The use of CA125, human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), risk of malignancy index (RMI) and subjective assessment (SA) in preoperative diagnosing of ovarian tumors.

OBJECTIVES: To compare utility of CA125, human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), risk of malignancy index (RMI) and subjective assessment (SA) in preoperative diagnosis of ovarian tumors. MATERIAL AND METHODS: Research was conducted among 456 patients qualified for surgery due to ovarian tumor. Preoperatively, CA125 and HE4 serum levels were estimated, and transvaginal ultrasound was performed. ROMA and RMI values and SA qualifications were obtained. Results were compared with pathomorphological findings. RESULTS: Receiver Operating Characteristic (ROC)-Area Under Curve (AUC) values for CA125, HE4, ROMA, RMI and SA in preoperative diagnosis of malignant lesions were 0.819, 0.909, 0.911, 0.895 and 0.895, respectively. Combinations of biochemical and sonographic methods increased sensitivity in diagnosis of ovarian tumors. Combinations utilizing serum HE4 concentrations were most useful. CONCLUSIONS: CA125, HE4, ROMA, RMI and SA proved to be useful in preoperative diagnosis of ovarian tumors. HE4 and ROMA occurred to be the most useful. Ultrasonographic methods are considerably useful in diagnosis of ovarian tumors. RMI and SA present similar overall diagnostic value.

Chemokine expression in patients with ovarian cancer or benign ovarian tumors.

Introduction: Chemokines play a crucial role in tumor growth and progression according to proangiogenic and immunosuppressive action. The aim of this study was to investigate the serum levels of selected chemokines in patients with ovarian cancer or benign ovarian tumors to assess their role in tumorigenesis and their potential use in preoperative diagnosis of an adnexal mass. Material and methods: The study group consisted of 59 women with ovarian cancer: 17 epithelial ovarian cancer (EOC) patients and 42 women with benign ovarian tumors. We measured in sera obtained preoperatively the level of CA125 and a panel of 5 chemokines - CX3CL1/fractalkine, CXCL1/GRO-α, CXCL12/SDF-1, CCL20/MIP-3α and IL-17F - using the chemiluminescence method with multiplexed bead based immunoassay. Results: CX3CL1 was significantly elevated in sera of advanced ovarian cancer patients compared to women with benign ovarian tumors. The significant elevation of CXCL1 was also observed (both early and advanced stages). A similar pattern was present with the standard ovarian cancer marker CA125. In our patients with endometriotic cysts CA125 levels were significantly higher than in women with other benign tumors, whereas all analyzed chemokines had similar serum titers in patients with endometriotic vs. other benign ovarian cysts. Conclusions: CX3CL1 and CXCL1 are elevated in sera of EOC patients, which indicates their role in cancer development. Moreover, they might be useful in preoperative differential diagnosis of ovarian tumors, especially as they were not elevated in cases of endometriosis.

The Effect of Recombinant Human TSH on Sclerostin and Other Selected Bone Markers in Patients after Total Thyroidectomy for Differentiated Thyroid Cancer.

The direct effect of TSH on bone metabolism in vivo is difficult to capture as the changes of its concentrations are followed by respective alterations of thyroid hormone levels. We evaluated the effect of recombinant human TSH (rhTSH) on sclerostin and other bone markers in 29 patients after total thyroidectomy for differentiated thyroid cancer (DTC), without any signs of disease recurrence, who received L-thyroxine, most at non-suppressive doses. For two consecutive days, the patients were administered a standard dose of 0.9 mg rhTSH, i.m. Concentrations of sclerostin, osteocalcin, ß-CrossLaps, PTH, and some other parameters, were measured before and five days after the first rhTSH administration. The greater the increase in TSH concentration (∆TSH), the greater the decrease in: ∆sclerostin (r = -0.672; p < 0.001), ∆ß-CrossLaps (r = -0.580; p < 0.001) and ∆osteocalcin (r = -0.405; p = 0.029) levels, were recorded. The degree of TSH increase depended on the baseline PTH (r = 0.651; p < 0.001), age, and creatinine concentrations. rhTSH strongly inhibited bone turnover, thus, TSH-independently of thyroid hormones-exerted a direct protective effect on bone metabolism. Baseline PTH affected the magnitude of TSH increase and the degree of lowering in sclerostin and ß-CrossLaps that suggest factors affecting PTH may play a role in the effect of TSH on the bone.

Is serum anti-Müllerian hormone (AMH) assay a satisfactory measure for ovarian reserve estimation? A comparison of serum and peritoneal fluid AMH levels.

BACKGROUND: Clinical cases have been reported with women who got pregnant with confirmed low serum anti-Müllerian hormone (AMH) concentrations, thus demonstrating that low serum AMH concentration cut-points could be fairly specific for poor ovarian response (POR) to gonadotrophin stimulation, but not for pregnancy. That observation prompted the question whether serum AMH concentration accurately corresponded to the whole amount of AMH secreted by granulosa cells. OBJECTIVES: To measure AMH levels in peritoneal fluid and their correlations with serum AMH concentrations. MATERIAL AND METHODS: The reported study involved 48 female patients, aged 18-40 years, diagnosed with benign ovarian cysts and qualified for a laparoscopic cystectomy. Prior to surgery, the ovarian reserve was assessed using serum AMH concentration assay. The peritoneal fluid was also collected during the laparoscopy and AMH concentrations in peritoneal fluid were measured. RESULTS: The AMH present in the peritoneal fluid strongly correlated with AMH levels in blood serum (r = 0.54; p < 0.001) and higher serum AMH concentrations corresponded to higher AMH concentrations in the peritoneal fluid. There was also a significant correlation between AMH levels in serum and in peritoneal fluid, collected from patients with endometrioma and other benign cysts (r = 0.61; p = 0.001 vs r = 0.43; p = 0.03). CONCLUSIONS: The AMH is present in the peritoneal fluid and its concentrations significantly correlate with AMH levels in serum. The assessment of AMH concentration in the peritoneal fluid may be a valuable complement to the evaluation of ovarian reserve and the diagnosis of infertility after adnexal surgery.

One-year follow-up of ovarian reserve by three methods in women after laparoscopic cystectomy for endometrioma and benign ovarian cysts.

OBJECTIVE: To determine the long-term impact of laparoscopic cystectomy for endometriomas and benign cysts on ovarian reserve and selection of the most effective method of assessment. METHODS: The present study was carried out between November 2013 and December 2016. Participants were assigned to laparoscopic cystectomy for diagnosed unilateral benign ovarian cysts and divided into groups: the endometrioma group (EG) (n=35) and the other benign ovarian tumor group (OG) (n=35). Before and at 3 and 12 months after the procedure, transvaginal ultrasonography was performed to assess antral follicle count (AFC) and ovarian volume (OvVol); laboratory tests were ordered for anti-Mullerian hormone (AMH) serum concentration assays. Pregnancy rates were counted in a 12-month follow-up. Statistica12 software was used for analysis. RESULTS: The present study included 70 women aged 18-40 years. AMH serum concentration decreased significantly 3 months after laparoscopic cystectomy (4.89 ± 3.66 ng/mL to 3.45 ± 3.37 ng/mL; P<0.001). A greater decrease of AMH concentrations was observed in the EG (45.39% vs 14.87%; P=0.021). Twelve months of observation revealed a suppression in the drop of the AMH concentration, while AFC and OvVol remained unaffected. The likelihood of spontaneous pregnancy was three times higher in the OG (hazard ratio [HR] 3.57, 95% confidence interval [CI] 1.08-12.5). CONCLUSION: There was a significant decline in AMH levels in the EG 3 months after cystectomy. No further fall in AMH concentration was observed in the 12-month follow-up. The serum AMH concentration could be considered a valuable marker for ovarian reserve assessment after laparoscopic cystectomy.

Serum concentrations of soluble (s)L- and (s)P-selectins in women with ovarian cancer.

INTRODUCTION: The aim of the study was to compare serum concentration of soluble L- and P-selectins in women with ovarian cancer (OC) and healthy controls, and to investigate sL- and sP-selectin levels with regard to clinical and pathological parameters. Correlation analysis was used to measure the following: sL- and sP-selectin concentration and Ca125; sP-selectin and platelet concentrations; and sL-selectin and serum leukocyte levels in women with OC. MATERIAL AND METHODS: The study included 29 patients with OC and 23 healthy controls. Serum concentrations of sL- and sP-selectins were measured in all subjects. Routine diagnostic tests: CBC and USG (both groups) and Ca125 (study group) were performed. RESULTS: Significantly higher serum concentrations of sL- and sP-selectins were found in the study group as compared to controls. Lower levels of serum sL-selectin were observed in women with poorly-differentiated OC (G3) and advanced stages of the disease (FIGO III, IV), but the results were statistically insignificant. No statistically significant relationship was detected between sP-selectin serum concentration in women with OC and tumour differentiation, histological type, and stage of the disease. No significant correlation was found between sL- and sP-selectins and Ca125 levels. A weak correlation was found between serum concentration of sP-selectin in women with OC and platelet count. No statistically significant correlation was observed between sL-selectin concentration and serum leukocyte levels in women with OC. CONCLUSIONS: The analysis of sL- and sP-selectin concentrations may be a useful tool in the diagnosis of OC. The levels of sL-selectin decrease with disease progression.

Glomerular filtration decrease after diagnostic cardiac catheterisation in children with congenital cardiac malformation - the role of serum creatinine, cystatin C, neutrophil gelatinase and urine output monitoring.

INTRODUCTION: Diagnosis of contrast induced-nephropathy (CIN) by a classic renal biomarker such as creatinine concentration can be delayed because of various factors that can influence this marker. Changes in new biomarkers such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C are postulated to be more sensitive for recognizing patients prone to CIN-acute kidney injury (AKI). AIM: To investigate the role of NGAL and cystatin C as early biomarkers in the diagnosis of kidney injury after cardiac catheterisation. MATERIAL AND METHODS: The study group consisted of 50 patients with congenital heart malformation admitted for scheduled cardiac catheterisation. The biomarkers serum creatinine, serum NGAL and serum cystatin C were tested at 5 time-points sequentially from start to 48 h after the procedure. RESULTS: Significant changes were noted during the research in the serum creatinine concentration (p < 0.001) and serum NGAL concentration (p < 0.001). CIN-AKI, diagnosed by the modified Schwartz formula, occurred in 16 (32%) patients after 24 h and in 8 (16%) after 48 h. Subsequent analysis showed that serum creatinine significantly rose in the first 2 h of the study with simultaneous reduction in the eGFR. Maximum growth in serum NGAL occurred at 6 h after contrast administration and then returned to the baseline values at 24 h. Serum cystatin C level did not significantly change during the study. CONCLUSIONS: We observed a transient decrease in eGFR and a rise of serum NGAL after 2 h but NGAL was most pronounced at 6 h after the procedure. The potential role of cystatin C as a biomarker of CIN-AKI was not proved.

Analysis of preoperative blood platelet parameters in terms of diversity of epithelial ovarian cancer.

Smouldering inflammation, thrombocytosis, and platelet hyper-reactivity are linked to malignancy. The relationships between preoperative diagnostic blood morphology parameters and cancer have been the focus of much interest, because some of these parameters are correlated with advanced cancer stages and poor patient survival rates. This study aimed to perform an observational, retrospective analysis of the intradiversity of blood platelet parameters in patients with different International Federation of Gynaecology and Obstetrics (FIGO) stages and different histological types of epithelial ovarian carcinomas (EOC), and also an analysis of the overall survival rate.In all, 94 EOC patients were included in this analysis (23 mucinous, 33 serous, 20 undifferentiated, 14 endometrioid, and 4 clear cell carcinoma cases). Peripheral blood samples were collected and analyzed before drug or surgical treatment.The platelet-to-neutrophil ratio (PNR) was related to the histological type of EOC, particularly mucinous carcinoma. In patients with mucinous cancer, the PNR was significantly lower compared with patients with nonmucinous cancer, and this parameter distinguished between mucinous and nonmucinous groups of patients (area under receiver-operating characteristic [ROC] curve 0.721 ±â€Š.056; sensitivity 82.6%; specificity 61%; P < .001; ROC analysis), regardless of the FIGO stage. Moreover, elevated PNR values were correlated with lower survival rate of EOC patients.The reduced PNR, similar to the lower level of cancer antigen 125, is characteristic for mucinous ovarian carcinoma patients. Moreover, elevated PNR index might correlate with poor survival of patients.

Does IGF-1 play a role in the biology of ovarian cancer?

OBJECTIVES: The aim of the study was to investigate serum concentrations of the insulin-like growth factor-1 in women with ovarian cancer and healthy controls, and to compare free IGF-1 levels with selected clinical and pathological param-eters. Correlation analysis was used to measure the following: IGF-1 concentration and Ca125; IGF-1 level and the height of the OC patients. MATERIAL AND METHODS: The study included 70 patients with OC and 50 healthy controls. Serum concentrations of free IGF-1 were measured in all subjects. Routine diagnostic tests (CBC and USG and Ca125) were performed. RESULTS: Significantly higher serum concentrations of free IGF-1 were found in the study group as compared to controls. No statistically significant relationships between IGF-1 serum concentrations and tumor differentiation, histological type, and disease stage were detected. No statistically significant correlations between IGF-1 and Ca125 level or between IGF-1 and growth of OC patients were found. CONCLUSIONS: Serum IGF-1 participates in the etiopathogenesis of ovarian cancer in menstruating women, while local synthesis of this factor and other components of the autocrine loop of the IGF-1 system play a greater role in their post-menopausal peers.

Sub-optimal primary surgery leads to unfavorable immunological changes in ovarian cancer patients.

Primary cytoreduction, followed by chemotherapy, is a standard treatment of patients with epithelial ovarian cancer (EOC). However, the effectiveness of this treatment depend on various elements e.g. type of operation. It is accepted that optimal surgery correlates with longer survival of patients. The other element, an efficiency of immune system after surgical intervention although important is less elucidated. The aim of this study was to establish the impact of optimal and sub-optimal operation on immunological status of EOC patients regarding also their overall survival (OS). On the day of primary cytoreduction and 7days after, the selected serum immunological parameters were determined in 49 patients with confirmed EOC. We found that, the level of immunosuppressive (interleukin 10; transforming growth factor-ß - TGF-ß1) and pro-inflammatory (interleukin-6 and 8) cytokines was significantly higher in the group of patients with advanced stage of disease, compared to early stage. However, the number of circulating CD3+, CD4+ or CD8+ cells, CD19+ and NK cells was similar in both group of EOC patients. The overall survival of patients who underwent optimal cytoreduction was significantly higher than that in whom only sub-optimal surgery was performed. Sub-optimal cytoreduction only partially weakened the serum level of TGF-ß1 and IL-8 and what is more enhanced the number of circulating CD4+CD25+high cells in patients with advanced stage of disease. Sub-optimal surgery and high post-operative level of TGF-ß1 increased the hazard ratio for patients. Besides, we noticed that the high pre-operative concentration of TGF-ß1 could distinguish all EOC patients (independently of FIGO classification) for whom optimal or sub-optimal surgery would be applied. Sub-optimal debulking resulted in higher immunosuppression and lower OS of EOC patients.

Secretion of cytokines and heat shock protein (HspA1A) by ovarian cancer cells depending on the tumor type and stage of disease.

Epithelial ovarian cancer is a heterogeneous disease comprising several tumor types that each have multiple histopathological features and different biological behaviors. Recent morphologic and molecular genetic studies have allowed for the categorization of various types of ovarian cancer into two groups: type I and type II. Type I tumors are low-grade and are genetically more stable, while type II tumors are high-grade and genetically unstable. The determination of the type of ovarian cancer may have implications in terms of the appropriate therapeutic strategy because different prognoses and responses to chemotherapeutic agents are observed. Therefore, the current challenge is better recognition of the features of cancer cells, which may result in more individualized therapy. The aim of the current studies was to compare the ability of ovarian cancer cells isolated from tumors, which were classified as type I or type II ovarian cancer, to release pro-inflammatory and immunosuppressive cytokines and heat shock protein (HspA1A). These factors are known to facilitate tumor cell survival, invasion and metastasis. Our studies demonstrated that ovarian cancer cells isolated from patients with type II tumors released high levels of immunosuppressive cytokines (i.e., interleukin 10 and transforming growth factor ß) and HspA1A in vitro. Conversely, ovarian cancer cells obtained from of type I tumors were significantly less active. We did not observe any difference in the ability of the isolated cancer cells to secrete pro-inflammatory cytokines, regardless of the type of ovarian cancer. In this study, we found that cancer cells from patients with type II tumors demonstrated more intense activity in regards to survival and metastasis, which should be considered during therapy.

The sL1CAM in sera of patients with endometrial and ovarian cancers.

PURPOSE: L1CAM is a cell adhesion molecule suspected to play an important role in carcinogenesis. The objective of the study was to evaluate the level of soluble L1CAM in the sera of patients with endometrial and ovarian carcinomas and verify the feasibility of the sL1CAM as a marker of these carcinomas. METHODS: 35 endometrial and 18 ovarian cancer patients were enrolled in the study. 43 patients with benign gynecological conditions constituted a control group. The sL1CAM serum level was measured with ELISA test in each patient and it was referred to the data from the surgical staging of the cancers. RESULTS: The sL1CAM serum level was significantly lower in patients with endometrial cancer than in healthy women and slightly lower in the ovarian cancer group than in the control group. In the endometrial cancer group there was no correlation between sL1CAM concentration and cancer histopathology, stage or grade. sL1CAM concentration positively correlated with ovarian cancer stage and (not significantly) with grade. CONCLUSIONS: Despite the increasing data about the possible role of L1CAM as a strong prognostic factor of poor outcome in many cancers, we did not find evidence supporting the use of sL1CAM as a marker of endometrial or ovarian cancers.

[Evaluation of applicability of HE4 and ROMA in the preoperative diagnosis of adnexal masses]. / Ocena uzytecznosci oznaczen bialka HE4 i algorytmnu ROMA w przedoperacyjnej diagnostyce guzow przydatków.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of HE4 alone and in combination with CA 125 (ROMA) in selecting patients at high risk of adnexal malignancy. MATERIAL AND METHODS: Serum CA 125 and HE4 levels were determined and the ROMA value was calculated in 259 women qualified for surgery due to adnexal mass. The results were compared with histopathological findings. RESULTS: Sensitivity and specificity in preoperative diagnosis of primary ovarian cancer were 93.2% and 71.5% for CA 125 and 95.4% and 81.3% for HE4, respectively ROMA algorithm achieved sensitivity of 95.4% and specificity of 79.8%. All methods reached sensitivity of 100% at specificity of 65.6% for CA125, 93.4% for HE4 and 82.0% for ROMA in premenopausal women, whereas in postmenopausal women sensitivity and specificity achieved levels of 92.1% and 81.7% for CA 125, 94.7% and 60.6% for HE4 and 94.7% and 76.1% for ROMA, respectively Serum levels of both CA 125 and HE4 were significantly higher in women with primary ovarian cancer as compared to benign disease. Concentrations of CA 125 in patients with endometriosis were significantly elevated as compared to women with other benign tumors. Such relation was not observed when HE4 levels were concerned. CONCLUSIONS: CA 125, HE4 and ROMA are useful in preoperative diagnosis of ovarian malignancy HE4 improves the diagnostic accuracy in cases of endometriosis, verifying false positive results of CA 125.

Spuriously high androstendione concentrations due to assay interference as a cause of diagnostic conundrum in women with oligomenorrhoea.

UNLABELLED: Polycystic ovary syndrome (PCOS) is a diagnosis of exclusion. We present two cases of women with oligomenorrhoea and high concentration of androstendione, suggestive of possible androgen-secreting tumour; caused by assay interference. The first patient, investigated for oligomenorrhoea, had no significant hirsutism or acne. Androstendione concentration was above 10.0 ng/ml (rr: 0.3-3.3 ng/ml). In order to rule out possible androgen-secreting tumour or hypercortisolaemia we performed 48-hour low dose dexamethasone suppression test (LDDST). This failed to demonstrate adequate suppression of androstendione (6.05 ng/ml and 9.32 ng/ml after the first and the second day respectively). Pelvic ultrasound examination showed polycystic ovaries, while abdominal CTscan failed to show any ovarian or adrenal lesion. Despite such high androstendione concentrations, urinary steroid profile (gas chromatography/mass spectrometry method) yielded normal results. Hence a possibility of androstendione assay interference was raised. The second patient was also admitted for investigations of oligomenorrhoea. Clinical examination was unremarkable. There was a high concentration of testosterone 0.78 ng/ml (rr. 0.084-0.481 ng/ml) and androstendione above 10.0 ng/ml (rr: 0.3-3.3 ng/ml). LDDST failed to demonstrate any suppression of androstendione, while recalculated concentrations of androstendione after serial dilutions were markedly lower in comparison to initial values. Therefore, such high androstendione concentrations (i.e. above the upper limit of the assay) must have resulted from assay interference. In both cases a final diagnosis of PCOS was established. CONCLUSIONS: In the absence of clinical features, contrasting with unusually high androgen levels, a possibility of androgen assay interference should be considered in differential diagnosis of hyperandrogenism or PCOS.

[Evaluation of the correlation between IL-1ß, IL-8, IFN-γ cytokine concentration in cervico-vaginal fluid and the risk of preterm delivery]. / Ocena korelacji miedzy stezeniem cytokin IL-1ß, IL-8, IFN-ß w wydzielinie szyjkowo-pochwowej, a ryzykiem wystapienia porodu przedwczesnego.

OBJECTIVES: The aim of the study was to evaluate IL-1ß, II-8, IFN-γ cytokine concentrations in cervico-vaginal fluid in patients with threatening preterm delivery. MATERIAL AND METHODS: The study group included 84 patients between 27 and 34 weeks of pregnancy admitted with symptoms of threatened preterm delivery. The cervico-vaginal fluid was taken from each patient qualified for the study and IL-1ß, II-8, IFN-γ concentration was analyzed by enzyme-linked immunosorbent assay (ELISA). The following factors were analyzed: maternal age and parity gestational age at admission for the examination and at delivery, sex of the newborn, Apgar evaluation at 1 and 5 minutes of life, umbilical blood pH, history of miscarriage or preterm delivery pre-pregnancy body mass index, and smoking. Their influence on the concentration of biochemical markers tested in patients at risk of preterm delivery was investigated. RESULTS: In the study group, patients who delivered preterm had significantly higher concentrations of IL-1ß and II-8 as compared to patients who delivered at term. Patients who delivered preterm more often had a history of a miscarriage and their newborns had lower birth weight, lower Apgar score, and lower pH of the umbilical blood. CONCLUSION: As far as factors significantly influencing cytokine concentrations are concerned, the level of IL-1ß and II-8 concentration is an independent predictor of preterm delivery in patients with threatened preterm labor. In the study group, the IFN-γ concentration did not significantly diversify patients who delivered preterm and at term.

Prognostic value of the immunological phenomena and relationship with clinicopathological characteristics of the tumor--the expression of the early CD69+, CD71+ and the late CD25+, CD26+, HLA/DR+ activation markers on T CD4+ and CD8+ lymphocytes in squamous cell laryngeal carcinoma. Part II.

One of the most important challenges in contemporary oncology is to find objective biomarkers of tumor aggressiveness, which help to identify more invasive phenotypes of the carcinoma. The purpose of this study was to investigate the relationships between the early and the late activation markers expression on T CD4(+) and CD8(+) cells subpopulations and certain clinicopathological characteristics of the neoplastic infiltration in order to determine their role as biomarkers for tumor behavior in squamous cell laryngeal carcinoma. Analysis of the early (CD69(+), CD71(+)) and the late activation antigens (CD25(+) (high), CD26(+), HLA/DR(+)) expression on T CD4+ and CD8(+) lymphocytes by cytofluorymetry in 55 patients treated for squamous cell laryngeal carcinoma was performed. Clinicomorphological analysis on the basis of TNM criteria and tumor front grading, which included tumor-related features and adjacent stroma-related characteristics of the peripheral edge of infiltration was carried out. The relationships between the activation markers expression and parameters of tumor aggressiveness were investigated. Our work revealed statistically significant differences in the expression of the studied activation markers on T cells with regard to certain clinicomorphological features. The expressions of CD69(+) and CD71(+) antigens on T CD3(+)CD4(+) and CD3(+)CD8(+) cells as well as CD4(+)HLA/DR(+) markers were higher for pT3 and pT4 tumors, in comparison with pT2 carcinomas. Moreover, tumors with the smallest number of TFG points were characterized by significantly lower values of the average expression of CD3(+)CD69(+) and CD3(+)CD71(+) as well as CD4(+)HLA/DR(+) markers on T lymphocytes. In addition, more aggressive and deeply infiltrating laryngeal carcinomas were most often characterized by significantly higher values of the average expression of CD69(+) and CD71(+) antigens on CD8(+) as well as HLA/DR(+) markers on CD4(+). Our study confirmed the implication of the early and the late activation antigens expression on CD4(+) and CD8(+) T lymphocytes in clinicomorphological parameters of the tumor, especially TFG total score and depth of invasion, and their importance as indicators of the invasive phenotype of laryngeal carcinoma.

The role of tumor cells in the modification of T lymphocytes activity--the expression of the early CD69+, CD71+ and the late CD25+, CD26+, HLA/DR+ activation markers on T CD4+ and CD8+ cells in squamous cell laryngeal carcinoma. Part I.

The role of interactions between tumor cells and autologous immunocompetent cells, the impact on the modulation of the activity of T CD4(+) and CD8(+) lymphocytes, as well as the influence on the regulation and determination of antitumor cellular immune response in patients with head and neck squamous cell carcinomas (HNSCC) is not completely clear. The aim of this study was to analyze early and late activation antigens expression on T cells subpopulations modified under the influence of the presence of cancer cells to investigate the regulatory mechanisms of the local cellular immune response in carcinoma of the larynx. Cytofluorymetric analysis of the early (CD69(+), CD71(+)) and late activation markers (CD25(+) (high), CD26(+), HLA/DR(+)) expression on T CD3(+)CD4(+) and CD3(+)CD8(+) cells subpopulations in mixed cellular cultures of freshly isolated tumor cells (MLTMC) and non-cancerous normal epithelial cells (MLNCC) with immunocompetent cells was performed in 55 cases of squamous cell laryngeal carcinoma. The whole peripheral blood concentrations of IL-10 and IFN-γ in 21 h and 72 h of experiments were also measured by ELISA. The relationships between the activation markers expression depending on the type of cells used in co-cultures, as well as the level of secreted cytokines, were investigated. Our work has revealed a statistically significant dependence of cytofluorymetric results on the presence of TMC or NCC in mixed cellular cultures. Increased expression of CD69(+), CD71(+) and CD25(+) (high), CD26(+), HLA/DR(+) antigens on T CD3(+)CD4(+) and CD3(+)CD8(+) cells was higher in MLTMC cultures, in comparison with MLNCC. We demonstrated negative significant relationships of IFN-γ and IL-10 secretion with regard to CD4(+)CD69(+), CD8(+)CD69(+), CD4(+)CD71(+), CD8(+)CD71(+) antigens expression in 21 h of experiments without mitogenic stimulation. Furthermore, this study revealed negative significant relationships of IFN-g secretion with regard to CD4(+)HLA/DR(+) and CD8(+)HLA/DR(+) as well as between IL-10 concentration and CD4(+)HLA/DR(+) in trials without PHA stimulation. Our findings have confirmed a key role for tumor cells in determining the function of T cells involved in the immunological processes and impact of neoplastic cells on modulating the activity of T CD4(+) and CD8(+) lymphocytes in laryngeal carcinoma.

Proinflammatory and immunosuppressive serum, ascites and cyst fluid cytokines in patients with early and advanced ovarian cancer and benign ovarian tumors.

OBJECTIVE: To analyze the profiles of interleukin-2 (IL-2), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) in serum and the tumor microenvironment (cyst fluid, ascites) in women with ovarian cancer or benign ovarian tumors to find the differences in their immunological status. We also estimated serum cytokines as biomarkers to distinguish preoperatively between malignant or benign character of tumors. DESIGN: Prospective study. SETTING: Tertiary referral hospital. POPULATION: 51 women with epithelial ovarian cancer, 26 with benign ovarian tumors of epithelial origin and 21 healthy controls. METHODS: The levels of cytokines were measured using ELISA sets. RESULTS: We did not found differences in the levels of IFN-gamma, TNF-alpha and IL-2 in all fluids isolated from patients with malignant or benign tumors. Women with advanced cancer had significantly higher serum IL-6, IL-10 and TGF-beta1 levels than women with early stages or benign tumors. Moreover, women with very advanced cancer in whom the optimal cytoreduction was disabled had the highest serum levels of IL-10, TGF-beta1 and IL-8. The concentrations of IL-6 and IL-8 were higher in ascites of cancer patients than in ascites of women with benign tumors. The areas under curves constructed for the selected cutoff serum cytokines levels (AUC-ROC) showed good predictive values for IL-6 (0.87), IL-10 (0.836) and IL-8 (0.797). CONCLUSIONS: Our results indicate on intensified inflammatory process in women with ovarian cancer (accompanied by their immunosuppression). Preoperative analysis of serum IL-6, IL-10 and IL-8 may improve the differential diagnosis of ovarian tumors.

Profile of peripheral blood neutrophil cytokines in diabetes type 1 pregnant women and its correlation with selected parameters in the newborns.

PROBLEM: Interleukin (IL)-12, IL-10, tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 alter as pregnancy progresses, implying continuous immune regulation associated with the maintenance of pregnancy. We aimed to evaluate the peripheral blood neutrophil-derived production of these cytokines in the course of pregnancy complicated by type 1 diabetes. METHOD: of study These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (P) and pregnant diabetic (PD) women. RESULTS: Neutrophil-derived secretion of TNF-alpha and IL-12 increased along with progression of pregnancy in PD and P groups. The concentration of IL-10 from lipopolysaccharide (LPS)-stimulated neutrophils increased during the course of uncomplicated pregnancy but decreased in diabetic pregnancy. Concentration of IL-8 decreased with the advancing gestational age in P and PD groups. LPS-stimulated neutrophil-derived IL-6 concentration increased only in PD patients. CONCLUSION: Our results show that diabetes creates pro-inflammatory environment thus potentially influencing the outcome of pregnancy. We conclude that neutrophil-derived cytokine production could contribute to the complications seen in pregnant women with type 1 diabetes.

EGFR immunoexpression and peripheral blood cytokine secretion as potential biomarkers of tumor behavior in laryngeal squamous cell carcinoma.

BACKGROUND: Epidermal growth factor receptor (EGFR) and proinflammatory cytokines have been implicated in the dysregulated cell growth and increased aggressiveness of human cancers. The purpose of this study was to analyze EGFR immunoexpression in neoplastic tissues and IL-6 and TNFalpha secretion by peripheral blood mononuclear cells (PBMCs) and to investigate their relationships with certain clinicopathological characteristics. MATERIAL/METHODS: Tumor expression of membranous and cytoplasmic EGFR was measured in 45 cases of laryngeal squamous cell carcinoma by IHC staining. IL-6 and TNFalpha concentrations in 21-h PBMC cultures were measured by ELISA. Relationships between EGFR and cytokine secretion and clinicopathological characteristics such as pT status, pN status, and TFG classification, which include the parameters of the most invasive zones of neoplastic tissue and histological grade, were analyzed. RESULTS: The membranous EGFR index had a very strong association with pT stage, mode of invasion, and lymphocytic plasma infiltration of the tumor stroma. Relationships between the cytoplasmic EGFR index and nuclear polymorphism as well as TFG score for advanced carcinomas and histological grade in less invasive tumors were highlighted. The correlations of IL-6 and TNFalpha levels with TFG score, pT status, histological grade, and mode of tumor invasion were also significant. CONCLUSIONS: These findings confirmed the importance of EGFR immunoexpression rate as well as IL-6 and TNFalpha secretion by PBMCs as potential biomarkers for assessing the aggressive tumor phenotype in laryngeal carcinoma.