Inhibition of Human Breast Carcinoma Growth by a Soluble Recombinant Human CD40 Ligand

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 2999-3007 ◽  
Author(s):  
Akio Hirano ◽  
Dan L. Longo ◽  
Dennis D. Taub ◽  
Douglas K. Ferris ◽  
Lawrence S. Young ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Cd40 Ligand ◽  
Interferon Γ ◽  
Human Breast Carcinoma ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Cd40 Stimulation

CD40 is present on B cells, monocytes, dendritic cells, and endothelial cells, as well as a variety of neoplastic cell types, including carcinomas. CD40 stimulation by an antibody has previously been demonstrated to induce activation-induced cell death in aggressive histology human B-cell lymphoma cell lines. Therefore, we wanted to assess the effects of a recombinant soluble human CD40 ligand (srhCD40L) on human breast carcinoma cell lines. Human breast carcinoma cell lines were examined for CD40 expression by flow cytometry. CD40 expression could be detected on several human breast cancer cell lines and this could be augmented with interferon-γ. The cell lines were then incubated with a srhCD40L to assess effects on in vitro growth. srhCD40L significantly inhibited the proliferation of the CD40+ human breast cancer cell lines. This inhibition could also be augmented with interferon-γ. Viability was also affected and this was shown to be due to increased apoptosis of the cell lines in response to the ligand. Treatment of tumor-bearing mice was then performed to assess the in vivo efficacy of the ligand. Treatment of tumor-bearing SCID mice with the ligand resulted in significant increases in survival. Thus, CD40 stimulation by its ligand directly inhibits human breast carcinoma cells in vitro and in vivo. These results suggest that srhCD40L may be of clinical use to inhibit human breast carcinoma growth.

Inhibition of Human Breast Carcinoma Growth by a Soluble Recombinant Human CD40 Ligand

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 2999-3007 ◽  
Author(s):  
Akio Hirano ◽  
Dan L. Longo ◽  
Dennis D. Taub ◽  
Douglas K. Ferris ◽  
Lawrence S. Young ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Cd40 Ligand ◽  
Interferon Γ ◽  
Human Breast Carcinoma ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Cd40 Stimulation

Abstract CD40 is present on B cells, monocytes, dendritic cells, and endothelial cells, as well as a variety of neoplastic cell types, including carcinomas. CD40 stimulation by an antibody has previously been demonstrated to induce activation-induced cell death in aggressive histology human B-cell lymphoma cell lines. Therefore, we wanted to assess the effects of a recombinant soluble human CD40 ligand (srhCD40L) on human breast carcinoma cell lines. Human breast carcinoma cell lines were examined for CD40 expression by flow cytometry. CD40 expression could be detected on several human breast cancer cell lines and this could be augmented with interferon-γ. The cell lines were then incubated with a srhCD40L to assess effects on in vitro growth. srhCD40L significantly inhibited the proliferation of the CD40+ human breast cancer cell lines. This inhibition could also be augmented with interferon-γ. Viability was also affected and this was shown to be due to increased apoptosis of the cell lines in response to the ligand. Treatment of tumor-bearing mice was then performed to assess the in vivo efficacy of the ligand. Treatment of tumor-bearing SCID mice with the ligand resulted in significant increases in survival. Thus, CD40 stimulation by its ligand directly inhibits human breast carcinoma cells in vitro and in vivo. These results suggest that srhCD40L may be of clinical use to inhibit human breast carcinoma growth.

The apoptotic effects of silibinin on MDA-MB-231 and MCF-7 human breast carcinoma cells

2016 ◽  
Vol 36 (6) ◽  
pp. 573-586 ◽  
Author(s):  
D Bayram ◽  
ES Çetin ◽  
M Kara ◽  
M Özgöçmen ◽  
IA Candan
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Human Breast Carcinoma ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Dead Cell ◽  
Human Breast ◽  
Human Breast Carcinoma Cells ◽  
Breast Carcinoma Cell Lines ◽  
Mcf 7

Background: Silibinin is a bioactive flavonolignan extracted from milk thistle, known as Silybum marianum. Silibinin exerts strong antiproliferative, proapoptotic, and anti-inflammatory effects. Many studies have shown that silibinin inhibits experimentally induced malignancies of the liver, prostate, skin, and colon as well as promotes inhibition of the proliferation of cancer cell lines in vitro. This study aimed to investigate the effects of silibinin on the human breast carcinoma cell lines MDA-MB-231 and MCF-7 in monolayer and spheroid cultures. Method: The MDA-MB-231 and MCF-7 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with silibinin at 24, 48, and 72 h of incubation. The 5-bromo-2′-deoxyuridine labeling index was used to determine the cells of the synthesis phase. Poly-ADP-ribose-polimerase immunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick and labeling assay were used to determine the death of cells in both the monolayer and spheroid cultures. Results: An half maximal inhibitory concentration dose of silibinin in MDA-MB-231 and MCF-7 cells was 100 µM/mL at 24, 48, and 72 h of incubation. Terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase were detected after treatment with silibinin in both the monolayer and spheroid cultures. The dead cell count was higher in the MDA-MB-231 and MCF-7 cell lines with silibinin applied than in the controls. Conclusions: Our study demonstrated that silibinin applications enhanced terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase in comparison to the control in both the monolayer and spheroid cultures.

Heterogeneity of MUC1 expression by human breast carcinoma cell lines in vivo and in vitro

1999 ◽  
Vol 58 (3) ◽  
pp. 253-264 ◽  
Author(s):  
Michael D. Walsh ◽  
Stuart M. Luckie ◽  
Margaret C. Cummings ◽  
Toni M. Antalis ◽  
Michael A. McGuckin
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Muc1 Expression ◽  
Human Breast ◽  
Human Breast Carcinoma Cell ◽  
Carcinoma Cell Lines ◽  
Breast Carcinoma Cell Lines

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

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