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Purpose: Colorectal cancer (CRC) is a common human cancer along with higher incidence and mortality, and this study aimed to identify the effect of cincumol on CRC and its potential mechanisms. Methods: CRC cell line HCT116 was used as the material. Cell proliferation was evaluated by CCK-8 assay, and cell migration was detected by scratch test and Transwell assay. TUNEL staining assay was used to evaluate cell apoptosis. The expression of target genes was detected by qualitative real-time polymerase chain reaction and western blot assays. Results: Cincumol significantly reduced the proliferative and migratory rate and enhanced apoptotic rate of HCT116 cells. Meanwhile, the elevated levels of RBUsuh, Nicd and Tace was also observed in cincumol-treated HCT116 cells. Moreover, our findings revealed that additional cincumol inhibited the expression of p-PI3K and p-AKT, suggesting the inhibition of PI3K/AKT signaling might be involved in the protective role of cincumol on the malignant phenotypes of CRC cells in vitro. Conclusions: Cincumol inhibited the malignant phenotypes of CRC cells in vitro through inactivating PI3K/AKT signaling, suggesting that cincumol might be a potential anti-CRC agent.
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Humanos , Técnicas In Vitro , Neoplasias Colorretais/prevenção & controle , Apoptose , Fosfatidilinositol 3-QuinasesResumo
Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.(AU)
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Animais , Osso e Ossos , Técnicas In Vitro , Neoplasias Colorretais , Metástase NeoplásicaResumo
Abstract Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.
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Purpose To evaluate the gene expression of peroxisome proliferator activated receptors gamma (PPARG) in colorectal tumors and to correlate this data with clinical variables of the patients. Methods We analyzed the gene expression of PPARG in 50 samples of colorectal tumors using real-time reverse transcription polymerase chain reaction, and 20 adjacent normal tissue samples as control. The results of these quantifications were correlated with the respective patients medical records clinical information. Results PPARG expression was not different in the tumor tissue compared to the control tissue. Patients older than 60 years, histological type with mucinous differentiation, more advanced staging at the time of diagnosis, and patients who evolved with recurrence of the disease or death did not present higher PPARG expression. Conclusion Expression of PPARGD was not associated with worse prognosis.(AU)
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Humanos , Masculino , Feminino , Adenocarcinoma , Neoplasias Colorretais/genética , Biomarcadores Tumorais , Prognóstico , PPAR gama , Tratamento FarmacológicoResumo
Purpose: To analyze gene and protein expression of metalloproteinases 1, 2, 9, 11 and 16 and their correlation with clinicopathological variables in colorectal adenocarcinoma. Methods: A retrospective study of 114 patients with colorectal adenocarcinoma treated surgically in the period 2006 to 2008 in Hospital de Câncer de Barretos - Fundação Pio XII. The evaluation of gene expression was performed by RT-PCR, and protein by immunohistochemistry. The analysis of gene expression was classified as overexpressed genes and poorly expressed (fold change of approximately 2, p 0.05). The positivity of the markers in the immunohistochemical study was performed by semi-quantitative analysis. The tissue of TMA (Tissue Microarray) was done by two independent pathologists. Results: The gene expression validated by immuno - histochemical was MMP-1(p= 0.00 and 1.57 fold change) and MMP 2 (p= 0.01 and 1.84 to fold change) when correlated with the histological types mucinous and adenocarcinoma NOS, MMP9 (p=0.01 and fold change of 1.13) and MMP-16 (p=0.03 and 1.61 fold change) when compared with the histological types villous and adenocarcinoma NOS, MMP - 11 statistically significant in relation to male (p = 0.04 and 1.65 fold change). Conclusions: The MMPs 1, 2, 9, 11 and 16 gene and protein expression with statistical significance in at least one of the clinicopathological variables studied. Thus, we conclude that these MMPs have potential as a prognostic factor in colorectal adenocarcinoma.(AU)
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Humanos , Masculino , Feminino , Neoplasias Colorretais/genética , Adenocarcinoma , Metaloproteases , Matriz ExtracelularResumo
Purpose: The benefits of laparoscopic approaches to treat colorectal cancer (CRC) and colorectal liver metastases (CRLM) separately are well established. However, there is no consensus about the optimal timing to approach the primary tumor and CRLM, whether simultaneously or staged. The objective of this review with practical reports is to discuss technical aspects required for patient selection to perform simultaneous laparoscopic approaches for CRC and CRLM. Methods: Literature review of oncological factors associated with patient selection for surgical treatment of CRLM and the use of laparoscopy in those cases, and report of technical aspects for simultaneous CRC and CRLM approaches. Results: Simultaneous laparoscopic resection has been successful in many series of selected patients, although it seems to be safer to perform minor and major liver resection with non-extended colorectal resections, and to avoid two high-risk procedures at the same time. Conclusions: Simultaneous CRC and CRLM resections seem to be safe when patients are carefully selected, also considering the risk of recurrence concerning oncologic outcomes. The pre-planning of simultaneous resection is mandatory to plan trocar positioning, procedure sequencing, and patient position.(AU)
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Humanos , Laparoscopia , Tomada de Decisões , Neoplasias Colorretais , Metástase Neoplásica , Neoplasias HepáticasResumo
Purpose:To evaluate red propolis, gum arabic and L-lysine activity on colorectal preneoplastic lesions induced by azoxymethane (AOM).Methods:The study featured 4 control groups (I-IV) and 4 experimental groups (V-VIII), totaling 48 rats. Once a week for 2 weeks, animals on control groups received saline, while animals in experimental groups received azoxymethane (15 mg/kg i.p.). The follow up along 16 weeks included daily oral gavage to administer water (I and V), L-lysine (150 mg/kg)(II and VI), própolis (100mg/5ml/kg)(III and VII), or gum arabic (5ml/kg)(IV and VIII). Was performed surgery on the animals in the end of this time in order to collect blood for biological assays (TBARS, GSH), followed by their sacrifice to tissue extract.Results:Oxidative stress (TBARS) and the number of aberrant crypt foci (ACF) in distal colon were lower using própolis (p<0.01 for both parameters). Gum arabic reduced preneoplastic lesions (ACF ≤ 4 crypts) on distal colon and on the entire colon (p<0.05).Conclusions:Red propolis reduced AOM-induced oxidative stress (TBARS) and total number of ACF in the distal colon. L-lysine neither protected against nor enhanced AOM-induced ACF. Gum arabic reduced the number of ACF.(AU)
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Animais , Ratos , Goma Arábica , Própole/uso terapêutico , Colo/lesões , Azoximetano , Lisina , Neoplasias ColorretaisResumo
PURPOSE: To assess weight changes in rats fed diets with different ratios of omegas 3, 6 and 9 submitted to colonic carcinogenesis induced by Azoxymethane (AOM). METHODS: Sixty rats with three weeks of life were distributed into five groups of specific diets containing 12 animals each: GI- Standard diet without adminstration of AOM, GII- Standard diet with adminstration of AOM; GIII- Hyperlipidic diet with adminstration of AOM; GIV-Normolipidic diet with adminstration of AOM; GV- Hypolipidic diet with adminstration of AOM. The weight and food intake of each group were assessed four times in each week throughout the experiment until euthanasia at 36th week. RESULTS: GI and GII had no significant difference in weight. GI showed a significant increase when compared to GIII, GIV and GV. GII also showed a significant increase when compared to GIII, GIV and GV. When comparing intake of GI as compared to GII no significant difference was found, however such groups had higher intake than groups III, IV and V. There were found no difference in weight when comparing amoung rats with and without cancer within each groups: GII, GIII, GIV and GV. CONCLUSIONS: Diets rich in omega 3, 6 and 9 reduced food intake and weight. Rats with colorectal cancer had no decrease in weight as compared to those without this condition in the same group.(AU)
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Animais , Ratos , Dieta , Neoplasias/patologia , Azoximetano/análise , Ratos/classificação , Gorduras/análiseResumo
PURPOSE: To investigate the hemopreventive effect of defatted flaxseed meal in C57BL/6 mice after induction of precancerous colon lesions with 1.2-dimethylhydrazine (DMH). METHODS: Thirty-six 12-week-old C57BL/6 mice were divided into three treatment groups(n=12 in each group): (1) diet with 10% defatted flaxseed meal; (2) diet with defatted flaxseed meal and precancerous colon lesions induced by DMH; and (3) precancerous colon lesions induced by DMH, without defatted flaxseed meal. The incidence of aberrant crypt foci (ACF), oxidative processes, expression of tumor suppressor proteins and cyclins, as well as the profile of short-chain fatty acids (SCFA) in animal feces were investigated in the presence and absence of DMH. RESULTS: The rats consuming defatted flaxseed meals showed lesions with lower multiplicity and a reduced incidence of lesions. No changes in the expression of tumor suppressor proteins and those involved in cell cycle control were detected. CONCLUSION: Defatted flaxseed meal protected the distal colon of mice from precancerous lesions.(AU)
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Animais , Camundongos , Colo/anatomia & histologia , Ferimentos e Lesões , Neoplasias/patologia , Linho/metabolismo , Camundongos/classificação , DietaResumo
PURPOSE:To investigate the impact of cafeteria diet on ghrelin expression in rectal tissue and identify the morphologic cell type. METHODS:Twenty-four male Wistar rats were divided into four subgroups of six animals each: RC1 (rat chow 1) and CAF1 (cafeteria diet 1) for a period of 30 days; RC2 (rat chow 2) and CAF2 (cafeteria diet 2) for a period of 60 days. The animal and rectal weight, the number and the type of immunoreactive ghrelin cells were recorded and compared between the subgroups. The statistical study was established by ANOVA and Student's t test. RESULTS:There was no difference in the total of immunoreactive cells (p=0.685) between the subgroups nor between weight and presence or absence of ghrelin expression (p=0.993). All the immunoreactive cells identified were closed-type. CONCLUSION:The cafeteria diet did not have influence on the amount of immunoreactive rectal cells of ghrelin and only one type (closed-type) of immunoreactive cells was expressed in the rectum.(AU)
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Animais , Ratos , Imuno-Histoquímica/instrumentação , Grelina/análise , Obesidade/metabolismo , Neoplasias Retais/patologia , Ratos Wistar/classificação , Dieta/métodosResumo
PURPOSE: To determine whether a hypercaloric and hyperlipidic diet enriched with polyunsaturated fatty acids influences the formation of aberrant crypt foci (ACF) in colonic mucosa of Wistar rats treated with azoxymethane (AOM). METHODS: At eight weeks of life, the rats were assigned to four groups: Group I―standard diet (STD) not treated with AOM; Group II―hypercaloric and hyperlipidic diet (FED), not treated with AOM; Group III―STD, treated with AOM; Group IV―FED, treated with AOM. At 16 weeks, the animals were injected intraperitoneal with 0.9 percent saline solution (Group I and II) or AOM at 15mg/Kg (Groups III and IV) once a week for two weeks. Fifteen weeks later, the animals were euthanized. RESULTS: FED promoted weight gain in Groups II and IV compared to Groups I and III, respectively. The groups did not differ with regard to the total number of ACF. The Chi-square test revealed no predominance of the presence of foci with <4 crypts. However, foci with ≥5 crypts were proportionally more prevalent in Group III than in Group IV (p=0.043). CONCLUSION: The administration of polyunsaturated fatty acids did not interfere with the formation of aberrant crypt foci, but reduced ACF multiplicity, exercising an attenuating effect on carcinogenesis.(AU)
OBJETIVO: Determinar se uma dieta hipercalórica, hiperlipídica, rica em ácidos graxos poliinsaturados (FED) tem influência na formação de focos de cripta aberrante (FCA) em mucosa cólica de ratos Wistar expostos ao azoximetano (AOM). MÉTODOS: Com oito semanas de vida, os ratos foram distribuídos em quatro grupos: Grupo I: Dieta padrão (SD) sem AOM; Grupo II: FED, sem AOM; Grupo III: SD, com AOM; Grupo IV: FED com AOM. Com 16 semanas, os animais dos grupos I e II receberam injeções intraperitoneais de solução salina 0,9 por cento, enquanto os dos grupos III e IV receberam AOM na dose de 15mg/Kg de peso, 1 vez por semana por duas semanas. Quinze semanas após, os animais foram mortos. RESULTADOS: FED promoveu aumento de peso nos grupos II e IV em relação aos grupos I e III. Não houve aumento significante no número total de FCA entre os grupos. Em relação à multiplicidade das criptas por FCA, o teste do qui-quadrado mostrou que não houve predominância da presença <4 criptas por foco. Contudo, focos ≥5 criptas foram proporcionalmente mais prevalentes no grupo III que no grupo IV (p=0,043). CONCLUSÃO: Os ácidos graxos poliinsaturados não interferem na formação de focos de cripta aberrante, contudo reduz sua multiplicidade, exercendo efeito atenuador na carcinogênese.(AU)
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Ratos , Dieta , Gorduras na Dieta , Neoplasias/patologia , Ácidos Graxos Ômega-3 , Ácidos Graxos Ômega-6Resumo
PURPOSE: The present a novel adenocarcinoma model in athymic mice. METHODS: Seven athymic mice were used. Colon diversion and distal fistula were made. Adenocarcinoma cells were inoculated in the submucosa of fistula. Tumor growth was monitored daily. Scintigraphy with 99mTc-MIBI was performed to identify the tumor. RESULTS: The model of distal colon cancer is feasible. Tumor detection was possible by both, macroscopically and molecular imaging. All resections demonstrated poorly differentiated tumors. Colon obstruction occurred in one case, similarly to evolution in human tumors of distal colon. CONCLUSION: The proposed model of distal colon cancer is feasible, allows for easy monitoring of tumoral growth by both, macroscopically and molecular imaging, and is suitable for studying the evolution of tumor with implementation of cytotoxic therapy in vivo.(AU)
OBJETIVO: Apresentar novo modelo de adenocarcinoma distal em camundongos atímicos. MÉTODOS: Foram utilizados sete camundongos atímicos. Desvio do cólon distal e fístula foram feitas. Células de adenocarcinoma foram inoculadas na submucosa da fístula. O crescimento do tumor foi monitorado diariamente. Cintilografia com 99mTc-MIBI foi realizada para identificar o tumor. RESULTADOS: O modelo de câncer de cólon distal é viável. Detecção do tumor foi possível macroscopicamente e por imagem molecular. Todas as ressecções demonstraram tumores pouco diferenciados. Obstrução do cólon ocorreu em um caso, de forma semelhante à evolução em tumores humanos do cólon distal. CONCLUSÃO: O modelo de câncer do cólon distal proposto é viável, permite a monitorização fácil do crescimento tumoral macroscopicamente e por imagem molecular, sendo adequado para o estudo da evolução de tumor com aplicação de terapia citotóxica in vivo.(AU)
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Animais , Neoplasias do Colo/patologia , Camundongos Nus/classificação , FístulaResumo
PURPOSE: To study the antitumor action of Tabebuia avellanedae in experimentally induced colon carcinogenesis by azoxymethane in mice. METHODS: Fifty (n=50) mice were divided into five groups: in group I azoxymethane (AOM) was administered, in Group II - β-lapachone, in group III - vehicle (diluent) and in group IV - vehicle + AOM and finally in group V - β-lapachone + AOM. RESULTS: It was observed the presence of aberrant crypt foci in all animals of groups I and IV, 50 percent in group II and 90 percent in group V. CONCLUSION: The β-lapachone extracted from the Tabebuia avellanedae showed no protective effect of lesions induced by azoxymethane in colon of mice.(AU)
OBJETIVO: Estudar a ação antitumoral da Tabebuia avellanedae (Ipê-Roxo) na carcinogênese colônica induzida experimentalmente pelo azoximetano em camundongos. MÉTODOS: Foram utilizados 50 camundongos divididos em 5 grupos: grupo I administrado Azoximetano (AOM); grupo II - β-lapachona; grupo III - veículo (diluente); grupo IV - veículo + AOM; e grupo V - β-lapachona + AOM. RESULTADOS: Observou-se presença de focos de criptas aberrantes em todos os animais dos grupos I e IV, 50 por cento no grupo II e 90 por cento no grupo V. CONCLUSÃO: A β-lapachona extraída da Tabebuia avellanedae não apresentou efeito protetor das lesões induzidas pelo azoximetano em cólon de camundongos.(AU)
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Animais , Camundongos/classificação , Antineoplásicos/análise , Tabebuia/classificação , Azoximetano/químicaResumo
Purpose: Test immersion of microscopy samples in water as an aid to visualizing and quantifying aberrant crypt foci (ACF) in rat colon mucosa. Methods: Carcinogenesis was induced with azoxymethane in Wistar rats kept on a conventional diet or a hypercaloric diet containing unsaturated fat. Fifteen weeks after induction, colon samples were retrieved and fixated in a 10 percent formaldehyde solution. The samples were divided into segments (distal, middle, proximal) and stained with 1 percent toluidine blue. The technique tested in the study consisted of immersing microscopy samples in distilled water in order to eliminate the problem of light reflection known from conventional microscopy. Results: When samples were immersed in water during microscopy, significantly more ACF could be visualized in all colon segments than with the conventional method proposed by Bird. Conclusion: Immersing microscopy samples in water aids the visualization and quantification of aberrant crypt foci in rat colon mucosa fixed in formaldehyde.(AU)
Objetivo: Otimizar a visibilização de focos de criptas aberrantes (FCA) em mucosa cólica de ratos Wistar. Métodos: Colo de rato Wistar, sob diferentes dietas e submetidos a iniciação de carcinogênese pelo azoximetano há 4 meses, foram previamente lavados, abertos e fixados em solução de formalina a 10 por cento por 24 horas. Após serem corados em azul de toluidina a 1 por cento, foram divididos em segmentos distal, médio e proximal e imersos em água destilada para quantificação de FCA. Resultados: No método de imersão foi visibilizado maior quantidade de focos de criptas aberrantes em todos os segmentos cólicos, com diferença significante, quando comparado com o método de Bird. Conclusão: O método de imersão otimiza a visibilização e quantificação de focos de criptas aberrantes em mucosa cólica (ratos Wistar) fixada em solução de formalina a 10 por cento.(AU)
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Ratos , Microscopia/métodos , Mucosa Intestinal/anatomia & histologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/induzido quimicamente , Azoximetano , RatosResumo
PURPOSE: To analyze the expression of metalloproteinase-1, metalloproteinase-7 and vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma, and to correlate these with the clinical-pathological prognostic factors. METHODS: Tumor tissue from 82 patients was fixed in formalin and embedded in paraffin blocks. These samples were analyzed by means of the streptavidin-biotin immunohistochemical method, using the tissue microarray technique. Marker positivity was evaluated using categorical scores that determined cutoff percentages of stained tumor cells. Protein tissue expression was correlated with the variables of degree of cell differentiation, staging, disease-free interval, recurrence, survival and specific mortality. The Fisher exact and Kaplan-Meier tests were used to assess associations between the markers and the study variables. The log-rank and Wilcoxon tests were used to assess the significance of differences between curves of disease-free interval and survival. RESULTS: All tumors were positive for metalloproteinase-1; 50 (61 percent) were positive and 32 (39 percent) were negative for metalloproteinase-7; and 60 (74.1 percent) were positive and 21 (25.9 percent) were negative for VEGF. Correlation of marker expression, both in groups and individually, did not show statistical significance in relation to the degree of cell differentiation, staging, disease-free interval, survival or specific mortality. Recurrence showed a statistically significant correlation with positive expression of the three markers, when analyzed as a group (p = 0.038). CONCLUSION: The associated expression of metalloproteinase-1, metalloproteinase-7 and VEGF in colorectal adenocarcinoma is related to the incidence of disease recurrence.(AU)
OBJETIVO: Analisar as expressões da metaloproteinase-1, metaloproteinase-7 e do fator de crescimento endotelial vascular no adenocarcinoma colorretal e correlacionar com os fatores prognósticos clínico-patológicos. MÉTODOS: Foram analisados tecidos fixados em formol e dispostos em blocos de parafina dos tumores de 82 pacientes, por imunohistoquímica, pelo método da estreptavidina-biotina, usando-se a técnica de arranjo em matriz de amostras teciduais (tissue microarray). Na avaliação da positividade dos marcadores foi utilizado um escore categórico, que predeterminou o valor de corte na percentagem de células coradas do tumor. As expressões teciduais das proteínas foram correlacionadas com as varáveis representadas pelo grau de diferenciação celular, estadiamento, tempo livre de doença, recidiva, sobrevida e mortalidade específica. Foram empregados os testes exato de Fisher e de Kaplan-Meier para verificar as associações dos marcadores com as varáveis estudadas. Para testar a significância das diferenças entre as curvas do tempo livre de doença e da sobrevida foram utilizados os testes de longrank e Wilcoxon. RESULTADOS: A metaloproteinase-1 foi positiva em todos os tumores. A metaloproteinase-7 foi positiva em 50 (61 por cento) e negativa em 32 (39 por cento) tumores. O fator de crescimento endotelial vascular foi positivo em 60 (74,1 por cento) e negativo em 21 (25,9 por cento) tumores. A correlação das expressões dos marcadores realizada separadamente e em conjunto não apresentou significância estatística com o grau de diferenciação celular, estadiamento, tempo livre de doença, sobrevida e mortalidade específica. A recidiva apresentou correlação estatística significante com a expressão positiva dos três marcadores, quando foram analisados em conjunto (p = 0,038). CONCLUSÃO: As expressões associadas da metaloproteinase-1, metaloproteinase-7 e do fator de crescimento endotelial vascular no adenocarcinoma colorretal se relacionam com ...(AU)
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Humanos , Imuno-Histoquímica , Adenocarcinoma , Neoplasias Colorretais , Biomarcadores TumoraisResumo
PURPOSE: To analyze the correlation between p53 and bcl-2 expression and colorectal adenocarcinoma staging and prognosis. METHODS: This was a retrospective series of 125 colorectal adenocarcinoma patients (67 women and 58 men; ages 30-87 years) who underwent surgery with curative intent. The mean follow-up was 28.5 months (range: 2-96 months). TNM staging, tumor recurrence, survival and cancer-related mortality were analyzed. Immunoreactivity was evaluated using DO7 (Dako) for p53 and K492 (Dako) for bcl-2. Tumors with accumulation of staining for cytoplasmic bcl-2 or nuclear p53 in more than 10% of cells were considered positive. Statistical analysis utilized Pearson chi-squared, log-rank and Wilcoxon tests, and Kaplan-Meier survival estimation (significance level: p 0.05). RESULTS: p53+ was found in 11.8% (14/118), bcl-2+ in 50% (58/116) and associated p53+/bcl-2+ in 6.4% (7/109) of the tumors. There was no significant correlation between expression of these biomarkers and TNM I, II, III and IV staging (p=0.385 for p53; p=0.461 for bcl-2). For tumor recurrence, p53+ was found in 9.5% (2/21), bcl-2+ in 50% (11/22), and associated p53+/bcl-2+ in 5.2% (1/19) of the tumors (p=0.714, p=1.000 and p=0.960, respectively). For survival analysis, p53+: 57 months (45.0-68.0), bcl-2+: 78 (37.0-89.0), and p53+/bcl-2+: 62 (56.0-68.0) (p=0.319). For cancer-related mortality, p53+: 8.3% (3/36), bcl-2+: 47.2% (17/36), and p53+/bcl-2+: 5.9% (2/36) of the patients (p=0.432, p=0.688 and p=0.907, respectively). CONCLUSION: No correlation was found between tumor expression of p53 and bcl-2 and the TNM staging, recurrence, survival and cancer-related mortality in colorectal adenocarcinoma.
OBJETIVO: Analisar a correlação entre a expressão da p53 e do bcl-2 com o estadiamento e prognóstico do adenocarcinoma colorretal. MÉTODOS: Foi realizado o estudo de uma série retrospectiva de 125 doentes com adenocarcinoma colorretal (67 mulheres e 58 homens; 30 a 87 anos de idade), que se submeteram ao tratamento cirúrgico com intenção curativa. O tempo médio de seguimento foi de 28,5 meses (variação de 2 a 96 meses). O estadiamento TNM, a recidiva tumoral, a sobrevida e a mortalidade relacionada com o câncer foram analisados. A reação imunohistoquímica utilizada foi o DO& (Dako) para o p53 e o K492 (Dako) para o bcl-2. Tumores com intensidade de coloração citoplásmica para o bcl-2 e nuclear para o p53, acima de 10% de células foram considerados positivos. A análise estatística utilizada foi o teste qui-quadrado de Pearson, log-rank, Wilcoxon e estimativa de sobrevida de Kaplan-Meier (nível de significância : p 0,05). RESULTADOS: p53+ foi encontrado em 11.8% (14/118), bcl-2+ em 50% (58/116) e associados p53+/bcl-2+ em 6.4% (7/109) dos tumores. Não foi encontrado correlação significante entre a expressão tumoral destes marcadores e o estadiamento TNM I, II, III e IV (p=0.385 para a p53; p=0.461 para o bcl-2). Na recidiva tumoral, p53+ foi encontrado em 9.5% (2/21), bcl-2+ em 50% (11/22), e p53+/bcl-2+ associados em 5.2% (1/19) dos tumores (p=0.714, p=1.000 e p=0.960, respectivamente). Na análise de sobrevida, p53+: 57 meses (45.0-68.0), bcl-2+: 78 (37.0-89.0), e p53+/bcl-2+: 62 (56.0-68.0) (p=0.319). Para mortalidade relacionada com câncer, p53+: 8.3% (3/36), bcl-2+: 47.2% (17/36), e p53+/bcl-2+: 5.9% (2/36) dos pacientes (p=0.432, p=0.688 and p=0.907, respectivamente). CONCLUSÃO: Nenhuma correlação significante foi encontrada entre a expressão tumoral da p53 e do bcl-2 com o estadiamento TNM, recidiva, sobrevida e mortalidade relacionada com câncer.
Resumo
PURPOSE: Carcinoembryonic antigen (CEA) determination in gallbladder bile was used in a prospective study concerning the morphological and clinical features of the neoplasm and the occurrence of hepatic metastasis. METHODS: CEA levels in the gallbladder and peripheral blood were studied in 44 patients with colorectal carcinoma and 10 patients with uncomplicated cholelithiasis from samples collected immediately before extirpating the colorectal neoplasms or cholecystectomy (values of up to 5 ng/ml were considered normal). RESULTS: In the 44 patients with colorectal carcinoma who underwent operation with curative intent, the average level of serum CEA was 8.5 ng/ml and for bile CEA, 74.5 ng/ml. In the patients with uncomplicated cholelithiasis who underwent cholecystectomy, the average level of serum CEA was 1.9 ng/ml and for bile CEA, 1.2 ng/ml. Four patients who underwent extirpation of the colorectal carcinoma without evidence of hepatic metastasis and with an average bile CEA value of 213.2 ng/ml presented hepatic metastasis between three and seventeen months after removal of the neoplasms. CONCLUSION: The high CEA levels in gallbladders of patients undergoing curative operation for colorectal carcinoma may indicate the presence of hepatic metastasis. Such patients must be followed up with special attention to the diagnosis of such lesions.
OBJETIVO: Analisar, prospectivamente, os resultados da determinação do antígeno carcinoembriário (CEA) na bile vesicular, relacionando-os com os aspectos morfológicos e clínicos da neoplasia e recidiva hepática. MÉTODOS: Os níveis do CEA foram estudados na bile vesicular e no sangue periférico de 44 doentes com carcinoma colorretal e 10 com colelitíase não complicada, a partir de amostras do CEA colhidas imediatamente antes da extirpação da neoplasia colo-retal e da colecistectomia (considerou-se valor normal até 5 ng/ml). RESULTADOS: Os 44 carcinomas colorretais extirpados com intenção curativa tiveram nível médio do CEA sérico de 8,5 ng/ml e CEA biliar, 74,5 ng/ml. Nas colelitíases não complicadas submetidas a colecistectomia, o nível médio do CEA sérico foi de 1,9 ng/ml e CEA biliar, 1,2 ng/ml. Quatro doentes submetidos à extirpação do carcinoma colo-retal, sem evidências de metástases hepáticas e com valor médio de CEA biliar de 213,2 ng/ml apresentaram metástases hepáticas entre três a 17 meses após a extirpação. CONCLUSÃO: o nível elevado de CEA biliar dos operados por carcinoma colo-retal pode indicar presença de metástases hepáticas e esses enfermos devem ser acompanhados com especial atenção para diagnosticar essas lesões.
Resumo
PURPOSE: Carcinoembryonic antigen (CEA) determination in gallbladder bile was used in a prospective study concerning the morphological and clinical features of the neoplasm and the occurrence of hepatic metastasis. METHODS: CEA levels in the gallbladder and peripheral blood were studied in 44 patients with colorectal carcinoma and 10 patients with uncomplicated cholelithiasis from samples collected immediately before extirpating the colorectal neoplasms or cholecystectomy (values of up to 5 ng/ml were considered normal). RESULTS: In the 44 patients with colorectal carcinoma who underwent operation with curative intent, the average level of serum CEA was 8.5 ng/ml and for bile CEA, 74.5 ng/ml. In the patients with uncomplicated cholelithiasis who underwent cholecystectomy, the average level of serum CEA was 1.9 ng/ml and for bile CEA, 1.2 ng/ml. Four patients who underwent extirpation of the colorectal carcinoma without evidence of hepatic metastasis and with an average bile CEA value of 213.2 ng/ml presented hepatic metastasis between three and seventeen months after removal of the neoplasms. CONCLUSION: The high CEA levels in gallbladders of patients undergoing curative operation for colorectal carcinoma may indicate the presence of hepatic metastasis. Such patients must be followed up with special attention to the diagnosis of such lesions.
OBJETIVO: Analisar, prospectivamente, os resultados da determinação do antígeno carcinoembriário (CEA) na bile vesicular, relacionando-os com os aspectos morfológicos e clínicos da neoplasia e recidiva hepática. MÉTODOS: Os níveis do CEA foram estudados na bile vesicular e no sangue periférico de 44 doentes com carcinoma colorretal e 10 com colelitíase não complicada, a partir de amostras do CEA colhidas imediatamente antes da extirpação da neoplasia colo-retal e da colecistectomia (considerou-se valor normal até 5 ng/ml). RESULTADOS: Os 44 carcinomas colorretais extirpados com intenção curativa tiveram nível médio do CEA sérico de 8,5 ng/ml e CEA biliar, 74,5 ng/ml. Nas colelitíases não complicadas submetidas a colecistectomia, o nível médio do CEA sérico foi de 1,9 ng/ml e CEA biliar, 1,2 ng/ml. Quatro doentes submetidos à extirpação do carcinoma colo-retal, sem evidências de metástases hepáticas e com valor médio de CEA biliar de 213,2 ng/ml apresentaram metástases hepáticas entre três a 17 meses após a extirpação. CONCLUSÃO: o nível elevado de CEA biliar dos operados por carcinoma colo-retal pode indicar presença de metástases hepáticas e esses enfermos devem ser acompanhados com especial atenção para diagnosticar essas lesões.