scholarly journals Time-Programmed Delivery of Sorafenib and Anti-CD47 Antibody via a Double-Layer-Gel Matrix for Postsurgical Treatment of Breast Cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Liping Huang ◽  
Yiyi Zhang ◽  
Yanan Li ◽  
Fanling Meng ◽  
Hongyu Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Near Infrared ◽  
Immune Escape ◽  
Regulatory Protein ◽  
In Vivo Studies ◽  
Breast Cancer Patients ◽  
Thermally Responsive ◽  
Immunosuppressive Microenvironment

AbstractThe highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients. Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising, yet greatly challenging, to reverse postoperative immunosuppression. Here, an injectable hierarchical gel matrix, composed of dual lipid gel (DLG) layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios, was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy. The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide (GO) nanoparticles. GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages (TAMs) and promote an immunogenic tumor microenvironment. The inner layer, loaded with anti-CD47 antibody (aCD47), could maintain the gel state for a much longer time, enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory protein α (SIRPα) pathway for a long-term antitumor effect. In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape, thereby boosting the systemic immune responses.

Safety and long-term maintenance of anti-HER2 immunity following booster inoculations of the E75 breast cancer vaccine.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2529-2529
Author(s):  
Raetasha Sheavette Dabney ◽  
Diane F Hale ◽  
Timothy J Vreeland ◽  
Guy T. Clifton ◽  
Alan K. Sears ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Vaccine ◽  
Peptide Vaccine ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Recurrence Rates ◽  
Specific Immunity

2529 Background: We have completed accrual and are in the follow up portion of phase I/II clinical trials evaluating the E75 HER2 peptide vaccine. E75 has been proven safe, capable of stimulating HER2 immunity, and effective in decreasing breast cancer recurrence rates. During the conduct of this trial, it was noted that E75-specific immunity waned after the Primary Vaccine Series (PVS) which corresponded with late recurrences. To maintain long-term immunity, a voluntary booster program was started. Here we present analysis of the booster inoculations. Methods: The trial enrolled node-positive or high-risk, node-negative breast cancer patients (pts) with tumors expressing any level of HER2 (IHC 1-3+). HLA-A2/A3+ pts comprised the vaccine group (VG), HLA-A2/A3- pts were followed as the control group (CG). The VG received 4-6 monthly inoculations of E75+GM-CSF. Volunteer booster program pts (BG) received inoculations every 6 months after the PVS. Pts were monitored for toxicities, in vivo responses by local reactions (LR) and DTH, and in vitro responses measured by enumeration of E75 specific cytotoxic T lymphocytes. Results: 53 pts received at least 1 booster, 34 received 2, 24 three, 20 four, 12 five, and 8 at least 6. 24% of pts had no local toxicity, 73% Grade 1 (G1), 3% G2. 74% had no systemic toxicity, 35% G1, 1% G2. LRs increased significantly from the initial vaccine (R1) during PVS to each booster (B) (R1: 59.5±3.1 v B1: 89.2±3.3, p<0.001; v B2: 95.15±5, p<0.001; v B3: 86.63±5.5, p<0.001; v B4: 83.26±4.6, p=<0.001; v B5: 80.67±6.7, p=0.006; v B6: 78.75±9.4, p=0.04). Dimer values increased from the end of PVS to each post-booster value (pre B1:1.29±0.25 v post B1: 1.46±0.38; post B2: 1.41±0.4; post B3: 1.84±0.35; post B4: 2.23±0.4; post B5:1.94±0.31; post B6: 2.73±0.09, p=0.02). At median 60 months, the recurrence rate for BG was 3.8% vs 18.9% in the CG (p=0.01). Conclusions: Booster inoculations are well-tolerated and appear to assist in the maintenance of long term peptide-specific immunity. Boosted pts have improved recurrence rates. Based on the success of this program, we have incorporated the practice of booster inoculations in our current cancer vaccine trials.

scholarly journals Rapidly liver-clearable rare-earth core–shell nanoprobe for dual-modal breast cancer imaging in the second near-infrared window

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhuxin Wei ◽  
Guangxin Duan ◽  
Baoxing Huang ◽  
Shanshan Qiu ◽  
Dandan Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rare Earth ◽  
In Vivo Imaging ◽  
Near Infrared ◽  
Preoperative Imaging ◽  
Core Shell ◽  
High Background ◽  
Earth Core

Abstract Background Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200–400 nm) and visible light (Vis, 400–650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000–1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue. Results Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core–shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What’s more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer. Conclusions The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision. Graphical abstract

Effect of Kaiso on immune signaling of breast cancer exosomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3088-3088
Author(s):  
Windy Marie Dean-Colomb ◽  
Shakir Ahmed ◽  
Balasubramanyanam Karanam ◽  
Honghe Wang ◽  
Melissa Davis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Cancer Patients ◽  
Immune Escape ◽  
European American ◽  
Breast Cancer Patients ◽  
Immune Signaling ◽  
Immune Profiling

3088 Background: Exosomes are communication vesicles that act as mediators of intracellular transfer of genetic information, an important role in intercommunication between tumor cells and immune cells. However, the mechanism underlining this cell-cell communication is not well understanding, particularly in African American breast cancer patients. Recently, our lab has demonstrated that Kaiso, a novel bi-modal transcription factor is highly expressed in African American breast cancer and notably, high Kaiso expression correlates with breast cancer aggressiveness and the disparity in survival outcomes of breast cancer patients of African American compared to European American patients. However, the differential expression and biological consequences of Kaiso in immune signaling of breast cancer exosomes has not been studied yet. Herein we demonstrate the biological role of Kaiso in immune signaling in breast cancer exosomes. Methods: In this study we utilized Nanostring immune profiling technology along with multiple in vitro and in vivo assays were used to study the role of Kaiso in breast cancer immune escape. Results: Nanostring pan cancer immune profiling demonstrated that European American breast cancer exosomes exhibited higher expression of TILs markers, T cell activation markers and CD8+T Cells markers compared to African American (p < 0.05, FDR), while we observed an increase in the expression of the anti-phagocytic molecule CD47 in breast cancer patient exosomes of African American compared to European American patients. In addition to that CD47 and SIRP-α (Signal Regulatory Protein) are highly expressed in Kaiso-scrambled MDA-MB-231 cells (sh-Scr) and exosomes, whereas THBS1, which is a regulator of CD47 expression and is regarded as angiogenesis inhibitor is significantly increased in sh-Kaiso MDA-231 cells and exosomes. Additionally, we observed that Kaiso directly binds methylated sequences in the promoter region of CD47 and THBS1 by ChIP assay. Furthermore, in vivo sh-Kaiso cells injected into athymic mice exhibited delayed tumor formation after four weeks with smaller tumor size as compared to sh-SCR cells (p < 0.05), and we observed higher expression of THBS1 with lower expression of CD47 and SIRP-α molecules by IHC and exosomes isolated from in vivo tumors (p < 0.05), indicating that Kaiso is associated with macrophage mediated immune escape. Conclusions: These findings demonstrate the important role of kaiso in immune signaling through exosomes which may be related with more aggressive cancer phenotype in breast cancer, especially in African Americans.

scholarly journals In Vivo Tumor Growth Rate Measured by US in Preoperative Period and Long Term Disease Outcome in Breast Cancer Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0144144 ◽  
Author(s):  
Tae-Kyung Yoo ◽  
Jun Won Min ◽  
Min Kyoon Kim ◽  
Eunshin Lee ◽  
Jongjin Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Rate ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Disease Outcome ◽  
Tumor Growth Rate ◽  
Preoperative Period ◽  
Breast Cancer Patients

scholarly journals Rational Designed Rapid Liver Clearance Rare-earth Core-shell Nanoprobe for Dual-Modal Breast Cancer Imaging in the Second Near-Infrared Window

2021 ◽  
Author(s):  
Zhuxin Wei ◽  
Guangxin Duan ◽  
Baoxing Huang ◽  
Shanshan Qiu ◽  
Dandan Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rare Earth ◽  
Near Infrared ◽  
Mri Contrast Agents ◽  
Preoperative Imaging ◽  
Core Shell ◽  
High Background ◽  
Earth Core

Abstract BackgroundFluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200-400 nm) and visible light (Vis, 400-650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000-1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue. ResultsHere, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core-shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What’s more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer. ConclusionsThe rational designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision.

The Force of Long-Term Mortality in Breast Cancer Patients

1998 ◽  
Vol 3 (3) ◽  
pp. 241-247
Author(s):  
Rowan T. Chlebowski ◽  
James Sayre ◽  
Linda M. Lillington
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Long Term Mortality

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

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