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Biomedical subjects

M Z Wojtukiewicz

Publications and source records attributed to M Z Wojtukiewicz.

At least 19 recordsLinked to original sources

Loss of heterozygosity on chromosomes 2p, 3p, 18q21.3 and 11p15.5 as a poor prognostic factor in stage II and III (FIGO) cervical cancer treated by radiotherapy.

Loss of heterozygosity (LOH) has been shown to be an important prognostic factor in a variety of malignant neoplasm's. Cervical cancer develops as result of multiple genetic alterations. The aim of this study was to analyze presence of LOH in cervical cancer and to identify the correlation between LOH and survival and relapse-free survival time in patients treated with radiotherapy. Studies were performed on tumor specimens and venous blood from 20 patients with cervical cancer (squamous cell carcinoma G2 and G3) in stage II and III (FIGO) treated with radiotherapy. DNA was isolated using organic extraction. Additional microcolumn purification was performed. The fluorescent multiplex polymerase chain reaction (PCR) was used to amplify 10 microsatellite loci included in commercially available human identification kits. Microsatellite marker BAT 26 was amplified in separate PCR reactions. 75% cervical cancers manifested LOH. LOH in BAT 26 analysis (chromosome 2) was present in all these specimens. 60% of the cases showed LOH at one or more of other examined loci (mostly on 3p, 18q21.3, and 11p15.5). Eight of nine cervical cancers in clinical stage III showed LOH. All cases of G3 squamous cell carcinoma of the cervix manifested LOH on 2p. Patients with LOH have worse prognosis for survival and relapse-free survival compared to patients without LOH.

Adult↗

Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients.

PURPOSE: Interleukins may stimulate cancer cells growth and contribute to locoregional relapse as well as metastasis. Permanent synthesis and release of these cytokines leads to augmentation of their serum concentration that might be utilized as a marker of immunity status and immune system activation in prognosis and monitoring of the course of cancer. MATERIAL AND METHODS: Therefore, in the present study we assessed the concentration of IL-6, IL-8 and IL-10 in blood serum of breast cancer patients to determine whether it correlates with the disease progression. RESULTS: We showed statistically higher serum concentrations of IL-6, IL-8 and IL-10 in breast cancer patients in comparison with healthy women, which also correlated with clinical stage of breast cancer. CONCLUSIONS: The present study indicates that elevated IL-6, IL-8, and IL-10 serum concentration, are strongly associated with breast cancer and correlate with clinical stage of disease. It was feasible that it can be used to diagnose women with breast cancer and to identify patients with a poor prognosis who may benefit from more aggressive management.

Adult↗

Localization of blood coagulation factors in situ in pancreatic carcinoma.

Blood coagulation is activated commonly in pancreatic carcinoma but the role of the tumor cell in this activation is undefined. Immunohistochemical procedures were applied to fixed sections of 22 cases of resected adenocarcinoma of the pancreas to determine the presence of components of coagulation and fibrinolysis pathways in situ. Tumor cell bodies stained for tissue factor: prothrombin: and factors VII, VIIIc, IX, X, XII, and subunit "a" of factor XIII. Fibrinogen existed throughout the tumor stroma, and tumor cells were surrounded by fibrin. Staining for tissue factor pathway inhibitor, and plasminogen activators was minimal and inconsistent. Plasminogen activator inhibitors -1, -2, and -3 were present in the tumor stroma, and on tumor cells and vascular endothelium. Extravascular coagulation activation exists associated with pancreatic carcinoma cells in situ that is apparently unopposed by naturally occurring inhibitors or the plasminogen activator-plasmin system. We postulate that such local coagulation activation may regulate growth of this malignancy. These findings provide a rationale for testing agents that modulate the blood coagulation/fibrinolytic system (that inhibit tumor growth in other settings) in pancreatic carcinoma.

Adenocarcinoma↗

Platelet activation and its role in thrombin generation in platelet-induced thrombin generation time.

Platelet-induced thrombin generation time (PITT) is a newly developed global coagulation assay in which a small amount of partially anticoagulated platelet-rich plasma (PRP) is rotated in a disc-shaped cuvette within the light beam of a photometer. The time intervals from onset of rotation until aggregation and coagulation of the sample are registered. The aim of our study was to compare platelet activation with generation of thrombin during rotation of PRP in PITT system. Aliquots of PRP were taken before, 1, 3, and 8 min after the onset of rotation as well as at the beginning of aggregation and shortly before coagulation. Thrombin activity was measured with chromogenic substrate S-2238. We have also measured the level of generated prothrombin activation fragment 1+2 (F1+2), which reflects the concentration of liberated thrombin. Platelet activation was assayed by means of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) concentration and registration of the aggregation. The concentrations of the F1+2, PF4, beta-TG increased very slowly from the beginning of the test until aggregation occurred. From the start of aggregation, the levels of F1+2 rose rapidly. In contrast to the F1+2 measurements, thrombin activity has not been detected from onset of rotation until the end of the test. Only trace thrombin activity was detectable just after the plasma sample had been clotted in the cuvette. Our results demonstrate that there exists a close relationship between platelet activation and thrombin generation. Viable platelets, which adhered to the cuvette walls, form an active template on which thrombin can be generated from prothrombin.

Adult↗

Expression of prothrombin fragment 1+2 in cancer tissue as an indicator of local activation of blood coagulation.

Immunohistochemistry was applied to AMeX-fixed tissue sections of 12 adenocarcinomas of the stomach (seven intestinal adenocarcinomas and five diffuse carcinomas), 12 adenocarcinomas of the pancreas (nine ductal adenocarcinomas and three signet ring carcinomas), and 12 squamous cell carcinomas of the larynx obtained at surgical resection to examine the possibility of extravascular activation of blood coagulation in cancer tissues by exploring the in loco patterns of distribution of fibrinogen, a final product of blood coagulation, fibrin, and a by-product of coagulation reactions (prothrombin fragment 1+2). Gastric, pancreatic, and laryngeal cancers exhibited fibrinogen antigen in abundance throughout the tumor stroma. Fibrin was detected along the edges of nests of carcinoma cells and at the host-tumor interface. Prothrombin fragment 1+2 was present in the blood vessels in areas of neoangiogenesis at the host-tumor interface (gastric and pancreatic cancer tissues) and on the tumor cell bodies (pancreatic and laryngeal cancer tissues). The presence of prothrombin fragment 1+2 in cancer tissues appears to be a good indicator of coagulation activation and thrombin generation at the tumor burden.

Adenocarcinoma↗

[Cardiotoxicity of anthracycline].

The anthracyclines are among the most active and useful anticancer agents, but they are also the most common chemotherapeutics associated with the development of congestive heart failure. Twenty seven to sixty percent of patients with anthracycline-induced cardiomyopathy die of congestive cardiac failure. The paper presents the pathomechanisms of anthracycline-induced cardiotoxicity and perspectives on prevention of congestive heart failure resulting from anthracycline chemo-therapy.

Adult↗

[Metastases of malignant melanoma of unknown primary site: an important diagnostic and therapeutic problem].

Malignant melanoma of an unknown primary site remains a diagnostic and therapeutic challenge in clinical practice. With this in mind, we have presented 12 patients with malignant melanoma of an unknown primary site, diagnosed and treated in the Regional Cancer Center in Białystok. This clinical presentation accounted for 2% of all malignant melanocytic lesions treated in our center during ten year period from 1987 to 1997.

Adult↗

Erythropoietin (r-HuEPO) in the treatment of anemia of nodular sclerosis type Hodgkin's disease--a preliminary report.

The purpose of the study was to evaluate the effectiveness of recombinant human erythropoetin (r-HuEPO) treatment in patients suffering from anemia in the course of Hodgkin's disease (HD). 6 patients suffering from HD (4 of nodular sclerosis type II (NS II) and 2 of nodular sclerosis type I (NS I)) were treated with r-HuEPO for 10 weeks. All patients suffering from the NS II of HD exhibited an increase in the level of Hb by more than 2 g/dl after 10 weeks of r-HuEPO therapy whereas patients suffering from the NS I subtype of HD did not benefit from such treatment.

Adult↗

Expression of tissue factor and tissue factor pathway inhibitor in situ in laryngeal carcinoma.

The blood coagulation mechanism may support tumor progression by several mechanisms including promotion of cell proliferation and angiogenesis. Immunohistochemical procedures were applied to AMeX-fixed sections of twelve cases of squamous cell carcinoma of the larynx obtained at surgical resection to determine the presence and distribution of tissue factor (TF), tissue factor pathway inhibitor (TFPI), other coagulation factors, fibrinogen, and fibrin in situ. TF antigen was present in normal squamous epithelial cells and tumor cells, predominantly in immature tumor cells in the vicinity of the host-tumor interface. Tumor cells stained also for factors VII and X. Staining for TFPI antigen was demonstrated in the connective tissue stroma adjacent to the tumor, in microvascular endothelial cells, and in normal squamous epithelial cells. Fibrinogen and factor XIIIa were distributed throughout the tumor connective tissue stroma. Fibrin (thrombin-cleaved fibrinogen) was detected at the host-tumor interface and along the margins of tumor nodules. Tumor cells in carcinoma of the larynx express a functional, TF-initiated pathway of blood coagulation. Interpretation of these findings together with the results of clinical trials of inhibitors of TF-induced coagulation activation versus effects of inhibitors of TF expression suggest novel approaches to the experimental therapy of laryngeal carcinoma.

Blood Coagulation↗

[The role of proteolytic enzymes in skin neoplasm progression and development of metastasis].

Proteases are reported to play an essential role in the proliferative, invasive, and metastatic potential of malignant tumor cells. Metastasis is characterized by a complex series of interactions between tumor cells and their environment. Tumor expansion and invasion are associated with the destruction of normal tissues around the tumor by a variety of classes of tumor and host-derived extracelullar matrix-degrading proteinases. Increased levels of the major lysosomal proteinases cathespin B, D, L, metalloproteinases and plasminogen activators, are correlated with tumor cell invasion and metastasis in human melanoma and other skin tumors, breast and colorectal cancer.

Animals↗

[Angiogenesis in brain neoplasms--biological and clinical aspects].

Solid tumors are dependent on angiogenesis for sustained growth, therefore anti-angiogenic treatment is a potential antineoplastic therapy. Glioblastoma multiforme has been considered a suitable candidate for such treatment. This review summarizes the fundamentals of angiogenic process in glioblastoma multiforme and in other types of brain tumors for which they represent a potential for anti-angiogenic therapy.

Animals↗

[Local activation of blood coagulation in pancreatic tissue in chronic pancreatitis].

Thromboembolic events may complicate clinical course of chronic pancreatitis. It is accepted that trypsin plays a role in the pathogenesis of these abnormalities. However there is a lack of information about local activation of blood coagulation in pancreatic tissue in chronic inflammation and contribution of tissue factor (TF) to this process. Immunohistochemistry was applied to AMeX-fixed sections of tissues of ten cases of chronic pancreatitis to explore the presence and distribution of components of the coagulation system in situ. TF antigen was present in cells of ductules. Fibrinogen and fibrin were detected in the inflammatory infiltrates of the pancreatic tissue. The data suggest that there is local activation of blood coagulation in pancreatic tissue in chronic inflammation that depends on tissue factor.

Antibodies, Monoclonal↗