Hepatic Stellate Cells in Inflammation‐Fibrosis‐Carcinoma Axis

Almost 80% of hepatocellular carcinoma (HCC) cases are associated with chronic hepatitis and cirrhosis resulting from inflammation and fibrosis. A three‐step process of “inflammation‐fibrosis‐carcinoma” is believed to be involved in hepatocarcinogenesis. The activation of hepatic stellate cells (HSCs) may serve as an important mediator in the process of inflammation‐fibrosis‐carcinoma axis, even in tumor metastasis. A remarkable knowledge of activated HSCs in the pathology of HCC development is mostly focused on the liver fibrosis. The molecular links that connects inflammation and cancer in the activation of HSC are not completely known. This highlights urgent need to increase our understanding of the cellular and molecular mechanisms, by which activation of HSCs is involved in the hepatic inflammation, carcinogenesis, and metastasis. Anat Rec 293:1492–1496, 2010. © 2010 Wiley‐Liss, Inc.     

抗人结肠癌杂交瘤细胞系的建立及单克隆抗体特性研究

本研究利用手术中取得的新鲜结肠癌组织免疫ＢＡＬＢ／ｃ小鼠，制得５株能持续、稳定分泌抗体的杂交瘤细胞系。其中ＨＣ６株杂交瘤细胞经过１８０ｄ连续培养，单克隆抗体ＭＣ６分泌稳定、选择性强、效价高。免疫组化检测发现，ＭＣ６相应抗原在结肠癌组织及结肠癌细胞系呈高度表达（９０～１００％），显著高于其它癌组织、癌旁组织、正常粘膜及癌细胞系（０～４４．４％）；中度以上染色者占阳性总数的８０％以上；主要分布于细胞膜上。除癌细胞膜和胞浆呈阳性反应外，腺腔内粘液亦可见不同程度的着色，表明ＭＣ６相应抗原是一种在结肠癌细胞膜上占优势的抗原，并可脱落至腺腔。此单克隆抗体的成功研制为发现新的结肠癌生化标志，结肠癌的早期诊断及术后病情的监测提供了可能性。     

LINC00662 Promotes Oral Squamous Cell Carcinoma Cell Growth and Metastasis through miR-144-3p/EZH2 Axis

PurposeLong non-coding RNA (lncRNA) is identified as an important regulator involved in oral squamous cell carcinoma (OSCC) tumorigenesis. This study aimed to investigate the functional role and underlying mechanism of LINC00662 in OSCC.Materials and MethodsThe expression levels of LINC00662, miR-144-3p, and enhancer of zeste homolog 2 (EZH2) mRNA were quantified with quantitative real-time polymerase chain reaction in OSCC tissues and cell lines. Western blot analysis was used to assay the expression levels of E-cadherin, Vimentin, and EZH2. Cell proliferation, migration, and invasion were monitored by cell counting kit-8 and Transwell assays. Dual-luciferase reporter and RNA immunoprecipitation assays were employed to verify the regulatory relationship between LINC00662 and miR-144-3p.ResultsThe expression of LINC00662, positively associated with the increased TNM stage and lymph node metastasis of the patients, was up-regulated in OSCC tissues and cells. The overexpression of LINC00662 facilitated the proliferation, migration, and invasion of OSCC cells. MiR-144-3p could bind to LINC00662, and the promoting effect of LINC00662 overexpression was counteracted by miR-144-3p mimic. Moreover, EZH2 expression was negatively regulated by miR-144-3p and positively regulated by LINC00662. The silencing of EZH2 attenuated the promoting effects of overexpression of LINC00662 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition.ConclusionLINC00662, as an oncogenic lncRNA of OSCC, accelerates OSCC progression by repressing miR-144-3p expression and increasing EZH2 expression.     

结缔组织生长因子在血吸虫病肝纤维化鼠肝窦内皮细胞中的表达及意义

目的:动态观察结缔组织生长因子(CTGF)蛋白在血吸虫病肝纤维化鼠肝窦内皮细胞表达水平的时相变化,探讨其与肝窦内皮细胞下基底膜形成的关系。方法:采用腹部敷贴法建立血吸虫病肝纤维化模型,HE、Masson染色和透射电镜观察其病理变化;免疫组化技术检测CTGF、Ⅳ型胶原(ColⅣ)和层粘连蛋白(LN)在小鼠肝脏组织中的表达和分布;并应用彩色图像分析仪进行定量分析。结果:与正常对照组比较,模型组鼠肝窦内皮细胞表达CTGF蛋白阳性或强阳性,肝窦壁LN、ColⅣ表达水平增高,且随着肝纤维化的发展,CTGF和LN、ColⅣ表达逐渐增强,肝窦内皮下基底膜逐渐增厚。图像定量分析两组平均吸光度值、平均灰度值和阳性面积比具有统计学差异;CTGF蛋白与LN、ColⅣ水平呈正相关。结论:血吸虫病肝纤维化时小鼠肝窦内皮细胞通过CTGF蛋白表达上调,调控细胞外基质产生,导致ColⅣ、LN分泌增加,参与肝窦内皮下基底膜形成,从而引起肝内微循环障碍。     

右美托咪定对口腔鳞癌细胞生长和运动能力的调节

目的 探究右美托咪定 ( dexmedetomidine, DEX) 对口腔鳞癌 ( oral squamous cell carcinoma, OSCC) 细胞生长和运动的调节作用。 方法 人 OSCC 细胞 CAL27 分为 DEX0、 5、 10 及 20 nmol / L 组。 运用 克隆形成实验和 BrdU 实验评估细胞增殖; Transwell 法检测细胞侵袭; 流式细胞术检测细胞凋亡率; ELISA 检测超氧化物歧化酶 (SOD) 和丙二醛 (MDA) 水平; 微管形成实验评估细胞微管形成能力; Western 印 迹检测血管内皮生长因子 (VEGF)、 纤连蛋白 ( FN)、 B 细胞淋巴瘤 2 ( Bcl-2) 和 Bcl-2 相关 X 蛋白 (Bax) 的表达。 结果 与对照组比较, DEX 处理可显著降低 CAL27 细胞克隆形成率和 BrdU 阳性细胞率, 减少侵袭细胞数和微管结节数, 下调 VEGF 和 FN 表达水平。 同时 DEX 处理可促进氧化应激, 提高 Bax / Bcl-2 比率。 结论 DEX 处理可抑制 CAL27 细胞增殖、 侵袭和微管形成能力, 并促进其氧化应激和凋亡。     

The Incidence of Invasion and Metastasis of Nasopharyngeal Carcinoma at Different Anatomic Sites in the Skull Base

This study aimed to investigate the incidence of direct invasion and metastasis of nasopharyngeal carcinoma (NPC) at different anatomic sites in the skull base using magnetic resonance imaging (MRI). MRI data from 101 NPC patients with skull base invasion were collected and we analyzed the incidence and anatomic sites of invasion of NPC in the skull base. Of the 101 NPC patients, 84 had direct invasion at the skull base (83.2%), and 17 had skull base metastasis (16.8%). Affected sites with direct invasion in the skull base included sphenoid sinus and sella base, cavernous sinus, internal carotid canal, and clivus blumenbachii. Skull base metastasis sites included the internal carotid canal and jugular foramen area. Because of early lymphatic metastasis of NPC to the skull base, MRI examination can be helpful in increasing the accuracy of diagnostic imaging for skull base invasion of NPC and selecting appropriate target sites, radiotherapy techniques, and operative approaches. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

小鼠肝B220~+/DEC205~+树突状细胞对结肠癌肝转移的影响

目的:研究小鼠肝内B220~+/DEC205~+树突状细胞对结肠癌肝转移的影响.方法:小鼠尾静脉大容量快速注射重组质粒plasmid-IL-3/CD40L,诱导肝B220~+/DEC205~+树突状细胞增殖,小鼠脾内接种结肠腺癌CT26细胞,检测肝表面转移癌结节数量及脾内癌结节大小和重量、血清癌胚抗原含量及小鼠生存期.结果:处理组小鼠肝非实质细胞较对照组明显增多.小鼠脾包膜下接种CT26细胞后第14天,脾均有癌结节形成,仅肝表面见癌转移结节,转移率为100%.处理组肝表面转移癌结节数量明显多于对照组.脾内癌结节的大小、重量,处理组与对照组比较无明显差别.处理组较对照组血清癌胚抗原水平显著升高,小鼠生存期较对照组缩短.结论:小鼠肝内经重组质粒plasmid-IL-3/CD40L诱导扩增的B220~+/DCE205~+树突状细胞对结肠癌肝转移具有促进作用.     

肿瘤局部湿热治疗乳腺癌实验动物模型的建立及意义

目的：探讨局部湿热治疗对肿瘤生长的影响及意义。方法：建立Balb／c乳腺癌4T1实验动物模型，并以不同温度和作用时间对肿瘤进行局部湿热处理。结果：结果发现43℃作用35min，每周1次，局部湿热治疗可有效控制肿瘤生长．减少肺转移的发生。结论：局部湿热治疗可以有效抑制肿瘤生长，具有潜在的临床推广应用价值。     

Galectin-3 Expression in Tumor Progression and Metastasis of Papillary Thyroid Carcinoma

Galectin-3 plays important roles in cell adhesion, cell proliferation, apoptosis, neoplastic transformation, and metastasis. Galectin-3 expression has been evaluated in various malignant neoplasms to determine its effectiveness in differential diagnosis from benign lesions and its effects on carcinogenesis. There are few and somewhat controversial results regarding its changes through cancer progression in thyroid malignancies. We studied the presence of galectin-3 expression immunohistochemically and its relation with tumor invasiveness and lymph node metastasis in 89 cases of papillary carcinoma of the thyroid. Galectin overexpression was less frequent in cases with lymph node metastases compared with cases without lymph node metastasis (P = 0.001). Metastatic foci in lymph nodes showed a lower degree of galectin-3 overexpression than their primary lesions (P = 0.001). Degree of galectin-3 overexpression was also lower in larger tumors (P = 0.009). Additionally, a decreased level of galectin-3 overexpression was observed at the invasive edges of the tumors (P = 0.001). Galectin-3 overexpression is more profound in early stages of papillary carcinoma, and its expression intensity decreases during tumor progression. This finding is consistent with roles for galectin-3 in cell adhesion to other tumor cells and the matrix.     

Low EphA7 Expression Correlated with Lymph Node Metastasis and Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma

As a member of the Eph family of receptor tyrosine kinases, EphA7 plays an important role in cancer. However, the expression and significance of Eph receptors in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we detected the expression of EphA7 by immunohistochemistry in a sample of 352 patients with ESCC, and aimed to investigate the expression status of EphA7 in ESCC and its impact on prognosis. The results showed that low EphA7 expression significantly correlated with lymph node metastases (N0: 29%; N1: 64%. p<0.001), poor degree of tumor differentiation (G1: 31%; G2: 49%; G3: 58%. p=0.009) and pTNM staging (I+II: 33%; III+IV: 58%. p<0.001). Furthermore, in a combined analysis, patients with low EphA7-expressing tumors showed a shorter overall survival than those with high expression, resulting in a five-year overall survival rate of 47.4% vs. 52.6%, respectively (p=0.016). Consequently, patients with a low EphA7 expression have poorer prognosis in ESCC compared with those manifesting high expression.     

Combined "Mixed Medullary-Follicular" and "Papillary" Carcinoma of the Thyroid with Lymph Node Metastasis

We report a case of combined “mixed medullary-follicular” and “papillary” carcinoma of the thyroid that occurred in a 44-yr-old Japanese woman. The grossly single 3 cm tumor was histologically composed of both mixed medullary-follicular carcinoma and papillary carcinoma, which abutted against each other with a clear border between two components. Immunohistochemically, the component of medullary carcinoma was positive for calcitonin and carcinomebryonic antigen (CEA), and the follicular carcinoma and papillary carcinoma components were positive for thyroglobulin. Lymph node metastasis was also noted. The patient has been alive without recurrence for 20 yr. To the best of our knowledge, this is the first reported case in the literature. We report this unique case of thyroid carcinoma and review related thyroid malignancies.     

环磷酰胺和LAK细胞联合应用对SHR大鼠乳腺癌肺转移的抑制作用

本实验研究了环磷酰胺和LAK细胞被动输入联合应用对SHR大鼠乳腺癌肺转移的影响。结果表明当投给50mg/kg环磷酰胺和被动输入LAK细胞(4×10~7/只)可以明显地抑制SHR大鼠乳腺癌的肺转移(P<0.01),并且能有效地延长荷瘤动物的生存时间(P<0.01);半治疗量的LAK细胞和环磷酰胺具有协同抗转移作用(P<0.05)。提示此方法是一个有效的免疫化学疗法。     

Clinicopathological and Molecular Histochemical Review of Skull Base Metastasis from Differentiated Thyroid Carcinoma

Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma.     

宫颈癌组织中PTEN和COX-2的表达与侵袭转移的关系

目的探讨宫颈癌组织中PTEN和COX-2的表达与侵袭转移的关系。方法采用免疫组化SP法检测68例宫颈癌组织中PTEN和COX-2的表达情况。结果 PTEN在宫颈癌组织中阳性表达率明显低于正常宫颈组织,差异有统计学意义（P〈0.01）,且与淋巴结转移显著相关（P〈0.05）;而COX-2阳性表达率显著高于正常宫颈组织（P〈0.01）,与淋巴结转移显著相关（P〈0.05）;在癌组织中PTEN和COX-2表达呈负相关。结论PTEN和COX-2的异常表达与宫颈癌的发生、发展及淋巴结转移密切相关,两者共同参与了宫颈癌发生和侵袭转移。     

Integrin α4 Induces Lymphangiogenesis and Metastasis via Upregulation of VEGF‐C in Human Colon Cancer

Vascular endothelial growth factor‐C (VEGF‐C) is a key regulator in lymphangiogenesis, and is overexpressed in various malignancies. Integrin α4β1, a new member of the VEGF‐C/VEGF receptor pathway, was found to be overexpressed in melanoma tumors. However, little is known regarding the potential role of integrin α4β1 in lymphangiogenesis and other solid tumors. The aim of this study was to investigate the expression patterns of integrin α4 and VEGF‐C in relation to lymphangiogenesis and clinicopathological parameters in human colon cancer. The expression of integrin α4, VEGF‐C, and VEGFR‐3 was assessed in 71 human colon cancer tissues and 30 paracancerous normal tissues by immunohistochemical staining. Lymphatic microvessel density (LMVD) was measured after D2‐40‐labeling, and the correlations among different factors were statistically analyzed. The expression of integrin α4, VEGF‐C, VEGFR‐3, and LMVD was higher in colon cancer tissues compared with the normal paracancerous colon tissues. There was a positive correlation between the expression of integrin α4 and VEGF‐C. Integrin α4 and VEGF‐C were significantly associated with the clinicopathological parameters (LMVD, Duke's stage, and lymph node metastasis). Kaplan–Meier analyses indicated that patients with high integrin α4 or VEGF‐C expression had significantly shorter overall survival and tumor‐free survival time. Multivariate analyses suggested that integrin α4 and VEGF‐C may serve as independent prognostic factors for human colon cancer. Both integrin α4 and VEGF‐C are involved in lymphangiogenesis and lymphatic metastasis. Our results demonstrated that integrin α4 is a novel prognostic indicator for human colon cancer. Anat Rec, 299:741–747, 2016. © 2016 Wiley Periodicals, Inc.     

VEGF和MMP-2的表达对肝细胞癌侵袭转移的影响

采用免疫组化 ABC法对 5 0例肝细胞癌手术切除标本的血管内皮生长因子 (VEGF)和基质金属蛋白酶- 2 (MMP- 2 )表达进行检测 ,以探讨 VEGF及 MMP- 2在肝细胞癌中的表达与其复发、转移的关系。结果发现 VEGF和 MMP- 2在肝细胞癌组织中的阳性表达率分别为 86 % (43/5 0 )和 6 0 % (30 /5 0 ) ,在正常肝组织中分别为 5 3.3%(16 /30 )和 30 % (9/30 ) ,癌组织与正常组织间存在着显著差异 (P<0 .0 5 ) ;VEGF和 MMP- 2的阳性表达率与肝细胞癌的转移和包膜形成相关 ,在肝细胞癌生长、侵袭和转移过程中起着重要的作用 ,对预测肝细胞癌复发、转移具有重要的意义     

碱性成纤维细胞生长因子在膀胱移行细胞癌中的表达

目的　研究碱性成纤维细胞生长因子 (bFGF)在膀胱移行细胞癌 (BTCC)中的表达及其意义。方法　SP法 ,对 5 5例BTCC及 10例正常膀胱组织中bFGF进行检测。结果　在正常移行细胞呈阴性表达 ,在BTCC中呈不同程度的阳性表达 ,且过表达率在不同病理分级、临床分期组间有显著性差异 (P <0 .0 5 ) ,复发组的阳性表达率明显高于初发组 (P <0 .0 5 )。结论　bFGF在BTCC侵润转移过程中起重要作用 ,BFGF表达可成为判断肿瘤预后的一项指标     

甲状腺乳头状癌颈部淋巴结转移特点及相关危险因素分析

目的 探讨甲状腺乳头状癌（PTC）临床病理特征及影响颈部淋巴结转移的危险因素。方法 回顾性分析我院2015年1月~2017年12月收治的515例PTC的临床资料,分析颈部淋巴结转移特点及相关危险因素。结果 PTC颈部淋巴结转移率为44.27%,中央组（Ⅵ区）淋巴结转移率高于侧区（P＜0.05）。单因素分析结果示性别、年龄、多灶、癌灶最大径、侵犯被膜和颈部淋巴结转移有关（P＜0.05）。多因素分析结果示男性、年龄＜55岁、多灶病变、癌灶最大径＞10 mm、被膜受侵犯是发生颈部淋巴结转移的独立危险因素（P＜0.05）。结论 Ⅵ区转移率最高,行颈淋巴结清扫时应将Ⅵ区作为常规清扫区域。对于男性、年轻、多灶病变、癌灶最大径＞10 mm、被膜受侵犯的患者应高度警惕颈部淋巴结转移的可能。     

syndecan-1表达对肝细胞癌增殖、血管生成和转移的影响

目的探讨syndecan-1在肝细胞癌（hepatocellular carcinoma,HCC）表达的临床病理意义,及其与肿瘤转移、增殖和血管生成的关系。方法用免疫组织化学染色检测了syndecan-1在30例HCC原发癌组织、癌旁组织和肝内转移灶的表达,血管内皮生长因子（vascularendothelial growth factor,VEGF）和CD34-微血管密度（microvessel density,MVD）在原发灶和肝内转移灶的表达,及Ki-67在原发灶的表达。结果与HCC癌旁组织相比,syndecan-1在原发癌组织表达水平明显增高,syndecan-1在肝内转移灶表达水平明显下降（χ2=25.62,P〈0.001）。在HCC原发癌组织中,syndecan-1表达强度与Ki-67指数呈正相关（r=0.386,P〈0.05）。在肝内转移灶中,syndecan-1表达强度与CD34-MVD呈正相关（r=0.370,P〈0.05）。结论 HCC组织syndecan-1表达可能影响肿瘤转移、增殖和血管生成,提示syndecan-1在HCC生长和转移中的特殊作用可能为HCC有效治疗策略提供新思路。     

VEGF和C-myc表达在胆囊癌形成、发展和转移中的作用

应用免疫组化ABC法对30例胆囊癌的癌组织VEGF和C－myc的表达进行检测，以探讨VEGF和C－myc在胆囊癌中的表达和二者之间的相关性以及胆囊癌形成，发展和转移中的作用。结果发现VEGF和C－myc二者在胆囊癌组织和正常胆囊组织中的阳性表达率均有显著性差异（P＜0．05），VEGF与C－myc的表达呈非常显著的相关性（P＜0．01），二者的表达与胆囊癌的转移行为有关，而与肿瘤的分化程度无关，VEGF与C－myc基因协同作用在胆囊癌形成，发展和转移中起着重要作用。