RESUMO
<p><b>OBJECTIVE</b>To investigate the effect of gefitinib on the migration of triple-negative breast cancer cell line MDA-MB-231 cells.</p><p><b>METHODS</b>Gefitinib was used in concentrations of 0 micromol/L, 0.1 micromol/L, 1 micromol/L, 10 micromol/L and 20 micromol/L, respectively. Phosphorylation levels of EGFR and Akt were analyzed by Western blot. The capability of migration was measured by scratch test and Boyden chamber assay. Microfilaments (cell skeleton ) remolding and polarization were evaluated by immunofluorescence microscopy.</p><p><b>RESULTS</b>Comparing with the control group (0 micromol/L gefitinib), gefitinib effectively inhibited the phosphorylation of EGFR and its downstream key proteins, and the effect displayed an obvious dose-effect relationship. At 24 hours after wound scratch, the cell migration distance of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was (36.3 +/- 4.0) microm, (30.3 +/- 3.8) microm, (26.8 +/- 3.3) microm, (17.0 +/- 2.6) microm, and (11.0 +/- 2.5) microm, respectively. At 3.5 hours after Boyden chamber assay, the cell count of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was 69.2 +/- 7.0, 51.8 +/- 7.5, 43.8 +/- 8.7, 30.6 +/- 4.8, and 28.4 +/- 3.4, respectively. Compared with the control group (0 micromol/L gefitinib), gefitinib could significantly prolong the wound-healing time and decrease the migrating cell count (P < 0.05), and significantly inhibit the lamellipodium formation, cell skeleton remolding and changes of the cytoskeleton polarization.</p><p><b>CONCLUSIONS</b>Gefitinib can reduce the migration capacity of triple-negative breast cancer cells through inhibiting phosphorylation of EGFR/PI3K/Akt pathway, suppressing the cell skeleton (microfilaments) remolding and changes of its polarization.</p>
Assuntos
Feminino , Humanos , Antineoplásicos , Farmacologia , Neoplasias da Mama , Metabolismo , Patologia , Linhagem Celular Tumoral , Movimento Celular , Citoesqueleto , Relação Dose-Resposta a Droga , Fosfatidilinositol 3-Quinases , Metabolismo , Fosforilação , Inibidores de Proteínas Quinases , Farmacologia , Proteínas Proto-Oncogênicas c-akt , Metabolismo , Quinazolinas , Farmacologia , Receptores ErbB , Metabolismo , Receptor ErbB-2 , Metabolismo , Receptores de Estrogênio , Metabolismo , Receptores de Progesterona , Metabolismo , Transdução de SinaisRESUMO
<p><b>OBJECTIVE</b>To study the expression of stomatin-like protein-2 (SLP-2) in esophageal squamous cell carcinoma (ESCC), and analyze the correlation between SLP-2 expression and clinicopathological features.</p><p><b>METHODS</b>The expression of SLP-2 protein in ESCC tissues (18 and 220 cases respectively) was detected by Western blot and IHC. The association between SLP-2 expression and clinicopathological features was analyzed.</p><p><b>RESULTS</b>Compared with normal epithelium, 13 cases of ESCC tissues showed a higher expression of SLP-2 on the protein level (72.2%, 13/18). IHC analysis on tissue microarray revealed that the expression rate of SLP-2 protein in ESCC was 54.1% and in normal esophageal mucosa was 3.6%, showing a significant difference (P < 0.001). SLP-2 high-level expression correlates with the extent of ESCC invasion (P = 0.033), but not with other clinicopathologic characteristics (P > 0.05).</p><p><b>CONCLUSION</b>SLP-2 as a novel cancer-related gene may play an important role in tumorigenesis of ESCC. The overexpression of SLP-2 may be closely associated with the invasion of esophageal cancer.</p>
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Sanguíneas , Metabolismo , Fisiologia , Western Blotting , Carcinoma de Células Escamosas , Metabolismo , Patologia , Neoplasias Esofágicas , Metabolismo , Patologia , Imuno-Histoquímica , Metástase Linfática , Proteínas de Membrana , Metabolismo , Fisiologia , Invasividade NeoplásicaRESUMO
<p><b>OBJECTIVE</b>To study the expression of stomatin like protein-2 (SLP-2) at mRNA and protein levels in two kinds of malignant epithelial tumors, including laryngeal squamous cell carcinoma (LSCC) and invasive breast cancer, and to study the relations of SLP-2 expression and clinicopathologic parameters with the prognosis.</p><p><b>METHODS</b>RT-PCR and Western blot were used to detect the expression of SLP-2 mRNA and protein in LSCC and their normal counterparts (46 and 10 pair, respectively). Immunohistochemistry was carried on tissue array constructed from LSCC (104 cases) and breast cancer (263 cases), respectively. The association between SLP-2 expression and clinicopathologic parameters was analyzed.</p><p><b>RESULTS</b>LSCC showed a higher expression of SLP-2 than that of their normal counterparts (negative expression) at mRNA (83%, 38/46) and protein (7/10) level. Immunohistochemical analysis of LSCC showed that compared with negative expression in normal laryngeal epithelium (0/20), a higher SLP-2 expression was detected in LSCC (36/104, P=0.000) and associated with the advanced clinical stage (P<0.01) and lymph node metastasis (P=0.003). Immunohistochemical study of invasive breast cancer demonstrated that compared with negative expression in normal breast tissue (0/10), more than one half of the cases showed a high SLP-2 expression (52.5%, 138/263, P=0.000) in breast cancer, which correlated with the tumor size (P=0.020), lymph node metastasis (P<0.01), advanced clinical stage (P<0.01), distant metastasis (P=0.002) and HER2/neu protein expression (P=0.037). Survival analysis showed a shorter overall survival probability in patients with a high SLP-2 expression. It was considered that lymph node metastasis, positive HER2/neu expression, and high-level SLP-2 expression may act as the independent prognostic factors for those tumors.</p><p><b>CONCLUSIONS</b>A high expression level of SLP-2 may be associating with the development of invasion and metastasis in LSCC and breast cancer, and SLP-2 is also considered working as an independent factor indicating a poor prognosis clinically in breast cancer.</p>
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Sanguíneas , Genética , Metabolismo , Neoplasias da Mama , Metabolismo , Patologia , Carcinoma Ductal de Mama , Metabolismo , Patologia , Carcinoma de Células Escamosas , Metabolismo , Patologia , Neoplasias Laríngeas , Metabolismo , Patologia , Metástase Linfática , Proteínas de Membrana , Genética , Metabolismo , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro , Metabolismo , Receptor ErbB-2 , Metabolismo , Análise de SobrevidaRESUMO
<p><b>OBJECTIVE</b>To investigate the method and clinical efficacy of laparoscopic excision of seminal vesicle cyst.</p><p><b>METHODS</b>Laparoscopic excision of seminal vesicle cyst was performed under general anaesthesia in two patients with symptomatic seminal vesicle cyst confirmed by ultrasonography and CT scanning preoperatively. The sizes of the seminal vesicle cysts were 3.3 cm x 3.7 cm x 2.5 cm and 4.1 cm x 4.3 cm x 5.3 cm, respectively.</p><p><b>RESULTS</b>The operations were performed successfully in both the patients, with the operation time of 140 min and 100 min, blood loss of 50 ml and 20 ml, and postoperative stay of 6 days. The patients were followed up for 6 and 7 months, respectively. All the preoperative symptoms disappeared, and no complications and recurrence were found.</p><p><b>CONCLUSION</b>Laparoscopic excision of seminal vesicle cyst, with a good visual field, refined procedure, minimal invasiveness and rapid recovery, is a safe and effective surgical option for patients with seminal vesicle cyst.</p>
Assuntos
Adulto , Humanos , Masculino , Cistos , Cirurgia Geral , Doenças dos Genitais Masculinos , Cirurgia Geral , Laparoscopia , Glândulas Seminais , Cirurgia GeralRESUMO
<p><b>OBJECTIVE</b>To study the clinical significance of extracapsular extension (ECE) of axillary lymph node metastases in breast cancer.</p><p><b>METHODS</b>The clinicopathological data of 1230 cases of nodal positive breast cancer treated in our department from 1989 to 1995 were analyzed retrospectively.</p><p><b>RESULTS</b>486 (39.5%) from the 1230 cases were ECE positive. There was a higher incidence of ECE in postmenopausal women than premenopausal ones (47.5% versus 35.5%, respectively, P < 0.001). The patients in ECE positive group had a larger tumor size (5.11 +/- 2.53 cm versus 3.90 +/- 1.80 cm, P < 0.001). 18.3% of patients with stage T1 were ECE positive, stage T2 were 36.4%, and stage T3 were 54.4%, and the difference was significant (P < 0.001). ECE was correlated with the number of positive axillary lymph nodes. The ECE positive group had more positive nodes than ECE negative group (16.96 +/- 12.16 versus 5.24 +/- 6.60, P < 0.001). 6.1% of patients with 1 positive node were ECE positive, 13.5% with 2 - 3, 35.8% with 4 - 9, 62.3% with 10 - 19, and 84.0% with more than 20 positive axillary nodes, and there was a significant difference among those groups (P < 0.001). ECE had no association with ER/PR status (P = 0.706). ECE was a risk factor of local-regional recurrence, but the relapse time had no significant difference (P = 0.559). ECE was also a risk factor of distant metastasis, and the relapse time had a significant difference (P < 0.001). The median metastasis free time was 30.0 (2 approximately 172) months in ECE positive group, while 37.5 (2 approximately 170) months in ECE negative group (P = 0.006). CE occurred in 60.4% of the patients with firstly diagnosed bone, skin and distant lymph node metastasis, but in 42.0% of the patients with firstly diagnosed visceral metastasis (P = 0.001). The metastasis-free survival rate, locoregional recurrence-free survival rate and overall survival rate of the ECE positive group were much shorter than that of the ECE negative group. COX proportional hazard regression single factor analysis and multi-factor analysis suggested that ECE is an independent factor of metastasis-free survival, locoregional free recurrence and overall survival.</p><p><b>CONCLUSION</b>The presence of ECE in breast cancer is positively related with tumor size and the number of positive lymph nodes. It is also a risk factor of locoregional recurrence and distant metastasis. ECE positive group has a much shorter metastasis-free survival, locoregional recurrence-free survival and overall survival. ECE is a risk factor of those three indexes.</p>
Assuntos
Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Axila , Neoplasias da Mama , Tratamento Farmacológico , Patologia , Radioterapia , Cirurgia Geral , Cisplatino , Terapia Combinada , Intervalo Livre de Doença , Fluoruracila , Seguimentos , Excisão de Linfonodo , Linfonodos , Patologia , Cirurgia Geral , Metástase Linfática , Mastectomia , Metotrexato , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pós-Menopausa , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
<p><b>OBJECTIVE</b>The study was designed to investigate the expression patterns of metalloproteinase (MMP)-13 protein in invasive breast carcinoma and to determine the clinicopathological and prognostic values of its various localization and relation to the tumor phenotypes.</p><p><b>METHODS</b>Immunohistochemistry was performed on paraffin-embedded tissue array from 263 invasive breast carcinomas to investigate the protein expressions of MMP-13, estrogen receptor, progesterone receptor, HER2, MMP-2, MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1, TIMP-2.</p><p><b>RESULTS</b>MMP-13 protein was detected in the cytoplasm of carcinoma cells and peritumoral fibroblasts. High level expression of MMP-13 protein in tumor cells was associated with more lymph node involvement and higher tumor grade (both P < 0.01), and positively correlated with HER2 (P = 0.015) and TIMP-1 protein (P < 0.01) expression in carcinoma cells. Moreover, high expression of MMP-13 was associated with shortened overall survival for the entire patient population and the patient group with positive lymph node. Tumor cell derived MMP-13 had different impact on patients with different HER2 status. Peritumoral fibroblasts derived MMP-13 protein, although correlated with tumor cell derived MMP-13 and associated with lymph node stage and HER2 expression, was found having less prognostic impact. Univariate survival analysis showed that the tumor size, grade, lymph node status, PR status, HER2 expression, tumors TIMP-1 and MMP-13 expression were prognostic factors. However, multivariate survival analysis showed that only tumor size, lymph node status, HER2 expression, tumors TIMP-1 and MMP-13 were independent prognostic factors.</p><p><b>CONCLUSION</b>MMP-13 protein expressed by tumor cells correlates with the invasion and metastasis of breast carcinoma, and therefore, may serve as a poor prognostic marker for the patient.</p>
Assuntos
Feminino , Humanos , Biomarcadores Tumorais , Metabolismo , Neoplasias da Mama , Metabolismo , Patologia , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Linfonodos , Patologia , Metaloproteinase 13 da Matriz , Genética , Metaloproteinase 9 da Matriz , Invasividade Neoplásica , Diagnóstico , Estadiamento de Neoplasias , Classificação , Prognóstico , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de ProgesteronaRESUMO
<p><b>OBJECTIVE</b>To study the expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in prostate cancer (PCa) and its biological significance.</p><p><b>METHODS</b>Specimens from 75 patients with PCa (32 cases), benign prostatic hyperplasia (BPH, 16 cases), high-grade prostate intraepithelial neoplasia (PIN, 15 cases) and normal prostate (NP, 12 cases) were comprised in the study. The PCa was divided into high Gleason score group (Gleason score > or = 7) and low Gleason score group (Gleason score < 7). Immunohistochemistry was performed with antibodies against HIF-1 alpha, VEGF and CD34. Microvessel density (MVD) was analyzed by staining with antibodies to CD34.</p><p><b>RESULTS</b>The positive rates of HIF-1alpha were significantly higher in PCa (62.5%) and PIN (60.0%) than those in BPH (6.3%) and NP(0) (P < 0.05), respectively. The positive rates of VEGF were significantly higher in PCa (78.1%) and PIN (73.3%) than those in BPH (18.7%) and NP (8.3%) (P < 0.05), respectively. A higher concentration of MVD was observed in PCa (66.9 +/- 18.0) compared with those in BPH (28.3 +/- 6.9) and NP (15.3 +/- 2.9) (P < 0.05). MVD and the positive rates of HIF-1alpha and VEGF were significantly higher in high Gleason score group than those in low Gleason score group.</p><p><b>CONCLUSION</b>The results suggest that the overexpression of HIF-1alpha and VEGF are closely related to PCa, and the son score group. up-regulation of HIF-1alpha and VEGF are early events in PCa.</p>
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Subunidade alfa do Fator 1 Induzível por Hipóxia , Imuno-Histoquímica , Hiperplasia Prostática , Metabolismo , Neoplasia Prostática Intraepitelial , Metabolismo , Neoplasias da Próstata , Metabolismo , Fator A de Crescimento do Endotélio VascularRESUMO
<p><b>OBJECTIVE</b>To observe the changes in plasma levels of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in burn patients with severe infection treated with Imipenem or Cefoperazone.</p><p><b>METHODS</b>Thirteen severe burn patients infected with gram negative bacilli were enrolled in the study in which 7 were treated with IPM and 6 with CPZ. Venous blood samples were harvested before and 2, 12, 24, 48 and 72 hours after the use of antibiotic for the determination of the plasma levels of LPS, TNF-alpha and IL-6, and correlative analysis was carried out among all the factors in regard to their changes.</p><p><b>RESULTS</b>The plasma levels of LPS in both groups were elevated 2 hours after the injection of either antibiotic, but it was more obvious in patients with CPZ when compared with that before treatment (13.95 +/- 5.44 pg/ml), and the levels were much higher than that after IPM (P < 0.05). The plasma LPS level declined thereafter. The plasma TNF-alpha level in CPZ group was 0.86 +/- 0.16 ng/ml at 2 hours after the use of antibiotic, and it was much higher than that before the use of the drug, and it was higher compared with IPM group. (P < 0.01). But there was no change in the plasma IL-6 level in all the patients at all the time points before and after the use of either drug. The plasma TNF-alpha levels in the two groups were positively correlated with the plasma levels of LPS and IL-6.</p><p><b>CONCLUSION</b>The release of LPS and TNF-alpha from bacteria could be induced by the administration of different kinds of antibiotics in the management of burn patients infected by gram negative bacilli in different releasing amounts. And the TNF-alpha production was correlated with the release of LPS and IL-6.</p>