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Biomedical subjects

Elzbieta Korobowicz

Publications and source records attributed to Elzbieta Korobowicz.

At least 19 recordsLinked to original sources

A rare case of nasopharyngeal angiofibroma in an elderly female.

Nasopharyngeal angiofibromas occur predominantly in males in their puberty and adolescence; the incidence in other age groups and in women is exceptional. This report describes a case of a 57-year-old woman with nasopharyngeal angiofibroma presenting typical radiological findings in computed tomography, MR imaging and angiography. The tumour was successfully removed and histopathological examination confirmed the diagnosis. In 6 years follow-up the patient is free of symptoms.

Angiofibroma↗

[Role of mitochondrial protein Smac/Diablo in regulation of apoptotic pathways].

This is a review of studies on recently identified protein Smac/Diablo, a factor that has been shown to exit mitochondria in response to apoptotic stimuli and potentate caspase activity, possibly by neutralizing members of IAP family. The current knowlege about structure and function of Smac/Diablo during programmed cell death, both in mitochondrial and receptor pathways are presented. Special attention was paid to the defects of transduction of apoptotic signals in chemoresistant tumor cells such as alteration in expression of IAP and Bcl-2-family and role of Smac/Diablo as an agent, which analyzed deeply may contribute to create new forms of anticancer therapies.

Animals↗

Estimation of prognostic value of Bcl-xL gene expression in non-small cell lung cancer.

The aim of our study was to estimate the expression of the Bcl-xL gene, a member of Bcl-2 family, in NSCLC patients. A total of 60 consecutive patients diagnosed with NSCLC that underwent chemotherapy prior to surgery were reviewed. Bcl-xL expression was assessed on paraffin sections by in situ hybridization (ISH) and immunohistochemistry (IMH). We observed the presence of mRNA of Bcl-xL gene and its protein product overexpression in most patients (60 and 81.7%, respectively). In material examined no significant correlation was observed between the pattern of Bcl-xL or protein expression and any clinicopathological factors evaluated. The expression of Bcl-xL protein was low (less than 10% positive cells) in 11 patients (median survival time 29 months) as compared to 49 patients with overexpression (median survival time 21.0 months). The difference was not of statistic significance (p=0.27). In examined group the Bcl-xL mRNA was found in 36 patients, while it was absent in 24 cases. Median survival time was 14.5 and 86.5 months, respectively (p=0.001). In addition, 19.4% of 5-year survivals were achieved in patients with overexpression and 54.2% in patients with no mRNA present (p=0.002). The percentage of 5-year survival in patients with protein expression assessed by IMH was 30.6% (p=0.31). The estimation of Bcl-xL expression on mRNA and protein level was compared by the means of sign test and the significant difference was found (p=0.009). The inconsistency was related to 35% of cases. In comparison with IMH, ISH technique appeared to be more specific and accurate in assessment of 5-year survival (25 and 65%; 65 and 70%, respectively). The results of our study indicate that Bcl-xL mRNA overexpression may suggest poor prognosis in NSCLC.

Adult↗

The immunohistochemical profile of the primary and metastatic carcinoma of the clitoris: a case report.

We describe the immunohistochemical profile of rare primary squamous carcinoma of the clitoris metastasizing to the bilateral inguinal lymph nodes. Several antigens were assessed immunohistochemically (pRb1, p16INK4A, cyclin D1, cdk4, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), p53, Ki-67, p27KIP1, PTEN, hMLh1, phospho-AKT, collagen IV, leptin and CD90) in both tumors. All the antibodies applied revealed a staining pattern that is typical of primary and metastatic carcinomas. Cyclin D1-cdk4 complex was overexpressed, whereas there was no p16INK4A immunostaining. Moreover, both tumors expressed positivity for p53 protein, but were negative for estrogen and progesterone receptors. The proliferative activity of cancer, assessed by MIB-1 Proliferative Index, amounted to 25% either for primary or for metastatic tumors. As a conclusion, immunohistochemical assessment of various cell-cycle-associated molecules yield clues as to their possible function during the process of spread of rare neoplasm originating from the clitoris.

Aged↗

Immunohistochemical demonstration of multiple HPV types in laryngeal squamous cell carcinoma.

The aim of this study was to determine the prevalence of human papillomaviruses (HPV) types 6, 11, 16, 18, 31, 33, 42, 51, 52, 56 and 58 in laryngeal squamous cell carcinoma specimens using immunohistochemical reactions and to correlate the presence of HPV with the clinical and pathological characteristics of these patients. Tissue samples were collected from 40 patients with primary laryngeal squamous cell carcinoma (LSCC) and from 33 subjects with non-neoplastic laryngeal lesions or laryngeal nodules, which served as a control group. Human papilloma virus was detected in 6 (15%) of the 40 patients. Five (83.4%) of six patients with HPV positive tumors had G2 (moderately differentiated), one patient (16.6%) had G3 (poorly differentiated), and no patient with HPV positive tumor had a G1 (well-differentiated) tumor. Four (66.6%) of the six HPV positive tumors were in the supraglottic region, one (16.6%) tumor was located in the glottis, and one (16.6%) HPV positive tumor was in the subglotic region. Five (83.4%) of six HPV positive tumors were T3-T4, and one was T2. Three of six HPV positive patients had no clinically evident cervical lymph nodes (N0), and three of the HPV positive patients were N1 or N2. Human papillomavirus was not detected in any of the samples from the control group. The presence of HPV infection in 15% of the cases may suggest a possible role in the etiology of laryngeal squamous cell carcinoma. However, no significant correlation between HPV incidence and histological grading and clinical staging could be demonstrated.

Adult↗

Activity of NADPH-cytochrome P-450 reductase of the human heart, liver and lungs in the presence of (-)-epigallocatechin gallate, quercetin and resveratrol: an in vitro study.

NADPH-cytochrome P-450 reductase (P-450 reductase) plays a crucial role in the metabolism of many endogenic compounds and xenobiotics detoxication. The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (-)-epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liver>heart>lung. However, no significant effect of resveratrol on P-450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P-450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine.

Anti-Bacterial Agents↗

Immunohistochemical detection of hMLH1 and hMSH2 proteins in vulvar carcinoma.

The immunohistochemical (IHC) detection of MMR proteins is an accurate and rapid method to predict the presence of defective DNA MMR genes. MMR protein expression could also serve as a prognostic indicator of human cancers. The results of many studies demonstrate the usefulness of IHC tests with monoclonal antibodies MSH2 and MLH1 in screening the microsatellite sequence instability within both spontaneous and hereditary malignant neoplasms. The aim of our study was to perform an IHC estimation of the hMLH1 and hMSH2 expression in a subset of vulvar carcinomas according to HPV 16/18 status. The level of MMR proteins was further analyzed in relation to histoclinical features of the disease in either HPV-positive or -negative cancers. We identified archival diagnostic phase tissue specimens from 46 cases of vulvar cancer. From the same paraffin blocks containing material from the margin of surgical section during vulvectomy, normal epithelial tissue fragments were collected and designated as the control group. The characteristic of the lesion was examined in comparison with the presence of HPV DNA. Identification of the HPV 16/18 types was performed using PCR. IgG1 monoclonal antibodies detecting those epitopes characteristic for hMLH1 and hMSH2 were used in the study. In the analyzed cases of vulvar cancer, we have observed increased expression of proteins of both hMSH2 and hMLH1 genes compared to the control group. A comparison of the hMLH1 and hMSH2 protein expression levels showed that hMSH2 expression was higher than that of hMLH1 in the case of vulvar carcinomas. The performed analysis of correlation between individual parameters did not reveal statistically significant relationship with both the gradient and status of HPV 16/18. hMSH2 and hMLH1 were definitely interrelated.

Adaptor Proteins, Signal Transducing↗

Sarcomatoid carcinoma of the esophagus.

The authors present two rare cases of sarcomatoid carcinoma of the lower thoracic esophagus in a 73-year-old woman and a 42-year-old man. The histogenesis, clinicopathological features and differential diagnosis of this unusual tumor are also discussed.

Adult↗

Gastrointestinal stromal tumors. A multicenter experience.

The report presents 200 cases of gastrointestinal stromal tumors (GIST). The material originated from six diagnostic centers in Poland and was reclassified according to the current criteria. Among lesions other than GISTs, 14 were identified as smooth muscle tumors and seven as neural tumors. GISTs were located in the stomach (51-63.3% of the investigated series), small intestine (27.4-33.8%), colon (approximately 4.5%), abdominal cavity, i.e. in the peritoneum and omentum (6%), and in the retroperitoneal space (2.5%). A slight predominance of women was noted (53-56%). The age of the patients ranged between 14 and 93 years of life, with the mean age of 62.4 years. Individuals younger than 45 years of age accounted for 10% of the group. In ten patients (five of them less than 45 years of life), multiple tumors were detected, their number ranging from two to less than 20; these individuals constituted 5% of the entire series. Moderately and highly aggressive tumors predominated. In the series, when multiple tumors were excluded, a total of 24 epithelioid GISTs (12%) were observed; of this number, 13 were situated in the stomach, six--in the small intestine, two--in the abdominal cavity and another two in the retroperitoneal space. Synchronic tumors observed in patients with GISTs were seen in seven patients, including an adenocarcinoma of the colon, two adenocarcinomas of the stomach, a carcinoid tumor of the small intestine, a pheochromocytoma of the retroperitoneal space, an anaplastic lymphoma and a disseminated squamous cell carcinoma. In immunohistochemical reactions (CD117, CD34, SMA, S-100, DES), attention was focused on the immunoreactivity of small GISTs, below 2 cm in size, and of multiple tumors. Immunohistochemical reactions were equally differentiated as to their presence and intensity in small tumors and in highly aggressive lesions above 5-10 cm in size. In multiple GISTs, immunohistochemical tests strongly indicated the heterogeneity of neoplastic cells, which, nevertheless, showed no consistent association with the location of the tumor, its aggressiveness, cellular structure or a tendency to form multiple foci.

Adolescent↗

Colonic adenocarcinoma with numerous paneth and endocrine cells.

Numerous granular eosinophilic cells corresponding to Paneth cells were unexpectedly revealed in a moderately differentiated adenocarcinoma of the hepatic flexure of the colon in a 76-year-old man. These cells were clearly seen in routine slides and their nature was confirmed by Masson's trichrome stain, by immunohistochemical reaction for lysozyme, and by electron microscopy. The tumor contained also cells intermediate between Paneth and goblet cells (with both supranuclear granules and mucous globules), observed in Masson's trichrome stain and in electron microscope. Additionally, immunohistochemical reaction for chromogranin A was performed and irregularly scattered neoplastic endocrine cells were visualized in the tumor. The light microscopic and ultrastructural features of this rare neoplasm are described together with detailed clinical data. The incidence and significance of the Paneth cell and endocrine differentiation in colorectal carcinomas are discussed with the review of the literature.

Adenocarcinoma↗

Therapeutic doses of topiramate are not toxic to the developing rat brain.

Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment. One of the implicated mechanisms is enhancement of apoptotic neuronal death, which occurs physiologically in the developing brain. We investigated whether topiramate, one of the newer antiepileptic drugs, has neurotoxic properties in the developing rat brain. Topiramate slightly but significantly enhanced apoptotic neuronal death in the 7-day-old rat brain at doses of 50 mg/kg and above. These doses are several folds higher than reported ED(50) doses in infant rodent seizure models that respond to topiramate. Electron microscopy confirmed that dying neurons following topiramate treatment displayed the same morphological features as neurons undergoing physiological cell death during development. When compared to the neurotoxicity profile of phenytoin, valproate, and phenobarbital, the separation between the effective anticonvulsant dose and the neurotoxic dose was greater for topiramate and the neurotoxic effect was lower.

Age Factors↗

Oxygen causes cell death in the developing brain.

Substantial neurologic morbidity occurs in survivors of premature birth. Premature infants are exposed to partial oxygen pressures that are fourfold higher compared to intrauterine conditions, even if no supplemental oxygen is administered. Here we report that short exposures to nonphysiologic oxygen levels can trigger apoptotic neurodegeneration in the brains of infant rodents. Vulnerability to oxygen neurotoxicity is confined to the first 2 weeks of life, a period characterized by rapid growth, which in humans expands from the sixth month of pregnancy to the third year of life. Oxygen caused oxidative stress, decreased expression of neurotrophins, and inactivation of survival signaling proteins Ras, extracellular signal-regulated kinase (ERK 1/2), and protein kinase B (Akt). The synRas-transgenic mice overexpressing constitutively activated Ras and phosphorylated kinases ERK1/2 in the brain were protected against oxygen neurotoxicity. Our findings reveal a mechanism that could potentially damage the developing brain of human premature neonates.

Aging↗

Human skeletal muscle lactate dehydrogenase activity in the presence of some alcohol dehydrogenase inhibitors.

Methanol, ethylene glycol and other alcohol intoxications are complicated by severe acidosis which could be caused by formation of metabolic acids and additionally lactic acid production. An increasing nicotinamide adenine dinucleotide reduced/nicotinamide adenine dinucleotide oxidized (NADH/NAD) ratio during alcohol biotransformation is responsible for the induction of lactic acidosis. The main purpose of the present paper was to evaluate the effect of 4-methylpyrazole, cimetidine, ethylenediaminetetraacetic acid disodium salt, ethanol and methanol on lactate dehydrogenase (E.C. 1.1.1.27) activity and to discuss this issue. The activity of the enzyme was determined spectrophotometrically, in vitro using human enzyme skeletal muscle homogenates. 4-Methylpyrazole, cimetidine and ethylenediaminetetraacetic acid disodium salt at concentrations 0.01, 0.1, 1.0 mM and 12.5, 25.0, 50.0 mM of ethanol and methanol were studied. Our results showed that cimetidine increased lactate dehydrogenase activity as compared to the control at all tested concentrations. Such activity was noted for 4-methylpyrazole at 0.1 mM and higher concentration. By contrast, no significant effect on lactate dehydrogenase activity in the presence of ethylenediaminetetraacetic acid disodium salt, methanol and ethanol was observed.

Alcohol Dehydrogenase↗

Effect of selected alcohol dehydrogenase inhibitors on the human heart lactate dehydrogenase activity--an in vitro study.

Metabolic acidosis complicates methanol, ethylene glycol and other alcohol intoxications. It is caused firstly by acid metabolites and secondly by the lactate elevation. The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH; EC 1.1.1.1) inhibitors and substrates: 4-methylpyrazole (4-MP), cimetidine, EDTA, ethanol and methanol on lactate dehydrogenase (LDH; EC 1.1.1.27) activity. The activity of LDH was determined spectrophotometrically in in vitro human heart homogenates with the mentioned compounds at 0.01, 0.1, 1.0 mM concentrations of 4-MP, cimetidine, EDTA, and 12.5, 25.0, 50.0 mM of ethanol and methanol. The LDH activity was significantly inhibited by 0.1 mM (p<0.05) and 1.0 mM (p<0.01) 4-MP and 1.00 mM EDTA (p<0.05). Higher LDH activity vs. control was observed in the samples incubated with all studied ethanol and methanol concentrations but these differences were not statistically significant. Thus, 4-MP was found to be the most effective inhibitor of LDH of all compounds tested. Therefore, such effect of 4-MP seems to be an additional advantage in methanol and ethylene glycol intoxications.

Adult↗

Rectal adenocarcinoma with osseous metaplasia.

A rare case of osseous metaplasia in a moderately differentiated rectal adenocarcinoma in a 79-year-old man is reported. A possible pathogenesis of this phenomenon is discussed.

Adenocarcinoma↗

[Soft tissue sarcoma as a result of uterine cervix cancer radiotherapy].

The secondary neoplasms due to previous radiotherapy occur rarely. They develop within the radiation field or on its border. In this paper we present the case of soft tissue sarcoma that evolved 11 years after uterine cervix cancer radiotherapy. The long-term survival of patients subjected to radiotherapy is linked with the risk of secondary neoplasms appearance. That is why the repeated regular observation after radical treatment is recommended.

Abdominal Neoplasms↗

[Human erythrocyte lactate dehydrogenase activity changes in the presence of some alcohol dehydrogenase inhibitors].

The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH; E.C. 1.1.1.1) inhibitors and substrates: cimetidine, 4-methylpyrazole (4MP), EDTA, ethanol and methanol on lactate dehydrogenase (LDH; E.C. 1.1.1.27) activity. The activity of LDH was spectrophotometrically determined in in-vitro prepared diluted hemolysates obtained from human erythrocytes with mentioned compounds at the concentrations 0.01, 0.1, 1.0 mM of cimetidine, EDTA, 4MP and 12.5, 25.0, 50.0 mM of ethanol and methanol. The reaction was conducted at 37 degrees C in pH 7.5 and changes of optical density was measured at lambda = 340nm. LDH activity was significantly inhibited by 0.10 mM (p < 0.05) and 1.0 mM (p < 0.01) of cimetidine and EDTA. There were no observed any significant changes vs. control in LDH activity when 4MP, ethanol or methanol was added to environment of reaction.

Adult↗