Osteopontin and endostatin concentrations in peripheral blood of patients with adrenal tumors undergoing unilateral adrenalectomy.

Peripheral blood osteopontin (OPN) and endostatin (END) levels were studied in 35 patients with adrenal cortex tumors and 10 patients with pheochromocytoma before unilateral adrenalectomy, as well as in 10 healthy subjects (controls). Thirty days after surgery, OPN and END were evaluated again in 16 patients with adrenal cortex tumors and 4 female patients with pheochromocytoma. Before surgery, OPN blood concentrations increased in the group of patients with adrenal cortex carcinomas as compared to controls (p < 0.001) and the group with Conn syndrome (p < 0.05); they did not change after surgery. Before adrenalectomy, OPN blood levels in pheochromocytoma patients were also lower than in Conn syndrome subjects (p < 0.05). After adrenalectomy, the normal concentrations of END decreased only in the group of patients with hormonally inactive cortical adenomas (p < 0.05). We were unable to demonstrate any relationships between removed tumor volumes and OPN or END blood levels.

Degradation of collagen by metalloproteinase 2 in patients with abdominal hernias.

BACKGROUND: The groin hernia is a significant social and economic problem of our times. The pathogenesis of the disease is not clear. The metalloproteinases (MMP) are the group of proteolytic enzymes responsible for the degradation of extracellular matrix proteins and the basic membrane of blood vessels. THE AIMS OF OUR STUDY WERE: (1) to estimate the MMP-2 levels in the blood and tissues of patients with a groin hernia; (2) to answer the question of whether changes in MMP-2 activity correlate with the occurrence of inguinal hernias. METHOD: The study was performed on a group of 90 male patients suffering from inguinal hernias, aged 28-70 years (mean: 49 years). The control group was made up of 10 healthy (free from hernia) males, aged 30-68 years (mean: 46 years). RESULTS: We noticed increased levels of MMP-2 in patients with all types of hernia and across all age groups. The MMP-2 mean serum levels were statistically higher in patients with a groin hernia when compared to the control group. The highest blood levels of MMP-2 were observed in young men with a direct hernia. CONCLUSIONS: This study confirmed the important role of MMP-2 in the pathogenesis of inguinal hernia. The increased activity may lead to dysfunctions in collagen fiber, which is responsible for forming fascial structures, and as a result weaken their durability.

P53 concentration and soluble FasL (sFasL) serum level as indicators of apoptosis in patients with benign and malignant thyroid tumors.

During embryonal development and morphogenesis, apoptosis may be induced by two pathways. The first is an external protein signal originating from other cell--also named as "death signal". The another one is a specific cell reaction to external stress factors. Plasma concentration of proteins regulating both apoptosis pathways may be useful in early diagnosis and staging of thyroid tumors. The aim of the study was to evaluate p53 and sFasL plasma concentration in patients with benign and malignant thyroid tumors. The study population was composed of 33 patients with thyroid carcinoma and 10 patients with follicular carcinoma (tumor types were verified by fine-needle biopsy). All patients underwent surgical procedures. p53 and sFasL levels were evaluated before surgery. Control group consists of 10 adult healthy volunteers. The results revealed high p53 and sFasL plasma concentration in patients with benign and malignant thyroid tumors. Such results confirm a significant role of p53 and sFasL in apoptosis in thyroid tumors. Expression of both proteins may be an indicator of an increased apoptosis and useful in preoperative diagnosis in thyroid tumors (Tab. 1, Ref. 31).

Angiogenesis of endocrine gland tumours--new molecular targets in diagnostics and therapy.

Angiogenesis is one of the key stages in the development of neoplastic tumours, in which a small group of mutated cells transforms into a large malignant tumour metastasising to the neighbouring tissues and organs. The studies on the significance of neoangiogenesis in the progression of endocrine gland neoplasms have recently become one of the most rapidly evolving branches of molecular endocrinology. The induction of angiogenesis has been demonstrated to result from the imbalance between positive and negative factors which control this process. Our paper presents the results of current studies on the role of factors such as molecular markers of angiogenesis (e.g. vascular endothelial growth factor and basic fibroblast growth factor), metalloproteinases (which regulate the decomposition of the extracellular matrix) and their inhibitors, and adhesive molecules (e.g. soluble vascular cellular adhesion molecule-1 and soluble intracellular adhesion molecule-1) in the pathogenesis and diagnostics of endocrine gland tumours in humans. Also, we discuss new therapeutic strategies for inhibiting the growth of neoplasms by blocking the formation of blood vessels using angiogenesis antagonists, which inhibit various stages of angiogenesis. More and more data are being accumulated suggesting that these preparations could, in the near future, be used in the pharmacotherapy of some endocrine gland neoplasms.

Evaluation of MMP-1, MMP-8, MMP-9 serum levels in patients with adrenal tumors prior to and after surgery.

The aim of the study is to evaluate MMP-1, MMP-8 and MMP-9 serum levels in patients with adrenal tumors prior to and after surgery. Metalloproteinase-1 (MMP-1), MMP-8 and MMP-9 serum levels were evaluated in 43 patients operated on at our clinic between 1997-1999. Forty-one (95.3%) patients underwent adrenalectomy. Two (4.7%) patients were disqualified from surgery due to infiltration of adjacent tissues. MMP-1, MMP-8 and MMP-9 serum levels were determined at the admission and in case of surgery again one month after the operation. ELISA assay (K&D) was applied. Tumor type was determined on the basis of clinical, hormonal and histopathological examination. The correlation between MMP levels and tumor sizes was also evaluated. Patients were divided into 6 groups. Group I included 11 patients with adrenocortical carcinoma (4 with Cushing's syndrome and 7 with incidentalomas); group II--6 patients with benign hormonally active adrenocortical adenoma (4 with Cushing's syndrome and 2 with Conn's syndrome); group III--patients with benign, hormonally inactive adenocortical adenoma; group IV--6 patients with benign, hormonally active phaeochromocytoma; group V--4 patients with hormonally inactive phaeochromocytoma; group VI--5 patients with hormonally inactive adrenal tumors of extraglandular origin (2 myolipomas, 2 fibrolipomas, 1 hammartoma). The control group comprised 10 healthy individuals. Increased MMP-8 and MMP-9 levels were noted in patients with benign and malignant adrenal tumors. No increase of MMP levels was found in patients with tumors of extraglandular origin. The increased MMP-8 and MMP-9 levels occurred most frequently in patients with adrenocortical and hormonally active adrenomedullar cancer, and most rarely in patients with hormonally active adrenocortical tumors. MMP-8 and MMP-9 serum levels did not significantly differ between patients with adrenocortical incidentaloma cancers and in patients with benign incidentalomas. MMP-8 and MMP-9 levels were not increased in patients with inoperable adrenocortical cancers. Serum MMP-1 levels were not increased in patients with benign and malignant adrenal tumors. After surgery, MMP-8 and MMP-9 levels decreased significantly in patients with adrenocortical cancers, whereas the decrease of these MMPs in patients with benign tumors, although noticeable, was not statistically significant. MMP-8 and MMP-9 levels decreased significantly in all patients with increased preoperative levels, although they remained higher than the maximum normal values only in few patients (in 7 and 2 patients, respectively). No correlation between the levels of evaluated MMPs and tumor sizes were found.

Usefulness of VEGF, MMP-2, MMP-3 and TIMP-2 serum level evaluation in patients with adrenal tumours.

OBJECTIVE: To estimate serum levels of vascular endothelial growth factor (VEGF), metalloproteases MMP-2 (gelatinase A), MMP-3 (stromyelisine 1) and metalloprotease tissue inhibitors (TIMP-2) in patients with various benign and malignant adrenal tumours before and after surgery, as well as to evaluate if there is a correlation between serum levels of these agents and tumour types. METHODS: Serum levels of VEGF, MMP-2, -3 and TIMP-2 were estimated in 43 patients with adrenal tumour at the admission and, in case of surgery, again one month after surgery. The patients were divided into 6 groups according to the type of the tumour (I - patients with adrenal cortex carcinoma, II - with benign hormonally active adrenocortical adenomas, III - with benign, hormonally inactive adenocortical adenomas (incidentaloma), IV - with benign, hormonally active phaeochromocytomas, V - with hormonally quiescent phaeochromocytomas, VI - hormonally inactive adrenal tumours of extraglandular origin. The control group consisted of 10 healthy individuals. RESULTS: There was no correlation between MMP-2 serum levels and tumour types and no significant difference between MMP-2 level before and after surgery. There were no significant differences between TIMP-2 serum levels in patients with adrenal tumours and the control values. Significant increase of serum MMP-3 level was found in patients with cortex cancer and hormonally active benign adrenocortical tumours. The MMP-3 mean serum level was also significantly higher in patients with malignant incidentalomas than in those with benign ones. In all groups of patients with adrenal tumours the means serum VEGF level was significantly higher than in control patients, and it was also significantly higher in patients with malignant incidantalomas than in those with benign ones. After surgery the VEGF level decreased significantly in patients with extraglandular tumours and cortex cancers who had no recurrence. CONCLUSIONS: Since MMP-3 and VEGF serum levels were found significantly higher in patients with malignant adrenal incidentalomas than in those with benign ones, they might be applied as markers of malignancy of incidentalomas. VEGF and MMP-3 levels decreased after tumour resection in all patients with malignant tumors and increased significantly in patients with recurrence. Therefore, they are supposed to be of prognostic value in these patients.

[The influence of thyroidectomy of serum VEGF levels in patients with Graves disease]. / Wplyw strumektomii na stezenie VEGF w surowicy krwi u chorych z choroba Gravesa-Basedowa.

Angiogenic cytokines, including vascular endothelial growth factor (VEGF), play an important role in patients after surgery because they facilitate proper wound healing. The aim of the paper was the comparison of serum VEGF levels in patients before and after thyroidectomy due to Graves disease (Gd). A serum VEGF level was determined by means of ELISA method before the operation as well as 3 and 7 days after it in 24 patients. The mean serum VEGF level was 61.2 pg/ml (range, 33.7-105.0 pg/ml) before the operation and increased after the operation to 115.6 pg/ml (range, 36.3-214.2 pg/ml). After thyroidectomy, the mean level of serum VEGF level in all patients rose by for 79.5% (range, 7.7-115.4%). These results suggest that serum VEGF level increases in patients with Gd after subtotal thyroidectomy, although disorder in secreting cytokines is observed in Gd patients and they were administered thyrostatics up to the operation, which have an immunosuppressive activity.

Vascular endothelial growth factor and basic fibroblast growth factor evaluation in blood serum of patients with hormonally active and inactive adrenal gland tumours.

The vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels of 36 patients with adrenal gland tumours were analysed. The mean age of patients was 43 years (29-67 years), and there were 25 women (69.4%) and 11 men (31.6%). In 34 patients adrenalectomy was performed and in two cases lesions were considered inoperable. In all cases VEGF and bFGF were measured preoperatively and in all operated patients the level of VEGF was measured at 1 month postoperatively. A statistically significant increase in VEGF levels before surgery in comparison with the controls was recorded in all patients with adrenal tumours. No correlation between the size of a tumour and VEGF levels was observed. The serum level of VEGF decreased in patients after surgical removal of the tumour, no matter which type of tumour, with the exception of a patient showing a recurrence of cortex cancer. A statistically significant decrease was found only in patients operated on for cortex cancers and hormonally active and inactive cortex and medulla inactive benign tumours. The postoperative recurrence of the malignant tumour may be preceded by an increase in plasma VEGF levels. Such correlations were not found with bFGF.

The surgical treatment of adrenal gland tumors--incidentaloma.

Analysis of 32 patients operated on because of accidentally discovered adrenal tumors "incidentaloma" is presented. In 12 of them there was subclinical hormonal activity, in 9 of them tumors turned out to be pheochromocytoma and 3 of them were cortex adenoma. There were 20 hormonally inactive tumors, in 5 of them there were malignant lesions (4 of the cortex and 1 of the medulla). For evaluation of hormonal activity of adrenal tumors evaluation of chromogranin A and cortisol serum blood level or urine free cortisol level is recommended. For precise localization of the tumor beside USG also CT examination is of use. According to the high percentage of malignant lesions in "incidentaloma" type tumors, surgery treatment without delay is recommended. BAC or DHES in blood serum examinations were not found helpful in preoperative evaluating the lesions as benign or malignant. In case of preoperatively found subclinical hormonal hyperactivity of medulla pharmacological treatment with alpha and beta blockers in surgery preparation is recommended. Lateral extraperitoneal access for adrenalectomy is considered safe and provides good operational view. Laparoscopic procedure because of high percentage of malignant lesions in this group of patients is not justified.

[Antigens CA-50 and CA-242 in digestive tract and thyroid neoplasms]. / Antygeny CA-50 i CA-242 w nowotworach przewodu pokarmowego i tarczycy.

The aim of the study was to assess the CEA antigen and glycoproteins associated antigen CA-50 and CA-242 in tumours of digestive tract and thyroid gland. 84 patients were the material of the study-33 with digestive tracts' neoplasms (among them 22 cases of large bowel cancer and 11 with cancer of pancreas) and 51 with thyroid neoplasms (30 patients with well differentiated thyroid cancer, 21 follicular adenomas of thyroid). There were assessed level of CA-50 and CA-242 glycoprotein associated antigens. Results were compared with CEA-for digestive tract cancer and Tg levels in thyroid neoplasm respectively. In large bowel cancer (22 cases) there were in 10 patients (45%) with elevated level of CEA, 14 patients with elevated CA-50 (63%) and the same number for CA-242 (14 patients-63%). In cancer of pancreas (total 11 patients) there were CEA elevated level in 3 (27%) patients, CA-50 in 7 (64%) patients and CA-242 in 6 (55%) patients. Patients with well differentiated thyroid cancer (30 cases) revealed elevated level of Tg in 24 (80%) patients, CA-50 in 4 (13%), and CA-242 in 4 (13%) ones. The patients with follicular adenomas (21) had elevated Tg level in 17 (80%) cases, CA-50 in 3 (14%) cases and CA-242 in one patient (4.7%).