骨桥蛋白与肿瘤转移的研究进展

骨桥蛋白是一种具有多种功能的细胞外基质蛋白,参与肿瘤转移的多个过程。骨桥蛋白与肿瘤转移的密切关系日益受到重视。骨桥蛋白及其相关受体是防治肿瘤转移的潜在靶点。     

骨桥蛋白与结直肠癌及肝转移关系研究进展

骨桥蛋白（ OPN）是一种具有分泌性、粘附性的磷酸化的酸性糖蛋白,因其在多个肿瘤的发生发展和转移过程中密切相关,被称为肿瘤相关性蛋白。骨桥蛋白通过调节肿瘤细胞的黏附、迁移和刺激周围血管的生成,促进肿瘤侵袭和转移。研究证实,骨桥蛋白可作为结直肠癌发生和肝转移良好的诊断标记,是肿瘤免疫治疗的新靶点。通过总结OPN结构、功能及作用机制,对骨桥蛋白与结直肠癌发生和肝转移的相关性研究展开综述。     

骨桥蛋白与肿瘤(文献综述)

骨桥蛋白 (osteopontin,OPN)是一种磷酸化糖蛋白 ,在一些正常组织中少量表达 ,但在许多癌组织中表达量增加 ,它特别与肿瘤的浸润与转移有密切关系。本文对 OPN的结构特点及其在癌组织中的表达以及与转移的关系予以综述。     

TMPRSS4与肿瘤侵袭转移的关系

Ⅱ型跨膜丝氨酸蛋白酶4（TMPRSS4）是一种新发现的Ⅱ型跨膜丝氨酸蛋白,目前研究发现它的表达与肿瘤的侵袭转移存在相关性,但具体作用机制目前尚不明确。本文就其基本结构、生物学功能及其在肿瘤侵袭转移方面的作用和机制作一综述。     

BMI-1在泌尿系肿瘤侵袭性转移中的研究进展

原癌基因B细胞特异性小鼠白血病病毒插入位点1(BMI-1)为多梳基因家族的一员,是一种原癌基因,今年来有研究发现BMI-1基因与多种肿瘤发生、增值、转移和复发密切相关。本文介绍BMI-1的结构及生物学功能,综述其在膀胱癌、前列腺癌、肾癌肿瘤侵袭、转移中的作用及其相关机制。     

骨桥蛋白信号通路与肿瘤转移

骨桥蛋白（osteopontin OPN）是一种具有多种功能的细胞外基质蛋白。OPN与其受体（整合素或CD44V）结合后激活细胞内多条信号通路,参与肿瘤转移的多个过程。本文综述OPN相关信号通路促进肿瘤转移的研究。     

骨桥蛋白与肿瘤（文献综述）

骨桥蛋白（ｏｓｔｅｏｐｏｎｔｉｎ，ＯＰＮ）是一种磷酸化糖蛋白，在一些正常组织中少量表达，但在许多癌组织中表达量增加，它特别与肿瘤的浸润与转移有密切关系。本文对ＯＰＮ的结构特点及其在癌组织中的表达以及与转移的关系予以综述。     

核转录因子κB与前列腺癌

核转录因子κB(nuclearfactorofkappaB ,NF κB)是一种多极性核转录因子 ,参与调控多种与免疫反应、凋亡、炎症、肿瘤形成和转移有关的基因表达。近年来 ,NF κB在肿瘤发生、耐药、转移中的作用及其机制逐渐成为医学研究的热点。本文主要综述了NF κB的结构、生物学功能及其抗凋亡诱发肿瘤的机制 ,NF κB调控的前列腺癌相关基因的表达和调控 ,NF κB参与前列腺癌浸润与转移的机制及其在前列腺癌基因治疗中的可能策略等。     

直肠癌患者外周血骨桥蛋白的检测

骨桥蛋白(Osteopontin,OPN)是一种磷酸化糖蛋白,骨桥蛋白的表达和恶性肿瘤的发生及远处转移的产生有关,是一种新的肿瘤标志物[1].本试验初步探讨了骨桥蛋白作为直肠癌肿瘤标志物的价值,并和CEA进行比较.     

次级淋巴组织趋化因子及其受体CCR7在肿瘤侵袭和淋巴转移中的研究进展

次级淋巴组织趋化因子（SLC）是近年发现的一种新的趋化因子,高表达于次级淋巴组织,能趋化并活化T淋巴细胞、树突状细胞和自然杀伤细胞等免疫效应细胞,在机体淋巴细胞的迁移归巢、抗肿瘤、抗感染过程中具有重要作用。CCR7是SLC的高亲和力受体,近年来研究发现,CCR7和SLC的表达与肿瘤的淋巴转移密切相关。现综述SLC及其受体CCR7的生物学特性和主要功能,并重点阐述SLC和CCR7在肿瘤侵袭和淋巴转移中的研究现状。     

Clinical significance of osteopontin expression in T1 and T2 tongue cancers

BACKGROUND: Osteopontin (OPN) is considered to be a tumor-related protein associated with tumor aggressiveness and metastasis. METHODS: Immunohistochemistry was used to study the clinical significance of OPN expression in T1 and T2 tongue cancers. RESULTS: Positive OPN expression significantly correlated with higher tumor classification (T) (p = .004), positive nodal classification (N) (p < .001), greater tumor thickness (p < .001), and presence of tumor necrosis (p = .016), respectively. The unfavorable cumulative 5-year disease-free survival rate significantly correlated with positive OPN expression (p < .001), T2 (p = .024), positive N (p < .001), greater tumor thickness (p = .023), and positive tumor necrosis (p = .003). However, taking CD105 into consideration, only CD105 expression was the independent prognostic factor for survival by Cox's regression analysis. CONCLUSION: Overexpression of OPN in the tumors implicated a more aggressive tumor behavior and was an important factor for survival. In addition, there might be relationship between OPN and CD105 expressions in angiogenesis.     

Importance of tumor/stroma interactions in prognosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third largest cause of cancer deaths worldwide. It seems to be needed to find new ways to address the mechanisms involved in the progression of HCC, which can provide a prognostic evaluation and new therapeutic targets. Several studies have established that crosstalk between tumor cells and the microenvironment plays a key role in tumor progression and metastasis. In this context, the work of Zhu et al. contributes to assess interactions between tumor and microenvironment associated-macrophages promoting tumor progression and metastasis. Indeed, they concluded that the interplay of osteopontin (OPN) and peritumoral macrophages (PTMs) represents a new insight into tumor progression and therapeutic targets for HCC. Historically, tumor-infiltrating leukocytes have been considered to be manifestations of an intrinsic defensive mechanism against developing tumors, however, now, it is know that that leukocytes infiltration can promote tumor phenotypes, such as angiogenesis, growth, and invasion. Characterization of functional heterogeneity of stromal cell components, and specifically the analysis of stromal fibroblasts can provide a new focus on mechanisms involved in the progression of HCC. All of this opens the possibility to provide prognostic information for HCC based on biological parameters derived from peritumoral status from tumors.     

Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor proliferation

BACKGROUND: Interactions between tumor cells and their host environment can play a major role in regulating survival programs required for tumor progression. Osteopontin (OPN) is a glycophosphoprotein overexpressed by tumors, and is a key molecule for tumor progression and metastasis. OPN also inhibits expression of autocrine and paracrine inducible nitric oxide synthase (iNOS). Given the cytotoxic effects of macrophage NO expression, we hypothesized that tumor-derived OPN inhibits expression of local macrophage iNOS to potentiate tumor survival. METHODS: We used a coculture system of murine CT26 colorectal cancer cells with RAW264.7 murine macrophage cells. CT26 expresses OPN at high levels. RNA interference was utilized to produce long-term specific silencing of OPN in CT26. RESULTS: Inhibition of constitutive OPN synthesis in CT26 upregulates local NO production with inhibition of CT26 proliferation and promotion of CT26 apoptosis. Macrophage iNOS expression is accompanied by increased binding activity of nuclear factor-kappaB DNA. When the CT26 culture media were examined for a panel of proinflammatory cytokines, elevated concentrations of granulocyte colony-stimulating factor (G-CSF) were found. Subsequently, in CT26 cells treated with antisense-G-CSF, NO levels in CT26-RAW cocultures were significantly decreased. CONCLUSION: In our system of CT26-RAW264.7 coculture, we conclude that inhibition of OPN synthesis in CT26 results in G-CSF-mediated induction of macrophage iNOS expression with resultant inhibition of CT26 proliferation via increased apoptosis. Our results suggest that tumor-derived OPN may enhance tumor survival by down regulating expression of NO in the local microenvironment. This is one mechanism by which OPN may potentiate cancer survival and progression.     

Osteopontin overexpression predicts poor prognosis of upper urinary tract urothelial carcinoma

Objectives

Studies indicate overexpression of osteopontin (OPN) promotes carcinogenesis, progression and metastasis of multiple human malignancies. However, the function of OPN in urothelial carcinoma (UC) of the upper urinary tract has not been investigated. This study evaluates the clinical significance of OPN expression in upper urinary tract UC.

Materials and methods

One hundred and ten cases (median age = 64, range = 24–84 years) of renal pelvic or ureter UC were retrospectively reviewed in this study. OPN expression were evaluated by immunohistochemistry staining on paraffin-embedded section of the tumor and scored by two qualified pathologists.

Results

High OPN expression was found in 54 (49.1%) of the cancer specimens. OPN expression was not significantly correlated with tumor T stage (P = 0.761), N stage (P = 0.339) or grade (P = 0.349). However, OPN expression was differently expressed by gender (P = 0.012) and cancer location (P = 0.026). OPN expression did not correlate with bladder recurrence-free (P = 0.661) or extra-bladder recurrence-free (P = 0.787) survival, but high OPN expression was a significant predictor for cancer-specific survival (P = 0.014).

Conclusion

Our findings indicated that higher OPN expression is a potential biomarker to predict patient survival. Further study is necessary to investigate the role of OPN in the carcinogenesis of upper urinary tract UC.     

胰腺癌血清肿瘤标志物的研究现状

胰腺癌的发病率在世界范围内呈逐年上升趋势,其早期诊断困难,手术切除率低,5年生存率仅为5%左右.改善胰腺癌不良预后的关键在于早期诊断和根治性切除.检测血清肿瘤标志物有助于胰腺癌的诊断、预后判断和治疗监测.尽管有一定的局限性,CA19-9仍是目前临床最常用的胰腺癌血清肿瘤标志物.近年来随着分子生物学技术的发展,不断有新的候选胰腺癌血清肿瘤标志物被发掘,如MIC-1、M2-PK、OPN和RCASl等.本文简要综述了胰腺癌血清肿瘤标志物的研究现状和进展.     

Increased Osteopontin-Positive Macrophage Expression in Colorectal Cancer Stroma with Synchronous Liver Metastasis

Background  

The macrophages that infiltrate the tumor stroma are termed tumor-associated macrophages (TAMs). TAMs contribute to hematogenous spread of cancer cells especially liver metastasis. Osteopontin (OPN) is also related to tumor metastasis and proliferation of tumors. OPN is mainly expressed in macrophages of stroma other than that of tumor cells. The aim of the present study was to investigate differences in OPN-positive TAMs between cases of colorectal cancer with synchronous liver metastasis and those without liver metastasis.     

Comparison of laparoscopic and open partial nephrectomy in clinical T1a renal tumors

PURPOSE: Partial nephrectomy has been established as a standard of care for T(1a) renal tumors. Laparoscopic partial nephrectomy (LPN) has been described as more difficult to perform than open partial nephrectomy (OPN). We compare our series of LPN and OPN. PATIENTS AND METHODS: From October 2002 to January 2006, 76 LPNs were performed for patients with clinical T(1a) tumors. These patients were matched with a cohort of patients who underwent OPN for solitary tumors of 4 cm or smaller in diameter. The cohorts were compared with regard to demographics, perioperative data, and outcomes. RESULTS: The patient populations were demographically similar. Although mean tumor size was smaller in the laparoscopic cohort (2.5 v 2.9 cm, P=0.002), the OPN cohort demonstrated shorter operative (193 v 225 min, P=0.004) and ischemia times (20.5 v 32.8 min). LPN was associated with less blood loss (212 v 385 mL, P<0.001) and shorter hospital stay (2.5 v 5.6 days, P<0.001), however. One positive margin occurred in each of the LPN and OPN cohorts. Intraoperative complications were similar, although LPN was associated with fewer postoperative complications. Of note, two LPN (2.6%) patients had emergent reoperation and complete nephrectomy because of postoperative hemorrhage. CONCLUSIONS: Despite increased operative and ischemia times, LPN patients demonstrated quicker recovery and fewer postoperative complications. Two patients in the LPN group, however, had emergent complete nephrectomy because of hemorrhage. We conclude that LPN is still an evolving alternative to OPN in patients with small renal tumors.