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1.
Oncol Lett ; 14(3): 3755-3759, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28927143

RESUMO

Early superficial non-ampullary duodenal tumors are particularly rare, the clinical manifestations, including typical endoscopic or imaging features, and treatment methods are not well-characterized. The present case report describes a case of an asymptomatic 74-year-old male who presented to the Taizhou People's Hospital (Taizhou, China) for a regular health screening, where a primary superficial non-ampullary duodenal tumor was identified. Upper endoscopy revealed ~1.2 cm lesion in the second portion of the duodenum. Chromoscopy and magnification endoscopy indicated an early cancer characteristic. Subsequent endoscopic submucosal dissection was performed to remove the lesion. Histopathology validated that the lesion was a high-grade intro-epithelial neoplasm without lymph node or blood vessel invasion.

2.
Int J Clin Exp Pathol ; 10(8): 8686-8694, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966726

RESUMO

Cancer-related systemic inflammation affects many aspects of malignancy. The platelet-to-lymphocyte ratio (PLR), an easily applicable inflammatory marker based on platelet and lymphocyte counts, is associated with the clinical outcome of some cancers. The present study aimed to investigate the prognostic significance of the preoperative PLR in a cohort of colorectal cancer (CRC) patients. A total of 138 patients with CRC were enrolled in this retrospective study. The optimal cutoff value for the PLR was calculated using receiver operating curve (ROC) analysis. The correlation of PLR with the clinicopathological characteristics of patients was explored. Cox proportional hazard analysis was applied to determine the independent prognostic effect of PLR. PLR of 248 yielded the most optimal predictive value for the prognosis of CRC [area under the curve (AUC) = 0.820]. High level of PLR was significantly associated with lymph node and distance metastasis (P<0.001 and = 0.003, respectively), vascular and perinural invasion (P<0.001), advanced TNM stage (P<0.001), and poor differentiation (P = 0.037). Furthermore, the univariable analysis showed a significant impact of increased PLR on OS (HR = 4.326, 95% CI: 2.903-6.445, P<0.001), while this association remained significant in multivariable analysis (adjusted HR = 4.605, 95% CI: 2.786-7.611, P<0.001). Our findings indicated that elevated preoperative PLR might have potential value in predicting poor outcome in patients with CRC.

3.
Int J Clin Exp Med ; 8(9): 15920-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26629095

RESUMO

This study aims to ascertain the relationship of tumor metastasis-associated markers cyclin D1, connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) with the clinicopathologic features and prognosis of patients with esophageal squamous cell carcinoma (ESCC), and to investigate their value in ESCC molecular classification. The expression of cyclin D1, CTGF and VEGF in 100 specimens from patients and 20 from normal esophageal mucosa were detected by immunohistochemistry. The relationship of their expression with prognosis of the patients with ESCC was evaluated by Cox regression model and Kaplan-Meier survival curve analysis. High levels of expression of cyclin D1, CTGF, and VEGF were observed in 61 (61%), 53 (53%), 49 (49%) cases, respectively. Univariate survival analysis indicated that the levels of expression of cyclin D1, CTGF and VEGF were associated with survival (all P-value < 0.05). Multivariate analysis indicated that cyclin D1 and VEGF were independent prognostic factors affecting the three-year survival rate of patients (P = 0.001, 0.017, respectively). Furthermore, high level expression of cyclin D1, CTGF and VEGF in stage I patients was found associated with poor three-year survival rate (all P-value < 0.05). The prognosis probably was favorable for patients with low expression of cyclin D1 even in stage III, or VEGF even in stage IV. Tumor metastasis-associated markers such as cyclin D1 and VEGF may be independent prognostic factors affecting survival rate of postoperative ESCC patients. It is possible to judge prognosis better and tailor treatments to each individual patient when these markers were applied to ESCC molecular classification.

4.
Int J Clin Exp Med ; 8(10): 19138-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26770545

RESUMO

Glasgow prognostic score (GPS), one information based prognostic score, has been previously shown to be a prognostic factor in varieties cancers mostly in advanced tumors. This study aimed to explore its value in patients with relatively early stage colorectal cancer (CRC). A total of 99 CRC patients with stage II from 2005 to 2010 operated in our hospital were enrolled in this study. C-reactive protein (CRP), albumin (ALB), Karnofsky Performance Status (KPS) score as well as a variety of biochemical variables before the operation was acquired from the database retrospectively. The value of GPS was calculated and its association with the clinical factors was further investigated. The prognostic significance was analyzed by univariate and multivariate analyses. Increased preoperative GPS was found associated with elevated carcinoembryonic antigen (CEA) and decreasing of KPS. Kaplan-Meier analysis and log-rank test revealed that a higher GPS predicted a higher risk of postoperative mortality in stage II CRC (P < 0.001). Furthermore, multivariate analysis demonstrated the GPS to be a risk factor for postoperative mortality (HR 3.215; P=0.025). The preoperative GPS might be a potential useful indicator for postoperative survival in patients with stage II CRC.

5.
Int J Clin Exp Med ; 7(3): 744-50, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24753772

RESUMO

Although carbohydrate antigen (CA19-9) level is frequently upregulated in pancreatobiliary cancer, it is also elevated in some benign diseases. This study aimed to determine whether CA19-9 levels could be used to distinguish between benign obstructive jaundice and pancreatobiliary cancer. Fifty-seven patients with obstructive jaundice were studied retrospectively. Endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, stone extraction, or stent placement were used to treat patients with benign bile duct stricture or inoperable malignant biliopancreatic diseases, whilst surgery was performed in suitable cases. Serum CA19-9 levels and some additional biochemical parameters were evaluated before and after treatment. CA19-9 levels were elevated in most patients, along with levels of total bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT), and 10 patients with benign disorders had extraordinarily high levels of these markers (> 1000 U/mL). The mean CA19-9 level in the malignant group was greater than that in the benign group (826.83 ± 557.34 vs. 401.92 ± 483.92 U/mL, P = 0.005), and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CA19-9 were 100%, 7.69%, 33.33% and 47.47%, respectively. CA19-9 levels in the whole cohort were correlated with ALP (r = 0.77, P < 0.001), GGT (r = 0.83, P < 0.001), bilirubin (r = 0.69, P < 0.001), and CRP (r = 0.37, P = 0.004). The reduction in serum level of CA19-9 after treatment in the malignant group was remarkably less than that observed in the benign group (97.26 ± 123.24 U/mL vs. 352.71 ± 397.29 U/mL, P < 0.001). CA19-9 levels may not be sufficient to distinguish between malignant and benign obstructive jaundice diseases.

6.
Int J Clin Exp Med ; 7(12): 5226-34, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25664025

RESUMO

Pancreatic cancer (PC) has the poorest survival rate among all types of human cancer due to the lack of sensitive and non-invasive diagnostic screen methods for PC screening. Our aim was to identify novel serum microRNA (miRNA) biomarkers for the early detection of PC. We used microarray to screen differential expression of miRNAs in two pooled serum samples (6 PC patients and 6 healthy controls). A panel of miRNAs (22 over-expression and 23 decreased) were deregulated in serum of PC patients in comparison to controls. The expressions of 8 selected miRNAs were further evaluated in sera from 49 PC patients and 27 controls using quantitative reverse transcription-polymerase chain reaction. The levels of serum miR-492 and miR-663a were significantly decreased in PC patients compared with controls (P < 0.05). ROC curve analysis showed that serum miR-492 and miR-663a yield an AUC of 0.787 with 75.5% sensitivity and 70.0% specificity and 0.870 with 85.7% sensitivity and 80.0% specificity, respectively, for discriminating between PC patients and healthy controls. In addition, the level of miR-663a was significantly and inversely associated with TNM stage (P = 0.027). These results suggested that serum miR-492 and miR-663a could have strong potential as novel non-invasive biomarkers for the early detection of PC.

7.
Oncol Lett ; 6(1): 13-18, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23946770

RESUMO

The aim of the present study was to detect the amplification of the human epidermal growth factor receptor 2 (HER2) gene in esophageal squamous cell carcinoma (ESCC), gastroesophageal junction adenocarcinoma (GEJAC) and gastric cancer (GC), as well as to understand the pathological meaning of HER2 gene amplification with regard to clinico-pathological parameters in these types of cancer. HER2 gene amplification was evaluated by fluorescence in situ hybridization (FISH) in surgically obtained specimens from 76 cases of ESCC, 50 of GEJAC and 48 of GC, as well as 21 specimens of tumor-adjacent normal epithelium as a control group. The HER2 gene amplification rates in ESCC, GEJAC and GC were 3.9 (3/76), 24.0 (12/50) and 18.8% (9/48), respectively. The rates of HER2 gene amplification in GEJAC and GC were significantly higher compared with ESCC (χ2=11.563, P<0.001 and χ2=7.375, P<0.007, respectively). HER2 gene amplification was not detected in the normal esophageal or gastric mucosa samples. In ESCC, HER2 gene amplification was correlated with the invasion of the ESCC cells, vascular invasion and lymph node metastasis (χ2=4.789, 3.858 and 5.354, respectively; all P<0.05). However, in GEJAC and GC, no correlations were observed between HER2 amplification and the gender, age, degree of differentiation, invasion, vascular invasion and lymph node metastases of the patients (all P>0.05). The rate of HER-2 gene amplification was low in ESCC, although the amplification of HER-2 was correlated with tumor metastasis in these patients. The rates of HER-2 gene amplification in GEJAC and GC were higher compared with ESCC. Therefore, compared with ESCC, GEJAC may be more similar to GC with regard to HER-2 gene amplification features.

8.
Oncol Lett ; 4(4): 607-611, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23205070

RESUMO

The aim of this study was to investigate the correlation between cyclin A expression and efficacy of paclitaxel-based chemotherapy in patients with esophageal squamous cell carcinoma (ESCC). The expression of cyclin A was examined in 48 newly diagnosed ESCC patients prior to treatment using the MaxVision immunohistochemistry method. The patients received four cycles of paclitaxel-based chemotherapy, the short-term treatment efficacy was evaluated and a 3-year follow-up was conducted. The response rate was greater in patients with positive cyclin A expression compared with those with negative expression (54.8 vs. 23.5%; χ(2)=4.373; P<0.05). Univariate and multivariate Cox analysis revealed that clinicopathological stage, degree of differentiation and expression of cyclin A were independent prognosis factors in patients with ESCC following paclitaxel-based chemotherapy. ESCC patients with positive cyclin A expression demonstrated an increased sensitivity to paclitaxel-based chemotherapy, suggesting that cyclin A may be used as a marker to predict the treatment efficacy of paclitaxel in patients with ESCC.

9.
Exp Ther Med ; 3(6): 1039-1048, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22970014

RESUMO

Accumulating evidence suggests that aberrant expression of microRNAs (miRNAs) is involved in several diseases, including cancer. This study aimed to investigate the miRNA expression pattern and its alteration following celecoxib intervention for human colorectal cancer (CRC). The miRNA expression profiles of CRC tissues, matched adjacent normal colorectal mucosae and HT-29 cells treated with celecoxib were determined using miRNA microarray, and further confirmed using the quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). The target genes of the aberrant miRNAs in HT-29 cells treated with celecoxib were further assessed through bioinformatic analysis. Results from this study demonstrated a significant increase in the expression of 35 miRNAs and a decrease in 30 miRNAs in the carcinoma tissues compared to the normal tissues (P<0.001). Of the 28 aberrantly expressed miRNAs, 20 were upregulated and 8 were downregulated in the HT-29 cells treated with celecoxib compared to the matched control cells (P<0.01). Furthermore, miR-552 was found to be correlated with clinical stage, lymph node and distant metastases (P<0.05). Stage and distant metastases revealed differential expression of miR-139-3p and grade disclosed aberrant expression of miR-142-3p. In addition, multiple target genes involved in several essential survival pathways were found be modulated by the aberrantly expressed miRNAs in HT-29 cells treated with celecoxib. Our data revealed that a common pattern of miRNA expression in the colorectum could distinguish malignant tissue from normal mucosa. Celecoxib inhibited HT-29 cell growth in vitro which was partly attributable to the altered expression of miRNAs. miRNAs may be involved in CRC tumorigenesis and can serve as potential therapeutic targets.

10.
Hepatogastroenterology ; 59(118): 1687-90, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22591645

RESUMO

BACKGROUNDS/AIMS: Thrombocytosis had been found to be associated with tumor metastasis and poor prognosis in malignant tumors including colorectal cancer (CRC). In the present study, we investigated the relationship between the platelet and the biological features in patients with CRC in China. METHODOLOGY: The correlation of platelet counts of 150 cases with CRC with their clinicopathological characteristics was explored. Furthermore, the survival impact of preoperative platelet count was also investigated. RESULTS: Statistically significant correlations between the platelet count and the lymph node and distance metastasis (p=0.016 and 0.014), vascular and perinural invasion (p=0.025 and 0.016) as well as TNM clinical stages (p=0.014) except for the age, gender and grades (p=0.245, 0.276 and 0.324, respectively) were found. In addition, 5-year survival of patients with high platelet count and normal platelet count were 13.30% and 56.30%, respectively (p=0.000). Meanwhile, concurrent with lymph node and distance metastasis, perinural invasion and clinical stages (p=0.000, 0.022, 0.034 and 0.000), platelet count (p=0.010) was also found to be an independent prognostic factor in CRC in our study through multivariate analysis. CONCLUSIONS: Elevated platelet might play some role in the progress of CRC and preoperative platelet count might be a prognostic indicator in the CRC patients.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Contagem de Plaquetas , Trombocitose/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombocitose/diagnóstico , Trombocitose/mortalidade , Fatores de Tempo
11.
Hepatogastroenterology ; 58(112): 1937-42, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22024062

RESUMO

BACKGROUNDS/AIMS: The cellular basis for rectal cancer development is still unclear. The aim of this study was to evaluate the relationship between the expression of p53, cyclinD1, bcl-2, ß-catenin, c-myc, cyclooxygenase-2 (COX-2) and nm23-H1 and the clinicopathological characteristics of rectal cancer. METHODOLOGY: Expressions of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 proteins were detected by immunohistochemical staining to two tissue microarrays containing tissues accumulated from 54 human rectal cancers and 40 para-cancer mucosa. RESULTS: Significant differences were demonstrated between the rectal cancers and their benign para-cancer counterparts according to the expressions of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 (p<0.05). Additionally, positive correlations of ß-catenin with cyclinD1 and c-myc (r=0.412, p=0.002; r=0.447, p=0.000) and of p53 with bcl-2 (r=0.332, p=0.001) were found. Cancer tissues with overexpression of ß-catenin or bcl-2 were less likely to differentiate to advanced grade. Expression of cyclinD1 had a correlation with clinical stages (p=0.039). In addition, a negative correlation was found between nm23-H1 expression and the histological grades, distance metastasis and Duke's stages. CONCLUSIONS: Aberrant expression of p53, cyclinD1, bcl-2, ß-catenin, c-myc, COX-2 and nm23-H1 might attribute to the carcinogenesis of human rectal cancer. Furthermore, cyclinD1 and nm23-H1 might be involved in rectal cancer progression. This study recommends the application of tissue microarrays in rectal cancer research for its reliable quick throughput.


Assuntos
Neoplasias Retais/metabolismo , Análise Serial de Tecidos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclina D1/análise , Ciclina D1/genética , Feminino , Genes p53 , Humanos , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/análise , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Retais/química , Neoplasias Retais/patologia , beta Catenina/análise , beta Catenina/genética
12.
Oncol Lett ; 2(6): 1219-1224, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22848291

RESUMO

Although aberrations of peroxisome proliferator-activated receptor γ (PPARγ) and phosphatase and tensin homolog (PTEN) expression have been identified in several other cancer types, certain previous studies have revealed that PPARγ is abundant in normal and malignant tissue in the colon. The question of whether aberrant PTEN is involved in the initial stage or is a later event during colorectal carcinogenesis remains controversial. Relatively few studies have focused on the correlation of expression of PPARγ and PTEN in various tissues. In the present study, paraffin-embedded blocks from 139 patients with CRC, 18 adenomatous polyps and 50 paired paracancerous benign mucosas were selected and analysed in 4 tissue microarray (TMA) blocks comprising 104, 72, 130 and 54 cores, respectively. Expression of PPARγ and PTEN was examined using immunohistochemical staining on TMAs. There were no significant differences in the expression of PPARγ (P=0.055) and PTEN (P=0.100) between the colorectal cancers, adenomas and paracancerous mucosas. However, correlations of PPARγ expression with clinical stage (P=0.004) and PTEN expression with histological grade (P=0.006) and distant metastasis (P=0.015) were demonstrated in the CRC specimens. Although the differences in PPARγ and PTEN protein expression in human colorectal cancer may not be considered as early diagnostic markers, our results indicate that CRCs with a low expression or deletion of PTEN may progress towards invasion and even metastasis; thus, PTEN may have potential as a prognostic marker in human CRC.

13.
World J Gastroenterol ; 16(47): 5975-81, 2010 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-21157974

RESUMO

AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemo- or radiotherapy prior to surgical resection. Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7 ± 61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P < 0.01). In contrast, the protein level of p27 was significantly lower in ESCC than in normal squamous epithelium (182.0 ± 69.0 vs 266.4 ± 28.0, P < 0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0 ± 42.3 vs 83.0 ± 66.5, P < 0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8 ± 31.7 vs 98.4 ± 84.8, 32.0 ± 19.0 vs 54.1 ± 53.7, 206.2 ± 61.5 vs 123.5 ± 68.3, respectively, all P < 0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r = 0.270, 0.233 and -0.311, respectively, all P < 0.05). CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Ciclo-Oxigenase 2/metabolismo , Neoplasias Esofágicas/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Carcinoma de Células Escamosas/patologia , Ciclina A/metabolismo , Neoplasias Esofágicas/patologia , Esôfago/citologia , Esôfago/metabolismo , Esôfago/patologia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias
14.
J Dig Dis ; 8(2): 82-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17532820

RESUMO

OBJECTIVE: To investigate the expression of peroxisome proliferator-activated receptors (PPAR)gamma and the effects of PPARgamma ligands on cells growth in colorectal cancer (CRC) cell line HT-29, and to explore whether the activation of PPARgamma by its selective ligand can induce apoptosis and the arrest of the cell cycle in these cells. METHODS: A CRC cell line, HT-29, was used in this study. PPARgamma mRNA and the protein expressions were measured by reverse transcriptase-polymerase chain reaction and Western blot. The HT-29 cells were treated with two specific PPARgamma ligands: rosiglitazone and 15-d-PGJ2. The effects of PPARgamma activated by rosiglitazone and 15-d-PGJ2 on the anchorage-dependent and anchorage-independent growth of the cells were assessed by methylthiazolyl terazolium (MTT) and soft agar colony assay, respectively. Apoptosis was measured by TUNEL staining and flow cytometry (FCM) assay by CaspSCREEN Flowcytometric Apoptosis Detection Kit (BioVision, Palo Alto, USA). Furthermore, the caspase-3 expression was determined by a immunocytochemical staining method before and after treatment with rosiglitazone and 15-d-PGJ2 for 48 h. The cell cycles were measured by flow cytometric analysis using propidium iodide (PI). RESULTS: PPARgamma mRNA and protein expressions were observed in the HT-29 cells. The MTT assay showed that treatment of these cells with 0, 0.1, 1 or 10 micromol/L PPARgamma activators rosiglitazone or 15-d-PGJ2 for 0, 24, 48 or 72 h resulted in the inhibition of anchorage-dependent cell growth in a dosage- and time-dependent way. Rosiglitazone treatment during cell growth resulted in the reduction of colony formation and the effects were not immediately reversible in the cell culture. TUNEL staining showed DNA fragmentation in positive cells after treatment with rosiglitazone and 15-d-PGJ2 for 48 h. In addition, FCM showed that the apoptosis rates were 14.8+/-0.8% and 28.5+/-1.3% or 15+/-0.7% and 40+/-1.2% after the cells were incubated with 10 micromol/L rosiglitazone or 15-d-PGJ2 for 24 h and 48 h, while the apoptosis rates of cells without treatment were 3.8+/-0.4% and 8.8+/-0.4%, respectively. Consistent with these results, the positivity rates of caspase-3 expression in cells treated with rosiglitazone or 15-d-PGJ2 increased significantly when compared with the control group. To explore whether the regulation of the cell cycle was involved in the effect of PPARgamma ligands on cell growth, FCM using PI staining was assessed. The ratio of G0/G1 phase cells increased after incubated with 10 micromol/L rosiglitazone or 15-d-PGJ2 for 24 h and 48 h. CONCLUSIONS: Our results showed that PPARgamma was expressed in HT-29 cells and PPARgamma activation could inhibit cell growth through inducing apoptosis and suppressing the cell cycle. PPARgamma may be considered as a new therapeutic target for colon cancer in humans.


Assuntos
Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , PPAR gama/metabolismo , Antineoplásicos/farmacologia , Apoptose/fisiologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Humanos , Hipoglicemiantes/farmacologia , Ligantes , PPAR gama/agonistas , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacologia , Rosiglitazona , Transdução de Sinais , Tiazolidinedionas/farmacologia
15.
World J Gastroenterol ; 13(5): 699-708, 2007 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-17278192

RESUMO

AIM: To explore the molecular events taking place during human colon cancer development and progression through high-throughput tissue microarray analysis. METHODS: We constructed two separate tissue microarrays containing 1.0 mm or 1.5 mm cylindrical samples acquired from 112 formalin-fixed and paraffin-embedded blocks, including carcinomas (n = 85), adenomatous polyps (n = 18), as well as normal para-cancerous colon tissues (n = 9). Immunohistochemical staining was applied to the analysis of the consecutive tissue microarray sections with antibodies for 11 different proteins, including p53, p21, bcl-2, bax, cyclin D1, PTEN, p-Akt1, beta-catenin, c-myc, nm23-h1 and Cox-2. RESULTS: The protein expressions of p53, bcl-2, bax, cyclin D1, beta-catenin, c-myc, Cox-2 and nm23-h1 varied significantly among tissues from cancer, adenomatous polyps and normal colon mucosa (P = 0.003, P = 0.001, P = 0.000, P = 0.000, P = 0.034, P = 0.003, P = 0.002, and P = 0.007, respectively). Chi-square analysis showed that the statistically significant variables were p53, p21, bax, beta-catenin, c-myc, PTEN, p-Akt1, Cox-2 and nm23-h1 for histological grade (P = 0.005, P = 0.013, P = 0.044, P = 0.000, P = 0.000, P = 0.029, P = 0.000, P = 0.008, and P = 0.000, respectively), beta-catenin, c-myc and p-Akt1 for lymph node metastasis (P = 0.011, P = 0.005, and P = 0.032, respectively), beta-catenin, c-myc, Cox-2 and nm23-h1 for distance metastasis (P = 0.020, P = 0.000, P = 0.026, and P = 0.008, respectively), and cyclin D1, beta-catenin, c-myc, Cox-2 and nm23-h1 for clinical stages (P = 0.038, P = 0.008, P = 0.000, P = 0.016, and P = 0.014, respectively). CONCLUSION: Tissue microarray immunohistochemical staining enables high-throughput analysis of genetic alterations contributing to human colon cancer development and progression. Our results implicate the potential roles of p53, cyclin D1, bcl-2, bax, Cox-2, beta-catenin and c-myc in development of human colon cancer and that of bcl-2, nm23-h1, PTEN and p-Akt1 in progression of human colon cancer.


Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Imuno-Histoquímica , Análise Serial de Proteínas/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem
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