Clinical significance of the CXCL8/CXCR1/R2 signalling axis in patients with invasive breast cancer.

The C-X-C motif chemokine ligand 8 (CXCL8)-C-X-C chemokine receptor (CXCR)1/2 signalling axis is among numerous mechanisms which stimulate the immune system to defend against tumour growth and influence the tumour microenvironment to promote tumour growth. This pathway plays an important role in the development of a number of cancers including breast cancer (BC). The aim of the present study was to analyse the levels of the chemokine CXCL8 and its receptors, CXCR1 and CXCR2, in the serum of female patients with invasive BC and to assess the expression of these parameters at the mRNA level, considering molecular subtypes and degrees of cancer malignancy. The study group consisted of 62 patients with histopathologically confirmed invasive BC. The control group consisted of 18 patients with histopathologically confirmed fibroadenoma, a benign breast tumour. The levels of CXCL8, CXCR1 and CXCR2 were determined by sandwich ELISA using the CLOUD-CLONE ELISA kit. CXCL8, CXCR1 and CXCR2 transcript levels were analysed using reverse transcription-quantitative PCR. Results showed that serum CXCL8 levels in female patients with invasive BC were significantly higher compared with those in the control group (P<0.05). In addition, significantly elevated CXCR1 levels were observed in luminal B human epidermal growth factor receptor 2+ carcinoma compared with those in the control group. Analysis of CXCL8 in the serum of female patients with BC showed a statistically significant difference between clinical stage G1 and G2 (P<0.05), G2 and G3 (P<0.01), and G1 and G3 (P<0.0001). On the other hand, the analysis of CXCR1 and CXCR2 levels in the serum of the patients revealed a statistically significant difference between G2 and G3 (P<0.05). The current study showed that abnormalities in the immune response involving the CXCL8-CXCR1/2 signalling axis in patients with invasive BC are involved in the development of these tumours. Moreover, the demonstrated severity of changes occurring at protein level may suggest the potential usefulness of their determination as potential diagnostic markers in the clinic.

Evaluation of potential prevalence of onconeural antibodies in women with breast cancer.

OBJECTIVE: Aim: To analyse onconeural antibodies in the blood serum of breast cancer patients without neurological symptoms.. PATIENTS AND METHODS: Materials and Methods: The study included 48 women with breast cancer. Paraneoplastic Neurologic Syndromes 12 Ag (IgG) Euroline by EUROIMMUN test was used to determine onconeural antibodies: anti-Hu, anti-Yo, anti-Ri, anti-CV2, anti-Ma/anti-Ta, anti-amphiphysin, anti-recoverin, anti-SOX1, anti-tytin, anti-zic4, anti-GAD65 and anti-Tr (DNER). RESULTS: Results: The conducted analysis revealed the presence of onconeural antibodies such as: anti-recoverin, anti-CV2, anti-Zic4, anti-SOX1, anti-MA2/Ta and antititin in blood serum of women with breast cancer. CONCLUSION: Conclusions: Further analysis may allow the assessment of the possible clinical usefulness of these determinations.

The Role of Extracellular Matrix Proteins in Breast Cancer.

The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell-cell and cell-matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors' action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets.

The immune complex p53 protein/anti-p53 autoantibodies in the pathogenesis of ovarian serous carcinoma.

OBJECTIVES: The tests conducted were intended to analyze the concentration of p53 protein and anti-p53 autoantibodies in serum of women with ovarian tumours. MATERIAL AND METHODS: The study included patients with diagnosed ovarian cancer: Cystadenoma serosum or Cystadenocarcinoma papillare serosum at IIIc stage (including 10 women who had G1, 14 women who had G2 and 30 women who had G3 staging). Concentrations of parameters were measured by ELISA. RESULTS: The analysis of the obtained results showed statistical significance between the concentration of p53 protein depending on the degree of differentiation of G1 and G3 (p < 0.001) and anti-p53 autoantibodies depending on the degree of differentiation of G1 and G2 (p < 0.05) as well as G2 and G3 (p < 0.01). In addition, the determined p53/anti-p53 autoantibodies ratio was only significant between G1 and G2 (p < 0.05), as was the assessment of the percentage of the tested parameters in the immune complex. CONCLUSIONS: Immune system disorders involving the p53 protein and anti-p53 autoantibodies may be one of the immune mechanisms involved in the pathogenesis of ovarian serous cancer.

Levels of complement components iC3b, C3c, C4, and SC5b-9 in peritoneal fluid and serum of infertile women with endometriosis.

OBJECTIVE: To assess whether complement components iC3b, C3c, C4, and SC5b-9 may be involved in the pathogenesis of endometriosis. DESIGN: Prospective, experimental trial. SETTING: Medical university. PATIENT(S): 112 women infertile women undergoing laparoscopy. INTERVENTION(S): Venipuncture and laparoscopic peritoneal fluid collection. MAIN OUTCOME MEASURE(S): Peritoneal fluid and serum iC3b, C3c, C4, and SC5b-9 levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. RESULT(S): Higher levels of C3c, C4, and SC5b-9 complement components were found in the serum compared with the peritoneal fluid, but the levels of iC3b were higher in the peritoneal fluid. We observed higher concentrations of C3c, C4, and SC5b-9 in the peritoneal fluid and serum of women with endometriosis compared with healthy women. However, the levels of iC3b in both peritoneal fluid and serum were statistically significantly lower than in the control group. CONCLUSION(S): The impairment of the mechanisms involved in the regulation of activation of complement system may be an important factor in the pathogenesis of endometriosis and endometriosis-associated infertility.