scholarly journals Anti-c-myc efficacy block EGFL7 induced prolactinoma tumorigenesis

2019 ◽  
Vol 17 (1) ◽  
pp. 1501-1508
Author(s):  
Xiaolei Lan ◽  
Qian Liu ◽  
Hua Gao ◽  
Zhenye Li ◽  
Yazhuo Zhang
Keyword(s):  
Mapk Signaling ◽  
Positive Staining ◽  
Akt Activation ◽  
Non Invasive ◽  
Normal Pituitary Gland ◽  
Key Factor ◽  
Epidermal Growth ◽  
High Level ◽  
Invasive Prolactinoma

AbstractResistance to Dopamine agonists therapy is still a key factor that hinders the clinical treatment of prolactinoma. Consequently, a large number of investigations have been carried out to identify novel therapeutic targets. Our previous studies have suggested that the epidermal growth factor-like domain 7 (EGFL7) plays a crucial role in tumorigenesis of pituitary adenomas via EGFR/AKT/MAPK signaling pathway. In the present research, we found a positive staining of c-myc intimately associated with high-level EGFL7 in invasive prolactinoma compared to non-invasive prolactinoma and the normal pituitary gland. Meanwhile, PI3K/Akt and MAPK signaling cascades closely related to the activation of c-myc. Therefore, this research was conducted to explore the cooperation effect of c-myc and EGFL7 in prolactinoma. The inhibition of c-myc with anti-c-myc antibodies significantly reduced the proliferation, PRL secretion and invasion of rat prolactinoma MMQ cells. Notably, down regulation c-Myc by in vitro administration of anti-c-Myc antibodies could significantly depress EGFL7 induced MMQ cell proliferation, PRL secretion and invasion. An anti-c-Myc antibody could block EGFL7 induced Akt activation, but the expression of p-ERK was not altered by an anti-c-Myc antibody. Thus, our results suggest that anti-c-myc efficacy could block EGFL7 induced prolactinoma tumorigenesis via inhibited Akt activation in MMQ cells.

P–582 High level of concordance between invasive and non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) at day5 and day6–7

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Biricik ◽  
V Bianchi ◽  
F Lecciso ◽  
M Surdo ◽  
M Manno ◽  
...  
Keyword(s):  
Data Analysis ◽  
Embryo Culture ◽  
Culture Media ◽  
Embryo Biopsy ◽  
Non Invasive ◽  
Culture Time ◽  
Ngs Data Analysis ◽  
High Level ◽  
Ngs Data

Abstract Study question To explore ploidy concordance between invasive and non-invasive PGTA (niPGT-A) at different embryo culture time. Summary answer High level (>84%) of concordance rate for ploidy and sex, sensitivity (>88%), and specificity (76%) were obtained for both day6/7 samples and day5 samples. What is known already The analysis of embryo cell free DNA (cfDNA) that are released into culture media during in vitro embryo development has the potential to evaluate embryo ploidy status. However, obtaining sufficient quality and quantity of cfDNA is essential to achieve interpretable results for niPGT-A. More culture time is expected to be directly proportional to the release of more cfDNA. But embryo culture time is limited due to in-vitro embryo survival potential. Therefore, it is important to estimate the duration of the culture that will provide the maximum cfDNA that can be obtained without adversely affecting the development of the embryo. Study design, size, duration A total of 105 spent culture media (SCM) from day5-day7 blastocyst stage embryos have been included in this cohort study. The cfDNA of SCM samples were amplified and analyzed for niPGT-A by NGS analysis. The SCM samples were divided into 2 subgroups according the embryo culture hours (Day5 and Day6/7 group). The DNA concentration, informativity and euploidy results have then been compared with their corresponding embryos after trophectoderm biopsy (TE) and PGT-A analysis by NGS Participants/materials, setting, methods Embryos cultured until Day3 washed and cultured again in 20µl fresh culture media until embryo biopsy on Day5, 6, or 7. After biopsy SCM samples were immediately collected in PCR tubes and conserved at –20 °C until whole genome amplification by MALBAC® (Yicon Genomics). The TE and SCM samples were analyzed by next-generation sequencing (NGS) using Illumina MiSeq® System. NGS data analysis has been done by Bluefuse Multi Software 4.5 (Illumina) for SCM and TE samples Main results and the role of chance Only the SCM samples which have an embryo with a conclusive result were included in this cohort (n = 105). Overall 97.1% (102/105) of SCM samples gave a successful DNA amplification with a concentration ranging 32.4–128.5ng/µl. Non-informative (NI) results including a chaotic profile (>5 chromosome aneuploidies) were observed in 17 samples, so 83.3%(85/102) of SCM samples were informative for NGS data analysis. Ploidy concordance rate with the corresponding TE biopsies (euploid vs euploid, aneuploid vs aneuploid) was 84.7% (72/85). Sensitivity and specificity were 92,8% and 76,7%, respectively with no significant difference for all parameters for day 6/7 samples compared with day 5 samples. The false-negative rate was 3.5% (3/85), and false-positive rate was 11.7% (10/85). Limitations, reasons for caution The sample size is relatively small. Larger prospective studies are needed. As this is a single-center study, the impact of the variations in embryo culture conditions can be underestimated. Maternal DNA contamination risk cannot be revealed in SCM, therefore the use of molecular markers would increase the reliability. Wider implications of the findings: Non-invasive analysis of embryo cfDNA analyzed in spent culture media demonstrates high concordance with TE biopsy results in both early and late culture time. A non-invasive approach for aneuploidy screening offers important advantages such as avoiding invasive embryo biopsy and decreased cost, potentially increasing accessibility for a wider patient population. Trial registration number Not applicable

scholarly journals Disinvasive efficacy of chlorine-based preparations of domestic production for eggs of nematodes of the species Aonchotheca bovis parasitizing in sheep

2018 ◽  
Vol 1 (2) ◽  
pp. 15-18 ◽  
Author(s):  
V. Melnychuk ◽  
I. Yuskiv
Keyword(s):  
Effective Means ◽  
Destructive Effect ◽  
Domestic Production ◽  
Non Invasive ◽  
Invasive Test ◽  
Test Culture ◽  
Nematode Eggs ◽  
Egg Shell ◽  
High Level

The paper presents the results of experimental researches on the determination of the disinvasion efficiency of chlorinated chemical preparations of domestic production of “Brovades-plus”, “Bi-dez” and “Dezsans” of NPF “Brovafarma” (Ukraine). The conducted researches on the basis of the parasitology laboratory found that the studied disinfectants possess disinvasive properties in respect of non-invasive test culture of eggs of nematodes of the species Aonchotheca bovis (son Capillaria bovis) López-Neyra, 1947, isolated from gonads of females of worms. The dissimilar stability of eggs of capillaries to the effect of the tested agents in vitro is proved. The most effective disinfectant in the case of eggs of capillaries of the species A. bovis was the preparation “Dezsan”. The high level of its disinvasive efficacy (DE – 91.14–100.0%) was registered at the application of the preparation in 1.0–2.0% of the exposure concentration for 10–60 minutes. The chemicals “Bi-dez” and “Brovadez-plus” proved to be less effective in the relatively non-invasive test culture of A. bovis eggs. The high level of efficiency (DE –92.41–100.00%) of the “Bi-dez” was achieved with its use at concentrations of 1.5% (exposure of 30 and 60 min) and 2.0% (exposure of 10–60 minutes) The “Brovadez plus” preparation in vitro proved to be the least effective means of non-invasive test culture of nematode eggs of the species A. bovis, since a high level of disinvasive efficacy (DE – 100.00%) was achieved only with the use of 2.0% solution per exposure 10–60 min. It was established that the experimentally tested chlorine-based means of domestic production resulted in the death of eggs in the culture in due to the destructive effect of the components of the preparations on the shell, the caps of eggs of the capillaries, as well as on the germ in the middle of the egg. In experimental cultures treated with the means, the destruction of the shell of the egg in the location of the caps, the exit of morulae outside, the cessation of development or shrinkage of the embryo and deformation of the egg shell were recorded.

scholarly journals Anti-EGFL7 antibodies inhibit rat prolactinoma MMQ cells proliferation and PRL secretion

2018 ◽  
Vol 16 (1) ◽  
pp. 621-626 ◽  
Author(s):  
Qian Liu ◽  
Taoyang Yuan ◽  
Hua Gao ◽  
Songbai Gui ◽  
Yazhuo Zhang ◽  
...  
Keyword(s):  
Pituitary Tumors ◽  
Dependent Manner ◽  
First Line ◽  
First Line Therapy ◽  
Normal Pituitary Gland ◽  
Promote Tumor Growth ◽  
Epidermal Growth ◽  
Dose Dependent ◽  
Novel Therapeutic

AbstractProlactinoma is the most frequently diagnosed pituitary tumors. Dopamine agonists (DAs) are recognized as first-line therapy; however, approximately 10% patients will develop resistance to DAs therapy. Consequently, a large number of investigations have been carried out to identify novel therapeutic targets. Recently, studies have suggested that epidermal growth factor-like domain 7 (EGFL7) can promote tumor growth, invasion, and angiogenesis. We previously reported that overexpression of EGFL7 might play a crucial role in hormone-producing pituitary adenomas. In the present study, we now demonstrated a significantly higher protein expression of EGFL7 in prolactinoma compared with the normal pituitary gland. However, inhibition of EGFL7 with anti-EGFL7 antibodies significantly reduced the proliferation and PRL secretion of rat prolactinoma MMQ cells. Notably, in vitro administration of anti-EGFL7 antibodies significantly induced MMQ cells apoptosis in a dose-dependent manner. In conclusion, our finding suggests that EGFL7 is significantly overexpressed in prolactinoma and inhibition of EGFL7 with antibodies promoted MMQ cells apoptosis and inhibited PRL secretion. Thus, EGFL7 may serve as a potential novel therapeutic target for prolactinomas.

scholarly journals A multilevel analysis identifies the different relationships between amino acids and the competence of oocytes matured individually or in groups

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rasoul Kowsar ◽  
Alireza Mansouri ◽  
Nima Sadeghi ◽  
Mohammad Heidaran Ali Abadi ◽  
Seyed Mehdi Ghoreishi ◽  
...  
Keyword(s):  
In Vitro Maturation ◽  
Predictive Power ◽  
Developmental Competence ◽  
Maturation Medium ◽  
Epidermal Growth ◽  
Multi Level ◽  
High Level ◽  
High Protein Diets ◽  
Protein Diets

Abstract High-protein diets contribute to an increase in urea follicular concentrations associated with decreased fertility. Urea has been shown to interfere with the epidermal growth factor (EGF)/EGFR system, which has been shown to have a beneficial effect during in vitro maturation (IVM) of oocytes. Of note, the number of cumulus-oocyte complexes (COCs) in the maturation medium can change the maturation and the developmental competence of COCs. Therefore, it was hypothesized that, the presence of urea and EGF may have a differential effect on the depletion/appearance of AAs and competence of COCs matured individually (I-IVM system) or in groups (G-IVM system). In the G-IVM system, COCs increased consumption (depletion) of AAs compared with other groups in the presence of high-level urea (40 mg/dl) + EGF (10 ng/ml). In the I-IVM system, the non-cleaved COCs depleted more AAs than the cleaved COCs, in particular in the presence of urea. The combination of urea and EGF increased the depletion of AAs in the G-IVM system. However, the EGF abrogated the urea-induced depletion of AAs by the I-IVM COCs. The use of N-acetyl-l-cysteine as an EGFR inhibitor canceled urea-induced depletion of AAs. This shows the inhibiting effect of urea over the EGF/EGFR system. In the presence of urea + EGF, COCs had a lower degree of developmental competence than control in both I- and G-IVM systems. Arginine had the best predictive power to identify highly competent COCs in the G-IVM system, while glutamine was the best predictor of the cleavage in the I-IVM system. In conclusion, this multi-level study shows that COCs matured individually or in groups may have different association with AAs metabolism. These findings provide new insights into the relationships between AA metabolism and the subsequent developmental competence of COCs.

scholarly journals Prostaglandin F2 α upregulates Slit/Robo expression in mouse corpus luteum during luteolysis

2013 ◽  
Vol 218 (3) ◽  
pp. 299-310 ◽  
Author(s):  
XueJing Zhang ◽  
JianHua Li ◽  
JiaLi Liu ◽  
HaoShu Luo ◽  
KeMian Gou ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Corpus Luteum ◽  
Mapk Signaling ◽  
Functional Studies ◽  
Kinase C ◽  
Key Factor ◽  
Prostaglandin F ◽  
Mapk Signaling Pathways

Prostaglandin F2 α (PGF2 α) is a key factor in the triggering of the regression of the corpus luteum (CL). Furthermore, it has been reported that Slit/Robo signaling is involved in the regulation of luteolysis. However, the interactions between PGF2 α and Slit/Robo in the progression of luteolysis remain to be established. This study was designed to determine whether luteolysis is regulated by the interactions of PGF2 α and Slit/Robo in the mouse CL. Real-time PCR and immunohistochemistry results showed that Slit2 and its receptor Robo1 are highly and specifically co-expressed in the mouse CL. Functional studies showed that Slit/Robo participates in mouse luteolysis by enhancing cell apoptosis and upregulating caspase3 expression. Both in vitro and in vivo studies showed that PGF2 α significantly increases the expression of Slit2 and Robo1 during luteolysis through protein kinase C-dependent ERK1/2 and P38 MAPK signaling pathways, whereas an inhibitor of Slit/Robo signaling significantly decreases the stimulating effect of PGF2 α on luteolysis. These findings indicate that Slit/Robo signaling plays important roles in PGF2 α-induced luteolysis by mediating the PGF2 α signaling pathway in the CL.

Follicular fluid and assisted reproductive technology programs outcomes (literature review)

GYNECOLOGY ◽  
2020 ◽  
Vol 21 (6) ◽  
pp. 36-40
Author(s):  
Anna G. Burduli ◽  
Natalia A. Kitsilovskaya ◽  
Yuliya V. Sukhova ◽  
Irina A. Vedikhina ◽  
Tatiana Y. Ivanets ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Assisted Reproductive Technology ◽  
Follicular Fluid ◽  
Economic Cost ◽  
Reproductive Technology ◽  
Art Programs ◽  
Vitro Fertilization ◽  
Non Invasive ◽  
Established Fact

The review presents data on metabolites in the follicular fluid (FF) from the perspective of reproductive medicine and their use in order to predict outcomes of assisted reproductive technology (ART) programs. It considers various components of this biological medium (hormones, lipids, melatonin, etc.) with an assessment of their predictive value in prognosis of the effectiveness of in vitro fertilization (IVF) programs. The data on experimental directions in this field and the prospects for their use in clinical practice are presented. The article emphasizes that the growing clinical need and the unsolved problem of increasing the effectiveness of ART programs determine the need for further studies of the FF composition. Materials and methods. The review includes data related to this topic from foreign and Russian articles found in PubMed which were published in recent years. Results. Given the established fact of a direct effect of FF composition on growth and maturation of oocytes, and further, on the fertilization process, various FF metabolites are actively investigated as non-invasive markers of quality of oocytes/embryos. The article provides data on the experimental directions in this field and the prospects for their use in clinical practice. However, clinical studies of a relation between various FF metabolites levels and outcomes of IVF programs are contradictory. Conclusion. Owing large economic cost for treatment of infertility with IVF, there is need for expansion and intensification of studies to identify and use reliable predictors in prognosis of ART programs outcomes.

Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Triple Negative ◽  
Growth Factor Receptor ◽  
Engineered Nanoparticles ◽  
Efficacy Evaluation ◽  
Dual Action ◽  
Epidermal Growth ◽  
Laminin 411 ◽  
Immunologic Analysis

Engineered nanoparticles are widely used for delivery of drugs but frequently lack proof of safetyfor cancer patient's treatment. All-in-one covalent nanodrugs of the third generation have beensynthesized based on a poly(β-L-malic acid) (PMLA) platform, targeting human triple-negativebreast cancer (TNBC). They significantly inhibited tumor growth in nude mice by blockingsynthesis of epidermal growth factor receptor, and α4 and β1 chains of laminin-411, the tumorvascular wall protein and angiogenesis marker. PMLA and nanodrug biocompatibility and toxicityat low and high dosages were evaluated in vitro and in vivo. The dual-action nanodrug and singleactionprecursor nanoconjugates were assessed under in vitro conditions and in vivo with multipletreatment regimens (6 and 12 treatments). The monitoring of TNBC treatment in vivo withdifferent drugs included blood hematologic and immunologic analysis after multiple intravenousadministrations. The present study demonstrates that the dual-action nanoconju-gate is highlyeffective in preclinical TNBC treatment without side effects, supported by hematologic andimmunologic assays data. PMLA-based nanodrugs of the Polycefin™ family passed multipletoxicity and efficacy tests in vitro and in vivo on preclinical level and may prove to be optimizedand efficacious for the treatment of cancer patients in the future.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

Computational Evaluation and In Vitro Validation of New Epidermal Growth Factor Receptor Inhibitors

2020 ◽  
Vol 20 (18) ◽  
pp. 1628-1639
Author(s):  
Sergi Gómez-Ganau ◽  
Josefa Castillo ◽  
Andrés Cervantes ◽  
Jesus Vicente de Julián-Ortiz ◽  
Rafael Gozalbes
Keyword(s):  
Cell Proliferation ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Binding Affinity ◽  
Cell Lines ◽  
Growth Factor Receptor ◽  
Significant Activity ◽  
Epidermal Growth

Background: The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein that acts as a receptor of extracellular protein ligands of the epidermal growth factor (EGF/ErbB) family. It has been shown that EGFR is overexpressed by many tumours and correlates with poor prognosis. Therefore, EGFR can be considered as a very interesting therapeutic target for the treatment of a large variety of cancers such as lung, ovarian, endometrial, gastric, bladder and breast cancers, cervical adenocarcinoma, malignant melanoma and glioblastoma. Methods: We have followed a structure-based virtual screening (SBVS) procedure with a library composed of several commercial collections of chemicals (615,462 compounds in total) and the 3D structure of EGFR obtained from the Protein Data Bank (PDB code: 1M17). The docking results from this campaign were then ranked according to the theoretical binding affinity of these molecules to EGFR, and compared with the binding affinity of erlotinib, a well-known EGFR inhibitor. A total of 23 top-rated commercial compounds displaying potential binding affinities similar or even better than erlotinib were selected for experimental evaluation. In vitro assays in different cell lines were performed. A preliminary test was carried out with a simple and standard quick cell proliferation assay kit, and six compounds showed significant activity when compared to positive control. Then, viability and cell proliferation of these compounds were further tested using a protocol based on propidium iodide (PI) and flow cytometry in HCT116, Caco-2 and H358 cell lines. Results: The whole six compounds displayed good effects when compared with erlotinib at 30 μM. When reducing the concentration to 10μM, the activity of the 6 compounds depends on the cell line used: the six compounds showed inhibitory activity with HCT116, two compounds showed inhibition with Caco-2, and three compounds showed inhibitory effects with H358. At 2 μM, one compound showed inhibiting effects close to those from erlotinib. Conclusion: Therefore, these compounds could be considered as potential primary hits, acting as promising starting points to expand the therapeutic options against a wide range of cancers.

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