scholarly journals Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
James F. Hainfeld ◽  
Sharif M. Ridwan ◽  
F. Yaroslav Stanishevskiy ◽  
Henry M. Smilowitz
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Enhancement Factor ◽  
Triple Negative ◽  
X Rays ◽  
Breast Cancers ◽  
Human Breast ◽  
Local Tumor ◽  
Athymic Nude Mice ◽  
The Brain

Abstract About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3–4 months, even with the best available treatments, including surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. The iodine then absorbs X-rays during radiotherapy (RT), creating free radicals and local tumor damage, effectively boosting the local RT dose at the tumor. Efficacy was tested using the very aggressive human triple negative breast cancer (TNBC, MDA-MB-231 cells) growing in the brains of athymic nude mice. With a well-tolerated non-toxic IV dose of the INPs (7 g iodine/kg body weight), tumors showed a heavily iodinated rim surrounding the tumor having an average uptake of 2.9% iodine by weight, with uptake peaks at 4.5%. This is calculated to provide a dose enhancement factor of approximately 5.5 (peaks at 8.0), the highest ever reported for any radiation-enhancing agents. With RT alone (15 Gy, single dose), all animals died by 72 days; INP pretreatment resulted in longer-term remissions with 40% of mice surviving 150 days and 30% surviving > 280 days.

scholarly journals BSCI-05. HOW MICROGLIA, BRAIN RESIDENT MYELOID CELLS, RESPOND TO BREAST CANCER METASTASIS INTO THE BRAIN?

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Kamil Wojnicki ◽  
Agata Kochalska ◽  
Anna Gieryng ◽  
Tomasz Czernicki ◽  
Ewa Matyja ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Triple Negative ◽  
Metastatic Cancer ◽  
Human Breast ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
The Brain ◽  
Metastatic Cancer Cells

Abstract Brain metastasis from different cancers, including lung, breast, melanoma, colorectal or renal cell carcinoma is relatively common and its frequency increases with a prolonged survival of cancer patients. New anti-cancer therapies frequently fail to reduce metastatic burden. While the important role of tumor-associated macrophages as pro-tumorigenic cells facilitating tissue remodeling, invasion and metastasis is well documented, much less is known about the immune microenvironment of brain metastases and potential mechanisms that mediate interactions of cancer cells with brain immune cells - microglia. Triple-negative breast cancer metastases to the brain were discovered in 46% of patients. We evaluated the abundance and morphology of microglia on sections from breast cancer metastases using immunohistochemistry. We found that microglia cells are activated, surround the breast tumor cells and do not infiltrate the solid tumor. Searching for a potential attractant of microglia, we determined osteopontin levels in six human breast cancer cell lines and found upregulation of osteopontin in transformed cells, with the highest level in the triple-negative MDA-MB-231 cells. MDA-MB-231 cells activated primary murine microglia cultures when co-cultured. Invasion of MDA-MB-231 cells in co-cultures with murine immortalized BV2 microglial cells and human SV40 immortalized microglia was increased, as demonstrated using Matrigel Invasion Assay. Using immunofluorescence we detected osteopontin in cancer cells in human breast cancer metastases. Moreover, we found that minocycline, a clinically used antibiotic, reduces the osteopontin production in human breast cancer cells and the most sensitive cells were MDA-MB-231 cells. Our study shows that metastatic cancer cells may employ microglia to facilitate extravasation and colonization of brain parenchyma. We postulate that osteopontin mediates interactions between microglia and metastatic cancer cells and minocycline may interfere with those interactions. Funding: TEAM TECH CORE FACILITY FNP: Development of comprehensive diagnostics and personalized therapy in neuro-oncology

scholarly journals ASNSD1 is differentially expressed in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Asparagine Synthetase ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that asparagine synthetase domain containing 1, encoded by ASNSD1, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. ASNSD1 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of ASNSD1 in primary tumors was significantly correlated with patient post-progression survival. Modulation of ASNSD1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals Palladin is differentially expressed in both lymph node and brain metastases in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that palladin, encoded by PALLD, was among the genes whose expression was most quantitatively different in the brain metastases of patients with metastatic breast cancer. PALLD mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of PALLD in primary tumors was significantly correlated with patient overall survival in patients with breast cancer. Modulation of PALLD expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain.

scholarly journals Extracellular Calcium-Sensing Receptor Expression and Its Potential Role in Regulating Parathyroid Hormone-Related Peptide Secretion in Human Breast Cancer Cell Lines*

Endocrinology ◽  
2000 ◽  
Vol 141 (12) ◽  
pp. 4357-4364 ◽  
Author(s):  
Jennifer L. Sanders ◽  
Naibedya Chattopadhyay ◽  
Olga Kifor ◽  
Toru Yamaguchi ◽  
Robert R. Butters ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Cancer Cell Lines ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Human Breast

Abstract Metastasis of breast cancer to bone occurs with advanced disease and produces substantial morbidity. Secretion of PTH-related peptide (PTHrP) from breast cancer cells is thought to play a key role in osteolytic metastases and is increased by transforming growth factor-β (TGFβ), which is released from resorbed bone. Elevated extracellular calcium (Cao2+) also stimulates PTHrP secretion from various normal and malignant cells, an action that could potentially be mediated by the Cao2+-sensing receptor (CaR) originally cloned from the parathyroid gland. Indeed, we previously showed that both normal breast ductal epithelial cells and primary breast cancers express the CaR. In this study we investigated whether the MCF-7 and MDA-MB-231 human breast cancer cell lines express the CaR and whether CaR agonists modulate PTHrP secretion. Northern blot analysis and RT-PCR revealed bona fide CaR transcripts, and immunocytochemistry and Western analysis with a specific anti-CaR antiserum demonstrated CaR protein expression in both breast cancer cell lines. Furthermore, elevated Cao2+ and the polycationic CaR agonists, neomycin and spermine, stimulated PTHrP secretion dose dependently, with maximal, 2.1- to 2.3-fold stimulation. In addition, pretreatment of MDA-MB-231 cells overnight with TGFβ1 (0.2, 1, or 5 ng/ml) augmented both basal and high Cao2+-stimulated PTHrP secretion. Thus, in PTHrP-secreting breast cancers metastatic to bone, the CaR could potentially participate in a vicious cycle in which PTHrP-induced bone resorption raises the levels of Cao2+ and TGFβ within the bony microenvironment, which then act in concert to evoke further PTHrP release and worsening osteolysis.

scholarly journals Chrysosplenol d, a Flavonol from Artemisia annua, Induces ERK1/2-Mediated Apoptosis in Triple Negative Human Breast Cancer Cells

2020 ◽  
Vol 21 (11) ◽  
pp. 4090
Author(s):  
Sophia J. Lang ◽  
Michael Schmiech ◽  
Susanne Hafner ◽  
Christian Paetz ◽  
Katharina Werner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
High Performance ◽  
Triple Negative ◽  
Artemisia Annua ◽  
Human Breast ◽  
Mitochondrial Membrane Potential Loss

Triple negative human breast cancer (TNBC) is an aggressive cancer subtype with poor prognosis. Besides the better-known artemisinin, Artemisia annua L. contains numerous active compounds not well-studied yet. High-performance liquid chromatography coupled with diode-array and mass spectrometric detection (HPLC-DAD-MS) was used for the analysis of the most abundant compounds of an Artemisia annua extract exhibiting toxicity to MDA-MB-231 TNBC cells. Artemisinin, 6,7-dimethoxycoumarin, arteannuic acid were not toxic to any of the cancer cell lines tested. The flavonols chrysosplenol d and casticin selectively inhibited the viability of the TNBC cell lines, MDA-MB-231, CAL-51, CAL-148, as well as MCF7, A549, MIA PaCa-2, and PC-3. PC-3 prostate cancer cells exhibiting high basal protein kinase B (AKT) and no ERK1/2 activation were relatively resistant, whereas MDA-MB-231 cells with high basal ERK1/2 and low AKT activity were more sensitive to chrysosplenol d treatment. In vivo, chrysosplenol d and casticin inhibited MDA-MB-231 tumor growth on chick chorioallantoic membranes. Both compounds induced mitochondrial membrane potential loss and apoptosis. Chrysosplenol d activated ERK1/2, but not other kinases tested, increased cytosolic reactive oxygen species (ROS) and induced autophagy in MDA-MB-231 cells. Lysosomal aberrations and toxicity could be antagonized by ERK1/2 inhibition. The Artemisia annua flavonols chrysosplenol d and casticin merit exploration as potential anticancer therapeutics.

p53 Mutational Status and Survival of Human Breast Cancer MCF-7 Cell Variants after Exposure to X Rays or Fission Neutrons

1995 ◽  
Vol 142 (3) ◽  
pp. 256 ◽  
Author(s):  
Elizabeth K. Balcer-Kubiczek ◽  
Jing Yin ◽  
Kui Lin ◽  
George H. Harrison ◽  
John M. Abraham ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
X Rays ◽  
Human Breast ◽  
Mutational Status ◽  
Fission Neutrons ◽  
Mcf 7
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