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 utility in clinic. Recent clinical findings indicate that the oncogenic Rho guanine nucleotide exchange factor AKAP13/Lbc is associated with clinical responsiveness, in support of an earlier genetic proof in mice that gain of the geranylgeranylated isoform of RhoB which blocks oncogenic Rho signaling is essential for FTI-induced apoptosis. Here we offer evidence that the RhoB effector mDia is a critical downstream player in this death program. Dominant inhibition of mDia ablated FTI-induced apoptosis but not actin reorganization or growth inhibition, the latter of which has been linked previously to interactions with a RhoB effector kinase pathway that downregulates c-Myc. In nude mice, dominant inhibition of mDia promoted tumor formation and ablated FTI antitumor efficacy. Our findings suggest that the RhoB-mDia pathway is critical for the cell death mechanism engaged by FTI. Further, they suggest that mDia may be important for Rho-dependent survival of oncogenically transformed cells, perhaps driven by AKAP13/Lbc.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Kamasani U,Duhadaway JB,Alberts AS,Prendergast GCdoi
10.4161/cbt.6.9.4546subject
Has Abstractpub_date
2007-09-01 00:00:00pages
1422-7issue
9eissn
1538-4047issn
1555-8576pii
4546journal_volume
6pub_type
杂志文章abstract::Cancer cells convert glucose preferentially to lactate even in the presence of oxygen (aerobic glycolysis-Warburg effect). New concepts in cancer treatment aim at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation. Therefore, the aim of this study ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.22003
更新日期:2012-12-01 00:00:00
abstract::Ovarian cancer ranks fifth in cancer related deaths for women in USA. The high mortality rate associated with ovarian cancer is due to diagnosis at later stages of disease and the high recurrence rate of 60-80%. Recurrent ovarian cancers are more likely to present as multidrug resistance (MDR) leading to unfavorable r...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1395118
更新日期:2018-07-03 00:00:00
abstract::Several agents targeting the epidermal growth factor receptor (EGFR) have been FDA-approved to treat cancer patients with varying tumor types including metastatic colorectal cancer. Many patients treated with anti-EGFR therapy however do not respond and those that do initially respond often acquire resistance. Here we...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.28179
更新日期:2014-05-01 00:00:00
abstract::We have previously identified tumor susceptibility gene101 (TSG101), overexpressed in vincristine-resistant human gastric adenocarcinoma cell line SGC7901/VCR using a modified subtractive hybridization method and Western blot. In the present study, we constructed two siRNA eukaryotic expression vectors of TSG101 and t...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.6.847
更新日期:2004-06-01 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::DNA methylation at the 5 position of cytosine (5-mC) has emerged as a key epigenetic marker that plays essential roles in various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family proteins, which is now widely recognized as the ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.27144
更新日期:2014-01-01 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::MDM2 antagonists stabilize and activate wild-type p53, and histone methyltransferase (HMT) inhibitors reduce methylation on histone lysines and arginines. Both MDM2 antagonists and HMT inhibitors are being developed as cancer therapeutics. Wild-type p53 expressing HCT116 colon cancer cells were resistant to apoptosis ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1433500
更新日期:2018-06-03 00:00:00
abstract::Colorectal cancer (CRC) is the second most prevalent and deadly cancer worldwide. Due to the mortality and morbidity associated with chemotherapeutic regimes, research is turning to natural product enhancement of the acute apoptotic response to genotoxic carcinogens (AARGC). Although Tyrian purple dye pigments and pre...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.5.10887
更新日期:2010-03-01 00:00:00
abstract::Tangeretin, a major phytochemicals in tangerine peels--an important Chinese herb, has been found to have anti-carcinogenic properties. To improve bioavailability and increase potency of tangeretin, its derivative, 5-acetyloxy-6,7,8,4'-tetramethoxyflavone (5-AcTMF), has been synthesized and shown potent inhibition of p...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1108491
更新日期:2016-01-01 00:00:00
abstract::Colorectal cancer (CRC) is the third most common form of cancer. Current treatments including chemotherapy, radiotherapy and surgery are all associated with a high risk of complications and are not always successful, highlighting the need to develop new treatment strategies. The ingestion of probiotics, prebiotics or ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.10.3296
更新日期:2006-10-01 00:00:00
abstract::Recently, some studies have placed additional research focus on microRNAs (miRNAs) in a bid to discover novel therapeutic approaches for cervical cancer (CC), which is one of the most common female reproductive tract malignancies with high rates of morbidity and mortality. Hence, the aim of the present study was to ev...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1491497
更新日期:2018-01-01 00:00:00
abstract::Sunitinib, a multi-targeted tyrosine kinase inhibitor, is frequently incorporated into the management of papillary thyroid carcinoma refractory to standard therapies. Although clinical trials are in progress, the mechanism of action in papillary thyroid carcinomas is not clear, especially regarding the effect on BRAF ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.5.16303
更新日期:2011-09-01 00:00:00
abstract::Circulating tumor cells (CTC) enter the blood from many carcinomas and represent a likely source of metastatic dissemination. In contrast to the peripheral circulation, KRAS mutation- positive CTC thrive in the portal venous blood of patients with pancreatic ductal adenocarcinoma (PDAC). To analyze the essential inter...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1480292
更新日期:2018-01-01 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::Fluids of body cavities result in a series of pathophysiological events associated with non-malignant and malignant conditions that lead to the formation of exudative effusion. Diagnosis of effusion from the patients is frequently troublesome for the cytologist because of the differentiation and biological behavior of...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.2.1573
更新日期:2005-02-01 00:00:00
abstract::B-cell chronic lymphocytic leukemia (CLL) is caused by the abnormal accumulation of non-functional B-cells in peripheral blood and bone marrow. However, the precise aetiology and mechanism of the disease are unclear. Recently, progress has been made in the identification of both the genetic deficiencies and environmen...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.7.2.5262
更新日期:2008-02-01 00:00:00
abstract::The colorectal cancer is the leading contributor of cancer-related mortality. Mammalian target of rapamycin (mTOR), existing in 2 complexes (mTORC1/2), is frequently dysregulated and constitutively activated in colorectal cancers. It represents an important drug target. Here we found that INK-128, the novel ATP-compet...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972274
更新日期:2015-01-01 00:00:00
abstract::Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (no...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1220453
更新日期:2016-10-02 00:00:00
abstract:AIMS:Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity resulting in severe morbidity and mortality. To date only few proteins have been suggested as potential biomarkers or targets for this type of cancer. Cancerous inhibitor of PP2A (CIP2A) is a protein expressed in epithelial tis...
journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.10.7.12895
更新日期:2010-10-01 00:00:00
abstract::Hes1 is one mammalian counterpart of the Hairy and Enhancer of split proteins that play a critical role in many physiological processes including cellular differentiation, cell cycle arrest, apoptosis and self-renewal ability. Recent studies have shown that Hes1 functions in the maintenance of cancer stem cells (CSCs)...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.1080/15384047.2015.1016662
更新日期:2015-01-01 00:00:00
abstract::Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies,...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1078022
更新日期:2015-01-01 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::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::The recurrence of colorectal cancer after chemotherapy is the leading cause of its high mortality. We propose that elucidating the mechanisms of tumor regrowth after chemotherapy in tumor-bearing mice may provide new insights into tumor relapse in cancer patients. We firstly report the identification of a chemokine, C...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1095404
更新日期:2015-01-01 00:00:00
abstract::We developed a DNA aptamer, Ap52, against the shared tumor-specific MAGE-A3111-125 peptide antigen that was used to target multiple types of cancer cells. Here we report the in vivo study of mice implanted with pancreatic tumor cells AsPC-1, which demonstrates accumulation of phosphorothioate-modified Ap52 (ThioAp52) ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1833156
更新日期:2021-01-02 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::Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, are the first targeted therapy drugs approved for the treatment of advanced non-small-cell lung cancer (NSCLC). Interestingly, treatment with these small molecule, reversible EGFR-TKIs leads to more positive respo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.9.8.11881
更新日期:2010-04-15 00:00:00
abstract::The cancer stem cell hypothesis suggests that rare populations of tumor-initiating cells may be resistant to therapy, lead to tumor relapse and contribute to poor prognosis for cancer patients. We previously demonstrated the feasibility of p53 pathway restoration in p53-deficient tumor cell populations using small mol...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.22.10446
更新日期:2009-11-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) remains recalcitrant to effective treatment due to tumor relapse and acquired resistance. Cancer stem cells (CSCs) are believed to be one mechanism for relapse and resistance and are consequently considered promising drug targets. We report that chetomin, an active component of Chaet...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1763147
更新日期:2020-08-02 00:00:00