Cytokines In Breast Cancer Research Articles

Pro-Inflammatory and Anti-Inflammatory Salivary Cytokines in Breast Cancer: Relationship with Clinicopathological Characteristics of the Tumor.

The aim of the work was to compare the salivary cytokine profile of breast cancer patients with the clinicopathological characteristics of the tumor. The study included 113 patients with breast cancer (main group, mean age 54.1 years) and 111 patients with breast fibroadenomas (control group, mean age 56.7 years). Before treatment, saliva samples were collected from all patients and the content of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, MCP-1, and TNF-α) was determined. The content of cytokines in saliva correlates well with the clinicopathological characteristics of breast cancer. The level of all salivary cytokines increases at advanced stages of breast cancer and at a low degree of tumor differentiation. The exception is MCP-1, for which there is an extremely high content for well-differentiated breast cancer. A statistically significant increase in the content of MCP-1, IL-1β, IL-2, IL-4, and IL-10 was found in triple-negative breast cancer. For the first time, the correlation of salivary levels of TNF-α, IL-1β, and IL-6 with HER2 status, MCP-1, IL-1β, IL-2, and IL-4 with the hormonal status of the tumor was shown. The relationship between the level of IL-2, IL-10, and IL-18 in saliva with the level of Ki-67 expression has been established.

Cytokine as an potential prognostic factor associated with absolute value of neutrophil and serum albumin in breast cancer patients.

e13007 Background: Cytokines are involved in many inflammatory diseases through various ways and play an important role in tumor immune regulation. With the development of molecular biology these years, researchers have found that breast cancer is not only related to genetic and environmental factors, but also to the chronic inflammation and immunity. But at the moment，there are few studies on the prognostic evaluation of serum cytokines in breast cancer. The correlation between serum cytokines and leukocytes was not clear. The purpose of this study is to investigate the value of serum cytokines in prognosis of breast tumors and their relationship with leukocyte characters and serum albumin level. Methods: A total of 75 serum samples and clinicopathological data of breast cancer patients from Tianjin Medical University Cancer Institute and Hospital were collected. The expression levels of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-α, IFN-γ) in serum were detected by immunofluorescence method. The absolute value of different kinds of leukocyte were determined by automatic blood analyzer. The concentration of albumin (ALB) was determined by bromocresol green method (BCG method). Univariate Cox regression and multivariate Cox regression were used to analyze the influence of the above indexes and clinicopathological features on the prognosis of patients. The correlation between the expression of cytokines and the absolute value of various kinds of leukocyte and serum albumin was studied by using multiple regression analysis. Results: A multivariate Cox proportional risk model was established by including breast cancer stage, molecular typing, IL-10, IL-12p70, absolute value of neutrophil, serum albumin and dipeptide aminopeptidase. It showed that different breast cancer stage (HR=0.415, 95%CI 0.191-0.902, P=0.026), and IL-10 (HR=0.177, 95%CI 0.038-0.821, P=0.027) were independent prognostic factors, Luminal B breast cancer had a statistically significant impact on survival compared with triple negative breast cancer (HR=0.193, 95%CI 0.067-0.554, P=0.002). The effect of other variables on survival was not statistically significant (P>0.05). Multiple linear regression analysis model demonstrated that the absolute value of neutrophils (b=1.498, t =2.938, P=0.005) and serum albumin (b=1.253, t=2.777, P=0.007) had statistically significant differences on IL-10, but breast cancer stage (b=0.635, t=1.776, P=0.08) and dipeptide aminopeptidase had no significant difference (b=0.952, t=1.715, P=0.091). Conclusions: Serum IL-10 plays an important role in indicating the prognosis of patients with breast cancer and its expression level was closely correlated with absolute value of neutrophil and serum albumin.

Revision of some Biomarkers with Cytokines in Breast Cancer

Breast cancer is the most repeatedly detected cancer category and the second reason cause of cancer-linked deaths among women worldwide. Tumor bio-indictor is a term utilized to describe possible indicators for carcinoma diagnosis, development and progression. The goal of this study is to evaluate part of some cytokines and biomarkers for both serum and saliva samples in breast cancer then estimate their potential value in the early diagnosis of breast cancer by doing more researches in saliva, and utilizing saliva instead of blood (serum and plasma) in sample collection from patients. Serum and salivary samples were taken from 72 patients with breast cancer and 45 healthy controls, in order to investigate the following cytokines such as: interleukin 12 (IL-12), interleukin 6 (IL-6), interleukin 4 (IL-4), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels with other bio-pointers such as: malondialdehyde (MDA), catalase, and 8-nitroguanine (8-NG). The results displayed that the levels of blood and saliva samples of IL-12 (P<0.0001), IL-6 (P<0.0001), IL-4 (P<0.001), 8-OHdG (P<0.0001), 8-NG (P<0.001, and P<0.004), TNF (P<0.002, and P<0.001) and IFN-γ (P<0.0001) were significantly higher in breast cancer, whereas there were significant lowering (P<0.0001) in catalase activates in breast cancer in both samples as compared with healthy subjects. The exchanging of blood to salivary components evaluation in this investigation may be utilized as a diagnostic tool, and designates the potential part for MDA, Catalase, and cytokines as important biochemical in breast cancer. Accordingly, the salivary diagnosis embraces a non-invasive process and tumor progression in breast malignancy patients. Beside saliva may well signify as an active new gate as blood evaluation but easier and cheaper.

Prognostic value of cytokines in breast cancer: Correlation with positive hormonal status and obesity

Abstract Background The relation of interleukin 6 (IL6) and molecular subtypes as well as body mass index is not well settled. Little is known about interferon gamma (IFγ) and prognosis of breast cancer. Patients and methods Serum level of IL6 and IFγ was assessed by enzyme-linked immunosorbent assay (ELISA) and correlated with the TNM staging, molecular subtypes, and body mass index. Results Among 78 patients, the median age was 54 years. The majority of the cases were T2 (62.8%), N1 (38.5%), and M0 (89.74%) with stage II being the most common (47.4%). Most females were estrogen receptor (97.9%) and progesterone receptor positive (96.9%) with high Ki67 ≥ 20 (61.5%). Her2 neu positive presented 16.7%. Luminal A and luminal B presented 29.5% and 53.8%, respectively. Obese patients presented by far the majority (82.1%). The median level of IL6 and IFγ was 56.20 ± 28.715 and 76.37 ± 41.54, respectively. IL6 was significantly correlated with tumor size (P = 0.001), nodal involvement (P = >0.0001), the presence of metastasis (P = 0.008), and the stage (P = >0.0001). High level of IL6 was associated with positive estrogen receptor, Her2 neu positive, luminal A, and being obese (P = 0.09, 0.07, 0.06, and 0.05, respectively). High IFγ was only associated with lower nodal burden being significantly higher in N1 than in N3 (118.15 ± 31.07 vs 76.37 ± 44.46, P = 0.01) and early stage (P = 0.02). Conclusions IL6 level was correlated to the initial staging, hormonal status, being Her2 positive, and obesity. The IFγ level was inversely correlated IL6 regarding the nodal status (P = 0.05).

Chitosan nano-vehicles as biocompatible delivering tools for a new Ag(I)curcuminoid-Gboxin analog complex in cancer and inflammation therapy

A novel anticancer and anti-inflammatory agent based on hybrid curcuminoid-Gboxin analog (FLLL49-GbA) and its macromolecular silver(I) complex (Ag(I)FLLL49-GbA) have successfully synthesized. In addition, chitosan nanoparticles (CNPs) were used to encapsulate this macromolecular complex, targeting enhancing its therapeutic effect and minimizing its side impacts. The encapsulated Ag(I) complex was significantly triggered apoptosis (P < 0.05) with much more rapidly release of Ag(I)FLLL49-GbA from the CNPs at pH 5.3 than at pH 7.4, which is beneficial for cancer-targeted drug delivery. Free complex showed promising ability in preventing glucose uptake and lactate production coupled with cellular ATP depletion in cancer cells. Additionally, there was significant decrease in the inflammatory cytokines in breast cancer (MCF-7) and lung cancer (A549) cells with values of P < 0.01 and P < 0.001 after 24 h incubation. Furthermore, the death-inducing proteins have been significantly up-regulated (P < 0.01 to P < 0.001) after 36 h incubation of cancer cells. Consequently, the novel curcuminoid macromolecule showed significant feasibility in triggering the high expression of apoptotic caspases caspase 3, caspase 8, P53, and Bax (P < 0.01 to P < 0.001) after 48 h of chemotherapy. Noteworthy, the cytotoxicity of Ag(I)FLLL49-GbA was significantly increased toward cancer cells (MCF-7 > A549), while, reduced toward normal cells (HeLa) after loading on chitosan Nano-vehicles.

Prognostic Value of Circulating Cytokines in Breast Cancer

Objectives: The aim of this study was to measure circulating cytokines (IL17, IL6, IL22, IL23 and TNFα) and to evaluate their role as markers and in prognosis in Tunisian patients with breast cancer. Materials and methods: Our prospective study enrolled 60 untreated patients affected by breast cancer. We evaluated their levels of TNF-α and IL6 within solid-phase, two-site chemoluminescent enzyme immunemetric assay. Seric levels of IL17, IL22 and IL23 were measured by ELISA sandwich technique and results compared by chi-2 square. Results: Our population, all females, have a mean age of 48 years, a localized disease in 75% of cases and metastatic in the resting 25%. The mean cytokines levels for IL6, IL17, TNFα, IL22 and IL23 were respectively 4.8 ± 7.2 pg/ml, 0.27 ± 0.69 pg/ml, 5.9 ± 2.2 pg/ml, 50.8 ± 34.7 pg/ml and 18 ± 30.9 pg/ml. Serum IL6 levels were significantly higher with advanced stages and particularly, metastatic stage IV and in relapsing patients. We observed also higher TNFα levels in advanced stages (III and IV) and IL22 in cases with grade III SBR. For IL23, higher levels were observed in axillary node positive cases and in patients younger than 35 years. IL17 was significantly higher with patients who relapsed. Conclusion: Our results highlight the role of cytokines in the serum as potential prognostic biomarkers in breast cancer patients, which could contribute to tumor growth and progression. Analyzing serum cytokine levels may help to identify patients with poor prognosis who may benefit from more aggressive treatment.

GP130 Cytokines in Breast Cancer and Bone

Breast cancer cells have a high predilection for skeletal homing, where they may either induce osteolytic bone destruction or enter a latency period in which they remain quiescent. Breast cancer cells produce and encounter autocrine and paracrine cytokine signals in the bone microenvironment, which can influence their behavior in multiple ways. For example, these signals can promote the survival and dormancy of bone-disseminated cancer cells or stimulate proliferation. The interleukin-6 (IL-6) cytokine family, defined by its use of the glycoprotein 130 (gp130) co-receptor, includes interleukin-11 (IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1), among others. These cytokines are known to have overlapping pleiotropic functions in different cell types and are important for cross-talk between bone-resident cells. IL-6 cytokines have also been implicated in the progression and metastasis of breast, prostate, lung, and cervical cancer, highlighting the importance of these cytokines in the tumor–bone microenvironment. This review will describe the role of these cytokines in skeletal remodeling and cancer progression both within and outside of the bone microenvironment.

Prognostic value of circulating cytokines in breast cancer: A prospective study in sixty breast cancer patients in Tunisia.

e12592 Background: Breast cancer is the second most common cancer and the fifth most common cause of cancer mortality worldwide. The functional relationship between inflammation and cancer is an old concept of cancero- genesis, and it is now clear that inflammatory process certainly potentiates and/or promotes neoplastic risk. However, many of the molecular and cellular mechanisms mediating this relationship remain unresolved. The aim of this study is to measure the level of circulating cytokines (IL17, IL6, IL22, IL23 and TNFα) in breast cancer patients in Tunisia, and to evaluate their implication as prognostic factors. Methods: Serum samples were collected prospectively from sixty breast cancer patients in Tunisia. TNF-α and IL6 levels were determined using the technique of a solid-phase, two-site chemo-luminescent enzyme immune-metric assay (Immulite 1000, USA). Serum levels of IL17, IL22 and IL23 were measured by enzyme-linked immunosorbent assays (ELISA) sandwich method. Results: The mean age of patients is 48 years, and fourth of them were metastatic. The mean level of cytokines IL6, IL17, TNFα, IL22 and IL23 were respectively 4.80 ± 7.26 pg/ ml (min 2, max 36.80 pg/ ml), 0.27 ± 0.69 pg/ ml (min 0, max 3.62 pg/ ml), 5.93 ± 2.27 pg/ ml (min 4, max 15.30 pg/ml), 50.82 ± 34.78 p/ml (min 26.48, max 199.48 pg/ ml) and 18.05 ± 30.91 pg/ ml (min 0, max 200.21 pg/ml). Serum IL6 level was significantly higher in advanced stages (p = 0.013), especially in metastatic cases (p = 0.001) and in patients who had recurrent disease (p = 0.010). High level of TNFα was also significantly associated with advanced stage (stage III and IV) (p = 0.019), and high level of IL22 was significantly associated with a high histopathological grade (Grade III of Bloom-Richardson grade (SBR)) (p = 0.028). IL23 was found to be significantly increased in lymph node metastatic cases (p = 0.042) and in young patients &lt; 35 years (p = 0.034). Finally, the level of IL17 was significantly higher in patients who had recurrent disease (p = 0.018). Conclusions: Our results highlight the role of certain circulating cytokines as potential prognostic biomarkers in breast cancer patients. The serum analysis of these cytokines, which could contribute to tumor growth and progression, may help to identify groups of patients with poor prognosis and who may need more aggressive treatment. This correlation needs to be evaluated in large prospective validating trials and suggests a rational for the development and use of cytokine blockade in treatment of some groups of breast cancer patients.

Mucoxin (Acetogenin) Reduces Proinflammatory Cytokines in Breast Cancer

Mucoxin is a potential compound used as an anticancer agent. Mucoxin induced apoptosis and inhibit proliferation in T47D breast cancer cells line. This study aims to determine the effect of mucoxin on proinflammatory cytokines in breast cancer. Proinflammatorycytokines play important role in the development and metastasis of cancer cells. Breast cancer cell line MCF-7 were grouped into five groups referred to mucoxin doses assays, they are 0 ng/mL; 0,1ng/mL; 0,5 ng/mL; 1 ng/mL; 5 ng/mL with three replication of each. Mucoxin was given for 48 hours. The levels of IL 6 and TNF-α assayed using ELISA methods. The results showed mucoxin decreases IL 6 levels in all treatment doses, but was not significant. Mucoxin also decreases TNF-α levels, with a significant reduction occurring at doses of 1 ng/mL and 5 ng/mL. It is suggested that mucoxin has potent to inhibit proinflammatory cytokines that play a role in the development and metastasis of breast cancer.

The Interleukin-17 Family of Cytokines in Breast Cancer.

Breast cancer (BC) is the most common cancer in women worldwide and remains a major cause of mortality with an expected 137,000 death this year in Europe. Standard management of metastatic BC comprises hormonotherapy, chemotherapy, and targeted therapies. Cyclin dependent kinase (CDK) and mammalian target of rapamycin (mTOR) inhibitors have recently proved their efficiency in hormonal receptor expressing BC. Checkpoint proteins inhibition is being evaluated in phase 3 studies. Since inflammation is constantly present in cancers, research teams have focused their attention on the interleukin-17 (IL-17) family of proinflammatory cytokines. Preclinical experiments have reported both pro and antitumor effects depending on the conditions. In the present article, we review the accumulating evidences about the roles of IL-17 in BC and discuss whether this family of cytokines could be a new target in anticancer treatments.

Huaier extract exerts immunomodulatory effects by regulating serum cytokines in breast cancer

Background: Huaier extract, a traditional Chinese medicine (TCM) with a 1,600-year history, has recently become a complementary anticancer drug in China. Previous studies have demonstrated that Huaier extract has multiple anticancer effects. However, whether Huaier extract has immunomodulatory effects on serum cytokine profiles in breast cancer patients remains unknown.

Dietary influence on estrogens and cytokines in breast cancer

Breast cancer affects one out of eight women in their lifetime. Many factors contribute to the development of breast cancer, such as hereditary mutations and lifetime exposure to environmental factors, including estrogen. In addition, overweight and obesity, especially with increased waist circumference, are known to be associated with breast cancer risk. This review will summarize our understanding of the effect of diet on breast cancer incidence and progression. Since some inflammatory cytokines that are changed by a high-fat diet are known to promote the growth of breast cancer cells, these cytokines may serve as biomarkers to monitor the dietary influence for women at high risk of breast cancer and as future therapeutic targets for breast cancer treatment.

Prognostic Value of Proinflammatory Cytokines in Breast Cancer

Cytokines are factors that are known to have both tumor-promoting and inhibitory effects on breast cancer growth. Different cytokines play an important role in controlling the immune system. This study was carried out to investigate the alterations in serum levels of proinflammatory cytokines (IL-1α, IL-6 and TNF-α) in breast cancer patients, and its relation with progression of this cancer. The current results revealed that there is significant elevation in median serum levels of IL-1α, IL-6 and TNF-α, P<0.001 in breast cancer patients, as compared with control groups, this elevation was significantly associated with advanced stage, P<0.001. These finding suggest that serum levels of IL-1α, IL-6 and TNF-α appears to be of some prognostic value in breast cancer.

The Emerging Role of Cytokines in Breast Cancer: From Initiation to Survivorship

The Emerging Role of Cytokines in Breast Cancer: From Initiation to Survivorship

Proinflammatory Cytokines in Breast Cancer: Mechanisms of Action and Potential Targets for Therapeutics

Inflammation within the tumor microenvironment correlates with increased invasiveness and poor prognosis in many types of cancer, including breast cancer. The cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha) and interleukin-1 beta (IL-1beta) are critical mediators of the inflammatory response. Numerous studies have also linked these cytokines to breast cancer progression. As a result, the mechanisms by which these cytokines promote breast cancer have been recently explored using both in vitro and in vivo models. The results from these studies have led to speculation regarding the possible usefulness of targeting these cytokines in breast cancer patients. This review summarizes the most recent studies pertaining to the mechanisms by which proinflammatory cytokines promote breast cancer. Furthermore, the possibilities of targeting these inflammatory mediators in breast cancer patients using inhibitors that are currently being used in the clinic for other inflammatory conditions are discussed. Understanding both the mechanisms by which inflammatory mediators promote breast cancer and the effectiveness of anti-inflammatory drugs in treating breast cancer will lead to novel therapeutic regimens to treat this devastating disease.

Cytokines in breast cancer

In recent decades many advances have occurred in the understanding of the role of cytokines in breast cancer. New signalling pathways of interleukin (IL)-1 family, IL-6, IL-11, IL-18, interferons (IFNs) and interferon regulatory factors 1 (IRF-1) and 2 (IRF-2) have been found within tumour microenvironments and in metastatic sites. Some cytokines (IL-1, IL-6, IL-11, TGFβ) stimulate while others (IL-12, IL-18, IFNs) inhibit breast cancer proliferation and/or invasion. Similarly, high circulating levels of some cytokines seem to be favourable (soluble IL-2R) while others are unfavourable (IL-1β, IL-6, IL-8, IL-10, IL-18, gp130) prognostic indicators. So far IL-2, IFNα, IFNβ and occasionally IFNγ, IL-6, IL-12 have been the cytokines used for anti tumour treatment of advanced breast cancer either to induce or increase hormone sensitivity and/or to stimulate cellular immunity. Disappointing results occurred in most trials; however, two long-term pilot studies suggest that IL-2 and IFNβ, when used appropriately can have a positive effect on clinical benefit and overall survival of patients with minimal residual disease after chemotherapy or with disseminated disease controlled by conventional endocrine therapy.

Potential prognostic and therapeutic roles for cytokines in breast cancer (Review)

Cytokines are known to have both stimulatory and inhibitory effects on breast cancer growth depending on their relative concentrations and the presence of other modulating factors in the tumour microenvironment. Certain cytokines appear to prevent an effective immune response being mounted, permitting cancer growth, whereas others promote the immune system's anti-tumour capability. Furthermore, the systemic levels of certain cytokines, e.g. IL-6 and IL-18, independently show promising correlations with disease stage and progression. With advances in methods for delivery of cytokines to a tumour site, the enhanced induction of anti-tumour immunity by targeted cytokine release is becoming a realistic option. Here, we review the role of cytokines in the immune response against breast cancer and assess their potential as prognostic indicators and/or use in immune therapy. A literature search was conducted using Medline, restricted to articles published in the English language, using combinations of the following MeSH terms: cytokines, breast cancer, immunology, immunotherapy and interleukins. Focused searches using keywords relevant to the role of cytokines in breast cancer immunology yielded >200 references.