RESUMO
PURPOSE: Cyclooxygenase-2 is thought to play a role in the development of intestinal tumors and levels are elevated in approximately 80 to 90 percent of human colorectal carcinomas. To clarify the role that cyclooxygenase-2 plays in the development of colorectal carcinoma, we studied the relationship between cyclooxygenase-2 expression and tumor morphology and that between cyclooxygenase-2 expression and K-ras mutation. METHODS: We classified 48 T1 colorectal carcinomas as polypoid or nonpolypoid and analyzed the clinicopathologic features. The expression of cyclooxygenase-2 was determined immunohistochemically, and nested polymerase chain reaction-restriction fragment length polymorphism detected a K-ras codon 12 mutation. RESULTS: Cyclooxygenase-2 expression was higher in polypoid carcinomas than in nonpolypoid carcinomas (P < 0.001). The K-ras codon 12 mutation was associated with higher levels of cyclooxygenase-2 expression compared with carcinomas without this mutation (P = 0.028). CONCLUSIONS: Polypoid growth and K-ras gene mutation are both associated with increased levels of cyclooxygenase-2 expression in T1 tumors.
Assuntos
Adenoma/genética , Adenoma/metabolismo , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Genes ras/genética , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Adenoma/patologia , Pólipos Adenomatosos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Códon , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2 , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Estatísticas não ParamétricasRESUMO
A 14-year-old female with Turner syndrome (karyotype 45,X) had a history of abdominal pain with distention, constipation, and fever. She was first operated on for the suspicion of appendicitis, failed to improve, and was later hospitalized for further investigation and treatment. Studies demonstrated an obstructing tumor of the transverse colon, and an emergency laparotomy was performed. The final diagnosis was a signet-ring cell carcinoma of the colon with diffuse peritoneal dissemination and metastasis to paracolic lymph nodes. On the basis of this case, we report the association of Turner syndrome with malignancies and also some aspects of colon cancer in childhood.
Assuntos
Carcinoma de Células em Anel de Sinete/complicações , Neoplasias do Colo/complicações , Síndrome de Turner/complicações , Adolescente , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/cirurgia , Aberrações Cromossômicas , Colectomia/métodos , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Cariotipagem , Laparotomia/métodosRESUMO
PURPOSE: The aim of this study was to examine the effect of a specific cyclooxygenase-2 inhibitor, rofecoxib, on rectal polyps in familial adenomatous polyposis patients. EXPERIMENTAL DESIGN: This was a randomized, double-blind, placebo-controlled study of the efficacy and safety of rofecoxib in the rectum. Initially, 21 patients were assigned randomly in a 1:1 ratio to receive either 25 mg rofecoxib once a day or a placebo p.o. for 9 months. Patients underwent endoscopy at the beginning of the study and then every 3 months thereafter. We reviewed the videotapes to measure the number and size of polyps in the same area throughout the study period in each individual patient. RESULTS: The polyp number, measured as the percentage of change from the baseline values, was significantly decreased in the rofecoxib group at 3, 6, and 9 months. At 9 months, the polyp number in the rofecoxib group decreased by 6.8% from the baseline values, whereas that in the placebo group increased by 3.1%. The 9.9% difference between the rofecoxib and placebo groups was statistically significant (P = 0.004). At 9 months, the rofecoxib group showed a significant reduction from the baseline in polyp size as compared with the placebo group (-16.2% versus 1.5%; P < 0.001). There was no statistically significant increase in the incidence of any adverse events in treatment with rofecoxib compared with placebo (P = 0.922). CONCLUSIONS: In this study, once-daily treatment with 25 mg rofecoxib, a cyclooxygenase 2-specific inhibitor, significantly decreased the number and size of rectal polyps in familial adenomatous polyposis patients.
Assuntos
Polipose Adenomatosa do Colo/tratamento farmacológico , Pólipos do Colo/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Isoenzimas/antagonistas & inibidores , Lactonas/uso terapêutico , Adulto , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Progressão da Doença , Método Duplo-Cego , Endoscopia , Feminino , Humanos , Masculino , Proteínas de Membrana , Microscopia de Vídeo , Pessoa de Meia-Idade , Placebos , Prostaglandina-Endoperóxido Sintases , Sulfonas , Fatores de TempoRESUMO
PURPOSE: Cyclooxygenase-2 is an important target for nonsteroidal anti-inflammatory drugs in suppressing colorectal tumorigenesis. To evaluate the role of cyclooxygenase-2 in sporadic colorectal adenoma, we correlated cyclooxygenase-2 expression in adenomas with other adenoma characteristics. METHODS: Cyclooxygenase-2 expression was evaluated immunohistochemically in 95 endoscopically resected colorectal adenomas. RESULTS: Cyclooxygenase-2 was expressed mainly in the cytoplasm of adenoma cells, where it was seen in 74 percent (70/95) of adenomas. Expression was related significantly to grade of dysplasia (P < 0.001) and tumor size (P = 0.028). Multivariate logistic regression analysis showed cyclooxygenase-2 expression in adenoma cells to be independently associated with grade of dysplasia (P = 0.001). CONCLUSION: Observed associations suggest that cyclooxygenase-2 plays an important role in progression of the adenoma-to-carcinoma sequence.
Assuntos
Adenoma/metabolismo , Neoplasias Colorretais/metabolismo , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Adenoma/enzimologia , Adenoma/patologia , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2 , Citoplasma/metabolismo , Progressão da Doença , Humanos , Imuno-Histoquímica , Modelos Logísticos , Proteínas de Membrana , Análise MultivariadaRESUMO
BACKGROUND: Cyclooxygenase (COX)-2 may be linked to carcinogenesis. In the previous study, we examined COX-2 expression immunohistochemically in 95 adenomas and reported a significant correlation between its expression and the grade of dysplasia. To clarify the correlation between COX-2 expression and cell proliferation, we investigated Ki-67 labeling index using immunohistochemistry and its correlation with COX-2 expression. METHODS: Immunohistological staining for Ki-67 antigen was performed on 95 colorectal adenomas previously reported. RESULTS: The Ki-67 labeling index was significantly higher in the high-COX-2 group than in the low-COX-2 and negative groups in adenomas with moderate (44.5 +/- 6.4% vs 33.0 +/- 2.6%, 39.0 +/- 6.2%; P = 0.01, P < 0.001, respectively) or severe dysplasia (47.2 +/- 7.6% vs 40.3 +/- 7.2%, 35.0 +/- 5.4%; P = 0.02, P = 0.005, respectively). There was no correlation between Ki-67 labeling index and COX-2 expression in mild dysplasia. CONCLUSIONS: These results suggest that COX-2 may play a causal role in cell proliferation in carcinogenesis.
Assuntos
Adenoma/metabolismo , Neoplasias Colorretais/metabolismo , Isoenzimas/biossíntese , Prostaglandina-Endoperóxido Sintases/biossíntese , Adenoma/patologia , Análise de Variância , Divisão Celular/fisiologia , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2 , Humanos , Imuno-Histoquímica , Isoenzimas/fisiologia , Antígeno Ki-67/análise , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases/fisiologiaRESUMO
In the present study, we have cloned the cDNA of ABCC13, a novel ABC transporter, from the cDNA library of adult human placenta. The ABCC13 gene spans approximately 70kb on human chromosome 21q11.2 and consists of 14 exons. The open reading frame of the ABCC13 cDNA encodes a peptide consisting of 325 amino acid residues. The amino acid sequence corresponding to putative membrane-spanning domains was remarkably similar to ABCC1, ABCC2, ABCC3, and ABCC6. The ABCC13 gene was expressed in the fetal liver at the highest level among the organs studied. While ABCC13 was expressed in the bone marrow, its expression in peripheral blood leukocytes of adult humans was much lower and no detectable levels were observed in differentiated hematopoietic cells. The expression of ABCC13 in K562 cells decreased during cell differentiation induced by TPA. These results suggest that the expression of human ABCC13 is related with hematopoiesis.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Feto/fisiologia , Fígado/fisiologia , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Células Cultivadas , Cromossomos Humanos Par 21 , Clonagem Molecular , Éxons , Feto/anatomia & histologia , Biblioteca Gênica , Humanos , Íntrons , Dados de Sequência Molecular , Proteína 2 Associada à Farmacorresistência Múltipla , Fases de Leitura Aberta , Placenta/fisiologia , Alinhamento de Sequência , Distribuição TecidualRESUMO
BACKGROUND: Cyclooxygenase-2 is considered to play an important role in colorectal tumorigenesis. The purpose of this study was to clarify the relationship between cyclooxygenase-2 expression and morphology in colorectal cancer. METHODS: We investigated cyclooxygenase-2 mRNA expression and type of growth (polypoid or non-polypoid according to Shimoda's classification) in 69 colorectal cancers by reverse transcription-polymerase chain reaction and histologic examination. Cyclooxygenase-2 mRNA expression was assessed as a ratio relative to cyclooxygenase-1 mRNA expression (cyclooxygenase-2 index). RESULTS: Cyclooxygenase-2 indices in normal colorectal mucosa, polypoid cancer and non-polypoid cancer were 0.7 +/- 0.1, 1.0 +/- 0.1 and 1.9 +/- 0.1, respectively. The cyclooxygenase-2 index in non-polypoid cancer was significantly higher than in polypoid cancer (P = 0.0002) or normal mucosa (P < 0.0001). No difference in cyclooxygenase-2 index was found between polypoid cancer and normal mucosa (P = 0.67). CONCLUSIONS: These results suggest that cyclooxygenase-2 overexpression in colorectal cancer is associated with non-polypoid growth.
Assuntos
Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Isoenzimas/biossíntese , Prostaglandina-Endoperóxido Sintases/biossíntese , Adenoma/enzimologia , Adenoma/patologia , Idoso , Pólipos do Colo/enzimologia , Pólipos do Colo/patologia , Neoplasias Colorretais/cirurgia , Ciclo-Oxigenase 2 , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Isoenzimas/genética , Metástase Linfática , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prostaglandina-Endoperóxido Sintases/genética , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
PURPOSE: We examined the frequency, mode, and extent of discontinuous spread of rectal cancer in the mesorectum to determine the optimal distal clearance margin in situ. METHODS: Forty consecutive patients with rectal cancer undergoing locally curative resection were studied prospectively. Discontinuous cancer spread in the mesorectum and the extent of distal spread was examined microscopically. A tissue shrinkage ratio comparing the distal clearance margin measured before transection to that measured after fixation in each case, was used to convert microscopically measured extent of distal spread to extent in situ. RESULTS: Discontinuous cancer spread in the mesorectum was observed in 17 cases (43 percent); lymph node metastasis in 15 cases (38 percent) and small deposits other than nodal metastases in 8 cases (20 percent). Distal cancer spread (either intramural or mesorectal) was observed in 6 cases (15 percent). The mean distal clearance margin before transection and after fixation was 3.2 cm and 2 cm, respectively. The mean tissue shrinkage ratio was 60 percent. The maximum extent of microscopic distal spread and adjusted distal spread in situ were 20 and 24 mm, respectively. CONCLUSIONS: Excising the mesorectum with fascia propria circumferentially intact is essential for rectal surgery. The optimal distal clearance margin for the rectal wall as well as the mesorectum in situ can be reduced to 3 cm with a right angle.
Assuntos
Invasividade Neoplásica , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Estudos ProspectivosRESUMO
Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1, were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers and their neighboring normal tissues. Our results reveal a new hBUB1 missense mutation (Ala130Ser) but not any hBUBR1 coding sequence mutations. hBUB1 and hBUBR1 mRNA levels were reduced to < 10% of the neighboring normal tissues in 3 of 103 and 3 of 109 carcinomas, respectively, and to < 50% in 7 and 7 carcinomas, whereas the overall expression levels were markedly higher in cancers than in normal tissues. Carcinomas with reduced hBUB1 and/or hBUBR1 mRNA levels, as well as the colon carcinoma harboring the hBUB1 mutation, were associated with lymph node metastasis (P < 0.005) and shorter relapse-free survival after surgery (P = 0.006). Thus, hBUB1 and hBUBR1 may contribute to a specific driving force in tumor metastasis and progression as a result of nonmutational, as well as mutational, inactivation.