Clinical study on the metastasis to the eyes from breast cancer

In our hospital, 24 patients who underwent surgery for breast cancer during 1980 to 2001 were diagnosed with metastasis to the eye. Metastasis to the choroid was found most frequently, making the choroid the most common site of metastasis. A few patients had metastasis in the orbit. Decreased visual acuity and tunnel vision were frequently found in patients who had metastasis to the choroid, and ocular floaters and blurred vision were also found in a few patients. Patients with metastasis to the orbit showed diplopia caused by ocular dyskinesia and eyelid swelling. The mean postoperative period until the diagnosis with metastasis to the eye was 3 years and 2 months, with most cases diagnosed between 20 and 40 months postoperatively, a relatively long period. We performed radiotherapy in 21 of the 24 patients, and more than half of the patients showed improvement. The mean survival period after diagnosis with metastasis to the eye was 10 months, and most of them already had recurrence to other organs such as the bones or lungs. Examination with consideration of metastasis to the eyes is required to improve the quality of life of cancer patients.     

Management of choroidal metastasis: a report

Cancers metastatic to the eye are the most common intraocular malignancy, the choroid being the most common site of affection. Breast and lung cancers are the two most common malignancies metastatic to the eye. Patients usually present with diminished visual acuity of field loss. Management of these cases is very gratifying with a large majority of patients showing resolution and maintenance of useful vision in the involved eye. This communication presents our experience in management of a case of choroidal metastasis from a breast primary. A combination of radiotherapy and chemotherapy lead to complete resolution of the lesion with no recurrences in a follow-up of over 6 months.     

原发鼻咽癌及颈部淋巴结转移灶中VEGF-C和E-cadherin的表达

目的 探讨血管内皮生长因子C（vascular endothelial growth factor C,VEGF-C）和E-cadherin在鼻咽癌组织及其淋巴结转移灶中的表达及意义.方法 采用免疫组化SP法检测45例鼻咽癌组织及28例相应淋巴结转移灶中VEGF-C和E-cadherin的表达.结果 VEGF-C和E-cadherin在45例鼻咽癌组织中阳性率分别为40.00%和55.56%,在28例淋巴结转移灶中阳性率分别为78.57%和25.00%,两者在鼻咽癌组织和鼻咽癌淋巴结转移组织中阳性率比较均有显著性差异（P＜0.05）;淋巴结转移的鼻咽癌组织中VEGF-C阳性率明显高于无淋巴结转移组;淋巴结转移的鼻咽癌组织中E-cadherin阳性率明显低于无淋巴结转移组织.结论 VEGF-C高表达或E-cadherin低表达可能与鼻咽癌淋巴结转移密切相关.     

High COX-2 expression in cancer-associated fibiroblasts contributes to poor survival and promotes migration and invasiveness in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. We have previously shown that high cyclooxygenase-2 (COX-2) expression is associated with a poor prognosis of patients with NPC and inhibits chemotherapy-induced senescence in NPC cells. In this study, we found that COX-2 was upregulated in cancer-associated fibroblasts (CAFs) derived from NPC by RNA-Seq. Furthermore, elevated COX-2 expression in CAF was detected in NPC patients with poor survival and distant metastasis by using immunohistochemistry. Then, we identified that COX-2 is highly expressed in CAF at the distant metastasis site in seven paired NPC patients. High expression of COX-2 and secretion of prostaglandin E2, a major product catalyzed by COX-2 in fibroblasts, promotes migration and invasiveness of NPC cells in vitro. On the contrary, inhibition of COX-2 has the opposite effect in vitro as well as in the COX-2^−/− mouse with the lung metastasis model in vivo. Mechanistically, we discovered that COX-2 elevates tumor necrosis factor-α expression in CAF to promote NPC cell migration and invasiveness. Overall, our results identified a novel target in CAF promoting NPC metastasis. Our findings suggested that high expression of COX-2 in CAF may serve as a new prognostic indicator for NPC metastasis and provide the possibility of targeting CAF for treating advanced NPC.     

趋化因子受体CXCR4在鼻咽癌中的表达及意义

目的探讨趋化因子受体CXCR4在人鼻咽癌中的表达及临床意义。方法采用Real-timeRT-PCR法检测鼻咽癌细胞株中CXCR4mRNA的表达,应用免疫组织化学法并结合组织阵列检测正常鼻咽组织、鼻咽癌和鼻咽癌淋巴结转移石蜡组织标本中CXCR4蛋白的表达情况。结果在7种鼻咽癌细胞株中,CXCR4基因在高成瘤、高转移潜能的5-8F细胞中表达水平最高,在无转移能力的610B细胞中表达最低。CXCR4蛋白在正常鼻咽组织、鼻咽癌和鼻咽癌淋巴结转移组织中表达差异具有统计学意义（P=0．002）;鼻咽癌组织中CXCR4表达高于正常鼻咽组（P=0．029）;伴发转移的鼻咽癌组织比未发生转移的鼻咽癌组织CXCR4表达增强,差异具有统计学意义（P=0．008）;淋巴结转移癌组织CX-CR4表达比鼻咽癌组织高（P=0．013）。结论本研究提示CXCR4表达与鼻咽癌转移存在密切关系,CXCR4表达可作为鼻咽癌转移过程中一个有价值的指标。     

鼻咽癌患者血清VEGF、CD44s、MMP-3蛋白定量分析及其临床意义

背景与目的:在人体液中可以检测到多种与肿瘤转移相关的因子,有文献报道这些因子与肿瘤分期、预后有关。本研究检测鼻咽癌(nasopharyngealcarcinoma,NPC)患者血清可溶性因子VEGF、CD44s、MMP-3表达水平,探讨其与肿瘤临床分期和预后的关系。方法:采用双抗体夹心ELISA法对46例无转移NPC患者、20例局部复发和/或器官转移的NPC患者和18例健康者外周血中VEGF、CD44S、MMP-3水平进行测定。结果:局部复发和/或远处转移的NPC患者血清VEGF平均水平(791.7±560.5)ng/L显著高于健康对照组(424.6±197.1)ng/L和无转移NPC组(429.0±249.7)ng/L;而健康组与无转移NPC组患者VEGF平均水平差异无显著性。初治患者中,T4期患者血清VEGF水平显著高于T1～T3期;初治NPC患者治疗前血清VEGF≥600ng/L与<600ng/L两组,治疗后2年无复发生存率有显著性差异(37.5%vs83.9%)。有转移NPC患者血清MMP-3水平(28.8±15.5)μg/L显著高于健康组(16.2±11.1)μg/L和无转移组(19.8±11.6)μg/L,健康组与无转移组患者MMP-3水平无显著性差异;治疗前血清MMP-3水平≥25μg/L与<25μg/L的初治NPC患者,治疗后2年无事件生存率无显著性差异。NPC患者血清CD44s水平显著高于健康对照组,但有转移与无转移NPC患者之间无显著性差异;治疗前血清CD44s浓度≥600μ     

Reduction of RKIP expression promotes nasopharyngeal carcinoma invasion and metastasis by activating Stat3 signaling

The role and underlying mechanism of Raf kinase inhibitory protein (RKIP) in nasopharyngeal carcinoma (NPC) metastasis remain unclear. Here, we showed that RKIP was downregulated in the NPC with high metastatic potentials, and its decrement correlated with NPC metastasis and poor patient survival, and was an independent predictor for reduced overall survival. With a combination of loss-of-function and gain-of-function approaches, we observed that high expression of RKIP reduced invasion, metastasis and epithelial to mesenchymal transition (EMT) marker alternations of NPC cells. We further showed that RKIP overexpression attenuated while RKIP knockdown enhanced Stat3 phosphorylation and activation in NPC cells; RKIP reduced Stat3 phosphorylation through interacting with Stat3; Stattic attenuated NPC cell migration, invasion and EMT marker alternations induced by RKIP knockdown, whereas Stat3 overexpression restored NPC cell migration, invasion and EMT marker alternations reduced by RKIP overexpression. In addition, there was an inverse correlation between RKIP and phospho-Stat3 expression in the NPC tissues and xenograft metastases. Our data demonstrate that RKIP is a metastatic suppressor and predictor for metastasis and prognosis in NPC, and RKIP downregulation promotes NPC invasion, metastasis and EMT by activating Stat3 signaling, suggesting that RKIP/Stat3 signaling could be used as a therapeutic target for NPC metastasis.     

Role of a novel EGF-like domain-containing gene NGX6 in cell adhesion modulation in nasopharyngeal carcinoma cells

The epidermal growth factor (EGF)-like domain is involved in receptor-ligand interactions, extracellular matrix formation, cell adhesion and chemotaxis. Nasopharyngeal carcinoma associated gene 6 (NGX6) is a novel EGF-like domain-containing gene located at the high frequent loss of heterozygosity (LOH) region 9p21-22 associated with nasopharyngeal carcinoma (NPC). It is down-regulated in NPC and its over-expression can delay the cell cycle G(0)-G(1) progression in NPC cells. In the present study, in situ hybridization analysis, using NPC tissue microarrays, showed that loss of NGX6 expression was associated with NPC lymph node metastasis. The Tet-on gene expression system and cDNA array techniques were used to profile the potential targets of NGX6. We found that NGX6 can influence the expression of some cell adhesion molecules in NPC cells. NGX6 can associate with ezrin, a linkage between the cell membrane and cytoskeleton. The NGX6 protein was expressed on the cell surface as a glycoprotein. Ectopic induction of NGX6 can impair NPC cell migration and invasive ability as well as improve cell adhesion and gap junctional intercellular communication, and can suppress tumor formation in vivo. The data revealed that NGX6 plays a role in cell adhesion modulation in NPC cells.     

鼻咽癌颈淋巴结转移的生物学基础研究

鼻咽癌是一种亲淋巴系统转移的恶性肿瘤,颈部淋巴结转移率可高达78.9%,并与预后密切相关,故研究鼻咽癌颈淋巴结转移的生物学机制具有重要的临床意义。目前已进行的研究发现鼻咽癌的颈淋巴结转移与细胞黏附机制、基质金属蛋白酶、肿瘤血管生成、肿瘤细胞基因改变及EB病毒编码膜潜伏蛋白等几方面因素有密切关系,但其确切机制仍未阐明。探究鼻咽癌颈部淋巴结转移的生物学机制可以为临床工作治疗淋巴结转移提供理论指导,从而为进一步提高鼻咽癌的疗效作出贡献。     

Matrix metalloproteinase 13‐containing exosomes promote nasopharyngeal carcinoma metastasis

Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13‐containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients’ plasma. Transwell analysis revealed that MMP13‐containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13‐containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13‐containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.     

Recombinant adeno-associated virus mediated RNA interference inhibits metastasis of nasopharyngeal cancer cells in vivo and in vitro by suppression of Epstein-Barr virus encoded LMP-1

Nasopharyngeal carcinoma (NPC) is a highly metastatic carcinoma characterized by consistent association with Epstein-Barr virus (EBV). Of the EBV-encoded product, latent membrane protein-1 (LMP-1) is considered to be an onco-protein playing an essential role in cell transformation and metastasis. In this study, we used a recombinant adeno-associated virus type 2 vector (rAAV-2) to deliver small hairpin RNA (shRNA) targeting EBV LMP-1 into the EBV-positive human NPC C666-1 cells and evaluated the effect of long-term suppression of LMP-1 on NPC growth and metastasis in vivo and in vitro. An NPC metastasis nude mouse model with NPC xenograft transplanted in liver was established. The NPC C666-1 cells infected with rAAV-shRNA-LMP-1 or rAAV-EGFP were inoculated in the livers of nude mice. Formation of liver and lung metastasis was evaluated at day 14 after tumor inoculation. Our results demonstrate that rAAV-shRNA-LMP-1 effectively infected C666-1 cells and suppressed LMP-1 expression. Such suppression, in turn, did not significantly inhibit tumor growth, but prevented NPC metastasis in the liver as well as in the lung. Consistent with in vivo data, the in vitro studies in NPC C666-1 cell cultures showed that suppression of LMP-1 by rAAV-shRNA-LMP-1 significantly reduced cell mobility and transmembrane invasion ability. These results demonstrated for the first time that long-term suppression of EBV-encoded LMP-1 in vivo is an effective means for preventing NPC metastasis.     

VEGF蛋白检测对预测鼻咽癌远处转移风险的价值

背景与目的:血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)是最重要的血管生长促进因子,并与多种肿瘤的恶性度及转移关系密切。本研究旨在通过同时检测鼻咽癌组织及血浆中的VEGF蛋白,评价其对预测鼻咽癌远处转移风险的价值。方法:同时收集59例鼻咽癌患者治疗前鼻咽癌组织及血清标本,用免疫组化LSAB法检测鼻咽癌组织中的VEGF蛋白,用ELISA法检测血清中的VEGF蛋白;并随访了解患者的远处转移情况,分析VEGF蛋白水平与患者远处转移的关系。结果:鼻咽癌组织及血清中的VEGF蛋白水平与远处转移均成正相关(均P<0.05)。鼻咽癌组织中VEGF蛋白表达阴性(-)、弱阳性(+)、阳性(++)和强阳性(+++)组患者的3年无转移生存率分别为100%、95.24%、65.19%、58.93%,各组之间有显著性差异(P=0.0193)。血清VEGF蛋白水平<466.78ng/L和≥466.78ng/L组的3年无转移生存率分别为82.57%,59.11%,两组比较有显著性差异(P=0.0211)。多因素分析发现鼻咽癌组织及血清VEGF蛋白水平对鼻咽癌远处转移都是独立的影响因素。结论:鼻咽癌组织及血清中VEGF蛋白检测均可用于判断鼻咽癌患者远处转移风险,二者联合检测可提高预测患者出现远处转移的能力。     

Occipital lymph node metastasis from nasopharyngeal carcinoma：a special case report and literature review

Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma (NPC), but occipital lymph node metastasis in NPC patients has not yet been reported. In this case report, we describe an NPC patient with occipital lymph node metastasis. The clinical presentation, diagnostic procedure, treatment, and outcome of this case were presented, with a review of the related literature.     

鼻咽癌远处转移及预后的相关因素

远处转移是鼻咽癌（NPC）治疗失败的主要原因.患者临床相关因素如年龄、性别、肿瘤分期等可影响鼻咽癌远处转移及预后.NPC远处转移的分子标志物包括EB病毒DNA、p53、表皮生长因子受体和血管内皮生长因子,其有望成为NPC预后的生物学指标.另外,病理分型和治疗手段也是NPC预后的影响因素.     

p53过量表达对鼻咽癌预后的影响

用免疫组织化学技术对部分鼻咽癌标本ｐ５３过量表达情况进行了分析，发现肿瘤ｐ５３过量表达与鼻咽癌患者肿瘤临床分期和常规放疗后的复发或转移没有明显的相关性（Ｐ＞０．０５），不同程度的ｐ５３过量表达对患者生存率无明显影响（Ｐ＞０．０５），肿瘤ｐ５３过量表达阳性组和阴性组患者远期生存率无显著性差异（Ｐ＞０．０５）。结果提示鼻咽癌中ｐ５３过量表达不宜作为判断患者预后的指标     

血管内皮生长因子C、D在鼻咽癌组织中的表达及其临床意义

背景与目的:血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C)和D(vascular endothelial growth factor-D,VEGF-D)是目前已鉴定出的淋巴管生长因子,有研究表明肿瘤组织中VECF-C或VEGF-D过表达与淋巴转移有关.本研究旨在探讨鼻咽癌组织中VEGF-C和VEGF-D的表达情况及其临床意义.方法:采用免疫组化SP法检测66例鼻咽癌组织中VEGF-C和VEGF-D的表达情况,同时检测血管内皮生长因子受体3(vascular endotheliaI growth factor receptor-3,VEGFR-3)和CD34染色情况并计数微淋巴管密度(lymphatic microvessel density,LMVD)和微血管密度(microvessel density,MVD).结果:VEGF-C高表达率在鼻咽癌组织中(54.5%)较鼻咽非肿瘤组织中(26.3%)高(P＜0.05);鼻咽癌伴区域淋巴结转移或T分期晚者,VEGF-C高表达率增高,单因素及多因素Logistic回归分析均表明区域淋巴结转移与VEGF-C高表达相关(P＜0.05),但VEGF-C高表达与性别、年龄、5年生存率、LMVD、MVD等因素无关(P＞0.05).VEGF-D阳性表达率在鼻咽癌组织中(69.7%)较鼻咽非肿瘤组织中(42.1%)高(P＜0.05);鼻咽癌中VEGF-D阳性表达与性别、年龄、T分期、区域淋巴结转移、LMVD、MVD等因素无关(P＞0.05),但与VEGF-C高表达显著正相关(P＜0.01),VEGF-D阳性表达者5年生存率(50.0%)显著低于VEGF-D不表达者(85.0%)(P＜0.01).结论:鼻咽癌中VEGF-C高表达与区域淋巴结转移密切相关;VEGF-D阳性表达与区域淋巴结转移无关,但与VEGF-C高表达正相关,且与5年生存率密切相关.     

Long survival in an untreated solitary choroid plexus metastasis from renal cell carcinoma: case report and review of the literature

Brain metastases from renal cell carcinoma (RCC) are rare. Among them, the metastases localized only in the choroid plexus are exceptional and only six cases are reported in the literature. Here we report on a patient with a single choroid plexus metastasis from RCC which presented an unusual biological behaviour. For several years, such metastasis was interpreted as a benign intraventricular tumor and was not treated. Four years after the initial neuroradiological evidence, because of the appearance of symptoms, the brain metastasis was excised. We think that this unusual biological behaviour of the tumor determined the late inset of the neurological symptoms, despite the location at the choroid plexus that usually leads to an early obstructive hydrocephalus. To our knowledge, this 46months survival is the longest survival of a patient affected by a single choroid plexus metastasis from RCC.     

鼻咽癌巨噬细胞浸润与细胞分化和转移的关系

目的 :研究鼻咽癌巨噬细胞的浸润与细胞分化和转移的关系。方法 :对 4 8例鼻咽癌(NPC)标本应用 (溶菌酶 )抗体以免疫组化技术标记NPC组织中巨噬细胞进行观察 ,同时进行了DNA含量及肿瘤转移率的测定和分析。结果 :首次发现不同DNA含量与NPC转移率之间存在显著性差异。二倍体巨噬细胞均数最高为 16 .3,高分化癌占 77.8% ,无一例发生淋巴结转移。四倍体肿瘤巨噬细胞均数降至 14.3,高分化癌占 4 0 % (8/ 2 0 ) ,且 6 5 %的标本发生了肿瘤的转移。非整倍体和异倍体肿瘤平均计数分别为 13.1%和 9.1%之间。结论 :这种依DNA含量分组揭示的巨噬细胞分布状况与肿瘤转移率间的规律性变化 ,可为临床和基础研究提供新途径。     

148例鼻咽癌肝转移的治疗与预后分析

目的探讨鼻咽癌肝转移的临床特点、治疗效果及预后因素。方法 采用SPSS 13.0统计软件回顾性分析148例鼻咽癌肝转移患者的临床特点、治疗、生存及预后因素。结果 全组中位无病生存期(DFS)8.5个月(0-247个月), 肝转移后的中位生存期7个月(1-76个月), 1、2和3年生存率分别为24.3%、6.6%和2.6%。未治组、化疗组与放化疗组生存差异有显著的统计学意义(P=0.000), 中位生存期分别为3、8和18.5个月。＞4疗程化疗较无治疗和≤4疗程化疗者死亡风险分别下降63%和31%。多因素分析显示年龄、DFS、初治即转移、肝转移的数目及转移后的治疗为影响预后的重要因素。结论 鼻咽癌肝转移预后不良, 须根据病情作合理的个体化治疗。对于非高龄(≤60岁)、肝功能无明显异常和无腹水的患者, 争取行多疗程化疗(＞4疗程)及综合放射治疗, 可提高肝转移的生存期。