Expression of PEBP4 protein correlates with the invasion and metastasis of colorectal cancer

This study aimed to investigate the expression of PEBP4 protein in colorectal carcinoma tissues and its correlation with the clinical pathology of colorectal cancer and to investigate the relationship between PEBP4 expression and the invasion and metastasis of colorectal cancer cells, which could provide an experimental basis for future biological treatments of human colorectal cancer. RT-PCR and western blot methods were applied to detect the mRNA and protein expressions, respectively, of PEBP4 in colorectal cancer tissues and normal pericarcinoma tissues, and their correlations with the tumorigenesis and development of colorectal cancer, as well as its clinical pathology, were analyzed. Using the RNA interference technology, the expression of PEBP4 was knocked down in the human colorectal cancer cell HCT116, and the changes of the invasion capability of HCT116 were monitored. The positive mRNA expression rate of PEBP4 in colorectal cancer tissue was significantly higher than that in the normal pericarcinoma tissue (p < 0.05). Also, the positive expression rate in the cancer tissues from patients with positive lymph node and distant metastasis was significantly higher than that from the patients negative for lymph node and distant metastasis (p < 0.05). The positive expression rate of PEBP4 in the cancer tissues from the patients in early stages (I, II) was significantly lower than the expression rate in patients in advanced stages (III, IV) (p < 0.05). A lower degree of differentiation in colorectal cancer corresponded to a higher positive mRNA expression rate of PEBP4 (p < 0.05). However, this was independent of the patient’s gender, age, and tumor size (p > 0.05). In colorectal cancer tissue, the expression of PEBP4 protein was consistent with its mRNA. Namely, PEBP4 protein expression in colorectal cancer tissues was significantly higher than that in the normal pericarcinoma tissues (p < 0.05), the expression in the cancer tissues from the patients with positive lymph node and distant metastasis was significantly higher than that from the patients who were negative for these metastases (p < 0.05), and a lower degree of differentiation in colorectal cancer corresponded to a higher TNM staging along with a higher PEBP4 protein expression (p < 0.05). After HCT116 cells transfected with PEBP4 siRNA, they showed a significantly lower expression level of PEBP4 protein (p < 0.05), and the number of cells that passed through the Transwell chamber was significantly lower compared to the non-transfected or the transfected controls (p < 0.05). The over-expression of PEBP4 protein may be related to the tumorigenesis, development, metastasis, and invasion of colorectal cancer.     

PEBP4 enhanced HCC827 cell proliferation and invasion ability and inhibited apoptosis

The purposes of this study were to investigate the effects of phosphatidylethanolamine-binding protein 4 (PEBP4) on the cell growth, proliferation, apoptosis, and invasion of non-small cell lung cancer (NSCLC) cells and to provide evidence for future treatment options for NSCLC. Western blot assays were performed to examine PEBP4 protein expression levels in NSCLC cell lines (HCC827, A549, NCI-H661, NCI-H292, and 95-D) and a normal human bronchial epithelial (HBE) cell line. A PEBP4 shRNA expression vector was constructed and transfected into HCC827 cells. Subsequently, the effects of PEBP4 on the cell viability, cell cycle distribution, apoptosis levels, and invasion properties of HCC827 cells were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry analyses, and transwell invasion assays. In addition, the effects of PEBP4 on the expression of proteins including cyclin D1, p53, Bcl-2, MMP-2, and MMP-9 were investigated. PEBP4 was highly expressed in lung cancer cells (HCC827, A549, NCI-H661, NCI-H292, and 95-D), but its expression was low in HBE cells. Cell viability, cell proliferation, and invasion of HCC827 cells in the PEBP4 knockdown group were significantly lower than that in the negative control and blank control groups (p?<?0.05), and there were no significant differences between the negative and blank control groups in terms of cell viability, cell proliferation, apoptosis, and invasion. In HCC827 cells, the expression levels of cyclin D1, Bcl-2, MMP-2, and MMP-9 in the PEBP4 knockdown group were significantly lower (p?<?0.05), and the expression of p53 protein was significantly higher than that in the negative and blank control groups (p?<?0.05). There were no significant differences between the negative and blank control groups in the expression levels of cyclin D1, p53, Bcl-2, MMP-2, and MMP-9. In conclusion, PEBP4 enhanced HCC827 cell proliferation and invasion ability and inhibited apoptosis. Decreased PEBP4 expression may play a role in the reduced invasion ability and increased apoptosis of the human NSCLC cell line HCC827.     

The expression of PEBP4 protein in lung squamous cell carcinoma

The phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP family. It not only plays a role in the inhibition of the MAPK signaling pathway but also is involved in the inhibition of the JNK pathway that promotes the activation of AKT. Recent research has also shown that overexpression of PEBP4 was related to the development, invasion, and metastasis of a variety of tumors. This study aimed to investigate the correlation between PEBP4 protein expression in lung squamous cell carcinoma tissue and the clinical pathology of lung squamous cell carcinoma. Immunohistochemistry was used to detect PEBP4 expression in lung squamous cell carcinoma tissue and adjacent normal tissue from 61 patients. Western blotting was used to detect changes in the expression of PEBP4 protein between lung squamous cell carcinoma tissue and adjacent normal tissues. The correlation of PEBP4 expression and the occurrence, development, and clinical pathology of lung squamous cell carcinoma was analyzed. Of 61 patients, four patients were PEBP4 negative (−; 6.6%) and 57 patients were positive (+ to +++; 93.4%). Of those positive for PEBP4 expression, 7 patients were weakly positive (+; 11.5%), 21 patients were positive (++; 34.4%), and 29 patients were strongly positive (+++; 47.5%). PEBP4 protein was more highly expressed in lung squamous cell carcinoma tissue than in the adjacent normal lung tissue (p < 0.05). In PEBP4-positive patients, PEBP4 protein expression was significantly greater in those with lymph node metastases than in those without (p < 0.05). PEBP4 expression was significantly lower in patients at early (I and II) stages than in patients at advanced (III and IV) stages (p < 0.05). In less differentiated lung squamous cell carcinomas, PEBP4 protein expression was greater (p < 0.05); however, this was unrelated to the gender, age, or tumor size of the patient (p > 0.05). PEBP4 protein overexpression was associated with the occurrence, invasion, and metastasis of lung squamous cell carcinoma.     

非小细胞肺癌中ARL4C的表达及其在EGFR-TKI耐药中的作用

目的探讨非小细胞肺癌中ARL4C的表达及其与临床病理特征的关系以及在EGFR-TKI耐药中的作用。方法收集63例NSCLC患者的癌组织和癌旁组织,qRT-PCR法检测ARL4C的表达并分析其与临床病理特征之间的关系。qRT-PCR和Western blot法检测ARL4C在各细胞株中的表达,MTS检测细胞活性及IC₅₀的变化,Transwell侵袭实验检测ARL4C表达变化对细胞侵袭能力的影响。结果非小细胞肺癌组织中ARL4C表达水平低于癌旁组织(P<0.05),其表达水平与淋巴结转移、TNM分期和肺膜侵犯密切相关(P<0.05)。TKI耐药细胞株HCC827/ER中ARL4C在mRNA以及蛋白表达水平相较对照细胞株HCC827显著下调(P<0.05);ARL4C过表达细胞株HCC827/ER/ARL4C-OE IC₅₀显著下降(P<0.05),Transwell分析结果显示过表达ARL4C后肺癌细胞的侵袭能力受到抑制(P<0.05)。结论 ARL4C异常表达与非小细胞肺癌淋巴结转移、TNM分期和肺膜侵犯密切相关...     

The significance of expression of autophagy-related gene Beclin,Bcl-2, and Bax in breast cancer tissues

The purpose of this study was to detect the expression of autophagy-related gene Beclin1 and apoptosis-related genes Bcl-2 and Bax in breast cancer tissues, to investigate their relationship and significance to the occurrence and development of breast cancer, and to provide an experimental basis for the biological treatment of breast cancer in the future. Human breast cancer tissues and relatively healthy breast tissue adjacent to the tumor were collected during surgical resection. By using RT–PCR and western blot, the mRNA and protein expressions of Beclin1, Bcl-2, and Bax were detected in the breast cancer tissues and the relatively healthy, adjacent tissues. The correlations of these expressions with the occurrence, development, and clinicopathology of breast cancer were analyzed. The mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues were significantly lower than those in the relatively healthy, adjacent breast tissues (p < 0.05); the lower the degree of tumor differentiation, the lower the mRNA and protein expressions of Beclin1 and Bcl-2 (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for lymph node metastasis were significantly lower than those negative for lymph node metastasis (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for distant metastasis were significantly lower than those negative for distant metastasis (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for ki67 were significantly lower than those negative for ki67 (p < 0.05). The mRNA and protein expressions of Bax were different from those of Beclin1 and Bcl-2. In breast cancer tissues, the mRNA and protein expressions of Bax were up-regulated (p < 0.05); the lower the degree of tumor differentiation, the higher the mRNA and protein expressions of Bax (p < 0.05); the mRNA and protein expressions of Bax in breast cancer tissues from patients positive for lymph node metastasis were significantly higher than those negative for lymph node metastasis (p < 0.05); and the mRNA and protein expressions of Bax in breast cancer tissues from patients positive for distant metastasis were significantly higher than those in patients negative for distant metastasis (p < 0.05). However, the mRNA and protein expressions of these three genes were not correlated with patient age, tumor size, progesterone receptor positivity, or human epidermal growth factor positivity (p > 0.05). The correlation of Bcl-2 and Bax mRNA with Beclin1 mRNA expressed in breast cancer tissues were both statistically significant (p < 0.05). The activity change of autophagy and apoptosis is associated with the tumorigenesis and tumor progression of breast cancer. The joint detection of these three genes (Beclin1, Bcl-2, and Bax) contributes to the early diagnosis of and predicts prognosis for breast cancer, and this also provides an experimental basis for the biological therapy of breast cancer.     

Identification of CD146 expression,angiogenesis, and lymphangiogenesis as progression,metastasis, and poor-prognosis related markers for gallbladder adenocarcinoma

Gallbladder cancers (GBC) are associated with high disease-specific mortality rates because of no means of early detection and effective therapies. In this study, we investigated CD146 expression, microvessel densities, and lymph vessel densities in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using immunohistochemistry. We demonstrated that positive CD146 expression, and average microvessel and lymph vessel counts in gallbladder adenocarcinomas were significantly higher than those in peritumoral tissues, polyps, and chronic cholecystitis (ps < 0.01). Positive CD146 expression, and average microvessel and lymph vessel counts were also significantly lower in cases with well-differentiated adenocarcinoma, maximal tumor diameter <2 cm, no metastasis of lymph node, and no invasion of regional tissues than in cases with poorly differentiated adenocarcinoma, maximal tumor diameter ≥2 cm, metastasis in lymph nodes, and invasion of regional tissues (p < 0.05 or p < 0.01). Univariate Kaplan–Meier analysis showed that increased expression of CD146 (p = 0.056), higher average microvessel counts (p < 0.05), and lymph vessel counts (p < 0.05) were associated with decreased overall survival. Multivariate Cox regression analysis showed that average microvessel and lymph vessel counts (ps < 0.05) were independent prognostic predictors in gallbladder adenocarcinoma. Our study suggested that the elevated expression of CD146, angiogenesis, and lymphangiogenesis might be closely related to progression, invasion, metastasis, and prognosis of gallbladder adenocarcinoma.     

Detection of Brk expression in non-small cell lung cancer: clinicopathological relevance

Breast tumor kinase (Brk), also known as protein tyrosine kinase 6, is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk upregulation and oncogenic properties have been found in several malignant tumors, including breast, colon carcinomas, and melanomas, but the expression of Brk and its clinical significance in non-small cell lung cancer (NSCLC) remains unclear. In the current study, we examined the expression of Brk and its correlation with clinicopathological features involving p53, ki67, and E-cadherin status in NSCLC tissue using immunohistochemistry. We also used immunocytochemistry and immunofluorescent staining to examine the Brk expression and its subcellular localization in NSCLC cell lines, including LTE and H460. We further confirmed cytoplasmic and nucleus expression of Brk in LTE and H460 cells using Western blotting. The Brk expression in NSCLC cells was mainly found in cytoplasm (59/122, 48.4%) with some nucleus staining (17/122, 13.9%) with a total positive rate of 53.3% (65/122). Cytoplasmic Brk expression in NSCLC was higher than that in normal lung tissues (24/122, 19.7%) (P < 0.05). Increased cytoplasmic Brk expression in NSCLC was associated with large tumor size (≥3 cm), lymph node metastasis, and advanced tumor–node–metastasis (TNM) stages (III and IV) (P < 0.05). Moreover, increased cytoplasmic Brk expression was positively associated with Ki67 status in NSCLC (P < 0.05). Reduced E-cadherin expression was also found to be associated with lymph node metastasis and advanced TNM stages (III and IV) in NSCLC (P < 0.05). Brk expression was not associated with E-cadherin expression and P53 status in NSCLC (P > 0.05). The present findings indicate an increase of cytoplasmic Brk expression in NSCLC which may play a role in tumor development, including tumor expansion and lymph node metastasis in which Ki67, but not E-cadherin, and P53 status may be involved.     

Increased NDRG1 Expression is Associated with Advanced T Stages and Poor Vascularization in Non-small Cell Lung Cancer

N-myc downstream regulated gene 1 (NDRG1) is a member of the N-myc downstream regulated gene family which belongs to the alpha/beta hydrolase superfamily. Earlier studies have shown its association with inhibition of tumor metastasis. However, its function in malignant tumors is not fully enunciated. Recently there was increasing evidence that NDRG1 is involved in stress responses. In the current study, we examined the expression of NDRG1 and its correlation with clinicopathological factors and microvessel density (MVD) in non-small cell lung cancer (NSCLC) using immunohistochemistry (IHC). NDRG1 expression in NSCLC (71/115, 61.7%) was higher than that in normal lung tissues (32/115, 27.8%) (p < 0.05). NDRG1 expression in NSCLC cells was found in cytoplasm (63/115, 54.8%), nuclear (24/115, 20.9%) and cell membrane (13/115, 11.3%). NDRG1 expression in NSCLC with advanced T stages (T2-4) (63/84, 75.0%) was significantly higher than that with T1 stage (8/31, 25.8%) (P < 0.05). No other clinicopathological factors including lymph node metastasis were found to be associated with NDRG1 expression (p > 0.05). Moreover increased NDRG1 expression was associated with lower MVD in NSCLC (P < 0.05). MVD in adenocarcinoma (33.4 ± 8.4/HP) was significantly higher than that in squamous cell carcinoma (SCC) (19.3 ± 8.1/HP) (P < 0.05). No other clinicopathological factors were associated with MVD in NSCLC (p > 0.05). The present findings indicate an increase of NDRG1 expression with the progress of tumour extent which may be due to unbalanced tumor oxygenation on account of poor vascularization in NSCLC.     

TOP2A在非小细胞肺癌中的高表达促进肿瘤细胞的增殖和侵袭能力

目的:探讨编码拓扑异构酶Ⅱα的基因TOP2A在非小细胞肺癌组织中的表达情况及其生物学功能。方法:采用荧光定量PCR方法检测102例非小细胞肺癌及其癌旁组织中TOP2A的mRNA表达水平,Western blot检测其中5对组织中TOP2A蛋白表达水平,分析TOP2A 表达与非小细胞肺癌主要临床病理特征的相关性。干扰非小细胞肺癌细胞株A549和HCC827中TOP2A的表达,MTT法检测其表达对肿瘤细胞增殖的影响,Transwell法检测TOP2A表达下调对肿瘤细胞侵袭能力的影响。应用流式细胞术检测TOP2A敲降后细胞的凋亡率和细胞周期。结果:TOP2A在非小细胞肺癌组织中的表达水平相较癌旁组织明显上升（P<0.05）,干扰TOP2A的表达会抑制非小细胞肺癌细胞的增殖和侵袭。流式细胞凋亡率实验结果显示转染siTOP2A后的非小细胞肺癌细胞早期凋亡率增加;流式周期分析显示siTOP2A转染后的细胞S期发生阻滞抑制细胞增殖。同时,TOP2A表达水平与非小细胞肺癌的肿瘤分期、淋巴结转移密切相关（P<0.05）。结论:TOP2A在非小细胞肺癌中表达上调,与肿瘤增殖和侵袭等生物学行为密切相关。     

CD24 and Galectin-1 Expressions in Gastric Adenocarcinoma and Clinicopathologic Significance

CD24 and galectin-1 expression in gastric adenocarcinoma and their clinicopathologic significance remained largely unknown. We aimed to evaluate expressions and staining intensities of CD24 and galectin-1 in gastric adenocarcinoma and to investigate the interrelation with clinicopathologic parameters including survival. 93 cases with gastric adenocarcinoma were reevaluated histopathologically and immunohistochemistry was performed with antibodies against CD24 and galectin-1. Staining intensities of both markers in tumor cells and staining intensity of galectin-1 in tumor-associated stromal cells were scored semiquantitatively. The relationship between expression and staining intensity of CD24 and galectin-1 and clinicopathologic variables were assessed. CD24 staining intensity was associated with lymphovascular invasion (p = 0.007), serosal invasion (p = 0.001), stage (p = 0.001) and lymph node metastasis (p = 0.005). Galectin-1 staining intensity in tumor-associated stromal cells was associated with tumor location (p = 0.031), lymphovascular invasion (p = 0.001), perineural invasion (p = 0.001), serosal invasion (p = 0.001), differentiation (p = 0.003), stage (p = 0.001) and lymph node metastasis (p = 0.001). Staining intensity of CD24 (p = 0.019) and gal-1 (p = 0.018) were associated with patient survival. Staining intensity of CD24 in tumor cells and galectin-1 in tumor-associated stromal cells were related with certain clinicopathologic variables. Our findings suggest that these markers are independent prognostic indicators of poor survival and may serve as useful targets for novel therapies.     

Expression of EphA2 and E-cadherin in Gastric Cancer: Correlated with Tumor Progression and Lymphogenous Metastasis

In this study, gastric cancer progression was correlated with the over-expression of erythropoietin-producing hepatocellular (Eph)A2 receptor and down-expression of epithelial cadherin (E-cadherin). Immunohistochemistry of EphA2 and E-cadherin were performed on these tumor samples from 165 primary lesions of gastric cancer. The results showed that expression of EphA2 was obviously increased in gastric cancer tissues (P < 0.01), which was positively correlated with the depth of cancer invasion, tumor-node-metastasis (TNM) stage and lymph node metastasis (P < 0.05). Meanwhile, the expression of E-cadherin was significantly reduced (P < 0.01), which was negatively correlated with the depth of cancer invasion, grade of tumor differentiation, TNM stage and lymph node metastasis (P < 0.05). The correlation between EphA2 and E-cadherin expression was negative (r = −0.198, P = 0.011). In conclusion, either the over-expression of EphA2 or the down-expression of E-cadherin is correlated with cancer progression and lymphogenous metastasis in gastric cancer, suggesting that both of them may play an important role in tumor progression and metastasis.     

PEBP4基因在食管癌中的表达及其临床意义

目的 探讨磷脂酰乙醇胺结合蛋白4(phosphatidylethanolamine-binding protein 4,PEBP4)基因在食管癌组织中的表达及其与食管癌临床病理的相关性,并探讨其在食管癌侵袭转移过程中的作用.方法 采用RT PCR、免疫组织化学和Western blot方法检测56例食管癌组织中PEBP4 mRNA和蛋白的表达情况,采用RNA干扰技术,下调Eca-109人食管癌细胞中PEBP4表达后,观察Eca-109细胞侵袭能力的变化.结果 全组56例食管癌患者,PEBP4 mRNA和蛋白在食管癌组织中的表达显著高于癌旁相对正常黏膜组织(P＜0.05),在淋巴结转移及远处转移阳性患者癌组织中的表达显著高于在淋巴结转移和远处转移阴性患者癌组织中的表达(P＜0.05);但PEBP4的表达与食管癌患者的性别、年龄及肿瘤大小及分化程度无关(P＞0.05).下调PEBP4蛋白表达可以显著降低Eca-109细胞的侵袭转移能力(P＜0.01).结论 PEBP4蛋白的过表达可能与食管癌的发生及侵袭转移有关.     

Upregulation of Bone Morphogenetic Protein 4 is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma

Bone morphogenetic protein (BMP) 4 plays a crucial role in tumor invasion and metastasis of various human cancers. However, little is known about the correlation of BMP4 expression with clinical aggressiveness and prognosis in hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression of BMP4 in HCC and determine its correlation with tumor progression and prognosis. Immunohistochemistry assay was used to determine the expression of BMP4 in HCC and corresponding paracarcinomatous tissues from 156 patients. The potential prognostic value of BMP4 was investigated by comparing the survival rates between the BMP4-positive and BMP4-negative HCC patients. Immunohistochemically, BMP4 protein expression in the HCC tissues (120/156, 76.9%) was significantly higher than that in the paracarcinomatous tissues (19/156, 12.2%, P < 0.01). The expression of BMP4 in HCC was associated with number of tumor nodules (P = 0.02), Edmondson grade (P = 0.03), TNM stage (P = 0.009), and vascular invasion (P = 0.006). In univariate survival analysis, the significant associations of the BMP4 protein overexpression with shortened patients’ overall and disease-free survival were found (P = 0.001 and 0.006, respectively). Furthermore, its expression was found to be an independent factor for predicting both overall (P = 0.009) and disease-free survival (P = 0.022) of HCC in multivariate analysis. Our data suggest for the first time that BMP4 is overexpressed in HCC tissues and may also act as a novel marker for predicting the recurrence and prognosis of HCC patients after surgery.     

Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer

Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis.     

Clusterin Expression Inversely Correlates with Chemosensitivity and Predicts Poor Survival in Patients with Locally Advanced Cervical Cancer Treated with Cisplatin-Based Neoadjuvant Chemotherapy and Radical Hysterectomy

Overexpression of clusterin, an antiapoptotic molecule, has been reported to induce resistance to chemotherapy in a variety of cancer cell types. The aim of this study was to evaluate the significance of clusterin expression to predict response to platinum-based neoadjuvant chemotherapy and survival of patients with invasive cervical cancer who subsequently underwent radical hysterectomy. Biopsy specimens of invasive cervical cancer before neoadjuvant chemotherapy were obtained from 46 patients who subsequently underwent radical hysterectomy at Hokkaido University Hospital and Gunma University Hospital from 1994 to 2007. The expression of clusterin protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed by the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of clusterin protein in cervical cancer tissues before neoadjuvant chemotherapy was significantly related to poor response to chemotherapy among factors analyzed. Univariate analysis on prognostic factors showed that response to chemotherapy (p = 0.01), lymph node metastasis (p = 0.02), and clusterin expression (p = 0.02) were related to survival. Multivariate analysis revealed that lymph node metastasis (p = 0.03), and clusterin expression (p = 0.03) were independent prognostic factors for survival of cervical cancer patients. We conclude that clusterin expression could be a new molecular marker to predict response to platinum-based chemotherapy and survival of patients with cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy.     

Recombinant Human Endostatin Endostar Inhibits Tumor Growth and Metastasis in a Mouse Xenograft Model of Colon Cancer

To investigate the effects of recombinant human endostatin Endostar on metastasis and angiogenesis and lymphangiogenesis of colorectal cancer cells in a mouse xenograft model. Colon cancer cells SW620 were injected subcutaneously into the left hind flank of nude mice to establish mouse xenograft models. The mice were treated with normal saline or Endostar subcutaneously every other day. The growth and lymph node metastasis of tumor cells, angiogenesis and lymphangiogenesis in tumor tissue were detected. Apoptosis and cell cycle distribution were studied by flow cytometry. The expression of VEGF-A, -C, or -D in SW620 cells was determined by immunoblotting assays. Endostar inhibited tumor growth and the rate of lymph node metastasis (P < 0.01). The density of blood vessels in or around the tumor area was 12.27 ± 1.21 and 22.25 ± 2.69 per field in Endostar-treated mice and controls (P < 0.05), respectively. Endostar also decreased the density of lymphatic vessels in tumor tissues (7.84 ± 0.81 vs. 13.83 ± 1.08, P < 0.05). Endostar suppresses angiogenesis and lymphangiogenesis in the lymph nodes with metastases, simultaneously. The expression of VEGF-A, -C and -D in SW620 cells treated with Endostar was substantially lower than that of controls. Endostar inhibited growth and lymph node metastasis of colon cancer cells by inhibiting angiogenesis and lymphangiogenesis in a mouse xenograft model of colon cancer.