scholarly journals Addition of an Fc-IgG induces receptor clustering and increases the in vitro efficacy and in vivo anti-tumor properties of the thrombospondin-1 type I repeats (3TSR) in a mouse model of advanced stage ovarian cancer

2021 ◽  
Author(s):  
Kathy Matuszewska ◽  
Simone ten Kortenaar ◽  
Madison Pereira ◽  
Lisa A. Santry ◽  
Duncan Petrik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Type I ◽  
Advanced Stage ◽  
Receptor Clustering ◽  
Thrombospondin 1

scholarly journals CX-5461 Treatment Leads to Cytosolic DNA-Mediated STING Activation in Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5056
Author(s):  
Robert Cornelison ◽  
Kuntal Biswas ◽  
Danielle C. Llaneza ◽  
Alexandra R. Harris ◽  
Nisha G. Sosale ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Time Frame ◽  
Interferon Response ◽  
Type I ◽  
Pol I ◽  
Downstream Effects ◽  
Immune Pathway ◽  
Polymerase I

Epithelial ovarian cancer (EOC) is the deadliest of the gynecologic malignancies, with an overall survival rate of <30%. Recent research has suggested that targeting RNA polymerase I (POL I) with small-molecule inhibitors may be a viable therapeutic approach to combating EOC, even when chemoresistance is present. CX-5461 is one of the most promising POL I inhibitors currently being investigated, and previous reports have shown that CX-5461 treatment induces DNA damage response (DDR) through ATM/ATR kinase. Investigation into downstream effects of CX-5461 led us to uncovering a previously unreported phenotype. Treatment with CX-5461 induces a rapid accumulation of cytosolic DNA. This accumulation leads to transcriptional upregulation of ‘STimulator of Interferon Genes’ (STING) in the same time frame, phosphorylation of IRF3, and activation of type I interferon response both in vitro and in vivo. This activation is mediated and dependent on cyclic GMP–AMP synthase (cGAS). Here, we show THAT CX-5461 leads to an accumulation of cytosolic dsDNA and thereby activates the cGAS–STING–TBK1–IRF3 innate immune pathway, which induces type I IFN. CX-5461 treatment-mediated immune activation may be a powerful mechanism of action to exploit, leading to novel drug combinations with a chance of increasing immunotherapy efficacy, possibly with some cancer specificity limiting deleterious toxicities.

Targeting Dormant Ovarian Cancer Cells In Vitro and in an In Vivo Mouse Model of Platinum Resistance

2020 ◽  
Vol 20 (1) ◽  
pp. 85-95
Author(s):  
Zhiqing Huang ◽  
Eiji Kondoh ◽  
Zachary R. Visco ◽  
Tsukasa Baba ◽  
Noriomi Matsumura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Platinum Resistance

125 BISPHENOL A-INDUCED GROWTH OF OVARIAN CANCER CELLS WAS REVERSED BY A PHYTOESTROGEN, GENISTEIN, BY INHIBITION OF A CROSSTALK BETWEEN ESTROGEN RECEPTOR AND INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR IN IN VITRO AND XENOGRAFT MOUSE MODELS

2014 ◽  
Vol 26 (1) ◽  
pp. 176
Author(s):  
K.-A. Hwang ◽  
S.-H. Kim ◽  
K.-C. Choi
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Mouse Model ◽  
Tumour Growth ◽  
Corn Oil ◽  
Signaling Cascades ◽  
Ovarian Cancer Cells ◽  
In Vitro Experiments

It has been shown that oestrogen (E2) up-regulated the expression of components of insulin-like growth factor-1 (IGF-1) signaling pathway and induced the downstream of mitogenic signaling cascades via phosphorylation of insulin receptor substrate-1 (IRS-1). An interaction between oestrogen receptor (ER) and IGF-1 receptor (IGF-1R) signaling pathway plays an important role in proliferation of and resistance to endocrine therapy to oestrogen-dependent cancers (i.e. breast and endometrial cancers). In the present study, we evaluated xenoestrogenic effect of bisphenol A (BPA) and antiproliferative activity of genistein (GEN) in accordance with the influence on this crosstalk. The gene expressions in mRNA and protein levels were examined by semiquantitative RT-PCR and Western blot analysis, in which the primers for ERα, IGF-1R, and GAPDH and the antibodies against pIRS-1, pAkt, and GAPDH were used, respectively. Total RNA and protein samples were isolated from BG-1 cells treated with dimethyl sulfoxide (DMSO), estradiol (E2; 10–9 M), BPA (10–5 M), E2 (10–9 M) + GEN (10–4 M), and BPA (10–5 M) + GEN (10–4 M). The DMSO was used a vehicle of E2, BPA, and GEN in in vitro experiments. All in vitro experiments were done in triplicates. The effects on tumour growth and immunohistologic alterations were identified in in vivo mouse models. The mice were injected subcutaneously with corn oil (vehicle, n = 6), E2 (n = 6), BPA (n = 6), E2+GEN (n = 6), and BPA+GEN (n = 6) for 8 weeks. The BPA treatment resulted in up-regulation of ERα and IGF-1R mRNA, and induced phosphorylation of IRS-1 and Akt proteins compared with a control (DMSO) in BG-1 ovarian cancer cells as E2 did in triplicates. In the mouse model xenografted with BG-1 cells, BPA significantly increased a tumour burden of mice and expressions of ERα, pIRS-1, and cyclin D1 in tumour mass compared with the vehicle (corn oil), indicating that BPA induces ovarian cancer growth by promoting the crosstalk between ER and IGF-1R signals. On the other hand, GEN effectively reversed estrogenicity of BPA by reversing mRNA and protein expressions of ERα, IGF-1R, pIRS-1, and pAkt induced by BPA in cellular model with triplicates. The GEN also significantly decreased tumour growth and in vivo expressions of ERα, pIRS-1, and pAkt in a xenografted mouse model. Also, GEN was confirmed to have an antiproliferative effect by inducing apoptotic signaling cascades. Taken together, these results suggest that GEN effectively reversed the increased proliferation of BG-1 ovarian cancer by suppressing the crosstalk between ER and IGF-1R signaling pathways up-regulated by BPA or E2. This work was supported by a grant from the Next-Generation BioGreen 21 Program (No. PJ009599), Rural Development Administration, Republic of Korea.

Peculiarities of the course of type I allergic reactions in patients with blood diseases

2020 ◽  
pp. 40-50
Author(s):  
A. Nikitina
Keyword(s):  
Search Engines ◽  
Anaphylactic Shock ◽  
Type I ◽  
Allergic Reactions ◽  
Common Cause ◽  
Blood Diseases ◽  
Treatment Regimens ◽  
Modern Methods

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.

scholarly journals Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review

2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell
Keyword(s):  
Systematic Review ◽  
Tissue Engineering ◽  
Collagen Type I ◽  
The Body ◽  
Pool Data ◽  
Type I ◽  
High Concentrations ◽  
Increased Strength

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.

scholarly journals Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 668
Author(s):  
Concetta Altamura ◽  
Maria Raffaella Greco ◽  
Maria Rosaria Carratù ◽  
Rosa Angela Cardone ◽  
Jean-François Desaphy
Keyword(s):  
Ovarian Cancer ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Gynecologic Cancer ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Platinum Resistance

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

scholarly journals A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejie Gao ◽  
Bo Li ◽  
Anqi Ye ◽  
Houcai Wang ◽  
Yongsheng Xie ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Burden ◽  
High Rate ◽  
Cell Counting ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Therapeutic Effects ◽  
Xenograft Mouse Model

Abstract Background Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. Methods We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. Results The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. Conclusion The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.

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