Centrosome Aberrations as Drivers of Chromosomal Instability in Breast Cancer

Endocrinology ◽  
2021 ◽  
Author(s):  
Katrina M Piemonte ◽  
Lindsey J Anstine ◽  
Ruth A Keri
Keyword(s):  
Breast Cancer ◽  
Chromosomal Instability ◽  
Dynamic Change ◽  
Structural Defects ◽  
Tumor Evolution ◽  
Therapeutic Approaches ◽  
Cancer Hallmarks ◽  
Aggressive Disease ◽  
Wide Range

Abstract Chromosomal instability (CIN), or the dynamic change in chromosome number and composition, has been observed in cancer for decades. Recently, this phenomenon has been implicated as facilitating the acquisition of cancer hallmarks and enabling the formation of aggressive disease. Hence, CIN has the potential to serve as a therapeutic target for a wide range of cancers. CIN in cancer often occurs as a result of disrupting key regulators of mitotic fidelity and faithful chromosome segregation. As a consequence of their essential roles in mitosis, dysfunctional centrosomes can induce and maintain CIN. Centrosome defects are common in breast cancer, a heterogeneous disease characterized by high CIN. These defects include amplification, structural defects, and loss of primary cilium nucleation. Recent studies have begun to illuminate the ability of centrosome aberrations to instigate genomic flux in breast cancer cells and the tumor evolution associated with aggressive disease and poor patient outcomes. Here, we review the role of CIN in breast cancer, the processes by which centrosome defects contribute to CIN in this disease, and the emerging therapeutic approaches that are being developed to capitalize upon such aberrations.

scholarly journals The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1160
Author(s):  
Giusi La Camera ◽  
Luca Gelsomino ◽  
Amanda Caruso ◽  
Salvatore Panza ◽  
Ines Barone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Endocrine Resistance ◽  
Disease Recurrence ◽  
Estrogen Receptor Α ◽  
Research Area ◽  
Tumor Evolution

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance. Unraveling the role of EVs, released by transformed cells during the tumor evolution under endocrine therapy, is still an open question in the cancer research area and the molecular mechanisms involved should be better defined to discover alternative therapeutic approaches to overcome resistance. In this review, we will provide an overview of recent findings on the involvement of EVs in sustaining hormonal resistance in breast cancer and discuss opportunities for their potential use as biomarkers to monitor the therapeutic response and disease progression.

scholarly journals Development of cancer metabolism as a therapeutic target: new pathways, patient studies, stratification and combination therapy

2019 ◽  
Vol 122 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Adrian L. Harris
Keyword(s):  
Metabolic Pathways ◽  
Trial Design ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Therapeutic Approaches ◽  
Preclinical Models ◽  
Wide Range ◽  
Patient Studies

AbstractCancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and clinical studies. What emerges are the large differences between tissues, tumour types and intratumour heterogeneity. However, synergies with inhibition of metabolic pathways have been found for many drugs and therapeutic approaches, and a critical role of window studies and translational trial design is key to success.

scholarly journals Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation

2019 ◽  
Vol 59 (1) ◽  
pp. 237-261 ◽  
Author(s):  
Miguel Moutinho ◽  
Juan F. Codocedo ◽  
Shweta S. Puntambekar ◽  
Gary E. Landreth
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Nuclear Receptors ◽  
Motor Impairment ◽  
Therapeutic Approaches ◽  
New Findings ◽  
Wide Range ◽  
Preclinical And Clinical Studies ◽  
Lost In Translation

Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases.

scholarly journals Personalized Dentistry: Approaching a New Way for Diagnosis and Treatment of Oral Diseases

2020 ◽  
Vol 10 (2) ◽  
pp. 35
Author(s):  
Romeo Patini
Keyword(s):  
In Vivo Studies ◽  
Oral Microbiota ◽  
Oral Diseases ◽  
Therapeutic Approaches ◽  
Bacterial Populations ◽  
Treatment Techniques ◽  
Wide Range ◽  
Analysis Of Results

For years, it has been thought that the field of dentistry was referring exclusively to some diseases that strictly affect the oral cavity. Dental caries, periodontal disease, and pathologies associated with their worsening were considered almost the only interest in scientific research in dentistry. Recent studies have begun to shed light on the effect of the oral microbiota on general health and on the crucial role of dentistry in its maintenance. In this way, we came to understand that the bacterial populations that make up the oral microbiota can vary profoundly between individuals and that contribute in a fundamental way to outlining the so-called “oral signature”. This characteristic is called into question to evaluate the susceptibility, or lack thereof, of the subject to the contraction of a wide range of pathologies, apparently not connected with oral health. From this evidence, it will also be possible to study therapeutic approaches aimed at the eradication of species considered at risk or colonization with species considered protective; thus, giving life to so-called “personalized dentistry”. Therefore, this Special Issue is aimed at spreading the scientific knowledge over the current limits in terms of new molecular and culturomic approaches towards the diagnosis of oral microbiota and the treatment techniques of eventually associated systemic diseases. In vivo studies and systematic literature reviews with quantitative analysis of results, when possible, will be given a high priority.

scholarly journals Lessons from Cancer Immunoediting in Cutaneous Melanoma

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mariana Aris ◽  
María Marcela Barrio ◽  
José Mordoh
Keyword(s):  
Cutaneous Melanoma ◽  
Tumor Stage ◽  
Experimental Models ◽  
Tumor Evolution ◽  
Special Focus ◽  
Therapeutic Approaches ◽  
Cancer Immunoediting ◽  
Future Challenges ◽  
Continuous Feedback

We will revisit the dual role of the immune system in controlling and enabling tumor progression, known ascancer immunoediting. We will go through the different phases of this phenomenon, exposing the most relevant evidences obtained from experimental models and human clinical data, with special focus on Cutaneous Melanoma, an immunogenic tumorper excellence. We will describe the different immunotherapeutic strategies employed and consider current models accounting for tumor heterogeneity. And finally, we will propose a rational discussion of the progress made and the future challenges in the therapeutics of Cutaneous Melanoma, taking into consideration that tumor evolution is the resulting from a continuous feedback between tumor cells and their environment, and that different combinatorial therapeutic approaches can be implemented according to the tumor stage.

scholarly journals The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas

2014 ◽  
Vol 21 (4) ◽  
pp. R331-R344 ◽  
Author(s):  
Eric Monsalves ◽  
Kyle Juraschka ◽  
Toru Tateno ◽  
Sameer Agnihotri ◽  
Sylvia L Asa ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Human Cancer ◽  
Tumor Biology ◽  
Pituitary Tumors ◽  
Mass Effect ◽  
Therapeutic Approaches ◽  
Hormone Production ◽  
New Therapeutic Approaches ◽  
Wide Range

Pituitary adenomas are common intracranial neoplasms. Patients with these tumors exhibit a wide range of clinically challenging problems, stemming either from results of sellar mass effect in pituitary macroadenoma or the diverse effects of aberrant hormone production by adenoma cells. While some patients are cured/controlled by surgical resection and/or medical therapy, a proportion of patients exhibit tumors that are refractory to current modalities. New therapeutic approaches are needed for these patients. Activation of the AKT/phophotidylinositide-3-kinase pathway, including mTOR activation, is common in human neoplasia, and a number of therapeutic approaches are being employed to neutralize activation of this pathway in human cancer. This review examines the role of this pathway in pituitary tumors with respect to tumor biology and its potential role as a therapeutic target.

scholarly journals Regulation of Blood and Lymphatic Vessels by Immune Cells in Tumors and Metastasis

2019 ◽  
Vol 81 (1) ◽  
pp. 535-560 ◽  
Author(s):  
Massimiliano Mazzone ◽  
Gabriele Bergers
Keyword(s):  
Immune Cells ◽  
Lymphatic Vessels ◽  
Tumor Vasculature ◽  
Therapeutic Approaches ◽  
Cancer Hallmarks ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Vessel Growth ◽  
Lymphatic Vasculature

Research over the last decades has provided strong evidence for the pivotal role of the tumor-associated blood and lymphatic vasculature in supporting immunoevasion and in subverting T cell–mediated immunosurveillance. Conversely, tumor blood and lymphatic vessel growth is in part regulated by the immune system, with infiltrating innate as well as adaptive immune cells providing both immunosuppressive and various angiogenic signals. Thus, tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and interregulated by cell constituents from compartments secreting both chemokines and cytokines. In this review, we discuss the implication and regulation of innate and adaptive immune cells in regulating blood and lymphatic angiogenesis in tumor progression and metastases. Moreover, we also highlight novel therapeutic approaches that target the tumor vasculature as well as the immune compartment to sustain and improve therapeutic efficacy in cancer.

Superconductivities and structure modulations in Tl-Ba-Ca-Cu-O oxides

1989 ◽  
Vol 47 ◽  
pp. 170-171
Author(s):  
Sumio Iijima
Keyword(s):  
Charge Carrier ◽  
Crystal Structures ◽  
Growth Conditions ◽  
Structural Defects ◽  
High Tc ◽  
Wide Range ◽  
Axis Length ◽  
Oxide Crystals ◽  
Sintering Method

Charge carrier sources for the superconductivities of high Tc oxides have been sought by various techniques. The role of lattice defects in the superconductivity, and structural defects which are common in these oxides, were investigated by electron microscopists. In this paper, microstructures on TBCCO oxide crystals, in particular, superlattice modulations in the 2201 phase, and Y-doped 2212 phases which are prepared under various growth conditions, are presented. All specimens were prepared in the standard sintering method.In contrast with the 2212 and 2223 compounds, the 2201 compounds showed a wide range of Tc values. Their variations were found to be strongly affected by oxygen content.This was concluded from the fact that the nonsuperconductive specimen became conductive by quenching after heating in O2 atmosphere at 400°C. This was further confirmed when the superconductivity vanished by annealing. It was also demonstrated that crystal symmetries of the compounds, orthorhombic and tetragona1 are not directly related to the superconductivity as was proposed by Hewat et al. The orthorhombic structures are obtained at preparation temperatures above 840°C. It was also found that the Tc value increases linearly with an increase in the c-axis length which is independent of crystal structures.

scholarly journals A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1842 ◽  
Author(s):  
Jürgen Geisler ◽  
Joel Touma ◽  
Afsar Rahbar ◽  
Cecilia Söderberg-Nauclér ◽  
Katja Vetvik
Keyword(s):  
Breast Cancer ◽  
Human Cytomegalovirus ◽  
Triple Negative ◽  
Breast Tumors ◽  
Active Role ◽  
Gene Products ◽  
Breast Cancers ◽  
Wide Range

Previously recognized classical human onco-viruses can regulate complex neoplastic events, and are estimated to play a role during carcinogenesis in 15–20% of cancer cases. Although the DNA and gene products of several viruses have been found in breast tumors, none of the classical onco-viruses have definitely been linked to the initiation of breast cancer. However, recent evidence shows that human cytomegalovirus (HCMV) gene products are found in >90% of tumors and metastases of breast cancers, and their increased expression can be correlated to a more aggressive breast cancer phenotype. Supporting the active role of HCMV in breast cancer, a specific HCMV strain, HCMV-DB, was recently shown to exert oncogenic transformational activity in breast epithelial cells in vitro, and to give rise to fast-growing, triple-negative breast tumors when injected into immune deficient mice. The same observation holds true for clinical studies implying increased HCMV protein expression in triple negative breast cancer biopsies. In addition to functionally being able to hijack tumor-promoting cellular events, HCMV is known to exhibit a wide range of immunosuppressive effects, which can have radical impact on the tumor microenvironment. HCMV infected cells can avoid recognition and elimination by the immune system by orchestrating polarization of immunosuppressive type II macrophages, preventing antigen presentation, by expressing T cell inhibitory molecules, and possibly, by the induction of regulatory T (Treg) cell responses. These actions would be especially deleterious for the antigenic activation and proliferation of tumor specific CD8+ cytotoxic T lymphocytes (CTLs), whose effector functions have recently been targeted by successful, experimental immunotherapy protocols. The recognition of alternative causes and drivers of breast cancer is a pivotal research topic for the development of diagnostics and novel, effective preventive and therapeutic strategies targeting both tumor cells and their microenvironments.

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