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1.
European heart journal. Cardiovascular imaging ; 21(supl. 1): 73-73, Jan., 2020. graf.
Article in English | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1052842

ABSTRACT

OBJECTIVES: To perform the cost-effectiveness analysis of three-dimensional transesophageal echocardiography (3DTEE) in comparison to two-dimensional transesophageal echocardiography (2DTEE) for the anatomic-functional evaluation and surgical planning of severe primary mitral regurgitation. METHODS: a complete economic study was based on a systematic review of 3DTEE and 2DTEE accuracy and private health system costs of two different surgical interventions: mitral valve plasty and mitral valve replacement. The prevalence of common postoperative complications was also predicted for elective procedures: atrial fibrillation (8.6%); acute myocardial infarction (1.4%); thrombosis (3.5%); bleeding (1.5%); endocarditis (6.3%). The decision tree method was adopted as a data analysis model. The Bayes" theorem was used based on sensitivity and specificity measurements. The costs, considering literature and professional tables, were: 3DTEE = US$ 349; 2DTEE = US$ 204; diagnostic evaluation = US$ 597; surgical procedure = US$ 3,643; surgical treatment = US$ 374. RESULTS: The deterministic analysis of the diagnostic test shows that 3DTEE (non-dominated) is superior to 2DTEE (absolutely dominated). The 3DTEE presents a cost reduction of US$ 1,147 and incremental effectiveness (true identification) of 22% when compared to 2DTEE. The multivariate probabilistic sensitivity analysis showed that after 100,000 iterations, the diagnosis based on the 3DTEE becomes the first choice regardless of the willingness to pay threshold. CONCLUSIONS: 3DTEE was cost-effective compared to 2DTEE. Thus, 3DTEE is a potential device to promote health compared to 2DTEE for surgical planning of severe primary mitral regurgitation. (AU)


Subject(s)
Cost-Benefit Analysis , Echocardiography, Transesophageal/economics , Mitral Valve Insufficiency
2.
Cochrane Database Syst Rev ; (4): CD001964, 2004 Oct 18.
Article in English | MEDLINE | ID: mdl-15495024

ABSTRACT

BACKGROUND: Surgeons disagree about the merits and risks of radical lymph node clearance during gastrectomy for cancer. OBJECTIVES: To evaluate survival and peri-operative mortality after limited or extended lymph node removal during gastrectomy for cancer. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CancerLit, LILACS, Central Medical Journal Japanese Database and the Cochrane register, references from relevant articles and conference proceedings. We contacted known workers in the field. SELECTION CRITERIA: Studies published after 1970 which reported 5 year survival or postoperative mortality rates, and clearly defined the node dissection performed, were considered. We excluded studies which overtly included patients receiving perioperative chemotherapy, and comparisons with clear systematic treatment allocation bias. Randomised controlled trials (RCTs), non-randomised comparisons and observational studies were considered separately. DATA COLLECTION AND ANALYSIS: Three reviewers selected trials for inclusion. Quality assessment and data extraction were performed independently by two reviewers. Results of trials of similar design were pooled. Meta-analysis was performed separately for randomised and non-randomised comparisons. MAIN RESULTS: Two randomised and two non-randomised comparisons of limited (D1) versus extended (D2) node dissection and 11 cohort studies of either D1 or D2 resection were analysed. Meta-analysis of randomised trials did not reveal any survival benefit for extended lymph node dissection (Risk ratio = 0.95 (95% CI 0.83 - 1.09), but showed increased postoperative mortality (RR 2.23, 95% CI 1.45 - 3.45). Pre-specified subgroup analysis suggested a possible benefit in stage T3+ tumours (RR = 0.68, 95% CI 0.42-1.10). Non-randomised comparisons showed no significant survival benefit for extended dissection (RR 0.92, 95% CI 0.83 -1.02), but decreased mortality (RR 0.65, 95% CI 0.45-0.93). Subgroup analysis showed apparent benefit in UICC stage II and IIIa. Observational studies of D2 resection reported much better mortality and survival than those of D1 surgery, but the settings were strikingly different. REVIEWERS' CONCLUSIONS: D2 dissection carries increased mortality risks associated with spleen and pancreas resection, and probably with inexperience and low case volumes. Randomised studies show no evidence of overall survival benefit, but possible benefit in T3+ tumours. These results may be confounded by surgical learning curves and poor surgeon compliance. Non-randomised comparisons suggest a possible survival benefit for D2 in intermediate UICC stages. Observational studies show high 5 year survival and low operative mortality after D2 dissection in experienced units, and poor results after D1 dissection in non-specialist units. Further studies, with precautions to eliminate learning curve effects, contamination and non-compliance, are needed to evaluate D2 dissection in intermediate stage gastric cancer.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy/mortality , Lymph Node Excision/mortality , Stomach Neoplasms/surgery , Gastrectomy/methods , Humans , Lymph Node Excision/methods , Randomized Controlled Trials as Topic , Survival Rate
3.
Cochrane Database Syst Rev ; (4): CD001964, 2003.
Article in English | MEDLINE | ID: mdl-14583942

ABSTRACT

BACKGROUND: Surgeons disagree about the merits and risks of radical lymph node clearance during gastrectomy for cancer. OBJECTIVES: To evaluate survival and peri-operative mortality after limited or extended lymph node removal during gastrectomy for cancer. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CancerLit, LILACS, Central Medical Journal Japanese Database and the Cochrane register, references from relevant articles and conference proceedings. We contacted known workers in the field. SELECTION CRITERIA: Studies published after 1970 which reported 5 year survival or postoperative mortality rates, and clearly defined the node dissection performed, were considered. We excluded studies which overtly included patients receiving perioperative chemotherapy, and comparisons with clear systematic treatment allocation bias. Randomised controlled trials (RCTs), non-randomised comparisons and observational studies were considered separately. DATA COLLECTION AND ANALYSIS: Three reviewers selected trials for inclusion. Quality assessment and data extraction were performed independently by two reviewers. Results of trials of similar design were pooled. Meta-analysis was performed separately for randomised and non-randomised comparisons. MAIN RESULTS: Two randomised and two non-randomised comparisons of limited (D1) versus extended (D2) node dissection and 11 cohort studies of either D1 or D2 resection were analysed. Meta-analysis of randomised trials did not reveal any survival benefit for extended lymph node dissection (Risk ratio = 0.95 (95% CI 0.83 - 1.09), but showed increased postoperative mortality (RR 2.23, 95% CI 1.45 - 3.45). Pre-specified subgroup analysis suggested a possible benefit in stage T3+ tumours (RR = 0.68, 95% CI 0.42-1.10). Non-randomised comparisons showed no significant survival benefit for extended dissection (RR 0.92, 95% CI 0.83 -1.02), but decreased mortality (RR 0.65, 95% CI 0.45-0.93). Subgroup analysis showed apparent benefit in UICC stage II and IIIa. Observational studies of D2 resection reported much better mortality and survival than those of D1 surgery, but the settings were strikingly different. REVIEWER'S CONCLUSIONS: D2 dissection carries increased mortality risks associated with spleen and pancreas resection, and probably with inexperience and low case volumes. Randomised studies show no evidence of overall survival benefit, but possible benefit in T3+ tumours. These results may be confounded by surgical learning curves and poor surgeon compliance. Non-randomised comparisons suggest a possible survival benefit for D2 in intermediate UICC stages. Observational studies show high 5 year survival and low operative mortality after D2 dissection in experienced units, and poor results after D1 dissection in non-specialist units. Further studies, with precautions to eliminate learning curve effects, contamination and non-compliance, are needed to evaluate D2 dissection in intermediate stage gastric cancer.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy/mortality , Lymph Node Excision/mortality , Stomach Neoplasms/surgery , Humans , Lymph Node Excision/methods , Randomized Controlled Trials as Topic , Survival Rate
4.
Cancer Res ; 61(9): 3544-9, 2001 May 01.
Article in English | MEDLINE | ID: mdl-11325815

ABSTRACT

To identify a set of genes involved in the development of colorectal carcinogenesis, we compared expression profiles of colorectal cancer cells from eight tumors with corresponding noncancerous colonic epithelia using a DNA microarray consisting of 9216 human genes. These cell populations had been rendered homogeneous by laser-capture microdissection. Expression change in more than half of the tumors was observed for 235 genes, i.e., 44 up-regulated and 191 down-regulated genes. The differentially expressed genes include those associated with signal transduction, metabolizing enzymes, production of reactive oxygen species, cell cycle, transcription, mitosis, and apoptosis. Subsequent examination of 10 genes (five up-regulated and five down-regulated) by semiquantitative reverse transcription-PCR using the eight tumors together with an additional 12 samples substantiated the reliability of our analysis. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of colorectal carcinogenesis and represents a source of novel targets for cancer therapy.


Subject(s)
Colorectal Neoplasms/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Oligonucleotide Array Sequence Analysis , Colorectal Neoplasms/metabolism , Dissection/methods , Down-Regulation , Epithelial Cells/metabolism , Epithelial Cells/physiology , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/physiology , Lasers , Up-Regulation
5.
Jpn J Cancer Res ; 91(8): 825-32, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10965024

ABSTRACT

Resistance to 5-fluorouracil (5-FU) has been frequently found in the treatment of digestive tract cancer patients. Our previous study suggested that high expression of endogenous Bcl-X(L), might be associated with resistance to 5-FU in colorectal cancer. The aim of this study is to analyze the role of Bcl-X(L) in 5-FU resistance and to explore a new therapeutic strategy using Bcl-X(L) antisense. First, western blot analysis shows that Bcl-X(L) rather than Bcl-2 is overexpressed in primary adenocarcinoma of colon. Second, when Colo320 cells, with undetectable endogenous Bcl-XL expression, were transfected with Bcl-XL gene, they acquired high resistance to 5-FU. Finally, antisense oligodeoxynucleotides (ODNs) that targeted the start codon of Bcl-X(L) mRNA (AS1) prove to be the most effective in DLD1 cells with high endogenous Bcl-X(L) expression. Bcl-X(L) protein expression was decreased in a dose-dependent manner when the cells were treated with AS1 ODNs, while non-sense and sense controls and 5-FU had no effect on Bcl-X(L) protein. 5-FU treatment induced a level of apoptosis 10-fold higher in DLD1 cells than in untreated control cells, while the same dose of 5-FU induced a 55-fold higher level of apoptosis in DLD1 cells treated with Bcl-XL antisense oligodeoxynucleotides (P = 0.0003). Moreover, AS1 ODNs coupled with 5-FU decreased viable colon cancer cells 40% more than did 5-FU alone (P < 0.05). These results suggest that Bcl-X(L) is an important factor for 5-FU resistance and the suppression of Bcl-X(L) expression by the specific antisense ODNs can increase the sensitivity of colon cancer cells to 5-FU.


Subject(s)
Apoptosis , Fluorouracil/pharmacology , Oligodeoxyribonucleotides, Antisense/pharmacology , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Adenocarcinoma/metabolism , Antimetabolites, Antineoplastic/pharmacology , Colonic Neoplasms , Drug Interactions , Drug Resistance, Neoplasm , Humans , Proto-Oncogene Proteins c-bcl-2/genetics , Transfection , Tumor Cells, Cultured , bcl-X Protein
6.
Ann Surg Oncol ; 7(3): 193-8, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10791849

ABSTRACT

BACKGROUND: Thymidylate synthase (TS) is regarded as a parameter of 5-fluorouracil (5-FU) chemosensitivity for colorectal carcinoma. Recent researchers indicate that the chemosensitivity of 5-FU for colorectal carcinoma with low expression of TS is better than tumors with high expression of TS. But the relation between TS expression and overall survival of curatively resected colorectal cancer patients has been less studied. METHODS: Specimens of curatively resected colon carcinoma from 148 patients were included in this study. TS expression in the tumor was assessed by immunohistochemical staining technique, and the patients were categorized into TS-(+) and TS-(-) groups. First, the relation between TS expression and survival of patients was examined. Next, for each group, we compared survival between the chemotherapy-(+) and the chemotherapy-(-) subgroup. RESULTS: Overall survival was significantly better in the TS-(-) group (n = 107) than in the TS-(+) group (n = 41) (P = .0003). In the TS-(-) group, there was little difference between the chemotherapy-(+) and the chemotherapy-(-) subgroup. In the TS-(+) group, the survival of the chemotherapy-(+) subgroup was significantly better than the chemotherapy-(-) subgroup (P = .0439). CONCLUSIONS: TS, itself, may be a prognostic factor for colon carcinoma; and 5-FU adjuvant chemotherapy may be appropriate for colon carcinoma with high expression of TS.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Carcinoma/drug therapy , Carcinoma/enzymology , Colonic Neoplasms/drug therapy , Colonic Neoplasms/enzymology , Fluorouracil/therapeutic use , Immunohistochemistry/methods , Thymidylate Synthase/metabolism , Carcinoma/surgery , Chi-Square Distribution , Colonic Neoplasms/surgery , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Statistics, Nonparametric , Survival Analysis , Treatment Outcome
7.
Ann Oncol ; 11(3): 273-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10811492

ABSTRACT

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the first enzyme that metabolizes 5-fluorouracil (5-FU). Until now, enzymatic activity or mRNA expression of DPD has been investigated. However, there are no papers on immunohistochemical evaluation of DPD. We investigated DPD staining on immunohistochemistry, and examined the relationship among immunohistochemical score, protein level and mRNA expression of DPD. MATERIALS AND METHODS: Forty-seven resected colon cancer specimens, four colon cancer cell lines, two xenografts by colon cancer cell lines, and human mononuclear cells were used. Immunohistochemistry was performed using DPD monoclonal antibody. Protein levels were determined by Western blot analysis. And mRNA levels were calculated by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: DPD was strongly expressed in the cytoplasm of cancer cells, and in the cytoplasm of macrophage and plasma cells. The immunohistochemical score was more correlated with protein levels (P = 0.0054) than mRNA expression (P = 0.9028). CONCLUSIONS: We investigated the characterization of DPD immunohistochemically, and showed that immunohistochemical expression of DPD can be used to predict the sensitivity of colorectal carcinomas to 5-FU.


Subject(s)
Antimetabolites, Antineoplastic/metabolism , Colonic Neoplasms/metabolism , Fluorouracil/metabolism , Oxidoreductases/metabolism , Aged , Antibodies, Monoclonal , Antimetabolites, Antineoplastic/therapeutic use , Biopsy , Blotting, Western , Colon/chemistry , Colon/metabolism , Colonic Neoplasms/drug therapy , Dihydrouracil Dehydrogenase (NADP) , Female , Fluorouracil/therapeutic use , Humans , Immunohistochemistry , In Vitro Techniques , Male , Middle Aged , Oxidoreductases/analysis , Oxidoreductases/genetics , Oxidoreductases/immunology , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction
8.
Br J Cancer ; 81(8): 1274-9, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10604722

ABSTRACT

It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2. Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer.


Subject(s)
Benzenesulfonates/therapeutic use , Colonic Neoplasms/pathology , Cyclooxygenase Inhibitors/therapeutic use , Lung Neoplasms/prevention & control , Oxazoles/therapeutic use , Animals , Benzenesulfonates/pharmacology , Cell Division/drug effects , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Disease Models, Animal , Isoenzymes/drug effects , Lung Neoplasms/secondary , Matrix Metalloproteinase Inhibitors , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Oxazoles/pharmacology , Prostaglandin-Endoperoxide Synthases/drug effects
9.
Ann Surg Oncol ; 6(5): 481-8, 1999.
Article in English | MEDLINE | ID: mdl-10458687

ABSTRACT

BACKGROUND: p21Waf1/Cip1 (p21), p27Kip1 (p27), p53, and Rb play critical roles in cell cycle regulation and may influence the clinical behavior of tumors. We examined whether their expression is useful to predict survival of patients with esophageal squamous cell carcinoma (ESC). METHODS: Expression of p21, p27, p53, and Rb was studied by the immunohistochemical method in specimens from 62 patients with curatively resected ESC tumors and scored by a computerized image analysis system. RESULTS: The median expression scores of p21, p27, p53, and Rb (14, 12, 27, and 50, respectively) were used as cut-off points to define low and high expression groups for each protein. The 5-year survival rate for the high p21 expression group was 68%; that for the low expression group was 31% (P = .0062). p27, p53, and Rb were not correlated with overall survival. When patients were categorized into four groups based on p21 expression level and lymph node involvement (pN), the survival curves were significantly different (P = .0017). Thus, patients without lymph node involvement but with low p21 expression had survival similar to that of patients with lymph node involvement and high p21 expression. Multivariate analysis showed that age (P = .0102), lymph node involvement (P = .0076), and p21 (P = .0276) were independent prognostic factors. CONCLUSIONS: Expression of p21 is an independent prognostic factor in curatively resected ESC. Definition of new subgroups of patients based on p21 expression may help to enhance the stratification of stage.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Cell Cycle Proteins , Cyclins/metabolism , Esophageal Neoplasms/metabolism , Tumor Suppressor Proteins , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Cyclin-Dependent Kinase Inhibitor p21 , Cyclin-Dependent Kinase Inhibitor p27 , Cyclins/genetics , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Female , Genes, Retinoblastoma , Humans , Immunohistochemistry , Male , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Middle Aged , Predictive Value of Tests , Prognosis , Survival Analysis , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
10.
Br J Cancer ; 78(8): 986-92, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9792140

ABSTRACT

Recently, apoptosis has been implicated as one of the end points of cells exposed to chemotherapeutic agents. The p53 and Bcl-2 family of proteins are involved in chemotherapy-induced apoptosis, but in a cell type-dependent manner. We sought to determine the roles played by the p53 and Bcl-2 family of proteins in 5-fluorouracil (5-FU)-induced apoptosis of human colon cancer cell lines. We first studied the p53 genetic and functional status, and then 5-FU, at inhibitory concentration of 50% (IC50) doses, was used to induce apoptosis, which was confirmed by morphological analysis and enzyme-linked immunosorbent assay (ELISA). Bcl-2, Bcl-X(L), Bax, Bad, Bak and p53 protein expression was analysed by Western blotting. Using five human colon cancer cell lines, we found that equitoxic (IC50) doses of 5-FU induced apoptosis in both wild-type p53 and mutant p53 cells. Analysis of the steady-state levels of Bcl-2 family proteins showed high expression of Bcl-X(L) in all of the cell lines except Colo320. Bcl-2 was expressed in two of them. Bax presented with the lowest basal expression and Bad showed homogeneous expression. On the other hand, Bak expression varied more than fivefold among these cells. In cells containing wild-type p53 (e.g. LoVo), 5-FU-induced apoptosis was accompanied by increased expression of Bax and Bak without consistent modulation of other bcl-2 family proteins. In contrast in cells containing mutant p53 (e.g. DLD1), Bak expression was remarkably increased. There was a significant correlation between chemosensitivity and Bcl-X(L) to Bax ratio, rather than Bcl-2 to Bax. In conclusion, these results suggest that some members of the Bcl-2 family of proteins, in human colon cancer cell lines, are modulated by 5-FU and that the ratio of Bcl-X(L) to Bax may be related to chemosensitivity to 5-FU.


Subject(s)
Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Fluorouracil/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Apoptosis/drug effects , Base Sequence , Drug Resistance, Neoplasm , Humans , Polymerase Chain Reaction , Proto-Oncogene Proteins/metabolism , Tumor Cells, Cultured , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein , bcl-X Protein
11.
Dis Colon Rectum ; 41(1): 68-74, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9510313

ABSTRACT

BACKGROUND: Recent studies showed that p53 and p21 may play major roles in determining tumor radiosensitivity through the apoptosis pathway. The aim of this study was to investigate the predicting value of radiosensitivity in human rectal carcinoma. METHODS: p53 and p21/WAF1 expressions in formalin fixed, paraffin-embedded, preradiation biopsy samples from 49 patients with primary rectal carcinoma were analyzed immunohistochemically. p53 and p21 expressions and their relationships with histopathologic changes after radiation and other clinical features were evaluated. RESULTS: Expressions of p53 and p21/WAF1 were 49 and 28.6 percent, respectively. In 36.7 percent of total tumors, significant histopathologic effect can be observed. There was a significant inverse expression of p53 and p21. Most of the p53(+) or p21(-) tumors were radioresistant, and the majority of p53(-) or p21(+) tumors were radiosensitive. Tumors size in the radiosensitive, p53(-), or p21(+) group decreased more significantly than in radioresistant, p53(+), or p21(-) group (P < 0.01), and patients with radioresistant, p53(+), or p21(-) tumors had more local recurrence, more distant metastasis, and a shorter five-year survival rate than those with radiosensitive, p53(-), or p21(+) tumors, but without statistic significance. No statistically significant correlation can be observed between other tumor clinical features and radiosensitivity, p53, or p21 expressions. CONCLUSION: Immunohistochemistry detection of p53 and p21 expressions may be useful parameters for more radiosensitive patients selected for preoperative radiotherapy.


Subject(s)
Carcinoma/radiotherapy , Cyclins/metabolism , Enzyme Inhibitors/metabolism , Patient Selection , Rectal Neoplasms/radiotherapy , Tumor Suppressor Protein p53/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma/metabolism , Carcinoma/mortality , Carcinoma/pathology , Cyclin-Dependent Kinase Inhibitor p21 , Female , Humans , Immunohistochemistry , Male , Middle Aged , Multivariate Analysis , Preoperative Care , Proto-Oncogene Proteins c-bcl-2/metabolism , Radiation Tolerance , Rectal Neoplasms/metabolism , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Survival Rate
12.
Dig Dis Sci ; 43(2): 306-10, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9512122

ABSTRACT

Mutation of the adenomatous polyposis coli (APC) gene is frequently found in colorectal tumors from both familial adenomatous polyposis (FAP) and non-FAP patients. Analysis of APC mutation is time-consuming and costly due to the large size of the APC gene. As the majority of APC mutations result in the truncation of gene products, the detection of truncated APC proteins may be used as a screening method for APC mutations. The aim of this study is to establish a practical method of detecting truncated APC proteins for the screening of APC mutations. APC proteins in human colorectal cancer cell lines were analyzed by western blotting. Truncated APC proteins were expressed in all of the colorectal cancer cell lines studied. Two species of truncated APC proteins were expressed in two cell lines. Western blotting is a rapid, reliable screening method for APC mutations and provides information on both alleles.


Subject(s)
Colorectal Neoplasms/metabolism , Genes, APC/genetics , Mutation , Antibodies, Monoclonal , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Humans , Immunoblotting , Molecular Weight , Tumor Cells, Cultured
13.
J Exp Clin Cancer Res ; 17(4): 491-6, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10089073

ABSTRACT

To study the altered mechanisms of cell cycle regulation in esophageal cancer, the expressions of cyclins involved in G1/S transition were analyzed in a series of 26 human esophageal cancer cell lines. To evaluate and compare the levels of cyclin expression, flow cytometric analysis was performed using human lymphocytes as control. Increased expressions of cyclin A, D1, D3 and E were found in 23.1% (6/26), 65.4% (17/26), 15.4% (4/26) and 57.7% (15/26) of the cell lines, respectively. All cell lines studied expressed less cyclin D2 than lymphocytes and the majority of the cell lines expressed cyclin D3 at levels similar to those of lymphocytes. Five cell lines expressed exceptionally high levels of cyclin E. Expressions of cyclin D1 and E were significantly elevated as compared to those of cyclin A, D2 and D3. These results suggest that increased expressions of the positive cell cycle regulators cyclin D1 and E may play an important role in esophageal carcinogenesis.


Subject(s)
Cyclins/analysis , Esophageal Neoplasms/chemistry , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Cell Cycle/physiology , Cyclins/metabolism , Esophageal Neoplasms/metabolism , Flow Cytometry , Humans , Tumor Cells, Cultured
14.
Hepatogastroenterology ; 45(24): 2117-22, 1998.
Article in English | MEDLINE | ID: mdl-9951876

ABSTRACT

BACKGROUND/AIMS: In planning adjuvant treatment of colorectal cancer, it is of critical importance to optimize the treatment by identifying subsets of patients that will respond or not to chemotherapy. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are key enzymes involved in the biochemical functions of the antimetabolite 5-fluorouracil (5-FU). In searching for the factors determining the 5-FU sensitivity of colorectal cancer, TS and DPD were analyzed in relation to the inhibitory effect of 5-FU on cell proliferation in a series of human colorectal cancer cell lines. METHODOLOGY: TS and DPD protein expressions were quantified in 5 human colorectal cancer cell lines, using TS binding assay and Western blotting, respectively. Cellular growth inhibition was assessed by MTT assay after 48 hours of continuous exposure to 5-FU or cisplatin (CDDP). RESULTS: TS protein expression was detected in all but one of the cell lines studied and varied within a 17-fold range, while DPD protein expression was detectable in only one cell line (CaR1). CaR1, which expressed the highest level of DPD and no detectable TS, showed remarkable resistance to 5-FU. The other colorectal cancer cell lines with undetectable DPD expression were sensitive to 5-FU. There was no correlation between TS expression and 5-FU sensitivity. All of the cell lines studied showed similar sensitivity to CDDP. CONCLUSIONS: These data suggest that DPD, but not TS, expression predicts 5-FU sensitivity in colorectal cancer cell lines.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Cell Division/drug effects , Colorectal Neoplasms/drug therapy , Fluorouracil/pharmacology , Oxidoreductases/genetics , Thymidylate Synthase/genetics , Tumor Cells, Cultured/drug effects , Cell Division/genetics , Colorectal Neoplasms/genetics , Dihydrouracil Dehydrogenase (NADP) , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Enzymologic/physiology , Humans , Prognosis , Tumor Cells, Cultured/enzymology , Tumor Stem Cell Assay
15.
Jpn J Cancer Res ; 88(9): 855-60, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9369933

ABSTRACT

To study the altered mechanisms of cell cycle regulation in colorectal cancer, the expressions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, p53 and retinoblastoma (Rb) protein were analyzed by western blotting in a series of human colorectal cancer cell lines. The colorectal cancer cell lines exhibited various expression patterns of cell cycle regulators, which may reflect differences in the biological characteristics of cancer cells and in the genetic backgrounds of carcinogenesis. A correlation was found between p53 gene alteration and p21 expression, suggesting that p53 gene mutation usually suppresses p21 expression, though p21 expression could be induced via both a p53-dependent and a p53-independent pathway in colorectal cancer. None of the cell lines studied expressed p16 protein, suggesting that inactivation of p16 may be a common alteration in colorectal cancer. Moreover, all the D-type cyclins, especially D2 and D3, were expressed at a high level in most of the cell lines. Loss of p16 expression and increased expression of D-type cyclins promote CDK-mediated Rb phosphorylation. All of the colorectal cancer cell lines studied herein expressed Rb protein, but the growth-suppressive properties of Rb may be inactivated by the loss of p16 expression and increased expressions of D-type cyclins. In view of the pivotal role of Rb in cell cycle regulation, loss of p16 expression and overexpression of D-type cyclins may be critical alterations in colorectal cancer.


Subject(s)
Cell Cycle/physiology , Colonic Neoplasms/pathology , Colorectal Neoplasms/pathology , Cyclin-Dependent Kinases/biosynthesis , Cyclins/biosynthesis , Colonic Neoplasms/metabolism , Colorectal Neoplasms/metabolism , Cyclin-Dependent Kinases/antagonists & inhibitors , Enzyme Inhibitors/metabolism , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Genes, p53 , Humans , Retinoblastoma Protein/biosynthesis , Tumor Cells, Cultured , Tumor Suppressor Protein p53/biosynthesis
16.
Rev Hosp Clin Fac Med Sao Paulo ; 51(4): 113-5, 1996.
Article in Portuguese | MEDLINE | ID: mdl-9163969

ABSTRACT

The use or not of drainage after elective cholecystectomy has been recently studied, and we will discuss the real incidence of the subhepatic biliary collection and its clinical significance. In this sense, we studied 20 patients with a mean age of 45 years (4 male and 16 female), submitted to elective cholecystectomy according to selective techniques patterned by our group, where we realized ligature of all vessels of the gallbladder bed, and subhepatic drainage. These patients receibed 99 mTc-DISIDA at the moment we closed the abdomen, and in a period of 24 and 48 hours we studied its presence in the subhepatic bed and in the drainage material. All the patients had not post-operative complications and none biliary drainage or subhepatic collection scanned. We concluded that using our preconized techniques, the subhepatic drainage is unnecessary after elective cholecystectomy.


Subject(s)
Biliary Fistula/etiology , Cholecystectomy/adverse effects , Elective Surgical Procedures/adverse effects , Adult , Aged , Biliary Fistula/epidemiology , Biliary Fistula/therapy , Drainage , Female , Humans , Incidence , Male , Middle Aged
17.
Arq Gastroenterol ; 32(3): 116-20, 1995.
Article in Portuguese | MEDLINE | ID: mdl-8728786

ABSTRACT

A 71-year-old female with a rupture of left intrahepatic artery aneurysm with acute upper abdominal pain, weight loss and fever. The diagnosis was established with doppler ultrasound, contrasted abdominal computer tomography scanning and celiac and mesenteric artery angiography. Prompt recognition and left hepatectomy led to a favourable outcome.


Subject(s)
Aneurysm, Infected/surgery , Hepatectomy , Hepatic Artery/surgery , Staphylococcal Infections/surgery , Aged , Aneurysm, Infected/diagnosis , Female , Hepatic Artery/pathology , Humans , Staphylococcal Infections/diagnosis
18.
Rev Hosp Clin Fac Med Sao Paulo ; 49(5): 221-4, 1994.
Article in Portuguese | MEDLINE | ID: mdl-7716376

ABSTRACT

Primary gastric lymphoma is a relatively rare entity that may have several different methods of treatment, including surgery, chemotherapy and radiotherapy. We describe a case of advanced primary gastric lymphoma treated with chemotherapy. A 51-year-old male patient underwent total gastrectomy after two cycles of chemotherapy. The histologic examination of the gross specimen revealed total regression of the lymphoma. Literature review of this condition and a discussion about the diagnosis and treatment are presented.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Stomach Neoplasms/drug therapy , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Humans , Lymphoma, Non-Hodgkin/radiotherapy , Lymphoma, Non-Hodgkin/surgery , Male , Middle Aged , Prednisone/administration & dosage , Remission Induction , Stomach Neoplasms/radiotherapy , Stomach Neoplasms/surgery , Vincristine/administration & dosage
19.
Rev Hosp Clin Fac Med Sao Paulo ; 49(4): 160-3, 1994.
Article in Portuguese | MEDLINE | ID: mdl-7871324

ABSTRACT

Pseudotumoral form of gastric ulcer is an infrequent clinical presentation of peptic disease. We present the findings in ten patients with this variety of gastric peptic ulcer treated in the last five years. All records including preoperative radiological and endoscopic examinations are reviewed. Five patients were women and five were men. The median age of patients was 62.1 years (range, 45 to 79 years). Epigastric pain was the main symptom in 90% of patients and weight loss in 70%. Six patients underwent surgical treatment. There was no perioperative mortality. A review of literature of this condition and a discussion about the differential diagnosis are presented.


Subject(s)
Stomach Ulcer/diagnosis , Stomach/pathology , Adult , Aged , Diagnosis, Differential , Female , Granuloma, Plasma Cell/diagnosis , Humans , Male , Middle Aged , Radiography , Stomach/diagnostic imaging , Stomach Ulcer/therapy
20.
Article in Portuguese | MEDLINE | ID: mdl-8235266

ABSTRACT

Duodenal perforation is a rare complication of endoscopic sphincterotomy and its treatment is controversial. The authors report three cases of duodenal perforation by endoscopic sphincterotomy. In two cases with history of a previous biliary infection, surgical treatment had to been performed because of a peripancreatic abscess.


Subject(s)
Duodenum/injuries , Intestinal Perforation/etiology , Sphincterotomy, Endoscopic/adverse effects , Aged , Female , Humans , Male , Middle Aged
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