Experimental Breast Cancer Models: Preclinical Imaging Perspective

2020 ◽  
Vol 13 ◽  
Author(s):  
Ulku Korkmaz ◽  
Funda Ustun
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Relevant Literature ◽  
Scientific Data ◽  
Suitable Model ◽  
Breast Cancer Patients ◽  
Tumor Models ◽  
Preclinical Imaging ◽  
Advantages And Disadvantages ◽  
Cancer Models

Background : Breast cancer is the leading cause of cancer in women. 13% of breast cancer patients are at distant stage and mortality is due to metastases rather than primary disease. The unique genetic structure and natural process of breast cancer makes it a very suitable area for targeted therapies. Experimental tumor models are validated methods to examine the pathogenesis of cancer, the onset of the neoplastic process and progression. Objective: The aim of this study is to review the current literature on experimental breast cancer models and to bring a new perspective to the use of these models in teranostic preclinical studies in terms of the imaging. Methods: Searching for relevant literature from academic databases using keywords (Breast cancer, theranostic, preclinical imaging, tumor models, animal study, tailored therapy). The full text of the articles was reached and reviewed. Current scientific data has been reevaluated and compiled according to subtitles. Results and Conclusion: The development of animal models for breast cancer research has been the last century. Imaging methods used in breast cancer are used for tumor localization, quantification of tumor mass, imaging of genes and proteins, evaluation of tumor microenvironment, evaluation of tumor cell proliferation and metabolism and treatment response evaluation. Since human breast cancer is a heterogeneous group of diseases in terms of genetics and phenotype; it is not possible for a single model to adequately address all aspects of breast cancer biology. Considering that each model has advantages and disadvantages compared to each other, the most suitable model should be chosen in order to verify the thesis of the study.

scholarly journals Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

2020 ◽  
Vol 21 (5) ◽  
pp. 1671 ◽  
Author(s):  
Anna Fabisiewicz ◽  
Malgorzata Szostakowska-Rodzos ◽  
Anna J. Zaczek ◽  
Ewa A. Grzybowska
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Current Status ◽  
Molecular Profile ◽  
Breast Cancer Patients

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.

scholarly journals Neutrophil extracellular traps in breast cancer and beyond: current perspectives on NET stimuli, thrombosis and metastasis, and clinical utility for diagnosis and treatment

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Hunter T. Snoderly ◽  
Brian A. Boone ◽  
Margaret F. Bennewitz
Keyword(s):  
Breast Cancer ◽  
Clinical Utility ◽  
Neutrophil Extracellular Traps ◽  
Breast Cancer Patients ◽  
Extracellular Traps ◽  
Disease States ◽  
Cancer Breast ◽  
Cancer Models ◽  
Prognostic Implications

AbstractThe formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including cancer. Breast cancer is the most commonly diagnosed malignancy in women. In breast cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET-targeted therapies have shown success in preclinical cancer models and may prove valuable clinical targets in slowing or halting tumor progression in breast cancer patients. We will briefly outline the mechanisms by which NETs may form in the tumor microenvironment and circulation, including the crosstalk between neutrophils, tumor cells, endothelial cells, and platelets as well as the role of cancer-associated extracellular vesicles in modulating neutrophil behavior and NET extrusion. The prognostic implications of cancer-associated NETosis will be explored in addition to development of novel therapeutics aimed at targeting NET interactions to improve outcomes in patients with breast cancer.

scholarly journals Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1709
Author(s):  
Jitka Špačková ◽  
Klára Gotvaldová ◽  
Aleš Dvořák ◽  
Alexandra Urbančoková ◽  
Kateřina Pospíšilová ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 2 ◽  
Enzyme Molecules ◽  
Analytical Approaches

Mitochondrial production of 2-hydroxyglutarate (2HG) can be catalyzed by wild-type isocitrate dehydrogenase 2 (IDH2) and alcohol dehydrogenase, iron-containing 1 (ADHFE1). We investigated whether biochemical background and substrate concentration in breast cancer cells promote 2HG production. To estimate its role in 2HG production, we quantified 2HG levels and its enantiomers in breast cancer cells using analytical approaches for metabolomics. By manipulation of mitochondrial substrate fluxes using genetic and pharmacological approaches, we demonstrated the existence of active competition between 2HG producing enzymes, i.e., IDH2 and ADHFE1. Moreover, we showed that distinct fractions of IDH2 enzyme molecules operate in distinct oxido-reductive modes, providing NADPH and producing 2HG simultaneously. We have also detected 2HG release in the urine of breast cancer patients undergoing adjuvant therapy and detected a correlation with stages of breast carcinoma development. In summary, we provide a background for vital mitochondrial production of 2HG in breast cancer cells with outcomes towards cancer biology and possible future diagnosis of breast carcinoma.

scholarly journals Biological and clinical impact of imbalanced progesterone receptor isoform ratios in breast cancer

2018 ◽  
Vol 25 (12) ◽  
pp. R605-R624 ◽  
Author(s):  
Caroline A Lamb ◽  
Victoria T Fabris ◽  
Britta M Jacobsen ◽  
Alfredo Molinolo ◽  
Claudia Lanari
Keyword(s):  
Breast Cancer ◽  
Current Knowledge ◽  
Hormone Replacement ◽  
Progesterone Receptors ◽  
Experimental Models ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Cognate Receptor ◽  
Estrogen Receptor Signaling ◽  
Cancer Models

There is a consensus that progestins and thus their cognate receptor molecules, the progesterone receptors (PRs), are essential in the development of the adult mammary gland and regulators of proliferation and lactation. However, a role for natural progestins in breast carcinogenesis remains poorly understood. A hint to that possible role came from studies in which the synthetic progestin medroxyprogesterone acetate was associated with an increased breast cancer risk in women under hormone replacement therapy. However, progestins have also been used for breast cancer treatment and to inhibit the growth of several experimental breast cancer models. More recently, PRs have been shown to be regulators of estrogen receptor signaling. With all this information, the question is how can we target PR, and if so, which patients may benefit from such an approach? PRs are not single unique molecules. Two main PR isoforms have been characterized, PRA and PRB, which exert different functions and the relative abundance of one isoform with respect to the other determines the response of PR agonists and antagonists. Immunohistochemistry with standard antibodies against PR do not discriminate between isoforms. In this review, we summarize the current knowledge on the expression of both PR isoforms in mammary glands, in experimental models of breast cancer and in breast cancer patients, to better understand how the PRA/PRB ratio can be exploited therapeutically to design personalized therapeutic strategies.

scholarly journals TRIM47 activates NF-κB signaling via PKC-ε/PKD3 stabilization and contributes to endocrine therapy resistance in breast cancer

2021 ◽  
Vol 118 (35) ◽  
pp. e2100784118
Author(s):  
Kotaro Azuma ◽  
Kazuhiro Ikeda ◽  
Takashi Suzuki ◽  
Kenjiro Aogi ◽  
Kuniko Horie-Inoue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Cancer Biology ◽  
Therapy Resistance ◽  
Clinical Samples ◽  
Breast Cancer Patients ◽  
Endocrine Therapy Resistance ◽  
Mcf 7

Increasing attention has been paid to roles of tripartite motif–containing (TRIM) family proteins in cancer biology, often functioning as E3 ubiquitin ligases. In the present study, we focus on a contribution of TRIM47 to breast cancer biology, particularly to endocrine therapy resistance, which is a major clinical problem in breast cancer treatment. We performed immunohistochemical analysis of TRIM47 protein expression in 116 clinical samples of breast cancer patients with postoperative endocrine therapy using tamoxifen. Our clinicopathological study showed that higher immunoreactivity scores of TRIM47 were significantly associated with higher relapse rate of breast cancer patients (P = 0.012). As functional analyses, we manipulated TRIM47 expression in estrogen receptor–positive breast cancer cells MCF-7 and its 4-hydroxytamoxifen (OHT)-resistant derivative OHTR, which was established in a long-term culture with OHT. TRIM47 promoted both MCF-7 and OHTR cell proliferation. MCF-7 cells acquired tamoxifen resistance by overexpressing exogenous TRIM47. We found that TRIM47 enhances nuclear factor kappa-B (NF-κB) signaling, which further up-regulates TRIM47. We showed that protein kinase C epsilon (PKC-ε) and protein kinase D3 (PKD3), known as NF-κB–activating protein kinases, are directly associated with TRIM47 and stabilized in the presence of TRIM47. As an underlying mechanism, we showed TRIM47-dependent lysine 27–linked polyubiquitination of PKC-ε. These results indicate that TRIM47 facilitates breast cancer proliferation and endocrine therapy resistance by forming a ternary complex with PKC-ε and PKD3. TRIM47 and its associated kinases can be a potential diagnostic and therapeutic target for breast cancer refractory to endocrine therapy.

Off-label drug use in women with breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1016-1016
Author(s):  
W. Dean-Colomb ◽  
S. Fang ◽  
W. Smith ◽  
L. Michaud ◽  
G. N. Hortabagyi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Scientific Data ◽  
Supporting Evidence ◽  
Breast Cancer Patients ◽  
Off Label Use ◽  
Off Label ◽  
Chemotherapy Drugs ◽  
Number Of Patients ◽  
Label Use

1016 Background: Despite reports of widespread use of off-label agents in cancer treatment, little is known about the off-label use of agents in the treatment of breast cancer patients. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) - Medicare linked database to identify 2082 persons older than 65 years who were diagnosed with distant stage breast cancer between 1991 and 2002 and who were treated with chemotherapy between diagnosis and death. Off versus on-label classification was based upon FDA-approved indication in the treatment of breast cancer. We calculated the percentage of patients receiving off-label chemotherapy and used multivariate logistic regression models to estimate predictors of off-label chemotherapy use. We also evaluated the appropriateness of off-label chemotherapy drugs using DRUGDEX classifications. Results: Overall, 34.9% of patients were treated with off-label chemotherapy drugs. Of the thirty-six agents that were used to treat these patients, only 8 (22%) were FDA-approved for use in the treatment of breast cancer. Off-label use was least common in patients age 80 years and older (OR 1.93, 95% 1.35–2.76 for 80+ vs. 66–70 years) and varied by diagnosis year and geographic region. The most commonly used off-label agents were vinorelbine and gemcitabine, with 16.0% and 8.4% of patients receiving these agents, respectively. While 71% of the drugs used off-label lacked supporting evidence for their use in the treatment of breast cancer, these drugs were used in a small number of patients. Only 6.7% of patients were treated with drugs considered inappropriate for use in the treatment of breast cancer. Conclusions: Off-label chemotherapy use is widespread among patients with metastatic breast cancer. However, the majority of patients who received off-label chemotherapy received drugs with scientific data supporting such use. No significant financial relationships to disclose.

scholarly journals Cancer Vaccines, Treatment of the Future: With Emphasis on HER2-Positive Breast Cancer

2021 ◽  
Vol 22 (2) ◽  
pp. 779
Author(s):  
Sandeep Pallerla ◽  
Ata ur Rahman Mohammed Abdul ◽  
Jill Comeau ◽  
Seetharama Jois
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Cancer Vaccines ◽  
Vaccine Therapy ◽  
Current Status ◽  
Breast Cancer Patients ◽  
Therapeutic Vaccines ◽  
Advantages And Disadvantages ◽  
Her2 Breast Cancer

Breast cancer is one of the leading causes of death in women. With improvements in early-stage diagnosis and targeted therapies, there has been an improvement in the overall survival rate in breast cancer over the past decade. Despite the development of targeted therapies, tyrosine kinase inhibitors, as well as monoclonal antibodies and their toxin conjugates, all metastatic tumors develop resistance, and nearly one-third of HER2+ breast cancer patients develop resistance to all these therapies. Although antibody therapy has shown promising results in breast cancer patients, passive immunotherapy approaches have limitations and need continuous administration over a long period. Vaccine therapy introduces antigens that act on cancer cells causing prolonged activation of the immune system. In particular, cancer relapse could be avoided due to the presence of a longer period of immunological memory with an effective vaccine that can protect against various tumor antigens. Cancer vaccines are broadly classified as preventive and therapeutic. Preventive vaccines are used to ward off any future infections and therapeutic vaccines are used to treat a person with active disease. In this article, we provided details about the tumor environment, different types of vaccines, their advantages and disadvantages, and the current status of various vaccine candidates with a focus on vaccines for breast cancer. Current data indicate that therapeutic vaccines themselves have limitations in terms of efficacy and are used in combination with other chemotherapeutic or targeting agents. The majority of breast cancer vaccines are undergoing clinical trials and the next decade will see the fruitfulness of breast cancer vaccine therapy.

scholarly journals My Alma: A Digital App Supporting Metastatic Breast Cancer Patients in Greece

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 98s-98s
Author(s):  
C. Mitsi ◽  
E. Tzintziropoulou ◽  
L. Panagiotopoulou
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Scientific Data ◽  
Emotional Impact ◽  
Breast Cancer Patients ◽  
Healthy Behaviors

Background: Current research has shown that women with MBC patients feel ashamed and isolated. In Greece, “Alma Zois”, as a patient group, has made several attempts to provide support, but with a moderate success. Nevertheless, MBC patients have unmet needs that consist of better information and knowledge about MBC, better support for physical and emotional impact of MBC and better quality of life. Especially when it comes to younger women, these needs seem to be less covered. The development of a specially designed digital application (app) will cover the gap between support services and MBC patients by embracing the digital era in a country where 66% of the population uses smartphones. Aim: The development of the app aims at: 1) providing useful information about metastatic breast cancer, 2) reaching out to MBC patients, 3) improving the quality of life, 4) increasing healthy behaviors, and 5) increasing compliance. Methods: The project “My Alma App” is designed according to three major pillars: 1) Awareness, 2) Support 3) Communication. The 1st part AWARENESS includes: information about MBC. Calendar - Daily record of healthy behaviors (walking, nutrition, etc.). The 2nd part SUPPORT includes: 1) Psychological advice provided by psycho-oncologists, 2) Emotional-meter: issue the daily question “How are you feeling today?” and based on the patient's answer, the app can provide multiple suggestions/call to action. The 3rd part COMMUNICATION includes: personalized motivation, calendar with reminders of medication, therapies and events that might be of interest according to each patient's profile. Results: To achieve the best quality for the project: 1) A technical development of the app is been held, 2) The app will be tested by a group of patients as a pilot study and 3) Updates and improvements based on users feedback (metastatic breast cancer patients) and latest scientific data will be made. After the official launch, a short satisfaction survey will be addressed to every registered user. Finally, to motivate patients to use the app, a special social media campaign about the app will be launched. Conclusion: It is expected that the app will provide to MBC patients ways and methods to deal with the emotional challenges, distress and ways to improve their daily activities and their quality of life. Upon the end of the launch of the app, it is expected that a number of 500 Stage III and IV breast cancer patients will start using the app. The number of people who will download the app, the data provided by app users and the ratings and answers on “emotion-meter” during a period of time will be indexes of impact of the project to the MBC community in Greece.

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