Plasma Brain-Derived Neurotrophic Factor and Opioid Therapy: Results of Pilot Cross-Sectional Study.

Objective: The neurotoxic effect of opioid has not been thoroughly described. No studies have been conducted to explain the effect of opioids in chronic non-cancer pain therapy on the neurotrophic factors level. Due to the ability to cross the blood-brain barrier, it seems the determination of serum Brain-derived neurotrophic factor (BDNF) concentration is a reliable presentation of the concentration in the central nervous system. The aim of the study was to explore the changes of plasma BDNF concentration during long-term opioid therapy.Methods: The study group included 28 patients with chronic low back pain treated with opioid therapy buprenorphine (n=10), tramadol (n=8), oxycodone (n=6), morphine (n=3), fentanyl (n=1). The control group included 11 patients. Measurements of plasma BDNF concentrations were performed, and information about opioid therapy were recorded (age, sex, opioid substance type, daily dose and the duration of opioid therapy). Data were analyzed using nonparametric tests.Results: The median BDNF level in the study group was significantly lower (2.73 ng/mL) than that in the control group (5.04 ng/mL, P<0.05). BDNF levels did not differ among groups based on the type of opioid substance used, but the lowest median value was observed for tramadol (2.62 ng/mL), and the highest median value was observed for buprenorphine (2.73 ng/mL). The widest minimum-maximum ranges of BDNF for oxycodone were noted, minimum 1.23 ng/mL and maximum 4.57 ng/mL, respectively. BDNF concentrations were correlated with age in the tramadol group and with the duration of opioid therapy in the buprenorphine group.Conclusion: Chronic opioid therapy for noncancer pain induces specific changes in the BDNF concentration. Tramadol and buprenorphine exerted an important effect on BDNF levels in the examined patients. The BDNF level depends on duration of opioid therapy with buprenorphine, and age in tramadol therapy.

Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage.

BACKGROUND: Anesthesia and surgery is commonly associated with central nervous system sequelae and cognitive symptoms, which may be caused by neuronal injury. Neuronal injury can be monitored by plasma concentrations of the neuronal biomarkers tau and neurofilament light protein (NFL). Currently, there are no studies examining whether neuronal injury varies between surgical procedures. OBJECTIVE: Our aim was to investigate if neuronal damage is more frequent after cardiac than after otolaryngeal surgery, as estimated by tau and NFL concentrations in plasma. METHODS: Blood samples were drawn before, during, and after surgery and concentrations of tau, NFL, Aß40, and Aß42 were measured in 25 patients undergoing cardiac surgery (9 off-pump and 16 on-pump) and 26 patients undergoing otolaryngeal surgery. RESULTS: Tau increased during surgery (1752%, p = 0.0001) and NFL rose seven days post-surgery (1090%, p < 0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients undergoing otolaryngeal surgery and only minor fluctuations were observed for Aß40 and Aß42. CONCLUSION: Cardiac surgery is associated with neuronal injury, which is aggravated by extracorporeal circulation. Analyses of NFL and tau in blood may guide development of surgical procedures to minimize neuronal damage, and may also be used in longitudinal clinical studies to assess the relationship of surgery with future neurocognitive impairment or dementia.

[Albuminuria in patients with type 2 diabetes mellitus in relation to percentage of HbA1c]. / Albuminuria u chorych na cukrzyce typu 2 w zaleznosci od odsetka HbA1c.

UNLABELLED: Albuminuria is an early marker of the microvascular and macrovascular complications in patients with type 2 diabetes mellitus. Metabolic complication accompanying the disease, especially hyperglicaemia, have significant influence on the range of albumin excretion. The aim of the study was to evaluate urinary albumin excretion and percentage of glycated hemoglobin (HbA1c), in relation to fasting and postprandial glycaemia. MATERIAL AND METHODS: Research was made in two groups of patients with confirmed albuminuria: in the 1st group with good glycemic control with HbA1c > or = 6,1%-< or = 6,5%, and in the 2-nd group with poor glycemic control with HbA1c > 6,5%-< or = 10%. The control group consisted of 21 patients with essential hypertension and coexisted albuminuria, not suffering from diabetes. The average fasting and postprandial glycemic were calculated for each patient on the basis of the last three values of glycaemia from the patient's self-control test. The extent of albuminuria and the percentage of HbA1c were determined by the immunoturbidimetric test. RESULTS: The highest albumin excretion in urine was noticed in the group with poor glycemic control, a slightly lower level of albuminuria was found in the group with good glycemic control, however the lowest level of albumin excretion was noticed in the control group. The differences were not statistically significant. The fasting glycaemia as well as postprandial glycaemia were increased in the group with higher percentage of HbA1c (p < 0,001) with comparison to the group with good glycemic control. The average percentage of HbA1c was 7,54% in the group with poor glycemic control and was significantly connected with larger glycaemia with comparison to the 2nd group with average percentage of HbA1c 6,3%. CONCLUSIONS: The excretion of albumin in urine rises with increased glycaemia and percentage of glycosylated hemoglobin. Fasting glycaemia as well as postprandial glycaemia have influence on the percentage of glycated hemoglobin.

[Assess the impact of concentrations of inflammatory markers IL-6, CRP in the presence of albuminuria in patients with type 2 diabetes]. / Ocena wplywu stezenia markerów stanu zapalnego: IL-6, CRP na wystepowanie albuminurii u chorych na cukrzyce typu 2.

UNLABELLED: Diabetic nephropathy is one of the most common complications of diabetes. Symptom of nephropathy is albuminuria, in which the mechanism of formation may participates CRP and IL-6. The aim of the study was to evaluate the concentrations of CRP and IL-6 depending on the irregularity of metabolic patients with type 2 diabetes and their impact on the occurrence of albuminuria. MATERIAL AND METHODS: The study was conducted among 68 patients with type 2 diabetes with albuminuria. Patients were divided into groups: group I - patients with type 2 diabetes with HbA1c > or = 6.1 - < or = 6.5%, group II - patients with type 2 diabetes with HbA1c > 6.5 - < or = 10.0%, K - control group, 21 patients with essential hypertension with albuminuria. The material was consisted of venal extracted for clot drawn from the basilic vain. IL 6 concentration was assessed using the ELISA method. The percentage of hemoglobin A1c (HbA1c), CRP, the extent of albuminuria was determined by immunoturbidimetric method. RESULTS: The mean urinary albumin excretion was highest in the second study group, lowerin the test group, the lowest in the control group. The average concentration of IL-6 and CRP was highest in group I, lower in group II, the lowest in the control group (p > 0.05). It has been shown a positive correlation between serum CRP and the magnitude of albuminuria in the test group of patients with type 2 diabetes with HbA1c > or = 6.1 - < or = 6.5% (p < 0.037). The relationship between serum CRP and the magnitude of albuminuria in the control group of patients with essential hypertension were at the border of statistical significance (p < 0.057). Not shown a positive correlation between these parameters in the second group of patients with type 2 diabetes with HbA1c >6.5 - < or = 10.0%. CONCLUSIONS: In patients with type 2 diabetes with better metabolic control, protein CRP is a sensitive marker of albuminuria.

Relationships between insulin-like growth factor i and selected clinico-morphological parameters in colorectal cancer patients.

UNLABELLED: Insulin Like Growth Factor (IGF I) as the one of the strongest growth factors which can affect cancers development including colorectal cancer. IGF I induces processes of the cells growth and division. It regulates cells cycle and inhibits apoptosis. There is limited data about correlation between IGF I and staging of the tumor. The aim of the study was estimation of the clinical usefulness of IGF I concentration in the serum of the patients with colorectal cancer. MATERIAL AND METHODS: We have examined 125 individuals with colorectal cancer. The age range was 36 to 92 years. They have been operated in the 2nd Departament of The Gastrointestinal Surgery of the Medical University in Bialystok. Serum concentration of the IGF I have been estimated using immunoassay ELISA before and after operation. Correlation between serum level of IGF I and clinicopathologic features: age, gender, localisation of the primary tumor, TNM stage of tumor, histological type and histological grade (G) of the cancer have been estimated. RESULTS: Our study revealed statistically significant increased serum concentration of IGF I in patients with locally advanced colorectal cancer (pT3 and pT4) comparing to less advanced (pT2) The investigations showed higher serum concentration of IGF I in patients with poorly differentiated cancers (G3) than in moderately differentiated. Similarly higher serum concentration of IGF I were found in male, in patients older than 60 years and in mucigenous colorectal cancers. CONCLUSIONS: Our results indicated that IGF I can be one of the factors of the prognosis in colorectal cancer development.

Correlation between Fas and FasL proteins expression in normal gastric mucosa and gastric cancer.

The study's objective was to assess the expressions of Fas and FasL proteins in gastric cancer in correlation with chosen clinicohistological parameters. Fas and FasL expression was analyzed in 68 patients with gastric cancer, using the immunohistochemical method. The expression of Fas was found to be lower in gastric cancer cells than in healthy mucosa, both in the lining epithelium and in glandular tubes (28% vs. 48% and 44%; p < 0.001). The expression of FasL was also markedly lower in cancer cells than in glandular tubes, yet higher than in the lining epithelium (51% vs. 73% and 14%; p < 0.01). Positive expressions of FasL and Fas were lower in less advanced gastric cancer cells (T1, T2), than in more advanced tumors (T3, T4), but only in the case of FasL was this difference statistically significant (p < 0.05). Our findings seem to confirm the theory of the impact of apoptotic disorders at the level of Fas receptor and FasL protein in the process of gastric cancer formation and growth, which is manifested in the varied expressions of these proteins in gastric cancer and in the normal lining and glandular epithelium of the stomach. However, the lack of significant differences in the expressions of Fas and FasL in correlation to other clinicohistological parameters indicates the existence of mechanisms that have a greater impact on the process of differentiation of gastric cancers. This in our opinion eliminates these proteins as prognostic factors.

The expression of E-cadherin-catenin complex in patients with advanced gastric cancer: role in formation of metastasis.

The E-cadherin-catenin complex plays an important role in the process of cell adhesion. Its dysfunction is associated with a decrease in cell differentiation and with increased invasiveness and metastasis. Our aim was to evaluate the expression of E-cadherin and B-catenin in advanced gastric cancer in relation to selected clinico-pathomorphological parameters. Formalin-fixed, paraffin-embedded tissue specimens were immunohistochemically stained with monoclonal antibodies E-cadherin (NCL-E-Cad, Novocastra Laboratiries Ltd; dilution 1:50), beta-catenin (NCL-B-CAT, Novocastra Laboratories Ltd; dilution 1:100), alpha-catenin (alpha-E-caten, Santa Cruz Biotechnology; dilution 1:300) and gamma-catenin (gamma-catenin, Santa Cruz Biotechnology; dilution 1:100). The expressions of E-cadherin and alpha-, beta-, gamma-catenins in the main mass of tumor and lymph node metastasis were investigated in 91 patients with gastric cancer. No statistically significant correlation was observed between the expressions of E-cadherin, alpha-, beta-catenins and histological differentiation and between the expressions of E-cadherin, alpha-, gamma-catenins and location or depth of invasion. Moreover, the expression of alpha-, gamma-catenins in the main mass of tumor was not associated with lymph node metastasis. However, we found a relationship between the expression of beta-catenin in the main mass of tumor and lymph node metastasis and tumor location. The depth of invasion was correlated with positive expression of beta-catenin in the main mass of gastric cancer. A statistically significant association was observed between the expressions of E-cadherin and beta-catenin in the main mass of tumor and lymph node involvement. The expression of alpha-catenin in the main mass of tumor was also associated with histological differentiation and Lauren's classification. Statistical analysis showed an association between the expression of E-cadherin and postoperative survival time. No significant correlation was found between the expression of alpha-, beta-, gamma-catenins and survival time. Our results may suggest that the E-cadherin-catenin complex is the factor indicative of metastasis and disease progression in gastric cancer. Also the expression of E-cadherin may play a role as a prognostic factor.

Expression of the E-cadherin-catenin complex in patients with pancreatic ductal adenocarcinoma.

Cadherins and catenins, mediators of intercellular interactions, play a major role in adhesion. Changes in their expression and functioning reflect invasive and metastatic properties of cancer cells. The study objective was to assess changes in the expressions of E-cadherin and alpha-, beta- and gamma-catenin proteins in pancreatic duct carcinoma in correlation with clinicopathological parameters, lymph node involvement and distant metastases. Twenty-nine patients with pancreatic duct carcinoma were analyzed in relation to gender and age, histological type, histological malignancy grade (G), local lymph node involvement and distant metastases. The expression levels of E-cadherin and alpha-, beta- and gamma-catenins were subjected to immunohistochemical labeling. Reduced expression or abnormal localization of E-cadherin and alpha-, beta- and gamma-catenins were observed in pancreatic duct carcinoma. The statistical analysis did not show any correlations of the expressions of these proteins with gender and age of patients, histological type (Hp), histological grade (G) and the presence of local lymph node involvement or distant metastases. However, correlations were found between the expression of E-cadherin and beta- catenin (p<0.001) as well of alpha-catenin with beta-catenin (p=0.006) and gamma-catenin (p=0.026). Disorders in the expression of E-cadherin reveal strong associations with abnormal expressions of alpha, beta- and gamma-catenins. Also enhanced tumor aggressiveness shows certain tendency correlations (although statistically insignificant) with the loss of E-cadherin expression and change in its localization.

Immunohistochemical evaluation of Ki-67, PCNA and MCM2 proteins proliferation index (PI) in advanced gastric cancer.

The current study objective was to assess the proliferation indices (PI) of Ki-67, PCNA and MCM2 proteins in advanced gastric cancer and in metastatic lymph node in correlation with certain clinicopathological features and with postoperative survival of patients. The study was conducted in a group of 100 patients with advanced gastric cancers. Involvement of local lymph nodes was present in 36 cases. Immunohistochemical investigations were carried out using monoclonal antibodies against Ki-67 (DAKO), PCNA (DAKO) and polyclonal antibody to MCM2 (Santa Cruz Biotechnology). Visualization of the antigen/antibody complex was performed using LSAB technique (biotin-streptavidin-peroxidase) followed by application of chromogene DAB (DAKO). Statistical analysis revealed no correlations of Ki-67, PCNA and MCM2 PI in tumour tissue or metastatic lymph node with patients' age and gender, tumour location, histological grade, macroscopic type according to Bormann's classification and histological grading by Lauren's and Goseki's classifications. Moreover, no correlation was observed of Ki-67 and MCM2 PI in tumour tissue with histological grading. No correlation was also noted between the proliferation indices of all the three proteins in the affected lymph node and grade of histological differentiation. Such clinicopathological parameters as patients' age and gender, histological grading by Lauren's and Goseki's classifications and lymph node involvement did not correlate with survival time of patients. Furthermore, no statistically significant correlation was shown of postoperative survival time with Ki-67 and MCM2 PI in tumour tissue and metastatic lymph nodes and with PCNA PI in the affected lymph nodes. However, a statistically significant correlation was found of Ki-67, PCNA and MCM2 PI in tumour tissue and metastatic lymph nodes with depth of wall invasion and local lymph node involvement. A statistically significant correlation was also noted between PCNA PI in the main mass of tumour and histological grading. The postoperative survival time of patients exhibited a statistically significant correlation with tumour location and macroscopic type according to Bormann's classification. Correlations on statistical borderline were noted between survival time and depth of gastric wall invasion and PCNA PI in the main mass of tumour.

Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer.

BACKGROUND: Colorectal cancer is a major oncological problem. The rate of cancer growth depends on proliferative activity and tumor cell death rate. Therefore, the study objective was to estimate the expression of Bcl-2 as an apoptotic protein representative, as well as other proteins involved in proliferation PCNA (proliferating cell nuclear antigen), Ki-67 and MCM-2 (minichromosome maintaince), and to analyze the correlations between them and chosen anatomo-clinical parameters. MATERIALS AND METHODS: The expressions of these proteins were analyzed in 47 patients with pT3, G2 colorectal cancer by immunohistochemistry. RESULTS: No association was found between the expressions of Bcl-2, PCNA, Ki-67, MCM-2 and histological type of tumor, distant metastasis, gender or age of patients. However, we observed a correlation of PCNA, Ki-67 and MCM-2 expressions, but not of Bcl-2, in the main mass of tumor in patients with lymph node metastases. Moreover, a very strong relationship was noted between the expression of Bcl-2 and PCNA, Ki-67 and MCM-2 in the main mass of tumor. Conlusion: These investigations seem to suggest that the expression of proliferative proteins (PCNA, Ki-67, MCM-2) in pT3, G2 of colorectal cancer may indicate the development of lymph node metastases and that inhibited apoptosis by Bcl-2 protein can enhance the action of these proteins in tumor progression.

Immunohistochemical assessment of Fhit protein expression in advanced gastric carcinomas in correlation with Helicobacter pylori infection and survival time.

Fhit protein is known to play a role in the process of neoplastic transformation. It has been demonstrated that FHIT gene inactivation is manifested by a lack or very low concentration of Fhit protein in tissues collected from tumours in many organs, including head, neck, breast, lungs, stomach or large intestine. The study included a group of 80 patients with advanced gastric carcinomas. The expression of Fhit protein was assessed by means of the immunohistochemical method (avidin-biotin-streptavidin) in the sections fixed in formalin and embedded in paraffin, using rabbit polyclonal antiFhit antibody (Abcam, UK) at 1: 200. Statistical analysis did not show any correlation of the expression of Fhit protein in the main mass of tumour and in the metastasis to lymph node with gender, depth of wall invasion, histological differentiation, Lauren's classification, Bormann's classification, metastases to local lymph nodes or Helicobacter pylori infection. However, a strong statistical correlation was revealed of Fhit protein expression in the main mass of tumour with patients' age (p=0.04) and tumour location in the stomach (p=0.02). No relationship was found between Fhit expression in the main mass of tumour and survival time (p=0.26).

Correlation of c-erbB-2, EGF and EGFR expression with postoperative survival of patients with advanced carcinoma of the stomach.

The c-erbB-2 (HER-2/neu), EGF and EGFR (erbB-1) proteins, members of the epidermal growth factor receptor family, play a role in cell growth by binding to cell membrane receptors. The aim of the current study was to evaluate the expression of c-erbB-2, EGF and EGFR in advanced gastric carcinoma and to analyze its relationship with chosen anatomo-clinical parameters and prognosis. Standard avidin-biotin-peroxidase was used for c-erbB-2, EGF and EGFR immuno-histochemical staining (Novostain Super ABC Kit Universal); anti-human c-erbB-2 protein monoclonal antibody NCL-cerbB-2-316, anti-Epidermal Growth Factor monoclonal antibody (clone EGF-10) and EGFR goat polyclonal IgG (p-EGFR). A statistically significant correlation was found between c-erbB-2, EGF, EGRF expressions in the main mass of tumor and lymph node metastasis (p=0.000; p=0.000; p=0.00001, respectively). Also an association was observed between c-erbB-2 expression and Bormann's and Lauren's classifications (p=0.05; p=0.006, respectively). Similarly, the expression of EGFR in main mass of tumor was correlated with the depth of invasion (p=0.007) and histological differentiation (p=0.04). Moreover, the expression of c-erbB-2 in the main mass of tumor and lymph node metastasis was associated with the age of the patients (p=0.03; p=0.0002 respectively). Strong association was found between the expression of EGRF in lymph node metastasis and histological differentiation (p=0.04). Positive expression of c-erbB-2 in lymph node metastasis was correlated with lymph node involvement (p=0.04). Positive expression of c-erbB-2 in the main mass of tumor and in lymph node metastasis was strongly correlated with postoperative survival (p=0.00001; p=0.003 respectively). We also found a relationship between EGF expression in gastric tumor and survival time (p=0.003). No association was noted between the expression of EGFR in the main mass of tumor and in lymph node metastasis and between the expression of EGF in lymph node metastasis and survival time. Our results suggest that the expression of c-erbB-2 and EGF protein can help predict the postoperative survival time.

Expression of epidermal growth factors and apoptosis markers in pancreatic ductal adenocarcinoma.

BACKGROUND: Epidermal growth factor family members: EGF, EGFR and the c-erbB-2(HER-2/neu) are involved in the growth of pancreatic ductal carcinoma, its invasiveness and metastases. Similarly, proteins regulating apoptosis can influence the development of pancreatic cancer. The aim of our study was to assess the expressions of EGF, EGFR, c-erbB-2, Bax and Bcl-xL in comparison with anatomo-clinical parameters. We also analyzed the relationship between the epidermal growth factors and apoptosis-regulating proteins. MATERIALS AND METHODS: The levels of these proteins were determined immunohistochemically in 29 pancreatic ductal carcinoma cases. RESULTS: We found no correlation of EGF, EGFR, c-erbB-2, Bax and Bcl-xL with age and gender of patients, or histological type and grade of malignancy (G). However, we observed a very strong correlation between EGF, EGFR, Bax, Bcl-xL and lymph node metastases (p=0.000, p=0.001, p=0.008, p=0.012, respectively) and between EGF, EGFR and distant metastases (p=0.002, p=0.008, respectively). Moreover, we found a correlation between Bcl-xL and c-erbB-2 (p=0.030) and between EGF and Bax (p=0.041). CONCLUSIONS: These investigations seem to suggest that both epidermal growth factors (EGF, EGFR) and apoptosis-regulating proteins (Bax and Bcl-xL) play an essential role in lymph node involvement. Moreover EGF and EGFR are involved in distant metastases. The apoptosis markers appear to cooperate with epidermal growth factor proteins in the process of tumor spread.

Helicobacter pylori infection and expressions of EGF, EGFR and c-erbB-2 proteins in gastric carcinoma.

The family of epidermal growth factor (EGF, EGFR, c-erbB-2) plays a pivotal role in gastric cancer progression, invasion and metastasizing. Helicobacter pylori infection is known to contribute significantly to the formation and progression of gastric cancer. However, the mechanisms responsible for this process have not been yet elucidated. We analysed the relationship between H. pylori infection and expression of proteins belonging to the family of epidermal growth factor (EGF, EGFR, c-erbB-2). Fifty-five patients with gastric cancer were analysed for Helicobacter pylori infection. The expressions of EGF, EGFR, c-erbB-2 proteins were determined using an immunohistochemical method. No statistically significant correlation was found between the degree of H. pylori infection and the expressions of EGF, EGFR and c-erbB-2 in gastric cancer. However, c-erbB-2 expression in the main mass of tumour correlated with tumour expression of EGF and EGFR and with c-erbB-2 expression in local lymph nodes. The expression of c-erbB-2 in lymph nodes was statistically significantly related to the expressions of EGF and EGFR both in the main mass of tumour and in lymph nodes. The expression of EGF was found to correlate with EGFR in the main mass of tumour and the expression of EGF in lymph nodes was related to lymph node EGFR level. Our study did not confirm the relationship between H. pylori infection and the expression of epidermal growth factor in gastric cancer.

Expression of matrix metalloproteinase-9 in the neoplastic and interstitial inflammatory infiltrate cells in gastric cancer.

Matrix metalloproteinases (MMPs) play an important role in the extracellular matrix degradation, that is an essential step in tumor invasion and metastases. The current study objective was to evaluate the expression of MMP-9 in the neoplastic and in the interstitial inflammatory infiltrate cells in gastric cancer (GC). Moreover, the relationship between expression of this enzyme and clinicopathological features of GC, such as TNM stage, the depth of tumor invasion, lymph node and distant metastases were assessed. The study comprised 54 patients with gastric cancer. Immunohistochemistry was used to determine the expression of MMP-9 in gastric cancer cells. The semi-quantitative scale was applied to evaluate the expression of metalloproteinase-9. Immunohistochemical testing revealed a positive reaction of MMP-9 in 98% of all cancer tissue specimens and in 93% of inflammatory cells. The expression of MMP-9 in the neoplastic and inflammatory cells increased with more advance tumor stage, depth of tumor invasion and presence of lymph node as well as distant metastases. These findings indicate the significance of interstitial inflammatory infiltrate cells in the MMP-9 synthesis and the role of this enzyme in the invasiveness and metastatic potential of GC.

Expression of tissue inhibitors of metalloproteinase 1 (TIMP-1) in gastric cancer tissue.

Degradation of extracellular matrix (ECM) is an essential step of invasion and metastasis of gastric cancer. The proteolysis of basement membranes depends on the balance between activities of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The aim of the study was to assess the expression of TIMP-1 in gastric cancer (GC) and interstitial inflammatory infiltrate cells within GC tissue in relation to clinico-pathological features of tumor and to estimate the prognostic significance of TIMP-1 expression for patients' survival. The presence of TIMP-1 in 54 cases of gastric cancer samples was investigated by immunohistochemistry. The expression of TIMP-1 in cancer and interstitial inflammatory infiltrate cells was evaluated in semi-quantitative scale. The immunoreactivity of TIMP-1 in cancer and inflammatory cells was positive in 100% of cases and varied from weak to intense reaction. The intensity of TIMP-1 expression increased with more advanced tumor stages and in patients who died of cancer during 2-year observation. TIMP-1 expression in interstitial inflammatory infiltrate cells was the independent prognostic factor for patients' survival. The results suggest the role of TIMP-1 in gastric tumorigenesis, although this issue requires further investigtions.

Expression of EGF and EGFR strongly correlates with metastasis of pancreatic ductal carcinoma.

BACKGROUND: The epidermal growth factor family members: EGF, EGFR and the c-erbB-2(HER-2/neu) gene product have been found to play a role in carcinomas of the stomach, liver, breast, ovary and lungs. Recent reports have indicated that they are also involved in the growth of pancreatic ductal carcinoma, its invasiveness and metastasis. PATIENTS AND METHODS: Thirty-six patients with pancreatic ductal carcinoma were analysed with respect to sex, age, histological type, malignancy grade (G), pTN status (pTN), local lymph node involvement and distant metastasis. The tumor levels of EGF, EGFR and c-erbB-2 expression were determined immunohistochemically. RESULTS: Expression of c-erbB-2 was observed in 24/36 cases, EGF in 13/36 cases and EGFR in 18/36 cases. Overexpression of EGF and EGFR was associated with metastasis to lymph nodes and other organs. A correlation was also found between EGF expression and the presence of EGFR in the tumour. The expression of c-erbB-2 protein was not found to correlate with any parameters. CONCLUSION: EGF and EGFR play a key role in neoplastic spread through lymph node involvement and metastasis to other organs.

The expression of matrix metalloproteinase 9 and cathepsin B in gastric carcinoma is associated with lymph node metastasis, but not with postoperative survival.

Degradation components of basement membrane could be crucial for tumor invasion. A key role in this process has been assigned to cysteine proteases, i.e. cathepsins and matrix metalloproteinases. The purpose of this study was to investigate the relationship of the expression of MMP-9 and cathepsin B with tumor aggressiveness expressed by lymph node metastases and survival rates in gastric carcinoma patients. Slides of 5 mum-thick serial sections from 91 patients with primary gastric carcinoma were prepared and analyzed for MMP-9 and cathepsin B expression using anti-human monoclonal antibody (NCL-MMP-9 clone; dilution 1:40 and NCL-CATH-B clone; dilution 1:40). The patients were clinically monitored for 84 months. We found no association between the expression of MMP-9 and cathepsin B in main mass of tumor and patients' gender, tumor location, Lauren's classification or histological differentiation. Also no correlation was observed between the expression of MMP-9 in main mass of tumor and depth of invasion. A strong statistically significant association was found between the expression of MMP-9 and cathepsin B in main mass of tumor and lymph node involvement (p<0.001; p<0.001, respectively). However, we observed no correlation between the expression of MMP-9 and cathepsin B in main mass of tumor and lymph node involvement or 5-year overall survival. Our results may suggest that the expression of matrix metalloproteinase-9 (MMP-9) and cathepsin B is correlated with lymph node metastasis in advanced gastric carcinoma, but not with patients' postoperative survival.