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Biomedical subjects

S Sulkowski

Publications and source records attributed to S Sulkowski.

At least 19 recordsLinked to original sources

Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer.

BACKGROUND: Gap junctions are intercellular channels composed of connexins, which mediate the direct passage of small molecules between neighbouring cells. They are involved in regulation of cell cycle, cell signalling, and differentiation, and probably invasion and metastasis. The role of connexins in the metastatic process is controversial, because some studies indicate that connexin expression is inversely correlated with metastatic capacity. In contrast, others demonstrate that connexins may be involved in metastasis. In addition, connexin status in breast cancer metastasis has not been widely studied. METHODS: We evaluated by immunohistochemistry the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in primary breast tumours (PTs) and matched paired metastases to lymph nodes (MLNs). RESULTS: In PTs, we observed predominantly cytoplasmic localisation of evaluated connexins, indicating alterations in connexin expression in breast cancer cells. We demonstrated that expression of Cx26 and Cx43 was increased in MLNs compared with PTs (p<0.00001 and p<0.001, for CX26 and Cx43, respectively). In addition, Cx26 and Cx43 negative PTs developed Cx26 and Cx43 positive MLNs. Furthermore, besides increased cytoplasmic staining, enhanced membranous localisation of Cx43, typical of normal cells, was found in MLNs. Additionally, membranous Cx26 expression appeared only in metastatic breast cancer cells. CONCLUSIONS: These findings suggest that connexins may contribute to the efficient metastasising of breast cancer to the lymph nodes.

Adult↗

P53 correlates positively with VEGF in preoperative sera of colorectal cancer patients.

Diversity of P53 impact on tumor angiogenesis is due to the fact that wild-type P53 decreases expression of vascular endothelial growth factor (VEGF), but mutant P53 upregulates it. Therefore, we aimed at uncovering relations between preoperative serum levels of VEGF and P53 in colorectal cancer (CRC) patients. Preoperative blood samples of 125 CRC patients and 16 control healthy volunteers were examined with an ELISA-kit for serum P53 levels and VEGF. P53 did not correlate with VEGF in the whole group of CRC patients. However, P53 associated with VEGF in case of colorectal cancer patients, whose serum values of VEGF were higher than in controls (VEGF{H} >5.9333 pg/ml) (r=0.274, p<0.009). We revealed a positive correlation between P53 and VEGF{H} in subsets of poorly differentiated (G3) cancers (p<0.02), lymph node positive (p<0.007), pT3 or pT4 patients (p<0.004) without analogous relation in moderately differentiated (G2) tumors, node negative patients or pT1 or pT2 patients. P53 and IGF-I negatively correlated in all CRC patients (p<0.04) and VEGF{H} individuals of pT3 or pT4 (p<0.05) without any significant linkage in tumors of pT1 or pT2. The positive correlation between serum P53 and VEGF points at mutation of P53 and is a highly probable sign of poor prognosis in colorectal cancer. For now it can not be excluded that the binary analysis of serum P53 and VEGF could help select CRC patients endangered by rapid growth and lymph node metastases.

Adenocarcinoma↗

Expression of insulin receptor substrate 1 in primary breast cancer and lymph node metastases.

BACKGROUND: Insulin receptor substrate 1 (IRS-1) transmits signals from the insulin-like growth factor I receptor (IGF-IR) and insulin receptor (IR) and has been associated with the pathogenesis of cancer. IRS-1 downregulation has been suggested to play a role in breast cancer progression, but no simultaneous assessments of IRS-1 expression in primary breast cancer and metastases have been performed. AIMS: To assess IRS-1 expression in primary and metastatic breast cancer. METHODS: IRS-1 expression was analysed by means of immunohistochemistry in 109 samples of primary breast cancer and in 42 matched primary and metastatic tumours. In addition, IRS-1 expression was correlated with selected clinicopathological features, including oestrogen receptor alpha (ERalpha) and proliferation marker Ki-67 status. RESULTS: Positive cytoplasmic IRS-1 immunostaining was found in 69.7% (76 of 109) and 76.2% (32 of 42) of the primary and metastatic tumours, respectively. Both IRS-1 positive and IRS-1 negative primary tumours produced IRS-1 positive and IRS-1 negative metastases. IRS-1 expression in primary tumours correlated with poorly differentiated (G3) breast cancer (p < 0.005) and with lymph node involvement (p <0.05). In the subgroup of ERalpha positive primary tumours, IRS-1 expression positively correlated with Ki-67 (p < 0.02, r = 0.351), but in the subgroup of ERalpha negative primary tumours there was a negative correlation (p < 0.03, r = -0.509). IRS-1 expression in lymph node metastases correlated with neither ERalpha nor Ki-67. CONCLUSIONS: IRS-1 might be involved in breast cancer progression. Knowledge about differences between primary and metastatic tumours might help to understand mechanisms of breast cancer progression and lead to the development of more effective anticancer drugs.

Adult↗

The activity of cancer procoagulant in cases of uterine leiomyomas.

PURPOSE: It is currently believed that cancer procoagulant (CP), an enzymatic protein, is a product of malignant neoplastic cells. The present study was designed to test whether it is also synthesized by benign neoplastic cells, namely uterine leiomyomas. MATERIALS AND METHODS: We determined the activity of CP in the blood serum of women with uterine leiomyomas (N = 24), normal women (N = 15), and genital cancer patients (N = 6) by the coagulative method according to Gordon and Benson. Also, the CP activity in 10% tissue homogenates of uterine leiomyomas, normal uterine muscle and tissues of cervical and endometrial carcinoma was determined by the chromogenic method according to Colucci et al. RESULTS: The mean CP activity in the sera of women with uterine leiomyomas was 181.1 seconds (s) +/- 19.9 s, in healthy women--293.2 s +/- 33.8 s, and in genital cancer patients--78.8 +/- 18.5 s (all differences: p < 0.001). Similarly, in homogenates of uterine leiomyomas the CP activity was 19.6 +/- 3.8 nmoles pNa/ml, in normal uterine muscle it was 13.2 +/- 2.2 nmoles pNa/ml, and in cancerous tissue--28.0 +/- 6.6 nmol pNa/ml (all values being significantly different from each other). There was a strong correlation (r = -0.8122; p < 0.001) between the CP activity in uterine leiomyomas and serum activity, suggesting that the source of the serum CP activity was from the leiomyoma. The coagulation time of 120 to 240 s by the Gordon and Benson method supported the diagnosis of uterine leiomyoma, and a value below 120 s--the suspicion of genital cancer. CONCLUSIONS: Uterine leiomyomas, representing benign genital neoplasia, synthesize CP and are the likely origin of CP activity in blood, as has been described for malignant tumors, but to a lesser degree. There may be a role for CP as a tumor marker of genital neoplasia.

Adult↗

Expression of the Insulin Receptor Substrate 1 in primary tumors and lymph node metastases in breast cancer: correlations with Bcl-xL and Bax proteins.

In our previous investigation Insulin Receptor Substrate 1 (IRS-1) correlated with proliferation marker Ki-67 in human breast cancer. The aim of the present study was to assess relationships between IRS-1 expression and anti-apoptotic Bcl-xL as well as proapoptotic Bax proteins, assessed by immunohistochemistry, in primary tumors and lymph node metastases of breast cancer. IRS-1 is positively associated with both Bcl-xL and Bax in primary and metastatic tumors. Thus, our results could suggest that IRS-1 might affect turnover of cancer cells and breast cancer progression through activation of mitogenesis and participation in the regulation of the balance between anti- and proapoptotic pathways.

Biomarkers, Tumor↗

The presence of sex hormone receptors in the vesicouterine fistula.

Although the traditional management of vesicouterine fistula is surgical, a recent review of world data showed high efficacy of hormonal manipulation by the induction of amenorrhea. The prerequisite for the action of sex hormones is the presence of target receptors in the given tissue. The current study examined the histology of the vesicouterine fistula in order to identify the possible cellular components containing sex hormone receptors. The presence of an epithelium similar to endometrium containing sex hormone receptors was demonstrated immunohistochemically and by hematoxylin-eosin staining, a finding in agreement with the definition of endometriosis. Our paper provides an explanation for the high efficacy of hormonal manipulation in the treatment of this relatively rare type of fistula.

Adult↗

Expression of glucose transporter GLUT-1 and estrogen receptors ER-alpha and ER-beta in human breast cancer.

We attempted to describe a GLUT-1 expression in breast cancer and characterize correlation between GLUT-1 and ERs alpha and beta expression as well as correlate this with clinicopathologic features. Sixty-nine patients were involved in the study. GLUT-1, ER-alpha and ER-beta immunocytochemistry was performed using the streptavidin- biotin method. Thirty-seven (53.6%) out of total 69 were GLUT-1 positive. Of GLUT- 1 positive 45.3% were ER-alpha-positive, whereas 81.3% of ER-alpha-negative were GLUT-1 positive. Statistically significant correlation was observed between GLUT-1 and ER-alpha expression status but neither between GLUT-1 and ER-beta nor with clinicopathologic features. No statistically significant correlation was found between expression level (expressed as immunocytoreactive score) of GLUT-1, ER-alpha and ER-beta. Since most of ER-alpha-negative (81.3%) were GLUT-1 positive and significant correlation exists between the two receptors it is reasonable to assume that some functional relation might exists between the expression of two receptors.

Breast Neoplasms↗

Bcl-xl and Bak protein expression in human optic nerve axons in eyeballs post-trauma and in the eyes with absolute glaucoma.

The aim of our study was an evaluation of Bcl-xl and Bak protein expressions in optic nerve axons in eyeballs after severe injury and absolute glaucoma. We examined a series of 41 eyeballs, which were enucleated, following extensive injury and a series of 19 eyeballs from patients with absolute glaucoma. The immunohistochemical reaction was performed, using antibodies against human Bcl-xl and Bak protein with LSAB and DAB. In the injured eyeballs in Group I, Bcl-xl protein expression was observed in 53.8%, Bak in 38.5%, in Group II, Bcl-xl in 40%, Bak 55%; in Group III, Bcl-xl in 62.5%, Bak in 62.5%. Nine (9), out of 19 (47.4%) cases showed Bcl-xl protein positivity, Bak 15, out of 19 (78.9%). The percentage of cases with Bak protein positivity was statistically higher than that for Bcl-xl (Bak/Bcl-xl p=0.0356). The results showed that there may be a dominance expression of proapoptotic proteins in optic nerve axons in glaucoma.

Apoptosis↗

Bcl-2 and Bax protein expression in human optic nerve axons in the eyeballs after severe trauma and in the eyes with absolute glaucoma.

The aim of our study was to evaluate the immunohistochemical expression of Bcl-2 and Bax protein in optic nerve axons after severe eyeball injury and in the eyes with absolute glaucoma. A series of 19 eyeballs, enucleated because of absolute glaucoma and 41 eyeballs, enucleated, following extensive injury, at the Department of Ophthalmology of the Medical University of Bialystok, were taken into our study. The immunohistochemical reaction was performed with Bcl-2 and Bax protein antibodies and by the LSAB technique. DAB was used in order to visualise the reaction. The optic nerve axons in glaucomatous eyeballs showed statistically significant higher Bax protein expressions than those of Bcl-2 proteins. In the optic nerve axons after severe eyeball injury, a non-significantly higher Bcl-2 protein expression was observed.

Axons↗

Glycoprotein CD44 variant 4 expression in tumour epithelial cells of patients with colorectal cancer.

The aim of this study was to check if the expression of CD44v4 in epithelial cells of the colorectal cancer correlates with the pTN stage and the histopathological grade of malignancy--G. Samples of tumour tissue (TT), as well as those of healthy tissue (HT) and of tumour adjacent tissue (TAT) were obtained from 25 patients. An evaluation of the expression of CD44v4 was performed in a flow cytometer. The mean value of the percentage of epithelial cells with co-expression of CD44v4 was lower in pT2 stage than that in pT3 only in HT. The expression of CD44v4 in epithelial cells was higher in cases without lymph node metastases only in TAT. The expression of CD44v4 in epithelial cells was higher in G2 than in G3 degree only in TAT as well. According to the obtained results, it is difficult to state if CD44v4 can influence the progress of colorectal cancer.

Antigens, CD↗

Influence of doxycycline on the epiphyseal plate cartilage of the rats in experimental osteoarthrosis, induced by iodoacetate.

In 36 Wistar rats with the iodoacetate-induced experimental osteoarthrosis (OA), effects of doxycycline, given orally, were determined on histochemical reactions of glycosaminoglycans (GAG) in the epiphyseal plate cartilage. The epiphyseal plate of rats with OA was reduced in height (especially the proliferative zone), cell columns were disorganized, many chondrocytes were irregular and polygonal, their nuclei were pycnotic, the intensity of GAG staining was irregular and predominantly reduced, which can be interpreted as signs of degeneration. A concomitant administration of doxycycline in the second group of rats prevented, to some extent, the negative effects of iodoacetate on chondrocytes and led to a more pronounced intensity of GAG reactions in the matrix of the epiphyseal plate.

Animals↗

P53 protein expression in oral squamous cell cancer in relation to some of its clinicopathological variables.

Oral squamous cell cancer develops through a multistep process by the accumulation of genetic and phenotypic changes. Loss of P53 tumor suppressor gene function represents the most common genetic lesion in human cancer. The significance of P53 expression for the development and progression of oral squamous cell cancer has still to be evaluated. The aim of this study was to estimate relationships between P53 protein expression and some clinicopathological variables of established or presumed prognostic value. A series of 129 oral squamous cell cancers was investgated retrospectively for expression of P53 protein by immunohistochemistry of paraffin-embedded tissue sections. The slides were stained with H+E and by immunohistochemistry with anti-human P53 antibody. Positive immunohistochemical staining for P53 protein was present in 75 (58%) oral cancer cases. There were no statistically significant correlations between oral cancer P53 expression and tumor site, grading, mitotic index, invasive margin type, as well as patients age and sex. Our results suggest that immunohistochemical overexpression of P53 is an important markerof accomplished neoplastic transformation in oral cavity lesions but it does not play a crucial role in the tumor progression.

Adult↗

Prognostic significance of CD34 expression in early cervical squamous cell carcinoma.

The aim of the study was to evaluate angiogenesis as an independent prognostic factor and to determine the correlation of the microvessel density (MD) with lymph node metastases and survival rate in 73 women operated because of invasive squamous cell carcinoma (SCC) of the uterine cervix at clinical stages lb and IIa (FIGO). The patients were divided into two groups: I--25 (34.4%) with survival rate <5 years and II--48 (65.6%) with survival rate >5 years. Angiogenesis was quantified in light microscope using an assay for CD34. The CD34 antibody intensely immunostained single endothelial cells as well as larger microvessels. In the study. differences were revealed by comparing the MD between both groups. The 5-year overall survival rate for patients with high MD was significantly worse than for those with low MD (p<0.003). A correlation was found between angiogenesis intensity and vascular involvement as well as the incidence of lymph node metastases. Thus, tissue expression of CD34 in SCC appears to be a significant prognostic indicator.

Adult↗

Antioxidant status and lipid peroxidation in colorectal cancer.

Colon carcinogenesis is a multistep process where oxygen radicals were found to enhance carcinogenesis at all stages: initiation, promotion, and progression. Since insufficient capacity of protective antioxidant system can result in cancer, the aim of this study was to examine the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and the levels of reduced glutathione, vitamin C, and vitamin E. The lipid peroxidation products were also determined by measuring malondialdehyde and 4-hydroxynonenal levels in colorectal cancer tissue collected from 55 patients. In these cases the activity of superoxide dismutase, glutathione peroxidase, and glutathione reductase was significantly increased while the activity of catalase was significantly decreased in cancer tissue. However, the level of nonenzymatic antioxidant parameters (glutathione, vitamin C, and vitamin E) was significantly decreased in cancer tissue. Further lipid peroxidation was enhanced during cancer development, manifested by a significant increase in malondialdehyde and 4-hydroxynonenal levels. The obtained results indicate significant changes in antioxidant capacity of colorectal cancer tissues, which lead to enhanced action of oxygen radicals, resulting in lipid peroxidation.

Antioxidants↗

Correlation between chromogranin A, neuron-specific enolase and synaptophysin expression, and some clinico-pathological features of colorectal cancer.

Several studies employing various techniques have demonstrated the occurrence of neuroendocrine cells in colorectal cancers. Chromogranin A (CGA), neuron-specific enolase (NSE) and synaptophysin (SYN) are general markers of neuroendocrine cells. The aims of the present study were to evaluate the possible correlations between CGA and/or NSE and/or SYN expression in colorectal cancer and some of its clinico-pathological features. The study was conducted on 48 patients with colorectal cancer treated with surgery only at the Department of Surgical Gastroenterology, Medical Academy and District Oncology Center, Białystok. There were no statistically significant relationships between colorectal cancer CGA and/or NSE and/or SYN expression and tumor site, histopathological type, grading, lymph node metastases, age and sex of patients. However, high ratio of lymph node metastases in colorectal cancers with neuroendocrine cells suggests their more agressive clinical course.

Adult↗

Study of P53 protein expression in colorectal cancer.

Mutations of the P53 gene, strictly associated with the carcinogenesis are a commonly observed in neoplastic cells. The aim of this study was the immunohistochemical evaluation of P53 protein expression in colorectal carcinomas and analysis of its relationship to chosen anatomo-clinical and morphological parameters of the tumours. The study used the material obtained during surgical treatment of 74 colorectal carcinomas. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the antihuman P53 protein monoclonal antibody. The immunolocalization of P53 protein was performed using the Labelled Streptavidin Biotin (LSAB) method. The P53 protein expression was semiquantitatively assessed in neoplastic cells and the reaction present in more than 25% of tumour cells was accepted as the threshold of positivity. No correlation was found between P53 protein expression and tumour histologic type and site, and age and sex of patients. However, P53 protein expression in primary and metastatic tumours was found statistically significantly correlated.

Adult↗

Expression of P53 protein in primary uveal melanoma.

Malignant melanomas are the commonest intraocular tumours. The aim of the present study was the immunohistochemical analysis of P53 protein expression in 39 primary ocular melanomas treated surgically in the years 1983-1997. Expression of P53 was estimated semiquantitatively with the use of a light microscope at a magnification of x 400. At least 200 neoplastic cells per sample were analysed. The expression of P53 in 3% of melanoma cells was considered the threshold of positive reaction. The results were subjected to statistical analysis with exact Fischer's test. No statistically significant correlations were found between P53 expression and anatomoclinical properties of tumours, although increased P53 expression was observed in epithelioid-cellular melanomas and in tumours growing in women. A lack of statistically significant relationship between P53 protein level and the parameters examined, and morphological specificity of ocular melanomas hindering immunohistochemical analysis, indicate the necessity for studies on a wider group of tumours or/and use of molecular biology techniques to establish possible relations between P53 gene mutation and ocular melanoma biology.

Adult↗

Expression of nucleolar organizer regions (NORs) in ovarian epithelial tumors.

AgNOR staining technique was tested in ovarian epithelial tumors to evaluate its diagnostic potential in distinguishing between borderline tumors and well-differentiated carcinomas. In our opinion, the AgNOR count appears useful for assessing differences only between borderline and well-differentiated serous ovarian tumors at stage I of FIGO clinical advancement.

Adult↗