scholarly journals Smart Gold-Polymer Nanostructures As Promising Drug Nanocarriers For Dual-Imaging Modality And Synergistic Chemo-Photothermal Therapy in Breast Cancer Cells

2021 ◽  
Author(s):  
Mehdi Azizi ◽  
Asrin Pakravan ◽  
Hadi Valizadeh ◽  
Reza Rahbarghazi ◽  
Hassan Dianat-Moghadam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photothermal Therapy ◽  
Apoptotic Cell ◽  
Folate Receptor ◽  
Cancer Therapeutics ◽  
Ct Imaging ◽  
Host Cells ◽  
Control Group ◽  
Polymer Nanostructures ◽  
Dual Imaging

Abstract To improve the efficacy of cancer therapeutics, highly sensitive imaging with precise accuracy is mandatory for timely diagnosis and selection of strategic approaches. Despite recent advances in technologies associated with tumor imaging, the application of conventional single-mode imaging is the subject of debate. Herein, two types of pH-responsive gold-polymer nanostructures, GNSts and GNRs, containing CD and MTX, GNSts-MTX@CD-Pol and GNRs-MTX@CD-Pol were designed. Dual-imaging modalities (fluorescence and CT imaging) and synergistic chemo-photothermal therapy were examined in human breast cancer MDA-MB 231 cells. MTT assay showed NIR irradiation of cells pre-treated with synthesized nanoparticles promoted tumoricidal synergy via the reduction of survival rate after 48 hours in comparison with the control group (p<0.05), indicating a high absorption coefficient in the NIR area and efficient heat production rate. Flow cytometry, real-time PCR and western blot, analyses indicated an apoptotic cell death induced by the up-regulation of Caspases 3, 6, 7, 8, and 9, Bax, and Annexin-V, confirming the activation of intrinsic and extrinsic apoptosis pathways inside the host cells. The elevation of p27 and p53 in line with the increase of cell percent at the subG1 phase showed apoptotic changes and inhibition of dynamic cell growth compared to the non-treated cells (p<0.05). Evident fluorescence intensity at lower pH values (6.3) showed pH-dependent activity of nanoparticles internalized by surface folate receptor. Of note, we showed strong capability for CT imaging in cells incubated with GNSts-MTX@CD-Pol and GNRs-MTX@CD-Pol. Taken together, all data show that gold-polymer nanostructures have considerable capability in theranostic applications like simultaneous diagnostic imaging and therapy.

scholarly journals The therapeutic effects of Physalis alkekengi hydroalcoholic extract on estrogen receptor-positive breast cancer mice model: possible role of autophagy in this therapeutic response

2020 ◽  
Vol 22 (4) ◽  
pp. 181-186
Author(s):  
Zahra Zare ◽  
Maryam Teimouri
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Body Weight ◽  
Apoptotic Cell ◽  
Breast Tumors ◽  
Effective Dosage ◽  
Control Group ◽  
Specific Gene ◽  
Therapeutic Effects ◽  
Hydroalcoholic Extract

Background and aims: Although some preclinical and clinical studies have extensively confirmed the pharmacological effects of the hydroalcoholic extract (HE) of Physalis alkekengi on several diseases, little is known about the effects of P. alkekengi HE (PAHE) on breast cancer. Therefore, this study aimed to investigate the therapeutic effect of PAHE on estrogen receptor+ breast cancer. Methods: To this end, tumors were created in mice by injecting MC4L2 cells into the sternum of the mice. Then, the animals were gavaged for 16 days at 10, 50, and 100 mg/kg daily of PAHE. In addition, the tumor growth and body weight of the mice were measured on the 16th day, and they were killed on 21st day. Finally, their tumor tissues were removed and the apoptotic cell tissue and expression of the ATG-5 gene were studied as well. The experiments were repeated three times, and the data were analyzed using SPSS software (P<0.001 and P<0.05). Results: The average body weight of the control group significantly decreased 16 days after tumor establishment (P<0.001). Further, the PAHE inhibited the growth of the breast cancer tumor in higher doses (50 & 100 mg/kg, P<0.001). Based on the results, a significant histopathological alteration was found in the breast tumors of the PAHE-treated groups compared with the control group, including the decreased level of mitotic cells the intensive level of necrotic cells and lymphocyte infiltration into the breast tumors bearing mice 21 days after PAHE administration (P=0.012). Eventually, PAHE significantly increased the mRNA level of the expression of the autophagy ATG-5 specific gene in the effective dosage-treated group (50 mg/kg, P=0.037). Conclusion: The evidence suggests that the PAHE has a suitable efficacy for the treatment of ER+ breast cancer by promoting autophagy mechanisms into these tumor types

Dual-imaging assessment of ultrasonography and mammography in nipple discharge patients: A cohort study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12079-e12079
Author(s):  
Bo Li ◽  
Yihe Yang
Keyword(s):  
Breast Cancer ◽  
Clinical Judgment ◽  
Nipple Discharge ◽  
Surgical Excision ◽  
Control Group ◽  
Clinical Approach ◽  
Surgical Indications ◽  
Diagnostic Ability ◽  
Palpable Mass ◽  
Dual Imaging

e12079 Background: Nipple discharge (ND) is a common complaint of women. There is no consensus on clinical approach in these patients. We investigated the diagnostic ability of combination of ultrasound (US) and mammogram (MG) in Chinese ND patients without palpable mass. Methods: 827 patients with ND as only chief complaint presented in the First Hospital of China Medical University (Shenyang, China) between 2008 and 2015 were included. Palpable mass, physiological NP and/or elevated PRL were excluded. All patients underwent dual-imaging examinations of US and MG. Indication of surgical excision included 1) BI-RADS categories 4b, 4c, 5 in either US or MG, and/or 2) US suspected papilloma. Patients met surgical indications served as study arm (N = 742). Patients did not meet surgical indications but underwent surgery served as control arm (N = 85). Reason of surgery in the control group were patients’ choices and surgeons’ clinical judgment. Histological diagnosis provided by surgery were analyzed. In our institution, breast cancer, papilloma, and/or papilloma with atypical dysplasia were regarded as histological indication of surgery. Chi-square tests were applied. Results: Histology revealed 88 (11.9%) breast cancer in the study arm and 0 breast cancer in the control arm ( p= 0.0008); 167 (22.5%) papilloma with atypical dysplasia in the study arm and 12 (13.6%) papilloma with atypical dysplasia in the control arm ( p= 0.08); 335 (45.1%) papilloma without atypical dysplasia in the study arm and 27 (30.7%) papilloma without atypical dysplasia in the control arm ( p= 0.02). A total of 590 (79.5%) in the study arm and 39 (44.3%) in the control arm met histological indication of surgical intervention ( p< 0.00001). Conclusions: This dual-imaging assessment of US and MG is sensitive in detecting breast cancer in ND without palpable mass patients. It showed diagnostic ability in detecting papilloma with/without atypical dysplasia, but needs further improvement.

Synthesis and Characterization of Folic Acid Conjugated Gemcitabine Tethered Silver Nanoparticles (FA-GEM-AgNPs) for Targeted Delivery

2020 ◽  
Vol 26 (26) ◽  
pp. 3141-3146 ◽  
Author(s):  
Arjunan Karuppaiah ◽  
Ravikumar Rajan ◽  
Sivaram Hariharan ◽  
Dinesh K. Balasubramaniam ◽  
Marslin Gregory ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Silver Nanoparticles ◽  
Folic Acid ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Cytotoxic Effect ◽  
Apoptotic Cell ◽  
Folate Receptor ◽  
Cancer Cell Line ◽  
One Pot

Background: Silver nanoparticles (AgNPs) have attracted considerable interest in the medical industry due to their physicochemical properties, small size, and surface plasmon behavior. Their smaller particle size and instability in blood circulation leads to toxicity due to its aggregation as Ag+ ions and accumulation at the deepseated organ. In the present study, we aimed at reducing the toxicity of AgNPs by conjugation with an anticancer drug GEM and to improve their internalization through folate receptors-mediated endocytosis by capping the nanoparticles with folic acid (FA). Methods: One-pot facile synthesis of FA capped silver nanoparticles (FA-AgNPs) has been achieved by using FA as a reducing agent. FA-AgNPs were mixed with Gemcitabine (GEM) to obtain tethered FA-GEM-AgNPs. Nanoparticles were characterized by Dynamic Light Scattering (DLS), UV-Visible spectroscopy, Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Analysis (EDAX), Selected Area Electron Diffraction (SAED), and Atomic Absorption Spectroscopy (AAS). The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cytotoxic effect of the prepared nanoformulations. The apoptotic cell death induced by FA-GEM-AgNPs in breast cancer cells were monitored with Acridine orange (AO)/Ethidium Bromide (EtBr) staining. Conclusion: Compared to GEM and AgNPs, FA-GEM-AgNPs showed enhanced cytotoxic effect and internalization in MDA-MB-453 breast cancer cell line. FA-GEM-AgNPs could be an ideal candidate for targeting cancer cells via folate receptor-mediated endocytosis.

scholarly journals Novel Butein Derivatives Repress DDX3 Expression by Inhibiting PI3K/AKT Signaling Pathway in MCF-7 and MDA-MB-231 Cell Lines

2021 ◽  
Vol 11 ◽  
Author(s):  
Shailima Rampogu ◽  
Seong Min Kim ◽  
Baji Shaik ◽  
Gihwan Lee ◽  
Ju Hyun Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Cancer Therapeutics ◽  
Docking Studies ◽  
Computational Method ◽  
Phase Cell ◽  
Apoptosis Protein ◽  
Mcf 7

BackgroundBreast cancer is one of the major causes of mortalities noticed in women globally. DDX3 has emerged as a potent target for several cancers, including breast cancer to which currently there are no reported or approved drugs.MethodsTo find effective cancer therapeutics, three compounds were computationally designed tweaking the structure of natural compound butein. These compounds were synthesized and evaluated for their anticancer property in MCF-7 and MDA-MB-231 cell lines targeting DDX3. The in silico molecular docking studies have shown that the compounds have occupied the binding site of the human DDX3 target. Furthermore, to investigate the cell viability effect of 3a, 3b, and 3c on MCF-7 and MDA-MB-231 cell lines, the cell lines were treated with different concentrations of compounds for 24 and 48 h and measured using MTT assay.ResultsThe cell viability results showed that the have induced dose dependent suppression of DDX3 expression. Additionally, 3b and 3c have reduced the expression of DDX3 in MCF-7 and MDA-MD-231 cell lines. 3b or 3c treated cell lines increased apoptotic protein expression. Both the compounds have induced the apoptotic cell death by elevated levels of cleaved PARP and cleaved caspase 3 and repression of the anti-apoptosis protein BCL-xL. Additionally, they have demonstrated the G2/M phase cell cycle arrest in both the cell lines. Additionally, 3c decreased PI3K and AKT levels.ConclusionsOur results shed light on the anticancer ability of the designed compounds. These compounds can be employed as chemical spaces to design new prospective drug candidates. Additionally, our computational method can be adapted to design new chemical scaffolds as plausible inhibitors.

scholarly journals Engineered Exosomes-Based Photothermal Therapy with MRI/CT Imaging Guidance Enhances Anticancer Efficacy through Deep Tumor Nucleus Penetration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1593
Author(s):  
Min Yang ◽  
Xiaohui Wang ◽  
Fang Pu ◽  
Ying Liu ◽  
Jia Guo ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Tumor Therapy ◽  
Ct Imaging ◽  
Cancer Site ◽  
Control Group ◽  
Anticancer Efficacy ◽  
In Vivo Experiments ◽  
Actual Application

Exosomes, as natural nanovesicles, have become a spotlight in the field of cancer therapy due to their reduced immunogenicity and ability to overcome physiological barriers. However, the tumor targeting ability of exosomes needs to be improved before its actual application. Herein, a multiple targeted engineered exosomes nanoplatform was constructed through rare earth element Gd and Dy-doped and TAT peptide-modified carbon dots (CDs:Gd,Dy-TAT) encapsulated into RGD peptide engineered exosomes (Exo-RGD), which were used to enhance the effect of cancer imaging diagnosis and photothermal therapy. In vitro and in vivo experiments showed that the resulting CDs:Gd,Dy-TAT@Exo-RGD could effectively accumulate at cancer site with an increased concentration owing to the targeting peptides modification and exosomes encapsulation. The tumor therapy effects of mice treated with CDs:Gd,Dy-TAT@Exo-RGD were heightened compared with mice from the CDs:Gd,Dy control group. After intravenous injection of CDs:Gd,Dy-TAT@Exo-RGD into tumor-bearing mice, the temperature of tumors rose to above 50 °C under NIR irradiation and the localized hyperpyrexia induced by CDs could remarkably ablate tumors. The survival rate of the mice was 100% after 60 days. In addition, the CDs:Gd,Dy-TAT@Exo-RGD exhibited higher MRI/CT imaging contrast enhancement of tumor sites than that of CDs:Gd,Dy. Our study identified that engineered exosomes are a powerful tool for encapsulating multiple agents to enhance cancer theranostic efficiency and provide insight into precise personalized nanomedicine.

THE LEVEL OF CYTOKINES IN THE SALIVA OF PATIENTS WITH BREAST CANCER

2019 ◽  
Vol 65 (6) ◽  
pp. 825-831
Author(s):  
Lyudmila Belskaya ◽  
Viktor Kosenok
Keyword(s):  
Breast Cancer ◽  
Control Group ◽  
Early Stages ◽  
Promising Tool ◽  
Urgent Task ◽  
Advanced Stages ◽  
New Biomarkers ◽  
Histological Verification ◽  
Control Study ◽  
Biochemical Examination

Currently, the urgent task is to search for new biomarkers as a promising tool for early detection and monitoring of breast cancer. The aim of the study was to study the level of cytokines in the saliva of patients with breast cancer. In the case-control study volunteers participated, which were divided into 3 groups: the main (breast cancer, n = 43), the comparison group (fibroadenoma, n = 32) and the control group (conditionally healthy, n = 39). All participants were questioned; biochemical examination of saliva, histological verification of the diagnosis was carried out. Intergroup differences are estimated by a nonparametric criterion. It is shown that in the context of breast cancer, the level of cytokines (IL-2, IL-4, IL-6, IL-10 and IL-18) is increasing, except for IL-8, the content of which decreases compared to the control group. When the disease progresses by the nature of the dynamics, the parameters are divided into two groups: IL-2, IL-4, IL-18 and IL-6, IL-8, IL-10. For the first group of cytokines, there was a decrease in content during the transition from the early stages to the more common ones. For the second group, when passing from stages T1-2N0M0 to T1-2NjM0, the level of cytokines remains practically constant. In the future, the level of cytokines is observed for stage T3_4N0_2M0, and for IL-2, IL-4 and IL-10, the level of cytokines reaches values corresponding to early stages, whereas for IL-6, IL-8 and IL-18 in the same direction, a significant increase in indicators was noted. Additionally, the IL-6/IL-8 ratio was calculated depending on the tumor size, as well as the presence / absence of metastasis. It is shown that this ratio is statistically significantly increased in the advanced stages of the disease. Particularly interesting is the increase in this ratio in saliva at the initial stages of the disease.

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