Paweł Sedlaczek

Comparative analysis of CA125, tissue polypeptide specific antigen, and soluble interleukin-2 receptor α levels in sera, cyst, and ascitic fluids from patients with ovarian carcinoma

The serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin‐2 receptor alpha (sIL‐2Rα) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms.

Tissue polypeptide specific antigen (TPS), a marker for differentiation between pancreatic carcinoma and chronic pancreatitis

The value of serum tissue polypeptide specific antigen (TPS) as a complement to CA 19‐9 in the detection of pancreatic carcinoma was determined prospectively. TPS and CA 19‐9 levels obtained at the time of diagnosis in patients suspected of having chronic pancreatitis or pancreatic carcinoma were evaluated in receiver operating characteristic (ROC) curve analysis.

Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation.

The influence of the immune system deregulation on the risk of schizophrenia is increasingly recognized. The aim of this study was to assess the influence of serum interleukin-6 (IL-6) level together with the polymorphism in its gene (IL6 -174G/C) and high sensitivity C-reactive protein (hsCRP) levels on clinical manifestation and cognition in schizophrenia patients. We recruited 151 patients with schizophrenia and 194 healthy control subjects. Psychopathology was evaluated using Operational Criteria for Psychotic Illness checklist, Positive and Negative Syndrome Scale (PANSS) and Scales for Assessment of Positive and Negative Symptoms. Cognitive performance in schizophrenia patients was assessed using following tests: Rey Auditory Verbal Learning Test, Trail Making Test, Verbal Fluency Tests, Stroop and subscales from Wechsler Adults Intelligence Scale-R-Pl (Similarities, Digit Symbol Coding, Digit Span Forward and Backward). Serum IL-6 and hsCRP levels were significantly higher in schizophrenia patients in comparison with healthy controls. Both hsCRP and IL-6 levels were associated with insidious psychosis onset, duration of illness and chronic schizophrenia course with deterioration. After adjustment for age, education level, number of years of completed education, illness duration, total PANSS score, depression severity and chlorpromazine equivalent, there was still a positive association between IL-6 and hsCRP levels and worse cognitive performance. The IL6 -174G/C polymorphism did not influence IL-6 level, but it was associated with the severity of positive symptoms. Our results suggest that elevated IL-6 levels may play the role in cognitive impairment and serve as potential inflammatory biomarker of deterioration in schizophrenia.

Serum Vascular Endothelial Growth Factors A, C and D in Human Breast Tumors

Available evidence suggests that vascular endothelial growth factor (VEGF) a potent regulator of vasculogenesis and tumor angiogenesis may be a predictor of recurrence in breast cancer patients. We sought to determine whether VEGF serum levels (VEGF-A, VEGF-C and VEGF-D) in 377 patients with malignant and benign breast tumors differ and whether there is association between vascular growth factors, clinicopathologic features and prognosis. There was no significant difference in investigated circulating angiogenic markers between patients with malignant and non malignant lesions. We found strong correlation between VEGF-A and VEGF-D and between VEGF- C and VEGF-D. Besides serum VEGF-D levels and estrogen receptor (ER) expressions no other correlations between VEGF and clinicopathologic variables were observed. However, elevated VEGF-A and VEGF-C concentrations were associated with increased number of erythrocytes, leukocytes and platelets. In Cox model values of angiogenic serum markers and recognized prognostic markers in breast cancer, VEGF-C turned out as independent prognostic factor. Our study is the first analysis showing correlation between serum concentrations of three angiogenic factors: VEGF-A, VEGF-C, VEGF-D. Associations between angiogenic cytokines and number of blood cells may be due to release of VEGF from platelets and leucocytes. Prognostic role of VEGF is still uncertain, though VEGF-C has a potential to serve as a prognostic marker.

TPS and CA 19-9 measurements in the follow-up of patients with pancreatic cancer and chronic pancreatitis

The aim of this study was to assess the value of TPS and CA 19–9 in a long-term follow-up analysis of 11 patients with chronic pancreatitis (CP) and 15 patients with pancreatic cancer (PC). In all monitored patients with chronic pancreatitis the initial TPS level was below 200 U/L, whereas CA 19–9 was elevated in two of them. In one patient a dramatic increase in the TPS concentration (820 U/L) was measured at the last follow-up visit (after 8.6 months), which led to the detection of PC. In all patients with PC the preoperative TPS level exceeded 200 U/L, whereas CA 19–9 was elevated in only nine patients. After the Kausch-Whipple operation 11 patients showed no evidence of disease and in eight of these patients both TPS and CA 19–9 were within the reference range; however, in three patients liver metastases were detected after 8–24 months from the last tumor marker measurement. In four of the 15 patients both markers were elevated at the end of the follow-up period and distant metastases were clinically confirmed. Our results indicate that in patients with CP and PC undergoing long-term follow-up, TPS reflects the clinical status of patients more accurately than CA 19–9.

Sex differences in TGFB-β signaling with respect to age of onset and cognitive functioning in schizophrenia

There are studies showing that gene polymorphisms within the transforming growth factor-β (TGF-β) signaling constitute schizophrenia risk variants. However, the association between TGFB1 gene polymorphisms (+869T/C and +915G/C), TGF-β level with schizophrenia course, and its symptomatology together with cognitive functioning has not been investigated so far. We included 151 patients with schizophrenia and 279 healthy controls. Cognitive functioning was assessed using Rey Auditory Verbal Learning Test, Trail Making Test (TMT)-A and TMT-B, Verbal Fluency task, Stroop test, as well as selected subtests from the Wechsler Adults Intelligence Scale – Revised, Polish adaptation (WAIS-R-Pl): Digit Symbol Coding, Digit Span Forward and Backward, and Similarities. Additionally, serum TGF-β levels were measured in 88 schizophrenia patients and 88 healthy controls. Serum TGF-β level was significantly higher among patients with schizophrenia in comparison with healthy controls; however, the studied polymorphisms were not associated with TGF-β level in schizophrenia patients. Subjects carrying the +869T allele performed significantly worse in comparison with +869CC homozygotes on Stroop task, Verbal Fluency task and Digit Symbol Coding task. There was a significant difference in age of psychosis onset in female schizophrenia patients with respect to the TGFB1 +869T/C polymorphism. Additionally, adjustment for possible confounders revealed that there was a significant difference in cognitive performance on Digit Symbol Coding task with respect to the TGFB1 +869T/C polymorphism among female schizophrenia patients. Our results suggest that TGF-β signaling might be a valid link contributing to observed differences in age of onset and the level of cognitive decline between male and female schizophrenia patients.

Carcinoembryonic Antigen Isotypes in Tissue Sections and Loose Cyst Fluid Cells of Ovarian Neoplasms

The aim of this study was to establish whether different subsets of ovarian neoplasms express a restricted isotype of carcinoembryonic antigen (CEA) which can be detected in solid tumors and detached cells. Sixty-one cases of mucinous, serous, endometrioid, and Krukenberg tumors were studied by immunohistochemistry using two monoclonal antibodies (MAbs), commercial anti-CEA and D14 with a higher specificity for colorectal adenocarcinomas. The results with both antibodies showed a considerable degree of heterogeneity between cases of nonserous tumors, with a more restrictive pattern observed with the D14 MAb. The proportion of immunostained cells was comparable in tumors and fluids.

Correlation between pre-therapeutic TPS and VEGF concentrations, in the serum of patients with cancer of the uterine cervix, and early effects of therapy

Summary Aim To assess the relationship between pre-therapeutic serum TPS and VEGF levels and the results of treatment as measured immediately after completion of therapy. Materials/Methods The study included 146 women treated for cancer of the uterine cervix. Of these, 37 women were in stage I, 43 in stage II, 59 in stage III and 7 in stage IV of disease progression according to the FIGO classification. The ages of the patients ranged from 31 to 80 years. The dominant cancer observed was squamous cell carcinoma which accounted for more than 97% of cases. Samples were taken before commencement of treatment. Patients were treated by a combination of methods including radiochemotherapy, radical radiotherapy and palliative radiotherapy. The effects of therapy were graded after completion of irradiation according to generally accepted criteria. For tested criteria, ROC curves were drawn, determining cut-off points of 58 U/l for TPS and 500 pg/l for VEGF. For statistical calculations the U Mann-Whitney test was used. Results The level of VEGF expression varied between groups of patients in certain stages of disease progression (stages 1 & 2 and stages 2 & 3). Statistically significant differences were found between group PR in stage 2 and a control group of healthy women. Entry levels of TPS rose with tumor advancement (in stages 2, 3 & 4) and were higher than in a group of healthy women. Detected differences were statistically significant. Conclusions Only pre-therapeutic TPS levels show definite differences between degrees of clinical advancement and also with early therapeutic effects. Comparatively higher levels of serum TPS were found in patients with the worst prognosis prior to treatment (group P) than in the control group. This difference is statistically significant. Pre-therapeutic VEGF levels showed statistically significant differences between early (I, II) and advanced (III) clinical stages of the tumor as well as some effects of therapy assessed immediately after completion of treatment (PR vs S).

10/Fluktuacje stężeń VEGF A w trakcie radioterapii u chorych na nowotwory gardła i krtani

Czynnik wzrostu środblonka naczyn (VEGF) odgrywa dominującą role w angiogenezie w guzach nowotworowych. Niedotlenienie komorek guza jest glownym bodźcem uruchamiającym aktywacje systemu VEGF A i receptorow o aktywności kinazy tyrozynowej (VEGFR-1 i VEGFR-2). W badaniach na liniach komorkowych wykazano, ze radioterapia aktywuje ekspresje VEGF, a raczej jego izoforme VEGF A 165. Aktywacja tej cytokiny powoduje ochrone naczyn krwionośnych guza przed cytotoksycznym dzialaniem promieniowania jonizującego i przez to wzmaga promienioopornośc guza. Gorski i wsp. wykazali, ze w ekstrakcie guza po dawce 40 Gy średnie stezenie VEGF wzrastalo ponad trzykrotnie. Celem naszego badania bylo ustalenie, czy u chorych na raka gardla lub krtani stezenia VEGF A w surowicy krwi ulegną zmianom w trakcie radioterapii i czy zmiany te bedą mialy znaczenie rokownicze. Badaniom poddano 22 pacjentow leczonych radykalnymi dawkami promieniowania jonizującego, u ktorych stezenia markera oznaczono przed rozpoczeciem napromieniania i po 4 tygodniach leczenia. Przed rozpoczeciem terapii podwyzszone miana cytokiny stwierdzono u wszystkich chorych przy poziomie odciecia 180 pg/ml), średnie stezenie VEGF A wynosilo 1001 pg/ml, a mediana 803 pg/ml. Po podaniu dawki 40 Gy u 21 chorych stwierdzono stezenia markera przekraczające norme, średnie stezenie wynosilo 867.5 pg/ml, a mediana 737 pg/ml. Nie wykazano zadnych istotnych statystycznie roznic w stezeniach VEGF A w surowicy krwi przed i w trakcie radioterapii, wahania stezen tego markera nie wykazywaly zadnych zalezności z wynikami leczenia i dwuletnim przezyciem. Monitorowanie radioterapii przez oznaczanie stezen VEGF A nie ma wartości rokowniczej a stezenie markera w obecnym badaniu malalo – odwrotnie niz stwierdzono to w dotychczasowych badaniach laboratoryjnych na liniach komorkowych.