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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.

DNA damage repair in breast cancer and its therapeutic implications (2016)
Journal Article
Ali, R., Rakha, E. A., Madhusudan, S., & Bryant, H. E. (2017). DNA damage repair in breast cancer and its therapeutic implications. Pathology, 49(2), 156-165. https://doi.org/10.1016/j.pathol.2016.11.002

The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in t... Read More about DNA damage repair in breast cancer and its therapeutic implications.

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 Impact of Sarcopenia and Myosteatosis on Outcomes of Unresectable Pancreatic Cancer or Distal 1 Cholangiocarcinoma (2016)
Journal Article
Rollins, K. E., Tewari, N., Ackner, A., Awwad, A., Madhusudan, S., Macdonald, I. A., …Lobo, D. N. (2016). The Impact of Sarcopenia and Myosteatosis on Outcomes of Unresectable Pancreatic Cancer or Distal 1 Cholangiocarcinoma. Clinical Nutrition, 35(5), 1103-1109. https://doi.org/10.1016/j.clnu.2015.08.005

Abstract
Background and aims: Patients with pancreatic cancer have a poor prognosis, are often cachectic, and frequently demonstrate features of systemic inflammation, which may contribute to the phenomenon of myosteatosis. Analysis of body compos... Read More about The Impact of Sarcopenia and Myosteatosis on Outcomes of Unresectable Pancreatic Cancer or Distal 1 Cholangiocarcinoma.

Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein (2016)
Journal Article
Alshareeda, A., Negm, O. H., Aleskandarany, M. A., Green, A. R., Nolan, C., Tighe, P. J., Madhusudan, S., Ellis, I. O., & Rakha, E. (2016). Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein. Breast Cancer Research and Treatment, 159(1), 41-53. https://doi.org/10.1007/s10549-016-3915-8

Impaired DNA damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is a key player in DNA double-strand break repair. In this study, we aimed to assess the biological and clinical significance of RAD51 exp... Read More about Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein.

Human helicase RECQL4 drives cisplatin resistance in gastric cancer by activating an AKT-YB1-MDR1 signaling pathway (2016)
Journal Article
Mo, D., Fang, H., Niu, K., Liu, J., Wu, M., Li, S., …Zhao, Y. (2016). Human helicase RECQL4 drives cisplatin resistance in gastric cancer by activating an AKT-YB1-MDR1 signaling pathway. Cancer Research, 76(10), https://doi.org/10.1158/0008-5472.CAN-15-2361

Elevation of the DNA-unwinding helicase RECQL4, which participates in various DNA repair pathways, has been suggested to contribute to the pathogenicity of various human cancers, including gastric cancer. In this study, we addressed the prognostic an... Read More about Human helicase RECQL4 drives cisplatin resistance in gastric cancer by activating an AKT-YB1-MDR1 signaling pathway.

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours (2016)
Journal Article
Green, A. R., Aleskandarany, M. A., Agarwal, D., Elsheikh, S., Nolan, C. C., Diez-Rodriguez, M., …Rakha, E. A. (2016). MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours. British Journal of Cancer, 114(8), 917-928. https://doi.org/10.1038/bjc.2016.46

Background:

MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We... Read More about MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer (2016)
Journal Article
Shamanna, R. A., Lu, H., Croteau, D. L., Arora, A., Agarwal, D., Ball, G., …Bohr, V. A. (2016). Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer. Oncotarget, 7(12), 13269-13284. https://doi.org/10.18632/oncotarget.7906

Werner syndrome protein (WRN) is a RecQ helicase that participates in DNA repair, genome stability and cellular senescence. The five human RecQ helicases, RECQL1, Bloom, WRN, RECQL4 and RECQL5 play critical roles in DNA repair and cell survival after... Read More about Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer.

RECQL4 helicase has oncogenic potential in sporadic breast cancers (2016)
Journal Article
Arora, A., Agarwal, D., Abdel-Fatah, T. M., Lu, H., Croteau, D. L., Moseley, P., …Madhusudan, S. (2016). RECQL4 helicase has oncogenic potential in sporadic breast cancers. Journal of Pathology, 238(4), 495-501. https://doi.org/10.1002/path.4681

RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund–Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer pr... Read More about RECQL4 helicase has oncogenic potential in sporadic breast cancers.

Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers (2015)
Journal Article
Arora, A., Abdel-Fatah, T. M., Agarwal, D., Doherty, R., Croteau, D. L., Moseley, P. M., …Madhusudan, S. (2016). Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers. Carcinogenesis, 37(1), 63-71. https://doi.org/10.1093/carcin/bgv163

RECQL5 is a member of the RecQ family of DNA helicases and has key roles in homologous recombination, base excision repair, replication and transcription. The clinicopathological significance of RECQL5 expression in breast cancer is unknown. In this... Read More about Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers.

Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer (2015)
Journal Article
Alsubhi, N., Middleton, F., Abdel-Fatah, T. M., Stephens, P., Doherty, R., Arora, A., …Madhusudan, S. (2016). Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer. Molecular Oncology, 10(2), 213-223. https://doi.org/10.1016/j.molonc.2015.09.009

Radiation‐induced DNA damage activates the DNA damage response (DDR). DDR up‐regulation may predict radio‐resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancer... Read More about Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer.

Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial (2015)
Journal Article
Valle, J. W., Wasan, H., Lopes, A., Backen, A. C., Palmer, D. H., Morris, K., …Bridgewater, J. A. (2015). Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial. Lancet Oncology, 16(8), https://doi.org/10.1016/S1470-2045%2815%2900139-4

BACKGROUND: Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. We aimed to assess the effect of the addi... Read More about Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial.

DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers (2015)
Journal Article
Abdel-Fatah, T. M., Arora, A., Moseley, P. M., Perry, C., Rakha, E. A., Green, A. R., …Madhusudan, S. (2015). DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers. Oncotarget, 6(26), 21964-21978. https://doi.org/10.18632/oncotarget.4157

Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol β,... Read More about DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers.

KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer (2015)
Journal Article
Alshareeda, A., Negm, O., Green, A., Nolan, C., Tighe, P., Albarakati, N., Sultana, R., Madhusudan, S., Ellis, I., & Rakha, E. (2015). KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer. British Journal of Cancer, 112(12), 1929–1937. https://doi.org/10.1038/bjc.2015.165

Background: It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) prote... Read More about KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer.

Monoclonal antibodies targeting LecLex-related glycans with potent antitumor activity (2015)
Journal Article
Chua, J., Vankemmelbeke, M., McIntosh, R. S., Clarke, P. A., Moss, R., Parsons, T., Spendlove, I., Zaitoun, A. M., Madhusudan, S., & Durrant, L. (2015). Monoclonal antibodies targeting LecLex-related glycans with potent antitumor activity. Clinical Cancer Research, 21(13), 2963-2974. https://doi.org/10.1158/1078-0432.CCR-14-3030

© 2015 American Association for Cancer Research. Purpose: To produce antitumor monoclonal antibodies (mAbs) targeting glycans as they are aberrantly expressed in tumors and are coaccessory molecules for key survival pathways. Experimental Design: Two... Read More about Monoclonal antibodies targeting LecLex-related glycans with potent antitumor activity.

Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer (2015)
Journal Article
Arora, A., Abdel-Fatah, T., Agarwal, D., Doherty, R., Moseley, P. M., Aleskandarany, M. A., …Madhusudan, S. (2015). Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer. Molecular Cancer Therapeutics, 14(4), https://doi.org/10.1158/1535-7163.MCT-14-0939

Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition... Read More about Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) 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.