肿瘤嗜神经侵袭机制的研究进展

肿瘤嗜神经侵袭（perineural invasion，PNI）被认为是一种新的恶性肿瘤转移方式，与多种肿瘤不良预后相关。神经与肿瘤细胞之间的相互作用主要包括细胞形态的改变和分子间作用。肿瘤微环境中的多种分子包括神经营养因子、趋化因子、黏附分子及神经递质等在肿瘤PNI形成过程中发挥重要作用。探究神经与肿瘤的相互作用，可为揭示肿瘤形成或转移的机制及优化临床诊疗提供帮助。     

肝门胆管癌神经周围侵袭的研究进展

肿瘤的神经周围侵袭（perineural invasion,PNI）是一种特殊的恶性肿瘤转移方式,与肝门胆管癌及胰腺癌等多种恶性肿瘤的不良预后相关。肝门胆管癌肿瘤细胞与神经之间的相互作用主要包括细胞形态改变和分子间相互作用。其微环境中的多种分子包括M3毒蕈碱乙酰胆碱受体、趋化因子、神经营养因子-β、MicroRNA及LncRNA等在肝门胆管癌及其他肿瘤PNI形成过程中发挥重要作用。探究肝门胆管癌与神经的相互作用,可为揭示肝门胆管癌转移侵袭的机制及优化临床诊疗提供帮助。     

头颈部恶性肿瘤嗜神经侵袭临床诊治现状

嗜神经侵袭是肿瘤通过神经扩散与转移的一种独特的生物学行为,与复发、转移、预后密切相关。随着研究的不断深入,人们普遍认识到嗜神经侵袭的临床意义。但由于头颈部肿瘤发病率相对较低,不同解剖部位、不同病理类型嗜神经发生率各不相同,故缺乏高级别的循证医学证据。目前嗜神经侵袭的病理学机制尚未完全阐明,也无针对神经侵犯的特异性治疗手段,因此头颈部肿瘤嗜神经侵袭的治疗对于临床医师是一个巨大的挑战。本文就头颈部恶性肿瘤中嗜神经侵袭的临床诊治现状做一综述。     

头颈部恶性肿瘤嗜神经侵袭临床诊治现状

嗜神经侵袭是肿瘤通过神经扩散与转移的一种独特的生物学行为,与复发、转移、预后密切相关。随着研究的不断深入,人们普遍认识到嗜神经侵袭的临床意义。但由于头颈部肿瘤发病率相对较低,不同解剖部位、不同病理类型嗜神经发生率各不相同,故缺乏高级别的循证医学证据。目前嗜神经侵袭的病理学机制尚未完全阐明,也无针对神经侵犯的特异性治疗手段,因此头颈部肿瘤嗜神经侵袭的治疗对于临床医师是一个巨大的挑战。本文就头颈部恶性肿瘤中嗜神经侵袭的临床诊治现状做一综述。     

Wnt/β-catenin信号转导通路影响神经胶质瘤侵袭的机制

神经胶质瘤的侵袭是一个多步骤、多因素参与的复杂过程,主要包括抑制肿瘤细胞黏附,降解细胞外基质,促进肿瘤细胞移动和肿瘤新生血管的生成四个部分.Wnt/β-catenin信号转导通路的异常激活与神经胶质瘤侵袭密切相关.研究Wnt/β-catenin通路影响神经胶质瘤的侵袭机制,将为神经胶质瘤的治疗提供新的思路和靶点.     

ADAM9与恶性肿瘤侵袭转移关系的研究进展

ADAM9是ADAM家族的一员，可通过影响肿瘤细胞与细胞及细胞外基质的黏附、蛋白水解、调节肿瘤细胞信号传导、诱导肿瘤血管的生成等作用参与肿瘤的发生、发展与转移。深入研究ADAM9在恶性肿瘤中的表达与功能，有助于进一步认识恶性肿瘤侵袭转移的分子机制，并为恶性肿瘤的诊断治疗和预后判断提供新指标。现就ADAM9与恶性肿瘤侵袭的关系作一综述。     

黏附分子与肿瘤侵袭和转移的研究进展

恶性肿瘤死亡多数是由转移所致,肿瘤转移是涉及恶性肿瘤侵袭和转移形成的全过程与临床有密切关系,但此过程在分子水平的研究很少,阐明这些机制在肿瘤研究和应用上是一个重要挑战。最近的研究证实了许多黏附分子,如上皮钙黏蛋白(E-cadherin)、神经钙黏蛋白(N-cadherin)、整合素(Integrin)等与肿瘤侵袭、转移的发生发展密切关联。     

黏附分子与肿瘤侵袭和转移的研究进展

恶性肿瘤死亡多数是由转移所致,肿瘤转移是涉及恶性肿瘤侵袭和转移形成的全过程与临床有密切关系,但此过程在分子水平的研究很少,阐明这些机制在肿瘤研究和应用上是一个重要挑战。最近的研究证实了许多黏附分子,如上皮钙黏蛋白（E-cadherin）、神经钙黏蛋白（N-cadherin）、整合素（Integrin）等与肿瘤侵袭、转移的发生发展密切关联。     

整合素αvβ6在卵巢癌中的作用

整合素是一类介导细胞与细胞外基质及细胞与细胞间黏附的细胞黏附分子受体，αvβ6是整合素家族的一员，参与肿瘤的发生、发展与转移。这种作用可能是通过影响肿瘤细胞与细胞外基质黏附、细胞外基质水解、诱导肿瘤血管生成、调节肿瘤细胞凋亡等作用而实现的。深入研究αvβ6在卵巢癌中的表达与功能，有助于进一步认识卵巢癌侵袭转移的分子机制，有可能为恶性肿瘤的诊断和预后判断提供新的指标．为开发肿瘤治疗新思路提供了理论依据。     

E-选择素及其配体与肿瘤关系的研究进展

肿瘤转移是一个多步骤、多环节、多因素参与的复杂过程。研究表明：肿瘤侵袭转移过程中均存在细胞黏附分子及其介导的黏附行为的改变。其中,肿瘤细胞与内皮细胞间的相互作用是造成肿瘤器官特异性转移的重要环节。E—selectin是黏附分子选择素家族中的一员,在激活的内皮细胞表达,其配体SleX、SleA存在于肝癌、食道癌、肠癌等多种肿瘤细胞表面,两者在肿瘤侵袭转移中起着重要的作用。现将E—selecfin及其配体与肿瘤关系的研究进展作一综述。     

Invasion of the hypoglossal nerve by adenoid cystic carcinoma of the tongue: case report and review of the literature

Adenoid cystic carcinoma (ACC) is a rare but highly aggressive malignancy mainly originating from the salivary glands. ACC is well known for its propensity toward neural invasion (NI). NI is the process of neoplastic invasion in and along nerves. It is a distinct and well-documented phenomenon in ACC; however, it is an underestimated route of metastatic spread. Multiple distant metastases can be established through NI route, and NI is believed to portend a poor prognosis. Despite increasing recognition of NI in many malignancies, the molecular mechanism behind NI is not well established. We present a unique case of hypoglossal nerve invasion by ACC arising from the minor salivary glands in the tongue of a 34-year-old man. We also review and discuss current theories on the pathogenesis and mechanism of NI.     

Incidence and prognostic significance of vascular and neural invasion in squamous cell carcinomas of the esophagus

The prognostic influence of blood-vessel invasion (BVI), lymphatic-vessel invasion (LVI) and neural invasion (NI) was evaluated retrospectively in a series of 161 patients with squamous cell carcinoma (SCC) of the esophagus who underwent esophageal resection. Evidence of BVI, LVI and NI was found in 32.9%, 48.5% and 26.1%, respectively. Incidence of BVI, LVI and NI was significantly higher in high pT categories (pT3 and pT4) than in low pT categories (pTI and pT2) and in patients with distant metastases than in patients without distant metastases. Incidence of LVI and NI in lymph-node-positive patients was significantly higher than in lymph-node-negative patients. The 5-year survival rate was significantly lower in patients with BVI or LVI than in patients without BVI or LVI. Patients with evidence of NI showed no significant differences in 5-year survival from patients without evidence of NI. By stepwise multivariate Cox regression analysis, BVI and LVI were shown to be independent prognostic factors. A search for vascular invasion may therefore provide additional prognostic precision in SCC of the esophagus. © 1995 Wiley-Liss, Inc.     

Diaphanous相关成蛋白家族的研究

具有两个formin同源结构域(FH1和FH2)的成蛋白(Formins)家族,是维持细胞骨架肌动蛋白的重要调节因子.Diaphanous相关成蛋白家族因具有GTPase结合结构域(GBD)和Diaphanous 自调控结构域(DAD)而被划分为成蛋白家族的一个亚类,该亚家族对细胞黏附、运动、胞质分裂、形态发生、细胞极性的形成、血清反应因子的激活等起重要的调控作用,参与Rho/Rock细胞信号转导通路,并通过调节肌动蛋白细胞骨架重组,促进肿瘤细胞的迁移、侵袭和转移.对Diaphanous相关成蛋白亚家族的深入研究,有助于进一步揭示肿瘤细胞的侵袭和转移机制,并可能为临床提供新的治疗靶点.     

Snail调控肿瘤细胞上皮间质转化的相关信号通路

肿瘤的转移和侵袭是肿瘤患者死亡的主要原因,肿瘤转移和侵袭的过程中涉及多种因素,上皮间质转化（EMT）是促进其中某一环节的关键因素。转录因子Snail作为肿瘤细胞EMT的关键调控因子,起到了重要的作用。通过对Snail调控肿瘤细胞EMT的相关信号通路的研究,有助于我们更好的理解肿瘤的转移及侵袭机制,为寻找有效的靶点提供理论依据。     

Screening for motility-associated genes in malignant astrocytoma cell lines

The most characteristic feature of a malignant astrocytoma is its early and extensive infiltration into adjacent parenchymal structures. We focused on detecting the possible expression changes as the determining factors for malignant astrocytoma’s motile ability. We confirmed that four of 39 genes showed different expression on DD-PCR by RT-PCR and Northern blot analysis. These findings suggest that the genes identified may be important for determining high motility in astrocytoma cell lines. These findings may help us understand the molecular invasion mechanism in astrocytomas.     

Utility of a Herpes Oncolytic Virus for the Detection of Neural Invasion By Cancer

Prostate, pancreatic, and head and neck carcinomas have a high propensity to invade nerves. Surgical resection is a treatment modality for these patients, but it may incur significant deficits. The development of an imaging method able to detect neural invasion (NI) by cancer cells may guide surgical resection and facilitate preservation of normal nerves. We describe an imaging method for the detection of NI using a herpes simplex virus, NV1066, carrying tyrosine kinase and enhanced green fluorescent protein (eGFP). Infection of pancreatic (MiaPaCa2), prostate (PC3 and DU145), and adenoid cystic carcinoma (ACC3) cell lines with NV1066 induced a high expression of eGFP in vitro. An in vivo murine model of NI was established by implanting tumors into the sciatic nerves of nude mice. Nerves were then injected with NV1066, and infection was confirmed by polymerase chain reaction. Positron emission tomography with [¹⁸F]-2′-fluoro-2′-deoxyarabinofuranosyl-5-ethyluracil performed showed significantly higher uptake in NI than in control animals. Intraoperative fluorescent stereoscopic imaging revealed eGFP signal in NI treated with NV1066. These findings show that NV1066 may be an imaging method to enhance the detection of nerves infiltrated by cancer cells. This method may improve the diagnosis and treatment of patients with neurotrophic cancers by reducing injury to normal nerves and facilitating identification of infiltrated nerves requiring resection.     

口腔鳞状细胞癌中上皮-间充质转化相关影响因素的研究进展

口腔鳞状细胞癌是最常见的头颈部恶性肿瘤。近年来，上皮－间充质转化（epithelial-mesenchymal transition,EMT）在肿瘤研究方面一度成为新的研究热点，EMT是由上皮细胞表型向间充质细胞表型转变的过程，在这个过程中，可促进癌细胞的侵袭，进而完成肿瘤的转移，影响患者的预后。本文综合目前的研究，对近年来口腔鳞状细胞癌在EMT方面的细胞因子、通路、RNA、细菌病毒微生物和微环境等相关影响因素进行综述。     

MUC4-promoted neural invasion is mediated by the axon guidance factor netrin-1 in PDAC

Neuralinvasion (NI) is an important oncological feature of pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanism of NI in PDAC remains unclear. In this study, we found that MUC4 was overexpressed in PDAC tissues and high expression of MUC4 indicated a higher NI incidencethan low expression. In vitro, MUC4 knockdown inhibited the migration and invasion of PDAC cells and impaired the migration of PDAC cells along nerve in dorsal root ganglia (DRG)-PDAC cell co-culture assay. In vivo, MUC4 knockdown suppressed the NI of PDAC cells in a murine NI model. Mechanistically, our data revealed that MUC4 silencing resulted in decreased netrin-1 expression and re-expression of netrin-1 in MUC4-silenced cells rescued the capability of NI. Furthermore, we identified that decreased netrin-1 expression was owed to the downregulation of HER2/AKT/NF-κB pathway in MUC4-silenced cells. Additionally, MUC4 knockdown also resulted in the downregulation of pFAK, pSrc, pJNK and MMP9. Taken together, our findings revealed a novelrole of MUC4 in potentiating NI via netrin-1 through the HER2/AKT/NF-κBpathway in PDAC.     

Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression

Background  

Cimetidine, a histamine type-2 receptor antagonist, has been reported to inhibit the growth of glandular tumors such as colorectal cancer, however the mechanism of action underlying this effect is unknown. Adenoid cystic carcinoma is well known as a malignant salivary gland tumor which preferentially invades neural tissues. We demonstrated previously that human salivary gland tumor (HSG) cells spontaneously express neural cell adhesion molecule (NCAM), that HSG cell proliferation may be controlled via a homophilic (NCAM-NCAM) binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors. We further demonstrated that cimetidine inhibited NCAM expression and induced apoptosis in HSG cells. Here, we investigated the effects of cimetidine on growth and perineural/neural invasion of salivary gland tumor cells.     

Nursing experience in palliative care at the outpatient clinic

Seven of the 17 patients reported that they were satisfied with the palliative care at our outpatient clinic. A patient's will to stay home, a devoted key person to the patient, procedures such as good pain control and an oral intake were considered to be important factors in palliative care at the outpatient clinic. We should understand that the patient's family attending the outpatient clinic is a part of their important daily life, so we try to make them feel comfortable whenever they come to see us. We should also strive for building more experience in palliative care for patients and their families. Based on our experience, we anticipate that outpatient care will be increased in the future. In the meantime, advanced nursing skills and techniques are needed.