Abstract:
:The present studies sought to further understand how the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib interact to kill tumor cells. Sorafenib activated SRC, and via SRC the drug combination activated ERK1/2. Expression of dominant negative SRC or dominant negative MEK1 abolished drug-induced ERK1/2 activation, together with drug-induced autophagy, acidic lysosome formation, and tumor cell killing. Protein phosphatase 2A is an important regulator of the ERK1/2 pathway. Fulvestrant resistant MCF7 cells expressed higher levels of the PP2A inhibitor SET/I2PP2A, had lower endogenous PP2A activity, and had elevated basal ERK1/2 activity compared with their estrogen dependent counterparts. Overexpression of I2PP2A blocked drug-induced activation of ERK1/2 and tumor cell killing. PP2A can be directly activated by ceramide and SET/I2PP2A can be inhibited by ceramide. Inhibition of the de novo ceramide synthase pathway blocked drug-induced ceramide generation, PP2A activation and tumor cell killing. Collectively these findings demonstrate that ERK1/2 plays an essential role downstream of SRC in pemetrexed and sorafenib lethality and that PP2A plays an important role in regulating this process.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Bareford MD,Hamed HA,Allegood J,Cruickshanks N,Poklepovic A,Park MA,Ogretmen B,Spiegel S,Grant S,Dent Pdoi
10.4161/cbt.20562subject
Has Abstractpub_date
2012-07-01 00:00:00pages
793-803issue
9eissn
1538-4047issn
1555-8576pii
20562journal_volume
13pub_type
杂志文章abstract::Multiple myeloma (MM) is an incurable B-cell malignancy characterized by accumulation of malignant plasma cells in the bone marrow and by recurrent or persistent infections. Toll-like receptors (TLRs) are essential in the host defense against infections. The aim of this study was to investigate TLR initiated responses...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.1.13878
更新日期:2011-01-01 00:00:00
abstract::Poor oxygenation is a unique and prevalent feature of solid tumors associated with poor patient prognosis. In part, this is caused by a series of adaptive cellular responses that together have a large impact on gene expression and cell phenotype. HIF plays a key role in this response by activating a transcriptional pr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.7.2972
更新日期:2006-07-01 00:00:00
abstract::5-fluorouracil forms classic (covalent, ternary) complexes consisting of thymidylate synthase, fluoro-deoxyuridine monophosphate, and 5,10-methylene tetrahydrofolate. Despite a high pharmacologic interest in the classic complexes formed in cells treated with fluorouracil anticancer agents, the in vivo stability of the...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.8.2976
更新日期:2006-08-01 00:00:00
abstract::Hepatocellular carcinoma (HCC), characterized by a high rate of metastasis and recurrence after surgery, is caused by malignant proliferation of hepatocytes with epigenetic and/or genetic mutations. In particular, abnormal activation of the hepatocyte growth factor (HGF)-/c-mesenchymal-epithelial transition receptor (...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2019.1647051
更新日期:2019-01-01 00:00:00
abstract::The androgen receptor is one of the central factors in mediating prostate cancer progression and is an important target for treatment. Several possible mechanisms have been put forth as to how it promotes this process. In the January 2004 issue of Nature Medicine, Chen et al. report that the androgen receptor is consi...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.3.785
更新日期:2004-03-01 00:00:00
abstract::Acute promyelocytic leukemia (APL) is one of the most fatal hematological malignancies. APL during pregnancy is a rare comorbidity and can lead to adverse outcomes, such as maternal and/or fetal death, without timely and appropriate management. Medical management for APL during pregnancy remains challenging. We report...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1529122
更新日期:2019-01-01 00:00:00
abstract::We investigated the role of vasculogenic mimicry (VM) in the progression of prostate cancer (PCa). Ninety-six patients who had undergone prostatectomy for treatment of PCa and for whom a complete record of clinical and follow-up data were available were reviewed. VM and matrix metalloproteinase-2 (MMP-2) were detected...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.19602
更新日期:2012-05-01 00:00:00
abstract::It was well known that cancer-associated fibroblasts (CAFs) were an essential factor in tumor progression. However, the actual mechanism of stromal fibroblasts activation and tumor promoting effects remain unclear. Here, we showed that KLF5 expression was more frequently observed in gastric cancer-associated fibroblas...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1373219
更新日期:2017-10-03 00:00:00
abstract::Rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) accounts for 1% of lung adenocarcinoma. Although small molecule agents with RET kinase inhibitory activity such as alectinib, vandetanib, and cabozantinib have been clinically evaluated in RET-fusion-positive NSCLC, an effective mo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1806643
更新日期:2020-09-01 00:00:00
abstract::The discovery of microRNAs (miRNAs) has opened a new avenue for both diagnosis and treatment of cancers. Accumulating experimental evidences indicate that miRNAs are aberrantly expressed in different tumor types and have a critical role in tumorigenesis. However, the miRNA expression profile in neuroblastoma (NB), one...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.6.10894
更新日期:2010-03-15 00:00:00
abstract::Advanced melanoma is the most virulent form of cancer and has a poor prognosis. In a previous study, myriocin, an inhibitor of serine palmitoyltransferase, was found to suppress melanoma cell proliferation by cell cycle arrest at the G 2/M phase through decreased sphingolipid levels and increased p53 and p21 (waf1/cip...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.13.2.18870
更新日期:2012-01-15 00:00:00
abstract::Hypoxia is known to play important role in cancer biology. In sarcomas, hypoxia-induced protein biomarkers such as Hypoxia Inducible Factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), and Erythropoietin (Epo) have been previously reported in only a few studies. Moreover, the biologic significance and rel...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.4.10744
更新日期:2010-02-01 00:00:00
abstract::Metastatic cervical cancer remains a clinical problem. The development of more efficient treatment modalities and the optimal use of chemo- and radiotherapy require better understanding of their impact on regulation of cell survival and apoptosis, but the issue is insufficiently explored. Human papillomavirus (HPV) E6...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.11.1340
更新日期:2004-11-01 00:00:00
abstract::WNT and FGF signaling pathways cross-talk during a variety of cellular processes, such as human colorectal carcinogenesis, mouse mammary tumor virus (MMTV)-induced carcinogenesis, E2A-Pbx-induced leukemogenesis, early embryogenesis, body-axis formation, limb-bud formation, and neurogenesis. Canonical WNT signals are t...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.9.3151
更新日期:2006-09-01 00:00:00
abstract::Decreased requirements for mitogens and diminished sensitivity to antiproliferative signals are among the hallmarks of human cancer. These attributes are due, at least partly, to mutations that directly or indirectly compromise the function of the retinoblastoma tumor suppressor protein (pRB), which is a negative regu...
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::The presence of tumor-infiltrating lymphocytes (TILs) in epithelial ovarian cancer indicates a host antitumor response and is associated with improved survival. We wished to determine the extent to which TIL density differs from site to site within a given patient. We initially studied multiple paired metastases from ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.4.16908
更新日期:2011-08-15 00:00:00
abstract::AMPK has been termed the fuel sensor of mammalian cells because it directly responds to the depletion of the fuel molecule ATP. In previous work, we found that AMPK is strongly activated by tumor-like hypoxia and glucose deprivation, independently of the oxygen response system associated with HIF-1. We also observed h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.1.12162
更新日期:2010-07-01 00:00:00
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::Furanodiene (C15H20O), a pure compound isolated from Traditional Chinese medicine, Curcuma wenyujin, named Ezhu in Chinese, which structure was determined on the basis of NMR, MS and UV spectrum. In this study, we attempted to characterize in detail the signaling cascades resulted from furanodiene-induced apoptosis in...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.7.4317
更新日期:2007-07-01 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::Despite its low transfer efficiency, suicide gene therapy with HSV-TK is known for its bystander killing effect. The connexin-based gap junction is believed to mediate the bystander effect. Recently, we found that resveratrol, a polyphenol compound, increased the expression of Cx26 and Cx43, which are connexins and im...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1523094
更新日期:2019-01-01 00:00:00
abstract::Tumor growth is often associated with insufficient apoptosis. The Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) and its proapoptotic receptors death receptor 4 (DR4) and DR5 agonistic monoclonal antibodies are being developed as targeted therapeutics because they kill cancer cells while sparing...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.4.17174
更新日期:2011-08-15 00:00:00
abstract::CP-31398, a styrylquinazoline, emerged from a screen for therapeutic agents that restore a wild-type DNA-binding conformation of mutant p53 to suppress tumors in-vivo (Science 286, 2507, 1999). We investigated the growth inhibitory mechanism of CP-31398 using nine human cancer cell lines containing wild-type, mutant o...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.1.1.41
更新日期:2002-01-01 00:00:00
abstract::Endostatin can inhibit tumor growth by blocking angiogenesis, whereas tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may function as a soluble cytokine to selectively kill cancer cells without toxicity to most normal cells. To establish the combined anti-tumor therapeutic effect of endostatin and solu...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.5.7687
更新日期:2009-03-01 00:00:00
abstract::Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1323597
更新日期:2017-07-03 00:00:00
abstract:INTRODUCTION:Germ-line mutations of the APC gene are associated with familial adenomatous polyposis, and somatic mutations occur frequently in sporadic colorectal cancer. However, to abrogate APC function, both alleles must be inactivated. Recently, it has been demonstrated that epigenetic modification of the APC promo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.10.1113
更新日期:2004-10-01 00:00:00
abstract::Double-strand breaks are one the most severe types of DNA damage with respect to cell survival and the preservation of genomic integrity. Therefore, cells have evolved complex mechanisms including cell cycle regulation, activation of repair pathways and in certain cases induction of apoptosis in response to these lesi...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.3.7.917
更新日期:2004-07-01 00:00:00
abstract::Antitumor imidazoacridinone C-1311 is a DNA-reactive topoisomerase II and FLT3 receptor tyrosine kinase inhibitor. Here, we demonstrate the mechanism of C-1311 inhibitory action on novel targets: hypoxia-inducible factor-1α (HIF-1α), vascular-endothelial growth factor (VEGF), and angiogenesis. In a cell-free system, C...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.7.15980
更新日期:2011-10-01 00:00:00
abstract::We previously reported that the mutant virus of HSV (mtHSV) mediated tumor therapy was efficacious in Balb/c and nude mice. However, it is significant to know whether mtHSV works in HSV-1 tumor seropositive individuals because many patients with HSV-1 seropositivity have been found in clinical trial. Here we asked whe...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.5.3953
更新日期:2007-05-01 00:00:00
abstract::Prostate cancer is the second leading cause of cancer-related deaths in men. Fatty acid synthase (FASN) is normally upregulated during human prostate cancer onset and metastatic progression and its expression positively correlates with the development of advanced metastatic disease. However, it remains unknown what mo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.8.4447
更新日期:2007-08-01 00:00:00