Clinical Significance of Annexin A1 Expression in Breast Cancer

Purpose: The expression of Annexin A1 (ANXA1) is known to be reduced in human breast cancer; however, the role of ANXA1 expression in the development of breast cancer remains unclear. In this study, we determined the relationship between the expression features of ANXA1 and the prognostic factors of breast cancer. Methods: Human breast tissues were obtained from patients specimens who had undergone breast surgery or core needle biopsies. The patterns of ANXA1 expression were analyzed by immunohistochemical staining in relation to histopathological diagnosis, clinical characteristics and outcomes. Results: One hundred eighty-two cases were included and the mean age of the patients was 46.34 ± 11.5 years. A significant loss of ANXA1 expression was noted in both ductal carcinoma in situ (DCIS) and invasive carcinomas compared to normal breast tissues (p<0.001) and benign breast diseases (p<0.001). There was a significan

Choosing the right cell line for breast cancer research

Breast cancer is a complex and heterogeneous disease. Gene expression profiling has contributed significantly to our understanding of this heterogeneity at a molecular level, refining taxonomy based on simple measures such as histological type, tumour grade, lymph node status and the presence of predictive markers like oestrogen receptor and human epidermal growth factor receptor 2 (HER2) to a more sophisticated classification comprising luminal A, luminal B, basal-like, HER2-positive and normal subgroups. In the laboratory, breast cancer is often modelled using established cell lines. In the present review we discuss some of the issues surrounding the use of breast cancer cell lines as experimental models, in light of these revised clinical classifications, and put forward suggestions for improving their use in translational breast cancer research

Laboratory information management system for COVID-19 non-clinical efficacy trial data

Background : As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results : In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions : This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.This research was supported by the National research foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2020M3A9I2109027 and 2021M3H9A1030260)

Progress on lead-free metal halide perovskites for photovoltaic applications: a review

ABSTRACT: Metal halide perovskites have revolutionized the field of solution-processable photovoltaics. Within just a few years, the power conversion efficiencies of perovskite-based solar cells have been improved significantly to over 20%, which makes them now already comparably efficient to silicon-based photovoltaics. This breakthrough in solution-based photovoltaics, however, has the drawback that these high efficiencies can only be obtained with lead-based perovskites and this will arguably be a substantial hurdle for various applications of perovskite-based photovoltaics and their acceptance in society, even though the amounts of lead in the solar cells are low. This fact opened up a new research field on lead-free metal halide perovskites, which is currently remarkably vivid. We took this as incentive to review this emerging research field and discuss possible alternative elements to replace lead in metal halide perovskites and the properties of the corresponding perovskite materials based on recent theoretical and experimental studies. Up to now, tin-based perovskites turned out to be most promising in terms of power conversion efficiency; however, also the toxicity of these tin-based perovskites is argued. In the focus of the research community are other elements as well including germanium, copper, antimony, or bismuth, and the corresponding perovskite compounds are already showing promising properties. GRAPHICAL ABSTRACT: [Image: see text

H-Ras induces Nrf2-Pin1 interaction: Implications for breast cancer progression

Aberrant activation of H-Ras is often associated with tumor aggressiveness in breast cancer. Peptidyl-prolyl cistrans isomerase NIMA-interacting 1 (Pin1) is a unique enzyme that interacts with phosphorylated serine or threonine of a target protein and isomerizes the adjacent proline residue. Pin1 is prevalently overexpressed in human cancers, and its overexpression correlates with poor prognosis. Nuclear factor E2-related factor 2 (Nrf2) is a master regulator of cellular redox homeostasis. The sustained activation/accumulation of Nrf2 has been observed in many different types of human malignancies, conferring an advantage for growth and survival of cancer cells. The activated form of H-Ras (GTP-H-Ras) is highly overexpressed in human breast cancer tissues. In our present study, silencing of H-Ras decreased the invasiveness of MDA-MB-231 human breast cancer cells and abrogated the interaction between Pin1 and Nrf2 in these cells. Pin1 knockdown blocked the accumulation of Nrf2, thereby suppressing proliferation and clonogenicity of MCF10A-Ras human mammary epithelial cells. We found that Pin1 binds to Nrf2 which stabilizes this transcription factor by hampering proteasomal degradation. In conclusion, H-Ras activation in cooperation with the Pin1-Nrf2 complex represents a novel mechanism underlying breast cancer progression and constitutive activation of Nrf2 and can be exploited as a therapeutic target.

STAT3 Stabilizes IKK alpha Protein through Direct Interaction in Transformed and Cancerous Human Breast Epithelial Cells

Simple Summary Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-kappa B) play a cooperative role in inflammation-associated tumorigenesis at multi-levels. The alpha subunit of the inhibitor of the kappa B kinase (IKK) complex, IKK alpha, is involved in both classical and non-classical activation of NF-kappa B. However, the interplay between STAT3 and IKK alpha has not been clarified yet. Here, we report overexpression and co-localization of IKK alpha and STAT3 in human breast cancer tissues as well as in human breast cancer cells, which promotes breast cancer promotion and progression. IKK alpha was stabilized and upregulated by STAT3. We identified the lysine 44 residue of IKK alpha as a putative binding site for STAT3. Taken together, these findings propose a novel mechanism responsible for NF-kappa B activation by STAT3 through stabilization of IKK alpha. Thus, STAT3 and IKK alpha could integrate, and coordinately mediate the growth and progression of human breast cancer. Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-kappa B) are two representative transcription factors that play a critical role in inflammation-associated tumorigenesis through multi-level cooperation. Unlike other types of tumors, breast carcinomas have shown a significant dependency on the non-classical NF-kappa B pathway as well as the classical one. The alpha subunit of the inhibitor of the kappa B kinase (IKK) complex, IKK alpha, is involved in both classical and non-classical activation of NF-kappa B. Although the cross-talk between STAT3 and NF-kappa B has been suggested in several studies, the interplay between STAT3 and the regulators of NF-kappa B including IKK alpha has not been fully clarified yet. In this study, we observed overexpression and co-localization of IKK alpha and STAT3 in human breast cancer tissues as well as in H-Ras transformed human breast epithelial (H-Ras MCF-10A) and breast cancer (MDA-MB-231) cells. By utilizing small interfering RNA (siRNA) technology, we were able to demonstrate that STAT3 up-regulated IKK alpha, but not IKK beta or IKK gamma, in these cells. This was attributable to direct binding to and subsequent stabilization of IKK alpha protein by blocking the ubiquitin-proteasome system. Notably, we identified the lysine 44 residue of IKK alpha as a putative binding site for STAT3. Moreover, siRNA knockdown of IKK alpha attenuated viability, anchorage-independent growth and migratory capabilities of H-Ras MCF-10A cells. Taken together, these findings propose a novel mechanism responsible for NF-kappa B activation by STAT3 through stabilization of IKK alpha, which contributes to breast cancer promotion and progression. Thus, breaking the STAT3-IKK alpha alliance can be an alternative therapeutic strategy for the treatment of breast cancer.