Involvement of epithelial-mesenchymal transition in adenoid cystic carcinoma metastasis

The high frequencies of recurrence and distant metastasis of adenoid cystic carcinoma (AdCC) are significant obstacles for the long-term cure of patients with AdCC and emphasize the need for better understanding of the biological factors associated with these outcomes. To identify proteins that mediate AdCC metastasis, we established three AdCC cell lines expressing green fluorescent protein (GFP) from the ACCS cell line using orthotopic transplantation and in?vivo selection in nude mice: Parental ACCS-GFP, highly tumorigenic ACCS-T GFP and metastatic ACCS-M GFP. ACCS-GFP and ACCS-M GFP were subjected to DNA microarray analysis and the results were used for data mining studies. DNA microarray analysis revealed significantly altered biological processes in the ACC-M GFP cells, including events related to cell adhesion (three categories) and signaling (three categories). In particular, a significant down-regulation of cell adhesion molecules, such as cadherins and integrin subunits was observed. The loss of E-cadherin and integrins and the gain of vimentin in ACCS-M GFP cells were confirmed by immunoblotting. These results suggest that epithelial-mesenchymal transition (EMT) is a putative event in AdCC metastasis that induces tumor cell dissemination from the primary tumor site. In summary, in this study we established a useful nude mouse metastasis model which will enable further AdCC metastasis research and clinical treatment trials and we also provide evidence that EMT is significantly involved in the AdCC metastatic process.     

涎腺腺样囊性癌的复发、转移及治疗初析

目的探讨影响涎腺腺样囊性癌的复发及转移的因素.方法对61例涎腺腺样囊性癌做临床病理分析.结果临床分期晚期位于颌下腺、舌下腺肿瘤神经受侵率高,复发率高;肿瘤复发是死亡的主要原因;局部总复发率为47.5%,远地转移率为29.5%,颈淋巴结转移率为9.8%.结论复发率与发病部位、临床分期及治疗方法等相关,外科是主要的治疗方法,放射治疗可以有效地控制病变的发展.     

RNAi-mediated ADAM9 gene silencing inhibits metastasis of adenoid cystic carcinoma cells

A disintegrin and metalloproteinase 9 (ADAM9) is a type I transmembrane protein that has been associated with cancer development and metastases. Here, we show that ADAM9 is highly expressed in metastatic cancer tissues and in an adenoid cystic carcinoma cell line with a high metastatic potential. Using RNA interference for gene silencing, we show that ADAM9 is essential for in vitro cancer cell proliferation and invasion as well as in vivo cancer metastasis in an experimental murine model of lung metastases. These data indicate that ADAM9 is potentially an important new therapeutic target for the prevention of tumor metastases in adenoid cystic carcinoma.     

NOTCH1 signaling contributes to cell growth,anti-apoptosis and metastasis in salivary adenoid cystic carcinoma

Background: Numerous studies have reported both the tumor-suppressive and oncogenic roles of the Notch pathway, indicating that Notch activity regulates tumor biology in a complex, context-dependent manner. The aim of the present study was to identify the role of NOTCH1 in the cell growth and metastasis of SACC.Methods: We analyzed the expression of NOTCH1 in clinical SACC samples using immunohistochemical staining. We silenced the expression of NOTCH1 and overexpressed activated NOTCH1 to elucidate the effects of NOTCH1 on proliferation, migration and invasion. NOTCH1 target genes were validated by real-time PCR.Results: Our results showed that NOTCH1 was upregulated in SACC tissues when compared with normal tissues, and this upregulation was further enhanced in SACC tissues with metastasis and recurrence when compared with SACC tissues without metastasis. Overexpression of NOTCH1 in SACC cells promoted cell growth, migration and invasion, and knockdown of NOTCH1 inhibited cell proliferation in vitro and tumorigenicity in vivo by inducing cell apoptosis.Conclusions:The results of this study suggest that NOTCH1 plays a key role in the cell growth, anti-apoptosis, and metastasis of SACC. NOTCH1 inhibitors might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.     

Radiotherapy in adenoid cystic carcinoma

Between 1962 and 1982, 45 patients with adenoid cystic carcinomas (ACC) of various localizations received a radiotherapy-treatment. Most of the cases had advanced tumors or recurrences. 41 patients underwent radiotherapy either alone or following an operation, in 35 cases with curative intention. 6 patients had already distant metastases at the beginning of treatment. In 4 cases only a palliative treatment of metastases of the skeleton and the lung was performed. Median two- and five-year survival of 35 patients with localized tumors was 83% and 45%, respectively (29/35 two-years and 14/31 five years). Best results were obtained by operation and postoperative radiotherapy (10/18 = 55.5% five year-survival). Radiotherapy alone resulted in a five-year survival of only 37.5% (3/8). Advanced ACC or postoperative recurrences should be treated by surgery as radically as possible, followed by a radiotherapy with generously sized portals and doses between 60 to 65 Gy. Radiotherapy alone leads to comparatively poor results. Large and inoperable tumors may well be treated by a combination of hyperthermia and radiotherapy.     

In vivo optical imaging of cancer cell function and tumor microenvironment

In vivo optical imaging using fluorescence and bioluminescence is superior to other methods in terms of spatiotemporal resolution and specificity, and represents a new technology for comprehensively studying living organisms in a less invasive way. Nowadays, it is an indispensable technology for studying many aspects of cancer biology, including dynamic invasion and metastasis. In observations of fluorescence or bioluminescence signals in a living body, various problems were caused by optical characteristics such as absorption and scattering and, therefore, observation of deep tissue was difficult. Recent developments in techniques for observation of the deep tissues of living animals overcame this difficulty by improving bioluminescent proteins, fluorescent proteins, and fluorescent dyes, as well as detection technologies such as two‐photon excitation microscopy. In the present review, we introduce these technological developments and in vivo application of bioluminescence and fluorescence imaging, and discuss future perspectives on the use of in vivo optical imaging technology in cancer research.     

Mammographic features of adenoid cystic carcinoma

Adenoid cystic carcinoma of the breast accounts for < 1% of breast malignancies. This case report describes the mammographic features and the pathology. Adenoid cystic carcinoma is a well-circumscribed carcinoma that has a relatively good prognosis.     

Brefeldin-A induces apoptosis in human adenoid cystic carcinoma cultured cells

Adenoid cystic carcinoma (ACC) of salivary glands is characterized by a high rate of local recurrences, neurotropism and metastasis. ACC long-term survival rate is not promising. Thus, different chemotherapeutical approaches had been proposed for this neoplasm, including apoptosis induction by different drugs. This work evaluates the efficacy of Brefeldin-A (BFA), a potent apoptosis inducer, on ACC cultured cells (CAC2 cell line). CAC2 cells were treated with a 375 microM BFA solution in serum-free medium during 18 h. CAC2 cells grown in DMEM supplemented with 10% fetal bovine serum served as controls. Apoptotic cell recognition and counting were carried out through Hoechst staining. Transmission electron microscopy and immunofluorescence assessed the effect of BFA on CAC2 cells phenotype. Treated cultures showed a high apoptotic index presenting +/-30% of cells in evident apoptosis, when compared to controls. Apoptotic CAC2 cells also exhibited different alterations such as cytoplasmic vesicles formation and mitochondrial changes. Cultured ACC cells are strongly susceptible to apoptosis induction under BFA treatment, which may constitute a promising tool in further chemotherapeutical approaches.     

Primary adenoid cystic carcinoma of larynx

A rare case of Adenoid cystic carcinoma of larynx is presented and discussed in brief.     

人涎腺腺样囊性癌嗜神经侵袭超微结构的观察研究

目的:通过电镜检测来进一步探索人涎腺腺样囊性癌嗜神经侵袭的超微形态特征.方法:将人涎腺腺样囊性癌Acc-M细胞系注射入5只裸鼠双侧臀部肌肉内,切取其中发生神经侵袭并出现功能障碍的荷瘤;通过透射电镜检测来观察腺样囊性癌的嗜神经侵袭过程. 结果:肿瘤细胞破坏神经外膜及神经束膜,进入神经纤维之间,并以吞噬的方式对神经纤维进行侵袭,致使髓鞘、轴突发生变性、溶解而被吸收.结论:涎腺腺样囊性癌细胞在对神经的侵袭过程中具有一定的吞噬作用,且这种现象在神经侵袭中起了很重要的作用.     

涎腺腺样囊性癌血道转移的临床分析

目的：探讨腺样囊性癌血道转移问题,期望在临床上对此类病例的治疗引起重视。方法：对６例腺样囊性癌血道转移的病人进行回顾性分析。结果：腺样囊性癌因其生物性特征,术后容易发生局部复发和血道转移。结论：对此类病例强调首期完成根治性手术和进行综合治疗。密切随访,及时发现和治疗转移灶。     

Nasopharyngeal adenoid cystic carcinoma: magnetic resonance imaging features in ten cases

Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with high local invasiveness. To date, there is no consensus on the imaging characteristics of NACC. To address this, we retrospectively reviewed 10 cases of NACC and summarized the magnetic resonance imaging (MRI) features. MR images of 10 patients with histologically validated NACC were reviewed by two experienced radiologists. The location, shape, margin, signal intensity, lesion texture, contrast enhancement patterns, local invasion, and cervical lymphadenopathy of all tumors were evaluated. Clinical and pathologic records were also reviewed. No patients were positive for antibodies against Epstein-Barr virus (EBV). The imaging patterns of primary tumors were classified into two types as determined by location, shape, and margin. Of all patients, 7 had tumors with a type 1 imaging pattern and 3 had tumors with a type 2 imaging pattern. The 4 tubular NACCs were all homogeneous tumors, whereas 3 (60%) of 5 cribriform NACCs and the sole solid NACC were heterogeneous tumors with separations or central necrosis on MR images. Five patients had perineural infiltration and intracranial involvement, and only 2 had cervical lymphadenopathy. Based on these results, we conclude that NACC is a local, aggressive neoplasm that is often negative for EBV infection and associated with a low incidence of cervical lymphadenopathy. Furthermore, MRI features of NACC vary in locations and histological subtypes.     

头颈部腺样囊性癌的磁共振成像特点

背景与目的：腺样囊性癌（adenoid cystic carcinoma,ACC）是起源于涎腺组织的一种少见恶性肿瘤,该研究旨在探讨磁共振成像（magnetic resonance imaging,MRI）在头颈部ACC中的应用价值。方法：回顾性分析上海市质子重离子医院2015年5月—2017年9月收治的26例（19例原发,7例复发）经手术病理证实的头颈部ACC患者的临床和MRI资料。结果：26例肿瘤中,位于鼻咽8例,腭6例,鼻腔4例,上颌窦3例,颌下腺和舌各2例,喉1例。23例肿瘤形态不规则,边界不清;其余3例呈类圆形,边界较清。所有病灶与肌肉相比在T1WI上呈等信号,在T2WI上呈高或稍高信号,增强后可见明显强化。17例侵犯神经中,累及翼腭窝16例,累及海绵窦10例,卵圆孔8例,圆孔4例,眶上裂2例,视神经管2例,舌下神经管2例,翼管1例。21例侵犯骨质,11例侵犯颅内。结论：MRI能够清晰显示ACC的肿瘤范围及神经受累情况,可为临床治疗提供更多信息。     

Primary adenoid cystic carcinoma of the esophagus

A case of primary adenoid cystic carcinoma of the esophagus is reported, and 45 cases are reviewed. The light and electron microscopic appearances are described in a 77-year-old woman. This patient manifested the intraepithelial spread of cancer cells, which suggested that the tumor arose from the mucosal epithelium of the esophagus. The patient died of mediastinal metastasis 11 months after resection. Adenoid cystic carcinoma of the esophagus is a relatively rare lesion, which exhibits a clinically aggressive behavior. Earlier resection and more intensive chemotherapy will be required.