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1.
World J Surg ; 38(8): 2145-52, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24668452

RESUMO

PURPOSE: Re-anastomosis after a Hartmann procedure is associated with a higher morbidity and mortality than other elective colorectal operations. The goal of this comparative study was to evaluate whether laparoscopic reversal is a justified operative approach, although the initial operation is most often an emergency laparotomy. METHODS: A retrospective analysis was conducted on data collected on all 70 patients who underwent laparoscopic and open reversal of a Hartmann procedure at the Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, between January 1999 and December 2011. Together with general demographic data, the analysis included the indication for the initial Hartmann procedure, time to reversal, intraoperative findings, the choice of operative method, operating time, postoperative pain control, return of normal bowel function, length of hospital stay, and peri- and postoperative morbidity and mortality. RESULTS: In most patients, the Hartmann procedure was performed after a perforated sigmoid diverticulitis. We were not able to find any statistically significant differences with respect to gender, body mass index (BMI) and American Society of Anesthesiologists classification between the laparoscopic group (LG) (N = 24 patients) and the open group (OG) (N = 46). In the LG, patients were significantly younger (p = 0.019). The median operating time was 210 min (75-245) in the LG, which was significantly longer than in the OG (166 min; 66-230). The statistical analysis of the duration of postoperative analgesic therapy (LG 7 days; OG 12 days), return to normal diet (LG 3 days; OG 4 days), return of normal bowel function (LG 3 days; OG 4 days) and length of hospital stay (LOS) (LG 10 days; OG 15 days) detected significant differences in advantage for the LG. Unplanned return to theatre during index admission was only necessary in the OG (N = 7, 15.2 %). With a median follow-up of 8 months (range 1-20), we observed a comparable number of minor complications in both groups but a significantly higher number of major complications in the OG (N = 27, 58.7%) (p = 0.001). Conversion occurred in three cases (12.5%). There was no mortality in either of the two groups. CONCLUSIONS: This study was able to demonstrate the feasibility of the laparoscopic approach. In terms of postoperative results it should be seen as equivalent to the open procedure. However, the laparoscopic approach requires profound surgical expertise. The indication should be made after a careful risk/benefit analysis for each individual patient.


Assuntos
Canal Anal/cirurgia , Colo/cirurgia , Doença Diverticular do Colo/cirurgia , Perfuração Intestinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/uso terapêutico , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Colostomia , Conversão para Cirurgia Aberta , Doença Diverticular do Colo/complicações , Ingestão de Alimentos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Perfuração Intestinal/etiologia , Laparoscopia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Recuperação de Função Fisiológica , Reoperação , Estudos Retrospectivos , Adulto Jovem
2.
Scand J Gastroenterol ; 48(6): 679-87, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23544594

RESUMO

INTRODUCTION: Aneuploidy has been suggested as independent prognostic marker in ulcerative colitis (UC) patients for developing UC-associated colorectal carcinomas (UCCs). UCCs are associated with a poorer prognosis and more frequently present with synchronous carcinomas when compared with sporadic colorectal carcinomas (SCCs). The authors therefore investigated if the adjacent non-malignant mucosa of aneuploid UCCs and aneuploid SCCs shows differences regarding the frequency of aneuploidy and if this aneuploidy is associated with histomorphological alterations. METHODS: Primary tumors of 25 UCCs and 20 SCCs were selected showing exclusively aneuploid DNA patterns and matching DNA stemlines. The UCCs' (n = 82) and SCCs' (n = 40) adjacent non-malignant mucosa were evaluated for histopathology and assessed for DNA ploidy status by image cytometry. RESULTS: UCCs' non-malignant mucosa showed dysplasia in 31.7% and aneuploidy in 89%. In contrast, SCCs' non-malignant mucosa revealed no dysplasia and aneuploidy in only 5%. Irrespective of dysplastic lesions, aneuploidy was observed more frequently in adjacent non-malignant mucosa of UCCs than of SCCs (p < 0.001). Neither a correlation between aneuploidy and inflammation (p = 0.916) nor between aneuploidy and dysplastic lesions (p = 0.159) could be observed. CONCLUSION: Aneuploidy is more frequent in adjacent non-malignant mucosa of aneuploid UCCs than in adjacent non-malignant mucosa of aneuploid SCCs. Furthermore, aneuploidy seems to be irrespective of inflammation or dysplasia. The results therefore emphasize the importance of aneuploidy for UC-associated carcinogenesis and its potential as new diagnostic target.


Assuntos
Aneuploidia , Carcinoma/genética , Colite Ulcerativa/genética , Neoplasias Colorretais/genética , Mucosa Intestinal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Colite Ulcerativa/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade
3.
Acta Chir Iugosl ; 59(1): 31-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22924300

RESUMO

BACKGROUND: Colorectal cancer is one of the most common forms of cancer in the Western world. A wide variety of prognostic factors for colorectal cancer have been identified. There is, however, a paucity of literature addressing the influence of multiple primary carcinomas on prognosis. We conducted the present study in order to investigate the influence of second or multiple primary tumours on the prognosis of colorectal cancer patients. PATIENTS AND METHODS: From 1992 to 2005, 1500 patients underwent surgery for colorectal cancer at the University Hospital of Luebeck. Of these, 276 patients (19%) had multiple primary malignant tumours. We performed statistical analyses only on patients who underwent surgery with curative intent in order to minimise additional prognostic factors. The patients were divided into groups according to the time of multiple primary tumour occurrence. Data were analysed for various variables. RESULTS: We did not detect any significant differences in survival either between the various groups or between patients with and without multiple primary tumours. CONCLUSION: The presence of multiple primary carcinomas is not an independent prognostic factor in patients with an index tumour of the colorectum. Multiple primary tumours are thus not necessarily associated with a poorer outcome and patients should receive curative intent surgery and appropriate follow-up care.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/mortalidade , Segunda Neoplasia Primária/mortalidade , Prognóstico , Taxa de Sobrevida
4.
Langenbecks Arch Surg ; 397(1): 75-84, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21968828

RESUMO

PURPOSE: The current study was designed to identify prognostic factors for long-term survival in patients with advanced colorectal cancer in a consecutive cohort. METHODS: A total of 123 patients were operated because of T4 colorectal cancer between 1 January 2002 and 31 December 2008 in the Clinic of Surgery, UK-SH Campus Luebeck. RESULTS: A total of 78 patients underwent a multivisceral resection. The postoperative morbidity was elevated in the patient group with multivisceral resections (34.6% vs. 26.7%). Nevertheless, we detected no significant differences concerning 30 days mortality (7.7% vs. 8.9%; p = 0.815). The main prognostic factor that reached significance in the multivariate analysis was the possibility to obtain a R0 resection (p < 0.0001) resulting in a 5-year survival rate of 55% for patients with curative resection. There were no statistically significant differences in 5-year survival between multivisceral and non-multivisceral resections (p = 0.608). Also we were not able to detect any significant differences for cancer of colonic or rectal origin (p = 0.839), for laparoscopic vs. open procedures (p = 0.610), and for emergency vs. planned operations (p = 0.674). Moreover, the existence of lymph node metastases was not a predictive factor concerning survival as there was no difference between patients with and without lymph node metastases (p = 0.658). CONCLUSIONS: Multivisceral resections are associated with the same 5-year survival as standard resections. Therefore, the aim to perform a R0 resection should always be the main goal in surgery for colorectal cancer. In planned operations, a laparoscopic approach is justified in selected patients.


Assuntos
Neoplasias Colorretais/cirurgia , Vísceras/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Humanos , Laparoscopia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Complicações Pós-Operatórias , Prognóstico , Taxa de Sobrevida
5.
J Biomol Screen ; 16(9): 1018-26, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21807963

RESUMO

Development and progression of colon cancer may be related to cytokines. Cytokines with diagnostic value have been identified individually but have not been implemented into clinical praxis. Using a multiplex protein array, the authors explore a panel of cytokines simultaneously and compared its performance to carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). Serum concentrations of 12 cytokines were simultaneously determined by multiplex biochip technology in 50 colon cancer patients and 50 healthy controls. Serum levels of interleukin-8 (IL-8) and CEA were significantly higher in cancer patients than in healthy controls. Areas under the receiver operating characteristic curves (AUCs) were largest for IL-8, followed by CEA, vascular endothelial growth factor (VEGF), and CA 19-9. Analyses regarding marker combinations showed an advantage over single marker performance for CEA, VEGF, and CA 19-9 but not for IL-8. Multiplex biochip array technology represents a practical tool in cytokine and cancer research when simultaneous determination of different biomarkers is of interest. The results suggest that the assessment of IL-8, CEA, VEGF, and possibly CA 19-9 serum levels could be useful for colon cancer screening with the potential of also detecting early stage tumors. Further validation studies using these and additional markers on a multiplex array format are encouraged.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/diagnóstico , Ensaios de Triagem em Larga Escala/normas , Interleucina-8/sangue , Análise Serial de Proteínas , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sensibilidade e Especificidade
6.
JOP ; 12(4): 364-71, 2011 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-21737898

RESUMO

OBJECTIVE: Pain is the main symptom of chronic pancreatitis. However, in addition to an improvement in pain symptoms, an increase in the quality of life also influences therapeutic success. The present paper evaluates the influence of surgery on chronic pancreatitis, and the early and late postoperative quality of life. PATIENTS: From March 2000 until April 2005, 51 patients underwent surgical treatment for chronic pancreatitis at our institution. INTERVENTION: Thirty-nine (76.5%) patients were operated on according to the Frey procedure and, in 12 (23.5%) patients, a Whipple procedure was performed. STUDY DESIGN: Patient data were documented throughout the duration of the hospital stay. Postoperative follow-up data were recorded retrospectively. MAIN OUTCOME MEASURES: Postoperative follow-up with postoperative pain scores and quality of life were carried out using a standardized questionnaire. RESULTS: During a median follow-up period of 50 months, an improvement in pain scores was observed in 92.3% of the patients in the Frey group and in 66.7% in the Whipple group. The indices for global quality of life and for physical and emotional status increased in both surgical groups. CONCLUSION: For patients with chronic pancreatitis, the decisive factor is the quality of life, particularly concerning pain and metabolic changes. The Frey procedure seems to offer advantages with respect to long-term freedom of pain and low risk of surgery-induced pancreatic insufficiency.


Assuntos
Pancreatectomia/reabilitação , Pancreatite Crônica/cirurgia , Qualidade de Vida , Adulto , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pancreatectomia/métodos , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
7.
Langenbecks Arch Surg ; 396(6): 851-5, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21562864

RESUMO

INTRODUCTION: A variety of surgical strategies have been suggested and many surgical techniques, both abdominal and perineal, have been introduced for treatment of rectal prolapse. All these techniques and approaches are based on the attempt to restore the normal anatomy and physiologic function. METHODS: In 1992, Berman et al. published the first laparoscopically performed rectopexy. Meanwhile, many different minimally invasive procedures have been described. Throughout the past century, more than 100 different surgical techniques have been introduced to treat patients with rectal prolapse. Unfortunately, there is still lack of one generally accepted standard technique for the surgical treatment of rectal prolapse. RESULTS AND DISCUSSION: Our current data strongly supports laparoscopic resection rectopexy to be a safe, fast, and very effective procedure to improve function in patients with rectal prolapse. More evaluations of long-term outcome are needed that focus on each particular laparoscopic procedure to adequately compare different techniques. The indication to perform a laparoscopic resection rectopexy in patients with a previous perineal procedure and a recurrent prolapse should be stated critically because these patients seem to have a high risk to develop yet another recurrence.


Assuntos
Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Prolapso Retal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Complicações Pós-Operatórias , Recidiva , Inquéritos e Questionários , Resultado do Tratamento
8.
Arch Physiol Biochem ; 116(4-5): 188-96, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20615064

RESUMO

Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a widely used technology platform for diagnostic biomarker discovery in tissue, plasma and serum. High-throughput and simplicity of experimental procedures have allowed this technology to become an important research tool for biomarker discovery during the last years. This review provides an overview of SELDI-TOF functionality, its advantages and drawbacks and gives a current literature overview of colorectal cancer based serum biomarker detection. Further improvements in instrumentation sensitivity and labelling chemistries will enable detection of novel, tissue-leakage biomarkers in serum. However, major emphasis should be given on subsequent identification of differentially observed protein peaks detected by SELDI-TOF. Clinical validation in large patient cohorts will then allow transferring novel biomarkers into clinical use.


Assuntos
Biomarcadores , Proteínas Sanguíneas/análise , Neoplasias Colorretais/sangue , Proteínas de Neoplasias , Análise Serial de Proteínas/métodos , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Biomarcadores/sangue , Biomarcadores/química , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Humanos , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/metabolismo , Proteômica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Cases J ; 2: 8545, 2009 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-19830080

RESUMO

INTRODUCTION: Diaphragmatic ruptures are a rare condition with an incidence of about 0.8-5.8% after blunt thoracoabdominal trauma. Right sided ruptures accompanied by a displacement of intraabdominal organs are very uncommon and account for approximately 5-19% of all diaphragmatic ruptures. The majority of diaphragmatic ruptures are based on high speed motor vehicle accidents (MVA) and high falls. CASE PRESENTATION: Herein we report a case of a 58-year old woman after a high-speed MVA with a right-sided diaphragmatic rupture and displacement of the liver into the thorax, mimicking a pleural effusion. CONCLUSION: Due to the low incidence and frequently present masking injuries, diagnosis is difficult and virtually always delayed. Thus, a high index of suspicion is important in cases of blunt thoracoabdominal trauma, as the 24 h mortality-rate of a right sided diaphragmatic rupture is up to 30%. In these situations a spiral CT-scan is the diagnostic tool of choice. Surgical intervention using an abdominal approach via a hockey-stick shaped incision is necessary even for small tears. Part of the polytrauma management following high speed MVAs is a critical review of the radiologic imaging.

10.
Int J Colorectal Dis ; 24(7): 755-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19283390

RESUMO

BACKGROUND AND AIMS: Endoscopic polypectomy still remains the cornerstone of therapy for colorectal polyps and adenomas. However, if colorectal polyps are too large or not accessible for endoscopic ablation or cannot be removed without an increased risk for perforation, operative procedures are required. In such circumstances, laparoscopic resection represents a minimally invasive alternative. MATERIALS AND METHODS: Between January 1993 and December 2004, more than 2,500 endoscopic polypectomies were performed at the Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, Germany. In patients which could not be treated by endoscopic polypectomy due to size, location, and/or risk of complications, a laparoscopic colorectal resection was performed. All data were prospectively assessed in our "colorectal resection" database. RESULTS: The database analysis revealed 58 patients with endoscopically not resectable colorectal polyps who underwent a laparoscopic colorectal resection (intend to treat). In 54 patients, the operative procedure could be finished by the laparoscopic approach (study population). The conversion rate was 6.9% (four of 58). An ileocolic resection was performed in 20 patients (37.0%), and 14 patients (25.9%) underwent an anterior rectal resection. A right colectomy was necessary in 12 patients (22.2%), and six patients (11.1%) underwent a sigmoid resection. In the remaining two patients, a left colectomy and a resection of the transverse colon were performed. Intra- and postoperative complications occurred in five patients (9.3%). Perioperative mortality was not registered. The histopathological work-up revealed benign disease in all cases. CONCLUSION: Laparoscopic resection of colorectal polyps is a safe and minimally invasive technique for the management of benign colorectal tumors. Thus, the laparoscopic approach to endoscopically not resectable polyps enriches the therapeutic spectrum.


Assuntos
Pólipos do Colo/patologia , Pólipos do Colo/cirurgia , Cirurgia Colorretal , Endoscopia , Laparoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia
11.
J Gastrointest Surg ; 12(12): 2212-20, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18636299

RESUMO

BACKGROUND AND PURPOSE: To this day, the diagnostic and therapeutic strategy for acute lower gastrointestinal hemorrhage requiring transfusion varies among different hospitals. The purpose of this paper was to evaluate our own data on the group of patients presented and to outline our diagnostic and therapeutic regime taking into account the literature of the past 30 years. METHODS: Following prospective data collection on 63 patients of a university hospital (40 male, 23 female patients) who received surgical intervention for acute lower intestinal hemorrhage requiring transfusion, we retrospectively analyzed the data. After a medical history had been taken, all patients underwent clinical examination, including digital palpation; 62 patients underwent procto-rectoscopy, 38 gastroscopy and colonoscopy, 52 patients colonoscopy only, and 45 patients gastroscopy only. Angiography was applied in 14 cases and scintigraphy in 20 cases. RESULTS: Diagnostic procedures to localize hemorrhage were successful in 61 cases, 41 of which through endoscopy, 12 through angiography, and eight through scintigraphy. Of our group of patients, 32 suffered from a bleeding colonic diverticulum, eight from angiodysplasia, and five from bleeding small bowel diverticula. Five patients had inflammatory bowel disease and three neoplasia. Among the surgical interventions, segmental resections were performed most frequently (15 sigmoidectomies, 11 small bowel segmental resections, 11 left hemicolectomies, seven right hemicolectomies, one proctectomy). Subtotal colectomies were carried out in ten cases. The complication rate for this group of critically ill, negatively selected patients was 60.3% and the mortality rate was 15.9%. CONCLUSIONS: Examination and stabilization of the patient is directly followed by diagnostic localization. Today, we primarily rely on nonsurgical control of hemorrhage by endoscopy or angiography; the indication for surgery is mainly limited to peracute, uncontrollable, and recurrent forms. In the case of surgery, intestinal segmental resection is recommended after identification of the lesion; if the localization of colonic hemorrhage is uncertain, subtotal resection is the method of choice. For stable patients with unverifiable small-bowel hemorrhage we recommend regular re-evaluation.


Assuntos
Hemorragia Gastrointestinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Transfusão de Sangue , Colonoscopia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada de Emissão , Resultado do Tratamento
12.
Int J Colorectal Dis ; 23(4): 401-7, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18064473

RESUMO

BACKGROUND AND AIMS: Because of their low morbidity and mortality, limited resection or local excision are accepted therapeutical approaches in early colorectal cancer treatment. Even though, recent publications report recurrence rates after local excision of rectal cancer in up to 30%. This prompted us to evaluate our data for T1N0 colorectal cancer treated by radical surgery regarding recurrence, morbidity, mortality, and survival rates. MATERIALS AND METHODS: Clinical, histopathological, and surveillance data from our prospective "colorectal cancer database" from 1979 to 2005 were analyzed to evaluate outcome and prognosis of T1N0 colorectal cancer treated by radical surgery. Only curative resections were included in this study. All patients were followed in an internal surveillance program, which enabled us to prospectively assess morbidity, mortality, and survival. RESULTS A total of 105 T1N0 colon and 69 rectal carcinomas were included in the study. Overall morbidity was 25% (colon) and 34% (rectum). Thirty-day mortality was 1.9% (colon) and 4.3% (rectum). After a median follow-up of 92 and 87 month, no isolated local recurrence occurred. One patient developed both local recurrence and liver metastases. Distant metastases were seen in 4.9% (colon) and 7.5% (rectum). The 5- and 10-year overall survival was 86 and 71% (colon) and 82 and 68% (rectum), respectively. CONCLUSION: Even if radical surgical approaches are associated with a higher rate of morbidity and mortality, our data show that radical surgery for T1N0 colorectal cancer results in excellent tumor control which is of paramount importance for the patients' prognosis and survival. Combining the data presented with those of the current literature suggests that local approaches to rectal cancer can be recommended for highly selected T1N0 tumors, in palliative situations, or if the patient is unfit for general surgery.


Assuntos
Colectomia/métodos , Neoplasias Colorretais/cirurgia , Idoso , Biópsia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Tomada de Decisões , Progressão da Doença , Endossonografia , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Masculino , Morbidade/tendências , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Tomografia Computadorizada por Raios X
13.
Proc Natl Acad Sci U S A ; 104(13): 5401-6, 2007 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-17372198

RESUMO

p53 triggers cell cycle arrest and apoptosis through transcriptional regulation of specific target genes. We have investigated the effect of p53 activation on the proteome using 2D gel electrophoresis analysis of mitomycin C-treated HCT116 colon carcinoma cells carrying wild-type p53. Approximately 5,800 protein spots were separated in overlapping narrow-pH-range gel strips, and 115 protein spots showed significant expression changes upon p53 activation. The identity of 55 protein spots was obtained by mass spectrometry. The majority of the identified proteins have no previous connection to p53. The proteins fall into different functional categories, such as mRNA processing, translation, redox regulation, and apoptosis, consistent with the idea that p53 regulates multiple cellular pathways. p53-dependent regulation of five of the up-regulated proteins, eIF5A, hnRNP C1/C2, hnRNP K, lamin A/C, and Nm23-H1, and two of the down-regulated proteins, Prx II and TrpRS, was examined in further detail. Analysis of mRNA expression levels demonstrated both transcription-dependent and transcription-independent regulation among the identified targets. Thus, this study reveals protein targets of p53 and highlights the role of transcription-independent effects for the p53-induced biological response.


Assuntos
Apoptose , Perfilação da Expressão Gênica , Proteína Supressora de Tumor p53/biossíntese , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Eletroforese em Gel Bidimensional , Humanos , Concentração de Íons de Hidrogênio , Espectrometria de Massas , Mitomicina/farmacologia , Metástase Neoplásica , Neoplasias/metabolismo , Oxirredução , Regiões Promotoras Genéticas , Proteômica/métodos , Proteína Supressora de Tumor p53/química
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