scholarly journals The potential of lunasin extract for the prevention of breast cancer progression by upregulating E-Cadherin and inhibiting ICAM-1

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 902
Author(s):  
Kusmardi Kusmardi ◽  
Elvan Wiyarta ◽  
Numlil Khaira Rusdi ◽  
Andi Muh. Maulana ◽  
Ari Estuningtyas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Soybean Protein ◽  
Negative Control ◽  
Intercellular Adhesion Molecule ◽  
Sprague Dawley ◽  
Intercellular Adhesion Molecule 1 ◽  
Significant Difference ◽  
E Cadherin

Background: Research in natural substances for their anticancer potential has become increasingly popular. Lunasin, a soybean protein, is known to inhibit cancer progression via various pathways.  The aim of this study was to investigate the effect of Lunasin Extract (LE) on the expression of Intercellular Adhesion Molecule 1 (ICAM-1) and epithelial cadherins (E-Cadherin) in breast cancer. Methods: In this true-experimental in vivo study, 24 Sprague-Dawley rats that were induced by 7,12-Dimethylbenz[a]anthracene (DMBA), were used. Based on the therapy given, the groups were divided into, normal, positive control (PC), negative control (NC), adjuvant, curative, and preventive. Lunasin was extracted from soybean seeds of the Grobogan variety in Indonesia. Tissue samples were obtained, processed, stained with anti-ICAM-1 and anti-E-Cadherin antibodies, examined under a microscope, and quantified using H-score. The data were analyzed using ANOVA, which was then followed by Duncan's test. Results: Statistically significant difference in ICAM-1 expression was observed between the following groups: adjuvant and NC, normal and NC, PC and NC, adjuvant and preventive, normal and preventive, PC and preventive, adjuvant and curative, normal and curative, PC and curative. E-Cadherin expression was significantly different between preventive and NC, adjuvant and NC, PC and NC, normal and NC, adjuvant and curative, PC and curative, normal and curative, normal and preventive. Significant negative correlation was found between ICAM-1 and E-Cadherin [-0.616 (-0.8165; -0.283)] with p = 0.001. Conclusion: Preventive dose of LE was able to reduce ICAM-1 expression while increasing E-Cadherin expression.

scholarly journals Fibrinogen and fragment D-induced vascular constriction

2005 ◽  
Vol 288 (3) ◽  
pp. H1257-H1264 ◽  
Author(s):  
David Lominadze ◽  
Nina Tsakadze ◽  
Utpal Sen ◽  
Jeff C. Falcone ◽  
Stanley E. D'Souza
Keyword(s):  
Femoral Artery ◽  
Vascular Wall ◽  
Intercellular Adhesion Molecule ◽  
Cremaster Muscle ◽  
Sprague Dawley ◽  
Intercellular Adhesion Molecule 1 ◽  
High Risk Factor ◽  
Arterial Constriction ◽  
Bq 610

Elevated fibrinogen (Fg) concentration in blood is a high risk factor for many cardiovascular diseases. We hypothesize that Fg and its early degradation product, fragment D, may result in arterial constriction by binding endothelial intercellular adhesion molecule-1 (ICAM-1). The vasoconstriction induced by Fg and fragment D was studied in third- and second-order arterioles (3As and 2As, respectively) of Sprague-Dawley rat cremaster muscle in vivo, in aortic and femoral artery rings, and in the segments of first-order arterioles (1As) isolated from rat cremaster muscle. Intravascular infusion of Fg induced significant constriction of 3As and 2As (by 33.4 ± 3.4 and 23.7 ± 4.3%, respectively) in vivo and was abolished in the presence of the specific endothelin type A receptor blocker BQ-610. Fg and fragment D produced significant constriction of both aortic and femoral artery rings. Isolated 1As constricted in response to Fg (0.3 μM) and fragment D (3 μM) by 31 ± 1.4 and 12 ± 1.5%, respectively. Fluorescently labeled Fg and fragment D bound to the vascular wall, whereas albumin bound to a significantly lesser degree. The binding of Fg and fragment D to the arteriolar wall and constriction of aortic and femoral artery rings as well as isolated 1As were abolished in the presence of anti-Fg and anti-ICAM-1 antibodies. These results indicate that binding of Fg and fragment D to the vascular wall through ICAM-1 may contribute to the increased vascular tone and resistance that compromise circulation.

Inflammatory Response of a New Synthetic Dialyzer Membrane. a Randomised Cross-over Comparison between Polysulfone and Helixone

2003 ◽  
Vol 26 (1) ◽  
pp. 26-32 ◽  
Author(s):  
S. Stefoni ◽  
L. Colì ◽  
G. Cianciolo ◽  
G. Donati ◽  
G. Ruggeri ◽  
...  
Keyword(s):  
Platelet Count ◽  
Inflammatory Response ◽  
Intercellular Adhesion Molecule ◽  
Complement Factor ◽  
Intercellular Adhesion Molecule 1 ◽  
Leukocyte Elastase ◽  
Inflammatory Parameters ◽  
Significant Difference ◽  
Wbc Count

Hemodialysis patients suffer from chronic inflammation due to intradialytic contact of blood with artificial materials. The FX 60 dialyzer which belongs to the new FX-class series of dialyzers is composed of the new membrane Helixone®. This membrane is derived from the original Fresenius Polysulfone® membrane. The FX-class design is based on modified geometry of fibres and housing and has resulted in a new dialyzer with improved efficiency, safety and ease of handling compared to the F series (F 60S) dialyzer. The aim of the study was to investigate whether the biocompatibility pattern in terms of inflammatory parameters of the new type of polysulfone dialyzer has changed compared to the standard. A clinical in vivo study was conducted to compare the intradialytic inflammatory response of the two dialyzers, FX 60 and F 60S. Eight chronic dialysis patients were selected for the study: mean age 65.5±15.5 years, mean time on dialysis 100±95 months. The randomized cross-over study involved a treatment period of 2 weeks (total 6 sessions), one week with each dialyzer, starting with one or the other according to the randomization scheme. Blood samples were taken at 0 (T0), 15, 60, and 240 minutes to evaluate white blood cell (WBC) count, complement factor C5a, leukocyte elastase, soluble intercellular adhesion molecule 1 (sICAM-1), platelet count, C-reactive protein (CRP). At 15 min, WBC count showed a comparably, low decrease for both dialyzers: −7.6 % for FX 60 versus −6.6 % for F 60S, p=not significant (ns). At the same time the C5a concentration decreased from 15.0±7.5 ng/ml to 13.5±6.7 ng/ml (p=ns) for FX 60, and from 15.1±12.5 ng/ml to 14.9±25.0 ng/ml for F 60S (p=ns). The elastase concentration progressively increased over time with no statistical difference between the two dialyzers. The levels of sICAM-1, CRP, and platelet count were similar at each time point for both dialyzers, varying around the baseline values (p=ns). No significant difference emerged in terms of inflammatory response between the two dialyzers, demonstrating that the biocompatibility of the F-series was maintained in the FX-class series of dialyzers and is independent of design factors.

scholarly journals Oral Administration of Tualang and Manuka Honeys Modulates Breast Cancer Progression in Sprague-Dawley Rats Model

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Sarfraz Ahmed ◽  
Siti Amrah Sulaiman ◽  
Nor Hayati Othman
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Estrogenic Activity ◽  
Tumour Size ◽  
Virgin Female ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Therapeutic Effects ◽  
Sprague Dawley

Breast cancer has been recognized as the leading cause of death in women worldwide. Research has shown the importance of complementary and alternative therapies in cancer. In this study, we investigated the antitumoural therapeutic effects of Malaysian Tualang honey (TH) and Australian/New Zealand Manuka honey (MH) against breast cancer in rats. Thirty syngeneic virgin female Sprague-Dawley (SD) rats were induced by the carcinogen 1-methyl-1-nitrosourea (MNU) 80 mg/kg. The treatment started when first palpable tumour reached 10–12 mm in size by dividing rats into following groups: Group 0 (negative control); Group 1 (positive control); and Groups 2 and 3 which received 1.0 g/kg body weight/day of TH and MH, respectively, for 120 days. The data demonstrate that cancer masses in TH and MH treated groups showed a lower median tumour size, weight, and multiplicity compared with the nontreated positive control (p<0.05). Treatment also showed a dramatic slower growth rate (up to 70.82%) compared with the nontreated control (0%) (p<0.05). The antitumoural effect was mediated through modulation of tumour growth, tumour grading, estrogenic activity, and haematological parameters. Our findings demonstrate that systemic administration of TH and MH increases the susceptibility of expression of proapoptotic proteins (Apaf-1, Caspase-9, IFN-γ, IFNGR1, and p53) and decreases the expression of antiapoptotic proteins (TNF-α, COX-2, and Bcl-xL 1) in its mechanism of action. This highlights a potential novel role for TH and MH in alleviating breast cancer.

scholarly journals Herring (Clupea harengus) intake influences lipoproteins but not inflammatory and oxidation markers in overweight men

2008 ◽  
Vol 101 (3) ◽  
pp. 383-390 ◽  
Author(s):  
Helen M. Lindqvist ◽  
Anna Maria Langkilde ◽  
Ingrid Undeland ◽  
Ann-Sofie Sandberg
Keyword(s):  
Risk Factors ◽  
Clupea Harengus ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Cvd Risk ◽  
Oxidised Ldl ◽  
Reactive Protein ◽  
Significant Difference ◽  
Lean Pork

Fish consumption is associated with a lower incidence of CVD and decreases in risk factors for atherosclerosis. Although fish contains other interesting components than fish oil, few studies focus on total fish composition and the influence food preparation might have on health-beneficial components. In the present cross-over intervention study the effect of a 6-week herring diet compared with a reference diet on CVD risk factors was investigated. Thirty-five healthy, but overweight, men (mean BMI 28·3 kg/m2) were randomised to a 6-week herring diet (150 g baked herring fillets/d, 5 d/week) or a reference diet (150 g baked lean pork and chicken fillets/d, 5 d/week). Diets were switched after a 12-week washout period. Plasma total cholesterol, TAG, HDL, HDL2, HDL3, LDL, C-reactive protein, IL-6, IL-18, intercellular adhesion molecule-1, oxidised LDL, oxygen radical absorbance capacity using perchloric acid (ORACPCA), whole-blood fatty acids, bleeding time and blood pressure were measured at the beginning and end of each dietary period. HDL was significantly higher after the herring diet period compared with after the reference diet period: 1·04v.0·99 mmol/l. TAG decreased after both diets, with no significant difference between the two diets. ORACPCAvalues did not indicate lower concentrations of non-protein plasma antioxidants, and oxidised LDL was not higher after the herring diet than after the reference diet. To conclude, a 6-week herring-rich diet significantly raised HDL compared with a diet of matched lean pork and chicken dishes. No adverse effects onin vivooxidation or serum antioxidants were found after herring intake.

scholarly journals ICAM-1 Targeted Drug Combination Nanoparticles Enhanced Gemcitabine-Paclitaxel Exposure and Breast Cancer Suppression in Mouse Models

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 89
Author(s):  
Linxi Zhu ◽  
Qingxin Mu ◽  
Jesse Yu ◽  
James I. Griffin ◽  
Xiaolin Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Drug Combination ◽  
Near Infrared ◽  
Metastatic Breast ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Targeted Drug

Despite the availability of molecularly targeted treatments such as antibodies and small molecules for human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and programmed death-ligand 1 (PD-L1), limited treatment options are available for advanced metastatic breast cancer (MBC), which constitutes ~90% mortality. Many of these monotherapies often lead to drug resistance. Novel MBC-targeted drug-combination therapeutic approaches that may reduce resistance are urgently needed. We investigated intercellular adhesion molecule-1 (ICAM-1), which is abundant in MBC, as a potential target to co-localize two current drug combinations, gemcitabine (G) and paclitaxel (T), assembled in a novel drug-combination nanoparticle (GT DcNP) form. With an ICAM-1-binding peptide (referred to as LFA1-P) coated on GT DcNPs, we evaluated the role of the LFA1-P density in breast cancer cell localization in vitro and in vivo. We found that 1–2% LFA1-P peptide incorporated on GT DcNPs provided optimal cancer cell binding in vitro with ~4× enhancement compared to non-peptide GT DcNPs. The in vivo probing of GT DcNPs labeled with a near-infrared marker, indocyanine green, in mice by bio-imaging and G and T analyses indicated LFA1-P enhanced drug and GT DcNP localization in breast cancer cells. The target/healthy tissue (lung/gastrointestinal (GI)) ratio of particles increased by ~60× compared to the non-ligand control. Collectively, these data indicated that LFA1 on GT DcNPs may provide ICAM-1-targeted G and T drug combination delivery to advancing MBC cells found in lung tissues. As ICAM-1 is generally expressed even in breast cancers that are triple-negative phenotypes, which are unresponsive to inhibitors of nuclear receptors or HER2/estrogen receptor (ER) agents, ICAM-1-targeted LFA1-P-coated GT DcNPs should be considered for clinical development to improve therapeutic outcomes of MBCs.

scholarly journals Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jun-Xian Du ◽  
Yi-Hong Luo ◽  
Si-Jia Zhang ◽  
Biao Wang ◽  
Cong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
High Risk Group ◽  
Clinical Samples ◽  
Binding Motif ◽  
Ki 67 ◽  
Tissue Samples

Abstract Background Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database. Results SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort. Conclusions SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.

scholarly journals Optimizing cisplatin delivery to triple-negative breast cancer through novel EGFR aptamer-conjugated polymeric nanovectors

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Lisa Agnello ◽  
Silvia Tortorella ◽  
Annachiara d’Argenio ◽  
Clarissa Carbone ◽  
Simona Camorani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Ex Vivo ◽  
Treatment Options ◽  
Negative Control ◽  
Therapeutic Effects ◽  
Metastatic Setting

Abstract Background Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic compound in neoadjuvant approaches and in the metastatic setting, but its use is limited by scarce bioavailability, severe systemic side effects and drug resistance. Novel site-directed aptamer-based nanotherapeutics have the potential to overcome obstacles of chemotherapy. In this study we investigated the tumor targeting and the anti-tumorigenic effectiveness of novel cisplatin-loaded and aptamer-decorated nanosystems in TNBC. Methods Nanotechnological procedures were applied to entrap cisplatin at high efficacy into polymeric nanoparticles (PNPs) that were conjugated on their surface with the epidermal growth factor receptor (EGFR) selective and cell-internalizing CL4 aptamer to improve targeted therapy. Internalization into TNBC MDA-MB-231 and BT-549 cells of aptamer-decorated PNPs, loaded with BODIPY505-515, was monitored by confocal microscopy using EGFR-depleted cells as negative control. Tumor targeting and biodistribution was evaluated by fluorescence reflectance imaging upon intravenously injection of Cyanine7-labeled nanovectors in nude mice bearing subcutaneous MDA-MB-231 tumors. Cytotoxicity of cisplatin-loaded PNPs toward TNBC cells was evaluated by MTT assay and the antitumor effect was assessed by tumor growth experiments in vivo and ex vivo analyses. Results We demonstrate specific, high and rapid uptake into EGFR-positive TNBC cells of CL4-conjugated fluorescent PNPs which, when loaded with cisplatin, resulted considerably more cytotoxic than the free drug and nanovectors either unconjugated or conjugated with a scrambled aptamer. Importantly, animal studies showed that the CL4-equipped PNPs achieve significantly higher tumor targeting efficiency and enhanced therapeutic effects, without any signs of systemic toxicity, compared with free cisplatin and untargeted PNPs. Conclusions Our study proposes novel and safe drug-loaded targeted nanosystems for EGFR-positive TNBC with excellent potential for the application in cancer diagnosis and therapy.

scholarly journals A Tumbling Magnetic Microrobot System for Biomedical Applications

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 861
Author(s):  
Elizabeth E. Niedert ◽  
Chenghao Bi ◽  
Georges Adam ◽  
Elly Lambert ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Biomedical Applications ◽  
Imaging System ◽  
Ex Vivo ◽  
Negative Control ◽  
Circular Path ◽  
Rotational Axis ◽  
Significant Difference

A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

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