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Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer (2014)
Journal Article

Background

The calpains are intracellular cysteine proteases that function in a variety of important cellular functions, including signalling, motility, apoptosis and survival. In breast cancer high calpain-1 and calpain-2 expression has been asso... Read More about Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer.

Biological and clinical significance of PARP1 protein expression in breast cancer (2014)
Journal Article
Green, A. R., Caracappa, D., Benhasouna, A. A., Alshareeda, A., Nolan, C. C., Macmillan, R. D., …Rakha, E. A. (2015). Biological and clinical significance of PARP1 protein expression in breast cancer. Breast Cancer Research and Treatment, 149(2), 353-362. https://doi.org/10.1007/s10549-014-3230-1

Poly(ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair. PARP inhibitors have gained recent attention as promising therapeutic agents for the treatment of solid tumours including breast cancer (BC). However, the biological and clinic... Read More about Biological and clinical significance of PARP1 protein expression in breast cancer.

Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer (2014)
Journal Article
Wishart, G. C., Rakha, E., Green, A., Ellis, I., Ali, H. R., Provenzano, E., …Pharoah, P. D. (2014). Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer. BMC Cancer, 14(1), Article 908. https://doi.org/10.1186/1471-2407-14-908

Background

PREDICT (http://www.predict.nhs.uk) is a prognostication and treatment benefit tool for early breast cancer (EBC). The aim of this study was to incorporate the prognostic effect of KI67 status in a new version (v3), and compare performa... Read More about Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer.

Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts (2014)
Journal Article
Abdel-Fatah, T. M., Arora, A., Alsubhi, N., Agarwal, D., Moseley, P. M., Perry, C., …Madhusudan, S. (2014). Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts. Neoplasia, 16(11), 982-991. https://doi.org/10.1016/j.neo.2014.09.009

ATM-Chk2 network is critical for genomic stability, and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n = 1650) and cohort 2 (n = 252)]. ATM and Chk2 mRNA expression w... Read More about Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts.

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer (2014)
Journal Article
Abdel-Fatah, T. M., Middleton, F. K., Arora, A., Agarwal, D., Chen, T., Moseley, P. M., …Madhusudan, S. (2015). Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer. Molecular Oncology, 9(3), 569-585. https://doi.org/10.1016/j.molonc.2014.10.013

ATR‐CHEK1 signalling is critical for genomic stability. ATR‐CHEK1 signalling may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. We investigated ATR, CHEK1 and phosphorylated CHEK1 Ser345 protein (pCHEK1)... Read More about Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer.

Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy (2014)
Journal Article

Metformin is under evaluation as a potential anticancer agent. Expression of total and phospho(Thr172)-adenosine monophosphate-activated kinase-α (AMPKα and pAMPKα(Thr172) respectively), a main metformin target, was examined in radiotherapy treated b... Read More about Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy.

Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells (2014)
Journal Article
Filipović, A., Lombardo, Y., Fronato, M., Abrahams, J., Aboagye, E., Nguyen, Q.-D., …Coombes, R. C. (2014). Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells. Breast Cancer Research and Treatment, 148(2), 455-462. https://doi.org/10.1007/s10549-014-3119-z

The goal of targeted cancer therapies is to specifically block oncogenic signalling, thus maximising efficacy, while reducing side-effects to patients. The gamma-secretase (GS) complex is an attractive therapeutic target in haematological malignancie... Read More about Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells.

Is there a role for base excision repair in estrogen/estrogen receptor-driven breast cancers? (2014)
Journal Article
Abdel-Fatah, T. M., Perry, C., Arora, A., Thompson, N., Doherty, R., Moseley, P. M., …Madhusudan, S. (2014). Is there a role for base excision repair in estrogen/estrogen receptor-driven breast cancers?. Antioxidants and Redox Signaling, 21(16), 2262-2268. https://doi.org/10.1089/ars.2014.6077

Estrogen and estrogen metabolite-induced reactive oxygen species generation can promote oxidative DNA base damage. If unrepaired, base damaging lesions could accelerate mutagenesis, leading to a “mutator phenotype” characterized by aggressive behavio... Read More about Is there a role for base excision repair in estrogen/estrogen receptor-driven breast cancers?.

The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis (2014)
Journal Article
Ullenhag, G. J., Al-Attar, A., Mukherjee, A., Green, A. R., Ellis, I. O., & Durrant, L. G. (2015). The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis. Journal of Cancer Research and Clinical Oncology, 141(3), 505-514. https://doi.org/10.1007/s00432-014-1822-0

Background

Breast cancer is the most common cancer in women. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway transmits apoptotic signals. Novel anticancer agents that activate this system are in clinical development, in... Read More about The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis.

Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy (2014)
Journal Article
Albarakati, N., Abdel-Fatah, T. M., Doherty, R., Russell, R., Agarwal, D., Moseley, P., …Madhusudan, S. (2015). Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy. Molecular Oncology, 9(1), 204-217. https://doi.org/10.1016/j.molonc.2014.08.001

BRCA1, a key factor in homologous recombination (HR) repair may also regulate base excision repair (BER). Targeting BRCA1‐BER deficient cells by blockade of ATM and DNA‐PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1... Read More about Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy.

ERK1/2 is related to oestrogen receptor and predicts outcome in hormone-treated breast cancer (2014)
Journal Article
Jerjees, D. A., Alabdullah, M., Alkaabi, M., Abduljabbar, R., Muftah, A., Nolan, C., …Rakha, E. A. (2014). ERK1/2 is related to oestrogen receptor and predicts outcome in hormone-treated breast cancer. Breast Cancer Research and Treatment, 147(1), 25-37. https://doi.org/10.1007/s10549-014-3066-8

The extracellular-regulated kinase (ERK) 1/2 is one of the members of the mitogen-activated protein kinases (MAPKs). MAPKs are transduction proteins that play a role in controlling diverse cellular functions including proliferation and survival. In b... Read More about ERK1/2 is related to oestrogen receptor and predicts outcome in hormone-treated breast cancer.

Biological characteristics and clinical outcome of triple negative primary breast cancer in older women - comparison with their younger counterparts. (2014)
Journal Article

Triple negative (ER, PgR and HER2 negative) breast cancers (TNBCs) are often considered as a poor prognostic phenotype. There is dearth of evidence showing the prevalence and biological behaviour of TNBCs in older women. This study aimed to analyse t... Read More about Biological characteristics and clinical outcome of triple negative primary breast cancer in older women - comparison with their younger counterparts..

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers (2014)
Journal Article
Abdel-Fatah, T., Arora, A., Agarwal, D., Moseley, P., Perry, C., Thompson, N., …Madhusudan, S. (2014). Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers. Breast Cancer Research and Treatment, 146(2), 309-320. https://doi.org/10.1007/s10549-014-3035-2

DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end-joining pathway required fo... Read More about Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers.

KSR1 regulates BRCA1 degradation and inhibits breast cancer growth (2014)
Journal Article
Stebbing, J., Zhang, H., Xu, Y., Lit, L. C., Green, A., Grothey, A., …Giamas, G. (2015). KSR1 regulates BRCA1 degradation and inhibits breast cancer growth. Oncogene, 34(16), 2103-2114. https://doi.org/10.1038/onc.2014.129

Kinase suppressor of Ras-1 (KSR1) facilitates signal transduction in Ras-dependent cancers, including pancreatic and lung carcinomas but its role in breast cancer has not been well studied. Here, we demonstrate for the first time it functions as a tu... Read More about KSR1 regulates BRCA1 degradation and inhibits breast cancer growth.

Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study (2014)
Journal Article
Aleskandarany, M. A., Negm, O. H., Green, A. R., Ahmed, M. A. H., Nolan, C. C., Tighe, P. J., …Rakha, E. A. (2014). Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study. Breast Cancer Research and Treatment, 145(2), 339-348. https://doi.org/10.1007/s10549-014-2927-5

Epithelial mesenchymal transition (EMT), as defined by loss of epithelial characteristics and gain of a mesenchymal phenotype, has been reported in vivo although the occurrence of events remains unclear. This study aims at exploration of EMT portrait... Read More about Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study.

Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer (2014)
Journal Article
Jerjees, D. A., Alabdullah, M., Green, A. R., Alshareeda, A., Macmillan, R. D., Ellis, I. O., & Rakha, E. A. (2014). Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer. Breast Cancer Research and Treatment, 145(2), 317-330. https://doi.org/10.1007/s10549-014-2941-7

The definition of Luminal-B subclass of breast cancer (BC) varies in literature. In this study, we have compared the proliferation status; assessed using KI67 labeling index (KI67-LI), and HER2-expression in estrogen receptor positive (ER+) BC to ass... Read More about Prognostic and biological significance of proliferation and HER2 expression in the luminal class of breast cancer.

HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer (2014)
Journal Article
Green, A. R., Barros, F. F., Abdel-Fatah, T. M., Moseley, P., Nolan, C. C., Durham, A. C., …Ellis, I. O. (2014). HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer. Breast Cancer Research and Treatment, 145(1), 33-44. https://doi.org/10.1007/s10549-014-2925-7

Human epidermal growth factor receptor 2 (HER2) plays an important role in breast cancer progression and provides predictive information for response to targeted therapy including trastuzumab although this is limited. Downstream pathways, such as PI3... Read More about HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer.