Cancer is the leading cause of death worldwide. In developed as well as developing countries, breast cancer is the most common cancer found among women. Currently, treatment of breast cancer consists mainly of surgery, chemotherapy, hormone therapy, and radiotherapy. In recent years, because of increased understanding of the therapeutic potential of immunotherapy in cancer prevention, cancer vaccines have gained importance. Here, we review various immunotherapeutic breast cancer vaccines including peptide-based vaccines, whole tumor cell vaccines, gene-based vaccines, and dendritic cell vaccines. We also discuss novel nanotechnology-based approaches to improving breast cancer vaccine efficiency.
Allergy and Immunology ; Breast Neoplasms* ; Breast* ; Cancer Vaccines ; Cause of Death ; Dendritic Cells ; Developing Countries ; Drug Therapy ; Female ; Humans ; Immunotherapy ; Radiotherapy ; Vaccines*

PURPOSE: In this study, the effects of laughter therapy on levels of depression, quality of life, resilience and immune responses in breast cancer survivors were examined. METHODS: A quasi-experimental nonequivalent control group, pretest-posttest design was used. Participants (n=37) included breast cancer survivors who finished chemotheraphy and radiation therapy: 16 in the experiment group and 21 in the control group. Data were collected from August to November 2009. The experimental group participated in laughter therapy eight times, twice a week for 60 min per session. Questionnaires were used to me-asure pretest and posttest levels of depression, quality of life and resilience. A blood test was used to analyze changes in Total T cell, T helper, T suppressor, Th/Ts ratio, Total B cell, T cell/B cell ratio and NK cell for immune responses. RESULTS: The results showed that laughter therapy was effective in increasing the quality of life and resilience in breast cancer survivors. but depression and immune responses did not differ significantly between the groups. CONCLUSION: The results of the study indicate that laughter therapy may be an effective nursing intervention to improve quality of life and resilience in breast cancer survivors.
Adult ; Aged ; B-Lymphocytes/immunology/metabolism ; Breast Neoplasms/immunology/*therapy ; *Depression ; Female ; Humans ; *Laughter Therapy ; Middle Aged ; *Quality of Life ; Questionnaires ; *Resilience, Psychological ; T-Lymphocytes/immunology/metabolism

The current modalities for treating cancer employ not only single but multiple approaches involving surgery, radiotherapy and chemotherapy. Unfortunately, the survival outcome is not promising even with these approaches. Alternative approaches for cancer therapy are now emerging. Immunotherapy is aiming at both increasing the power, and in redirecting the specificity of the patients' immune system to attack the tumor cells. Recently, many studies using tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in a media containing interleukin-2 exhibit antitumor responses. IL-2 is a lymphokine produced by T-cells. It facilitates activation, sustained growth and rescue from apoptosis. Lately, newly developed IL-15 has also exhibited antitumor activity similar to IL-2. IL-15 is a newly described cytokine produced from monocytes-marcrophages and T-cells. It has a different molecular structure but it functions like IL-2 by binding to the IL-2R beta and gamma c chain. These antitumor responses are mediated by the cytotoxic T lymphocytes (CTL) that recognize the antigen in the context of the MHC molecules using the T cell receptors. CD8+-CTL recognize the peptide epitopes that are processed from the cellular proteins in the context of the MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% in breast cancers. The FBP is the source of the antigenic peptides that are recognized by a number of these CTL-TAL, and is antigenic to both ovarian and breast cancer in vivo. To define the antitumor response of IL-15 and its' FBP immunogenicity, a peptide defining epitope E39 and E75 were presented by the PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulating both ovarian and breast CTL- TAL by E39 or E75 pulsed DC (DC-E39, DC-E75), in the presence of IL-15 and IL-2 can rapidly enhance or induce the E39 or E75 specific CTL activity. The antitumor activities were measured by a chromium release assay for the tumor specific lysis activity using the ovarian and breast cancer cell lines. The tumor specific lysis activity for the ovarian TALs for IL-15 vs IL-2 were 28.6+/-3.9% and 30.3+/-3.2%, respectively and in the breast TALs, they were 14.8+/-3.1% vs 13.5+/-2.9%, respectively. Using autologous tumor cells, a slightly higher tumor specific lysis activity was obtained for the ovarian TALs cultured in IL-15 compared to IL-2 (72.0+/-8.2% vs 68.5+/-3.6%). However, for the breast TALs, they were 39.5+/-4.2% vs 41.5+/-3.3%, respectively. IL-15 is a newly developed cytokine that shows promising antitumor activity similar to IL-2. However, it requires lower dosage and is less toxic. Therefore, IL-15 might be a potential anticancer immunotherapeutic agent.
Breast Neoplasms/*immunology/therapy ; Carrier Proteins/*physiology ; Cells, Cultured ; Comparative Study ; Dendritic Cells/drug effects/*immunology ; Female ; Human ; Interleukin-15/*pharmacology ; Interleukin-2/*pharmacology ; Middle Age ; Ovarian Neoplasms/*immunology/therapy ; T-Lymphocytes, Cytotoxic/*immunology

It has been well established that immune surveillance plays critical roles in preventing the occurrence and progression of tumor. More and more evidence in recent years showed the host anti-tumor immune responses also play important roles in the chemotherapy and radiotherapy of cancers. Our previous study found that tumor- targeting therapy of anti-HER2/neu mAb is mediated by CD8(+) T cell responses. However, we found here that enhancement of CD8(+) T cell responses by combination therapy with IL-15R/IL-15 fusion protein or anti-CD40, which are strong stimultors for T cell responses, failed to promote the tumor therapeutic effects of anti-HER2/neu mAb. Analysis of tumor microenviornment showed that tumor tissues were heavily infiltrated with the immunosuppressive macrophages and most tumor infiltrating T cells, especially CD8(+) T cells, expressed high level of inhibitory co-signaling receptor PD-1. These data suggest that tumor microenvironment is dominated by the immunosuppressive strategies, which thwart anti-tumor immune responses. Therefore, the successful tumor therapy should be the removal of inhibitory signals in the tumor microenvironment in combination with other therapeutic strategies.
Animals ; Antibodies, Monoclonal ; immunology ; therapeutic use ; Breast Neoplasms ; drug therapy ; immunology ; pathology ; Cell Line, Tumor ; Female ; Humans ; Immune Tolerance ; immunology ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Receptor, ErbB-2 ; immunology ; Tumor Microenvironment ; immunology

Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4 T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.
Animals ; Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Breast Neoplasms ; drug therapy ; genetics ; immunology ; CD4-Positive T-Lymphocytes ; immunology ; pathology ; Female ; Humans ; Interleukin-17 ; antagonists & inhibitors ; genetics ; immunology ; Interleukins ; antagonists & inhibitors ; genetics ; immunology ; Macrophages ; immunology ; pathology ; Mammary Neoplasms, Animal ; drug therapy ; genetics ; immunology ; Mice ; Neoplasm Metastasis ; Tumor Microenvironment ; drug effects ; genetics ; immunology

OBJECTIVETo observe the clinical efficacy of Shenqi Fuzheng Injection (SFI) combined with chemotherapy in treating patients with advanced breast cancer.

METHODSSixty patients were randomly assigned to two groups by digital table, the control group and the treatment group, 30 in each group. All patients were treated with the same CTF regimen of chemotherapy for 21 days as one therapeutic cycle, while those in the treatment group were given SFI additionally in the meanwhite. The therapeutic efficacy was evaluated after 2 cycles of treatment by observing the changes of short-term efficacy, TCM syndrome, quality of life and immune function, as well as the adverse reaction.

RESULTSThe total short-term remission rate, the improvement rate of clinical syndrome and quality of life was 50.0%, 70.0% and 76.7% in the treatment group, and 43.3%, 46.7% and 50.0% in the control group, respectively, showing significant difference between the two groups (all P < 0.05). The occurrence of adverse reaction in the treatment group was lower than that in the control group (P < 0.05). The level of CD3+ CD4+ and CD4+/CD8+ ratio increased (P < 0.05) and CD8+ decreased in the treatment group (P < 0.01), while they showed insignificant change in the control group.

CONCLUSIONFor treatment of advanced breast cancer, SFI can alleviate the bone marrow inhibition caused by chemotherapy, improve clinical symptoms and quality of life and prolong the survival period by regulating cellular immune function of patients, so as to enhance the therapeutic effect of chemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; immunology ; pathology ; CD3 Complex ; analysis ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes ; cytology ; drug effects ; immunology ; Carcinoma, Ductal, Breast ; drug therapy ; immunology ; pathology ; Diagnosis, Differential ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Injections, Intravenous ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Quality of Life ; Syndrome ; Treatment Outcome

PURPOSE: This study was to determine the effects of abdominal breathing training using biofeedback on stress, immune response, and quality of life. METHOD: The study design was a nonequivalent control group pretest- posttest, quasi-experimental design. Twenty-five breast cancer patients who had completed adjuvant chemotherapy were enrolled. The experimental group(n=12) was provided with abdominal breathing training using biofeedback once a week for 4 weeks. State anxiety, cancer physical symptoms, serum cortisol, T cell subsets(T3, T4, T8), NK cell and quality of life were measured both before and after the intervention. RESULT: Though state anxiety, cancer physical symptoms, and serum cortisol were reduced after 4 weeks of abdominal breathing training using biofeedback, there was no statistical significance. It showed, however, improvement in quality of life (p=.02), and T3(p=.04). CONCLUSION: Abdominal breathing training using biofeedback improves quality of life in breast cancer patients after a mastectomy. However, the mechanism of this beneficial effect and stress response requires further investigation with special consideration in subject selection and frequency of measurement. Nurses should consider this strategy as a standard nursing intervention for people living with cancer.
*T-Lymphocyte Subsets ; Stress, Psychological/psychology/therapy ; *Quality of Life ; Middle Aged ; Mastectomy/*psychology/rehabilitation ; Hydrocortisone/blood ; Humans ; Female ; *Breathing Exercises ; Breast Neoplasms/immunology/*psychology/surgery ; *Biofeedback (Psychology) ; Adult

Cyclooxygenase-2 (COX-2) is an important enzyme in inflammation. In this study, we investigated the underlying molecular mechanism of the synergistic effect of rottlerin on interleukin1beta (IL-1beta)-induced COX-2 expression in MDA-MB-231 human breast cancer cell line. Treatment with rottlerin enhanced IL-1beta-induced COX-2 expression at both the protein and mRNA levels. Combined treatment with rottlerin and IL-1beta significantly induced COX-2 expression, at least in part, through the enhancement of COX-2 mRNA stability. In addition, rottlerin and IL-1beta treatment drove sustained activation of p38 Mitogen-activated protein kinase (MAPK), which is involved in induced COX-2 expression. Also, a pharmacological inhibitor of p38 MAPK (SB 203580) and transient transfection with inactive p38 MAPK inhibited rottlerin and IL-1beta-induced COX-2 upregulation. However, suppression of protein kinase C delta (PKC delta) expression by siRNA or overexpression of dominant-negative PKC delta (DN-PKC-delta) did not abrogate the rottlerin plus IL-1beta-induced COX-2 expression. Furthermore, rottlerin also enhanced tumor necrosis factor-alpha (TNF-alpha), phorbol myristate acetate (PMA), and lipopolysaccharide (LPS)-induced COX-2 expression. Taken together, our results suggest that rottlerin causes IL-1beta-induced COX-2 upregulation through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells.
Acetophenones/*pharmacology ; Benzopyrans/*pharmacology ; Breast Neoplasms/drug therapy/*genetics/immunology ; Cell Line, Tumor ; Cyclooxygenase 2/*genetics ; Enzyme Activation/drug effects ; Enzyme Inhibitors/*pharmacology ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Interleukin-1beta/*immunology ; MAP Kinase Signaling System/drug effects ; Mallotus Plant/chemistry ; NF-kappa B/immunology ; Protein Kinase C-delta/antagonists & inhibitors ; Reactive Oxygen Species/immunology ; p38 Mitogen-Activated Protein Kinases/*immunology

OBJECTIVETo discuss the anti-tumor effect of Xihuang pill on tumor-bearing rats and its effect on the immune clearance function of tumor-bearing organisms.

METHODWalker256 tumor cells were adopted to establish the tumor-bearing rat model. The rats were randomly divided into five groups: the normal control group, the model control group, the lentinan group and Xihuang pill low dose, middle dose and high dose groups, with 10 rats in each group, and continuously treated and given drugs for 14 d after modeling. Blood and tumors were collected from abdominal aorta to calculate the tumor inhibition rate. The content of CD3+, CD4+, CD8+ T cells and adhesion molecule B7-1 (CD80) in peripheral blood were detected by flow cytometry (FCM). The expressions of IL-2 and IFN-gamma in were determined by ELISA.

RESULTThe tumor inhibition rate of the Xihuang pill high dose group was 33. 1 percent. Compared with the model group, the Xihuang pill large dose group showed significantly low IL-2, IFN-gamma, CD3+, CD4+, B7-1 in peripheral blood, with statistical significance in their differences (P < 0.05).

CONCLUSIONXihuang pill could show its anti-tumor effect by enhancing the immune clearance function and increasing IL-2, IFN-gamma, CD3+ T, CD4+ T, B7-1 in peripheral blood.

Animals ; Antineoplastic Agents ; administration & dosage ; B7-1 Antigen ; genetics ; immunology ; Breast Neoplasms ; drug therapy ; genetics ; immunology ; CD4-Positive T-Lymphocytes ; drug effects ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Flow Cytometry ; Humans ; Immune System ; drug effects ; Immunologic Factors ; administration & dosage ; Interferon-gamma ; genetics ; immunology ; Interleukin-2 ; genetics ; immunology ; Rats ; Rats, Wistar ; Tumor Burden ; drug effects

Metastasis is the main cause of death in cancer patients. To improve the outcomes of patients undergoing a surgery, new adjuvant therapies that can effectively inhibit metastases have to be developed. Studies have shown that flavonoid naringenin, a natural product that is mainly present in grapes and citrus, may contribute to cancer prevention. It has many advantages compared to traditional chemotherapeutic drugs, such as low toxicity. To determine whether naringenin can also inhibit metastases, a breast cancer resection model that mimics clinical situations was established. We found that orally administered naringenin significantly decreased the number of metastatic tumor cells in the lung and extended the life span of tumor resected mice. Flow cytometry analysis revealed that T cells displayed enhanced antitumor activity in naringenin treated mice, with an increased proportion of IFN-γ and IL-2 expressing T cells. In vitro studies further demonstrated that relief of immunosuppression caused by regulatory T cells might be the fundamental mechanism of metastasis inhibition by naringenin. These results indicate that orally administered naringenin can inhibit the outgrowth of metastases after surgery via regulating host immunity. Thus, naringenin can be an ideal surgical adjuvant therapy for breast cancer patients.
Animals ; Anticarcinogenic Agents ; administration & dosage ; therapeutic use ; Antigens, CD ; analysis ; Breast Neoplasms ; drug therapy ; immunology ; pathology ; surgery ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chemotherapy, Adjuvant ; Female ; Flavanones ; administration & dosage ; therapeutic use ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Interferon-gamma ; biosynthesis ; immunology ; Interleukin-2 ; biosynthesis ; immunology ; Lung Neoplasms ; drug therapy ; immunology ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; drug effects ; immunology ; metabolism