scholarly journals Anti-Angiogenic Treatments Interact with Steroid Secretion in Inflammatory Breast Cancer Triple Negative Cell Lines

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3668
Author(s):  
Ángela Alonso-Diez ◽  
Sara Cáceres ◽  
Laura Peña ◽  
Belén Crespo ◽  
Juan Carlos Illera
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Steroid Hormones ◽  
Cell Lines ◽  
Inflammatory Breast Cancer ◽  
Steroid Hormone ◽  
Sex Steroid ◽  
Antiangiogenic Therapies

Human inflammatory breast cancer (IBC) is a highly angiogenic disease for which antiangiogenic therapy has demonstrated only a modest response, and the reason for this remains unknown. Thus, the purpose of this study was to determine the influence of different antiangiogenic therapies on in vitro and in vivo steroid hormone and angiogenic growth factor production using canine and human inflammatory breast carcinoma cell lines as well as the possible involvement of sex steroid hormones in angiogenesis. IPC-366 and SUM149 cell lines and xenotransplanted mice were treated with different concentrations of VEGF, SU5416, bevacizumab and celecoxib. Steroid hormone (progesterone, dehydroepiandrostenedione, androstenedione, testosterone, dihydrotestosterone, estrone sulphate and 17β-oestradiol), angiogenic growth factors (VEGF-A, VEGF-C and VEGF-D) and IL-8 determinations in culture media, tumour homogenate and serum samples were assayed by EIA. In vitro, progesterone- and 17β-oestradiol-induced VEGF production promoting cell proliferation and androgens are involved in the formation of vascular-like structures. In vivo, intratumoural testosterone concentrations were augmented and possibly associated with decreased metastatic rates, whereas elevated E1SO4 concentrations could promote tumour progression after antiangiogenic therapies. In conclusion, sex steroid hormones could regulate the production of angiogenic factors. The intratumoural measurement of sex steroids and growth factors may be useful to develop preventive and individualized therapeutic strategies.

scholarly journals LPTO-06. A NOVEL BRAIN-PERMEANT CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Jiaojiao Deng ◽  
Sophia Chernikova ◽  
Wolf-Nicolas Fischer ◽  
Kerry Koller ◽  
Bernd Jandeleit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Tumors ◽  
Cell Lines ◽  
Chemotherapeutic Agent ◽  
Leptomeningeal Metastasis ◽  
Breast Cancer Cell Lines ◽  
Normal Brain ◽  
Breast Cancers

Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). The compound is active in suppressing the growth of GBM tumor cell lines implanted into the brain. Radiolabel distribution studies have shown significant tumor accumulation in intracranial brain tumors while sparing the adjacent normal brain tissue. Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106 photons/sec, mice were dosed i.p. twice a week with either 4 or 8 mg/kg for nine weeks. Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43

scholarly journals Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Farnaz Dabbagh Moghaddam ◽  
Iman Akbarzadeh ◽  
Ehsan Marzbankia ◽  
Mahsa Farid ◽  
Leila khaledi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cell Lines ◽  
Encapsulation Efficiency ◽  
Inbred Mice ◽  
Breast Cancer Treatment ◽  
Anticancer Effect ◽  
Anti Cancer

Abstract Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

Steroid-induced cell proliferation in vivo is associated with increased c-myc proto-oncogene transcript abundance

Development ◽  
1988 ◽  
Vol 104 (1) ◽  
pp. 87-95
Author(s):  
S.A. Rempel ◽  
R.N. Johnston
Keyword(s):  
Cell Proliferation ◽  
Growth Factors ◽  
Steroid Hormones ◽  
Steroid Hormone ◽  
Normal Liver ◽  
Transcript Abundance ◽  
Chicken Oviduct ◽  
Massive Cell ◽  
In Cells

Enhanced c-myc transcript abundance has been observed in a variety of human malignancies, in normal liver tissue induced to proliferate in vivo by partial hepatectomy and in cells in culture induced to proliferate with the addition of protein hormones and growth factors. Little is known, however, about the expression of cellular proto-oncogenes in cells induced to proliferate in vivo by steroid hormones. Experiments reported here indicate that when cells of the immature chicken oviduct are induced to undergo rapid in vivo proliferation by application of the estrogen hormone 17 beta-estradiol, the onset of this proliferation is associated with a rapid, large, and transient increase in c-myc transcript abundance. When estrogen is administered to chickens in which the oviduct has already differentiated, neither massive cell proliferation nor large increases in c-myc transcript abundance are induced. We conclude that the abundance of c-myc transcripts in vivo correlates well with the degree of cell proliferation induced by steroid hormone.

Effects of oestrogen on human breast cancer cells in culture

1989 ◽  
Vol 95 ◽  
pp. 119-132 ◽  
Author(s):  
Philippa D. Darbre ◽  
Roger J. Daly
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Breast Cancer Cell Lines ◽  
Phenol Red ◽  
Human Breast ◽  
Cells In Culture ◽  
D Cells

SynopsisOestrogen regulates the growth of human breast cancer cell lines ZR-75–1, T-47-D and MCF-7 (KO and McGrath). Basal cell growth can be reduced (T-47-D) or eliminated (ZR-75–1) by prior growth in the absence of steroid and phenol red for three weeks, demonstrating that oestrogens can have long-lasting effects on cells in culture (termed “steroid memory”). Effects of oestradiol on different cell biological parameters are described and interaction with other steroids and serum growth factors is discussed. Antioestrogen action in these cell lines is affected by at least five parameters: (1) presence of phenol red, (2) time in culture, (3) cell density, (4) antioestrogen concentration, (5) steroid memory.An in vitro model for loss of oestrogen sensitivity in breast cancer is presented. Both dependent (ZR-75–1) and responsive (T-47-D) cells lose oestrogen sensitivity when deprived of steroid in the long term but show a gradual increase in growth. For ZR-75–1 cells, the effects appear to be clonal but occur at a high frequency (about 1 in 1,000 cells). Parallel alterations in sensitivity to other steroids, antioestrogens and serum growth factors are shown. Molecular markers of this action are described and the results compared with the well-established model for loss of androgen/glucocorticoid sensitivity in SI 15 cells.

scholarly journals Structural characterization, antioxidant and cytotoxic effects of iron nanoparticles synthesized using Asphodelus aestivus Brot. aqueous extract

2020 ◽  
Vol 9 (1) ◽  
pp. 153-163 ◽  
Author(s):  
Burcu Sumer Tuzun ◽  
Tugce Fafal ◽  
Pelin Tastan ◽  
Bijen Kivcak ◽  
Besra Ozmen Yelken ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Receptor Gene ◽  
Control Cell ◽  
Antioxidant Properties ◽  
Gene Expressions ◽  
Vis Spectroscopy ◽  
Mcf 7

AbstractASP was used to synthesize FeNPA. They were characterized by UV-vis spectroscopy, FT-IR, TEM, SEM, XRD and ZP. The aim of this study was to evaluate in vitro cytotoxic activity and antioxidant acitivities of FeNPA and ASP. The antioxidant properties were evaluated using DPPH, ABTS+ and H2O2 assays. FeNPA had higher antioxidant activity comparing to ASP according to DPPH (IC50: 3.48 μg/mL) and ABTS+ (60.52%) assays. Anti-cancer activities of FeNPA and ASP were investigated in breast cancer, melanoma and control cell lines. FeNPA was more cytotoxic than ASP in MCF-7, MeWo, CHL-1, and HEL 299 cells. FeNPA had shown that mitochondria induce apoptosis through stress in MDA-MB-231, and cells MeWo. ASP also induced apoptosis 2.23-fold in MCF-7 cells. Progesterone receptor gene expression showed a 10-fold increase in a hormone-dependent MCF-7 cell line in ASP, and FeNPA treatment. Expressions of BCL6, CXCL12, DNAJC15, RB1 and TPM1 in melanoma cancer cell lines were significantly increased in ASP and FeNPA administration. It had been shown that FeNPA regulates gene expressions that may be considered important in terms of prognosis in breast cancer and melanoma cell lines and it is suggested that gene expressions regulated by FeNPA are also evaluated in animal models in vivo.

TeBG- and CBG-bound steroid hormones in rabbits are available for influx into uterus in vivo

1988 ◽  
Vol 254 (1) ◽  
pp. E79-E83
Author(s):  
G. Chaudhuri ◽  
K. A. Steingold ◽  
W. M. Pardridge ◽  
H. L. Judd
Keyword(s):  
Steroid Hormones ◽  
Plasma Proteins ◽  
Steroid Hormone ◽  
Rabbit Serum ◽  
Injection Technique ◽  
Metabolic Clearance ◽  
Adrenal Steroid ◽  
Corticosteroid Binding Globulin

The metabolic clearance rate (MCR) of gonadal or adrenal steroid hormones in rabbits often does not bear the expected inverse relationship with hormone binding to testosterone-binding globulin (TeBG) or corticosteroid-binding globulin (CBG). This suggests TeBG or CBG may not impede steroid hormone delivery to tissues. The effects of rabbit plasma proteins on the influxes of 3H-labeled steroids from the circulation into the rabbit uterus were measured in vivo using a tissue sampling single-injection technique. In the absence of plasma proteins, estradiol (E2) and testosterone (T) were freely diffusible through the uterine microvasculature (i.e., extraction greater than 80%). The extractions of dihydrotestosterone (DHT) and corticosterone (B) ranged from 60 to 72%, while that of cortisol (F) was reduced at 40%. Rabbit serum exerted no inhibition of the influxes of the steroids tested. The influxes of T and B greatly exceeded the rates that would be expected if only the free and albumin-bound fractions estimated in vitro were diffusible in vivo. However, the extraction of [3H]corticosteroid-binding globulin or bovine [3H]albumin were low, consistent with little, if any, extravascular uptake of the plasma proteins. The results indicate both albumin-bound and globulin-bound steroid hormone are available for transport into the uterus in the rabbit in vivo without significant exodus of the plasma protein, per se.

scholarly journals The Effect of Leucine Restriction on Akt/mTOR Signaling in Breast Cancer Cell Lines In Vitro and In Vivo

2011 ◽  
Vol 63 (2) ◽  
pp. 264-271 ◽  
Author(s):  
Gopal Singh ◽  
Argun Akcakanat ◽  
Chandeshwar Sharma ◽  
David Luyimbazi ◽  
Katherine Naff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Mtor Signaling ◽  
Breast Cancer Cell Lines

Recombinant Human Erythropoietin (rHuEPO) In Combination with Chemotherapy Increases Breast Cancer Metastasis In Pre-Clinical Mouse Models

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3345-3345
Author(s):  
Anargyros Xenocostas ◽  
Benjamin D Hedley ◽  
Jenny E Chu ◽  
D. George Ormond ◽  
Michel Beausoleil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Research Funding ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
In Vivo Studies ◽  
Metastatic Process

Abstract Abstract 3345 Background: Erythropoietin (EPO) is a key regulator of erythropoiesis, and has been shown to stimulate growth, maintain viability, and promote differentiation of red blood cell precursors. The EPO receptor (EPO-R) is expressed by erythroid cells and by several non-hematopoietic cell types including various neoplastic cells. Erythropoiesis-stimulating agents (ESAs) are used clinically for the treatment of chemotherapy-induced anemia. The results of some recent randomized clinical trials have reported an increased incidence in adverse events and reduced survival in ESA-treated metastatic breast cancer patients receiving chemotherapy, potentially related to EPO-induced cancer progression. These results have raised concerns over ESA treatment in metastatic cancer patients. However, very little pre-clinical data is available regarding the impact of EPO on breast cancer metastasis. The goal of the current study was therefore to determine if EPO can influence the malignant behavior of breast cancer cells and/or influence the metastatic process. Methods: MDA-MB-468, MDA-MB-231, MDA-MB-435, and 4T-1 breast cancer cell lines were treated with recombinant human EPO (rHuEPO; 10 U/ml) or control media and screened for EPO-R mRNA expression levels by RT-PCR, and for EPO-R protein expression by Western blot and flow cytometry. MDA-MB-231 (231) and MDA-MB-435 (435) cell lines were used for functional assays in vitro and in vivo. Untreated or rHuEPO treated cells were grown in 2D and 3D in vitro systems (standard tissue culture plates and 0.6% soft agar, respectively) to determine if rHuEPO influenced growth. In vitro cell survival was also assessed in response to treatment with rHuEPO in the presence or absence of paclitaxel chemotherapy (10mg/ml), radiation (10G), or hypoxic conditions (1% O2). Following mammary fat pad injection, in vivo effects of rHuEPO (300U/kg) alone or in combination with paclitaxel treatment (10mg/kg) were assessed in mouse models of tumorigenicity and spontaneous metastasis. Results: Expression analysis of EPO-R mRNA and protein revealed a large variation in levels across different cell lines. The majority of cell lines did not express cell surface EPO-R by flow cytometry, although two cell lines (231 and 435) did show weak expression of EPO-R mRNA, with only the 231 cell line showing EPO-R expression by Western blot. In vitro, a small protective effect from rHuEPO on radiation-treated 435 cells was seen (p<0.05); however, rHuEPO treatment alone or combined with chemotherapy or hypoxia did not cause a significant increase in cell survival relative to untreated controls cells. In contrast, in vivo studies demonstrated that rHuEPO increased the incidence and burden of lung metastases in immunocompromised mice injected with 231 or 435 cells and treated with paclitaxel relative to mice treated with paclitaxel alone (p<0.05). Conclusions: The lack of an in vitro effect of rHuEPO highlights the importance of in vivo studies to delineate the effects of EPO on the metastatic process. Our novel findings demonstrate that rHuEPO can reduce the efficacy of chemotherapy in the metastatic setting in vivo, and in some cases enhance the inherent metastatic growth potential of human breast cancer cells. This work was supported by funding from the London Regional Cancer Program and Janssen Ortho Canada Disclosures: Xenocostas: Janssen Ortho: Consultancy, Honoraria, Research Funding. Allan:Janssen Ortho: Research Funding.

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