Publications
205 results found
Tzafetas M, Mitra A, Kalliala I, et al., 2018, iKnife - improving surgical outcomes in pre-invasive and invasive cervical disease, RCOG World Congress 2018, Publisher: Wiley, Pages: 17-17, ISSN: 1470-0328
Arbyn M, Redman CWE, Verdoodt F, et al., 2017, Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis, Lancet Oncology, Vol: 18, Pages: 1665-1679, ISSN: 1470-2045
BACKGROUND: Incomplete excision of cervical precancer is associated with therapeutic failure and is therefore considered as a quality indicator of clinical practice. Conversely, the risk of preterm birth is reported to correlate with size of cervical excision and therefore balancing the risk of adequate treatment with iatrogenic harm is challenging. We reviewed the literature with an aim to reveal whether incomplete excision, reflected by presence of precancerous tissue at the section margins, or post-treatment HPV testing are accurate predictors of treatment failure. METHODS: We did a systematic review and meta-analysis to assess the risk of therapeutic failure associated with the histological status of the margins of the tissue excised to treat cervical precancer. We estimated the accuracy of the margin status to predict occurrence of residual or recurrent high-grade cervical intraepithelial neoplasia of grade two or worse (CIN2+) and compared it with post-treatment high-risk human papillomavirus (HPV) testing. We searched for published systematic reviews and new references from PubMed-MEDLINE, Embase, and CENTRAL and did also a new search spanning the period Jan 1, 1975, until Feb 1, 2016. Studies were eligible if women underwent treatment by excision of a histologically confirmed CIN2+ lesion, with verification of presence or absence of CIN at the resection margins; were tested by cytology or HPV assay between 3 months and 9 months after treatment; and had subsequent follow-up of at least 18 months post-treatment including histological confirmation of the occurrence of CIN2+. Primary endpoints were the proportion of positive section margins and the occurrence of treatment failure associated with the marginal status, in which treatment failure was defined as occurrence of residual or recurrent CIN2+. Information about positive resection margins and subsequent treatment failure was pooled using procedures for meta-analysis of binomial data and analysed using rando
Jones BP, Saso S, Farren J, et al., 2017, Ultrasound-Guided Laparoscopic Ovarian Wedge Resection in Recurrent Serous Borderline Ovarian Tumours, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 27, Pages: 1813-1818, ISSN: 1048-891X
Arbyn M, Charles R, Verdoodt F, et al., 2017, PREDICTION OF THE OUTCOME AFTER EXCISION OF CERVICAL PRECANCER BY THE RESECTION MARGINS OR BY POST-TREATMENT HPV TESTING: A SYSTEMATIC REVIEW AND META-ANALYSIS, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 1910-1910, ISSN: 1048-891X
Sehouli J, Vergote I, Ferron G, et al., 2017, RANDOMIZED CONTROLLED PHASE III STUDY TO EVALUATE SECONDARY CYTOREDUCTIVE SURGERY IN PLATINUM-SENSITIVE RECURRENT OVARIAN CANCER - AGO DESKTOP III/ENGOT OV20, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 18-18, ISSN: 1048-891X
Sehouli J, Vergote I, Ferron G, et al., 2017, RANDOMIZED CONTROLLED PHASE III STUDY TO EVALUATE SECONDARY CYTOREDUCTIVE SURGERY IN PLATINUM-SENSITIVE RECURRENT OVARIAN CANCER - AGO DESKTOP III/ENGOT OV20, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 1662-1662, ISSN: 1048-891X
Marcus D, Savage A, Phelps D, et al., 2017, PROOF OF CONCEPT: CAN THE INTELLIGENT SURGICAL KNIFE DIAGNOSE ENDOMETRIAL CANCER?, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 1152-1152, ISSN: 1048-891X
Whilding LM, Parente-Pereira AC, Zabinski T, et al., 2017, Targeting of Aberrant alpha v beta 6 Integrin Expression in Solid Tumors Using Chimeric Antigen Receptor-Engineered T Cells (vol 25, pg 259, 2017), MOLECULAR THERAPY, Vol: 25, Pages: 2427-2427, ISSN: 1525-0016
Du Bois A, Vergote I, Ferron G, et al., 2017, Randomized controlled phase III study evaluating the impact of secondary cytoreductive surgery in recurrent ovarian cancer: AGO DESKTOP III/ENGOT ov20, 53rd Annual Clinical Science Meeting of the American-Society-of-Clinical-Oncology (ASCO) / Symposium on Old Targets, New Drugs - Her2 and MET, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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- Citations: 108
Coombes RC, Caballero OL, Shousha S, et al., 2017, NY-ESO-1 expression in DCIS: A new predictor of good prognosis, Oncoscience, Vol: 4, Pages: 33-40, ISSN: 2331-4737
BACKGROUND: At present, it is difficult to predict which patients with ductal carcinoma-in-situ (DCIS) will subsequently develop frank invasive breast cancer (IDC). A recent survey by our group has shown that NY-ESO-1 and MAGEA are both expressed in DCIS. This study was aimed at determining whether expression of these antigens was related to the later development of IDC. RESULTS: 14 of 42 (33%) of patients developed invasive breast cancer during the follow up period. Only one of those DCIS cases that relapsed was positive for NYESO-1 at diagnosis. In contrast, DCIS samples of 15 of the 28 (54%) of those patients who remained disease-free expressed NY-ESO-1. (Permutation chi square p=0.0033). METHODS: We identified 42 patients with DCIS, and followed them up for more than 10 years. NY-ESO-1 and MAGEA were demonstrated by immunostaining as were CD8+ infiltrates on all sections together with the conventional markers, ER, PR, and HER2. CONCLUSIONS: Expression of NY-ESO-1 may predict those patients who will not subsequently develop invasive breast cancer and could therefore potentially be helpful in defining prognosis in patients with DCIS.
Phelps DL, Borley J, Flower K, et al., 2017, Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multi-centre study, British Journal of Cancer, Vol: 116, Pages: 1287-1293, ISSN: 1532-1827
BackgroundSurvival benefit from surgical debulking of ovarian cancer (OC) is well established but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery.MethodsClinical data from women debulked for high-stage OC was analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium’s HumanMethylation27 array interrogated tumour-DNA for differentially-methylated CpG sites, correlated to survival, in patients with the least residual disease (RD) (Hammersmith Array). Validation was performed using bisulphite pyrosequencing (Charité Hospital, Berlin, Germany cohort) and The Cancer Genome Atlas’ (TCGA) methylation dataset. Kaplan-Meier curves and Cox models tested survival.ResultsAltogether 803 women with serous ovarian cancer were studied. No RD was associated with significantly improved overall- (OS) (hazard ratio [HR] 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS) (HR 1.23, 1.05-1.43; P=0.012) (Hammersmith database n=430). Differentially-methylated loci within FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE associated with survival. Patients with the least RD had significantly better OS with higher methylation of MYLK3 (Hammersmith (HR 0.51, 0.31-0.84; P=0.01), Charité (0.46, 0.21-1.01; P=0.05), TCGA (0.64, 0.44-0.93; P=0.02)). ConclusionMYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.
Flower KJ, Ghaem-Maghami S, Brown R, 2017, Is there a role for epigenetic enhancement of immunomodulatory approaches to cancer treatment?, Current Cancer Drug Targets, Vol: 17, ISSN: 1873-5576
The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance. One such mechanism of non-efficacy or resistance is the epigenetic silencing of a specific gene required in the immunotherapy response pathway. Epigenetics is the study of the control of expression patterns in a cell via mechanisms not involving a change in DNA sequence. All tumour types show aberrant epigenetic regulation of genes involved in all the hallmarks of cancer, including immunomodulation. Inhibition of key enzymes involved in maintenance of epigenetic states is another important area of research for new treatment strategies for cancer. Could epigenetic therapies be used to successfully enhance the action of immunomodulatory agents in cancer, and are they acting in the way we imagine? An understanding of the effects of epigenetic therapies on immunological pathways in both the tumour and host cells, especially the tumour microenvironment, will be essential to further develop such combination approaches.
Kyrgiou M, Kalliala I, Mitra A, et al., 2017, Immediate referral to colposcopy versus cytological surveillance for minor cervical cytological abnormalities in the absence of HPV test, Cochrane Database of Systematic Reviews, Vol: 1, ISSN: 1469-493X
BackgroundA significant number of women are diagnosed with minor cytological abnormalities on cervical screening. Many authorities recommendsurveillance as spontaneous regression might occur. However,attendance for cytological follow-up decreases with time and might putsome women at risk of developing invasive disease.ObjectivesTo assess the optimum management strategy for women with minor cervical cytological abnormalities (atypical squamous cells ofundetermined significance - ASCUS or low-grade squamous intra-epithelial lesions - LSIL) at primary screening in the absence of HPV(human papillomavirus) DNA test.Search methodsWe searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 2016), MEDLINE,and Embase from inception to 21 April 2016.Selection criteriaWe included randomised controlled trials (RCTs) comparing immediate colposcopy to cytological surveillance in women with atyp-ical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/milddyskaryosis).Data collection and analysisThe primary outcome measure studied was the occurrence of cervicalintra-epithelial neoplasia (CIN). The secondary outcome measuresstudied included default rate, clinically significant anxiety and depression, and other self-reported adverse effects.We classified studies according to period of surveillance, at 6, 12, 24 or 36 months, as well as at 18 months, excluding a possibleexit-examination. We calculated pooled risk ratios (RR) and 95%confidence intervals (CI) using a random-effects model with inversevariance weighting. Inter-study heterogeneity was assessedwith I2statistics.Main resultsWe identified five RCTs with 11,466 participants that fulfilledthe inclusion criteria. There were 18 cases of invasive cervical cancer,seven in the immediate colposcopy and 11 in the cytological surveillance groups, respectively. Although immediate colposcopy detectsCIN2+ and CIN3+ earlier
Whilding LM, Parente-Pereira AC, Zabinski T, et al., 2017, Targeting of Aberrant alpha v beta 6 Integrin Expression in Solid Tumors Using Chimeric Antigen Receptor-Engineered T Cells, Molecular Therapy, Vol: 25, Pages: 259-273, ISSN: 1525-0016
Expression of the αvβ6 integrin is upregulated in several solid tumors. In contrast, physiologic expression of this epithelial-specific integrin is restricted to development and epithelial re-modeling. Here, we describe, for the first time, the development of a chimeric antigen receptor (CAR) that couples the recognition of this integrin to the delivery of potent therapeutic activity in a diverse repertoire of solid tumor models. Highly selective targeting αvβ6 was achieved using a foot and mouth disease virus-derived A20 peptide, coupled to a fused CD28+CD3 endodomain. To achieve selective expansion of CAR T cells ex vivo, an IL-4-responsive fusion gene (4αβ) was co-expressed, which delivers a selective mitogenic signal to engineered T cells only. In vivo efficacy was demonstrated in mice with established ovarian, breast, and pancreatic tumor xenografts, all of which express αvβ6 at intermediate to high levels. SCID beige mice were used for these studies because they are susceptible to cytokine release syndrome, unlike more immune-compromised strains. Nonetheless, although the CAR also engages mouse αvβ6, mild and reversible toxicity was only observed when supra-therapeutic doses of CAR T cells were administered parenterally. These data support the clinical evaluation of αvβ6 re-targeted CAR T cell immunotherapy in solid tumors that express this integrin.
Chatterjee J, Dai W, Abd Aziz NH, et al., 2016, Clinical use of programmed cell death-1 (PD-1) and its ligand (PD-L1) expression as discriminatory and predictive markers in ovarian cancer, Clinical Cancer Research, Vol: 23, Pages: 3453-3460, ISSN: 1557-3265
Purpose We aimed to establish whether PD-1 and PD-L1 expression, in ovarian cancer (OC) tumour tissue and blood, could be used as biomarkers for discrimination of tumour histology and prognosis of OC. Experimental Design Immune cells were separated from blood, ascites and tumour tissue obtained from women with suspected OC and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumour associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses. Results Biomarkers from the discovery cohort that associated with PD-L1+ cells were found. PD-L1+ CD14+ cells and PD-L1+ CD11c+ cells in the monocyte gate showed a distinct expression pattern when comparing benign tumours and epithelial ovarian cancers (EOC) - confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+ and PD-L1+ CD14+ cells in the monocyte gate performed better than the well-established tumour marker CA-125 alone. Plasma soluble PD-L1 was elevated in EOC patients compared to healthy women and patients with benign ovarian tumours. Low total PD-1+ expression on lymphocytes was associated with improved survival. Conclusions Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti PD-1/PD-L1 therapy in ovarian cancer.
Doria ML, McKenzie JS, Mroz A, et al., 2016, Epithelial ovarian carcinoma diagnosis by desorption electrospray ionization mass spectrometry imaging, Scientific Reports, Vol: 6, ISSN: 2045-2322
Ovarian cancer is highly prevalent among European women, and is the leading cause of gynaecological cancer death. Current histopathological diagnoses of tumour severity are based on interpretation of, for example, immunohistochemical staining. Desorption electrospray mass spectrometry imaging (DESI-MSI) generates spatially resolved metabolic profiles of tissues and supports an objective investigation of tumour biology. In this study, various ovarian tissue types were analysed by DESI-MSI and co-registered with their corresponding haematoxylin and eosin (H&E) stained images. The mass spectral data reveal tissue type-dependent lipid profiles which are consistent across the n = 110 samples (n = 107 patients) used in this study. Multivariate statistical methods were used to classify samples and identify molecular features discriminating between tissue types. Three main groups of samples (epithelial ovarian carcinoma, borderline ovarian tumours, normal ovarian stroma) were compared as were the carcinoma histotypes (serous, endometrioid, clear cell). Classification rates >84% were achieved for all analyses, and variables differing statistically between groups were determined and putatively identified. The changes noted in various lipid types help to provide a context in terms of tumour biochemistry. The classification of unseen samples demonstrates the capability of DESI-MSI to characterise ovarian samples and to overcome existing limitations in classical histopathology.
Wahba J, Natoli M, Whilding L, et al., 2016, Synergistic immuno-chemotherapy for ovarian cancer, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 123, Pages: E6-E7, ISSN: 1470-0328
Clancy NT, Saso S, Stoyanov D, et al., 2016, Multispectral imaging of organ viability during uterine transplantation surgery in rabbits and sheep., Journal of Biomedical Optics, Vol: 21, ISSN: 1083-3668
Uterine transplantation surgery (UTx) has been proposed as a treatment for permanent absolute uterine factor infertility (AUFI) in the case of the congenital absence or surgical removal of the uterus. Successful surgical attachment of the organ and its associated vasculature is essential for the organ’s reperfusion and long-term viability. Spectral imaging techniques have demonstrated the potential for the measurement of hemodynamics in medical applications. These involve the measurement of reflectance spectra by acquiring images of the tissue in different wavebands. Measures of tissue constituents at each pixel can then be extracted from these spectra through modeling of the light–tissue interaction. A multispectral imaging (MSI) laparoscope was used in sheep and rabbit UTx models to study short- and long-term changes in oxygen saturation following surgery. The whole organ was imaged in the donor and recipient animals in parallel with point measurements from a pulse oximeter. Imaging results confirmed the re-establishment of adequate perfusion in the transplanted organ after surgery. Cornual oxygenation trends measured with MSI are consistent with pulse oximeter readings, showing decreased StO2 immediately after anastomosis of the blood vessels. Long-term results show recovery of StO2 to preoperative levels.
Phelps DL, Balog J, El-Bahrawy M, et al., 2016, Diagnosis of borderline ovarian tumours by rapid evaporative ionisation mass spectrometry (REIMS) using the surgical intelligent knife (iKnife), Royal College of Obstetricians and Gynaecologists - Blair Bell Academic Meeting, Publisher: Wiley, Pages: e4-e4
Mitra A, MacIntyre D, Lee Y, et al., 2016, Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity, Blair Bell Research Society Annual Academic Meeting, Publisher: Wiley, Pages: E11-E12, ISSN: 1470-0328
Wahba J, Natoli M, Whilding L, et al., 2016, Determining a mechanism of synergistic immuno-chemotherapy in ovarian cancer, 24th Biennial Congress of the European Association for Cancer Research, Publisher: Elsevier, Pages: S217-S218, ISSN: 0014-2964
Wahba J, Natoli M, Whilding L, et al., 2016, PD-1 blockade enhances synergistic killing of ovarian tumour cells by combination chemotherapy and T cell immunotherapy, 24th Biennial Congress of the European Association for Cancer Research, Publisher: Elsevier, Pages: S218-S218, ISSN: 0014-2964
Chatterjee J, Howden S, Saso S, et al., 2016, Metastatic low-grade fibromyxoid sarcoma of the broad ligament: A case report and literature review., Journal of Obstetrics and Gynaecology, Pages: 1-3, ISSN: 1364-6893
Saso S, Clarke A, Bracewell-Milnes T, et al., 2016, Psychological Issues Associated With Absolute Uterine Factor Infertility and Attitudes of Patients Toward Uterine Transplantation, PROGRESS IN TRANSPLANTATION, Vol: 26, Pages: 28-39, ISSN: 1526-9248
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- Citations: 32
Hopkins TG, Blagden S, Mura M, et al., 2016, The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer, Nucleic Acids Research, Vol: 44, Pages: 1227-1246, ISSN: 1362-4962
RNA-binding proteins (RBPs) are increasingly identifiedas post-transcriptional drivers of cancer progression.The RBP LARP1 is an mRNA stability regulator,and elevated expression of the protein in hepatocellularand lung cancers is correlated with adverseprognosis. LARP1 associates with an mRNA interactomethat is enriched for oncogenic transcripts.Here we explore the role of LARP1 in epithelial ovariancancer, a disease characterized by the rapid acquisitionof resistance to chemotherapy through theinduction of pro-survival signalling. We show, usingovarian cell lines and xenografts, that LARP1 is requiredfor cancer cell survival and chemotherapy resistance.LARP1 promotes tumour formation in vivoand maintains cancer stem cell-like populations. Usingtranscriptomic analysis following LARP1 knockdown,cross-referenced against the LARP1 interactome,we identify BCL2 and BIK as LARP1 mRNAtargets. We demonstrate that, through an interactionwith the 3 untranslated regions (3 UTRs) of BCL2and BIK, LARP1 stabilizes BCL2 but destabilizes BIKwith the net effect of resisting apoptosis. Together,our data indicate that by differentially regulating thestability of a selection of mRNAs, LARP1 promotesovarian cancer progression and chemotherapy resistance.
Bonito NA, Borley J, Wilhelm-Benartzi CS, et al., 2016, Epigenetic Regulation of the Homeobox Gene MSX1 Associates with Platinum-Resistant Disease in High-Grade Serous Epithelial Ovarian Cancer., Clinical Cancer Research, Vol: 22, Pages: 3097-3104, ISSN: 1557-3265
PURPOSE: Although high-grade serous ovarian cancer (HGSOC) is frequently chemoresponsive, a proportion of patients do not respond to platinum-based chemotherapy at presentation or have progression-free survival (PFS) of less than 6 months. Validated predictive biomarkers of lack of response would enable alternative treatment stratification for these patients and identify novel mechanisms of intrinsic resistance. Our aim was to identify DNA methylation biomarkers of poor response to chemotherapy and demonstrate involvement of the associated gene in platinum drug cell sensitivity. EXPERIMENTAL DESIGN: DNA methylation was investigated in independent tumor cohorts using Illumina HumanMethylation arrays and gene expression by Affymetrix arrays and qRT-PCR. The role of Msh homeobox 1 (MSX1) in drug sensitivity was investigated by gene reintroduction and siRNA knockdown of ovarian cancer cell lines. RESULTS: CpG sites at contiguous genomic locations within theMSX1gene have significantly lower levels of methylation in independent cohorts of HGSOC patients, which recur by 6 months compared with after 12 months (P< 0.05,q< 0.05,n= 78), have poor RECIST response (P< 0.05,q< 0.05,n= 61), and are associated with PFS in an independent cohort (n= 146). A decrease in methylation at these CpG sites correlates with decreasedMSX1gene expression.MSX1expression is associated with PFS (HR, 0.92; 95% CI, 0.85-0.99;P= 0.029;n= 309). Cisplatin-resistant ovarian cancer cell lines have reducedMSX1expression, andMSX1overexpression leads to cisplatin sensitization, increased apoptosis, and increased cisplatin-induced p21 expression. CONCLUSIONS: Hypomethylation of CpG sites within theMSX1gene is associated with resistant HGSOC disease at presentation and identifies expression ofMSX1as conferring platinum drug sensitivity.Clin Cancer Res; 1-8. ©2016 AACR.
Whilding LM, Parente-Pereira AC, Zabinski T, et al., 2016, Chimeric antigen receptor T-cells targeting the alpha v beta 6 integrin demonstrate potent antitumor activity in multiple solid tumors, CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival, Publisher: American Association for Cancer Research, ISSN: 2326-6074
Saso S, Louis LS, Doctor F, et al., 2015, Does fertility treatment increase the risk of uterine cancer? A meta-analysis, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 195, Pages: 52-60, ISSN: 0301-2115
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- Citations: 15
Consolaro F, Ghaem-Maghami S, Bortolozzi R, et al., 2015, FOXO3a and Post-translational Modifications Mediate Glucocorticoid Sensitivity in Acute B-ALL, Molecular Cancer Research, ISSN: 1557-3125
Glucocorticoids are widely used to treat B acute lymphoblastic leukemia (B-ALL); however, the molecular mechanism underlying glucocorticoid response and resistance is unclear. In this study, the role and regulation of FOXO3a in mediating the dexamethasone response in B-ALL was investigated. The results show that FOXO3a mediates the cytotoxic function of dexamethasone. In response to dexamethasone, it was found that FOXO3a translocates into the nucleus, where it induces the expression of downstream targets, including p27Kip1 and Bim, important for proliferative arrest and cell death in the sensitive RS4;11 and SUP-B15 B-ALL cells. FOXO3a activation by dexamethasone is mediated partially through the suppression of the PI3K-Akt signaling cascade. Furthermore, two post-translational modifications were uncovered, phosphorylation on Ser-7 and acetylation on Lys-242/5, that associated with FOXO3a activation by dexamethasone. Immunoblot analysis showed that the phosphorylation on Ser-7 of FOXO3a is associated with p38/JNK activation, whereas the acetylation on Lys-242/5 is correlated with the downregulation of SIRT1/2/6 and the induction of the acetyltransferase CBP/p300. Collectively, these results indicate that FOXO3a is essential for dexamethasone response in B-ALL cells, and its nuclear translocation and activation is associated with its phosphorylation on Ser-7 and acetylation on Lys-242/245. These post-translational events can be exploited as biomarkers for B-ALL diagnosis and as drug targets for B-ALL treatment, particularly for overcoming the glucocorticoid resistance.
Teo PY, Yang C, Whilding LM, et al., 2015, Ovarian Cancer Immunotherapy Using PD-L1 siRNA Targeted Delivery from Folic Acid-Functionalized Polyethylenimine: Strategies to Enhance T Cell Killing, ADVANCED HEALTHCARE MATERIALS, Vol: 4, Pages: 1180-1189, ISSN: 2192-2640
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- Citations: 122
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