Adenoviral Vectors Expressing Lymphotactin and Interleukin 2 or Lymphotactin and Interleukin 12 Synergize to Facilitate Tumor Regression in Murine Breast Cancer Models

1999 ◽  
Vol 10 (5) ◽  
pp. 697-709 ◽  
Author(s):  
P.C.R. Emtage ◽  
Y. Wan ◽  
M. Hitt ◽  
F.L. Graham ◽  
W.J. Muller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Regression ◽  
Interleukin 2 ◽  
Adenoviral Vectors ◽  
Interleukin 12 ◽  
Cancer Models

scholarly journals TLR4/IFNγ pathways induce tumor regression via NOS II-dependent NO and ROS production in murine breast cancer models

2015 ◽  
Vol 5 (5) ◽  
pp. e1123369 ◽  
Author(s):  
Myriam Lamrani ◽  
Nejia Sassi ◽  
Catherine Paul ◽  
Nadhir Yousfi ◽  
Jean-Luc Boucher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Regression ◽  
Ros Production ◽  
Induce Tumor Regression ◽  
Cancer Models

scholarly journals Tie2-mediated vascular remodeling by ferritin-based protein C nanoparticles confers antitumor and anti-metastatic activities

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Young Sun Choi ◽  
Hyeonha Jang ◽  
Biki Gupta ◽  
Ji-Hak Jeong ◽  
Yun Ge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Protein C ◽  
Immune Cell ◽  
Tumor Regression ◽  
Tumor Vasculature ◽  
Growth Factor Signaling ◽  
Antitumor Effects ◽  
Cancer Models

Abstract Background Conventional therapeutic approaches for tumor angiogenesis, which are primarily focused on the inhibition of active angiogenesis to starve cancerous cells, target the vascular endothelial growth factor signaling pathway. This aggravates hypoxia within the tumor core and ultimately leads to increased tumor proliferation and metastasis. To overcome this limitation, we developed nanoparticles with antiseptic activity that target tumor vascular abnormalities. Methods Ferritin-based protein C nanoparticles (PCNs), known as TFG and TFMG, were generated and tested in Lewis lung carcinoma (LLC) allograft and MMTV-PyMT spontaneous breast cancer models. Immunohistochemical analysis was performed on tumor samples to evaluate the tumor vasculature. Western blot and permeability assays were used to explore the role and mechanism of the antitumor effects of PCNs in vivo. For knocking down proteins of interest, endothelial cells were transfected with siRNAs. Statistical analysis was performed using one-way ANOVA followed by post hoc Dunnett’s multiple comparison test. Results PCNs significantly inhibited hypoxia and increased pericyte coverage, leading to the inhibition of tumor growth and metastasis, while increasing survival in LLC allograft and MMTV-PyMT spontaneous breast cancer models. The coadministration of cisplatin with PCNs induced a synergistic suppression of tumor growth by improving drug delivery as evidenced by increased blood prefusion and decreased vascular permeability. Moreover, PCNs altered the immune cell profiles within the tumor by increasing cytotoxic T cells and M1-like macrophages with antitumor activity. PCNs induced PAR-1/PAR-3 heterodimerization through EPCR occupation and PAR-1 activation, which resulted in Gα13-RhoA-mediated-Tie2 activation and stabilized vascular tight junctions via the Akt-FoxO3a signaling pathway. Conclusions Cancer treatment targeting the tumor vasculature by inducing antitumor immune responses and enhancing the delivery of a chemotherapeutic agent with PCNs resulted in tumor regression and may provide an effective therapeutic strategy.

The truncated somatostatin receptor sst5TMD4 stimulates the production of pro-angiogenic factors in in vitro and in vivo breast cancer models

2014 ◽  
Author(s):  
Raul M Luque ◽  
Mario Duran-Prado ◽  
David Rincon-Fernandez ◽  
Marta Hergueta-Redondo ◽  
Michael D Culler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Somatostatin Receptor ◽  
Angiogenic Factors ◽  
Cancer Models

scholarly journals A 3D Bioprinted Material That Recapitulates the Perivascular Bone Marrow Structure for Sustained Hematopoietic and Cancer Models

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 480
Author(s):  
Caitlyn A. Moore ◽  
Zain Siddiqui ◽  
Griffin J. Carney ◽  
Yahaira Naaldijk ◽  
Khadidiatou Guiro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Translational Medicine ◽  
Drug Response ◽  
Drug Approval ◽  
3D Models ◽  
3D Bioprinting ◽  
Effective Evaluation ◽  
Experimental Systems ◽  
Cancer Models

Translational medicine requires facile experimental systems to replicate the dynamic biological systems of diseases. Drug approval continues to lag, partly due to incongruencies in the research pipeline that traditionally involve 2D models, which could be improved with 3D models. The bone marrow (BM) poses challenges to harvest as an intact organ, making it difficult to study disease processes such as breast cancer (BC) survival in BM, and to effective evaluation of drug response in BM. Furthermore, it is a challenge to develop 3D BM structures due to its weak physical properties, and complex hierarchical structure and cellular landscape. To address this, we leveraged 3D bioprinting to create a BM structure with varied methylcellulose (M): alginate (A) ratios. We selected hydrogels containing 4% (w/v) M and 2% (w/v) A, which recapitulates rheological and ultrastructural features of the BM while maintaining stability in culture. This hydrogel sustained the culture of two key primary BM microenvironmental cells found at the perivascular region, mesenchymal stem cells and endothelial cells. More importantly, the scaffold showed evidence of cell autonomous dedifferentiation of BC cells to cancer stem cell properties. This scaffold could be the platform to create BM models for various diseases and also for drug screening.

scholarly journals A bispecific antibody agonist of the IL-2 heterodimeric receptor preferentially promotes in vivo expansion of CD8 and NK cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katherine E. Harris ◽  
Kyle J. Lorentsen ◽  
Harbani K. Malik-Chaudhry ◽  
Kaitlyn Loughlin ◽  
Harish Medlari Basappa ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Bispecific Antibody ◽  
T Regulatory Cells ◽  
Tumor Regression ◽  
Interleukin 2 ◽  
In Vivo Studies ◽  
Preferential Binding

AbstractThe use of recombinant interleukin-2 (IL-2) as a therapeutic protein has been limited by significant toxicities despite its demonstrated ability to induce durable tumor-regression in cancer patients. The adverse events and limited efficacy of IL-2 treatment are due to the preferential binding of IL-2 to cells that express the high-affinity, trimeric receptor, IL-2Rαβγ such as endothelial cells and T-regulatory cells, respectively. Here, we describe a novel bispecific heavy-chain only antibody which binds to and activates signaling through the heterodimeric IL-2Rβγ receptor complex that is expressed on resting T-cells and NK cells. By avoiding binding to IL-2Rα, this molecule circumvents the preferential T-reg activation of native IL-2, while maintaining the robust stimulatory effects on T-cells and NK-cells in vitro. In vivo studies in both mice and cynomolgus monkeys confirm the molecule’s in vivo biological activity, extended pharmacodynamics due to the Fc portion of the molecule, and enhanced safety profile. Together, these results demonstrate that the bispecific antibody is a safe and effective IL-2R agonist that harnesses the benefits of the IL-2 signaling pathway as a potential anti-cancer therapy.

scholarly journals Neratinib plus trastuzumab is superior to pertuzumab plus trastuzumab in HER2-positive breast cancer xenograft models

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jamunarani Veeraraghavan ◽  
Carolina Gutierrez ◽  
Vidyalakshmi Sethunath ◽  
Sepideh Mehravaran ◽  
Mario Giuliano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Regression ◽  
Complete Response ◽  
Estrogen Deprivation ◽  
Short Term ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Proliferative Markers ◽  
Xenograft Models ◽  
Positive Breast Cancer

AbstractLapatinib (L) plus trastuzumab (T), with endocrine therapy for estrogen receptor (ER)+ tumors, but without chemotherapy, yielded meaningful response in HER2+ breast cancer (BC) neoadjuvant trials. The irreversible/pan-HER inhibitor neratinib (N) has proven more potent than L. However, the efficacy of N+T in comparison to pertuzumab (P) + T or L + T (without chemotherapy) remains less studied. To address this, mice bearing HER2+ BT474-AZ (ER+) cell and BCM-3963 patient-derived BC xenografts were randomized to vehicle, N, T, P, N+T, or P+T, with simultaneous estrogen deprivation for BT474-AZ. Time to tumor regression/progression and incidence/time to complete response (CR) were determined. Changes in key HER pathway and proliferative markers were assessed by immunohistochemistry and western blot of short-term-treated tumors. In the BT474-AZ model, while all N, P, T, N + T, and P + T treated tumors regressed, N + T-treated tumors regressed faster than P, T, and P + T. Further, N + T was superior to N and T alone in accelerating CR. In the BCM-3963 model, which was refractory to T, P, and P + T, while N and N + T yielded 100% CR, N + T accelerated the CR compared to N. Ki67, phosphorylated (p) AKT, pS6, and pERK levels were largely inhibited by N and N + T, but not by T, P, or P + T. Phosphorylated HER receptor levels were also markedly inhibited by N and N + T, but not by P + T or L + T. Our findings establish the efficacy of combining N with T and support clinical testing to investigate the efficacy of N + T with or without chemotherapy in the neoadjuvant setting for HER2+ BC.

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