scholarly journals Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Author(s):  
Xiangdong Lv ◽  
Lacey E. Dobrolecki ◽  
Yao Ding ◽  
Jeffrey M. Rosen ◽  
Michael T. Lewis ◽  
...  
2020 ◽  
pp. 25-31
Author(s):  
M. L. Mazo ◽  
O. E. Jacobs ◽  
O. S. Puchkova ◽  
M. V. Feldsherov ◽  
E. V. Kondratyev

The rate of detection of breast cancer by MRI, while other methods of radiological diagnosis are not sufficiently informative, ranges from 5.2 to 26.3 per cent. Suspicious breast tumors of category BI-RADS 4, 5 show morphological image-guided biopsy verification, in particular MRI with contrast. Purpose. To show the possibilities and features of carrying out MRI-guided vacuum breast biopsy, including after aesthetic breast augmentation. Material and methods. A comprehensive X-ray, ultrasound and MRI examination of 54 women aged between 28 and 70 years with different breast tumors was conducted. Of these, five were detected only by breast MRI with contrast, and were morphologically verified by MRI-guided vacuum aspiration biopsy. Results. 14 of the 54 patients with breast mass were diagnosed with breast cancer and 26 were diagnosed with benign diseases. The effectiveness of comprehensive examination and low-invasive high-tech MRI-guided procedures in early refined screening for breast cancer, including after aesthetic breast augmentation, has been demonstrated. MRI-guided vacuum-assisted breast biopsy is a fast, safe and accurate diagnostic method of morphological verification of suspicious breast tumors that do not have X-ray and ultrasound.


2021 ◽  
Vol 22 (2) ◽  
pp. 477
Author(s):  
Guendalina Froechlich ◽  
Chiara Gentile ◽  
Luigia Infante ◽  
Carmen Caiazza ◽  
Pasqualina Pagano ◽  
...  

Background: HER2-based retargeted viruses are in advanced phases of preclinical development of breast cancer models. Mesothelin (MSLN) is a cell-surface tumor antigen expressed in different subtypes of breast and non-breast cancer. Its recent identification as a marker of some triple-negative breast tumors renders it an attractive target, presently investigated in clinical trials employing antibody drug conjugates and CAR-T cells. The availability of MSLN-retargeted oncolytic viruses may complement the current immunotherapeutic panel of biological drugs against HER2-negative breast and non-breast tumors. Methods: A fully virulent, tumor-targeted oncolytic Herpes simplex virus-1 (MSLN-THV) with a selectivity for mesothelin-expressing cancer cells was generated. Recombineering technology was used to replace an essential moiety of the viral glycoprotein D with antibody fragments derived from clinically validated MSLN monoclonal antibodies, and to allow IL12 cargo expression in infected cells. Panels of breast and female reproductive system cell lines were used to verify the oncolytic potential of the viral constructs. A platform for production of the retargeted viruses was developed in HEK 293 cells, providing stable expression of a suitable chimeric receptor. Results: We demonstrated the selectivity of viral infection and cytotoxicity by MSLN-retargeted viruses in a panel of mesothelin-positive cancer cells, originating from breast and female reproductive system tumors. We also developed a second-generation oncolytic MSLN-THV, encoding IL12, to enhance the immunotherapeutic potential of the viral backbone. A non-tumor cell line expressing a chimeric MSLN/Nectin-1 receptor, de-sensitized from antiviral responses by genetic inactivation of the Stimulator of Interferon Genes (STING)-dependent pathway was engineered, to optimize viral yields. Conclusions: Our proof-of-concept study proposes MSLN-retargeted herpesviruses as potential cancer immunotherapeutics for assessments in preclinical models of MSLN-positive tumors, complementing the available panel of oncolytic viruses to HER2-negative breast tumors.


2012 ◽  
Vol 18 (9) ◽  
pp. 2603-2612 ◽  
Author(s):  
Celina García-García ◽  
Yasir H. Ibrahim ◽  
Violeta Serra ◽  
Maria Teresa Calvo ◽  
Marta Guzmán ◽  
...  

2014 ◽  
pp. n/a-n/a ◽  
Author(s):  
Miljana Tanic ◽  
Kira Yanowski ◽  
Gonzalo Gómez-López ◽  
María Socorro Rodriguez-Pinilla ◽  
Iván Marquez-Rodas ◽  
...  

2011 ◽  
Vol 17 (2) ◽  
pp. 218-219 ◽  
Author(s):  
Saeed Reza Ghaffari ◽  
Tayebeh Sabokbar ◽  
Zahra Meshkat ◽  
Forouzandeh Fereidooni ◽  
Jila Dastan ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12557-e12557
Author(s):  
Zachary Spigelman ◽  
Jo-Ellen Murphy

e12557 Background: Biologic lateralization broadly impacts breast cancer. Malignancies originating in the left breast compared to the right breast tend to be more frequent, larger and of poorer prognosis. Left breast tumors respond differently to HER2-neu signaling and have lateralized Ki67 expression. In a prior study a right-left asymmetry in the neutrophil/lymphocyte ratio (NLR) of breast cancers was identified (ASCO 2018, e13094). As a follow-up, retrospective analysis of results from comprehensive genomic profiling (CGP) of right and left side breast cancer specimens was performed to determine a potential genomic etiology for the observed NLR lateralization. Methods: Tumors from 43 consecutive breast cancer patients underwent analysis for all classes of genomic alterations by hybrid capture-based CGP (Foundation Medicine). The CGP results from the 25 left- and 18 right-sided breast cancer samples were analyzed along with the histologic grade and status of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Results: In this cohort of advanced breast cancer patients (stage 3-4), no statistically significant differences in lateralization were identified based on patient age, tumor stage, or frequency of ER or Her2 expression (Table). A predominance of PR positivity (p=0.14 chi square analysis) and amplifications in the ERBB2 (p=0.37) and RAD21 (p=0.08) genes were detected in right side tumors. Conclusions: Together with the prior study, trends in asymmetry based on genomic, pathologic, and immunohistologic differences have been detected in breast cancers, including an increased incidence of ERBB2 and RAD21 amplification in right-side breast tumors in this cohort. The predominance of lower PR positivity in the left breast tumors may be due to preferential hypermethylation, consistent with reports that it mediates biologic lateralization changes, downregulates PR expression, and alters amplification rates. Epigenetic methylation, may contribute to asymmetric breast cancer biology and have implications for therapeutic strategy. Further study is warranted.[Table: see text]


2003 ◽  
Vol 89 (06) ◽  
pp. 1081-1088 ◽  
Author(s):  
Maroulio Talieri ◽  
Eleftherios Diamandis ◽  
Nikos Katsaros ◽  
Dimitrios Gourgiotis ◽  
Andreas Scorilas

SummaryApoptosis, a normal physiological form of cell death, is critically involved in the regulation of cellular homeostasis. If the delicate balance between cell death and cell proliferation is altered by a defect in the normal regulation of apoptosis signaling, a cell population is able to survive and accumulate, thereby favoring the acquisition of further genetic alterations and promoting tumorigenesis. Dysregulation of programmed cell death mechanisms plays an important role in the pathogenesis and progression of breast cancer, as well as in the responses of tumors to therapeutic intervention. Overexpression of anti-apoptotic members of the Bcl-2 family such as Bcl-2 and Bcl-XL has been implicated in cancer chemoresistance, whereas high levels of pro-apoptotic proteins such as Bax promote apoptosis and sensitize tumor cells to various anticancer therapies. Recently, a new member of the Bcl-2 family, BCL2L12, was cloned. The BCL2L12 gene is constitutively expressed in many tissues, suggesting that the encoded protein serves an important function in different cell types. In the present study, the expression of BCL2L12 gene was analyzed by reverse transcription-PCR (PT-PCR) in 70 breast cancer tissues. Our results indicate that BCL2L12 positive breast tumors are mainly of lower stage (I/II) or grade (I/II) (p=0.02 or p=0.04 respectively). Cox regression analysis revealed that BCL2L12 expression is positively related to disease-free (DFS) and overall survival (OS) at both univariate and multivariate analysis (p=0.021, p=0.029, p=0.032, p=0.044 respectively). Kaplan-Meier survival curves also demonstrated that patients with BCL2L12-positive tumors have significantly longer DFS and OS (p=0.002 and p<0.001 respectively). BCL2L12 expression may be regarded as a new independent favorable prognostic marker for breast cancer.Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.


2018 ◽  
Vol 4 (4) ◽  
pp. 40 ◽  
Author(s):  
Carolyn Klinge

Non-coding RNAs (ncRNAs) are regulators of intracellular and intercellular signaling in breast cancer. ncRNAs modulate intracellular signaling to control diverse cellular processes, including levels and activity of estrogen receptor α (ERα), proliferation, invasion, migration, apoptosis, and stemness. In addition, ncRNAs can be packaged into exosomes to provide intercellular communication by the transmission of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) to cells locally or systemically. This review provides an overview of the biogenesis and roles of ncRNAs: small nucleolar RNA (snRNA), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), miRNAs, and lncRNAs in breast cancer. Since more is known about the miRNAs and lncRNAs that are expressed in breast tumors, their established targets as oncogenic drivers and tumor suppressors will be reviewed. The focus is on miRNAs and lncRNAs identified in breast tumors, since a number of ncRNAs identified in breast cancer cells are not dysregulated in breast tumors. The identity and putative function of selected lncRNAs increased: nuclear paraspeckle assembly transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), steroid receptor RNA activator 1 (SRA1), colon cancer associated transcript 2 (CCAT2), colorectal neoplasia differentially expressed (CRNDE), myocardial infarction associated transcript (MIAT), and long intergenic non-protein coding RNA, Regulator of Reprogramming (LINC-ROR); and decreased levels of maternally-expressed 3 (MEG3) in breast tumors have been observed as well. miRNAs and lncRNAs are considered targets of therapeutic intervention in breast cancer, but further work is needed to bring the promise of regulating their activities to clinical use.


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