Abstract:
:The efficient treatment of lung carcinomas with chemotherapeutics still poses a challenge for anti-cancer therapy. Since stromal cells of the tumor may alter the responsiveness of tumor cells to chemotherapeutics, we studied the impact of lung fibroblasts (WI-38) on the chemotherapy-induced death of non-small cell lung carcinoma cells (H358). Conditioned medium from WI-38 fibroblasts impaired the H358 cell death induced by paclitaxel but not by cisplatin. Comparable results were observed when culturing H358 cells in conditioned medium from primary tumor fibroblasts or co-culturing H358 cells with fibroblasts. This anti-apoptotic effect induced by paracrine signaling from fibroblasts was associated with less necrosis (membrane leakage, mitochondrial dysfunction) and apoptosis (outer membrane phosphatidylserine exposure, pycnotic nuclei, nuclear translocation of the apoptosis-inducing factor from mitochondria, caspase-9 and -3/-7 activation) in response to paclitaxel but not cisplatin. Additionally, we demonstrated that WI-38 fibroblasts mediate activation of both extracellular signal-regulated kinases (Erk) 1/2 and Akt kinase in H358 cells. Subsequent application of specific inhibitors revealed that the paclitaxel-induced cell death is highly impaired by active Erk1/2 and Akt, whereas the cisplatin-induced cell death is independent of both kinases. Pro-apoptotic Bcl-2 family proteins such as Bim cannot explain the differential impact of fibroblasts on the H358 cell death induced by paclitaxel compared with cisplatin. Our data support the preferential use of the cisplatin-based lung carcinoma therapy, because the cell death-inducing efficiency of cisplatin is not impaired by stromal fibroblasts.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Bartling B,Hofmann HS,Silber RE,Simm Adoi
10.4161/cbt.7.8.6264subject
Has Abstractpub_date
2008-08-01 00:00:00pages
1250-61issue
8eissn
1538-4047issn
1555-8576pii
6264journal_volume
7pub_type
杂志文章abstract::The Chemohormonal Therapy vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) was a randomized phase III trial that evaluated the outcomes of men with metastatic prostate cancer who received castration with or without docetaxel. Patients from this trial were genotyped in a recent ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1796195
更新日期:2020-09-01 00:00:00
abstract::Any drug selects for drug resistance. But super-antagonistic drug combinations can select for drug sensitivity. This has important application not only for antibacterial therapy but also for cancer therapy: to control cancer with lesser side effects and to eliminate drug-resistant cancer cells, while sparing sensitive...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.7.4340
更新日期:2007-07-01 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::Bone metastases are a common occurrence in patients with breast cancer, lung cancer and prostate cancer. Bone metastases cause considerable morbidity including pain, impaired mobility, pathologic fracture, spinal cord or nerve root compression, bone marrow infiltration and hypercalcemia of malignancy. These complicati...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.9.3308
更新日期:2006-09-01 00:00:00
abstract::The development of microarray technology has allowed researchers to measure expression levels of thousands of genes simultaneously. Analysis of these data requires the best normalization and statistical approaches to account for the biological and technical variability inherent in the technique. To approach this probl...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.2.4.431
更新日期:2003-07-01 00:00:00
abstract::Although daunomycin and adriamycin are considered effective antitumor drugs and have been used in the clinic for over 40 years, their mechanism of action is still a matter of debate. We investigated the influence of daunomycin on interaction between linker or core histones and DNA in live HeLa cells in vitro, using im...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.25328
更新日期:2013-09-01 00:00:00
abstract::Rhabdomyosarcoma (RMS) is an aggressive childhood sarcoma with two distinct subtypes, embryonal (ERMS) and alveolar (ARMS) histologies. More effective treatment is needed to improve outcomes, beyond conventional cytotoxic chemotherapy. The pan-histone deacetylase inhibitor, Suberoylanilide Hydroxamic Acid (SAHA), has ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1529093
更新日期:2019-01-01 00:00:00
abstract::Resistance to apoptosis is one reason for the poor response of malignant brain tumors to therapy. The PPARgamma-modulating drug Troglitazone downregulates the anti-apoptotic FLIP protein and sensitizes glioblastoma cells to apoptosis induced by the death ligand TRAIL. To investigate the molecular basis of an experimen...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.12.6966
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:The expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells has been considered as a major tumor immune escape mechanism. The aim of this study was to investigate the expression of IDO in lung cancer cell lines as well as in surgically resected lung cancer specimens comparing the latter, to the expres...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.8.4446
更新日期:2007-08-01 00:00:00
abstract::In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8(+) memory T (Tems) cells glycolyt...
journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.28160
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND AND AIM:H. pylori interacts with gastric epithelial cells, which may activate signaling pathways important for gastric cancer invasion. Ezrin, a membrane cytoskeletal crosslinker protein, is well documented to regulate cell adhesion and cell motility. The aim of the present study was to determine whether ezr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.8.14691
更新日期:2011-04-15 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::Two peptides derived from the C1B domain of protein kinase Cγ (PKCγ) were shown to associate with classical PKC isozymes and modulate their activities. These C1B peptides are designated C1B1 (amino acid residues 101-112) and C1B5 (residues 141-151). Since PKC enzyme activity is shown to be involved in colon cancer dev...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20840
更新日期:2012-08-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is a critical early event in tumorigenesis. The contribution of heparan sulfate (HS) to EMT has not been fully elucidated. HS D-glucosaminyl 3-O-sulfotransferase-3B1 (3-OST-3B1) participates in the final step of HS fine structure biosynthesis, whose involvement in cancer has yet...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.5.15957
更新日期:2011-09-01 00:00:00
abstract::The reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlying this disease. Th...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1250986
更新日期:2016-12-01 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::In order to demonstrate the role of the pituitary tumor transforming gene 1 (PTTG1) in the development of hepatocellular carcinoma (HCC) and its value as a molecular target for cancer therapy, we analyzed the expression of PTTG1 mRNA and protein, and their relation to clinicopathological characteristics and basic fibr...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.3.14102
更新日期:2011-02-01 00:00:00
abstract::Our previous studies have demonstrated that atorvastatin induces autophagy in the androgen receptor negative prostate cancer PC3 cells through inhibition of geranylgeranyl biosynthesis [Parikh et al., Prostate. 70(9): 971-981 (2010)]. This study attempts to elucidate the molecular mechanism underlying atorvastatin-ind...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.8.15978
更新日期:2011-10-15 00:00:00
abstract::Clear cell RCC is the most common, and more likely to metastasize, of the three main histological types of RCC. Pathologic stage is the most important prognostic indicator and nuclear grade can predict outcome within stages of localized RCC. Epithelial tumors are thought to accumulate a series of genetic and epigeneti...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.27314
更新日期:2014-03-01 00:00:00
abstract::Heterotypic hybrids created between dendritic cells (DC) and tumor cells represent an efficient approach for loading DC with tumor-associated antigens (TAA) and DC-tumor hybrid vaccines have shown promising outcomes in various preclinical and clinical studies. Conventional DC-tumor hybrid preparations, however, are un...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.11.1217
更新日期:2004-11-01 00:00:00
abstract::Adenoid cystic cancers (ACC) in the head and neck are rare yet present a clinical dilemma. Although 5-y survivals are excellent, they have a propensity for late recurrences. Most of these cancers are initially treated with surgery followed by radiation. When recurrences happen, treatment options are limited both by th...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.20.9596
更新日期:2009-10-01 00:00:00
abstract::The 26S proteasome is a large multi-subunit protein complex found in the cytoplasm and nucleus of mammalian cells which plays a critical role in intracellular proteolysis. It has been found that the 26S proteasome degrades multiple important substrates which are associated with tumor growth and development. Emerging e...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.7.2971
更新日期:2006-07-01 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::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::Invariant natural killer T (iNKT) cells are a distinct subset of human T cells, which expresses an invariant T cell receptor Vα24 Jα18 and recognizes glycolipid antigens in the context of CD1d molecules. iNKT cells exert pivotal regulatory roles in many immune responses, including antitumor immune responses. Alteratio...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20553
更新日期:2012-07-01 00:00:00
abstract::MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Genes encoding miRNAs are located in regions of the genome that are commonly amplified, deleted or rearranged. They are commonly dysregulated in human cancers and known to act as oncogenes ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.10.3.12548
更新日期:2010-08-01 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::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:OBJECTIVE:Angiogenesis is one of the key processes in the development of malignant tumors. The vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) signaling pathway regulates branching angiogenesis in cancer. In this study, we analyzed the associations of VEGF/VEGFR-2 proteins and VEGFR-2 genetic va...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1537575
更新日期:2019-01-01 00:00:00
abstract:EXPERIMENTAL DESIGN:To investigate the antitumor effect of sunitinib and FAK/Pyk2 tyrosine kinase inhibitor (PF-562,271)combination therapy in vivo, utilizing human hepatocellular carcinoma (HCC) cells Huh7.5. Nude rats were inoculated subcutaneously with Huh7.5 hepatoma cells. Dosing for Phase 1 was initiated on day 5...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.9.8246
更新日期:2009-05-01 00:00:00