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M Tenderenda

Publications and source records attributed to M Tenderenda.

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A study on the prognostic value of cyclins D1 and E expression levels in resectable gastric cancer and on some correlations between cyclins expression, histoclinical parameters and selected protein products of cell-cycle regulatory genes.

Cyclins condition the course of a cell cycle through the activation of appropriate serine-threonine kinases. Any variation in the cyclins' expression result in pathologies of the cell division, including neoplastic proliferation. Activity of the complexes of cyclins D1 and E with appropriate cyclin-dependent kinases may be inhibited by protein P21 (WAF1/CIP1) which functions as a cell growth cycle inhibitor. As yet, there have been rather few reports on the prognostic value of this cyclin expression assessment in gastric cancer, the kind of neoplasm still characterized by very poor prognosis. The study aimed at the assessment of expression levels of cyclins D1 and E in surgically removed gastric cancers, including the analysis of this prognostic value parameter, and attempted to determine some correlations between the expression of the examined cyclins and selected histoclinical and molecular parameters such as: patients' age and gender, histological type according to the Lauren classification, cancer stage (TNM), degree of histological malignancy (G) and level of expression of the cell-cycle regulatory genes protein products--P53, P21, P27. Immunohistochemical analysis was performed on specimens obtained from radical stomach resections of 80 patients treated in the period 1992-1997 for gastric cancer stage I-IIIB (TNM-UICC) at the Department of Surgical Oncology, Medical University of Lodz. For immunohistochemical examinations, the LSAB system was used, designed for assessment of antigen expression. In statistical analysis, Fisher's exact test was applied to evaluate correlations between the analyzed variables and Mantel-Haenschel's test to evaluate their collinearity. For the evaluation of the effect of the analyzed variables on postoperation survival and recurrence-free survival the Cox regression model was used. When analyzing the prognostic value and survival period in association to the cyclins D1 and E expression levels, a statistically significant correlation was found only in relation to cyclin E expression: a survival period of minimum 5 year duration was significantly higher in the group displaying a negative, or only faintly positive, reaction to the presence of cyclin E, than in the group with a strongly positive response. Moreover, the analysis showed statistically significant non-linear dependence between the histological type of cancer in the Lauren classification as well as a degree of histological malignancy and the level of cyclin E expression, and a negative correlation between the level of cyclin E expression and the stage of cancer; In addition, a positive correlation between the level of P53 and cyclin E expression as well as statistically significant non-linear correlation between the level of cyclin E expression and the level of protein P21 expression was observed. However, no statistically significant correlations were found between the level of expression of the two cyclins and the level of protein P27 expression or between the levels of cyclin D1 and E expression in gastric cancer. Out of the two types of evaluated cyclins only cyclin E can be considered a significant regulatory factor and a useful prognostic parameter in gastric cancer.

Cell Cycle↗

Extent of spontaneous apoptosis in gastric cancer: relation to proliferative index, p53 expression, CD 34 expression and histopathological features.

Gastric cancer, characterized by poor prognosis, remains a global health problem. Thus, it is important to describe the biological factors which can affect the prognosis in this disorder. The aim of our study was the determination of the relationship between apoptotic index (AI) and other clinicopathological features (Ki67 labeling index = Ki-67 LI, neovascularity defined as CD-34 immunoreactivity - intratumoral microvessel density = IMVD, p53 immunopositivity, grade of malignancy, histological type, depth of tumour invasion, lymph node status) in 49 cases of gastric carcinoma. Recognition of apoptotic cells was performed applying the terminal deoxynucleotydil transferase mediated dUTP-digoxigenin nick end labeling technique (TUNEL). Among the tumours, 30 were intestinal type and 19 were diffuse type, including 17 cases of well and moderately differentiated tumours (G1 and G2) and 32 poorly differentiated tumours (G3). Apoptotic index was determined in all the examined tumours, and the mean value of AI was 5.8% +/- 4.7%. We found a significant relationship between AI, grade of malignancy and Ki-67 LI. Significantly higher AI -8.1% +/- 5.7% was observed in G1-G2 tumours in comparison to 4.7 +/- 3.8% (p<0.05) in G3 tumours. In tumours with high proliferative potential (above mean value of Ki-67 LI -29.77% +/- 24.9%) we observed higher apoptotic index, mean value 7.9% +/- 5.7%, and in tumours with low proliferation (Ki-67 LI below 29%) mean AI was 4.4% +/- 3.7% (p<0.05). The p53 positive immunoreactivity was found in 30 out of 49 cases (mean AI = 6.75% +/- 4.8%). No apparent correlation between AI, histopathological type of gastric cancer, lymph node status and p-53 and CD-34 immunoreactivity was found.

Antigens, CD34↗

Expression of CD34 in gastric cancer and its correlation with histology, stage, proliferation activity, p53 expression and apoptotic index.

The formation of new blood vessels is essential for tumor growth and progression. Until today there are only few studies of the immunohistochemical assessment of angiogenesis in gastric cancer by the evaluation of the expression of CD34 antigen. The aim of this study was to analyze the relationship between microvessel density (MVD) expressed as the mean count of CD34 immunostained vessels and clinicopathologic features of gastric tumors (the histological type according to the Lauren classification, tumor grade G; presence of lymph node metastases N; depth of tumor invasion; stage of disease (UICC-AJCC 1988 1992), p53 expression, tumor cell proliferative activity described as the Ki67 labelling index and apoptotic index of tumor cells TUNEL method). We assessed formalin-fixed, paraffin-embedded tissue samples obtained during potentially radical gastrectomy from 58 patients with primary gastric adenocarcinoma. The representative tissue blocks from each tumor were used for the immunohistochemical assay and examined by two pathologists independently. MVD was counted in five tumor areas of the most intensive neovascularization (x 200 field by light microscopy) and the mean counts were recorded. The mean MVD (CD34 expression value+/-SD) in this study was 43,15+/-19,8 per x 200 field. The study demonstrated the statistically significant correlation between MVD and two main histological parameters: tumor grading (p < 0.001) and tumor histological type according to Lauren s classification (p<0.05). In well and moderately differentiated tumors (G1/2) MVD was significantly lower in comparison to the group of poorly differentiated cancer G3 (mean value: 31,62 vs. 49,89). MVD was higher in diffuse type of gastric cancer comparing to intestinal type (50.05+/-19,03 vs. 39.17+/-20,09). However, the authors failed to find a significant correlation between MVD and other investigated histopathological features in malignant gastric tumors. The close relationship between CD34 immunostaining, gastric cancer tumor vascularity and main histological parameters was shown in this study. It can be stated that analysis of expression of angiogenesis in gastric cancer may be helpful for better estimation of hematogenous recurrence and the selection of the group of patients for adjuvant antiangiogenic treatment.

Adenocarcinoma↗

Surgical and combined treatment of gastric cancer--own experience.

PURPOSE: In Poland, as well as all over the world, gastric cancer is still among the leading causes of mortality and morbidity from malignant diseases. Many attempts were made to improve the results of the treatment. In this paper we present our 25-year experience in this field. MATERIAL AND METHODS: From 1977 to 2000 in the Clinical Department of Surgical Oncology, Medical University of Łódź, we treated 353 patients (males 63%; females 37%) with the diagnosis of gastric cancer, confirmed histologically. We analysed the age of patients, location of primary tumor, histologic type, stage of the disease, type of surgery, type of reconstruction of GI tract, type of adjuvant therapy and survival. RESULTS: In patients with the disease in stage I and II according to UICC Fielding classification, the best results were achieved. Five year survival reached 76% which means that early recognised gastric cancer may be cured. However, patients from this group constituted only 6.7% of all the treated population. In patients with stage III disease, 5 year survival was 34.5%. In patients with IVA stage of the disease (72 cases), in whom only cytoreductive-palliative surgery was performed, 5-year survival was 16.7%. No patient with IVB stage of the disease (purely palliative procedures performed) survived 5 years. Significant improvement of distant results was, observed in patients receiving EAP as an adjuvant therapy (25.1% of 5-year survivors) in comparison to control group patients treated solely with surgery (18.2% of 5 year survivors). In 97 patients after total gastrectomy, significantly lower complication rate was observed in patients in whom intestinal pouch was created (Hunt-Lawrence) than in patients in whom the pouch was not created (Roux-Y, Engel-Graham). CONCLUSION: In our opinion, we should consequently implement guidelines known as the "Polish Consensus of Gastric Cancer Treatment", like extensive radical stomach resection (whenever possible) with regional lymphadenectomy and adjuvant therapy.

Adult↗

Activation of blood coagulation and the activity of cancer procoagulant (EC 3.4.22.26) in breast cancer patients.

The activity of cancer procoagulant (CP), prothrombin time (PT), activated partial thromboplastin time (APTT), the concentration of thrombin-antithrombin complexes (TAT) and the concentration of fibrinogen were analysed in blood of breast cancer patients scheduled for surgery. The serum level of CP activity was dependent on the stage of the disease. The CP activity was increased in 72% of patients with an early stage of cancer and in only 20% of patients with an advanced stage of the disease when compared to the baseline level for non-cancer controls. In all patients PT remained at normal levels (80-120%). There was no significant change in APTT (27-39 s) in early stage cancer patients. Only one patient with advanced cancer had APTT shortened to 23 s. Also one advanced stage patient had significantly elevated level of TAT (14.96 microg/l); in all other patients the concentration of TAT remained at normal levels (1-4.1 microg/l). Forty-four percent of early stage cancer patients and 22% of advanced cancer patients had an elevated level of fibrinogen (Fg) ( > 350 mg%). However, there was no correlation between the level of Fg and the CP activity (P > 0.05). The data suggest that: (1) serum CP activity increases at the early stage of breast cancer and decreases down to the normal level in the advanced stage of the disease; (2) there is no evidence of blood clotting activation in the early stage breast cancer patients; and (3) CP does not facilitate the activation of coagulation in the breast cancer patients or the level of such activation is below the sensitivity of assays used in the experiment.

Antithrombin III↗

[Reconstruction methods for the continuous digestive tract using surgical stapling after gastrectomy with lymphadenectomy in patients undergoing surgery for stomach cancer. Personal evaluation].

From 1984 to 1994, 152 patients were operated for gastric cancer in Clinical Department of Surgical Oncology, Medical University of Lodz. Patients age ranged from 31 to 82 years (mean age-61.2). The purpose of this study was to evaluate the methods of reconstruction of gastrointestinal tract (GIT) continuity. Our material comprised patients who underwent total gastrectomy for gastric cancer. In 52 patients radical procedure--total gastrectomy--was performed, with reconstruction of gastrointestinal tract continuity. The latter part of surgery was accomplished using different methods: Roux-Y anastomosis-10 patients (19.2%); esophago-jejunal "end to side" anastomosis-8 patients (15.4%); Hunt-Lawrence-Rodino anastomosis-34(65%). During procedures staplers and VALTRAC rings were used, as well as ultrasound selector and argon coagulator for hepatic and pancreatic resections. Quality of life after gastrectomy was determined on the basis of interviews taken from patients, in whom GIT continuity was reconstructed with or without intestinal pouch creation. We also evaluated incidence and type of complications after such procedures. Perioperative mortality in our material was 7.7%. We concluded that the best results was achieved when continuity of gastrointestinal tract after total gastrectomy was reconstructed with intestinal (first loop of jejunum) pouch creation (Hunt-Lawrence procedure). This method warranted high quality of life and low incidence of complications. Staplers enables us to shorten time of procedure and to decrease the number of anastomosis leaks, so that our results of surgical treatment of patients with gastric cancer were better.

Adult↗