Ovarian cancer stem cells and targeted therapy Keyvani, Vahideh; Farshchian, Moein; Esmaeili, Seyed-Alireza ...
Journal of ovarian research,
12/2019, Letnik:
12, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Ovarian cancer has the highest ratio of mortality among gynecologic malignancies. Chemotherapy is one of the most common treatment options for ovarian cancer. However, tumor relapse in patients with ...advanced tumor stage is still a therapeutic challenge for its clinical management.
Therefore, it is required to clarify the molecular biology and mechanisms which are involved in chemo resistance to improve the survival rate of ovarian cancer patients. Cancer stem cells (CSCs) are a sub population of tumor cells which are related to drug resistance and tumor relapse.
In the present review, we summarized the recent findings about the role of CSCs in tumor relapse and drug resistance among ovarian cancer patients. Moreover, we focused on the targeted and combinational therapeutic methods against the ovarian CSCs.
Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. ...Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis.
Data envelopment analysis (DEA) is a widely used non-parametric technique for measuring the relative efficiencies of decision-making units with multiple inputs and multiple outputs. The main caveat ...of traditional DEA models is that they are applicable to positive inputs and outputs, while negative data are commonly present in most real applications. To accommodate variables that can take both negative and positive values, Emrouznejad et al. (Eur J Oper Res 200(1):297–304,
2010a
) introduced the Semi-Oriented Radial Measure (SORM) model, which was later modified by Kazemi Matin et al. (Measurement 54:152–158,
2014
). The present study proposes a new version of the modified SORM model, using directional distance function and choosing a relevant direction to efficiently deal with variables with both positive and negative values. Our Directional SORM (DSORM) model is superior to its predecessors from both computational and target settings perspectives while it allows for the dual formulation of linear programming. To illustrate our proposed model, we employ two widely used selections of inputs and outputs to estimate the efficiency scores for a sample of banks operating in Persian Gulf Council Countries (GCC) over the period of 2002–2011. The estimated efficiency scores are then used to study the impact of financial system stability on technical efficiency of individual banks.
The goal of this study was to synthesize nickel oxide nanoparticles (NiO-NPs) by the sol–gel method, which involved the use of salvia macrosiphon Boiss plant extract, Ni(NO
3
)
2
·6H
2
O as a capping ...agent, and a nickel precursor, respectively. The synthesized NiO-NPs were characterized by Fourier transform infrared spectroscopy (FTIR), ultraviolet–visible (UV–Vis) spectrophotometer, X-ray diffraction (XRD), field electron scanning electron microscopy (FESEM)/energy-dispersive X-ray spectroscopy (EDX), thermo-gravimetric analysis/differential thermal analysis (TGA/DTA) and vibrating sample magnetometer (VSM) analyzes. Also, according to the results of UV–Vis, the gap band of nanoparticles was calculated to be in the range of about 2.9–3.9 eV. The photocatalytic activity of nanoparticles on methylene blue (MB) degradation was investigated and according to the results, about 80% MB was apparently degraded in the presence of NiO-NPs under UV-A light (11 W) after 5 h in pH ~ 11. We have evaluated the cytotoxicity of NiO-NPs on the multiple tumor cells by materials method, and all the utilized concentrations were observed to cause non-toxic effects; therefore, it can be suggested that these samples have the potential of being employed in different fields of medicine.
Graphic abstract
PurposeThe objective of this paper is to propose a new data envelopment analysis (DEA) model for assessing sustainability of suppliers with partial impacts between inputs, desirable outputs and ...undesirable outputs.Design/methodology/approachThis paper examines partial impacts of inputs on desirable and undesirable outputs and applies weak disposability assumption to propose a novel DEA model to determine the sustainability of suppliers.FindingsThis paper shows the type of resource sharing in DEA models and takes into account sustainable development and sustainability assessment concepts for sustainable supplier selection problem and develops a DEA model for selecting the most sustainable suppliers with partial sharing of resources. To select the most sustainable suppliers, this model helps managers to consider aggregate efficiency, overall efficiency and bundle efficiency. The paper introduces the supplier which is efficient at all levels as the most sustainable supplier.Originality/valueFor the first time, this paper suggests a new DEA model by partial impact between inputs and good outputs/bad outputs for selecting sustainable supplier and deals with the situations in which each supplier has several subunits. The new model calculates aggregate efficiency, overall efficiency and subunit efficiency of supplier. paper introduces the supplier which is efficient in all levels including aggregate efficiency, overall efficiency and subunit efficiency as the best supplier.
The crosstalk between osteoblasts and endothelial cells is critical for bone vascularization and regeneration. Here, we used a coaxial 3D bioprinting method to directly print an osteon‐like structure ...by depositing angiogenic and osteogenic bioinks from the core and shell regions of the coaxial nozzle, respectively. The bioinks were made up of gelatin, gelatin methacryloyl (GelMA), alginate, and hydroxyapatite (HAp) nanoparticles and were loaded with human umbilical vascular endothelial cells (HUVECs) and osteoblasts (MC3T3) in the core and shell regions, respectively. Conventional monoaxial 3D bioprinting was used as a control method, where the hydrogels, HAp nanoparticles, MC3T3 cells, and HUVECs were all mixed in one bioink and printed from the core nozzle. As a result, the bioprinted scaffolds were composed of cell‐laden fibers with either a core‐shell or homogenous structure, providing a non‐contact (indirect) or contact (direct) co‐culture of MC3T3 cells and HUVECs, respectively. Both structures supported the 3D culture of HUVECs and osteoblasts over a long period. The scaffolds also supported the expression of osteogenic and angiogenic factors. However, the gene expression was significantly higher for the core‐shell structure than the homogeneous structure due to the well‐defined distribution of osteoblasts and endothelial cells and the formation of vessel‐like structures in the co‐culture system. Our results indicated that the coaxial bioprinting technique, with the ability to create a non‐contact co‐culture of cells, can provide a more efficient bioprinting strategy for printing highly vascularized and bioactive bone structures.
25‐Hydroxyvitamin D3 as a main circulating metabolite of vitamin D is usually measured in serum to evaluate the vitamin D status of humans. So, developing an accessible, fast response, sensitive, and ...selective detection method for 25‐hydroxyvitamin D3 is highly important. In this study, we designed a sensitive and selective electrochemical sensor based on the modification of glassy carbon electrode by nanocomposite of CuCo2O4/nitrogen‐doped carbon nanotubes and phosphorus‐doped graphene oxide. Then 25‐hydroxyvitamin D3‐imprinted polypyrrole was coated on the electrode surface through electropolymerization. Moreover, ferricyanide was used as a mediator for the creation of a readable signal, which was considerably decreased after rebinding of 25‐hydroxyvitamin D3 on the electrode. The proposed sensor successfully detected 25‐hydroxyvitamin D3 in the range of 0.002–10 μM, with a detection limit of 0.38 nM, which was highly lower than deficiency concentration (20 ng/ml; 49.92 nM). Finally, the proposed sensor was checked for detection of 25‐hydroxyvitamin D3 in serum samples with recovery in the range of 80%–106.42%. The results demonstrated the applicability of the designed sensor for the detection of 25‐hydroxyvitamin D3 in biological samples.
Application of CuCo2O4/N‐doped CNTs/P‐doped GO nanocomposite and molecularly imprinted polymer for
electrochemical detection of 25‐hydroxyvitamin D3.
Display omitted
•KALA-LMWP-NLS chimeric peptide (KLN) was designed and expressed in E. coli Bl21.•KLN/pDNA/Aptamer nanoparticles were synthesized using electrostatic self-assembly.•Functionality of ...each segment in the vector structure was evaluated.•Synthesized nanoparticles significantly protected plasmid against serum nucleases.•Nanoparticles showed remarkable transfection efficiency and low cytotoxicity.
In this study, we developed a peptide-based non-viral carrier decorated with aptamer to overcome the specific gene delivery barriers. The carrier (KLN/Apt) was designed to contain multiple functional segments, including 1) two tandem repeating units of low molecular weight protamine (LMWP) to condense DNA into stable nanosize particles and protect it from enzymatic digestion, 2) AS1411 aptamer as targeting moiety to target nucleolin and promote carrier internalization, 3) a synthetic pH-sensitive fusogenic peptide (KALA) for disrupting endosomal membranes and enhancing cytosol escape of the nanoparticles, and 4) a nuclear localization signal (NLS) for active cytoplasmic trafficking and nuclear delivery of DNA. The obtained results revealed the developed carrier capacity in terms of specific cell targeting, overcoming cellular gene delivery barriers, and mediating efficient gene transfection. The KLN/pDNA/aptamer nanoparticles offer remarkable potential for the conceptual design and formation of promising multi-functionalized carriers towards the most demanding therapeutic applications.
Cerium oxide nanoparticles (CNPs) with desired particle size and spherical morphology were prepared from cerium nitrate in bio media of Salvia macrosiphon Boiss seeds extract, as a green synthesis ...route. Then they were characterized by XRD, UV–Vis and FTIR spectroscopies, FESEM and TGA. Band gap energy of the prepared powders was also determined which was found in the range of 2.5–3.5 eV. Determination of DLS and zeta potential were showed that CNPs had the small size and unique colloidal stability, respectively. Then the photo-catalytic activity of them was investigated by degradation of Rhodamine B (RhB) dye as a model of waste water pollutants, under UV-irradiation and optimum conditions were evaluated. Results showed that decreasing the particle size increased the rate of photo-catalytic reaction remarkably but ascending the band gap energy, in contrast. The photo-catalytic mechanism was also studied by using different scavengers.
MicroRNAs, which are micro-coordinators of gene expression, have been recently investigated as a potential treatment for cancer. The study used computational techniques to identify microRNAs that ...could target a set of genes simultaneously. Due to their multi-target-directed nature, microRNAs have the potential to impact multiple key pathways and their pathogenic cross-talk.
We identified microRNAs that target a prostate cancer-associated gene set using integrated bioinformatics analyses and experimental validation. The candidate gene set included genes targeted by clinically approved prostate cancer medications. We used STRING, GO, and KEGG web tools to confirm gene-gene interactions and their clinical significance. Then, we employed integrated predicted and validated bioinformatics approaches to retrieve hsa-miR-124-3p, 16-5p, and 27a-3p as the top three relevant microRNAs. KEGG and DIANA-miRPath showed the related pathways for the candidate genes and microRNAs.
The Real-time PCR results showed that miR-16-5p simultaneously down-regulated all genes significantly except for
in LNCaP; miR-27a-3p simultaneously down-regulated all genes significantly, excluding MET in LNCaP and PIK3CA in PC-3; and miR-124-3p could not down-regulate significantly
,
, and
in LNCaP and
in PC-3. Finally, we used a cell cycle assay to show significant G0/G1 arrest by transfecting miR-124-3p in LNCaP and miR-16-5p in both cell lines.
Our findings suggest that this novel approach may have therapeutic benefits and these predicted microRNAs could effectively target the candidate genes.