scholarly journals Self-Assembling RADA16-I Peptide Hydrogel Scaffold Loaded with Tamoxifen for Breast Reconstruction

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Huimin Wu ◽  
Ting Zhou ◽  
Lin Tian ◽  
Zhengchao Xia ◽  
Feng Xu
Keyword(s):  
3D Culture ◽  
Fat Absorption ◽  
Breast Cancer Patients ◽  
Hydrogel Scaffold ◽  
Hydrogel Scaffolds ◽  
In Vivo Experiments ◽  
Self Assembling ◽  
Apoptosis Related Protein ◽  
Mcf 7

More and more breast cancer patients prefer autologous fat tissue transfer following lumpectomy to maintain perfect female characteristics. However, the outcome was not satisfactory due to the transplanted fat absorption. In this study, we prepared two RADA16-I peptide scaffolds with and without tamoxifen. Both scaffolds were transparent, porous, and hemisphere-shaped. The hADSCs isolated from liposuction were attached to the scaffold. The growth inhibition of the hADSCs induced by TAM in 2-demensional (2D) culture was higher than that in TAM-loaded hydrogel scaffold 3D culture (P<0.05); however, the same outcomes were not observed in MCF-7 cells. Correspondingly, the apoptosis of the hADSCs induced by TAM was significantly increased in 2D culture compared to that in scaffold 3D culture (P<0.05). Yet the outcomes of the aoptosis in MCF-7 were contrary. Apoptosis-related protein Bcl-2 was involved in the process. In vivo experiments showed that both scaffolds formed a round mass after subcutaneous implantation and it retained its shape after being pressed slightly. The implantation had no effect on the weight and activity of the animals. The results suggested that TAM-loaded RADA16-I hydrogel scaffolds both provide support for hADSCs cells attachment/proliferation and retain cytotoxic effect on MCF-7 cells, which might be a promising therapeutic breast tissue following lumpectomy.

The role of circCNIH4 in the adipocyte's effects on metastasis of breast cancer cells.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13086-e13086
Author(s):  
Xiu Chen ◽  
Jinhai Tang
Keyword(s):  
Breast Cancer ◽  
Wound Healing ◽  
Cell Invasion ◽  
Invasion And Migration ◽  
Non Invasive ◽  
In Vivo Experiments ◽  
And Migration ◽  
Mcf 7

e13086 Background: Obesity is associated with the risk of breast cancer(BCa) incidence and development. However, biological changes in obesity BCa individuals are still uncertain. Nowadays, circCNIH4, one of novel non-coding RNAs, was found to be a non-invasive biomarker in cancers. Methods: We verified the cancer-promoting role of obesity in BCa patients by comparing BMI indexes of 33 BCa and 44 benign tumor patients. Then we cocultured viscera adipose cells(HPA-v) and BCa cells(MCF-7/H and MDA-MB-231/H) to confirm the function of adipocytes on metastasis of BCa cells through wound healing, transwell assays. In vivo experiments were also performed. We analyzed the expression level of circCNIH4 in MCF-7/H, MDA-MB-231/H and different subtypes of BCa cells by quantitative polymerase chain reaction. Simultaneously, we identified inhibited effects of circCNIH4 on metastasis of BCa cells by wound healing, transwell assays and verified the location of circCNIH4 by FISH. Luciferase Assay was used to detect harbored miRNA. Rescue experiments were then applied. Results: We found the BMI of BCa patients(24.37±2.51) was much higher than benign patients(22.97±2.91). Metastasis of BCa cells were obviously promoted after in vitro and in vivo experiments. Then we found the expression of circCNIH4 in MCF-7/H and MDA-MB-231/H were down-regulated 0.71 and 0.52 than that in MCF-7 and MDA-MB-231. Also, circCNIH4 was positively correlated with less aggressive types of BCa cells. Overexpression of circCNIH4 in MDA-MB-231 could suppress cell invasion and migration, while silencing of it in MCF-7 promoted cell invasion and migration. The FISH assay demonstrated that circCNIH4 mainly located in the cytoplasm and might function as a “sponge” for miRNA. MiR-135b functioned as a tumor promoter gene from data of 93 BCa patients (HR = 2.27; 1.01 − 5.12), and it could be captured by circCNIH4 via luciferase and rescued assays. Conclusions: In this study, we revealed that BMI or viscera adipocytes could deteriorate prognosis of BCa and circCNIH4 could be a novel biomarker for non-invasive BCa. In details, circCNIH4 mainly suppressed the adipocyte's pro-metastasis effects on BCa by capturing miR-135b.

scholarly journals 3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Yu Wu ◽  
Tangzhao Liang ◽  
Ying Hu ◽  
Shihai Jiang ◽  
Yuansen Luo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Umbilical Vein ◽  
3D Bioprinting ◽  
Severe Burn ◽  
Burn Wound ◽  
Hydrogel Scaffold ◽  
Hydrogel Scaffolds ◽  
Burn Wound Healing ◽  
Severe Burns

Abstract Severe burns are challenging to heal and result in significant death throughout the world. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising treatment for full-thickness burn healing but are impeded by their low viability and efficiency after grafting in vivo. Nitric oxide (NO) is beneficial in promoting stem cell bioactivity, but whether it can function effectively in vivo is still largely unknown. In this study, we bioprinted an efficient biological scaffold loaded with ADSCs and NO (3D-ADSCs/NO) to evaluate its biological efficacy in promoting severe burn wound healing. The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting. Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs). Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition. Notably, immunohistochemistry of CD31 suggested an increase in neovascularization, supported by the upregulation of vascular endothelial growth factor (VEGF) mRNA in ADSCs in the 3D biosystem. These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway. This scaffold may be considered a promising strategy for healing severe burns.

scholarly journals In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2255 ◽  
Author(s):  
Abd El-Galil E. Amr ◽  
Alhussein A. Ibrahimd ◽  
Mohamed F. El-Shehry ◽  
Hanaa M. Hosni ◽  
Ahmed A. Fayed ◽  
...  
Keyword(s):  
Chloroacetic Acid ◽  
Aromatic Aldehydes ◽  
Mercaptoacetic Acid ◽  
Inhibitory Effects ◽  
In Vivo Experiments ◽  
Schiff Base Derivatives ◽  
Anti Cancer ◽  
Mcf 7

In this study, some of new thiophenyl thienopyrimidinone derivatives 2–15 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cyclization of ethyl ester derivative 1 with formamide. Treatment of 2 with ethyl- chloroacetate gave thienopyrimidinone N-ethylacetate 3, which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide 4 and benzo[d][1,3]oxazin-4-one 5, respectively. Condensation of 4 with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives 6,7, and thiosemicarbazise 10, which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones 8, 9, and phenylimino-thiazolidinone 11, respectively. Treatment of 4 with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole 12 and acetyl acetohydrazide 13 derivatives, respectively. The latter compound 13 was reacted with ethyl cycno-acetate or malononitrile to give 14 and 15, respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8th day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities.

scholarly journals SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer

Oncogene ◽  
2020 ◽  
Vol 39 (49) ◽  
pp. 7166-7180
Author(s):  
Hao Chen ◽  
Sarah Libring ◽  
Kasi Viswanatharaju Ruddraraju ◽  
Jinmin Miao ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitor ◽  
Therapeutic Potential ◽  
Tyrosine Phosphatase ◽  
3D Culture ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Growth And Survival

AbstractMetastatic breast cancer (MBC) is an extremely recalcitrant disease capable of bypassing current targeted therapies via engagement of several growth promoting pathways. SH2 containing protein tyrosine phosphatase-2 (SHP2) is an oncogenic phosphatase known to facilitate growth and survival signaling downstream of numerous receptor inputs. Herein, we used inducible genetic depletion and two distinct pharmacological inhibitors to investigate the therapeutic potential of targeting SHP2 in MBC. Cells that acquired resistance to the ErbB kinase inhibitor, neratinib, displayed increased phosphorylation of SHP2 at the Y542 activation site. In addition, higher levels of SHP2 phosphorylation, but not expression, were associated with decreased survival of breast cancer patients. Pharmacological inhibition of SHP2 activity blocked ERK1/2 and AKT signaling generated from exogenous stimulation with FGF2, PDGF, and hGF and readily prevented MBC cell growth induced by these factors. SHP2 was also phosphorylated upon engagement of the extracellular matrix (ECM) via focal adhesion kinase. Consistent with the potential of SHP2-targeted compounds as therapeutic agents, the growth inhibitory property of SHP2 blockade was enhanced in ECM-rich 3D culture environments. In vivo blockade of SHP2 in the adjuvant setting decreased pulmonary metastasis and extended the survival of systemic tumor-bearing mice. Finally, inhibition of SHP2 in combination with FGFR-targeted kinase inhibitors synergistically blocked the growth of MBC cells. Overall, our findings support the conclusion that SHP2 constitutes a shared signaling node allowing MBC cells to simultaneously engage a diversity of growth and survival pathways, including those derived from the ECM.

Self-assembling Peptides: From Bio-inspired Materials to Bone Regeneration

2008 ◽  
Vol 87 (7) ◽  
pp. 606-616 ◽  
Author(s):  
C. E. Semino
Keyword(s):  
Bone Regeneration ◽  
Nerve Repair ◽  
Three Dimensional ◽  
3D Culture ◽  
Functional Differentiation ◽  
Therapeutic Drug ◽  
Functional Requirements ◽  
Self Assembling

In recent years, the development of new biomaterials with specifications for tissue and organ functional requirements—such as proper biological, structural, and biomechanical properties as well as designed control for biodegradation and therapeutic drug-release capacity—is the main aim of many academic and industrial programs. Hence, the concept of molecular self-assembly is the driving force for the development of new biomaterials that support the growth and functional differentiation of cells and tissues in a controlled manner. The discovery, properties, and development of self-assembling peptides to be used as three-dimensional (3D) scaffolds based on their similarity (in structure and mechanical features) to extracellular matrices are described. Self-assembling peptides can be used for in vitro applications for cell 3D culture as well as in vivo for tissue regeneration such as bone and optical nerve repair, as well as for drug delivery of mediators to improve therapy, as in the case of myocardial infarction. Finally, the use of self-assembling materials in combination with a bioengineering platform is proposed to assist functional bone regeneration in cases of larger bone defects, including exposed fractures due to trauma and spinal disorders dealing with high loadings, as well as replacement of big bone structures due to tumors.

scholarly journals Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianhui Liu ◽  
Shaoliang Zhu ◽  
Wei Tang ◽  
Qinghua Huang ◽  
Yan Mei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Line ◽  
Bioinformatic Analysis ◽  
In Vivo Experiments ◽  
Luciferase Activity Assay ◽  
Tamoxifen Resistant ◽  
Mcf 7

Abstract Background Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM. Methods Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA. Results Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM. Conclusions Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.

Update of a phase II trial of bevacizumab in combination with hormonal therapy to reverse acquired estrogen independence in metastatic breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12027-e12027
Author(s):  
C. Falkson ◽  
J. Rossman ◽  
L. Nabell ◽  
J. Carpenter ◽  
A. Forero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Hormonal Therapy ◽  
Metastatic Breast ◽  
Hormone Resistance ◽  
Breast Cancer Patients ◽  
Grade 3 ◽  
Mcf 7

e12027 Background: Metastatic breast cancer (MBC) remains the second most common cause of cancer death in women in the US. More than 80% of breast cancers are potentially hormone responsive, but resistance eventually precludes cure. Various mechanisms of acquired hormone resistance have been postulated. Our Breast Cancer SPORE showed that increased expression of VEGF caused acquired tamoxifen resistance in MCF-7 xenografts. VEGF over-expressing MCF-7 cells displayed increased tumor growth rates and estrogen independence in vivo, and reversal of VEGF over-expression in vivo returned tumors to estrogen dependent growth. Methods: We hypothesized that adding the anti-VEGF monoclonal antibody, bevacizumab, to hormonal therapy would result in reversal of acquired hormone resistance. This multi-center, open-label, single arm phase II study was designed to evaluate safety and efficacy of this combination. Primary end point was time to progression (TTP), and the secondary endpoints were response rate and toxicity. Eligible patients had MBC and had progressed on hormonal therapy after previously responding for at least 6 months.Results: We previously reported a planned interim analysis. Results of further analysis after completion of accrual will be reported here. All 27 patients were female with median age of 63 years, and all had ER and/or PR positive MBC. Patients were continued on the same hormonal therapy to which they had become refractory, and bevacizumab (15mg/kg IV every 3 weeks) was added. Treatment was stopped early in 3 patients due to a grade 3 leg ulcer, grade 3 hypertension, and grade 3 fatigue, respectively. Overall, the therapy was tolerated well, and no treatment related deaths or thromboembolic events were seen. Stable disease was documented in 18 (66%) patients. There were no complete or partial responses. Updated median TTP will be reported. Conclusions: The combination of bevacizumab plus hormonal therapy is well tolerated in patients with metastatic breast cancer. This combination may prolong the TTP with acceptable toxicity. Further investigation utilizing this combination in metastatic breast cancer are ongoing. [Table: see text]

scholarly journals Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ping-Hsiu Wu ◽  
Yasuhito Onodera ◽  
Amato J. Giaccia ◽  
Quynh-Thu Le ◽  
Shinichi Shimizu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Small Gtpase ◽  
Breast Cancer Patients ◽  
Critical Determinant ◽  
Invasive Tumor ◽  
Lysosomal Trafficking ◽  
In Vivo Experiments

Abstract Enhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits. Knockdown of Arl8b or BORC-subunits decreases lysosomal exocytosis and the invasiveness of radiation-surviving cells. Notably, high expression of ARL8B and BORC-subunit genes is significantly correlated with poor prognosis in breast cancer patients. Sp1, an ATM-regulated transcription factor, is found to increase BORC-subunit genes expression after radiation. In vivo experiments show that ablation of Arl8b decreases IR-induced invasive tumor growth and distant metastasis. These findings suggest that BORC-Arl8b-mediated lysosomal trafficking is a target for improving radiotherapy by inhibiting invasive tumor growth and metastasis.

scholarly journals Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

2021 ◽  
Author(s):  
Juan Du ◽  
Lanlan Zong ◽  
Mengmeng Li ◽  
Yonghui Qiao ◽  
Keke Yu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Human Life ◽  
Tumor Therapy ◽  
Subcutaneous Tumor ◽  
Tumor Bearing ◽  
In Vivo Experiments ◽  
Alternative Delivery ◽  
Mcf 7

Abstract Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug-resistance as a carrier to overcome MDR and improve the anti-tumor effect of paclitaxel (PTX). The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells, and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of DOX to H22 subcutaneous tumor-bearing mice. This work proves the reduction sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.

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