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We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies and real-time monitoring of tumors, nanorobots are designed to perform multiple tasks at a small scale, even at the organelles or molecular level. Over the last few years, most nanorobots have been bioengineered as biomimetic and biocompatible nano(bio)structures, resembling different organisms and cells, such as urchin, spider, octopus, fish, spermatozoon, flagellar bacterium or helicoidal cyanobacterium. In this review, readers will be able to deepen their knowledge of the structure, behavior and role of several types of nanorobots, among other nanomaterials, in BC theranostics. We summarized here the characteristics of many functionalized nanodevices designed to counteract the main neoplastic hallmark features of BC, from sustaining proliferation and evading anti-growth signaling and resisting programmed cell death to inducing angiogenesis, activating invasion and metastasis, preventing genomic instability, avoiding immune destruction and deregulating autophagy. Most of these nanorobots function as targeted and self-propelled smart nano-carriers or nano-drug delivery systems (nano-DDSs), enhancing the efficiency and safety of chemo-, radio- or photodynamic therapy, or the current imagistic techniques used in BC diagnosis. Most of these nanorobots have been tested in vitro, using various BC cell lines, as well as in vivo, mainly based on mice models. We are still waiting for nanorobots that are low-cost, as well as for a wider transition of these favorable effects from laboratory to clinical practice. [ABSTRACT FROM AUTHOR]

Precision oncology is based on deep knowledge of the molecular profile of tumors, allowing for more accurate and personalized therapy for specific groups of patients who are different in disease susceptibility as well as treatment response. Thus, onco-breastomics is able to discover novel biomarkers that have been found to have racial and ethnic differences, among other types of disparities such as chronological or biological age-, sex/gender- or environmental-related ones. Usually, evidence suggests that breast cancer (BC) disparities are due to ethnicity, aging rate, socioeconomic position, environmental or chemical exposures, psycho-social stressors, comorbidities, Western lifestyle, poverty and rurality, or organizational and health care system factors or access. The aim of this review was to deepen the understanding of BC-related disparities, mainly from a biomedical perspective, which includes genomic-based differences, disparities in breast tumor biology and developmental biology, differences in breast tumors' immune and metabolic landscapes, ecological factors involved in these disparities as well as microbiomics- and metagenomics-based disparities in BC. We can conclude that onco-breastomics, in principle, based on genomics, proteomics, epigenomics, hormonomics, metabolomics and exposomics data, is able to characterize the multiple biological processes and molecular pathways involved in BC disparities, clarifying the differences in incidence, mortality and treatment response for different groups of BC patients. [ABSTRACT FROM AUTHOR]

Known as a diverse collection of neoplastic diseases, breast cancer (BC) can be hyperbolically characterized as a dynamic pseudo-organ, a living organism able to build a complex, open, hierarchically organized, self-sustainable, and self-renewable tumor system, a population, a species, a local community, a biocenosis, or an evolving dynamical ecosystem (i.e., immune or metabolic ecosystem) that emphasizes both developmental continuity and spatio-temporal change. Moreover, a cancer cell community, also known as an oncobiota, has been described as non-sexually reproducing species, as well as a migratory or invasive species that expresses intelligent behavior, or an endangered or parasite species that fights to survive, to optimize its features inside the host's ecosystem, or that is able to exploit or to disrupt its host circadian cycle for improving the own proliferation and spreading. BC tumorigenesis has also been compared with the early embryo and placenta development that may suggest new strategies for research and therapy. Furthermore, BC has also been characterized as an environmental disease or as an ecological disorder. Many mechanisms of cancer progression have been explained by principles of ecology, developmental biology, and evolutionary paradigms. Many authors have discussed ecological, developmental, and evolutionary strategies for more successful anti-cancer therapies, or for understanding the ecological, developmental, and evolutionary bases of BC exploitable vulnerabilities. Herein, we used the integrated framework of three well known ecological theories: the Bronfenbrenner's theory of human development, the Vannote's River Continuum Concept (RCC), and the Ecological Evolutionary Developmental Biology (Eco-Evo-Devo) theory, to explain and understand several eco-evo-devo-based principles that govern BC progression. Multi-omics fields, taken together as onco-breastomics, offer better opportunities to integrate, analyze, and interpret large amounts of complex heterogeneous data, such as various and big-omics data obtained by multiple investigative modalities, for understanding the eco-evo-devo-based principles that drive BC progression and treatment. These integrative eco-evo-devo theories can help clinicians better diagnose and treat BC, for example, by using non-invasive biomarkers in liquid-biopsies that have emerged from integrated omics-based data that accurately reflect the biomolecular landscape of the primary tumor in order to avoid mutilating preventive surgery, like bilateral mastectomy. From the perspective of preventive, personalized, and participatory medicine, these hypotheses may help patients to think about this disease as a process governed by natural rules, to understand the possible causes of the disease, and to gain control on their own health. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is characterized by an extensive genotypic and phenotypic heterogeneity. In-depth investigations into the molecular bases of BC phenotypes, carcinogenesis, progression, and metastasis are necessary for accurate diagnoses, prognoses, and therapy assessments in predictive, precision, and personalized oncology. This review discusses both classic as well as several novel omics fields that are involved or should be used in modern BC investigations, which may be integrated as a holistic term, onco-breastomics. Rapid and recent advances in molecular profiling strategies and analytical techniques based on high-throughput sequencing and mass spectrometry (MS) development have generated large-scale multi-omics datasets, mainly emerging from the three "big omics", based on the central dogma of molecular biology: genomics, transcriptomics, and proteomics. Metabolomics-based approaches also reflect the dynamic response of BC cells to genetic modifications. Interactomics promotes a holistic view in BC research by constructing and characterizing protein–protein interaction (PPI) networks that provide a novel hypothesis for the pathophysiological processes involved in BC progression and subtyping. The emergence of new omics- and epiomics-based multidimensional approaches provide opportunities to gain insights into BC heterogeneity and its underlying mechanisms. The three main epiomics fields (epigenomics, epitranscriptomics, and epiproteomics) are focused on the epigenetic DNA changes, RNAs modifications, and posttranslational modifications (PTMs) affecting protein functions for an in-depth understanding of cancer cell proliferation, migration, and invasion. Novel omics fields, such as epichaperomics or epimetabolomics, could investigate the modifications in the interactome induced by stressors and provide PPI changes, as well as in metabolites, as drivers of BC-causing phenotypes. Over the last years, several proteomics-derived omics, such as matrisomics, exosomics, secretomics, kinomics, phosphoproteomics, or immunomics, provided valuable data for a deep understanding of dysregulated pathways in BC cells and their tumor microenvironment (TME) or tumor immune microenvironment (TIMW). Most of these omics datasets are still assessed individually using distinct approches and do not generate the desired and expected global-integrative knowledge with applications in clinical diagnostics. However, several hyphenated omics approaches, such as proteo-genomics, proteo-transcriptomics, and phosphoproteomics-exosomics are useful for the identification of putative BC biomarkers and therapeutic targets. To develop non-invasive diagnostic tests and to discover new biomarkers for BC, classic and novel omics-based strategies allow for significant advances in blood/plasma-based omics. Salivaomics, urinomics, and milkomics appear as integrative omics that may develop a high potential for early and non-invasive diagnoses in BC. Thus, the analysis of the tumor circulome is considered a novel frontier in liquid biopsy. Omics-based investigations have applications in BC modeling, as well as accurate BC classification and subtype characterization. The future in omics-based investigations of BC may be also focused on multi-omics single-cell analyses. [ABSTRACT FROM AUTHOR]

The analysis of archaeological human bone tissue can provide valuable information on cellular activity related to diseases from the past. The application of histology has become an essential and integral part in the study of human dry bone pathologies. Although paleopathology of human remains has been intensely studied, particularly by a macroscopical approach, the microscopical analysis of the affected archaeological bone tissue is an issue that has not been addressed at the same scale. This study represents the first paleohistological approach of some pathological lesions suggestive for syphilis from Romania. The aim of this study is to describe the paleohistological features (i.e., periosteal new bone formation and adjacent compact bone tissue morphology) of typical syphilitic changes in the long bones of a human skeleton (R30) from the 15th -19th centuries, discovered at the Roman Catholic Cathedral from Iaşi. The tissue material was subjected to the methodology for histological examination of dry bone samples. Samples were cleaned in multiple sonic baths and embedded in Buehler EpoThin 2 epoxy resin. The sections were ground and polished using carbide paper and visualized through a Confocal Laser Scanning Microscope CLSM--Leica TCS SPE DM. The preservation of the archaeological samples was assessed using the Oxford Histological Index stages. The taphonomic evaluation showed that the bone samples were very well preserved in archaeological context. During the microscopic analysis periosteal, new bone formation (e.g., polsters) and grenzlinie or remnants of these structures were identified, suggesting an inflammatory process. Sinuous lacunae were also observed in the compact bone tissue, indicating an osteolytic activity. [ABSTRACT FROM AUTHOR]

MCF7 is a commonly used luminal type A non-invasive/poor-invasive human breast cancer cell line that does not usually migrate or invade compared with MDA-MB-231 highly metastatic cells, which emphasize an invasive and migratory behavior. Under special conditions, MCF7 cells might acquire invasive features. The aberration in expression and biological functions of the jumping translocation breackpoint (JTB) protein is associated with malignant transformation of cells, based on mitochondrial dysfunction, inhibition of tumor suppressive function of TGF-β, and involvement in cancer cell cycle. To investigate new putative functions of JTB by cellular proteomics, we analyzed the biological processes and pathways that are associated with the JTB protein downregulation. The results demonstrated that MCF7 cell line developed a more "aggressive" phenotype and behavior. Most of the proteins that were overexpressed in this experiment promoted the actin cytoskeleton reorganization that is involved in growth and metastatic dissemination of cancer cells. Some of these proteins are involved in the epithelial-mesenchymal transition (EMT) process (ACTBL2, TUBA4A, MYH14, CSPG5, PKM, UGDH, HSP90AA2, and MIF), in correlation with the energy metabolism reprogramming (PKM, UGDH), stress-response (HSP10, HSP70A1A, HSP90AA2), and immune and inflammatory response (MIF and ERp57-TAPBP). Almost all upregulated proteins in JTB downregulated condition promote viability, motility, proliferation, invasion, survival into a hostile microenvironment, metabolic reprogramming, and escaping of tumor cells from host immune control, leading to a more invasive phenotype for MCF7 cell line. Due to their downregulated condition, four proteins, such as CREBZF, KMT2B, SELENOS and CACNA1I are also involved in maintenance of the invasive phenotype of cancer cells, promoting cell proliferation, migration, invasion and tumorigenesis. Other downregulated proteins, such as MAZ, PLEKHG2, ENO1, TPI2, TOR2A, and CNNM1, may promote suppression of cancer cell growth, invasion, EMT, tumorigenic abilities, interacting with glucose and lipid metabolism, disrupting nuclear envelope stability, or suppressing apoptosis and developing anti-angiogenetic activities. Therefore, the main biological processes and pathways that may increase the tumorigenic potential of the MCF7 cells in JTB downregulated condition are related to the actin cytoskeleton organization, EMT, mitotic cell cycle, glycolysis and fatty acid metabolism, inflammatory response and macrophage activation, chemotaxis and migration, cellular response to stress condition (oxidative stress and hypoxia), transcription control, histone modification and ion transport., Competing Interests: None., (AJCR Copyright © 2022.)

Jumping translocation breakpoint (JTB) gene acts as a tumor suppressor or an oncogene in different malignancies, including breast cancer (BC), where it was reported as overexpressed. However, the molecular functions, biological processes and underlying mechanisms through which JTB protein causes increased cell growth, proliferation and invasion is still not fully deciphered. Our goal is to identify the functions of JTB protein by cellular proteomics approaches. MCF7 breast cancer cells were transfected with sense orientation of hJTB cDNA in HA, His and FLAG tagged CMV expression vector to overexpress hJTB and the expression levels were confirmed by Western blotting (WB). Proteins extracted from transfected cells were separated by SDS-PAGE and the in-gel digested peptides were analyzed by nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS). By comparing the proteome of cells with upregulated conditions of JTB vs control and identifying the protein dysregulation patterns, we aim to understand the function of this protein and its contribution to tumorigenesis. Gene Set Enrichment Analysis (GSEA) algorithm was performed to investigate the biological processes and pathways that are associated with the JTB protein upregulation. The results demonstrated four significantly enriched gene sets from the following significantly upregulated pathways: mitotic spindle assembly, estrogen response late, epithelial-to-mesenchymal transition (EMT) and estrogen response early. JTB protein itself is involved in mitotic spindle pathway by its role in cell division/cytokinesis, and within estrogen response early and late pathways, contributing to discrimination between luminal and mesenchymal breast cancer. Thus, the overexpressed JTB condition was significantly associated with an increased expression of ACTNs, FLNA, FLNB, EZR, MYOF, COL3A1, COL11A1, HSPA1A, HSP90A, WDR, EPPK1, FASN and FOXA1 proteins related to deregulation of cytoskeletal organization and biogenesis, mitotic spindle organization, ECM remodeling, cellular response to estrogen, proliferation, migration, metastasis, increased lipid biogenesis, endocrine therapy resistance, antiapoptosis and discrimination between different breast cancer subtypes. Other upregulated proteins for overexpressed JTB condition are involved in multiple cellular functions and pathways that become dysregulated, such as tumor microenvironment (TME) acidification, the transmembrane transport pathways, glycolytic flux, iron metabolism and oxidative stress, metabolic reprogramming, nucleocytosolic mRNA transport, transcriptional activation, chromatin remodeling, modulation of cell death pathways, stress responsive pathways, and cancer drug resistance. The downregulated proteins for overexpressed JTB condition are involved in adaptive communication between external and internal environment of cells and maintenance between pro-apoptotic and anti-apoptotic signaling pathways, vesicle trafficking and secretion, DNA lesions repair and suppression of genes involved in tumor progression, proteostasis, redox state regulation, biosynthesis of macromolecules, lipolytic pathway, carbohydrate metabolism, dysregulation of ubiquitin-mediated degradation system, cancer cell immune escape, cell-to-cell and cell-to-ECM interactions, and cytoskeletal behaviour. There were no significantly enriched downregulated pathways., Competing Interests: None., (AJCR Copyright © 2022.)