Abstract 4205: The role of non-muscle myosin IIA in HER2+ breast cancers

Abstract Background Glioblastoma (GBM) is the most aggressive form of brain tumor and has vascular-rich features. The S100A4/non-muscle myosin IIA (NMIIA) axis contributes to aggressive phenotypes in a variety of human malignancies, but little is known about its involvement in GBM tumorigenesis. Herein, we examined the role of the S100A4/NMIIA axis during tumor progression and vasculogenesis in GBM Methods We performed immunohistochemistry for S100A4, NMIIA, and two hypoxic markers including hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase 9 (CA9) in samples from 94 GBM cases. The functional impact of S100A4 knockdown and hypoxia were also assessed using a GBM cell line. Results In clinical GBM samples, overexpression of S100A4 and NMIIA was observed in both non-pseudopalisading (Ps) and Ps (-associated) perinecrotic lesions, consistent with stabilization of HIF-1α and CA9. CD34(+) microvascular densities (MVDs) and the interaction of S100A4 and NMIIA were significantly higher in non-Ps perinecrotic lesions compared to those in Ps perinecrotic areas. In non-Ps perinecrotic lesions, S100A4(+)/HIF-1α(-) GBM cells were recruited to the surface of host preexisting vessels in the vascular-rich areas. Elevated vascular endothelial growth factor A (VEGFA) mRNA expression was found in S100A4(+)/HIF-1α(+) GBM cells adjacent to the vascular-rich areas. In addition, GBM patients with high S100A4 protein expression had significantly worse OS and PFS than did patients with low S100A4 expression. Knockdown of S100A4 in the GBM cell line KS-1 decreased migration capability, concomitant with decreased Slug expression; the opposite effects were elicited by blebbistatin-dependent inhibition of NMIIA. Conclusion S100A4(+)/HIF-1α(-) GBM cells are recruited to (and migrate along) preexisting vessels through inhibition of NMIIA activity. This is likely stimulated by extracellular VEGF that is released by S100A4(+)/HIF-1α(+) tumor cells in non-Ps perinecrotic lesions. In turn, these events engender tumor progression via acceleration of pro-tumorigenic vascular functions.

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Faculty Opinions recommendation of Expansion and concatenation of non-muscle myosin IIA filaments drive cellular contractile system formation during interphase and mitosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726209995.793528479 ◽

2017 ◽

Author(s):

Pekka Lappalainen

Keyword(s):

System Formation ◽

Contractile System ◽

Myosin Iia ◽

Muscle Myosin

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Role of General Adversarial Networks in Mammogram Analysis: A Review

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/1573405614666191115102318 ◽

2020 ◽

Vol 16 (7) ◽

pp. 863-877

Author(s):

Annapoorani Gopal ◽

Lathaselvi Gandhimaruthian ◽

Javid Ali

Keyword(s):

Breast Tumor ◽

Deep Neural Networks ◽

Training Data ◽

Learning Technology ◽

Breast Cancers ◽

Generative Adversarial Network ◽

Adversarial Network ◽

Adversarial Networks ◽

Tumor Extraction

The Deep Neural Networks have gained prominence in the biomedical domain, becoming the most commonly used networks after machine learning technology. Mammograms can be used to detect breast cancers with high precision with the help of Convolutional Neural Network (CNN) which is deep learning technology. An exhaustive labeled data is required to train the CNN from scratch. This can be overcome by deploying Generative Adversarial Network (GAN) which comparatively needs lesser training data during a mammogram screening. In the proposed study, the application of GANs in estimating breast density, high-resolution mammogram synthesis for clustered microcalcification analysis, effective segmentation of breast tumor, analysis of the shape of breast tumor, extraction of features and augmentation of the image during mammogram classification have been extensively reviewed.

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The role of the clinical pharmacist in guiding adjuvant hormonal therapy in patients with breast cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211029361 ◽

2021 ◽

pp. 107815522110293

Author(s):

Amanda V Pirolli ◽

Tatiana Brusamarello ◽

Stella S Everton ◽

Vânia M S Andrzejevski

Keyword(s):

Breast Cancer ◽

Hormone Therapy ◽

Hormonal Therapy ◽

Clinical Pharmacist ◽

Tertiary Care ◽

Structured Interview ◽

Care Hospital ◽

Adjuvant Hormonal Therapy ◽

Breast Cancers

Breast cancer is the most prevalent type of cancer among women, affecting about 2.1 million worldwide and is responsible for the highest number of cancer-related deaths among women. Approximately 80% of breast cancers express on the surface of hormone receptor cells, such as progesterone and estrogen. In these cases, Adjuvant Hormonal Therapy (AHT) is indicated for a period of five to ten years and consists of taking a daily oral pill. The two most used drugs in AHT are tamoxifen and Aromatase Inhibitors. One of the issues most faced by individuals who are subjected to long periods of treatment is the lack of medication adherence and, consequently, therapeutic inefficiency. It is believed that the monitoring by the pharmacist can contribute to the reduction of errors inherent to the medication, making the treatment more effective and improving the patient's quality of life. The present study aimed to know the perception of patients who live with breast cancer and who do AHT in relation to the educational performance of the clinical pharmacist. This is a qualitative, descriptive and exploratory study, carried out from March to October 2020, with 15 women undergoing treatment at the oncology unit of a tertiary-care hospital in south of Brazil. The data were obtained through a semi-structured interview using an instrument composed of two parts, one referring to the characterization of the participants and the other with the guiding question of the research: "How do you perceive the role of the pharmacist in relation to the guidelines for the use of adjuvant hormonal therapy?". The method of theoretical saturation was used to perform the sample closure and the thematic analysis was used to analyze the data. The participants were between 32 and 74 years old, seven were on tamoxifen therapy and eight on anastrozole, ten were on the first year of treatment, two on the second and three on the third year. The themes that emerged were: pharmacist-patient interaction as a safety factor in hormone therapy; role of the pharmacist in the development of strategies for self-management of the patients during hormone therapy; and, challenges for the pharmacist in relation to hormone therapy through continued guidance. It was evident that the pharmacist's educational action encouraged the participants to carry out the treatment in a more confident and assertive manner according to their particularities and beliefs.

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Role of domain 3 of calmodulin in activation of calmodulin-stimulated phosphodiesterase and smooth muscle myosin light chain kinase

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)89456-5 ◽

1994 ◽

Vol 269 (24) ◽

pp. 16761-16765

Author(s):

Z. Su ◽

D. Fan ◽

S.E. George

Keyword(s):

Smooth Muscle ◽

Light Chain ◽

Myosin Light Chain Kinase ◽

Myosin Light Chain ◽

Smooth Muscle Myosin ◽

Domain 3 ◽

Muscle Myosin

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The Roles of DNA Demethylases in Triple-Negative Breast Cancer

Pharmaceuticals ◽

10.3390/ph14070628 ◽

2021 ◽

Vol 14 (7) ◽

pp. 628

Author(s):

Shoghag Panjarian ◽

Jean-Pierre J. Issa

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Tumor Suppressor Genes ◽

Hormone Receptors ◽

Triple Negative ◽

Breast Cancers ◽

Therapeutic Implications ◽

High Propensity ◽

Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

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