Nuclear factor-kappa B as potential therapeutic target in human colon cancer.

BACKGROUND: It has been proved that nuclear factor-kappa B (NF-κB) is activated in all cells, promotes proliferation of cells, regulates the immunological and inflammatory response, and contribute to the pathogenesis of many conditions, including cancer. Many studies pointed to constitutive activation of NF-κB in cells of certain malignant tumors. OBJECTIVE: The aim of the study was to analyze the role of nuclear growth factor κB as colon cancer marker and prognostic factor. MATERIALS AND METHODS: The study included 59 primary colorectal tumor patients and 15 patients in control group. The tumor samples were taken during partial colectomy and colonoscopy in control group. Tissues samples were fixed and embedded in paraffin blocks and cut. Sections were used for schedule immunohistochemical staining with the application of specific antibody for NF-κB epitope. The marker expression was compared with well-known prognostic factors in colon tumors such as tumor type, stage, and grade to establish if it might be a potential prognostic factor. RESULTS: The results showed statistically significant difference between control group and cancer group. CONCLUSIONS: The expression NF-κB did not depend on the stage and grade of colon tumors.

The relation between plasma α-synuclein level and clinical symptoms or signs of Parkinson's disease.

INTRODUCTION: Parkinson disease (PD) is the common neurodegenerative disease. α-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was found in peripheral fluids. Testing ASN in plasma is potential test for diagnose PD, but previous studies are controversial. The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms. METHODS: Patients with PD hospitalized in Neurology Department, Medical College were performed sequencing the 8th and 9th exon of GBA gene. Next plasma ASN level was tested in 58 patients with sequenced GBA gene and in 38 healthy volunteers (HV), matched by the age (respectively 68.43 vs. 64.57 years of age) and sex (female %, respectively: 43.10 vs.44.74). Patients were assessed with the scales: UPDRS (II, III, IV), Hoehn-Yahr (HY) and qualified to PIGD or TD subtype. For homogeneity of the group patients with GBA mutation were excluded from the analysis. RESULTS: The ASN level did not differ between patients and HV (respectively: 4.53 vs. 3.73ng/ml) and between patients with different subtypes. There was inverse correlation between ASN and HY in PIGD subtype. CONCLUSIONS: Plasma ASN level is not valuable marker of the disease. It does not differ in subtypes of the disease. There is relation between plasma ASN level and the severity of the disease in PIGD subtype.

Expression of VEGF isoforms and their receptors in uterine myomas.

OBJECTIVES: The aim of the study was to determine the expression of VEGF (vascular endothelial growth factor) isoforms and their receptors in uterine myomas. MATERIAL AND METHODS: The study included 40 women with myomas of reproductive age and 40 perimenopausal women (the study group). Myometrial samples (the control group) were taken from 10 women undergoing hysterectomy for ovarian tumors and 10 older women undergoing hysterectomy for uterine prolapse. RESULTS: A significantly increased expression of VEGF-A has been found in myomas, both small and large, in the younger women, which may by a sign of increased angiogenesis and intensive tumor growth. In perimenopausal women, the increase of VEGF expression was observed only in the endothelium and vascular smooth muscle. CONCLUSION: An important conclusion of this study is that angiogenesis is independent of myoma size, which may suggest intensive tumor growth and the related increased angiogenesis. High expression of VEGF-A and VEGF-R1 receptors in large myomas can probably cause malignant transformation and more extensive growth, regardless of patient age.

Survivin in ovary tumors.

INTRODUCTION: Survivin is a member of the inhibitor of apoptosis protein (IAP) family which are selectively overexpressed in human neoplasms, and its expression has been shown to be connected with cell proliferation. We analyzed survivin expression in ovarian epithelial neoplasms to evaluate its role in the development of ovarian tumors. MATERIAL AND METHODS: Immunohistochemistry assays were conducted in 137 cases (48 ovarian carcinoma, 43 borderline ovarian carcinoma, 46 benign ovarian tumor and 20 samples of normal ovarian tissue of ovarian epithelial neoplasms. Histological types included serous (n = 68) and mucinous (n = 69) tumors. All tumors were reviewed histopathologically and classified according to the WHO criteria. RESULTS: Survivin expression in the group of serous neoplasms was detected in 24.0% (6 of 25) of benign cases, in 60.0% (12 of 20) of borderline tumors, and 91.0% (24 of 47) of ovarian carcinomas. In the group of mucinous tumors, survivin expression was found in 33.5% (7 of 21) of benign cases, 43.5% (10 of 23) of borderline tumors, and 80.0% (20 of 25) of malignant tumors. CONCLUSIONS: Our results demonstrate that survivin overexpression may play a crucial role in the development of epithelial ovarian neoplasms and be an important prognostic factor for the influence of survivin expression on epithelial ovarian cancers.

Immunohistochemical visualization of pro-inflammatory cytokines and enzymes in ovarian tumors.

Epithelial ovarian cancer represents one of the most deadly gynaecological neoplasms in developed countries and is a highly heterogeneous disease. Epidemiological studies show that anti-inflammatory drugs reduce the incidence and mortality of several types of cancer, indicating the potential role of pro-inflammatory factors in carcinogenesis. The expression of pro-inflammatory factors in various cancer types, including ovarian cancer, was assessed in many studies, yielding in consistent results, often due to the histological heterogeneity of various cancers. The aim of the study was to investigate the expression of IL-1, IL-6, TGF-ß, TNF-α, COX-2, iNOS, and NF-kB in serous and mucinous ovarian cancers. Ninety cases of ovarian tumors classified into mucous and serous type (45 patients in each group) were selected. Each group was classified into subgroups according to the three stages of tumor differentiation, i.e. into (i) benign, (ii) borderline and (iii) malignant tumors. The presence of proteins of interest in paraffin sections was analysed by immunohistochemistry. The expression of most of the studied factors depended on the histological tumor subtype and the degree of malignancy. Expression of NF-κB appears to be related to the level of the neoplastic differentiation only in the group of serous tumors, while the presence of IL-6 in the mucinous tumor subtype was observed only in the case of benign lesions. Expression of IL-1, TNF-α and COX-2 increased with the stage of the disease in both serous and mucinous tumors. The highest level of TGF-ß expression was observed in serous borderline tumors. The different levels of iNOS immunoreactivity between the groups of serous and mucinous tumors were observed only in borderline tumors. The results of our study may be helpful in designing therapeutic strategies depending on the type of ovarian cancer.

Receptors of hypothalamic-pituitary-ovarian-axis hormone in uterine myomas.

In this study the expression of GnRH, FSH, LH, ER-α, ER-ß, and PR receptors was examined in uterine myomas of women in reproductive and perimenopausal age. In cases of GnRH and tropic hormones a membranous and cytoplasmic immunohistochemical reaction was detected, in cases of ER-α and PR the reaction was located in cell nucleus, and in the case of ER-ß it manifested also a cytoplasmic location. In some of the examined cases the expression was detected in endometrium, myocytes, and endothelium of blood vessels, in uterine glands and myoma cells. In myometrium the level of GnRH and LH receptors increases with age, whereas the level of progesterone and both estrogen receptors decreases. In myomas of women in reproductive age, independently of their size, expression of GnRH, FSH, and LH receptors was more pronounced than in myometrium. In women of perimenopausal age, independently of myoma size, expression of LH and estrogen α receptors was higher while expression of GnRH receptors was lower than in myometrium. FSH receptor expression was not observed. Expression of estrogen receptor ß was not affected by age of the woman or size of myoma. Analysis of obtained results indicates on existing in small myomas local feedback axis between GnRH-LH-progesterone.

Expression of selected cytochrome P450 isoforms and of cooperating enzymes in colorectal tissues in selected pathological conditions.

The current interest in CYP expression in the colon results from its uniqueness as a target organ for cancer. To date, the CYP expression profiles in the colon have not yet been subject of comprehensive research. In this study, we investigated 40 patients with Crohn's disease, 40 with ulcerative colitis, and 40 healthy subjects as a control group. Colon tissues were fixed, dehydrated, cleared in xylene and embedded in paraffin. Sections were prepared from paraffin blocks for immunohistochemical staining with specific antibodies. We used antibodies to the human CYP1A1, CYP2B6, CYP2C9, CYP2E1 and CYP3A4 isoforms, as well as antibodies to the human glycoprotein P, glutathione-S transferase and antibody to the UDP-glucuronosyltransferase. The sections were stained immunohistochemically and examined using light microscopy. Cellular localization was determined, and computer image analysis was used. In all cases with Crohn's disease, the proteins studied showed at least a twofold expression. Ulcerative colitis showed a much weaker influence regarding the expression of the proteins studied but in case of CYP2C9 and UDP-glucuronosyltransferase, a decrease of expression was observed.

The TRAF2 and TRAF6 expression in myomas and myometrium of women in reproduction and perimenopausal age.

Uterine myomas represent one of the most common female diseases. Uterine myomas or fibromas are benign, hormone-responding tumours of, respectively, smooth muscles and fibroblasts and their aetiology induces a significant interest. In myomas the presence of aromatase was detected and, in addition, oestrogen was found to be synthesized in myoma cells. The studies were performed on myoma patients of generative age and those in peri-menopausal age. Expression of TRAF2 and TRAF6 proteins was examined using immunohistochemistry and Western blot approach in small and large uterine myomas isolated from women of various age. In addition, the evaluation was conducted at the periphery of every myoma. We indicated that the level of both tested proteins in myomas is higher than in control. TRAF2 level in myometrium was lower than in myomas but higher than in control. In the case of TRAF6 those changes were ambiguous. Age didn't have influence the level of expression in both tested TRAF in studied structures.

[Effect of Helicobacter pylori infection on proliferation and apoptosis in stomach antrum in smoking patients]. / Wplyw infekcji Helicobacter pylori na proliferacje i apoptoze komórek odzwiernika zoladka u pacjentów palacych papierosy.

Peptic ulcer disease develops if the balance between aggressive and defensive factors is destroyed. Among the identified risk factors are Helicobacter pylori infection (Hp), stress, cigarette smoking and taking nonsteroidal anti-inflammatory drugs. However, the exact ulcerogenic mechanism of these factors remains not fully elucidated; yet habitual smoking is the most controversial. The aim of this study was to investigate the influence of cigarette smoking and/or Hp infection on gastric mucosa expression of COX-2, iNOS and proliferation and apoptosis processes (Ki-67 and active caspase 3 expressions, respectively). In smokers without Hp all studied parameters were higher than in nonsmoker without Hp group. Hp infection increases iNOS , COX-2 and active caspase 3 expression. Highest values for iNOS, COX-2 and Ki-67 was observed in smoker with Hp infection group. Hp infection in smokers significantly decrease active caspase 3 expression.