The role of FOXM1 and its cofactors HMGA1 and HMGN1 in breast cancer progression

FOXM1 is a potent oncogenic transcription factor that plays essential roles in multiple hallmarks of cancer progression, thus having impacts on tumour initiation, invasion, angiogenesis, cancer stemness and drug sensitivity. Likewise, high mobility group proteins, HMGA1 and HMGN1 are also involved in tumorigenic and metastatic processes in cancer. The human protein-protein interactions prediction database has reported the potential interactions between these proteins, but no further experimental evidence to confirm and characterise this link. In my project, I demonstrated that FOXM1 binds to HMGA1 or HMGN1 as protein-protein complex, and such interactions affect the transcriptional regulation of KIF20A and SQSTM1/p62. Disruption of the complex or their protein expression levels significantly affects drug sensitivity, cell migration and invasion in breast cancer cells. Apart from the essential roles of HMGA1 and HMGN1 in DNA repair mechanisms, they influence these malignant processes may partially through regulating FOXM1 activities. Thus, the functions of these FOXM1’s transcriptional targets, KIF20A and p62 were further examined. The results showed the p62 is involved in modulating angiogenic and metastatic processes in breast cancer as silencing of p62 significantly attenuated tumour-induced angiogenesis and cell migration in zebrafish. Furthermore, KIF20A is a novel target which KIF20A inhibition increased drug sensitivity and reduced cell migration, invasion and mammosphere formation. In addition, the new KIF20A inhibitor, BKS0349 compound offers a viable therapeutic option for cancer treatment in future. In summary, my results have established a potential mechanism underlying the interactions between FOXM1, HMGA1 and HMGN1 in breast cancer cells. Collectively, these findings strengthen our current understanding of the oncogenic protein FOXM1-mediated cancer progression and provide new insights into cancer diagnosis and treatment.Open Acces

The Influence of Subhaloes on Host Halo Properties

Within the ΛCDM cosmology, dark matter haloes are composed of both a smooth component and a population of smaller gravitationally bound subhaloes. These components are often treated as a single halo when properties, such as density profiles, are extracted from simulations. Recent work has shown that density profiles change substantially when subhalo mass is excluded. In this paper, we expand on this result by analysing three specific host halo properties – concentration (cNFW), spin (λB), and shape (c/a) – when calculated only from the smooth component of the halo. This analysis is performed on both Milky Way-mass haloes and cluster-mass haloes in high-resolution zoom-in N-body simulations. We find that when subhaloes are excluded, the median value of (1) cNFW is enhanced by ≈ 30 ± 11 and ≈ 77 ± 8.1 per cent for Milky Way-mass (1012.1M⊙) and cluster-mass (1014.8M⊙) haloes, respectively, (2) λB is reduced for Milky Way-mass by ≈ 11 ± 4.9 per cent and cluster-mass haloes by ≈ 27 ± 3.5 per cent. Additionally, with the removal of subhaloes, cluster-mass haloes tend to become more spherical as the ratio of minor-to-major axis, c/a, increases by ≈ 11 ± 3.6 per cent, whereas Milky Way-mass haloes remain approximately the same shape with c/a changed by ≈ 1.0 ± 5.8 per cent. Fractional changes of each of these properties depend primarily on the amount of mass in subhaloes and, to a lesser extent, mass accretion history. Our findings demonstrate that the properties of the smooth components of dark matter haloes are biased relative to the total halo mass

An audit of the management of elderly patients with glioblastoma in the UK: have recent trial results changed treatment?

Aim: We investigated uptake of short-course chemo-radiotherapy and compared outcomes with other treatment schedules in elderly patients with glioblastoma (GBM). Methods: Patients aged 65 or over with a diagnosis of GBM were identified from an 18-month period from three centers in the UK. The primary end point of this study was overall survival from the date of diagnosis. Results: The analysis included 210 patients. Overall median survival was 5.0 months. Approximately 31.9% of patients received combined chemoradiation; multivariate analysis showed that patients who received standard chemoradiation were at a reduced risk of death than those receiving hypofractionated chemoradiation. Discussion: In this retrospective study, patients treated with standard chemoradiation experienced better outcomes than patients receiving hypofractionated chemoradiation. Patient selection likely contributed to these findings

Mobile Messenger rating, sharing and engagement in global social commerce

The use of the Short Message Service (SMS), available on mobile phones and other devices, for exchanging text messages is gradually diminishing. SMS has been replaced by Smart Phone Apps offering free messaging services; example include Whatsapp, Kakao, WeChat and Viber. The use of these platforms is constantly evolving; they are now used for advertising, group chatting, the sharing of information, and e-commerce communication. This paper provides a review of the currently available Mobile Messenger Applications, comparing their abilities, function and features. In particular the paper focuses on the engaging of these Apps in Global Social Commerce. In addition, the engagement of users towards sharing, commenting and rating the products and services were also discussed