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Dynamics of 5-carboxylcytosine during hepatic differentiation: potential general role for active demethylation by DNA repair in lineage specification (2017)
Journal Article
Lewis, L. C., Lo, P. C. K., Foster, J. M., Dai, N., Correa, I. R., Durczak, P. M., …Ruzov, A. (in press). Dynamics of 5-carboxylcytosine during hepatic differentiation: potential general role for active demethylation by DNA repair in lineage specification. Epigenetics, 12(4), https://doi.org/10.1080/15592294.2017.1292189

Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-c... Read More about Dynamics of 5-carboxylcytosine during hepatic differentiation: potential general role for active demethylation by DNA repair in lineage specification.

Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers (2017)
Journal Article
Green, A. R., Aleskandarany, M. A., Ali, R., Hodgson, E. G., Atabani, S., De Souza, K., …Madhusudan, S. (2017). Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers. Cancer Immunology Research, 5(4), 292-299. https://doi.org/10.1158/2326-6066.CIR-16-0195

© 2017 American Association for Cancer Research. Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand br... Read More about Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers.

Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial (2017)
Journal Article
Middleton, G., Palmer, D. H., Greenhalf, W., Ghaneh, P., Jackson, R., Cox, T., …Neoptolemos, J. P. (2017). Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncology, 18(4), 486-499. https://doi.org/10.1016/S1470-2045%2817%2930084-0

Methods: The Vandetanib in Pancreatic Cancer (ViP) trial was a phase 2 double-blind, multicentre, randomised placebo-controlled trial in previously untreated adult patients (aged ≥18 years) diagnosed with locally advanced or metastatic carcinoma of t... Read More about Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial.

Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development (2017)
Journal Article
Metzler, V. M., de Brot, S., Robinson, R. S., Jeyapalan, J. N., Rakha, E., Walton, T., …Mongan, N. P. (2017). Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development. Placenta, 56, 79-85. https://doi.org/10.1016/j.placenta.2017.02.018

The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy,... Read More about Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development.

HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells (2017)
Journal Article
Shah, M., Cardenas, R., Wang, B., Persson, J., Mongan, N. P., Grabowska, A. M., & Allegrucci, C. (2017). HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells. Molecular Cancer, 16(38), https://doi.org/10.1186/s12943-017-0605-z

Background: Homeobox genes are master regulators of cell fate during embryonic development and their expression is altered in cancer. By regulating the balance between cell proliferation and differentiation, they maintain homeostasis of normal tissue... Read More about HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells.

Medulloblastoma and ependymoma cells display levels of 5-carboxylcytosine and elevated TET1 expression (2017)
Journal Article
Ramsawhook, A., Lewis, L., Coyle, B., & Ruzov, A. (2017). Medulloblastoma and ependymoma cells display levels of 5-carboxylcytosine and elevated TET1 expression. Clinical Epigenetics, 9(18), https://doi.org/10.1186/s13148-016-0306-2

Background Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (... Read More about Medulloblastoma and ependymoma cells display levels of 5-carboxylcytosine and elevated TET1 expression.

Development of potent, selective SRPK1 inhibitors as potential topical therapeutics for neovascular eye disease (2017)
Journal Article
Batson, J., Toop, H. D., Redondo, C., Babaei-Jadidi, R., Chaikaud, A., Wearmouth, S. F., …Morris, J. C. (2017). Development of potent, selective SRPK1 inhibitors as potential topical therapeutics for neovascular eye disease. ACS Chemical Biology, 12(3), 825-832. https://doi.org/10.1021/acschembio.6b01048

Serine/arginine-protein kinase 1 (SRPK1) regulates alternative splicing of VEGF-A to pro-angiogenic isoforms and SRPK1 inhibition can restore the balance of pro/antiangiogenic isoforms to normal physiological levels. The lack of potency and selectivi... Read More about Development of potent, selective SRPK1 inhibitors as potential topical therapeutics for neovascular eye disease.

Differential regulation of blood flow induced neovascularisation and mural cell recruitment by VEGF and angiopoietin signaling (2017)
Journal Article
Stone, O. A., Carter, J. G., Lin, P. C., Paleolog, E., Machado, M. J. C., & Bates, D. O. (2017). Differential regulation of blood flow induced neovascularisation and mural cell recruitment by VEGF and angiopoietin signaling. Journal of Physiology, 595(5), 1575-1591. https://doi.org/10.1113/JP273430

Signalling through VEGF receptors and the Tie2 receptor by angiopoietins is required in combination with blood flow for the formation of a functional vascular network. We tested the hypothesis that VEGF and Ang1 contribute differentially to neovascul... Read More about Differential regulation of blood flow induced neovascularisation and mural cell recruitment by VEGF and angiopoietin signaling.

Spheroid arrays for high-throughput single-cell analysis of spatial patterns and biomarker expression in 3D (2017)
Journal Article
Ivanov, D. P., & Grabowska, A. M. (2017). Spheroid arrays for high-throughput single-cell analysis of spatial patterns and biomarker expression in 3D. Scientific Reports, 7(1), Article 41160. https://doi.org/10.1038/srep41160

We describe and share a device, methodology and image analysis algorithms, which allow up to 66 spheroids to be arranged into a gel-based array directly from a culture plate for downstream processing and analysis. Compared to processing individual sa... Read More about Spheroid arrays for high-throughput single-cell analysis of spatial patterns and biomarker expression in 3D.

Cyclin E overexpression as a biomarker for combination treatment strategies in inflammatory breast cancer (2017)
Journal Article
Alexander, A., Karakas, C., Chen, X., Carey, J. P., Yi, M., Bondy, M., …Keyomarsi, K. (2017). Cyclin E overexpression as a biomarker for combination treatment strategies in inflammatory breast cancer. Oncotarget, 8, 14897-14911. https://doi.org/10.18632/oncotarget.14689

Inflammatory breast cancer (IBC) is a virulent form of breast cancer, and novel treatment strategies are urgently needed. Immunohistochemical analysis of tumors from women with a clinical diagnosis of IBC (n = 147) and those with non-IBC breast cance... Read More about Cyclin E overexpression as a biomarker for combination treatment strategies in inflammatory breast cancer.

RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers (2017)
Journal Article
Irshad, S., Flores-Borja, F., Lawler, K., Monypenny, J., Evans, R., Male, V., …Martin, S. G. (2017). RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers. Cancer Research, 77(5), 1083-1096. https://doi.org/10.1158/0008-5472.CAN-16-0598

Cancer cells tend to metastasize first to tumor-draining lymph nodes, but the mechanisms mediating cancer cell invasion into the lymphatic vasculature remain little understood. Here, we show that in the human breast tumor microenvironment (TME), the... Read More about RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers.

Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer (2016)
Journal Article
Rakha, E. A., Agarwal, D., Green, A. R., Ashankyty, I., Ellis, I. O., Ball, G., & Alaskandarany, M. A. (2017). Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer. Histopathology, 70(4), 622-631. doi:10.1111/his.13108

Aims Multigene assay is recommended currently for prognostic stratification of the clinically indeterminate group of breast cancer (BC) patients defined as lymph node (LN)?negative, oestrogen receptor (ER)?positive, HER2?negative (LN?/ER+/HER2?) t... Read More about Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer.

Molecular classification of breast cancer: what the pathologist needs to know (2016)
Journal Article
Rakha, E. A., & Green, A. R. (2017). Molecular classification of breast cancer: what the pathologist needs to know. Pathology, 49(2), 111-119. doi:10.1016/j.pathol.2016.10.012

Breast cancer is a heterogeneous disease featuring distinct histological, molecular and clinical phenotypes. Although traditional classification systems utilising clinicopathological and few molecular markers are well established and validated, they... Read More about Molecular classification of breast cancer: what the pathologist needs to know.

Diagnostic concordance of breast pathologists: lessons from the National Health Service Breast Screening Programme Pathology External Quality Assurance Scheme (2016)
Journal Article
Rakha, E. A., Ahmed, M. A., Aleskandarany, M. A., Hodi, Z., Lee, A. H. S., Pinder, S. E., & Ellis, I. O. (2017). Diagnostic concordance of breast pathologists: lessons from the National Health Service Breast Screening Programme Pathology External Quality Assurance Scheme. Histopathology, 70(4), 632-642. https://doi.org/10.1111/his.13117

Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs (2016)
Journal Article
Bertero, A., Pawlowski, M., Ortmann, D., Snijders, K., Yiangou, L., Cardoso de Brito, M., …Vallier, L. (2016). Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs. Development, 143(23), 4405-4418. https://doi.org/10.1242/dev.138081

© 2016. Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods are complex, lack robustness and do not work in multiple cell types. Here we address thes... Read More about Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs.

Designer matrices for intestinal stem cell and organoid culture (2016)
Journal Article
Gjorevski, N., Sachs, N., Manfrin, A., Giger, S., Bragina, M. E., Ordóñez-Morán, P., …Lutolf, M. P. (2016). Designer matrices for intestinal stem cell and organoid culture. Nature, 539(7630), 560-564. https://doi.org/10.1038/nature20168

Epithelial organoids recapitulate multiple aspects of real organs, making them promising models of organ development, function and disease. However, the full potential of organoids in research and therapy has remained unrealized, owing to the poorly... Read More about Designer matrices for intestinal stem cell and organoid culture.

Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers (2016)
Journal Article
Arora, A., Parvathaneni, S., Aleskandarany, M. A., Agarwal, D., Ali, R., Abdel-Fatah, T., …Madhusudan, S. (2017). Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers. Molecular Cancer Therapeutics, 16(1), https://doi.org/10.1158/1535-7163.MCT-16-0290

RECQL1, a key member of the RecQ family of DNA helicases, is required for DNA replication and DNA repair. Two recent studies have shown that germline RECQL1 mutations are associated with increased breast cancer susceptibility. Whether altered RECQL1... Read More about Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers.

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF) (2016)
Journal Article
Mesa, R., Byrne, J., Vannucchi, A. M., Yacoub, A., Zachee, P., Garg, M., …Martino, B. (2017). The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF). British Journal of Haematology, 176(1), 76-85. https://doi.org/10.1111/bjh.14382

The randomized, double‐blind, double‐dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV)‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV‐related symptom... Read More about The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF).

Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins? (2016)
Journal Article
Toss, M. S., Pinder, S. E., Green, A. R., Thomas, J., Morgan, D. A., Robertson, J. F., …Rakha, E. A. (2017). Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins?. Histopathology, 70(5), 681-692. https://doi.org/10.1111/his.13116

The introduction of mammographic screening has resulted in a rise in the detection rate of ductal carcinoma in situ (DCIS), currently accounting for one‐fifth of screen‐detected breast cancers. Although 60–70% of DCIS are treated with breast‐conservi... Read More about Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins?.