Expression of p53 protein in Barrett’s adenocarcinoma and adenocarcinoma of the gastric cardia and antrum

Background/Aim. Most studies of esophageal and gastric adenocarcinomas have shown a very high rate of p53 gene mutation and/or protein overexpression, but the influence of the tumor site upon the frequency of p53 protein expression has not been evaluated (gastroesophageal junction, Barret's esophagus, and antrum). The aim of our study was to analyze the correlation between the selected clinico-pthological parameters, and p53 protein overexpression in regards to the particular tumor location. Methods. The material comprised 66 surgical specimens; 10 were Barrett’s carcinomas, 25 adenocarcinomas of the gastric cardia (type II adenocarcinoma of the esophagogastric junction - EGJ), and 31 adenocarcinomas of the antrum. Immunostaining for p53 protein was performed on formalin-fixed, paraffin-embedded tissue sections, using the alkaline phosphatase - antialkaline phosphatase (APAAP) method. The cases were considered positive for p53 if at least 5% of the tumor cells expressed this protein by immunostaining. Results. There was no significant difference observed between the studied groups in regards to age, sex, Lauren’s classification and tumor differentiation. There was, however, a significant difference observed in the depth of tumor invasion between Barrrett’s adenocarcinoma and adenocarcinoma of the cardia compared with the adenocarcinoma of the antrum. Namely, at the time of surgery, both Barrett’s adenocarcinomas and adenocarcinomas of the cardia, were significantly more advanced comparing with the adenocarcinomas of the antrum. Overexpression of p53 was found in 40% (4/10) of Barrett’s adenocarcinomas, 72% (18/25) of adenocarcinoma of the cardia and 65% (20/31) of adenocarcinoma of the antrum. No significant differences in p53 expression in relation to sex, type (Lauren) of tumor, depth of invasion, lymph node involvement, or tumor differentiation were observed in any of the analyzed groups of tumors. Patients with more advanced Barrett’s adenocarcinoma and in the cases of lymph node invasion revealed tendency for the greater p53 positivity compared with the early forms and lymph node-negative cases; however, this difference was not significant according to the statistical analysis. With regard to adenocarcinoma of the cardia, higher rates of p53 positivity were recorded in poorly differentiated, more advanced cases with lymph node invasion. Nevertheless, none of these differences was statistically significant. On the contrary, in the patients with adenocarcinoma of the antrum, greater p53 positivity was revealed in early forms without lymph node involvement, but the observed difference was not statistically significant. Conclusion. No significant differences in p53 protein expression in terms of sex, type (Lauren) of tumor, depth of invasion, lymph node involvement, or tumor differentiation were observed in any of the analyzed groups of tumors (Barrett’s adenocarcinoma, adenocarcinoma of the cardia and adenocarcinoma of the antrum)

Redox Parameters in Blood of Thyroid Cancer Patients After the Radioiodine Ablation

The radioactive iodine (I-131) ablation is a well-accepted treatment modality for differentiated thyroid cancer patients. Unfortunately, the radiation induces the oxidative stress and damages cells and tissues, simultaneously activating the mechanisms of antioxidative defense. Since the mechanisms of those processes are not completely known, we wanted to examine the changes in the most important reactive oxygen species and antioxidative components, as well as their correlation and significance for lipid peroxidation. Our results showed that the level of thiobarbituric acid reactive substances was increased during the first 30 days after the radiotherapy. Among antioxidant components, superoxide dismutase was increased in the 3rd and 30th day; catalase in 7th and reduced glutathione in 3rd and 7th day after the radiotherapy. As regards the prooxidants, the reduction of hydrogen peroxide (H2O2) was recorded in 7th and 30th day, and superoxide anion radical (O-2(center dot-)) was unchanged after the exposure to I-131. These results indicate that differentiated thyroid cancer patients are under constant oxidative stress despite the observed increase in antioxidative and reduction in prooxidative parameters. The understanding of these early processes is important since their progress determines the latter effects of I-131 therapy

Age-related changes in the content of insulin: Like growth factor-l in rat brain

Although there has been extensive research on the effect of IGF-I on muscles and bone tissue, the effect on brain aging has received little attention. We investigated the IGF-I content in brains of differently aged rats. The IGF-I contents in cerebellar and cerebral cortex were found to be higher in immature rats (4-5 days old) compared to young adult (2.5 months old) and middle-aged (7.5-9 months old) rats. However, the decrease of mean IGF-I in middle-aged rats compared to immature animals was statistically significant only in the cerebellar codex. Our results indicate that IGF-I content decreases through the lifespan and maybe selectively in some brain regions.Vršena su istraživanja insulinu sličnog faktora rasta (IGF-I) na mišićno i koštano tkivo, ali je posvećena mala pažnja efektu na mozak u toku starenja. Mi smo ispitivali sadržaj IGF-I u moždanom tkivu pacova različite starosti. Nađeno je da su IGF-I koncentracije u kori malog mozga kao i velikog mozga mladih pacova (4-5 dana starih) više u poređenju sa sadržajima grupe tek-odraslih pacova starosti 2,5 meseca i grupe nešto starijih odraslih pacova (7,5-9 meseci starih). Međutim, smanjenje koncentracije IGF-I sadržaja samo u kori malog mozga nešto starijih pacova (7,5-9 meseci) bilo je značajno u odnosu na vrednosti u novorođenih (4-5 dana starih pacova). Naši rezultati ukazuju da IGF-I opada tokom života i moguće - selektivno u određenim moždanim regionima.nul

Age-related changes in the content of insulin: Like growth factor-l in rat brain

Although there has been extensive research on the effect of IGF-I on muscles and bone tissue, the effect on brain aging has received little attention. We investigated the IGF-I content in brains of differently aged rats. The IGF-I contents in cerebellar and cerebral cortex were found to be higher in immature rats (4-5 days old) compared to young adult (2.5 months old) and middle-aged (7.5-9 months old) rats. However, the decrease of mean IGF-I in middle-aged rats compared to immature animals was statistically significant only in the cerebellar codex. Our results indicate that IGF-I content decreases through the lifespan and maybe selectively in some brain regions.Vršena su istraživanja insulinu sličnog faktora rasta (IGF-I) na mišićno i koštano tkivo, ali je posvećena mala pažnja efektu na mozak u toku starenja. Mi smo ispitivali sadržaj IGF-I u moždanom tkivu pacova različite starosti. Nađeno je da su IGF-I koncentracije u kori malog mozga kao i velikog mozga mladih pacova (4-5 dana starih) više u poređenju sa sadržajima grupe tek-odraslih pacova starosti 2,5 meseca i grupe nešto starijih odraslih pacova (7,5-9 meseci starih). Međutim, smanjenje koncentracije IGF-I sadržaja samo u kori malog mozga nešto starijih pacova (7,5-9 meseci) bilo je značajno u odnosu na vrednosti u novorođenih (4-5 dana starih pacova). Naši rezultati ukazuju da IGF-I opada tokom života i moguće - selektivno u određenim moždanim regionima.nul

Effect of a single dose of ethanol on granulopoiesis in female rats: Relationship to phase of estrous cycle

Objective: The purpose of this study was to investigate the acute effect of ethanol (4g/kg, IP) on granulopoiesis at two phases of the rat estrous cycle, proestrus and diestrus Day 1. Method: The following parameters were estimated: in peripheral blood, the ethanol concentration, progesterone and estradiol levels, the total number of WBC and differential count; in the bone marrow, the total number of nucleated cells, the number of granulocyte-macrophage committed stem cells (CFU-GM) and differential count at various time points (.5, 3, 6 and 20 hours) after treatment. The experiments were conducted twice and 4 to 7 rats were used per groups for each time point. Results: The results indicated that a single dose of ethanol significantly increased the number of granulocytes and decreased the number of lymphocytes in peripheral blood. These changes were observed earlier at the proestrus compared to the diestrus Day 1, and were consistent with faster ethanol disappearance from blood during the proestrus. Additionally, the ethanol treatment induced a significant increase in progesterone levels at both phases. This effect was prolonged at the diestrus Day 1 and thus was also associated with differences in ethanol metabolism. In the bone marrow, the total number of nucleated cells and morphologically recognizable hematopoietic cells were not affected by ethanol treatment at any of the observed time points. However, at both phases of the estrous cycle ethanol treatment induced an increase in the number of CFU-GM derived colonies 20 hours after administration which is modulated by the current hormone status of the treated animals

Hematopoiesis during acute Toxoplasma gondii infection in mice

We studied hematopoiesis in bone marrow and blood of CBA mice following infection with Toxoplasma gondii. Our data showed that acute infection with the virulent RH strain was associated with leucopenia, thrombocytopenia and bone marrow hypoplasia while, in spite of the infection-induced damage of the granulocyte cell lineage, in bone marrow stimulated production of granulocytes was revealed. In peripheral blood, T gondii infection caused a significant decrease in the total number of white blood cells, reticulocytes and platelets. However, the relative proportion of granulocytes and lymphocytes was changed in favor of granulocytes, as compared to pre-infection levels. The functional activity of granulocytes was also increased. The bone marrow alterations were characterized by a decrease in the total number of nucleated cells due to the reduced numbers in all cell compartments of erythroid and megakaryocytic lineage, as well as in the number of mature granulocytes and lymphocytes. In contrast, femoral granulocytic proliferative compartments, colony forming unite granulocyte-macrophage (CFU-GM) and morphologically recognizable proliferative granulocytes (PG), exhibited stimulated granulopoiesis, while the number of mature monocytes was close to the control value. In summary, we have shown that acute T gondii infection results in profound alterations of the hematopoietic system that markedly contribute to the clinical onset of the disease and the, ultimately lethal, outcome

Expression of heat shock protein 70 (HSP70) in patients with colorectal adenocarcinoma - immunohistochemistry and Western blot analysis

The role of heat shock protein 70 (HSP70) expression has been investigated in various types of tumors. There are only little and controversial data about its clinical relevance in colorectal carcinoma, one of the most common carcinomas observed in humans. In this study we investigated expression of HSP70 in human colonic carcinoma and possible correlation with clinicopathology. To assess patterns (cytosolic and membrane) of HSP70 expression, the 48 surgically removed colorectal adenocarcinomas and 12 normal colonic and rectal mucosal samples were examined by immunohistochemistry and Western-blot. According to results of immunohistochemistry, expression of cytoplasmic HSP72 was significantly higher in colorectal carcinoma compared with normal and adjacent mucosa (p LT 0.01). In addition, there was significant increase in HSP72 expression in lymph node-positive compared to node-nevative group (p LT 0.001). Dukes C2 stage of colonic cancer showed significantly higher immunohistochemical score than Dukes B2 and B1 stage groups (p LT 0.05 i.e. p LT 0.02). There was no relation between expression of HSP72 and degree of tumor differentiation. Using Western blot analyses, we noticed elevated levels of cytosolic HSP70 in colorectal cancer cells compared to normal. Densitometric analysis of blots of plasma membrane HSP70 expression has shown decrease in colorectal cancer cells compared to normal mucosa. According to our results, overexpression of HSP72 in malignant tissues of patients with colorectal carcinoma is related to tumor progression, suggesting that these proteins could play an important role not only in tumorigenesis but also in the development of drug resistance. Further research is necessary to clarify the mechanisms responsible for differential HSP70 expression as well as its definitive role in colorectal cancer

Cytochemical & ultrastructural alteration of cytoplasmic granules of rat peripheral blood neutrophils induced by chronic alcoholism & malnutrition

The specific influence of malnutrition on the pathophysiologic changes induced by chronic alcoholism is controversial. In an attempt to determine and demarcate the effects of protein malnutrition from those produced by alcoholism and to evaluate the precise effect of alcohol per se on cytochemical and ultrastructural properties of rat polymorphonuclear neutrophil (PMN) granules, we investigated the influence of chronic protein malnutrition or chronic alcoholism alone and in combination, in rats, After a 4 month experimental period various PMN properties, such as cytochemical, morphometrical and ultrastructural, as well, as neutrophil functions were studied. It was found that the degree of damage of PMNs induced either by ethanol or protein malnutrition alone was similar whereas their combination led to worsening of all markers of PMN functional ability. Ultrastructural changes of neutrophil granules including reduction, redistribution and atypical accumulation as well as appearance of autophagic vacuoles, confirmed their alteration which was emphasised by the additive pathophysiological interaction of alcoholism and chronic hypoprotein malnutrition

Expression of heat shock protein 70 (HSP70) in patients with colorectal adenocarcinoma - immunohistochemistry and Western blot analysis

The role of heat shock protein 70 (HSP70) expression has been investigated in various types of tumors. There are only little and controversial data about its clinical relevance in colorectal carcinoma, one of the most common carcinomas observed in humans. In this study we investigated expression of HSP70 in human colonic carcinoma and possible correlation with clinicopathology. To assess patterns (cytosolic and membrane) of HSP70 expression, the 48 surgically removed colorectal adenocarcinomas and 12 normal colonic and rectal mucosal samples were examined by immunohistochemistry and Western-blot. According to results of immunohistochemistry, expression of cytoplasmic HSP72 was significantly higher in colorectal carcinoma compared with normal and adjacent mucosa (p LT 0.01). In addition, there was significant increase in HSP72 expression in lymph node-positive compared to node-nevative group (p LT 0.001). Dukes C2 stage of colonic cancer showed significantly higher immunohistochemical score than Dukes B2 and B1 stage groups (p LT 0.05 i.e. p LT 0.02). There was no relation between expression of HSP72 and degree of tumor differentiation. Using Western blot analyses, we noticed elevated levels of cytosolic HSP70 in colorectal cancer cells compared to normal. Densitometric analysis of blots of plasma membrane HSP70 expression has shown decrease in colorectal cancer cells compared to normal mucosa. According to our results, overexpression of HSP72 in malignant tissues of patients with colorectal carcinoma is related to tumor progression, suggesting that these proteins could play an important role not only in tumorigenesis but also in the development of drug resistance. Further research is necessary to clarify the mechanisms responsible for differential HSP70 expression as well as its definitive role in colorectal cancer