Anderson transition of the plasma oscillations of 1D disordered Wigner lattices

We report the existence of a localization-delocalization transition in the classical plasma modes of a one dimensional Wigner Crystal with a white noise potential environment at T=0. Finite size scaling analysis reveals a divergence of the localization length at a critical eigenfrequency. Further scaling analysis indicates power law behavior of the critical frequency in terms of the relative interaction strength of the charges. A heuristic argument for this scaling behavior is consistent with the numerical results. Additionally, we explore a particular realization of random-bond disorder in a one dimensional Wigner lattice in which all of the collective modes are observed to be localized.Comment: 4 pages, 3 figures, Typo for the localization length corrected. Should read 1 / \n

Exact longitudinal plasmon dispersion relations for one and two dimensional Wigner crystals

We derive the exact longitudinal plasmon dispersion relations, $\omega(k)$ of classical one and two dimensional Wigner crystals at T=0 from the real space equations of motion, of which properly accounts for the full unscreened Coulomb interactions. We make use of the polylogarithm function in order to evaluate the infinite lattice sums of the electrostatic force constants. From our exact results we recover the correct long-wavelength behavior of previous approximate methods. In 1D, $\omega(k) \sim | k |\log ^{1/2} (1/k)$, validating the known RPA and bosonization form. In 2D $\omega(k) \sim \sqrt k$, agreeing remarkably with the celebrated Ewald summation result. Additionally, we extend this analysis to calculate the band structure of tight-binding models of non-interacting electrons with arbitrary power law hopping.Comment: 4 pages, 1 figure. Important typos and errors fixed, 2D dispersion adde

The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes

Purpose: BMI-1, which is a major component of the polycomb groupcomplex 1 is an essential epigenetic repressor of multiple regulatory genes and has been identified as a cancer stem cell (CSC) marker in several cancers. However, its role in breast cancer (BC) remains to be defined. In this study, we have evaluated the prognostic significance of BMI-1 among the different molecular subtypes and assessed its association with other breast CSC markers (BCSC).Material and Method: BMI-1 copy number and mRNA was assessed in large and well-characterised cohorts of early-stage BC patients [METABRIC (n=1980) and the Bc-GenExMiner (n=9616) databases]. BMI-1 protein expression was assessed using tissue microarray and immunohistochemistry in a cohort of 870 invasive BC patients with long- term outcome data and the expression of a panel of BCSC markers was monitored.Result: BMI-1 expression, prognostic significance and its association with BCSC markers were differed between molecular classes. In the luminal oestrogen receptor positive (ER+) BC, BMI-1 showed significantly higher expression compared to ER- tumours. BMI-1 showed positive correlation with favourable prognostic features and it was negatively associated with the expression of key BCSC markers (ALDH1A1, CD24, CD44, CD133, SOX10 and SOX9). High expression of BMI-1 was associated with longer breast cancer specific survival (BCSS) independent of other prognostic variables. In the basal triple negative BC subtype, BMI-1 expression showed positive association with CD133 and SOX10 and it was significantly associated with shorter BCSS.Conclusion: High variables and outcome in BC. However, this association is dependent on the molecular subtypes. Further functional assessment to detect its underlying mechanistic roles in BC subtypes is warranted

SLC30A8 Gene rs13266634 C/T Polymorphism in Children with Type 1 Diabetes in Tamil Nadu, India

Objective:Zinc transporter 8 (ZnT8) is a multi-transmembrane protein situated in the insulin secretory granule of the islets of β-cells and is identified as a novel auto-antigen in type 1 diabetes (T1D). The gene coding for ZnT8, solute carrier family 30 member 8 (SLC30A8) is located on chromosome 8q24.11. This study aimed to identify the association of SLC30A8 rs13266634 C/T gene polymorphism with T1D in a sample of T1D children in Tamil Nadu, India.Methods:The family based study was conducted in 121 T1D patients and 214 of their family members as controls. The SLC30A8 gene rs13266634 C/T polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism.Results:No significant differences were observed in either allele (odds ratio: 0.92; confidence interval: 0.33-2.58; p=0.88) and genotype (CC: p=0.74; CT: p=0.82; TT: p=0.80) frequencies of rs13266634 C/T between T1D patients and controls. Transmission disequilibrium test has identified over-transmission of mutant T allele from parents to affected children (T: U=9:7) without statistical significance. Metaanalysis on the overall effects of rs13266634 C allele frequency was not different (p=0.10 and Pheterogeneity=0.99) in T1D patients as compared to the controls.Conclusion:The present study along with the meta-analysis does not show any substantial association of the rs13266634 C/T polymorphism with T1D development in this population

Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer

Background: Breast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is involved in the cellular antiviral mechanism, plays a role in some solid tumours; however, its role in invasive BC remains unknown. In this study, we aimed to explore the clinicopathological and prognostic significance of MX1 in BC.Methods: MX1 was assessed at the protein level using tissue microarrays from a large well-annotated BC cohort (n=845). The expression of MX1 mRNA was assessed at the transcriptomic level using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=1980) and validated using three publicly available cohorts on Breast Cancer Gene-Expression Miner (bc-GenExMiner version 4.4). The associations between MX1 expression and clinicopathological factors, and outcome were evaluated.Results: High MX1 protein expression was associated with features of aggressiveness, including large tumour size, high tumour grade, high Nottingham prognostic index scores, hormone receptor negativity and high Ki67 expression. High MX1 expression showed an association with poor patient outcome and it was an independent predictor of short BC- specific survival (p=0.028; HR=1.5; 95%CI=1.0–2.2). Consistent with the protein results, high MX1 mRNA levels showed an association with features of aggressive behaviour and with shorter survival.Conclusion: This study identified MX1 as an independent predictor of poor outcome in patients with BC. Further functional studies are needed to investigate the biological role of MX1 in BC and its potential value as a therapeutic target

The prognostic significance of ALDH1A1 expression in early invasive breast cancer

Aims: Aldehyde dehydrogenase family 1 member A1 (ALDH1A1)is reportedly a key ALDH isozyme linked to the cancer stem cells (CSC) of many solid tumours, where it is involved in self-renewal, differentiation and self-protection. In this study, the prognostic significance of ALDH1A1 expression in early invasive breast cancer (BC) and its role as a BC stem cell (BCSC) were evaluated.Methods: ALDH1A1 expression was assessed, using immunohistochemistry and tissue microarrays, in a large well- characterised BC cohort. ALDH1A1 mRNA expression was also assessed at the transcriptomic levels, utilising data from the Molecular Taxonomy of Breast Cancer International Consortium. The associations of ALDH1A1 with clinicopathological parameters, other stem cell markers and patient outcomes were determined.Results: ALDH1A1 was expressed in 71% of BC cases, at both the protein and mRNA levels. High ALDH1A1 expression was associated with poor prognostic features, including high grade, poor Nottingham Prognostic Index (NPI), lymph node metastasis and highly proliferative ER+ (luminal B) and triple negative (TNBC) subtypes. ALDH1A1 expression was positively correlated with the expression of CD44, CD24, TWIST, SOX9, EPCAM and CD133. The high immunoexpression of ALDH1A1 was significantly associated with poor BC-specific survival [less than] 0.001), and specifically in the luminal B and TNBC subtypes (P=0.042 and P=0.003, respectively). The immunoexpression of ALDH1A1 was an independent predictor of poor prognosis (P=0.015).Conclusions: ALDH1A1, as assessed using IHC, seems to act as a BCSC marker associated not only with other BCSC markers but also with poor prognostic characteristics and poor outcomes, particularly in the luminal B and TNBC subtypes

Prognostic Significance of KN Motif and Ankyrin Repeat Domains 1 (KANK1) in Invasive Breast Cancer

Background: KN Motif and Ankyrin Repeat Domains 1 (KANK1) plays an important role in cytoskeleton maintenance and contributes to the regulation of cell proliferation, adhesion and apoptosis. KANK1 is involved in progression of a variety of solid tumours, however, its role in invasive breast cancer (BC) remains unknown. This study aims to evaluate the clinicopathological and prognostic value of KANK1 expression in operable BC.Methods: KANK1 expression was assessed at the transcriptomic level using multiple BC cohorts; the Molecular Taxonomy of BC International Consortium cohort (METABRIC; n=1980), The Cancer Genome Atlas BC cohort (TCGA; n=949) and the publicly available BC transcriptomic data hosted by BC Gene-Expression Miner (bc- GenExMiner v4.0) and Kaplan Meier-plotter?. The Nottingham BC cohort (n=1500) prepared as tissue microarrays was used to assess KANK1 protein expression using immunohistochemistry (IHC). The association between clinicopathological variables and patient outcome was investigated.Results: In the METABRIC cohort, high expression of KANK1 mRNA was associated with characteristics of good prognosis including lower grade, absence of lymphovascular invasion and HER2 negativity (all;

Novel C-terminal heat shock protein 90 inhibitors target breast cancer stem cells and block migration, self-renewal, and epithelial–mesenchymal transition

In patients with triple-negative breast cancer (TNBC), evidence suggests that tumor-initiating cells (TIC) have stem cell-like properties, leading to invasion and metastasis. HSP90 plays a critical role in the conformational maintenance of many client proteins in TIC development. Therefore, we hypothesize that the novel C-terminal HSP90 inhibitors KU711 and KU758 can target TIC and represent a promising strategy for overcoming metastasis. Human breast cancer cells (MDA-MB-468LN, MDA-MB-231) treated with the HSP90 inhibitors KU711, KU758, and 17-AAG showed a 50–80% decrease in TIC markers CD44 and aldehyde dehydrogenase (P < 0.01) as assessed by flow cytometry. A decrease in sphere formation, which was used to assess self-renewal, was observed after the treatment of TNBC cells starting at 2.5 µm KU711 and 0.31 µm KU758. KU compounds also blocked the invasion and migration of TNBC cells in a dose-dependent manner. The knockdown of HSP90 clients was observed without any change in prosurvival HSP70 levels. In vivo, in a murine orthotopic breast cancer model, treatment with KU758 and KU711 yielded an approximately twofold and a fourfold reduction in tumor volumes versus control, respectively, without demonstrated toxicity. In conclusion, C-terminal HSP90 inhibitors are potent novel therapeutics against TNBC in vitro and in vivo as they target TICs and block invasion, EMT transition, and self-renewal

The prognostic significance of immune microenvironment in breast ductal carcinoma in situ

BackgroundThe role of different subtypes of tumour infiltrating lymphocytes (TILs) in breast ductal carcinoma in situ (DCIS) is still poorly defined. This study aimed to assess the prognostic significance of B and T lymphocytes and immune checkpoint proteins expression in DCIS.MethodsA well characterised DCIS cohort (n = 700) with long-term follow-up comprising pure DCIS (n = 508) and DCIS mixed with invasive carcinoma (IBC; n = 192) were stained immunohistochemically for CD20, CD3, CD4, CD8, FOXP3, PD1 and PDL1. Copy number variation and TP53 mutation status were assessed in a subset of cases (n = 58).ResultsCD3+ lymphocytes were the predominant cell subtype in the pure DCIS cohort, while FOXP3 showed the lowest levels. PDL1 expression was mainly seen in the stromal TILs. Higher abundance of TILs subtypes was associated with higher tumour grade, hormone receptor negativity and HER2 positivity. Mutant TP53 variants were associated with higher levels of stromal CD3+, CD4+ and FOXP3+ cells. DCIS coexisting with invasive carcinoma harboured denser stromal infiltrates of all immune cells and checkpoint proteins apart from CD4+ cells. Stromal PD1 was the most differentially expressed protein between DCIS and invasive carcinoma (Z = 5.8, p

Triazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors

Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with Hsp90 N-terminal inhibitors under clinical investigation. Based upon prior SAR trends, a 1,2,3-triazole side chain was placed in lieu of the aryl side chain and attached to both the coumarin and biphenyl scaffold. Antiproliferative studies against SKBr3 and MCF-7 breast cancer cell lines demonstrated these triazole-containing compounds to exhibit improved activity. These compounds were shown to manifest Hsp90 inhibitory activity through Western blot analysis and represent a new scaffold upon which more potent inhibitors can be pursued