乳腺癌survivin和TK1的表达及其与腋窝淋巴结转移的关系

目的 探讨乳腺癌survivin蛋白的表达及其与肿瘤细胞增生和腋窝淋巴结转移的关系。方法收集乳腺癌60例，其中有腋窝淋巴结转移的28例，用免疫组化染色检测survivin和胞质胸腺嘧啶核苷激酶(cytosolic thymidinekinase，TK1)蛋白的表达情况。结果 ①乳腺癌组织中有survivin蛋白的表达，其阳性表达率为64．9‰②survivin蛋白表达阳性的乳腺癌细胞TK1的标记指数明显高于survivin蛋白表达阴性者。③无腋窝淋巴结转移的乳腺癌survivin蛋白阳性表达率明显低于有腋窝淋巴结转移者。结论 乳腺癌组织中有survivin蛋白的表达，且其表达与肿瘤细胞增生和腋窝淋巴结转移有关。     

血浆MMPs水平与甲状腺乳头状癌浸润转移的关系

背景与目的:甲状腺乳头状癌是常见的甲状腺恶性肿瘤,目前尚无理想的血液学指标来反映其生物学特性,本研究观察血浆基质金属蛋白酶(MMP)-2、-9活性与甲状腺乳头状癌侵袭和转移的关系。方法:温州医学院附属第二医院1999～2003年共有经病理确诊、行甲状腺癌改良根治术的甲状腺乳头状癌患者74例,用明胶酶谱法测定患者血浆MMP-2和MMP-9活性。结果:淋巴结转移组的血浆活化MMP-2和MMP-9水平(71.9±11.7、15.5±6.1)明显高于无淋巴结转移组(35.2±6.6、7.3±2.3)(P<0.001);包膜及包膜外浸润组的血浆活化MMP-2和MMP-9水平(70.5±13.0、14.7±6.1)明显高于包膜内浸润组(35.4±7.9、8.0±4.2)(P<0.001);而肿瘤直径≥1cm组和<1cm组血浆活化MMP-2和MMP-9水平(55.4±20.4vs.59.3±20.8,10.8±5.7vs.13.7±6.8)无显著性差异(P>0.05),各组之间血浆总MMP-2和MMP-9水平无显著性差异(P>0.05)。结论:明胶酶的活化形式MMP-2和MMP-9的血浆水平与甲状腺乳头状癌的转移、侵袭有关,与肿瘤的大小无关。     

Breast cancer stem cells: Multiple capacities in tumor metastasis

Breast cancer is the leading cause of cancer death among women worldwide. Accumulating evidence indicates that the local recurrent and/or distant metastatic tumors, the major causes of lethality in the clinic, are related to the aggressive phenotype of a small fraction of cancer cells loosely termed as cancer stem cells (CSCs), tumor initiating cells (TICs), or cancer metastasis-initiating cells (CMICs). Breast cancer stem cells (BCSCs) are shown to exhibit unique growth abilities including self-renewal, differentiation potential, and resistance to most anti-cancer agents including chemo- and/or radiotherapy, all of which are believed to contribute to the development and overall aggressiveness of the recurrent or metastatic lesions. It is in the urgent need not only to further define the nature of heterogeneity in each tumor but also to characterize the precise mechanisms governing tumor–host cross-talk which is assumed to be initiated by BCSCs. In this review, we will focus on recently identified key factors, including the BCSCs among circulating tumor cells, interaction of BCSCs with the host, epithelial mesenchymal transition (EMT), tumor microenvironment, the intrinsic resistance due to HER2 expression, potential biomarkers of BCSCs and cancer cell immune signaling. We believe that new evidence coming from both bench and clinical research will help to develop more effective approaches to control or significantly reduce the aggressiveness of metastatic tumors.     

Down-regulation of ARNT promotes cancer metastasis by activating the fibronectin/integrin β1/FAK axis

The aryl hydrocarbon receptor nuclear translocator (ARNT) is broadly involved in regulating tumorigenesis by inducing genes that are involved in tumor growth and angiogenesis. Tumorigenesis usually involves normoxic conditions. However, the role of ARNT in tumor metastasis during normoxia remains unclear. Here, we demonstrate that ARNT protein levels were decreased in late-stage human colorectal cancer using immunohistochemical analysis. Down-regulation of ARNT protein promoted cancer cell migration and invasion, which was mediated by activation of the fibronectin/integrin β1/FAK signaling axis. In addition, the enhancement of migration and invasion in ANRT knockdown cells was blocked when ARNT was restored in the cells. In xenografts in severe combined immunodeficiency mice, tumor growth was significantly inhibited in the ARNT-knockdown condition. However, the tail-vein injection animal model revealed that the depletion of ARNT-induced metastatic lung colonies was further enhanced when ARNT expression was recovered post-injection. Interestingly, chemotherapeutic drugs inhibited ARNT expression and promoted the invasion of residual tumor cells. These results suggest that ARNT may play a positive role during tumor growth (either in early-stage tumor growth or in organ metastases), but plays a negative role in tumor migration and invasion. Therefore, the efficiency of ARNT-targeted therapy during different cancer stages should be carefully evaluated.     

An insight into electrical resistivity of white matter and brain tumors

BackgroundThere is a lack of information regarding electrical properties of white matter and brain tumors.ObjectiveTo investigate the feasibility of in-vivo measurement of electrical resistivity during brain surgery and establish a better understanding of the resistivity patterns of brain tumors in correlation to the white matter.MethodsA bipolar probe was used to measure electrical resistivity during surgery in a prospective cohort of patients with brain tumors. For impedance measurement, the probe applied a constant current of 0.7 μA with a frequency of 140 Hz. The measurement was performed in the white matter within and outside peritumoral edema as well as in non-enhancing, enhancing and necrotic tumor areas. Resistivity values expressed in ohmmeter (Ω1m) were compared between different intracranial tissues and brain tumors.ResultsNinety-two patients (gliomas WHO II:16, WHO III:10, WHO IV:33, metastasis:33) were included. White matter outside peritumoral edema had higher resistivity values (13.3 ± 1.7 Ω1m) than within peritumoral edema (8.5 ± 1.6 Ω1m), and both had higher values than brain tumors including non-enhancing (WHO II:6.4 ± 1.3 Ω1m, WHO III:6.3 ± 0.9 Ω1m), enhancing (WHO IV:5 ± 1 Ω1m, metastasis:5.4 ± 1.3 Ω1m) and necrotic tumor areas (WHO IV:3.9 ± 1.1 Ω1m, metastasis:4.3 ± 1.3 Ω1m), p=<0.001. No difference was found between low-grade and anaplastic gliomas, p = 0.808, while resistivity values in both were higher than the highest values found in glioblastomas, p = 0.003 and p = 0.004, respectively.ConclusionsThe technique we applied enabled us to measure electrical resistivity of white matter and brain tumors in-vivo presumably with a significant effect with regard to dielectric polarization. Our results suggest that there are significant differences within different areas and subtypes of brain tumors and that white matter exhibits higher electrical resistivity than brain tumors.     

Bone Sialoprotein Promotes Tumor Cell Migration in Both In Vitro and In Vivo Models

The present study was conducted to determine the effects of bone sialoprotein (BSP) in promoting vascular invasion of tumor cells in metastasis. We used a Matrigel system and the MDA-231 human breast cancer cells transfected with human BSP cDNA (MDA-231/BSP). Quantative analysis indicated an average of 1.7-fold increase in cell numbers that migrated through the endothelial cells in MDA-231/BSP cells compared with empty vector-transfected MDA-231 cells (MDA-231/EV). In an in vivo assay, the MDA-231 cells were incubated with or without BSP antibodies and were then inoculated onto the upper chorioallantoic membrane (CAM) of chicken embryos, in which the only route for the tumor cells to reach the lower CAM was to migrate through the embryonic vasculature. PCR amplification using human Alu primers and genomic DNA from harvested lower CAM showed an average reduction of 67% in the samples treated with BSP antibodies. These preliminary data suggest that, in metastasis, BSP may enhance the penetrating ability of tumor cells through endothelial cells and basement membrane into blood vessels. BSP antibodies can specifically hinder this effect in an in vivo system.     

Primary Inflammatory Myofibroblastic Tumors of the Breast with Metastasis: Radiographic and Histopathologic Predictive Factors

Primary inflammatory myofibroblastic tumors (IMTs) of the breast are uncommon and metastasis of IMTs is extremely rare. To date, the natural course of this disease is not fully understood. Although patients with IMTs should undergo regular follow-up after complete surgical resection of the tumor, the appropriate interval and method of follow-up are unclear. We report the case of a patient with an IMT of the breast that metastasized 2 years after complete surgical resection. This unusual case emphasizes the importance of preoperative examinations to determine whether the IMT has atypical features that should guide the interval and method of follow-up.     

Clinicopathological features and prognostic analysis of metastatic pulmonary sarcomatoid carcinoma: a SEER analysis

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare type of non-small cell lung cancer (NSCLC). Metastases are often detected at the first diagnosis. Despite high rates of distant metastasis, there is insufficient data describing the characteristics of PSC metastasis.MethodsWe performed a Surveillance, Epidemiology, and End Results (SEER) database-based analysis of clinicopathological features and prognosis of distant metastasis in PSC patients. Data queried for this analysis included PSC patients in the database between 2010 and 2016.ResultsA total of 934 patients met the criteria for inclusion in the analysis and included, at the time of diagnosis, 512 (54.8%) patients with metastasis, including bone (n=152; 16.3%), brain (n=108; 11.6%), liver (n=70; 7.5%), lung (n=142; 15.2%) metastases. Binary logistic regression showed that patients with giant cell carcinoma [odds ratio (OR) 4.023, 95% confidence interval (CI): 2.113–7.661, P<0.001] and spindle cell carcinoma (OR 3.151, 95% CI: 1.699–5.843, P<0.001) were associated with metastasis. Log-rank test and Kaplan-Meier plots indicated poor prognosis in metastatic patients [the 1-, 3-, and 5-year overall survival (OS) rates were 14.1%, 5.5%, and 4.8%, respectively]. Multivariable analysis showed younger and chemotherapy as improved prognostic factors of PSC patients with single metastasis site.ConclusionsThe SEER database-based analysis revealed the clinical features of distant metastasis of PSC and showed that different histological types posed distinct metastasis potential. Besides, age and chemotherapy were the independent prognostic factors of PSC patients with single metastasis site.