Heat shock protein 27 (hsp27) in patients with ovarian cancer

Objectives: Ovarian cancer remains a very common cause of death among women worldwide. The cause is to be found in too late of a diagnostic process and therapeutic difficulties The presence of heat shock proteins in the serum of ovarian cancer patients is still a new area of study. It is necessary to continue studies on the possibilities for using these markers to predict a patient’s response to a specific therapy and to monitor treatment progress. Material and methods: The study included 52 women with ovarian cancer, hospitalised at the Department of Obstetrics, Gynaecology and Oncological Gynaecology, Medical University of Silesia. The control group consisted of 25 healthy women. The levels of HSP27 in the studied sera were determined by an immunoenzymatic method (ELISA). Results: The mean concentration of HSP27 in the group of patients with ovarian cancer was significantly higher than in the control group of healthy women. We have shown that mean HSP27 levels in ovarian cancer patients increase with tumour progression and further depend on the clinical stage of the disease (FIGO). Positivity values analysis revealed in all clinical stages of ovarian cancer, excluding stage 1, it was significantly higher than in the control group, and at the 4th stage, it is significantly higher than at the 1st, 2nd, and 3rd stages. However, both for the untreated patients and those patients after chemotherapy, the mean HSP27 levels were significantly higher than in the control group. Conclusions: Our studies indicate a significant contribution of HSP27 to the pathogenesis of ovarian cancer. It seems that serum HSP27 can be a marker for this cancer’s development, and a marker for the clinical stage

Are IgG antibodies to heat shock proteins HSP27 and HSP60 useful markers in endometrial cancer and cervical cancer?

Objectives: Heat shock proteins are overexpressed in many human malignancies. The role of heat shock proteins as a therapeutic target in cancer as well as their association with drug resistance were widely documented. The aim of this study was to evaluate the concentration of IgG class HSP27 and HSP60 antibodies in serum of patients with endometrial and cervical cancer, as well as to analyse the variability of concentrations of the examined antibodies depending on the cancer stage. Results:  In both endometrial and cervical cancer, the serum concentration of IgG anti-HSP27 antibody was significantly higher than in the healthy control group. The concentration of IgG anti-HSP60 antibody in endometrial cancer, cervical cancer and healthy control was similar. The median IgG anti-HSP27 antibody serum concentration of endometrial cancer patients was not correlated with FIGO-stage. In cervical cancer inverse correlation between concentration of this antibody and FIGO stage was observed. The median IgG anti-HSP60 antibody concentration in serum of endometrial cancer patients was lower in FIGO stage I and II compared to FIGO stage IV and in FIGO stage IA compared to FIGO stage IB. Concentrations of examined antibodies correlated positively with each other, both in the group of women with cancer and in the group of healthy women. The strongest correlations were found in the group of patients with endometrial cancer. Conclusions: Concentration of anti-HSP27 antibody could help in detection of cervical and endometrial cancer. We need to look for the cut-off point in large cohort studies. Anti-HSP27 and anti-HSP60 antibodies should be further evaluated for their potential usage as biomarkers in cervical and endometrial cancer as they shown some correlation with stage of disease

Wybrane hormony tkanki tłuszczowej, metabolizm kostny a osteoprotegeryna i ligand receptora aktywatora czynnika jądrowego-kB u otyłych kobiet po menopauzie

Introduction: It has been suggested that changes in the production of adipose tissue hormones in obese postmenopausal women might affect their bone status. The aim of this study was to determine whether obese postmenopausal women exhibited any relationship between serum levels of LP, ADIPO, RES, VISF, APE and bone metabolism markers (OC and CTx), OPG, sRANKL, the OPG/sRANKL ratio as well as BMD.Material and methods: 80 postmenopausal women (60 obese and 20 healthy) underwent BMD measurement using dual-energy X-ray absorptiometry (DXA) at lumbar spine L2–L4. Serum levels of selected adipose tissue hormones, OC, CTx, OPG and its soluble ligand, sRANKL, were assessed by ELISA.Results: Obese postmenopausal women demonstrated a significant increase in body mass, BMI and WHR associated with significant increases in LP and RES levels, a decrease in ADIPO concentration, suppression of OC, CTx, OPG and sRANKL and an increase in the OPG/sRANKL ratio and BMD. BMI correlated positively with BMD, LP, RES, OPG and the OPG/sRANKL ratio, whereas in the case of ADIPO, OC, CTx, sRANKL the relationship was negative. WHR was positively correlated with the OPG/sRANKL ratio, and negatively with ADIPO and APE. A positive correlation was found between BMD and LP, APE and the OPG/sRANKL ratio, while the correlation between BMD and ADIPO, CTx, sRANKL was negative. Significant positive correlations were also revealed between OC, CTx and ADIPO; OPG and ADIPO; sRANKL and ADIPO, RES; the OPG/sRANKL ratio and LP. OC correlated negatively with LP, RES, VISF, APE; CTx with LP, VISF, APE; OPG with LP; sRANKL with LP and APE; the OPG/sRANKL ratio with VISF. ADIPO was an independent predictor of OC, OPG and sRANKL, while LP turned out to be an independent predictor of CTx, OPG, sRANKL and the OPG/sRANKL ratio.Conclusions: Obesity in postmenopausal women can lead to changes in BMD, circulating levels of bone markers, OPG, sRANKL and/or the OPG/sRANKL ratio; these changes are associated with alterations in the concentrations of adipose tissue hormones under investigation. The relationships between bone status indicators and adipose tissue hormones, especially LP and ADIPO, seem to suggest that changes in these hormones observed in obese postmenopausal women might have a protective effect on bone tissue, most probably via a shift in the OPG/sRANKL ratio towards a functional excess of OPG. (Endokrynol Pol 2014; 65 (6): 438–448)Wstęp: Istnieją sugestie, że zmiany w produkcji hormonów tkanki tłuszczowej u otyłych kobiet po menopauzie mogą wpływać na stan kośćca. Celem pracy było wykazanie, czy u otyłych kobiet po menopauzie istnieje związek między stężeniami w surowicy LP, ADIPO, RES, VISF, APE a markerami metabolizmu kostnego (OC i CTx), OPG, sRANKL, wskaźnikiem OPG/sRANKL oraz BMD.Materiał i metody: U 80 kobiet po menopauzie (60 otyłych i 20 zdrowych) wykonano badanie BMD metodą dwuwiązkowej absorpcjometrii rentgenowskiej (DXA) obejmujące część lędźwiową kręgosłupa L2–L4 oraz oznaczono metodą ELISA stężenia wybranych hormonów tkanki tłuszczowej, OC, CTx, OPG i jej rozpuszczalnego ligandu sRANKL.Wyniki: Istotnemu wzrostowi masy ciała oraz wskaźników BMI i WHR u otyłych kobiet po menopauzie towarzyszyło znamienne zwiększenie stężeń LP i RES, obniżenie stężenia ADIPO, supresja stężeń OC, CTx, OPG i sRANKL oraz wzrost wskaźnika OPG/sRANKL i BMD. Wykazano, istotną dodatnią korelację między BMI a BMD, LP, RES, OPG i wskaźnikiem OPG/sRANKL oraz ujemną z ADIPO, OC, CTx i sRANKL. Wartości wskaźnika WHR korelowały dodatnio ze wskaźnikiem OPG/sRANKL a ujemnie ze stężeniami ADIPO i APE. Wykazano ponadto dodatnią korelację między BMD a stężeniami LP, APE i wskaźnikiem OPG/sRANKL oraz ujemną ze stężeniami ADIPO, CTx, sRANKL. Stwierdzono także dodatnią korelację między stężeniami: OC, CTx a ADIPO; OPG a ADIPO; sRANKL a ADIPO i RES; wskaźnikiem OPG/sRANKL a LP. Ujemną korelację wykazano natomiast między OC a LP, RES , VISF i APE; CTx a LP, VISF i APE; OPG a LP; sRANKL a LP i APE; wskaźnikiem OPG/sRANKL a VISF. Stwierdzono, że niezależnym predyktorem dla OC, OPG i sRANKL jest ADIPO, a dla CTx, OPG, sRANKL i wskaźnika OPG/sRANKL — LP.Wnioski: Otyłość u kobiet po menopauzie wywołuje zmiany w BMD, stężeniach markerów kostnych, OPG, sRANKL i/lub wskaźniku OPG/sRANKL, którym towarzyszą zmiany w stężeniach badanych hormonów tkanki tłuszczowej. Wykazane zależności między wykładnikami stanu kośćca a badanymi hormonami tkanki tłuszczowej, zwłaszcza LP i ADIPO, sugerują, że obserwowane u otyłych kobiet po menopauzie zmiany w stężeniach tych hormonów mogą wpływać ochronnie na tkankę kostną, najprawdopodobniej poprzez przesunięcie relacji OPG do sRANKL na korzyść funkcjonalnej przewagi OPG. (Endokrynol Pol 2014; 65 (6): 438–448

Ocena stężenia produków zaawansowanej glikacji białek i przeciwciał anty-CEL i anty-CML w surowicy pacjentów chorujących na orbitopatię Gravesa przed i po leczeniu metyloprednizolonem

  Introduction: The glycation process is a non-enzymatic modification of proteins occurring due to the reactions of reductive carbohydrates. The glycated residues lose their biological functions, and their removal process is ineffective. They accumulate, and as a result they cause an immunological response. The aim of this study was a determination of the concentrations of advanced glycation end-products and antibodies against carboxymethyl lysine (anti-CML) and carboxyethyl lysine (anti-CEL) in the sera of Graves’ orbitopathy patients. Material and methods: The study group were patients from the Division of Endocrinology of the Medical University of Silesia (n = 25) suffering from Graves’ orbitopathy. The concentration of AGE-peptides using flow spectrofluorimetry method, and anti-CML and anti-CEL IgG antibodies using immunoenzymatic technique (ELISA), were measured in patients sera before and after methylprednisolone treatment. Results: In sera of the study group the concentrations of AGE-peptides and anti-CML were significantly lower before and after treatment in comparison to the control group (p < 0.05). Mean values of anti-CEL concentrations were comparable (at both phases of treatment) with the value observed in the control group. After treatment the concentrations of AGE-peptides and anti-CEL significantly decreased (p < 0.05); however, the concentration of anti-CML was also lower but the observed change was not significant (p > 0.05). Conclusions: In the course of Graves’ orbitopathy the glycation process is disturbed. The treatment modifies significantly the process by lowering the concentration of advanced glycation end-products and suppressing the immune response to them. (Endokrynol Pol 2016; 67 (4): 383–389)    Wstęp: Glikacja jest nieenzymatyczną modyfikacją białek zachodzącą z udziałem cukrów redukujących. Produkty glikacji białek tracą swoje biologiczne funkcje, przez co ich usuwanie staje się nieefektywne. Kumulują się one, a jako neoepitopy wywołują odpowiedź immunologiczną. Celem pracy była ocena stężeń końcowych produktów zaawansowanej glikacji białek (AGE-peptydów) i przeciwciał przeciwko karboksymetylolizynie (anty-CML) i karboksyetylolizynie (anty-CEL) w surowicy chorych na orbitopatię Gravesa. Materiał i metody: Badaną grupę stanowili pacjenci Kliniki Endokrynologii Śląskiego Uniwersytetu Medycznego (n = 25) cierpiący na orbitopatię Gravesa. W surowicy krwi żylnej oznaczono zawartość AGE-peptydów przy użyciu metody spektrofluorymetrii przepływowej oraz przeciwciał anty-CML i anty-CEL w klasie IgG przy użyciu techniki immunoenzymatycznej (ELISA), przed i po leczeniu preparatem metyloprednizolonu. Wyniki: W próbkach surowicy grupy badanej wykazano istotne statystycznie niższe stężenia AGE-peptydów i anty-CML zarówno przed, jak i po leczeniu w porównaniu z grupą kontrolną (p < 0,05). Średnie stężenia anty-CEL były porównywalne (w obu etapach leczenia) do obserwowanych w grupie kontrolnej. Po zastosowanym leczeniu stężenie AGE-peptydów oraz anty-CEL uległo znaczącemu obniżeniu (p < 0,05); stężenie anty-CML również było niższe, lecz zaobserwowana różnica nie była znamienna statystycznie (p > 0,05). Wnioski: W przebiegu orbitiopatii Gravesa procesy glikacji białek ulegają zaburzeniu. Na podstawie wyników wstępnych badań można stwierdzić, że leczenie istotnie modyfikuje ten proces, zmniejszając stężenie końcowych produktów zaawansowanej glikacji oraz hamując odpowiedź immunologiczną przeciwko nim. (Endokrynol Pol 2016; 67 (4): 383–389)

Concentrations of N6-Carboxymethyllysine (CML), N6-Carboxyethyllysine (CEL), and Soluble Receptor for Advanced Glycation End-Products (sRAGE) Are Increased in Psoriatic Patients

Psoriasis is a chronic, recurrent, and often severe skin disease which is frequently associated with metabolic disorders and increased risk of cardiovascular complications. One of the postulated links is an intensified process of advanced protein glycation and/or glycoxidation. Therefore, the aim of the study was to assess concentrations of N6-carboxymethyllysine (CML), N6-carboxyethyllysine (CEL), and soluble form of receptor for advanced glycation end-products (sRAGE) in psoriasis patients at different phases of the disease activity, in comparison to healthy individuals. The study material consisted of sera from psoriasis patients in active phase, in the remission phase, and healthy controls. Concentrations of CML, CEL, and sRAGE were determined using ELISA technique. In the patients with psoriasis (in both phases of the disease), concentrations of CML, CEL and sRAGE were significantly higher than in healthy individuals but they did not correlate with psoriasis area severity index (PASI) values. The remission of the disease was followed by a significant decrease in CML, CEL, and sRAGE concentrations when compared to active patients; however, these concentrations were still significantly higher than in the controls. Our data suggest that psoriasis is accompanied by an intense glycoxidation process and that high sRAGE levels seem to reflect permanent RAGE overstimulation

The Assessment of Serum Concentrations of AGEs and Their Soluble Receptor (sRAGE) in Multiple Sclerosis Patients

Background: Advanced glycation end products (AGEs) are involved in the pathogenesis of many diseases, including neurodegenerative diseases such as multiple sclerosis (MS). The aim of the study was to determine serum concentrations of AGEs and their soluble receptor (sRAGE) in MS patients and healthy controls and to investigate their possible influence on disease activity. Methods: Serum concentrations of AGE and sRAGE in patients with MS and healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Results: The mean serum AGE concentration in patients with MS was higher than in healthy controls, whereas the mean serum sRAGE concentration was lower than in the control group. However, the differences were not statistically significant. In MS patients, serum AGE and sRAGE concentrations did not differ significantly, depending on the duration of the disease and the Expanded Disability Status Scale (EDSS) score. Conclusions: Multiple sclerosis may be accompanied by disturbances of the AGE-sRAGE axis. However, further studies are warranted to confirm it. The duration of the disease and the degree of disability do not seem to affect the progression of the glycation process, particularly in the stable phase of the disease

Czy AGEs mogą być markerami stanu przedrzucawkowego? Badanie stężenia zaawansowanych produktów glikacji białek u kobiet ciężarnych z ciążą fizjologiczną i ciążą powikłaną stanem przedrzucawkowym

INTRODUCTION: The role of advanced glycation end products (AGEs) in the pathomechanism of arterial hypertension has been demonstrated, but little information is available on the influence of AGEs on the course of pre-eclampsia (PE). The aim of the study was to assess the concentration profile of advanced protein glycation products in pregnant women diagnosed with PE. MATERIAL AND METHODS: The concentrations of AGEs, carboxymethyllysine (CML), carboxyethyllysine (CEL) and methylglyoxal (MG) in the sera of female respondents were determined using the enzyme immunoassay method. RESULTS: The levels of AGE and CML were lower in the group of women with PE compared to the group of non- -pregnant women (p = 0.0411 and p = 0.0072). A lower CML concentration was found in healthy pregnant women as compared to healthy non-pregnant women (p = 0.00068). Positive correlations were found between AGE and CML levels in women with PE (R = 0.339, p = 0.032) and between CML and CEL in healthy non-pregnant women (R = 0.447, p = 0.012). CONCLUSIONS:We suggest that there is a decrease in the intensity of non-enzymatic protein glycation during pregnancy. Moreover, our study indicates that isolated PE may be associated with a different pathomechanism than chronic hypertension, and therefore AGEs cannot be at present considered a marker of PE.WSTĘP: Rola końcowych produktów zaawansowanejglikacji (advanced glycation end products – AGEs) w patomechanizmie nadciśnienia tętniczego została udowodniona, jednak niewiele jest informacji na temat wpływu AGEs na prze-bieg stanu przedrzucawkowego (pre-eclampsia – PE). Celem pracy była ocena profilu stężeń zaawansowanych produktów glikacji białek u kobiet ciężarnych z rozpoznaniem PE. MATERIAŁ I METODY: Oznaczenia stężeń AGEs, karboksymetylolizyny (carboxymethyllysine – CML), karboksyetylolizyny (carboxyethyllysine – CEL) i metyloglioksalu (methylglyoxal – MG) w surowicy badanych kobiet wykonano metodą immunoenzymatyczną. WYNIKI: Stężenia AGE i CML były niższe w grupie kobiet z PE w porównaniu z grupą kobiet nieciężarnych (p = 0,0411 i p = 0,0072). Stwierdzono niższe stężenie CML u zdrowych ciężarnych w porównaniu ze zdrowymi nieciężarnymi (p = 0,00068). Stwierdzono dodatnie korelacje pomiędzy stężeniem AGE i CML u kobiet z PE (R = 0,339, p = 0,032) oraz pomiędzy CML i CEL u zdrowych kobiet nieciężarnych (R = 0,447, p = 0,012). WNIOSKI: Sugerujemy, że w czasie ciąży dochodzi do zmniejszenia intensywności nieenzymatycznej glikacji białek. Ponadto nasze badanie wskazuje, że izolowane PE może być związane z innym patomechanizmem niż przewlekłe nadciśnienie tętnicze i dlatego AGEs nie mogą być obecnie uważane za marker PE

The relationship between circulating concentrations of interleukin 17 and C reactive protein in chronic spontaneous urticaria

Abstract Background Up-regulation of interleukin 17 (IL-17) family cytokines and acute phase response have been observed in patients with chronic spontaneous urticaria (CSU). It has been demonstrated that IL-17 stimulates C-reactive protein (CRP) expression. Aim To determine relationship between circulating concentrations of IL-17 and CRP in CSU. Methods Concentrations of IL-17 in plasma and CRP in serum were measured in patients with CSU of varying severity and in the healthy subjects. Results IL-17 and CRP concentrations were significantly higher in CSU patients as compared to the healthy subjects. In addition, there were significant differences in IL-17 and CRP concentrations between CSU patients with mild, moderate-severe symptoms and the healthy subjects. CRP did not correlate significantly with IL-17. Conclusions Increased circulating IL-17 concentration may represent an independent index of systemic inflammatory response in CSU, which is not related to increased CRP concentration

Interplay between acute phase response and coagulation/fibrinolysis in chronic spontaneous urticaria

Abstract Background Chronic spontaneous urticaria (CSU) is associated with activation of systemic inflammatory response and coagulation/fibrinolysis. Aim To study whether there is a relationship between the acute phase response and coagulation/fibrinolysis in chronic spontaneous urticaria (CSU) patients. Methods Serum concentrations of C-reactive protein (CRP) and interleukin 6 (IL-6), key markers of acute phase response and of D-dimer, a marker of fibrin turnover were investigated in 58 CSU patients assessed with the urticaria activity score (UAS) and the controls. Results Serum concentrations of IL-6, CRP, and D-dimer were significantly higher in CSU patients as compared with the controls. We found statistically significant correlations between D-dimers concentrations and the inflammatory markers: CRP and IL-6 as well as UAS. Conclusions Markers of inflammation (IL-6 and CRP) and of fibrinolysis (D-dimer) are related to each other in CSU, suggesting a possible cross-talk between inflammation and coagulation/fibrinolysis. It might be implicated in pathogenesis of the disease and may be associated with higher risks of cardiovascular diseases in CSU patients

IL-6 Transsignaling in Patients with Chronic Spontaneous Urticaria.

IL-6 trans-signaling is critically involved in the initiation and promotion of inflammatory and autoimmune diseases. Therefore, we investigated the clinical relevance of soluble members of IL-6 trans-signaling system in chronic spontaneous urticaria (CSU).IL-6, interleukin 6 soluble receptor (IL-6 sR) and soluble gp130 (sgp130) were measured by ELISA method in plasma from CSU patients and the healthy subjects. The data were related to activation of the acute phase response as indicated by serum C-reactive protein (CRP) concentration and compared between patients stratified by the disease activity.Concentrations of IL-6, IL-6 sR, sgp130 in plasma and CRP in serum were significantly elevated in CSU patients compared with the healthy controls. CRP correlated significantly with IL-6 and sgp130, similarly IL-6 correlated significantly with sgp130. By contrast, CRP and IL-6 did not correlate significantly with IL-6 sR. However, significant correlation was noted between IL-6 sR and sgp130.Concentrations of IL-6 and its soluble receptors were significantly elevated in patients with CSU, suggesting upregulation of the IL-6 trans-signaling in the disease. In addition, our results support the concept that the system may be involved in pathogenesis of the systemic inflammatory activation in CSU patients