Effects of Resistance Training at Different Loads on Inflammatory Biomarkers, Muscle Mass, Muscular Strength, and Physical Performance in Postmenopausal Women.

ABSTRACT: Carneiro, MAS, de Oliveira Júnior, GN, de Sousa, JFR, Murta, EFC, Orsatti, CL, Michelin, MA, Cyrino, ES, and Orsatti, FL. Effects of resistance training at different loads on inflammatory biomarkers, muscle mass, muscular strength, and physical performance in postmenopausal women. J Strength Cond Res 36(6): 1582-1590, 2022-It has been suggested that the effect of resistance training (RT) on circulating proinflammatory biomarkers may be dependent on muscle mass gain. A few recent studies have suggested that lower-load RT (LLRT; loads <50% of 1 repetition maximum [1RM] and repetition performed until, or close to, voluntary concentric failure) may be superior to higher-load RT (HLRT; loads >70% of 1RM) in increasing muscle mass. Hence, this study aimed to test whether LLRT is superior to HLRT for increasing muscle mass (total fat-free mass [TFFM] and leg fat-free mass [LFFM]) and improving circulating inflammatory biomarkers (interleukin [IL]-6, IL1-ra, tumor necrosis factor [TNF]-α, and extracellular heat shock protein [eHSP]70) in postmenopausal women (PW) (primary outcome). The secondary outcome was to compare the changes in muscular strength and physical performance (4-meter walking test [4-M], timed-up-and-go [TUG] test, and sit-to-stand [STS] test) between the LLRT and HLRT. The PW were randomized into 2 groups: LLRT (n = 14; loads necessary to perform 30-35 repetitions) and HLRT (n = 15; loads necessary to perform 8-12 repetitions). The greater magnitude of increase in LFFM (p = 0.033) was observed in LLRT when compared with HLRT. Moreover, there was a trend for a greater increase in TFFM in LLRT over HLRT (p = 0.070). However, there were similar improvements in TNF-α and muscular strength (p < 0.001). Furthermore, there was no significant difference between the RT schemes on IL-6, IL-1ra, and eHSP70 levels. Thus, although performing LLRT until, or close to, voluntary concentric failure seems to provide a greater stimulus for an increase in muscle mass than HLRT, it does not seem to affect the responses in circulating inflammatory biomarkers, muscular strength, and physical performance in PW.

ICAM2 is related to good prognosis in dendritic cell immunotherapy for cancer.

Objective: To evaluate the behavior of adhesion molecules ICAM-1 and ICAM-2 in dendritic cell (DC) immunotherapy. Materials & methods: 88 female Balb/c mice were divided into experimental groups. Tumors and lymph nodes were evaluated 7 and 14 days after immunotherapy. Results: Higher mean fluorescence intensity of ICAM-1 in the lymph nodes and tumors in the tumor group at 14 days was observed. Higher mean fluorescence intensity of ICAM-2 in the tumor DC vaccine group was observed after 14 days. A positive correlation was observed in the lymph nodes with ICAM-1 against tumoral volume in the tumor group. A negative correlation was found between ICAM-2 and tumoral volume in the lymph nodes of the tumor group. Conclusion: An increase in ICAM-2 in tumor DC vaccine and a decrease in ICAM-1 suggests the DC vaccine positively influences the immune system and that ICAM-2 could be a marker of good prognosis.

Dendritic cell vaccines are a type of immunotherapy that can reduce tumor volume and increase the expression of immune proteins that fight cancer. However, some improvements are needed to better analyze tumor development and cell characteristics in patients given these vaccines. This research was designed to clearly describe what happens to the body's natural defense during treatment with dendritic cell vaccines. Animals were induced to develop breast cancer and parts of their immune system were analyzed after receiving a dendritic cell vaccine. A specific molecule, called ICAM-2, which is involved in the immune response, was linked to a reduction in tumor volume. The authors conclude that ICAM-2 might be a marker of good prognosis in patients receiving a dendritic cell vaccine.

Effect of whole-body resistance training at different load intensities on circulating inflammatory biomarkers, body fat, muscular strength, and physical performance in postmenopausal women.

The primary purpose of this study was to identify the impact of whole-body resistance training (RT) at different load intensities on adipokines, adhesion molecules, and extracellular heat shock proteins in postmenopausal women. As secondary purpose, we analyzed the impact of RT at different load intensities on body fat, muscular strength, and physical performance. Forty participants were randomized into lower-load intensity RT (LIRT, n = 20, 30-35 repetition maximum in the first set of each exercise) or higher-load intensity RT (HIRT, n = 20, 8-12 repetition maximum in the first set of each exercise). Adipokines (adiponectin and leptin), adhesion molecules (MCP-1 and ICAM-1), extracellular heat shock proteins (HO-1 and eHSP60), body fat, muscular strength (1RM), and physical performance [400-meter walking test (400-M) and 6-minute walking test (6MWT)] were analyzed at baseline and after 12-weeks RT. There was a significant time-by-group interaction for eHSP60 (P = 0.049) and 400-M (P = 0.003), indicating superiority of HIRT (d = 0.47 and 0.55). However, both groups similarly improved adiponectin, ICAM-1, HO-1, body fat, 1RM, and 6MWT (P < 0.05). Our study suggests that load intensity does not seem to determine the RT effect on several obesity-related pro-inflammatory and chemotactic compounds, body fat, 1RM, and 6MWT in postmenopausal women, although a greater improvement has been revealed for eHSP60 and 400-M in HIRT. Novelty: Higher-load intensity resistance training improves eHSP60 and 400-M in postmenopausal women. Resistance training improves the inflammatory profile, body fat, muscle strength, and 6MWT, regardless of load intensity.

Local expression of interferon-alpha and interferon receptors in cervical intraepithelial neoplasia.

PURPOSE: The present study evaluated mRNA expression of interferon-alpha (IFN-alpha), IFN-alpha receptor subunits (IFNAR-1 and IFNAR-2) and an IFN-stimulated gene encoding the enzyme 2',5'-oligoadenylate synthetase (2'5'OAS) in biopsies on patients with varying grades of cervical intraepithelial neoplasia (CIN I, II and III). METHODS: Uterine cervix biopsies were collected from women with CIN I, II and III (n = 28) and controls without CIN lesions or human papilloma virus (HPV) infection (n = 17). The presence of high and low-risk HPV DNA was determined using hybrid capture. The mRNA levels of IFNAR-1, IFNAR-2, IFN-alpha and 2'5'OAS were determined by RT-PCR with specific primers. RESULTS: The control group exhibited a greater frequency of IFNAR-1 expression (10/17; 58.3%) than the CIN samples (4/28; 14.2%) (P = 0.0018), while, the expression of IFNAR-2 was also greater in the control samples (11/17; 64.7%) than in the patients with lesions (2/28; 7.1%) (P = 0.0018). Importantly, simultaneous expression of both receptors was observed only in the control group (8/17; 47.0%) (P = 0.0001). Among the CIN samples, there was one case of low expression of mRNA of IFNAR-1 and IFNAR-2. IFN-alpha was present in 14.2% (4/28) of the CIN samples but was not expressed in the control group. mRNA 2'5'OAS were expressed in 28.5% (8/28) of the CIN samples and 11.7% (2/17) of the control samples (not statistically significant). Fifty percent (14/28) of the CIN samples were positive for HPV DNA. CONCLUSIONS: Cervical biopsy samples from control women or those without neoplasia or HPV infection displayed higher IFN-alpha receptor expression than those with CIN, while simultaneous expression of both IFN-alpha receptor subunits was found only in the control group. There was no significant difference in mRNA expression of IFN-alpha and 2'5'OAS between the control and CIN groups. Then we concluded that the samples obtained from patients with CIN present low levels of the IFN-alpha receptor mRNA.

Comparative effects of high-intensity interval training with combined training on physical function markers in obese postmenopausal women: a randomized controlled trial.

OBJECTIVES: This study compared the effects of high-intensity interval training (HIIT) with effects of combined training (CT) on physical function, body composition, and muscle strength in obese postmenopausal women (PW) (trial registration: NCT03200639). METHODS: PW were randomized to CT (n = 12) and HIIT (n = 12). The CT group performed 30 minutes of moderate walking at 70% of maximum heart rate (MHR) and five resistance exercises at 70% of one repetition maximum (1RM) for 12 weeks. The HIIT group performed 10 sets of vigorous exercises (30 seconds (s) of stair climbing and 30 s of body weight squats) at >80% MHR interspersed by a light walk (recovery period at 60% MHR). RESULTS: Both groups reduced body fat percentage (0.5%), chair stand (3 s) and increased leg lean mass (0.3 kg). Only the CT, however, increased muscle strength (29%) and fast walking speed (5%) compared with HIIT. The fast walking speed changes were partially explained by the muscle strength changes (36%, r = 0.60, P = 0.027) in the CT group. CONCLUSIONS: These results suggest that HIIT is an alternative time-efficient protocol for improving chair stand and body composition when compared with CT, whereas only CT is an efficient protocol for improving muscular strength and fast walking speed in obese PW. Thus, CT must be prioritized when the increase of muscular strength and fast walking speed are the goals of training. : Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A443.

Effect of high-intensity interval training on body composition and inflammatory markers in obese postmenopausal women: a randomized controlled trial.

OBJECTIVES: This study tested whether high-intensity interval training is a time-efficient strategy for improving visceral adiposity tissue and inflammatory markers in obese postmenopausal women when compared with combined training. Moreover, we tested whether change in visceral adiposity tissue is associated with alterations in these inflammatory markers. METHODS: Postmenopausal women were randomized in two groups: combined training (n = 13) and high-intensity interval training (n = 13). The combined training group performed 60 minutes of walking at 70% of maximum heart rate and resistance exercises at 70% of one repetition maximum. The high-intensity interval training group performed 28 minutes of high-intensity exercises (> 80% of maximum heart rate). Both groups trained three times a week for 12 weeks. Body composition and inflammatory markers were analyzed with dual-energy x-ray absorptiometry scanning and enzyme-linked immunosorbent assay, respectively. RESULTS: All groups reduced body fat percentage (P = 0.026), visceral adiposity tissue (P = 0.027), leptin (P = 0.043), and increased interleukin (IL)-1 receptor antagonist (P < 0.01). The high-intensity interval training group reduced visceral adiposity tissue (P = 0.021) in a greater magnitude and increased interleukin-6 (P = 0.037) level when compared with the combined training group. Moreover, the visceral adiposity tissue changes explained the changes in IL-6 (56%; P = 0.002) only in the high-intensity interval training group. CONCLUSIONS: These results suggest that high-intensity interval training is a time-efficient strategy for improving visceral adiposity tissue and inflammatory markers in obese postmenopausal women. Moreover, we observed that serum cytokine changes, at least in part, depend on visceral adiposity tissue alterations.

Bone marrow-derived dendritic cells under influence of experimental breast cancer and physical activity.

Immune cells are required in the immune response against tumours, although sometimes without success. The present study aimed to investigate dendritic cell (DC) maturation in animals with induced immunosuppression that were subjected to physical activity (PA). Immunosuppression was induced using 7,12-dimethyl-benzanthracene (DMBA). A total of 56 Balb/c mice were divided into four groups, including the control group, non-DMBA administered/PA group (GII), DMBA administered/non-PA group (GIII) and the DMBA administered/PA group (GIV). Bone marrow was removed from the leg bones following sacrifice. Bone marrow-derived DCs were stimulated to differentiate by granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4 and tumour necrosis factor-α, after which the phenotype was assessed by flow cytometry and the cytokine profile was assessed using ELISAs. PA significantly increased the percentage of DCs in GII (55.38±2.63%) and GIV (50.1±3.1%) mice, as compared with GI (34.61±1.28%) and GIII (36.25±1.85%) mice (P<0.05). In addition, GIV mice showed a significantly higher level of cluster of differentiation (CD) 80+/CD86+ DCs (76.38±6.31%), as compared with GI (54.03±6.52%) and GIII (52.07±5.74%) mice (P<0.05). Furthermore, GIV mice showed a significantly higher level of CD80+/major histocompatibility complex class II double labelling (P<0.05), as compared with GIV (95.35±1.22%) and GIII (76.15±5.53%) mice. The expression of interferon-γ was significantly increased in GIV mice [5.89 (5.2-7.12)], as compared with GIII mice [2.75 (1.33-4.4)] (P<0.05). Similarly, the expression of IL-12 was markedly increased in GIV mice [1.27 (0.26-2.57)] compared with GIII mice [0.73 (0.44-1.47)], although the difference was not significant (P=0.063). The results of the present study suggested that PA was able to promote the maturation of DCs and their secretion of anti-tumour cytokines. Therefore, PA may emerge as a tool in immunotherapy.

The influence of physical activity in the anti-tumor immune response in experimental breast tumor.

This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analysed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow. Were used female Balb/c mice divided into 4 groups: two controls without tumor, sedentary (GI) and trained (GII) and two groups with tumor, sedentary (GIII) or trained (GIV). The physical activity (PA) was realized acoording swimming protocol. Tumor was induced by injection of 4T1 cells. All experiments were performed in biological triplicate. After the experimental period, the tumor was removed and the cells were identified by flow cytometry with labeling to CD4, CD8, CD11c, CD11b, CD80, CD86 and Ia, and intracelular staining IL-10, IL-12, TNF-α, IFN-γ, IL-17, Tbet, GATA3, RORγt and FoxP3. The bone marrow of the animals was obtained to analyse the derivated DCs by flow cytometry and culture cells to obtain the supernatant to measure the cytokines. Our results demonstrated that the PA inhibit the tumoral growth although not to change the number of TILS, but reduced expression of GATA-3, ROR-γT, related with poor prognosis, and TNF-α intracellular; however occur one significantly reduction in TIDCS, but these cells expressed more co-stimulatory and presentation molecules. Furthermore, we observed that the induced PA stimulated the gene expression of Tbet and the production of inflammatory cytokines suggesting an increase of Th1 systemic response. The results evaluating the systemic influence in DCs showed that the PA improve significantly the number of those cells in bone marrow as well the number of co-stimulatory molecules. Therefore, we could conclude that PA influence the innate immunity by interfering to promote in process of maturation of DCs both in tumor and systemically, that by its turn promote a modification in acquired immune cells, representing by T helper to induce an important alteration transcription factors that are responsible to maintain a suppressive microenviroment, and thereby, allowing the latter cells can thus activate antitumor immune response. The PA was able improve the Th1 systemic response by enhance to Tbet gene expression, promote a slightly increased of Th1-type cytokines and decrease Gata3 and Foxp3 gene expression in which can inhibit the Th1 immune response.

Evaluation of T, B and natural killer lymphocyte in the cervical stroma of HIV-positive and negative patients with cervical intraepithelial neoplasia.

Cervical intraepithelial neoplasias (CIN) are closely associated with oncogenic subtypes of the human papillomavirus (HPV). In the presence of this virus, it is known that the activation or suppression of immune system is the key to the development, progression and/or regression of cervical lesions. Therefore, the objective of this study is to compare the local immune response among HIV-seropositive and seronegative patients with cervical intraepithelial neoplasia regarding the expression of T lymphocytes (CD3+, CD4+ and CD8+), B lymphocytes (CD20+) and natural killers cells (CD56+) in the cervical stroma. A cross-sectional study of paraffin blocks containing cervical tissue after conization by the Loop Electrosurgical Excision Procedure (LEEP) from 47 HIV-seropositive and 38 seronegative patients with CIN. Cervical stroma immunohistochemistry was performed in the CIN area. The Fisher's exact test was used for the statistical analysis. When HIV-seropositive and seronegative women were compared, the seropositive women had a higher count of CD8+ T lymphocytes (52.1% versus 28.9%, P<0.04). Considering CIN degree (CIN 1 and CIN 2/3), the HIV-seronegative patients with CIN 1 had a low count of CD20+B-lymphocytes (7.1%) in comparison with CIN 1 HIV seropositive and with CIN 2/3 HIV-seronegative patients, respectively 50% (P<0.018) and 54.5% (P<0.0048). The HIV infection and degree of CIN influenced the cytotoxic lymphocytes inducing an increase in the number of cells high count of CD20+ lymphocytes with CIN 1.

Angiogenesis Markers in Gynecological Tumors and Patents for Anti-Angiogenic Approach: Review.

The formation of a tumor-associated vascular network is an important step in understanding the stages of tumor progression. This review aims to highlight the main markers of induction, proliferation and inhibition of angiogenesis, as well as the quantification of microvessel density, correlated with preclinical and clinical research in gynecologic cancers and also discussed related patents. Studies show that in the most advanced cases of gynecological cancers, biomarkers such as VEGF (Vascular Endothelial Growth Factor), MMP (Matrix Metalloproteinase), CD105 (Endoglin), TIMP (tissue inhibitors of metalloproteinases) and VASH (Vasohibin) are more expressed compared to healthy individuals. Continuous evaluation of these biomarkers in cancer cases could serve in the future as a basis for development of new therapeutic approaches, leading to a good response to cancer treatment, and thus increase survival of cancer patients.

Interleukin-12 in patients with cancer is synthesized by peripheral helper T lymphocytes.

The production of cytokines by helper T lymphocytes is a critical event in the immune response, as alterations in the regulation of this process may result in an appropriate immune response, persistent infection or the development of autoimmune disease. Previously, this group has used flow cytometry to demonstrate the expression of interleukin-12 (IL-12) in peripheral blood CD4+ T lymphocytes from patients and mice with advanced cancer. The aim of the present study was to investigate whether CD4+ T lymphocytes from the peripheral blood (PB) of patients with cancer produce IL-12, using molecular approaches, flow cytometry and cellular imaging techniques. CD3+ and CD4+ cells, and cells producing IL-12, were isolated from the PB obtained from patients with cancer, using a cell sorting flow cytometry technique. The positivity of cells for CD3, CD4 and IL-12, which were identified by cell sorting, was visualized using immunofluorescent cellular imaging. Total RNA was extracted from the CD3+CD4+IL-12+ cells, obtained by cell sorting, for confirmation of the presence of IL-12 mRNA, using reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR demonstrated the presence of IL-12 mRNA in all patients (n=14), in contrast to the control group, in whom IL-12 expression was not detected. Immunofluorescent analysis of CD4+ T lymphocytes showed positive intracytoplasmatic IL-12 staining. These results demonstrated that CD3+CD4+ T lymphocytes in the PB of patients with cancer have the capacity to synthesize and express IL-12.

Dendritic cell vaccine and cancer treatment: new patents.

Dendritic cell (DC) immunotherapy has been used to treat various types of tumors. Although it is already in use in clinical practice, the mechanisms through which it acts need clarification. In addition, the processes used to obtain DCs need to be improved so that more effective treatments can be offered. In this article, we present an update on the application of DC immunotherapy and the patents involved in the process.

Pattern response of dendritic cells in the tumor microenvironment and breast cancer.

Breast cancer (BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development, including malignancy grade and patient prognosis, is influenced by various mutations that occur in the tumor cell and by the immune system's status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Among the immune response cells, dendritic cells (DCs) play a key role in the induction and maintenance of anti-tumor responses owing to their unique abilities for antigen cross-presentation and promotion of the activation of specific lymphocytes that target neoplasic cells. However, the tumor microenvironment can polarize DCs, transforming them into immunosuppressive regulatory DCs, a tolerogenic phenotype which limits the activity of effector T cells and supports tumor growth and progression. Various factors and signaling pathways have been implicated in the immunosuppressive functioning of DCs in cancer, and researchers are working on resolving processes that can circumvent tumor escape and developing viable therapeutic interventions to prevent or reverse the expression of immunosuppressive DCs in the tumor microenvironment. A better understanding of the pattern of DC response in patients with BC is fundamental to the development of specific therapeutic approaches to enable DCs to function properly. Various studies examining DCs immunotherapy have demonstrated its great potential for inducing immune responses to specific antigens and thereby reversing immunosuppression and related to clinical response in patients with BC. DC-based immunotherapy research has led to immense scientific advances, both in our understanding of the anti-tumor immune response and for the treatment of these patients.

Innate immune response adaptation in mice subjected to administration of DMBA and physical activity.

Although there is growing interest in studies that promote the benefits of exercise and the correlation between exercise and fighting cancer, previous studies have not been able to elucidate the underlying mechanisms. The aim of the present study was to investigate cytokine synthesis by peritoneal macrophages in the presence of mammary tumors and the effect of physical activity. Female BALB/c virgin mice (age, eight weeks) were obtained for the present study and divided into four groups: A no tumor/non-trained control group; a no tumor/trained group subjected to swim training; a tumor/non-trained group in which the mice received the carcinogenic drug, DMBA and a tumor/trained group in which the mice were subjected to DMBA and swim training protocols. Following the experimental period, immune cells were collected from the peritoneal fluid, placed in culture medium and stimulated with lipopolysaccharide. The presence of the cluster of differentiation-14 marker and expression of the interleukin (IL)-12 cytokine was assessed by flow cytometry and measured via an enzyme-linked immunosorbent assay. The following cytokines were also identified: Interferon-γ, IL-4, IL-10, IL-12, tumor necrosis factor-α and transforming growth factor-ß. Physical activity increased the quantity of IL-12 producing macrophages, whereas the presence of a tumor decreased the quantity of macrophages expressing IL-12. Tumor induction, in the absence of swim training, reduced macrophage-profile 1 (M1) cytokine levels while increasing the presence of macrophage-profile 2 cytokines. Physical activity in mice with tumors resulted in reductions in tumor development and promoted immune system polarization towards an antitumor M1 response pattern profile.

The influence of physical activity on the profile of immune response cells and cytokine synthesis in mice with experimental breast tumors induced by 7,12-dimethylbenzanthracene.

This study aims to investigate cytokine synthesis by lymphocytes in the presence of mammary tumors and the interaction with physical activity. For this study, we used 56 female Balb/c, 8-week-old, virgin mice with a body mass between 20 and 30 g. The mice were divided into four groups: a no tumor/nontrained control group; a no tumor/trained group subjected to physical training of swimming in water (30 ± 4°C) for 45 min, five times per week for 8 weeks; a tumor/nontrained (sedentary) group in which the animals received 7,12-dimethylbenzanthracene [(DMBA) 1 mg/ml weekly for 6 weeks)]; and a tumor/trained group in which animals were subjected to the aforementioned DMBA tumor induction and swim training protocols. After the experimental period, immune cells were collected from spleen cell specimens, placed in culture, and stimulated with lipopolysaccharide. The presence of cluster of differentiation (CD)3, CD4, and CD8 markers and the expression of interferon-γ, interleukin (IL)-2, IL-4, IL-10, IL-12, transforming growth factor ß, and tumor necrosis factor α cytokines were assessed by flow cytometry and enzyme-linked immunosorbent assay. Physical activity increased the quantities of lymphocytes producing interferon γ, IL-2, IL-12, and tumor necrosis factor α and decreased the quantities of lymphocytes and macrophages expressing IL-4, IL-10, and transforming growth factor ß. In contrast, tumor induction, in the absence of swim training, reduced Th1 cytokine levels while increasing the presence of Th2 cytokines and Treg cells. Physical activity promoted reductions in the incidence of tumor development and promoted immune system polarization toward an antitumor Th1 response pattern profile.

Peripheral helper lymphocytes produce interleukin 12 in cancer patients.

The aim of the study was to seek evidence for the production of IL-12 by CD4(+) T lymphocytes in in vitro and ex vivo trials. We performed in vitro trials with spleen cells from mice subjected to carcinogenesis, as well as ex vivo trials with cells obtained from the peripheral blood of healthy individuals and cancer patients. We were able to verify a significantly increased expression of IL-12 in CD4(+) T lymphocytes from mice and patients with tumors, compared to controls. Follow-up studies are needed to clarify whether this difference is related to being in a chronic disease state or whether it is an attempt by the immune system to produce an anti-tumor response, since T lymphocytes from healthy donors were not able to produce IL-12 when in contact with polyclonal stimuli. We concluded that, in cancer, T helper cells are capable of synthesizing IL-12, raising the question of whether we are faced with another profile, Th12.

Immunotherapy with dendritic cells as a cancer treatment: perspectives and therapeutic potential.

The immune system, which is indispensible for controlling neoplasias, relies on its innate and acquired immunity components to mount an effective response against tumors. In this context, dendritic cells (DCs) are seen as the best antigen-presenting cells because of their capacity for cross-presentation, which can activate both T-helper and cytotoxic lymphocytes. Thus immunotherapy with DCs is considered promising, especially for early-stage cancers. This article provides a clarifying review of recent perspectives on the development of cancer immunotherapy, which has a wide potential for therapeutic applications, and of patents related to immunotherapy with DCs.

Influence of immunotherapy with autologous dendritic cells on innate and adaptive immune response in cancer.

The objective of this study was to evaluate some of the mechanisms involved in the activation of the immune system in patients with advanced-stage cancer (n = 7) who received an autologous dendritic cell vaccine. We examined the immune response mediated by macrophages (CD14+), natural killer cells (CD56+), and B lymphocytes (CD19+) by flow cytometry and assessed the expression of Th1 (IFN-γ, TNF-α, IL-2, and IL-12), Th2 (IL-4), and Treg (TGF-ß) cytokines by flow cytometry and an enzyme-linked immunosorbent assay. The CD14+ TNF-α+ population was significantly increased (P < 0.04) when patients received the vaccine; IL-2 expression in both NK cells and in B lymphocytes was increased after a transient initial increase showed a nearly significant decrease (P < 0.07 and P < 0.06 respectively), whereas the CD19+ and CD56+ populations did not show significant changes. Dendritic cell-based immunotherapy led to increased secretion of IFN-γ and IL-12 and reduced secretion of TGF-ß. In conclusion, it is likely that the autologous dendritic cell vaccine stimulated the immune cells from the peripheral blood of patients with cancer and generally increased the production of Th1 cytokines, which are related to immunomodulatory responses against cancer.

Rheumatoid arthritis-increased gene expressions in muscle atrophy are restored back to control as a response to acute resistance exercise / Estímulo agudo de musculação promove regulação de genes alterados pela atrofi a muscular

This study had as objective to analyze the acute eff ects of resistance exercise (RE) on the mRNA levels of the following genes (MyoD, myogenin, IGF-1, atrogin-1, MuRF-1, and myostatin) in rheumatoid arthritis (experimental arthritis). Therefore, 26 females rats were randomly allocated into four groups, control (CT, n=7), exercise (Ex, n=6), rheumatoid arthritis (RA, n=6) and RA with exercise (RAEx, n=7). Met-BSA was injected into the tibiotarsal joint in the RA and RAEx groups. After 15 days from injection, the animals were submitted to an acute bout of RE and six hours post protocol the animals were euthanized. We evaluated the joint thickness, infl ammation score, cross-sectional area (CSA) of gastrocnemius muscle fi bers and mRNA expression of the IGF-1, MyoD, myogenin, myostatin, MuRF-1, atrogin-1 and GAPDH. It was observed that the joint thickness and score strongly increased in arthritic rats (p <0.001) while the CSA decreased (p ≤ 0.05). Increased mRNA levels of IGF-1 (2.0 fold), myostatin (4.5 fold), atrogin-1 (2.5 fold), MyoD (3.7-fold) and myogenin (5 fold) were observed in muscle of arthritic rats. The mRNA expression of myostatin, atrogin-1, MyoD and myogenin decreased in the RAEx group. In this way, we can conclude that experimental arthritis-increased gene expressions in muscle atrophy myostatin, atrogin-1, MyoD and myogenin) are restored back to control as a response to acute RE....(AU)

O presente estudo teve como objetivo analisar o efeito agudo do Exercício com pesos sobre os níves de mRNA de genes envolvidos no anabolismo ou catabolismo muscular em um modelo experimental de Artrite Reumatóide. Para tanto, 26 ratas fêmeas foram randomicamente alocadas em quatro grupos, controle (CT, n=7), Exercício (Ex, n=6), Artrite Reumatóide (AR, n=6) e Artrite Reumatóide com exercício (AREx, n=7). Uma substância contendo Albumina bovina metilada foi injetada na articulação tíbio-tarsal nos grupos AR e AREx para indução da Artrite Reumatóide. Após 15 dias da injeção, os animais foram submetidos a um estímulo agudo de treinamento com pesos e 6 horas após o exercício os animais foram eutanasiados. Nós avaliamos a espessura da articulação, escore de infl amação, a área de secção transversa (AST) das fi bras do músculo Gastrocnêmio e a mRNA de IGF-1, MyoD, Myogenina (genes envolvidos no anabolismo muscular), e MuRF-1, atrogina-1 (genes envolvidos no catabolismo muscular), além do gene controle , GAPDH. Foi observado que a espessura articular e o escore de infl amação aumentaram fortemente nas ratas induzidas a Artrite Reumatóide (p <0,001), enquanto a AST reduziu (p ≤ 0,05). Um aumento nos níveis de mRNA de IGF-1 (2,0 vezes), miostatina (4,5 vezes), atrogina-1 (2,5 vezes), MyoD (3,7 vezes) e miogenina (5 vezes) foi observado no músculo das ratas induzidas a Artrite Reumatóide. mRNA de miostatina, atrogina-1, MyoD e miogenina reduziu no grupo RAEx. Desta forma, podemos concluir, que o modelo experimental de Artrite Reumatóide induziu um aumento da expressão de genes durante a atrofi a muscular (myostatin, atrogin-1, MyoD and myogenin) e que estas alterações foram reguladas pelo Exercício com peso....(AU)

The role of T lymphocytes in cancer patients undergoing immunotherapy with autologous dendritic cells.

INTRODUCTION: Cancer stems from mutations in specific genes that induce uncontrolled cell proliferation. Dendritic cells (DCs) are important immunologic cells and play a crucial role in the induction of an antitumour response. PATIENTS AND METHODS: We examined the immune response mediated by T lymphocytes, helper T cells, cytotoxic T cells, and regulatory T cells, as well as the cytokines [interleukin (IL)-2, IL-12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-10], produced by these cell populations, in cancer patients (N = 7) undergoing immunotheraphy with autologous DCs. RESULTS: We observed an initial increase in T helper cells (CD4+) expressing IL-2, IFN-γ, IL-12, TNF-α, and IL-10 after initiation of treatment, with statistically significant for the cytokines IL-2, TNF-α and IL-10. A similar significant effect was observed for IL-2-expressing cytotoxic T cells (CD8+). The percentage of total T cells (CD3+) remained elevated throughout immunotherapy. Regulatory T cells (CD25+/FOXP3+) only showed high percentage of their maximum value when analyzed the pretreatment levels, with statistically significant. CONCLUSION: Immunotherapy with DCs stimulated the immune response, as evidenced by an increase in percent fluorescence of most cell populations investigated during the specified treatment period.