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ABSTRACT: Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2 % grape juice control group; 1 % grape juice 24 h after TNBS colitis induction; 1 % grape juice on day 7 after colitis induction; 2 % grape juice 24 h after colitis induction; 2 % grape juice on day 7 after colitis induction. The 1 % grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1 % grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (P< 0·05) of TNF-α and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1 % dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1 % dose.
The British journal of nutrition 03/2013; · 3.45 Impact Factor
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ABSTRACT: The aim of this study was to analyze the immunoexpression of (Smac) DIABLO, AIF, cytochrome c, Ki-67 and cleaved caspase-3 in gastric cancer. A tissue microarray (TMA) paraffin block was constructed using gastric adenocarcinoma tissue and adjacent normal adjacent mucosa from 87 patients who had not previously undergone radiotherapy or chemotherapy. Immunohistochemistry was used to evaluate the protein levels. Samples were positive for (Smac) DIABLO in 37 (45.6%) and 37 (46.8%), for AIF in 31 (36.9%) and 36 (45.6%), for cytochrome c in 60 (68.9%) and 44 (54.4%), for Ki-67 in 63 (72.4%) and 52 (61.9%) and for cleaved caspase-3 in 21 (24.1%) and 3 (3.4%) cases of tumor and adjacent normal tissues, respectively. Our results suggest that increased expression of Ki-67 and cleaved caspase-3 could contribute to carcinogenesis. The expression of these proteins indicates an attempt of cells to maintain tissue homeostasis.
Anticancer research 02/2013; 33(2):647-53. · 1.73 Impact Factor
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ABSTRACT: To evaluate the immunohistochemical expression of p16, Ki-67, p53 and Bcl-2 proteins in gastrointestinal stromal tumors (GIST); to assess the possible association between these variables and clinical and histopathological factors of cancer; and to check for prognostic value of these variables (survival and recurrence).
A sample of 55 patients treated surgically for GIST in three hospitals was studied. The surgically excised tumors were confirmed as GIST by KIT, vimentin, desmin S100 protein, CD117, 1A4 and CD34 assessment in paraffin blocks.
Only 9 (16%) cases of GIST were positive for p53, p16 was positive among 43.6%; 80% of GISTs showed staining for Bcl-2. The proliferative index (expressed as the proportion of positive cells) assessed by immunohistochemical expression of Ki-67 was high in 49% of cases. Elevated Ki-67 scores were associated to high histological grade (p=0.0026) and mitosis index, MI (p=0.0001). High Ki-67 index was associated to death. Expression of p53, p16 and Bcl-2 did not correlate to morphological or clinical variables.
Ki-67 immunohistochemical evaluation should be included in preoperative evaluation of GIST biopsies or surgical specimens as a prognostic tool for clinical staging; and all other proteins studied (Bcl-2, p53 and p16) did not play a role in GIST metabolic or carcinogenic process, remaining without prognostic value.
Acta cirurgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia 05/2012; 27(5):315-21. · 0.48 Impact Factor
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ABSTRACT: Crohn's disease (CD) is associated with gut barrier dysfunction. Besides the baseline barrier defect, a subgroup of patients also expresses an intestinal barrier hyperresponsiveness to nonsteroidal anti-inflammatory drugs. On the other hand, the anti-tumour necrosis factor alpha (TNF-α) treatment has brought benefits to these patients. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, and Etanercept (ETC), a TNF-α antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 47 Wistar rats were randomized into seven groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: nontreated induced-colitis; (3) Lumiracoxib control; (4) Lumiracoxib-treated induced-colitis; (5) ETC control; (6) ETC-treated induced-colitis; (7) Lumiracoxib-ETC-treated induced-colitis. Rats from groups 6 and 7 presented significant improvement of macroscopic and histopathological damages in the distal colon. The gene expression of COX-2 mRNA, as well of TNF-α mRNA, decreased significantly in groups 6 and 7 compared to the TNBS nontreated and lumiracoxib-treated groups. The treatment only with lumiracoxib did not reduce the inflammation on TNBS-induced experimental colitis. ETC attenuated the damage seen in the colon and reduced the inflammation caused by TNBS. Our results suggest that down-regulation of TNF-α and COX-2 resulted in a decrease in inflammation caused by TNBS and thus provided some protection from the colonic damage caused by TNBS.
Journal of molecular histology 03/2012; 43(3):307-17. · 1.75 Impact Factor
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ABSTRACT: Since the first data from a patient with colorectal adenocarcinoma are obtained by biopsy, this study evaluated the accuracy of diagnosis by biopsy as compared with the diagnostic potential of the surgical specimen, considering the histological type, grade of differentiation, and immunohistochemical expression of p53.
The specimens were obtained from 80 patients assisted at Hospital São Paulo. The biopsy and surgical specimen sections were stained by hematoxylin-eosin and immunohistochemistry and compared by 3 pathologists blinded to the evaluations.
The accuracy for the histological types was 88%. The grade of differentiation presented an accuracy of 70% with Kappa = .48. The expression of protein p53 exhibited an accuracy of 68% with Kappa = .22.
The preoperative biopsy of colorectal adenocarcinoma presented good accuracy compared with histopathological examination of the surgical specimen, but with weak to moderate effective degree of agreement between the results.
International Journal of Surgical Pathology 03/2012; 20(4):355-9. · 1.00 Impact Factor
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ABSTRACT: In spite its relative rarity, gallbladder adenocarcinoma is a neoplasm who presents an aggressive biologic behavior. The single curative treatment has been radical surgical resection with free margin. Prognostic factors has been studied because are very important to identify long-term survival patients which may benefit of aggressive surgical resection.
To evaluate long-term prognostic predictors from gallbladder cancer.
The medical records of all patients that presented confirmed histological diagnosis of gallbladder adenocarcinoma operated over a 14 year period were identified and retrospectively reviewed. Uni and multivariate analysis was done.
Total sample was 100 patients. Median age was 71 years (34 to 93). There were 17 men and 83 women. Lesion distribution according to TNM stage system was: I (n=22), II (n=59), III (n=6), IV (n=4) and unknown (n=9). Fifty two patients underwent radical resection (R0) while 48 to palliative surgery (R1-R2). Overall major morbidity was 14%, while postoperative surgical mortality rate (30th postoperative day) was 12 %. Five-year survival rate was 28% while median of survival was 10 months. Multivariate analysis identified six prognostic factors: T stage, serum level of CA 19.9, gallbladder perforation, lymphatic embolization, surgical historical cohort (after 2002) and hilar lymphadenectomy.
Prognostic factors were: T stage, serum level of CA 19.9, gallbladder perforation, lymphatic embolization, surgical historical cohort and hilar lymphadenectomy.
Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery. 03/2012; 25(1):13-9.
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01/2012; , ISBN: 978-953-307-891-5
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ABSTRACT: Crohn's disease (CD) is associated with gut barrier dysfunction. Tumour necrosis factor-α (TNF-α) plays an important role into the pathogenesis of several inflammatory diseases because its expression is increased in inflamed mucosa of CD patients. Anti-TNF therapy improves significantly mucosal inflammation. Thus, this study aimed to evaluate the effect of Etanercept (ETC), a tumour necrosis factor alpha (TNF-α) antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 18 Wistar rats were randomized into four groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: non-treated induced-colitis; (3) ETC control; (4) ETC-treated induced-colitis. Rats from group 4 presented significant improvement either of macroscopic or of histopathological damage in the distal colon. The gene expression of TNF-α mRNA, decreased significantly in this group compared to the TNBS non-treated group. The treatment with etanercept attenuated the colonic damages and reduced the inflammation caused by TNBS. Taken together, our results suggest that ETC attenuates intestinal colitis induced by TNBS in Wistar rats by TNF-α downregulation.
Journal of molecular histology 08/2011; 42(5):443-50. · 1.75 Impact Factor
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ABSTRACT: NM23, a metastasis suppressor gene, may be associated with prognosis in patients with colorectal carcinoma.
To analyze NM23 expression and its association with the presence of lymph node and liver metastases and survival in patients operated on for colorectal carcinoma.
One hundred thirty patients operated on for colorectal carcinoma were investigated. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic mucosa were obtained and analyzed by immunohistochemical staining using a monoclonal anti-NM23 antibody. Immunohistochemical expression was assessed using a semiquantitative scoring method, counting the percentage of stained cells. The results were compared regarding morphological and histological characteristics of the colorectal carcinoma, presence of lymph node and liver metastases, tumor staging, and patient survival. Statistical analysis was performed using the Mann-Whitney test, the Kruskal-Wallis test and Fisher's exact test. Survival analysis was performed using the Kaplan-Meier method and the log-rank test.
NM23 expression was higher in colorectal carcinoma tissue than in adjacent non-neoplastic mucosa (P<0.0001). NM23 protein expression did not correlate with degree of cell differentiation (P = 0.57), vascular invasion (P = 0.85), lymphatic invasion (P = 0.41), perineural infiltration (P = 0.46), staging (P = 0.19), lymph node metastases (P = 0.08), or liver metastases (P = 0.59). Disease-free survival showed significant association (P = 0.01) with the intensity of NM23 protein immunohistochemical expression in colorectal carcinoma tissue, whereas overall survival showed no association with NM23 protein expression (P = 0.13).
NM23 protein expression was higher in neoplastic colorectal carcinoma tissue than in adjacent non-neoplastic mucosa, showing no correlation with morphological aspects, presence of lymph node or liver metastases, colorectal carcinoma staging, or overall survival. Disease-free survival was higher in patients with increased NM23 expression.
Arquivos de gastroenterologia 12/2010; 47(4):361-7.
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ABSTRACT: Adjuvant or neoadjuvant chemoradiotherapy (CRT) increases the survival rates significantly, but it also increases morbidity. Molecular markers may help on prognosis evaluation and treatment choice.
The purpose of this study is to evaluate the imunoexpression of p53 and Ki-67 in rectal cancer tissue after CRT treatment.
Stage II or III rectal cancer patients were evaluated and treated with RT and 5-FU preoperatively (neoadjuvant treatment, NG) or after surgical resection of the cancer (adjuvant treatment, AG).
Thirty-one patients were enrolled in the NG and 30 in the AG; 63.95% were between 50 and 70 years, 50.8% were male, and 53% were in stage III. Of the tumors, 64.5% of the NG and 63.34% of the AG had not overexpressed p53 (p = 0.865) and 9.67% of NG and 33.33% of the AG tumors had a high proliferative index (HPI) of Ki67, p = 0.052. We have not found any difference among metastasis development in the groups (p = 0.708). After 5 years, patients with low proliferative index (LPI) of Ki67 tumors had the best survival rate (p = 0.041). Patients with positive or negative p53 tumors had similar survival (p = 0.35). Patients with HPI of Ki67 had an increased marginal risk for death (p = 0.069).
The rate of tumors that overexpressed p53 was similar in both groups. Patients with p53 positive tumors survived as long as those with p53 negative. Patients treated with chemoradiotherapy before surgical resection, expressed Ki67 in a small percentage. Rectal cancer patients with LPI of Ki67 had the best prognosis.
Journal of Gastrointestinal Cancer 11/2010; 42(1):34-9.
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ABSTRACT: Objective: To determine the expression of p53, p16 and Ki-67 and its relevance in survival and cell differentiation. Methods: Fifteen duodenopancreatectomized patients were included. Immunohistochemical expression of p53, p16 and Ki-67 was determined in paraffin embedded tumor blocks. The relation of these expressions with different variables was studied. Results: Ninety-three per cent of tumors showed expression of p53 and p16. Ki-67 was expressed in 86.66% of tumors (labeling index – LI 11.91 ± 9.47). The presence of combined alterations was not related to significant differences in tumor type, stage or survival; similar results were obtained analyzing isolated expressions. When groups of p16 and Ki-67 expressions where created, the median survival was not significant. However, there was a slightly better survival in patients with focal expression of p16 (median survival 20.75 versus 14.34), when compared to patients with diffuse expression. Conclusion: The overexpression of p53, p16 and Ki-67 was not related to survival or tumor grade, when comparing isolated or combined expressions.
Einstein. 01/2010;
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ABSTRACT: The aim of the present study was to evaluate by immunohistochemistry the prognostic meaning of the tumor marker MET (hepatocyte growth factor) in patients submitted to surgical resection due to primary colorectal adenocarcinoma.
A retrospective study was carried out that included 286 consecutive patients with colorectal adenocarcinoma, submitted to surgical resection at Barretos Cancer Hospital, from 1993 to 2002. The histopathological expression of the MET tumor marker was evaluated using an anti-protein monoclonal antibody against MET by the streptavidin-biotin-peroxidase technique. The expression of the tumor marker was semi-quantitative, and the slide samples were independently analyzed by three pathologists unaware of patient clinical and histopathological data.
The tumor marker expression was positive in 236 (79%) out of a total of 286 patients. This expression was statistically significantly different between stages I and IV (p=0.004), for overall survival (p=0.009), and for cancer-related mortality rates (p=0.022). However, no association between the tumor marker and recurrence (p=0.89) or disease-free interval (p=0.91) was observed.
MET has shown significant expression at advanced stages of the disease, as well as for overall survival and cancer-related mortality rates demonstrating to be a valuable marker for poor prognosis in colorectal cancer patients.
Anticancer research 11/2009; 29(11):4807-11. · 1.73 Impact Factor
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ABSTRACT: The inhibitors of apoptosis proteins (IAPs) act by directly blocking cleaved caspase-3 (XIAP) or the protein SMAC/DIABLO, an antagonist. The inhibition of XIAP activity or the increase of SMAC activity might improve the therapeutic response of the patients. This work evaluated the immunoexpression of IAPs and SMAC in colorectal carcinoma and their correlation with apoptotic index (AI), cellular proliferation, p53 protein immunoexpression and patient survival rate. TMA paraffin blocks were made with colorectal cancer tissue and adjacent non-tumorous mucosa of 130 patients, not submitted to radio or chemotherapy. Sections of 4 microm were processed by immunohistochemistry for survivin, XIAP, cIAP-1, cIAP-2 and SMAC, and the immunoexpression scores were obtained. They were correlated between each other and with the AI obtained by anti-cleaved caspase-3 and M30 (cleaved cytokeratin-18) antibodies, the cellular proliferation index, p53 protein immunoexpression and patient survival data. Direct correlation occurred between the four IAPs studied in tumor and non-tumorous mucosa tissues. SMAC, survivin, cIAP-1 and cIAP-2 were positively correlated with tumoral tissue AI. Cellular proliferation and p53 immunoexpression was positively correlated with XIAP, SMAC and cIAP-1 scores. Low cIAP-1 immunoexpression showed a tendency for correlation with shorter patient survival. Equilibrium between the activities of IAPs and SMAC was demonstrated by the direct correlation between their immunoexpression. Correlation between SMAC and AI confirmed the pro-apoptotic activity of this protein. XIAP showed no inverse correlation with AI. XIAP, SMAC and cIAP-1 play a role in colorectal tumorigenesis, as demonstrated by their direct correlation with cellular proliferation and p53 protein. The tendency for correlation between low cIAP-1 immunoexpression and survival might indicate a role for this protein as a prognostic marker in colorectal cancer.
Oncology Reports 09/2009; 22(2):295-303. · 1.84 Impact Factor
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ABSTRACT: To evaluate the effects of iodine contrast media and gadoteric acid in acute necrotizing pancreatitis.
Fifty rabbits were distributed in 5 groups: 10 rabbits were assigned in the control group (group 5) and 40 rabbits were assigned in the pancreatitis group, wherein acute necrotizing pancreatitis was induced through retrograde injection of 5% sodium taurocholate (1 mL/kg weight) in the main pancreatic duct. After 3 hours, they were randomized to receive endovenous iodinized nonionic contrast medium (group 1), iodinized ionic contrast medium (group 2), gadoteric acid (group 3), and physiological serum at 0.9% (group 4). Six hours after induction of pancreatitis, these animals were reoperated. During surgery, pancreatic tissue flow through laser Doppler, hematometric values, biochemistry, and histopathology analysis by hematoxylin and eosin were done. Statistical analysis using Kruskal-Wallis, Fisher-Freeman-Halton, and parametric t tests was performed.
There was statistical significance when comparing tissue flow before and after induction of pancreatitis (P < 0.0001). Ionic and nonionic contrast media and gadoteric acid did not increase the grade of pancreatic necrosis (P > 0.05).
Ionic and nonionic contrast media and gadoteric acid did not produce adverse effects in the present model of acute necrotizing pancreatitis.
Pancreas 11/2007; 35(4):e41-4. · 2.39 Impact Factor
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ABSTRACT: Objective: To evaluate the effects of iodine contrast media and gadoteric acid in acute necrotizing pancreatitis.
Methods: Fifty rabbits were distributed in 5 groups: 10 rabbits were assigned in the control group (group 5) and 40 rabbits were assigned in the pancreatitis group, wherein acute necrotizing pancreatitis was induced through retrograde injection of 5% sodium taurocholate (1 mL/kg weight) in the main pancreatic duct. After 3 hours, they were randomized to receive endovenous iodinized nonionic contrast medium (group 1), iodinized ionic contrast medium (group 2), gadoteric acid (group 3), and physiological serum at 0.9% (group 4). Six hours after induction of pancreatitis, these animals were reoperated. During surgery, pancreatic tissue flow through laser Doppler, hematometric values, biochemistry, and histopathology analysis by hematoxylin and eosin were done. Statistical analysis using Kruskal-Wallis, Fisher-Freeman-Halton, and parametric t tests was performed.
Results: There was statistical significance when comparing tissue flow before and after induction of pancreatitis (P < 0.0001). Ionic and nonionic contrast media and gadoteric acid did not increase the grade of pancreatic necrosis (P > 0.05).
Conclusions: Ionic and nonionic contrast media and gadoteric acid did not produce adverse effects in the present model of acute necrotizing pancreatitis.
Pancreas 10/2007; 35(4):e41-e44. · 2.39 Impact Factor
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ABSTRACT: CONTEXT AND OBJECTIVE: Castleman's disease, or giant lymph node hyperplasia, is a rare disorder of the lymphoid tissue that causes lymph node enlargement. It is considered benign in its localized form, but aggressive in the multicentric type. The definitive diagnosis is based on postoperative pathological findings. The aim here was to describe a case of retroperitoneal unicentric Castleman's disease in the retroperitoneum. CASE REPORT: A 61-year old white male with weight loss and listlessness presented with moderate arterial hypertension and leukopenia. Abdominal tomography revealed a 5 x 4 x 5 cm oval mass of low attenuation, with inner calcification and intense enhancement on intravenous contrast, located in the retroperitoneal region, between the left kidney and the aorta, at the renal hilus. Exploratory laparotomy revealed a non-pulsatile solid oval mass situated in the retroperitoneum, adjacent to the left renal hilus. The retroperitoneal lesion was removed in its entirety. Examination of frozen samples revealed benign lymph node tissue and histopathological examination of the surgical sample revealed hyaline-vascular giant lymph node hyperplasia (Castleman's disease). The patient was discharged on the 12th day without significant events. Two months after the operation, the patient was readmitted with severe cardiac insufficiency, acute renal failure and bronchopneumonia, which progressed to acute respiratory insufficiency, sepsis and death.
Sao Paulo Medical Journal 08/2007; 125(4):253-5. · 0.71 Impact Factor
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ABSTRACT: To quantify the degree of angiogenesis by conventional method (microvessel density, MVD) and computerized method (endothelial area, EA), and to evaluate their relationships with the prognosis of patients operated on for colorectal adenocarcinoma.
Tumoral angiogenesis was studied by means of an immunohistochemical technique, using CD 34, on 126 patients; to quantify the angiogenesis, MVD (defined as number of microvessels per mm(2)) and EA measurement (defined as the area occupied by EA in the microscope field). A computerized method, IMAGELab software was utilized to quantify endothelial area.
The mean number of microvessels was 128.6 MV/mm(2) (SD = 44.5) and the mean EA was 4.3% (SD = 2.1). The Pearson method demonstrated a low correlation coefficient between MVD and EA (r = 0.429). No relationship between MVD and EA was observed with regard to relapse-free interval and overall survival.
The histological analysis of angiogenesis expression in patients with colorectal adenocarcinoma can be performed either by computer-assisted image analysis of endothelial area or by conventional microvessels counting. Both methods did not show any significant relationship between these angiogenesis parameters with relapse-free interval and overall survival.
Acta Cirurgica Brasileira 21(6):392-7. · 0.58 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor. Cellular proliferation and apoptosis is gaining importance for predicting prognosis in several cancers.
To investigate the Ki67 and p53 immunostaining in GISTs.
Specimens from 40 patients with GIST were assessed for immunohistochemical expression of Ki67 and p53. The tumors were divided according the risk of recurrence in two groups: I with high or intermediate risk and; II with low or very low risk.
Among the 40 patients, 21 were men, the mean age was 56 years, 16 occurred in the small intestine and 13 in the stomach, 5 in the retroperitonium, 4 in the colon or rectum and 2 in the mesenterium. Thirty two tumors were from group I and 8 from group II. Half of the patients developed recurrence, being 90% of the group I (P = 0.114). The tumor Ki67 labelling index ranged from 0.02 to 0.35 (mean level 0.12). This index was marginally higher in the group I patients with recurrence (P = 0.09) compared to the patients of the same group without recurrence. p53 staining was expressed in 65% of the GISTs. A higher frequency of p53 and Ki67 had been found in the group I tumors when compared to the other group (P = 0.022; OR = 8.00 - IC 95%: 1.32-48.65).
The most common site was the small intestine and 80% had a malignant potential justifying the high recurrence observed. No significant correlation was found between p53 and overall outcome of the patients. In group I patients, the evaluation Ki67LI may be a marker of prognosis. The positivity of both markers is higher among the patients with worst prognosis than in the others.
Arquivos de gastroenterologia 46(2):116-20.
