scholarly journals Matriptase-2 Inhibits Breast Tumor Growth and Invasion and Correlates with Favorable Prognosis for Breast Cancer Patients

2007 ◽  
Vol 13 (12) ◽  
pp. 3568-3576 ◽  
Author(s):  
Christian Parr ◽  
Andrew J. Sanders ◽  
Gaynor Davies ◽  
Tracey Martin ◽  
Jane Lane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Breast Tumor ◽  
Breast Cancer Patients ◽  
Favorable Prognosis ◽  
Tumor Growth And Invasion

scholarly journals Investigating New Therapeutic Strategies Targeting Hyperinsulinemia's Mitogenic Effects in a Female Mouse Breast Cancer Model

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1701-1710 ◽  
Author(s):  
Ran Rostoker ◽  
Keren Bitton-Worms ◽  
Avishay Caspi ◽  
Zila Shen-Orr ◽  
Derek LeRoith
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Breast Tumor ◽  
Experimental Studies ◽  
Tumor Development ◽  
Treated Group ◽  
Tumor Growth Rate ◽  
Breast Cancer Patients ◽  
Mitogenic Effect

Abstract Epidemiological and experimental studies have identified hyperinsulinemia as an important risk factor for breast cancer induction and for the poor prognosis in breast cancer patients with obesity and type 2 diabetes. Recently it was demonstrated that both the insulin receptor (IR) and the IGF-IR mediate hyperinsulinemia's mitogenic effect in several breast cancer models. Although IGF-IR has been intensively investigated, and anti-IGF-IR therapies are now in advanced clinical trials, the role of the IR in mediating hyperinsulinemia's mitogenic effect remains to be clarified. Here we aimed to explore the potential of IR inhibition compared to dual IR/IGF-IR blockade on breast tumor growth. To initiate breast tumors, we inoculated the mammary carcinoma Mvt-1 cell line into the inguinal mammary fat pad of the hyperinsulinemic MKR female mice, and to study the role of IR, we treated the mice bearing tumors with the recently reported high-affinity IR antagonist-S961, in addition to the well-documented IGF-IR inhibitor picropodophyllin (PPP). Although reducing IR activation, with resultant severe hyperglycemia and hyperinsulinemia, S961-treated mice had significantly larger tumors compared to the vehicle-treated group. This effect maybe secondary to the severe hyperinsulinemia mediated via the IGF-1 receptor. In contrast, PPP by partially inhibiting both IR and IGF-IR activity reduced tumor growth rate with only mild metabolic consequences. We conclude that targeting (even partially) both IR and IGF-IRs impairs hyperinsulinemia's effects in breast tumor development while simultaneously sparing the metabolic abnormalities observed when targeting IR alone with virtual complete inhibition.

Micropallet Technology for Investigating Tumor Cellular Profiles and Analysis of Rare Cell Subsets

2008 ◽  
Author(s):  
Nicholas M. Gunn ◽  
Mark Bachman ◽  
Edward L. Nelson ◽  
G.-P. Li
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Breast Tumor ◽  
The United States ◽  
Therapeutic Strategies ◽  
Cellular Heterogeneity ◽  
Breast Cancer Patients ◽  
Critical Limits

Rationally designed, individualized therapeutic strategies have long been a desired objective for breast cancer patients and clinicians as an estimated 178,480 new cases of invasive breast cancer will be diagnosed among women in the United States this year and over 40,000 women are expected to die from the disease. [1] The increasing appreciation of breast tumor cellular heterogeneity raises fundamental questions as to the relative contributions of cellular subsets to the biologic behavior of an individual patient’s tumor. [2] As such, it has become increasingly clear that in many cases, an individualized strategy for the treatment of breast cancer would be of great benefit, and that the ability to isolate relevant cellular subsets from the main tumor population is one of the critical limits to accomplishing this goal.

Involvement of NK cell molecular signatures in favorable prognosis of breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10565-10565
Author(s):  
Maria Libera Ascierto ◽  
Michael O Idowu ◽  
Yingdong Zhao ◽  
Davide Bedognetti ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Cancer Patients ◽  
Adhesion Molecules ◽  
Nk Cell ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Favorable Prognosis ◽  
Activating Receptors

10565 Background: Tumor cell recognition by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with their ligands expressed on tumor cells. In addition, NK cells express adhesion molecules that facilitate formation of the immunological synapse with the tumor targets. Here, we investigated whether the coordinate expression of NK activating receptors and adhesion molecules could provide a signature to segregate breast cancer patients into relapse and relapse-free outcomes. Methods: Gene expression profiling, RT-PCR screening and survival analysis were performed on RNA extracted from primary breast cancers. Tumors were obtained from patients experiencing either 5-8 years relapse-free survival or tumor relapse within 1-3 years following initial treatment. Results: Tumors from patients with a favorable prognosis were characterized by increased expression of genes involved in NK cell interaction with tumor cells and its activation signaling. In particular, up-regulation of Natural Cytotoxicity Receptors (NCRs), leukocyte function-associated antigen 1 (LFA-1), CD226 (DNAM-1) and CD96 was observed in relapse-free patients. Thus, the expression of the NK activating receptors and relevant adhesion molecules involved in NK cell:target interactions can predict relapse free survival in breast cancer patients. Conclusions: Results from the present study, highlighted the effector cooperation between the innate and adaptive immune components within the tumor microenvironment. The NK cells parameters identified in this study, together with the prognostic B and T cell signatures previously reported by us, represent a powerful tool for predicting breast cancer outcome which might be easily introduced in clinical practice.

scholarly journals Clinical value of peripheral blood M2/M1 like monocyte ratio in the diagnosis of breast cancer and the differentiation between benign and malignant breast tumors

2019 ◽  
Author(s):  
Mustafa Fadhil ◽  
Omar Abdul- Rasheed ◽  
Manwar Al-Naqqash
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Breast Tumor ◽  
Healthy Subjects ◽  
Breast Tumors ◽  
Breast Cancer Patients ◽  
Cancer Tumor ◽  
Malignant Breast

Background: During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. In response to multiple microenvironmental signals from the tumor and stromal cells, macrophages change their functional phenotypes. Based on their function, macrophages are commonly classified into both, classical M1 and alternative M2 macrophages. M2-like tumor-associated macrophages promote breast tumor growth and survival, and may migrate into the peripheral blood. However, the level of circulating M2/M1-like monocyte ratio in the peripheral blood of breast cancer patients has not been yet clarified. Aim: To compare peripheral blood M2/M1 monocyte ratio among breast cancer patients, benign breast tumor patients and healthy subjects. Also, to investigate the role of peripheral blood M2/M1 monocyte ratio as a circulating breast cancer tumor marker and to asses the validity of this marker in differentiation between benign and malignant breast tumors. Methods: Flow cytometry technique was used to determine the peripheral blood M2/M1 monocyte ratio in three groups of subjects, i.e. 45 patients with breast cancer, 40 patients with benign breast tumor, and 40 healthy subjects as a control group. The results of carbohydrate antigen15-3 (CA15-3) determination were analyzed comparatively. Results: The peripheral blood M2/M1 monocyte ratio in patients with breast cancer (0.27±0.1) was significantly higher (P<0.001) than that in healthy subjects (0.07±0.05) and than in benign tumor subjects (0.08±0.04). The area under the receiver operating characteristic (ROC) curve of peripheral blood M2/M1 monocyte ratio determination was significantly higher (P≤0.001) than that of CA15-3 levels. Conclusion: M2/M1-like monocyte ratio is of a high diagnostic value for breast cancer and is a promising differentiating marker between benign and breast cancer tumor groups.

EXTH-02. AAV MEDIATED BRAIN DELIVERY OF AN ADCC-ENHANCED ANTIBODY OBVIATES XENOGRAFT GROWTH IN MOUSE MODELS OF HER2+ BREAST CANCER BRAIN METASTASIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi163-vi163
Author(s):  
Dan Laks ◽  
Kenny Chen ◽  
Xiaoqin Ren ◽  
Ishan Shah ◽  
Usman Hameedi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Aav Vector ◽  
Orthotopic Xenograft ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis

Abstract BACKGROUND HER2+ tumors constitute approximately 20% of breast cancer patients and are characterized by overexpression of the growth factor receptor HER2 (ERBB2), a cell proliferation driver. Effective anti-HER2 therapies confer prolonged patient survival necessitating the need for transformative treatments targeting brain metastases, a major cause of mortality in ~30-50% of HER2+ metastatic breast cancer patients. HER2-directed antibody immunotherapy, while efficacious for peripheral disease, has limited central nervous system exposure (CNS). To overcome these challenges, we transduced CNS cells with a novel AAV vector carrying an anti-HER2 antibody payload. METHODS We assessed the biochemical equivalence and functional effectiveness of AAV vector-encoded antibodies using in vitro assays. After selecting promising vector-encoded antibody candidates, a novel, blood-brain barrier penetrant AAV capsid was administered via i.v. dosing to an orthotopic xenograft mouse model of HER2+ brain metastases. Bioluminescent imaging provided a longitudinal measure of brain tumor burden. At study termination, we measured antibody biodistribution in cerebrospinal fluid (CSF), serum, and brain homogenates with AlphaLISA assays. RESULTS Using HER2+ breast cancer cell lines, we determined that an antibody-dependent cell cytotoxicity (ADCC) enhanced anti-HER2 antibody was most effective and demonstrated that AAV-vector encoded forms of the antibody performed comparably to recombinant reference antibodies. Following i.v. administration of a HER2 antibody encoding AAV vector, we measured &gt;1 ug/mL of the antibody in CSF. Importantly, AAV-mediated expression of the ADCC-enhanced HER2-directed antibody significantly abrogated tumor growth in orthotopic xenograft models. CONCLUSIONS Peripheral administration of an AAV vector was able to transduce brain tissue such that efficacious levels of HER2-directed antibodies were produced. This strategy was successful at preventing tumor growth in our physiologically relevant model of breast cancer brain metastases. Such a treatment modality should be further evaluated in patient derived PDX models to validate translational efficacy for human patients.

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