Purpose. Previous studies have shown that melanoma cells produce excessive levels of cytokines, which have various biological roles during melanoma development. The aim of this study was to expand the profile of serum cytokines, chemokines, growth factors, and angiogenic factors that are associated with melanoma, to find more cytokines with abnormal concentrations in melanoma patients, to identify whether the level of cytokines correlated with prognostic variants, such as Breslow thickness and BRAF mutation, and, finally, to find out the cytokines that play important roles during melanoma development. Materials and Methods. Multiplex immunobead assay technology and 45-plex immunoassays ProcartaPlex™ kits were used to simultaneously compare the levels of cytokines, growth factors, angiogenic factors, and chemokines between the serum of healthy patients (n = 30) and those with melanoma (n = 72). Data were analyzed according to the clinical characteristics of the designated patient subgroups. Results. Compared to the control group, melanoma patients had higher levels of VEGF-A, PDGF-BB, IL-1RA, PIGF-1, IFN-γ, TNF-α, MIP-1α, and SCF, but lower levels of BDNF, SDF-1α, MCP-1, Eotaxin, EGF, and IL-7. Furthermore, the levels of TNF-α ( P = 0.320 , r = 0.019), IFN-γ ( P = 0.311 , r = 0.023), VEGF-A ( P = 0.014 , r = 0.337), and BDNF (0.004, r = −0.391) showed a significant correlation with Breslow thickness. IL-7 was of lower levels in patients harboring BRAF mutants. Melanoma patients with high levels of MIP-1α and MCP-1 showed the poorest overall survival. Conclusions. We found that the levels of VEGF-A and PDGF-BB in the serum of both primary and metastatic melanoma patients are elevated. TNF-α, IFN-γ, and VEGF-A presented a positive correlation with Breslow thickness, whereas BDNF showed a negative association. MIP-1α and MCP-1 correlated negatively with survival. In addition, lower levels of IL-7 were found in patients harboring BRAF mutants. These findings indicate that these cytokines may play critical roles in the progression of melanoma.

Breast cancer is the leading cause of death among women worldwide. Over the years, oxidative stress has been linked to the onset and progression of cancer. In addition to the classical histological classification, breast carcinomas are classified into phenotypes according to hormone receptors (estrogen receptor—RE—/progesterone receptor—PR) and growth factor receptor (human epidermal growth factor receptor—HER2) expression. Luminal tumors (ER/PR-positive/HER2-negative) are present in older patients with a better outcome. However, patients with HER2-positive or triple-negative breast cancer (TNBC) (ER/PR/HER2-negative) subtypes still represent highly aggressive behavior, metastasis, poor prognosis, and drug resistance. Therefore, new alternative therapies have become an urgent clinical need. In recent years, anticancer agents based on natural products have been receiving huge interest. In particular, carotenoids are natural compounds present in fruits and vegetables, but algae, bacteria, and archaea also produce them. The antioxidant properties of carotenoids have been studied during the last years due to their potential in preventing and treating multiple diseases, including cancer. Although the effect of carotenoids on breast cancer during in vitro and in vivo studies is promising, clinical trials are still inconclusive. The haloarchaeal carotenoid bacterioruberin holds great promise to the future of biomedicine due to its particular structure, and antioxidant activity. However, much work remains to be performed to draw firm conclusions. This review summarizes the current knowledge on pre-clinical and clinical analysis on the use of carotenoids as chemopreventive and chemotherapeutic agents in breast cancer, highlighting the most recent results regarding the use of bacterioruberin from haloarchaea.

Advances in immunotherapy have increased interest in knowing the role of the immune system in breast cancer (BC) pathogenesis. Therefore, immune checkpoints (IC) and other pathways related to immune regulation, such as JAK2 and FoXO1, have emerged as potential targets for BC treatment. However, their intrinsic gene expression in vitro has not been extensively studied in this neoplasia. Thus, we evaluated the mRNA expression of tumor-cell-intrinsic CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FoXO1 in different BC cell lines, derived mammospheres, and co-cultures with peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction (qRT-PCR). Our results showed that intrinsic CTLA-4, CD274 (PD-L1), and PDCD1LG2 (PD-L2) were highly expressed in triple-negative cell lines, while CD276 was predominantly overexpressed in luminal cell lines. In contrast, JAK2 and FoXO1 were under-expressed. Moreover, high levels of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), and JAK2 were found after mammosphere formation. Finally, the interaction between BC cell lines and peripheral blood mononuclear cells (PBMCs) stimulates the intrinsic expression of CTLA-4, PCDC1 (PD1), CD274 (PD-L1), and PDCD1LG2 (PD-L2). In conclusion, the intrinsic expression of immunoregulatory genes seems very dynamic, depending on BC phenotype, culture conditions, and tumor-immune cell interactions.

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the most frequently used rheumatoid arthritis (RA) diagnostic markers, but they are unable to anticipate the patient’s evolution or response to treatment. The aim of this study was to identify possible severity biomarkers to predict an upcoming flare-up or remission period. To address this objective, sera and anticoagulated blood samples were collected from healthy controls (HCs; n = 39) and from early RA (n = 10), flare-up (n = 5), and remission (n = 16) patients. We analyzed leukocyte phenotype markers, regulatory T cells, cell proliferation, and cytokine profiles. Flare-up patients showed increased percentages of cluster of differentiation (CD)3+CD4− lymphocytes (p < 0.01) and granulocytes (p < 0.05) but a decreased natural killer (NK)/T lymphocyte ratio (p < 0.05). Analysis of leukocyte markers by principal component analysis (PCA) and receiver operating characteristic (ROC) curves showed that CD45RO+ (p < 0.0001) and CD45RA+ (p < 0.0001) B lymphocyte expression can discriminate between HCs and early RA patients, while CD3+CD4− lymphocyte percentage (p < 0.0424) and CD45RA+ (p < 0.0424), CD62L+ (p < 0.0284), and CD11a+ (p < 0.0185) B lymphocyte expression can differentiate between flare-up and RA remission subjects. Thus, the combined study of these leukocyte surface markers could have potential as disease severity biomarkers for RA, whose fluctuations could be related to the development of the characteristic pro-inflammatory environment.

Background. The influence of HLA class I and II loci on the susceptibility to melanoma remains an area of intense debate. This study aimed to examine whether the HLA system was related to melanoma susceptibility and prognosis in a southern Spanish population. Methods. In this study, HLA class I and class II genotyping were performed using polymerase chain reaction sequence-specific oligonucleotides (PCR-SSO) in 237 Spanish melanoma patients and 636 ethnically matched controls. Data were analyzed according to the clinical characteristics of the defined subgroups. Results. Compared to the control group, DRB1 ∗ 16:01 (4% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 3.28) and DQB1 ∗ 05:02 (4.9% vs. 2%, p = 0.001 , Pc = 0.017, OR = 2.54) were positivity associated with the susceptibility to melanoma. Both DRB1 ∗ 16:01 (5.4% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 4.46) and DQB1 ∗ 05:02 (6.5% vs. 2%, p = 0.001 , Pc = 0.017, OR = 3.44) also showed a positive correlation with Breslow thickness >1.5 mm, most notably at an early age of diagnosis (≤58 years), DRB1 ∗ 16:01 (4.2% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 3.41) and DQB1 ∗ 05:02 (5.4% vs. 2%, p = 0.002 , Pc = 0.034, OR = 2.86). Conclusion. These findings established HLA-DRB1 ∗ 16:01 and HLA-DQB1 ∗ 05:02 loci as melanoma risk factors in the southern Spanish population.