Induction of cytokines and growth factors by rapamycin in the microenvironment of brain metastases of lung cancer

Kim, Se Hoon; Lee, Jung Eun; Yang, Seung Ho; Lee, Sang Won

doi:10.3892/ol.2013.1135

Cited by 13 publications

(9 citation statements)

References 30 publications

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“…Astrocytes are a subset of glial cells responsible for maintaining intracranial homeostasis by regulating cerebral blood flow, neuronal activity through neuron–astrocyte metabolic coupling and protect neurons from toxic wastes and chemotherapeutic drugs ( 41 , 42 ). Small, early stage tumors that develop in this microenvironment can harness the protective effects of astrocytes as shown by Kim and colleagues, who reported that brain metastases from NCI-H358 lung cancer cells were less sensitive to rapamycin-induced apoptosis when co-cultured with astrocytes but not when co-cultured with fibroblasts ( 41 ). These authors also showed that co-culture of human MDA-MB-231 breast cancer cells with murine astrocytes protected the cancer cells from apoptosis by vincristine through upregulation of the anti-apoptotic survival genes, BCL2L1, TWIST1, and GSTA5.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Doses of Daily Ascorbate Protect Tumors from Radiation Damage after a Single Dose of Radiation in an Intracranial Mouse Glioma Model

et al. 2014

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Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumor environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionizing radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumor, glioblastoma multiforme (GBM), is very resistant to radiation; radiosensitizing GBM cells will improve survival of GBM patients. Here, we demonstrate that a single fraction (6 Gy) of radiation combined with a 1 h exposure to ascorbate (5 mM) sensitized murine glioma GL261 cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy) of whole brain radiation combined with daily intraperitoneal injections of ascorbate (1 mg/kg) in an intracranial GL261 glioma mouse model. Tumor-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain 8 days after tumor implantation, a second group received daily intraperitoneal injections of ascorbate (day 8–45) after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumor progression, intraperitoneal ascorbate alone had no effect on tumor progression. Tumor progression was faster in tumor-bearing mice treated with radiation and daily ascorbate than in those treated with radiation alone. Histological analysis showed less necrosis in tumors treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumor microenvironment, which determines whether ascorbate remains outside the cell, acting as a pro-oxidant, or whether it enters the cells and acts as an anti-oxidant.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Doses of Daily Ascorbate Protect Tumors from Radiation Damage after a Single Dose of Radiation in an Intracranial Mouse Glioma Model

et al. 2014

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“…Growth factors and cytokines in the tumor microenvironment play a role in the survival of metastatic cancer cells in the brain. Upon rapamycin treatment, IL-1, IL-3, IL-6, TNF-α, TGF-β, PDGF, MCP-1, and MIP-1 expression were higher in murine models of NSCLC brain metastases, but IGF-1 expression was lower compared to controls [ 27 ]. Interestingly, colony stimulating factor 1 (CSF-1) can reprogram myeloid cells, specifically into tumor-promoting macrophages in the brain parenchyma [ 20 ].…”

Section: Cytokines In Lung Cancer Brain Metastasesmentioning

confidence: 99%

The Network of Cytokines in Brain Metastases

Fares

Cordero

Kanojia

et al. 2021

Cancers

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Brain metastases are the most common of all intracranial tumors and a major cause of death in patients with cancer. Cytokines, including chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors are key regulators in the formation of brain metastases. They regulate the infiltration of different cellular subsets into the tumor microenvironment and affect the therapeutic outcomes in patients. Elucidating the cancer cell-cytokine interactions in the setting of brain metastases is crucial for the development of more accurate diagnostics and efficacious therapies. In this review, we focus on cytokines that are found in the tumor microenvironment of brain metastases and elaborate on their trends of expression, regulation, and roles in cellular recruitment and tumorigenesis. We also explore how cytokines can alter the anti-tumor response in the context of brain metastases and discuss ways through which cytokine networks can be manipulated for diagnosis and treatment.

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“…In the study of Kim et al 42 , many agents were investigated in a brain metastasis model IL-6 and several other proteins. It was found that among others, IL-6 levels were increased.…”

Section: Inflammatory Proteinsmentioning

confidence: 99%

Use of Proteins as Biomarkers and Their Role in Carcinogenesis

Zarogoulidis¹,

Tsakiridis²,

Karapantzou³

et al. 2015

J. Cancer

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Summary: Improved diagnostic methods and medical therapies are necessary for early detection and treatment and an improved prognosis. It is thus vital to both examine and evaluate the role of the various existing proteins as biomarkers in carcinogenesis and to assess the contribution of these proteins in anti-cancer activity, for consideration in therapeutic strategies. It is essential to both examine and evaluate the role of the various existing proteins as biomarkers in carcinogenesis and to assess the contribution of these proteins in anti-cancer activity, for consideration in therapeutic strategies. The purpose of this review is twofold. Firstly, it is to evaluate recent data about which proteins can be utilized as biomarkers in carcinogenesis. The proteins reviewed include: CPTP, IL-6, CCN, and S100. Secondly, it is to evaluate the contribution of dietary proteins in cancer activity. Specifically, how whey protein, soy proteins and lectin, a phytochemical could be useful in cancer prevention and treatment.Recent Findings: Whey protein, present in dairy products, is an excellent source of the sulphur amino acid cysteine, the rate limiting substrate in glutathione synthesis. Notably, this protein survives digestion and has been shown to have anti-carcinogenic properties in animal studies. Lectins are phytochemicals present in plant foods, and have active components which alters cancer initiation, promotion and progression. Lectins have been characterized as a useful tool in biochemistry, cell biology, immunology and in diagnostic and therapeutic purposes in cancer research. Soy proteins contain various compounds, including isoflavones, protease inhibitors and protein kinase inhibitors, which have been proven effective in tumor growth inhibition. They have therefore, been greatly emphasized in cancer prevention and treatment. It has been proved that soy food consumption was associated with decreased risk of death and recurrence of breast cancer. CPTP is a recently discovered protein whose main role is to transport C1P, a pro-inflammatory molecule. The discovery of CPTP may shine a light on the mechanism of inflammatory diseases, and hopefully offer a potential target for therapeutic purposes in cancer research. Interleukin-6 is a multifunctional cytokine that affects the activity of cancer cells. It is involved in tumor growth, and elevated levels is associated with an increased risk of cancer. S100B is a well-established biomarker for malignant melanoma, and useful in assessing tumor load, stage and prognosis for patients with this disease. Other members of this family of proteins include S100A4, which has been associated with several malignancies and S100A2, which has been found to be decreased in some cancers. CCN are a group of regulatory proteins, located in the extracellular matrix (maricellular). They are involved in cellular adhesion, mitogenesis, chemotaxis, cell survival, and wound healing. CCN proteins are also able to modulate the signals of several proteins, which may also influence skeletal develo...

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Induction of cytokines and growth factors by rapamycin in the microenvironment of brain metastases of lung cancer

Cited by 13 publications

References 30 publications

Pharmacological Doses of Daily Ascorbate Protect Tumors from Radiation Damage after a Single Dose of Radiation in an Intracranial Mouse Glioma Model

Pharmacological Doses of Daily Ascorbate Protect Tumors from Radiation Damage after a Single Dose of Radiation in an Intracranial Mouse Glioma Model

The Network of Cytokines in Brain Metastases

Use of Proteins as Biomarkers and Their Role in Carcinogenesis

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