypomethylation at repeated DNA sequences are very frequently found in cancers. We provide the first report that a DNA sequence (NBL2) can be either extensively hypermethylated or hypomethylated in cancer. Previously, it was shown that NBL2, a complex tandem DNA repea...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.4.1622
更新日期:2005-04-01 00:00:00
abstract::Multidrug resistance (MDR) is an important cause of treatment failure in acute lymphoblastic leukemia (ALL). The ABC family of membrane transporters is proposed, albeit with controversy, to be involved in this process. The present study aims to investigate the mRNA expression profile of several genes of this family, i...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26603
更新日期:2014-01-01 00:00:00
abstract::Arsenic trioxide (As2O3) induces apoptosis in certain types of cancer cells. But the detailed mechanisms of As2O3 efficacy are not completely known. Here we demonstrate that As2O3 has a therapeutic effect on cervical cancer in vitro and in vivo. We investigated the As2O3-induced apoptosis in various cervical cancer ce...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.4.3887
更新日期:2007-04-01 00:00:00
abstract::Cellular adhesion molecules of the cadherin, integrin, and immunoglobulin superfamilies are important to both growth and metastasis of many cancers, including malignant melanoma. Malignant melanoma is an excellent model for studying these molecules, due in part to a sequential series of five defineable stages. As the ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.1.5.158
更新日期:2002-09-01 00:00:00
abstract:BACKGROUND:Intestinal mucositis is a common and debilitating side-effect of chemotherapy, associated with severe small intestinal inflammation. Marine oils, such as Lyprinol, a lipid extract derived from New Zealand Green-lipped Mussels, rich in long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA), have demonstrat...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.2.5332
更新日期:2008-02-01 00:00:00
abstract::The molecular phenotype of tumor vasculature is different from normal vasculature, offering new opportunities for diagnosis and therapy of cancer, but the identification of tumor-restricted targets remains a challenge. We investigated 13 tumor vascular markers (TVMs) from 50 candidates identified through expression pr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.3.16260
更新日期:2011-08-01 00:00:00
abstract::Small-molecule inhibitors of cyclin-dependent kinases (CDKs) are known to induce cell cycle arrest and apoptosis in certain cancer cells. In order to evaluate the antitumor activity of one such inhibitor, GW8510, against human lung cancers, we analyzed the effects of GW8510 on six nonsmall cell lung cancer (NSCLC) cel...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.2.2316
更新日期:2006-02-01 00:00:00
abstract::Ovarian cancer (OC) is xenogeneic that is influenced by many generated factors related to epigenetic factors to accelerate tumor metastasis. This study was conducted with the objective of investigating the effect of microRNA-23a-3p (miR-23a) on the biological characteristics of OC stem cells by targeting discs large h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2019.1579960
更新日期:2019-01-01 00:00:00
abstract::Most sporadic colorectal cancer reflects acquired mutations in the adenomatous polyposis coli (APC) tumor suppressor gene, while germline heterozygosity for mutant APC produces the autosomal dominant disorder Familial Adenomatous Polyposis (FAP) with a predisposition to colorectal cancer. In these syndromes, loss of h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1779005
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Primary brain tumors have always been associated with high morbidity and mortality. Glioma is the most common type of malignant brain tumors,with a high probability of recurrence after surgical excision and with poor prognosis.The purpose of this study was to compare the therapeutic efficacy of computed tomo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20834
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVE:To achieve effective delivery of siRNA into target cells in vivo, we have developed a novel approach of siRNA delivery by using local drug delivery systems. RESULTS:The chitosan hydrogel (CH-HG) displayed a liquid-solid phase transition in a temperature-dependent manner and formed an endothermic hydrogel in ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.9.15185
更新日期:2011-05-01 00:00:00
abstract::The Id (Inhibitor of differentiation or Inhibitor of DNA-binding) proteins act as dominant negative inhibitors of differentiation-specific basic Helix-Loop-Helix (bHLH) transcription factors. Id proteins negatively regulate cellular differentiation and they induce proliferation by modulating different cell cycle regul...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.50
更新日期:2002-03-01 00:00:00
abstract::Angiogenesis inhibitors belong to a new class of drugs. Many of these drugs are in clinical trials to treat cancer, while others have recently received FDA approval. However, angiogenesis inhibitors operate by different mechanisms than conventional cytotoxic chemotherapies, and require different guidelines for their o...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:
更新日期:2003-07-01 00:00:00
abstract::Antiangiogenic or metronomic chemotherapy, the frequent administration of conventional cytotoxic agents at low doses, is believed to target activated tumor endothelial cells. The mechanisms of action of such regimen remain poorly understood. In the March 2004 issue of Cancer Research, Hamano et al. demonstrated that l...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.3.12.1369
更新日期:2004-12-01 00:00:00
abstract::The molecular regulation of growth and progression of hormone refractory breast and prostate cancers remains challenging. The Division of Cancer Biology, NCI organized a small "think tank" style workshop and invited scientists in relevant areas to assess the state of science on the biology of hormone refractory tumors...
journal_title:Cancer biology & therapy
pub_type:
doi:10.4161/cbt.8.21.9918
更新日期:2009-11-01 00:00:00
abstract::Mutationally activated and oncogenic versions of the ras genes were first identified in human tumors in 1982. This discovery prompted great interest in the development of anti-Ras strategies as novel, target-based approaches for cancer treatment. The three human ras genes represent the most frequently mutated oncogene...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.306
更新日期:2002-11-01 00:00:00
abstract::Beneficial bacteria (probiotics) and probiotic-derived factors have the potential to ameliorate disorders of the intestine. The aim of this study was to compare live Streptococcus thermophilus TH-4 (TH-4), dead TH-4 and TH-4 supernatant in rats treated with 5-Fluorouracil. Rats were randomly allocated to five treatmen...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:
更新日期:2009-03-15 00:00:00
abstract::Aggressive fibromatosis (AF) or desmoid tumors is an aggressive fibroblastic proliferation which is locally invasive but can not metastasize. The treatment of AF is challenging. Surgery was the main treatment modality for AF in the past, other strategies including radiotherapy, systemic therapies and wait-and-see poli...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1373215
更新日期:2017-10-03 00:00:00