共查询到20条相似文献,搜索用时 703 毫秒
1.
Purpose
The lung is one of the most common sites of breast cancer metastasis. While metastatic seeding is often accompanied by a dormancy-promoting mesenchymal to epithelial reverting transitions (MErT), we aimed to determine whether lung epithelial cells can impart this phenotype on aggressive breast cancer cells.Methods
Co-culture experiments of normal lung epithelial cell lines (SAEC, NHBE or BEAS-2B) and breast cancer cell lines (MCF-7 or MDA-MB-231) were conducted. Flow cytometry analysis, immunofluorescence staining for E-cadherin or Ki-67 and senescence associated beta-galactosidase assays assessed breast cancer cell outgrowth and phenotype.Results
Co-culture of the breast cancer cells with the normal lung cells had different effects on the epithelial and mesenchymal carcinoma cells. The epithelial MCF-7 cells were increased in number but still clustered even if in a slightly more mesenchymal-spindle morphology. On the other hand, the mesenchymal MDA-MB-231 cells survived but did not progressively grow out in co-culture. These aggressive carcinoma cells underwent an epithelial shift as indicated by cuboidal morphology and increased E-cadherin. Disruption of E-cadherin expressed in MDA-MB-231 using shRNA prevented this phenotypic reversion in co-culture. Lung cells limited cancer cell growth kinetics as noted by both (1) some of the cells becoming larger and positive for senescence markers/negative for proliferation marker Ki-67, and (2) Ki-67 positive cells significantly decreasing in MDA-MB-231 and MCF-7 cells after co-culture.Conclusions
Our data indicate that normal lung epithelial cells can drive an epithelial phenotype and suppress the growth kinetics of breast cancer cells coincident with changing their phenotypes. 相似文献2.
Wei-En Yang Chuan-Chen Ho Shun-Fa Yang Shu-Hui Lin Kun-Tu Yeh Chiao-Wen Lin Mu-Kuan Chen 《PloS one》2016,11(3)
Background
Cathepsin B (CTSB), a member of the cathepsin family, is a cysteine protease that is widely distributed in the lysosomes of cells in various tissues. It is overexpressed in several human cancers and may be related to tumorigenesis. The main purpose of this study was to analyze CTSB expression in oral squamous cell carcinoma (OSCC) and its correlation with patient prognosis.Methodology/Principal Findings
Tissue microarrays were used to detect CTSB expression in 280 patients and to examine the association between CTSB expression and clinicopathological parameters. In addition, the metastatic effects of the CTSB knockdown on two oral cancer cell lines were investigated by transwell migration assay. Cytoplasmic CTSB expression was detected in 34.6% (97/280) of patients. CTSB expression was correlated with positive lymph node metastasis (p = 0.007) and higher tumor grade (p = 0.008) but not with tumor size and distant metastasis. In addition, multivariate analysis using a Cox proportional hazards model revealed a higher hazard ratio, demonstrating that CTSB expression was an independent unfavorable prognostic factor in buccal mucosa carcinoma patients. Furthermore, the Kaplan–Meier curve revealed that buccal mucosa OSCC patients with positive CTSB expression had significantly shorter overall survival. Moreover, treatment with the CTSB siRNA exerted an inhibitory effect on migration in OC2 and CAL27 oral cancer cells.Conclusions
We conclude that CTSB expression may be useful for determining OSCC prognosis, particularly for patients with lymph node metastasis, and may function as a biomarker of the survival of OSCC patients in Taiwan. 相似文献3.
Yongxiang Yin Ke Zeng Man Wu Yun Ding Min Zhao Qi Chen 《Cell biochemistry and biophysics》2014,70(2):1145-1151
Breast cancer is the most common cancer in women worldwide. In this study, we evaluate the potential risk factors for lymph node metastasis in invasive breast cancer patients with axillary dissection. 147 patients were included into this prospective study. The prognostic biomarkers including Ki-67, human epidermal growth factor receptor 2 (HER-2), hormone receptor status, p53, and lymph node involvement were determined by immunohistochemistry. The association between lymph node metastasis and these biomarkers was analyzed. Lymph node metastasis was found in 62 patients out of 147 patients. The high levels of Ki-67 positive (greater than 20 %) were positively correlated with a higher incidence of lymph node metastasis, including the numbers of lymph nodes that contain tumor cells and the lymph node metastatic rate. The high rate of positive lymphovascular invasion (LVI) is associated with lymph node metastasis. However, the levels of Ki-67 positive were not correlated with the positive rate of LVI. There was also no association between lymph node metastasis and other prognostic biomarkers, such as HER-2, estrogen receptor, progesterone receptor, and p53. In addition, apart from p53, the levels of Ki-67 positive were correlated with other prognostic biomarkers. Our data suggest that Ki-67 positivity has value as a prognostic and predictive biomarker in breast cancer and may be a valuable proliferation marker in routine diagnosis of breast cancer. 相似文献
4.
Background
Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L), also known as ALC1 (amplified in liver cancer 1 gene), is a new oncogene amplified in many solid tumors. Whether this gene plays a role in invasion and metastasis of breast cancer is unknown.Methods
Immunohistochemistry was performed to detect the expression of CHD1L in patients with invasive ductal carcinoma and normal mammary glands. Chemotaxis, wound healing, and Transwell invasion assays were also performed to examine cell migration and invasion. Western blot analysis was conducted to detect the expression of CHD1L, MMP-2, MMP-9, pAkt/Akt, pARK5/ARK5, and pmTOR/mTOR. Moreover, ELISA was carried out to detect the expression levels of MMP-2 and MMP-9. Nude mice xenograft model was used to detect the invasion and metastasis of breast cancer cell lines.Results
CHD1L overexpression was observed in 112 of 268 patients (41.8%). This overexpression was associated with lymph node metastasis (P = 0.008), tumor differentiation (P = 0.020), distant metastasis (P = 0.026), MMP-2 (P = 0.035), and MMP-9 expression (P = 0.022). In the cell experiment, reduction of CHD1L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1L knockdown via siRNA suppressed EGF-induced pAkt, pARK5, and pmTOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.Conclusions
CHD1L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ARK5/mTOR/MMP signaling pathway. This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer. 相似文献5.
Hyung Sun Kim Seho Park Ja Seung Koo Sanghwa Kim Jee Ye Kim Sanggeun Nam Hyung Seok Park Seung Il Kim Byeong-Woo Park 《PloS one》2016,11(3)
Purpose
The Ki-67 labelling index is significant for the management of breast cancer. However, the concordance of Ki-67 expression between preoperative biopsy and postoperative surgical specimens has not been well evaluated. This study aimed to find the correlation in Ki-67 expression between biopsy and surgical specimens and to determine the clinicopathological risk factors associated with discordant values.Patients and Methods
Ki-67 levels were immunohistochemically measured using paired biopsy and surgical specimens in 310 breast cancer patients between 2008 and 2013. ΔKi-67 was calculated by postoperative Ki-67 minus preoperative levels. The outliers of ΔKi-67 were defined as [lower quartile of ΔKi-67–1.5 × interquartile range (IQR)] or (upper quartile + 1.5 × IQR) and were evaluated according to clinicopathological parameters by logistic regression analysis.Results
The median preoperative and postoperative Ki-67 levels were 10 (IQR, 15) and 10 (IQR, 25), respectively. Correlation of Ki-67 levels between the two specimens indicated a moderately positive relationship (coefficient = 0.676). Of 310 patients, 44 (14.2%) showed outliers of ΔKi-67 (range, ≤-20 or ≥28). A significant association with poor prognostic factors was found among these patients. Multivariate analysis determined that significant risk factors for outliers of ΔKi-67 were tumor size >1 cm, negative progesterone receptor (PR) expression, grade III cancer, and age ≤35 years. Among 171 patients with luminal human epidermal growth factor receptor 2-negative tumors, breast cancer subtype according to preoperative or postoperative Ki-67 levels discordantly changed in 46 (26.9%) patients and a significant proportion of patients with discordant cases had ≥1 risk factor.Conclusion
Ki-67 expression showed a substantial concordance between biopsy and surgical specimens. Extremely discordant Ki-67 levels may be associated with aggressive tumor biology. In patients with luminal subtype disease, clinical application of Ki-67 values should be cautious considering types of specimens and clinicopathological risk factors. 相似文献6.
Purpose
The present study investigated the clinical significance of transmembrane protease, serine 4(TMPRSS4) and extracellular signal-regulated kinases 1 (Erk1) in the development, progression and metastasis of gastric cancer.Methods
Immunohistochemistry was employed to analyze TMPRSS4 and Erk1 expression in 436 gastric cancer cases and 92 non-cancerous human gastric tissues.Results
Protein levels of TMPRSS4 and Erk1 were up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues. High expression of TMPRSS4 correlated with age, size, Lauren’s classification, depth of invasion, lymph node and distant metastases, regional lymph node stage and TNM stage, and also with expression of Erk1. In stages I, II and III, the 5-year survival rate of patients with high TMPRSS4 expression was significantly lower than in patients with low expression. Further multivariate analysis suggests that up-regulation of TMPRSS4 and Erk1 were independent prognostic indicators for the disease, along with depth of invasion, lymph node and distant metastasis and TNM stage.Conclusions
Expression of TMPRSS4 in gastric cancer is significantly associated with lymph node and distant metastasis, high Erk1 expression, and poor prognosis. TMPRSS4 and Erk1 proteins could be useful markers to predict tumor progression and prognosis of gastric cancer. 相似文献7.
Yunhui Zeng Qiongwen Zhang Yujie Zhang Minxun Lu Yang Liu Tianying Zheng Shijian Feng Meiqin Hao Huashan Shi 《PloS one》2015,10(9)
Objective
To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC).Methods
Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis.Results
A total of 18 studies (n = 3271) met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS) score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63–3.29). The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23–4.00). In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke’s stage (OR = 3.02, 95% CI = 2.11–4.33). No publication bias was found in the mate-analysis by Begg’s test or Egger’s test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg’s test p = 0.729, Egger’s test p = 0.000).Conclusions
Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis. 相似文献8.
Objectives
The purpose of this study was to demonstrate the incidence rates and predictive factors of superior mediastinal lymph node (SMLN) metastasis in PTC (papillary thyroid carcinoma) patients.Methods
A prospective observational study was performed between January 2009 and January 2011. PTC patients who had tumors with a maximal diameter greater than 1 cm and clinically negative SMLNs were included in this study. Finally, a total of 217 patients who underwent total thyroidectomy with central compartment neck dissection (CND) and elective superior mediastinal lymph node dissection (SMLND), with or without modified radical neck dissection (MRND) and revisional CND, were included.Results
Occult SMLN metastasis was present in 15.7% (34/217). Cytological classifications of tumor, BRAFV600E mutation, Tumor size, T-stage, perithyroidal extension, lymphovascular invasion, multifocality, and paratracheal pN(+) were not predictive of SMLN metastasis (P > .05), while revision surgery, pretracheal pN(+), and multiple lateral pN(+) were associated with SMLN metastasis. There were no major complications related to SMLND. Transient and permanent hypoparathyroidism was observed in 69 cases (31.8%) and 8 cases (3.6%), respectively.Conclusions
Despite clinically negative SMLN in preoperative evaluation, SMLN metastasis can be predicted for patients with a PTC tumor size larger than 1 cm, pretracheal LN metastasis, multiple lateral metastasis, and revisional surgery. 相似文献9.
Tae-Kyung Yoo Jun Won Min Min Kyoon Kim Eunshin Lee Jongjin Kim Han-Byoel Lee Young Joon Kang Yun-Gyoung Kim Hyeong-Gon Moon Woo Kyung Moon Nariya Cho Dong-Young Noh Wonshik Han 《PloS one》2015,10(12)
Objective
The aim of our study was to evaluate the effect of tumor growth rate, calculated from tumor size measurements by US, on breast cancer patients’ outcome.Patients and Methods
Breast cancer patients who received at least two serial breast ultrasonographies (US) in our institution during preoperative period and were surgically treated between 2002 and 2010 were reviewed. Tumor growth rate was determined by specific growth rate (SGR) using the two time point tumor sizes by US.Results
A total of 957 patients were analyzed. The median duration between initial and second US was 28 days (range, 8–140). The median initial tumor size was 1.7cm (range, 0.4–7.0) and median second size was 1.9cm (range, 0.3–7.2). 523(54.6%) cases had increase in size. The median SGR(x10-2) was 0.59 (range, -11.90~31.49) and mean tumor doubling time was 14.51 days. Tumor growth rate was higher when initial tumor size was smaller. Lymphovascular invasion, axillary lymph node metastasis, and higher histologic grade were significantly associated with higher SGR. SGR was significantly associated with disease-free survival (DFS) in a univariate analysis (p = 0.04), but not in a multivariate Cox analysis (p>0.05). High SGR was significantly associated with worse DFS in a subgroup of initial tumor size >2cm (p = 0.018), but not in those with tumor size <2cm (p>0.05).Conclusion
Our results showed that tumor growth rate measured by US in a relatively short time interval was associated with other worse prognostic factors and DFS, but it was not an independent prognostic factor in breast cancer patients. 相似文献10.
Fang Liu Li Qi Bao Liu Jie Liu Hua Zhang DeHai Che JingYan Cao Jing Shen JianXiong Geng Yi Bi LieGuang Ye Bo Pan Yan Yu 《PloS one》2015,10(3)
Objective
Fibroblast activation protein (FAP) plays a vital role in tumor invasion and metastasis. Previous studies have reported its prognostic value in different tumors. However, the results of these reports remain controversial. In this study, a meta-analysis was performed to clarify this issue.Methods
A search of the PubMed, Embase and CNKI databases was conducted to analyze relevant articles. The outcomes included the relations between FAP expression and histological differentiation, tumor invasion, lymph node metastasis, distant metastasis and overall survival (OS). Sensitivity analysis by FAP expression in different cells and tumor types were further subjected to sensitivity analyses as subgroups. Pooled odds ratios (ORs) and hazard ratios (HRs) were evaluated using the random-effects model.Results
The global analysis included 15 studies concerning various solid tumors. For global analysis, FAP overexpression in tumor tissue displayed significant associations with poor OS and tumor progression (OS: HR = 2.18, P = 0.004; tumor invasion: OR = 4.48, P = 0.007; and lymph node metastasis: OR = 3.80, P = 0.004). The subgroup analyses yielded two notable results. First, the relation between FAP overexpression and poor OS and tumor lymph node metastasis was closer in the patients with FAP expression in tumor cells. Second, the pooled analyses of colorectal cancers or pancreatic cancers all indicated that FAP overexpression was associated with a detrimental OS (HR: 1.72, P = 0.009; HR: 3.18, P = 0.005, respectively). The magnitude of this effect was not statistically significant compared with that in patients with non-colorectal cancers or non-pancreatic cancers. These analyses did not display a statistically significant correlation between FAP expression and histological differentiation and distant metastasis in all of the groups.Conclusions
FAP expression is associated with worse prognosis in solid tumors, and this association is particularly pronounced if FAP overexpression is found in the tumor cells rather than the stroma. 相似文献11.
Ting Hu Xiong Li Qinghua Zhang Kecheng Huang Yao Jia Ru Yang Fangxu Tang Qiang Tian Ding Ma Shuang Li 《PloS one》2015,10(4)
Background
The effect of neoadjuvant chemotherapy (NACT) on topographical distribution patterns of lymph node metastasis in cervical cancer was unknown.Methods
Patients with FIGO stage IB1-IIB who underwent radical surgery with or without NACT were enrolled (3527 patients). A matched-case comparison design was used to compare the effects of NACT on lymph node metastasis.Results
We analyzed groups of 167 and 140 patients who were diagnosed with lymph node metastasis in the matched primary surgery group and NACT group, respectively, and no significant difference was observed (p = 0.081). The incidence of lymph node metastasis was significantly decreased in the NACT-responsive group compared to the non-responsive group (18.4% vs. 38.6%, P<0.001). The metastatic rates for every lymph node group also declined in the NACT-responsive group except for the deep inguinal and the para-aortic lymph node groups. Clinical response, deep stromal, parametrial and lymph vascular invasions were independent risk factors for lymph node metastasis in the NACT group. Furthermore, deep stromal invasion and lymph vascular invasion, but not the response to NACT, were independently associated with upper LNM. The number of lymph nodes involved, response to NACT, tumor histology and a positive vaginal margin were independent prognostic factors affecting DFS or OS rates in node-positive patients treated with NACT plus radical surgery.Conclusion
The frequency and topographic distribution of LNM are not modified by NACT, and clinical non-responders showed more involved LNs. A systemic and extensive lymphadenectomy should be performed in patients treated with NACT plus surgery regardless of the response to NACT. 相似文献12.
Hongxiang Yu Diana L. Simons Ilana Segall Valeria Carcamo-Cavazos Erich J. Schwartz Ning Yan Neta S. Zuckerman Frederick M. Dirbas Denise L. Johnson Susan P. Holmes Peter P. Lee 《PloS one》2012,7(12)
Background
Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression.Methodology/Principal Findings
We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and down-regulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors.Conclusions/Significance
This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens up epigenetic drug development possibilities for the treatment and prevention of lymph node metastasis in breast cancer. 相似文献13.
Purpose
To investigate the distribution of Ki67+ cells in breast cancer in relation to clinical-pathological parameters and prognosis.Materials and Methods
Ki67 expression status was detected in 1,086 breast cancer specimens using immunohistochemistry staining and examining the relationship between the Ki67+ cells'' location. Subsequently, clinical-pathological parameters and prognosis were determined.Results
In total, Ki67 protein expression was found in 781 (71.92%) of the 1,086 breast cancer specimens. Among the 781 Ki67+ cases, 461 were defined as diffuse type and 320 were defined as borderline type. After universal correlation analysis, significant differences were observed in age, histological grade, metastatic nodes, postoperative distant metastasis, and molecular subtype between Ki67+ and Ki67− cases (P = 0.01, 0.001, 0.001, 0.001, and 0.001, respectively). After subgroup analysis, the borderline cases were found to be characterized by a high distant metastasis rate compared to the diffuse cases as well as the Ki67− cases (P = 0.001). No differences were observed between diffuse type or Ki67− cases (P = 0.105). Multivariate analysis showed that age, tumor size, histological grade, lymph node metastasis, molecular subtype, and the Ki67 distribution pattern were observed to be related to postoperative distant metastasis (all P<0.05). Furthermore, borderline type was shown to attain a significantly more distant bone and liver metastasis and worse disease-specific survival than the other types (P = 0.001). In the Cox regression test, the Ki67 distribution pattern was detected as an independent prognostic factor (P = 0.001).Conclusion
The distribution pattern of Ki67 may be a new independent prognostic factor for breast cancer. 相似文献14.
Cai Shirong Chen Jianhui Chen Chuangqi Wu Kaiming Zhang Xinhua Song Wu He Yulong 《PloS one》2015,10(3)
Background and Aims
There is a discrepancy between the American Joint Committee on Cancer (AJCC) guidelines (7th edition) and the Japanese treatment guidelines (3rd edition) with regard to the extent of D2 lymphadenectomy for gastric cancer. In the AJCC, hepatic artery station (No.12a) lymph node (LN) metastasis is classified as distant metastasis, whereas in the Japanese guidelines, this classified is regional metastasis. This study aimed to evaluate whether it is appropriate to reclassify No.12a LN metastasis as distant metastasis in consideration of survival outcome.Methods
In this retrospective analysis, data from patients with gastric cancer who underwent regular D2 or greater lymphadenectomy between 1996 and 2006 were evaluated to determine any association between the clinicopathological features of hepatic artery LNs and survival prognosis.Results
Among the 247 patients with gastric cancer who underwent No.12 LN harvest, 45 (18.2%) were positive for No.12a LN metastasis. No.12a LN metastasis was significantly associated with poor clinicopathological features, advanced tumor stage, and poor overall survival. The 5-year survival rate of patients with No.12a LN metastasis was significantly better than that of patients with distant metastasis (P < 0.05), but was similar to that of patients with LN involvement in the D2 lymphadenectomy region (P > 0.05). No.12a LN metastasis was shown to significantly influence survival outcome in univariate analysis, but was not identified as a significant independent predictor in multivariate analysis. In logistic multivariate regression analysis, T stage, N stage, and station No.3, 5, and 6 LN metastasis were independent predictors of No.12a LN involvement.Conclusions
It is inappropriate to reclassify No.12a LN metastasis as distant metastasis. We propose that this be considered as regional metastasis and be included in the extent of D2 lymphadenectomy to improve survival outcomes in patients with gastric cancer. 相似文献15.
16.
Julia Krammer Anja Dutschke Clemens G. Kaiser Andreas Schnitzer Axel Gerhardt Julia C. Radosa Joachim Brade Stefan O. Schoenberg Klaus Wasser 《PloS one》2016,11(2)
Background
To evaluate whether tumor localization and method of preoperative biopsy affect sentinel lymph node (SLN) detection after periareolar nuclide injection in breast cancer patients.Methods and Findings
767 breast cancer patients were retrospectively included. For lymphscintigraphy periareolar nuclide injection was performed and the SLN was located by gamma camera. Patient and tumor characteristics were correlated to the success rate of SLN mapping. SLN marking failed in 9/61 (14.7%) patients with prior vacuum-assisted biopsy and 80/706 (11.3%) patients with prior core needle biopsy. Individually evaluated, biopsy method (p = 0.4) and tumor localization (p = 0.9) did not significantly affect the SLN detection rate. Patients with a vacuum-assisted biopsy of a tumor in the upper outer quadrant had a higher odds ratio of failing in SLN mapping (OR 3.8, p = 0.09) compared to core needle biopsy in the same localization (OR 0.9, p = 0.5).Conclusions
Tumor localization and preoperative biopsy method do not significantly impact SLN mapping with periareolar nuclide injection. However, the failure risk tends to rise if vacuum-assisted biopsy of a tumor in the upper outer quadrant is performed. 相似文献17.
Ali H. Zaidi Lindsey T. Saldin Lori A. Kelly Linda Bergal Ricardo Londono Juliann E. Kosovec Yoshihiro Komatsu Pashtoon M. Kasi Amit A. Shetty Timothy J. Keane Shyam J. Thakkar Luai Huleihel Rodney J. Landreneau Stephen F. Badylak Blair A. Jobe 《PloS one》2015,10(3)
Objective
To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC).Background
The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies.Methods
The modified Levrat’s surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors.Results
The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2.Conclusion
In vivo metastasis was confirmed in the modified Levrat’s model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized. 相似文献18.
Chi Zhang Fangfeng Liu Hong Chang Hongguang Li Xu Zhou Jun Lu Chengkun Qin Yongjie Sun Huidong Sun Jianbo Lin 《PloS one》2015,10(11)
Objectives
To evaluate the clinical characteristics and radiological features of solid pseudopapillary tumor (SPT) and assess surgical therapy strategy.Methods
A retrospective review was performed in 62 patients pathologically confirmed of SPT treated between 2003 and 2014. The clinical features, radiological examinations and surgical strategies were analyzed.Results
56 females and 6 males were included in this study, mean age was 26 years old (range: 8–66 years old) with mean size of the tumor was 7.2 cm (range: 3–15 cm), and most tumor were commonly located in the head of pancreas (n = 29). Among all the cases, 3 patients had liver metastasis and underwent resection of SPT and liver metastasis. Furthermore, we performed 29 cases of local tumor excision; other patients underwent pancreaticoduodenectomy, middle pancreatectomy, middle pancreatectomy with splenectomy, distal pancreatectomy with spleen preservation, distal pancreatectomy with splenectomy and duodenum-preserving pancreatic head resection. No patient suffered from lymph node metastases. After median follow-up of 46 months (range: 2–135 months), no mortality or local recurrence or distant metastasis was found.Conclusions
Solid pseudopapillary tumor is a latent malignant tumor with excellent prognosis. If feasible, less aggressive resection without regular lymphadenectomy is recommended for treatment of patients with SPT. 相似文献19.
Jia-Min B. Pang David J. Byrne Elena A. Takano Nicholas Jene Lara Petelin Joanne McKinley Catherine Poliness Christobel Saunders Donna Taylor Gillian Mitchell Stephen B. Fox 《PloS one》2015,10(6)
Aim
To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.Methods
Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31) slides and correlated to mammographic density.Results
Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22) = 0.5226, p = 0.0088) and significantly inversely associated with adipose tissue proportion (rs (22) = -0.5409, p = 0.0064). Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%). There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026).Conclusions
The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density. 相似文献20.